Activated by tyrosine and threonine phosphorylation
Binds heme and acts as a three-way sensor with three levels of activity (PubMed:25333974). The oxidation of the heme by oxygen leads to the activation of the autokinase activity, whereas the deoxy-ferrous state confers a moderate kinase activity (PubMed:25333974). Kinase activity is strongly inhibited by binding of NO and CO, which lock SenX3 in an inactive state (PubMed:25333974). Activation of the SenX3-RegX3 two-component system is inhibited by PhoY1 and PhoY2 when phosphate is readily available (PubMed:28698272)
Inhibited by captopril and, to a lesser extent, by lisinopril, trandolaprilat, fosinoprilat and enalaprilat
Has very low E3 ubiquitin ligase activity in the absence of sphingosine-1-phosphate. E3 ubiquitin ligase activity is strongly activated by cytoplasmic sphingosine-1-phosphate
Repressed by abscisic acid-bound PYL1
The formation of the proteasomal ATPase PAN-20S proteasome complex, via the docking of the C-termini of PAN into the intersubunit pockets in the alpha-rings, triggers opening of the gate for substrate entry. Interconversion between the open-gate and close-gate conformations leads to a dynamic regulation of the 20S proteasome proteolysis activity
Allosterically activated by HslU binding
ATP hydrolysis occurs at the interface between the nucleotide-binding domains of subunits A and B (By similarity). ATP hydrolysis triggers a conformational change in the subunits D and F, which induces a shift of subunit d (By similarity). The c-ring is subsequently rotated and results in a continuous proton translocation across the membrane (By similarity)
The enzyme is activated by S-adenosyl-methionine. Activity is dependent on the levels of Fe(2+), S(2-) and Co(2+). Activity is stimulated by addition of EDTA. S-adenosylhomocysteine competitively inhibits the activity whereas 5'-methylthioadenosine is not inhibitory in the presence of S-adenosylmethionine. Competitively inhibited by 4-thialysine. Inhibited by sodium borohydride (1 mM) when added with 2 mM dithionate. Moderately inhibited by beta-mercaptoethanol (30 mM) along with dithionate. Higher concentrations of Fe(2+) partially inhibit the activity and Co(2+) at 1 mM is a strong inhibitor. Hydroxylamine, isonicotinic acid hydrazide inhibit effectively, in addition, hydrazine, D-penicillamine and D-cycloserine are also inhibitory at high concentrations
Inhibited by EDTA
Subject to competitive inhibition by the product ADP-ribose
Inhibited by bee venom neurotoxin apamin (PubMed:10991935, PubMed:9287325). Inhibited by UCL 1684 and tetraethylammonium (TEA) (By similarity)
The covalent binding to the substrate causes inactivation of the enzyme, and possibly serves as a signal for the export of the protein
Activated by phosphorylation on threonine and tyrosine by MAP2K3/MKK3, MAP2K4/MKK4 and MAP2K6/MKK6. MAP2K3/MKK3 and MAP2K6/MKK6 are both essential for the activation of MAPK11 induced by environmental stress. HDAC3 interacts directly and selectively with MAPK11 to repress ATF2 transcriptional activity, and regulate TNF gene expression in LPS-stimulated cells. Inhibited by SB203580 and pyridinyl-imidazole related compounds
Inhibited by cyclosporin A (CsA)
Allosterically activated by GTP
Deoxyglucose transport is inhibit by D-glucose, D-galactose and maltose. Galactose transport is inhibited by D-glucose and maltose
Activated by dual phosphorylation on Ser-234 and Thr-238 in response to a variety of cellular stresses, including UV radiation, osmotic shock, hypoxia, inflammatory cytokines, interferon gamma (IFNG), and less often by growth factors. MAP2K6/MKK6 is activated by the majority of M3Ks (By similarity)
In the male gonad, probably maintained inactive by swm-1
Na(+) is not transported, but it plays an essential structural role and its presence is essential for fluoride channel function
The phospholipase C-like activity toward cardiolipin is inhibited by amyloid-beta peptide
Activated by N-ethylmaleimide (NEM). Inhibited by DIOA, bumetanide and furosemide. Inhibited by WNK3
Inhibited by dietary sesamin
Allosterically activated by fructose-1,6-bisphosphate (F16BP) and inhibited by AMP
Contains an N-terminal autoinhibitory domain. Activated by phosphorylation at Thr-816, inhibited by phosphorylation at Ser-928 (By similarity)
Inhibited by heavy metal compounds, Zn(2+), and heme. Also competitively inhibited by glutamycin
Inhibited by fructose 1,6-bisphosphate (FBP)
Competitively inhibited by lysophosphatidic acid
Feedback inhibited by histidine
Inhibited by PMSF, bovine aprotinin (APR), and soybean trypsin inhibitor (STI). Is not inhibited by EDTA, beta-mercaptoethanol, and high temperature (85 degrees Celsius)
Unlike for mammalian OATs, activity is increased by TRX1-mediated reduction of the disulfide bond between Cys-154 and Cys-163 (PubMed:20673832). Binding to TRX1 may also induce conformational changes that facilitate substrate binding (PubMed:20673832)
Protein stability and endopeptidase activity are calcium dependent (PubMed:17287215). First cleavage on prophenoloxidase PPO1 and PPO2 is not dependent on calcium; however, cleavage of PPO1 and PPO2 to their active forms is dependent on calcium and on the presence of PPAF2 and PPAF3 (PubMed:12185078). Cleavage of PPAF2 is inhibited by calcium (PubMed:11012672, PubMed:12185078). Inhibited by ethylenediaminetetraacetic acid (EDTA), p-nitrophenyl-p'-guanido-benzoate, diisopropylphosphorofluoridate (iPr2PF) and p-(Amidinophenyl)methanesulfonyl fluoride (p-APMSF) (PubMed:9652393, PubMed:17287215)
PE domain down-regulates lipase activity
Cleavage by PecA does not affect surface localization and lipase activity
Inhibited by diethyl-p-nitrophenyl phosphate (E-600) at 0.5 uM, by phenylmethanesulfonyl fluoride at 5 mM and by polyethylene glycol sorbitan monolaurate (Tween 20). Also inhibited by CaCl(2), CoCl(2), MnCl(2), ZnCl(2) and MgCl(2) (PubMed:16354661). Inhibited by several hydrazides compounds (PubMed:23684389). Stimulated slightly by SDS at concentrations up to 2 mM, above which the activity is severely inhibited (PubMed:16354661)
Activated by phosphorylation on Thr-173
Activated by N-ethylmaleimide (NEM). Inhibited by furosemide, DIDS and bumetanide. The inhibition is much stronger in the presence of 50 mM K(+) in the uptake medium. Inhibited by DIOA. Inhibited by WNK3
Allosterically activated by various compounds, including ATP. Activated by cAMP; the nucleotide acts as a dynamic and allosteric activator by coupling the two lobes of apo PKA, enhancing the enzyme dynamics synchronously and priming it for catalysis
Activated by partially methylated beta-cyclodextrin
Activated by magnesium and inorganic phosphate
Inhibited by the metal chelators EDTA and 1,10-phenanthroline
Activated by threonine and tyrosine phosphorylation
Activated by agonist muscimol (PubMed:8016117, PubMed:12805302, PubMed:8389005, PubMed:24823815). Insensitive to zinc, glycine, glutamate, and baclofen, loreclezole, to antagonist bicuculline, glycine-receptor antagonist strychnine, and nonselective GABA and glycine antagonist RU 5135 (PubMed:8016117, PubMed:8389005, PubMed:8882620, PubMed:12805302). Insensitive to flunitrazepam, pentobarbitone or pregnane steroids such as 5alpha-pregnan-3alpha-ol-20-one (PubMed:8016117, PubMed:8882620, PubMed:12805302). Inhibited by insecticides picrotoxin (PTX), cyclodiene dieldrin, TBPS and lindane (PubMed:8016117, PubMed:8389005, PubMed:7527461). Inhibited by ivermectin, fipronil and pyrafluprole (PubMed:24823815)
Inhibited by insecticides picrotoxin (PTX)
Magnesium-independent phospholipid phosphatase. Inhibited by N-ethylmaleimide
Inhibited by WNK3
Active in the presence of octyl-glucoside or Triton X-100, but completely inhibited by CTAB
Inhibited by both FK506 and rapamycin
Apical membrane chloride-bicarbonate exchange activity of the pancreatic duct is inhibited by 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS). Oxalate secretion in the duodenum and chloride-formate exchange activity is inhibited by DIDS
Chloride-formate exchange activity and transcellular sulfate absorption is inhibited by 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS)
Activated by interaction with WDR48
Inhibited by zinc and EDTA
Stimulated by methyl jasmonate (MeJA)
100-fold more active in the presence of saturating ATP
Okadaic acid, an inhibitor of protein phosphatase 1 (PP1), protein phosphatase 2A (PP2A) and protein phosphatase 5 (PP5), increases AURKC activity. AURKC is also stabilized through its interaction with INCENP, which acts also as an activator
Inhibited by diisopropylfluorophosphate (DFP), but not by SBTI, Antithrombin III/heparin and BPTI, probably due to steric hindrance caused by its huge carbohydrate moietie
Inhibited by UTP
Activated by glutamine and dihydroxyacetone phosphate. Inhibited by glutamate, aspartate, 2-oxoglutarate and malate
Allosterically activated by ADP and other diphosphonucleosides, and allosterically inhibited by phosphoenolpyruvate
Mycophenolic acid (MPA) is a non-competitive inhibitor that prevents formation of the closed enzyme conformation by binding to the same site as the amobile flap. In contrast, mizoribine monophosphate (MZP) is a competitive inhibitor that induces the closed conformation. MPA is a potent inhibitor of mammalian IMPDHs but a poor inhibitor of the bacterial enzymes. MZP is a more potent inhibitor of bacterial IMPDH
Increases in stationary phase in a strain lacking the WprA protease
Activated by calmodulin
Allosterically activated by GTP, when glutamine is the substrate; GTP has no effect on the reaction when ammonia is the substrate. The allosteric effector GTP functions by stabilizing the protein conformation that binds the tetrahedral intermediate(s) formed during glutamine hydrolysis. Inhibited by the product CTP, via allosteric rather than competitive inhibition
Has different conformational states with differential Ca2+ affinity. The E1 conformational state (active form) shows high Ca(2+) affinity, while the E2 state exhibits low Ca(2+) affinity. Reversibly inhibited by phospholamban (PLN) at low calcium concentrations. Inhibited by sarcolipin (SLN) and myoregulin (MRLN). The inhibition is blocked by VMP1 (PubMed:28890335). Enhanced by DWORF; DWORF increases activity by displacing sarcolipin (SLN), phospholamban (PLN) and myoregulin (MRLN) (By similarity). Stabilizes SERCA2 in its E2 state (PubMed:28890335)
Ca(2+) switches the cyclization mechanism of delta(6)-protoilludene synthase from 1,11 to 1,10 cyclization which leads to the production of beta-elemene
NAD(+) hydrolase activity is strongly stimulated by c-di-GMP, weakly by 3'3'-cGAMP, very weakly by c-di-AMP but not at all by 2'3'-cGAMP (Probable). Self-association of TIR domains is required for NADase activity (By similarity)
Activated by the ototoxic drug cisplatin. Activated by NOXO1. Cooperatively activated by NCF1 and NCF2 or NOXA1 in a phorbol 12-myristate 13-acetate (PMA)-dependent manner. Inhibited by diphenyleneiodonium chloride (By similarity)
Activated by ADP
Inhibited by Z-VAD-fmk, a well-known caspase inhibitor, which inhibits enzyme activity through covalent binding of the carbohydrate to the single Cys-306 residue
Intracellular DIC accumulation is sensitive to CCCP (carbonyl cyanide-m-chlorophenylhydrazone) and DCCD (N,N-dicyclohexylcarbodiimide) and therefore likely driven by either proton gradient, ATP, or both
Inhibited by neomycin. Up-regulated by PIP2 binding
Phosphatase activity is strongly reduced by the protein phosphatase inhibitor 2 (I-2)
Activated by potassium phosphate
Allosterically activated by fructose 1,6-bisphosphate (FBP)
Inhibited by S-adenosyl-N-decyl-aminoethyl (SADAE) and thiacetazone (TAC)
Activity is inhibited by the phosphodiesterase PdeR. Inhibition is relieved by high cellular c-di-GMP levels
Inhibited by EDTA, partially inhibited by o-phenantropine, and not inhibited by PMSF, pepstatin A, and aprotinin
Activated by ADRM1. Inhibited by interaction with NFRKB (By similarity)
The presence of a 5'-monophosphate on substrate RNA accelerates its cleavage by catalytically activating the enzyme (PubMed:15197283). In contrast, another group has shown that the enzyme has a higher affinity for 5'-monophosphorylated substrate, which enhances substrate binding in vitro and the decay of RNA in vivo (PubMed:18078441)
Specifically inhibited by cardiac glycosides such as digoxin or ouabain
The cyclooxygenase activity is inhibited by nonsteroidal anti-inflammatory drugs (NSAIDs) including ibuprofen, flurbiprofen, ketoprofen, naproxen, flurbiprofen, anirolac, fenclofenac and diclofenac
The E3 ubiquitin-protein ligase activity is stimulated by PEX12
Activity is increased by EGF, HGF, FGF1 or FGF2 treatments, and slightly decreased by NGF treatment
Activated by ADRM1. Inhibited by interaction with NFRKB
Inhibited by the bleaching herbicide 2-(4-methylphenoxy)triethylamine hydrochloride (MPTA)
Allosterically activated by GTP. Inhibited by UTP
Feedback inhibited by L-histidine
In the resting state, through the dimerization of its C-terminal domain, HSP90 forms a homodimer which is defined as the open conformation. Upon ATP-binding, the N-terminal domain undergoes significant conformational changes and comes in contact to form an active closed conformation. After HSP90 finishes its chaperoning tasks of assisting the proper folding, stabilization and activation of client proteins under the active state, ATP molecule is hydrolyzed to ADP which then dissociates from HSP90 and directs the protein back to the resting state
Uridylyltransferase (UTase) activity is inhibited by glutamine, while glutamine activates uridylyl-removing (UR) activity
Inhibited by gabaculine (Gcn)
TPS activity is potently inhibited by several molecules such as 4-{[(2-hydroxy-5-nitrophenyl)methylidene]amino}-5-methyl-2-(propan-2-yl)phenol (NSC compound 33472) and 2-{5-[2,4,6-(trinitrophenyl)amino]-1H-tetrazol-1-yl}ethanol (NSC compound 116720)
Binding to SSBP1 in mitochondria inhibits glycosylase activity in the context of a single-stranded DNA (ssDNA), but not a double-stranded DNA (dsDNA) substrates
Activated by phosphorylation at Ser-343, Thr-568 and Thr-687 by MAPK1/ERK2, MAPK3/ERK1 and MAPK14/p38-alpha, and by further autophosphorylation of Ser-196, Ser-360 and Ser-365 by the activated C-terminal kinase domain
Inhibited by C/VIF1 and C/VIF2
FtsK may regulate the catalytic switch between XerC and XerD in the heterotetrameric complex during the two steps of the recombination process
Activated by a monovalent cation that binds near, but not in, the active site. The most likely occupant of the site in vivo is potassium. Ion binding induces a conformational change that may alter substrate affinity
Competitively inhibited by methylglyoxal bis-guanylhydrazone. Irreversibly inhibited by NaBH(4) in vitro
Strongly inhibited by sodium orthovanadate
By membrane damage, for example, by phage-induced lysis or temperature shock. The protein is inactive in the monomeric form and active in the dimeric form; calcium is essential for dimer stability
Activated by calcium. Autophosphorylation may play an important role in the regulation of the kinase activity
Enzyme is oxygen sensitive
Inhibited by ammonium and thiosulfate
Inhibited by triazolodiamine 1 (5-amino-3-([4-(aminosulfonyl)phenyl]amino)-N-(2,6-difluorophenyl)-1H-1,2,4-triazole-1-carbothioamide), (S)-propane-1,2-diol, 2-({6-[(3-chlorophenyl)amino]-9-isopropyl-9H-purin-2-yl}amino)-3-methylbutan-1-ol, N2-[(1R,2S)-2-aminocyclohexyl]-N6-(3-chlorophenyl)-9-ethyl-9H-purine-2,6-diamine and [4-amino-2-(3-chloroanilino)-1,3-thiazol-5-yl](4-fluorophenyl)methanone
Inhibited by malonate
Not regulated by feedback inhibition by CoA and its thioesters as described for many other pantothenate kinases. Not inhibited by N-pentylpantothenamide (N5-Pan), and this compound cannot act as a substrate either
Inhibited by diisopropyl fluorophosphate (DFP), phenylmethanesulfonyl fluoride (PMSF) or p-chloromercuribenzoic acid (PCMB), but not by N-ethylmaleimide (NEM) or iodoacetamide
Negatively regulated by the anti-sigma-I factor RsgI2 (By similarity). Binding of the polysaccharide substrate to RsgI2 may lead to the release and activation of SigI2 (By similarity)
Activated by bis-(3'-5') cyclic diguanylic acid (c-di-GMP)
Activity of this regulatory enzyme is affected by several metabolites. Allosterically and non-competitively inhibited by fructose 1,6-bisphosphate (FBP) and unphosphorylated phosphocarrier protein EIIA-Glc (III-Glc), an integral component of the bacterial phosphotransferase (PTS) system
Activation requires autophosphorylation of Ser-356. Phosphorylation of Ser-352 also promotes increased activity (By similarity)
Does not require divalent metal ions for optimal activity
Cooperatively feedback inhibited by tryptophan
Up-regulated in the tail by thyroid hormone
Allosterically activated by phosphatidylinositol 5-phosphate (PI5P)
Tyrosine, phenylalanine, and tryptophan moderately enhance chorismate mutase activity at low concentrations, but allosterically inhibit the enzyme at higher concentrations
Inhibited by high concentration of manganese
Perturbation in protein folding in the endoplasmic reticulum (ER) promotes reversible dissociation from HSPA5/BIP and oligomerization, resulting in transautophosphorylation and kinase activity induction
Inhibited by EDTA and Zn(2+). Activated by high concentrations of monovalent cation with a preference for K(+) over Na(+)
L-lactate and ethanol are non-competitive inhibitors, whereas succinate, citrate, and D-tartrate show competitive type inhibitions
Helicase activity is stimulated in the presence of NurA
Inhibited by EDTA, Zn(2+), Cd(2+), DTT, p-chloromercuribenzoate and L-ascorbic acid (AsA)
Activated by cAMP, and at 10-100 times higher concentrations, also by cGMP. cAMP binding causes a conformation change that leads to the assembly of an active tetramer and channel opening. Compared to other family members, cAMP has less stimulatory effect on HCN1 because part of the molecules already contain bound cAMP and form homotetramers when cAMP levels are low
DNA binding is strongly activated by Mn(2+)
Strongly inhibited by the cysteine peptidase inhibitors mersalyl acid, iodoacetic acid and cystatin. Inhibited by N-ethylmaleimide, Gly-Phe-diazomethane, TLCK, TPCK and, at low pH, by dithiodipyridine. Not inhibited by the serine peptidase inhibitor PMSF, the aminopeptidase inhibitor bestatin, or metal ion chelators
Inhibited by Ser- or Thr-derived imine
Protease activity is activated upon binding to 1D-myo-inositol hexakisphosphate (InsP6), which induces conformational reorganization
RFU1 is an inhibitor of deubiquitination activity
In resting state, adopts an open conformation, anion-binding promoting the inactive configuration. Upon aromatic amino acid-binding, the groove in the extracellular venus flytrap module is closed, thereby inducing the formation of a novel homodimer interface between subunits. Calcium ions stabilize the active state by enhancing homodimer interactions between membrane-proximal domains to fully activate the receptor
Insensitive to okadaic acid
Protein archease stimulates the activity of the tRNA ligase complex with high efficiency in the presence of GTP
Inbibited by ammonium sulfate at millimolar concentrations and by O-benzylhydroxylamine (Obe)
DNA supercoiling is inhibited by EDTA, novobiocin, coumermycin and ciprofloxacin (PubMed:7503546)
Is inhibited by divalent cations such as Zn(2+) and Cu(2+), but not by Mg(2+), Mn(2+) and Ca(2+). Is not inhibited by several known inhibitors of the GH13 family such as ADP, ADP glucose, tunicamycin, castenospermine, nojirimycin, or acarbose
Allosterically activated by N-acetylglucosamine 6-phosphate (GlcNAc6P)
Exhibits positive allosteric property with acetyl-CoA and fructose 1,6-bisphosphate, and a negative one with L-aspartate and L-malate
Inhibited by iodoacetamide and diethylpyrocarbonate in vitro, but is insensitive to iodoacetate treatment
Activation is generally mediated by guanine exchange factor (GEF), while inactivation through hydrolysis of bound GTP is catalyzed by GTPases activating protein (GAP). Inactivated by ACAP1 and ACAP2 (By similarity). Activated by NGF via NTRK1 (By similarity)
Channel activity is inhibited by mercury ions
Alternates between an inactive form bound to GDP and an active form bound to GTP. Activated by a guanine nucleotide-exchange factor (GEF) and inactivated by a GTPase-activating protein (GAP)
Isoform M2 is allosterically activated by D-fructose 1,6-bisphosphate (FBP). Inhibited by oxalate and 3,3',5-triiodo-L-thyronine (T3). The activity of the tetrameric form is inhibited by PML. Selective binding to tyrosine-phosphorylated peptides releases the allosteric activator FBP, leading to inhibition of PKM enzymatic activity, this diverts glucose metabolites from energy production to anabolic processes when cells are stimulated by certain growth factors. Glycolytic flux are highly dependent on de novo biosynthesis of serine and glycine, and serine is a natural ligand and allosteric activator of isoform M2
Has high pyruvate kinase activity by itself and does not require allosteric activation by D-fructose 1,6-bisphosphate (FBP) for activity
Phosphorylation at Thr-14 or Tyr-15 inactivates the enzyme, while phosphorylation at Thr-161 activates it. Activated through a multistep process; binding to cyclin-B is required for relocation of cyclin-kinase complexes to the nucleus, activated by CAK/CDK7-mediated phosphorylation on Thr-161, and CDC25-mediated dephosphorylation of inhibitory phosphorylation on Thr-14 and Tyr-15. Inhibited by flavopiridol and derivatives, pyrimidine derivatives, pyridine derivatives, purine derivatives, staurosporine, paullones, oxoindoles, indazole analogs, indolin-2-ones, pyrazolo[3,4-b]pyridines, imidazo[1,2-a]pyridine (AZ703), thiazolinone analogs(RO-3306), thiazol urea, macrocyclic quinoxalin-2-one, pyrrolo[2,3-a]carbazole, pyrazolo[1,5-a]-1,3,5-triazine, pyrazolo[1,5-a]pyrimidine (Dinaciclib, SCH 727965), 2-(1-ethyl-2-hydroxyethylamino)-6-benzylamino-9-isopropylpurine (roscovitine), olomoucine, AG-024322, AT-7519, P276-00, R547/Ro-4584820 and SNS-032/BMS-387032. Repressed by the CDK inhibitors CDKN1A/p21 and CDKN1B/p27 during the G1 phase and by CDKN1A/p21 at the G1-S checkpoint upon DNA damage. Transient activation by rapid and transient dephosphorylation at Tyr-15 triggered by TGFB1
Probably not activated by nitric oxide (NO). Heterodimer exhibits some stimulation, compounds (SIN-1 and two of the NONOates) that were ineffective at stimulating Gyc-88E homodimer did stimulate the heterodimer
Phosphorylation on Ser-46 inhibits the phosphoryl transfer from enzyme I to HPr
Dimerization activates the kinase domain of unphosphorylated PknD via an allosteric mechanism, triggering autophosphorylation and phosphorylation of target proteins. Phosphorylated PknD is fully active even in the absence of dimerization
Fructose uptake is inhibited by cytochalasin B
Under nitrogen limitation, binding of the intracellular nitrogen metabolite 2-oxoglutarate to NrpR decreases the binding affinity of NrpR to DNA, leading to initiation of transcription
Inhibited by ethoxyzolamide
Activated by guanine nucleotide-exchange factor (GEF) EPAC2 in a cAMP-dependent manner
The regulatory domain is involved in the regulation of cyclase activity by the carbon source
Feedback inhibition by tryptophan
Activated by ascorbate
Inhibited by 1,2-dideoxy-2'-methyl-alpha-D-glucopyranoso-[2,1-d]-delta 2'-thiazoline (NAG-thiazoline) and O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino-N-phenyl-carbamate (PUGNAc). Not inhibited by Streptozotocin
Specifically and reversibly inhibited by salicylic acid (SA)
Not inhibited by AMP and slightly innibited by hydrogen peroxyde
Pre-crRNA processing is inhibited by EDTA
By zinc. Zinc-binding negatively regulates WalK kinase activity and thus autophosphorylation
The 3',5'-cyclic-AMP phosphodiesterase activity is stimulated by 3',5'-cyclic GMP
Competitive inhibition by mevinolin (Mev) is leading to a significant reduction of total ginsenoside in adventitious roots. Triggered by darkness
The relative activities of the inhibitory tyrosine-protein kinase CSK and the activating tyrosine-protein phosphatase PTPRC/CD45 determine the level of LCK activity. These interactions allow rapid and efficient activation of LCK in response to TCR stimulation (By similarity)
Activated by pro-inflammatory cytokines and in response to physical and chemical stresses, including osmotic stress, oxidative stress, arsenic and ultraviolet light irradiation (PubMed:20060931). Activated by 'Lys-63'-linked polyubiquitination and by autophosphorylation (PubMed:29291351). Association with TAB1/MAP3K7IP1 and TAB2/MAP3K7IP2 promotes activation through autophosphorylation, whereas PPM1B/PP2CB, PP2A and PPP6C dephosphorylation leads to inactivation (By similarity). Ceramides are also able to activate MAP3K7/TAK1 (By similarity)
Inhibited by N-ethyl-maleimide (NEM) and divalent cations. Tolerates high concentrations of NaCl but is inhibited at concentrations of 195 mM and higher
Inhibited by HgCl(2)
MK 571 inhibits sphingosine 1-phosphate and leukotriene C4 export
Negatively regulated by hyperphosphorylation during mitosis. The plk1/plk1 protein kinase may be required for mitotic phosphorylation. Inactivated during oocyte maturation by phosphorylation by RSK2 and Mos kinase
Several bivalent metal ions, such as nickel, copper, zinc, mercury, and lead, inhibit the activity to some extent. Inhibited by structural analogs such as citrate, cis-aconitate, isocitrate, 2-methylisocitrate, tricarballylate and fluorocitrate, but not by trans-aconitate or adipate
Inhibited by EDTA and EGTA, but not by cysteine or soybean trypsin inhibitor (SBTI)
Activated by pro-inflammatory cytokines and in response to physical and chemical stresses, including osmotic stress, oxidative stress, arsenic and ultraviolet light irradiation (PubMed:16893890). Activated by 'Lys-63'-linked polyubiquitination and by autophosphorylation (PubMed:10702308, PubMed:11460167, PubMed:12242293, PubMed:29291351). Association with TAB1/MAP3K7IP1 and TAB2/MAP3K7IP2 promotes activation through autophosphorylation, whereas PPM1B/PP2CB, PP2A and PPP6C dephosphorylation leads to inactivation (PubMed:11104763, PubMed:17079228). Ceramides are also able to activate MAP3K7/TAK1 (PubMed:9079627)
Strongly inhibited by 1 mM Zn(2+) ions (PubMed:9864312). Also inhibited by pyridine-2,4-dicarboxylic acid, 5-hydroxyisophthalic acid and 5,5'-dithiobis(2-nitrobenzoic acid) (Ellman reagent) (PubMed:22475079, PubMed:9864312)
Not inhibited by lithium (By similarity). Partial allosteric regulation on ions sodium binding (PubMed:16629640)
Inhibited by N-ethylmaleimide. Redox-regulated during autophagy since reducing conditions activate ATG4A whereas an oxidizing environment such as the presence of H(2)O(2) inhibits its activity
Activated by pfl-activating enzyme under anaerobic conditions via generation of an organic free radical (Probable). Exposure of activated pfl to oxygen results in a cleavage at the glycine residue harboring its organic radical with loss of the 25 C-terminal amino acids
Inhibited by Tris-HCl and phosphate buffer. Also competitively inhibited by sugars with L configuration at C2, such as D-arabinose-5-phosphate and L-glyceraldehyde
Inhibited by 10-hydroxystearamide and methoxy-arachidonyl fluorophosphate
Inhibited by alpha-amylase inhibitors from wheat and rye. The most effective inhibitors are the wheat tetrameric alpha-amylase inhibitor (WTAI) and the rye dimeric alpha-amylase inhibitor (RDAI-1). Not inhibited by alpha-amylase inhibitor from barley
Allosterically activated by ADP, AMP, or fructose 2,6-bisphosphate, and allosterically inhibited by ATP or citrate
Inhibited by zinc ions at neutral pH. Zinc ions in plasma may keep the enzyme from hydrolyzing inappropriate substrates
Activity is inhibited by thimerosal
Inhibited competitively by AMP and IMP and non-competitively by fructose 1,6-bisphosphate
Stimulated by calcium/calmodulin. Inhibited by NOSIP and NOSTRIN (By similarity)
Can be converted from the dehydrogenase form (D) to the oxidase form (O) irreversibly by proteolysis or reversibly through the oxidation of sulfhydryl groups
IRAK1 and TRAF6 synergistically activate RSAD2 increasing its activity with CTP as substrate about 10-fold
Strongly inhibited by lithium
Activated by magnesium or manganese ions. Inhibited by concentrations of 4-methyl-5-nitrocatechol (MNC) above 2 mM
May be inhibited by divalent cations
Inhibited by NaCl (Probable). Inhibited by GDP in a concentration dependent manner, with an IC(50) value of 93 uM (PubMed:9405391, PubMed:15632313). Also inhibited by GMP and GTP (PubMed:9405391). Inhibited by N-ethylmaleimide (Probable). Activated by poly(ethylene glycol) by enhancing the thermal stability of FUT7 (PubMed:9405391). Activated by Mn2+, Ca2+, and Mg2+ (PubMed:9405391). Both panosialin A and B inhibit activity with IC(50) values of 4.8 and 5.3 ug/ml, respectively (PubMed:10386892). Inhibited by gallic acid (GA) and (-)-epigallocatechin gallate (EGCG) in a time-dependent and irreversible manner with IC(50) values of 60 and 700 nM, respectively (PubMed:15081893)
Inhibited by iodoacetate, iodoacetamide and by high amounts (10 mM) of pyrrole-2-carboxylic acid (PYC). Not inhibited by PYC at 1 mM
Strongly inhibited by glycine and L-alanine. AMP at 10 mM displays a very weak inhibitory effect. The activity of this enzyme is not controlled by adenylation
The first methylation is rate-limiting
Inhibited by heparin
Product-inhibited by both uracil and apurinic/apyrimidinic sites
Activated by phosphorylation at Ser-189
The activity of RuvB is enhanced by E.coli RuvA
Regulated by oxidation of Cys-139 in response to the redox state of the cell. Results in the alternative formation of cystine or glutathione-bound cysteine, the latter modification leading to reduced enzyme activity
ATP inhibits the cADPR hydrolyzing activity
Inhibited by niacin
Both phosphorylation at Thr-172 and binding of a D-type cyclin are necessary for enzymatic activity. Full activation of the cyclin-D-CDK4 complex appears to require other factors such as recruitment of the substrate via a substrate recruitment motif, and/or formation of the CDKN1B ternary complex. Inhibited by INK4 family members. In resting cells, the non-tyrosine-phosphorylated form of CDKN1B prevents phosphorylation at Thr-172 and inactivation, while, in proliferating cells, tyrosine phosphorylation of CDKN1B allows phosphorylation of Thr-172 of CDK4 and subsequennt activation
Inhibited by SERPINA5
Inhibited by sanguinarine
Present in an inactive conformation in the absence of bound ligand. Binding of pdgfa and/or pdgfb leads to dimerization and activation by autophosphorylation on tyrosine residues (By similarity)
Activity is stimulated by AMP
(Microbial infection) Inhibited by ADP-ribosylation
Activated by nitric oxide in the presence of magnesium or manganese ions
Requires the three urease accessory proteins URED, UREF AND UREG for its activation
Inhibited by leupeptin, heparin, and 1.10-phenantroline
Three specific sites, one in the kinase domain (Thr-308) and the two other ones in the C-terminal regulatory region (Ser-473 and Tyr-474), need to be phosphorylated for its full activation
Activated by phosphorylation and inhibited by fructose 1,6-bisphosphate (FBP)
Inhibited by Zn(2+). Inhibited by pyrrole-2-carboxylate and its derivative 2-thiophenecarboxylate
Activity of CodY is modulated by interaction with the branched-chain amino acids (BCAAs) leucine, isoleucine and valine, which are signals of the nutritional status of the cell (PubMed:11401725, PubMed:15228538, PubMed:16040604). Whereas both BCAA and GTP are CodY effectors in B.subtilis, L.lactis CodY responds to the intracellular BCAA concentrations, but not to physiological fluctuations in intracellular GTP (PubMed:15228538)
Activated rapidly in response to an osmotic upshift
Inhibited by 1-isobutyl-3-oxo-3,5,6,7-tetrahydro-2H-cyclopenta[c]pyridine-4-carbonitrile
Inhibited by coumarins, saccharin, sulfonamide derivatives such as acetazolamide (AZA) and Foscarnet (phosphonoformate trisodium salt)
Inhibited by the proteinase inhibitors amprenavir, indinavir, lopinavir, isovaleryl pepstatin, ritonavir and saquinavir
Inhibited by TIMP1, TIMP2 and TIMP3. Inhibited by acetohydroxamic acid and other zinc chelators
Phosphorylation at Thr-170 is required for enzymatic activity. The association of p53/TP53 to the CAK complex in response to DNA damage reduces kinase activity toward CDK2 and RNA polymerase II repetitive C-terminal domain (CTD), thus stopping cell cycle progression (By similarity)
Inhibited by the specific serine esterase inhibitor diisopropylfluorophosphate
Activated by forskolin. After forskolin treatment, activity is further increased by calcium/calmodulin. In the absence of forskolin, calcium/calmodulin has little effect on enzyme activity
Isoform 1 and isoform 3 are activated by phosphate. Inhibited by BPTES. BPTES binds between subunits and favors dissociation of the tetramer into dimers (PubMed:22049910). Inhibited by 6-diazo-5-oxo-L-norleucine (DON) (PubMed:24451979). Enzyme activity is stimulated by phosphorylation (PubMed:22538822)
Helicase activity and function in translation are inhibited by interaction with PDCD4
Positively regulated by the regulatory subunit ppk26/pan3
Kinase activity is activated upon binding to Rho proteins (RHOA, RHOB and RAC1). Activated by lipids, particularly cardiolipin and to a lesser extent by other acidic phospholipids. Activated by caspase-3 (CASP3) cleavage during apoptosis. Two specific sites, Thr-776 (activation loop of the kinase domain) and Ser-918 (turn motif), need to be phosphorylated for its full activation (By similarity)
ATPase activity and YopE secretion are inhibited by selected small-molecule ATPase inhibitors
Increased by L-arginine
Inhibited by 8 mM 1,10-phenanthroline and 10 mM EDTA, but not by PMSF
The apolipoprotein APOC2 acts as a coactivator of LPL activity (By similarity). Ca(2+) binding promotes protein stability and formation of the active homodimer. Interaction with GPIHBP1 protects LPL against inactivation by ANGPTL4 (By similarity)
Constitutively active protein kinase whose activity is not directly affected by phosphorylation. Seems to be regulated by level of expression and localization (By similarity)
Regulated by several post-translational modifications such as ubiquitination/deubiquitination, phosphorylation and O-GlcNAcylation (PubMed:32993960, PubMed:30394292, PubMed:28604766, PubMed:22887999, PubMed:20507985, PubMed:21228273). The enzymatic activity depends on the availability of UDP-GlcUA and UDP-GlcNAc (PubMed:23303191, PubMed:22887999)
Feedback inhibition by glutathione
Azole transport activity is inhibited by milbemycin oxime
8-formyl-7-hydroxy-4-methylcoumarin inhibits the endonuclease activity and prebvent the splicing if the hacA mRNA (PubMed:33087521). The kinase domain is activated by trans-autophosphorylation (By similarity). Kinase activity is required for activation of the endoribonuclease domain (By similarity)
The enzymatic reaction requires the aid of a Rab escort protein (also called component A), such as CHM
Enzyme activity is inhibited by cyclosporin A
Regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP, GTPase activating proteins (GAPs) which increase the GTP hydrolysis activity, and GDP dissociation inhibitors which inhibit the dissociation of the nucleotide from the GTPase
The chaperone activity is regulated by ATP-induced allosteric coupling of the nucleotide-binding (NBD) and substrate-binding (SBD) domains. In the ADP-bound and nucleotide-free (apo) states, the two domains have little interaction. In contrast, in the ATP-bound state the two domains are tightly coupled, which results in drastically accelerated kinetics in both binding and release of polypeptide substrates. J domain-containing co-chaperones stimulate the ATPase activity and are required for efficient substrate recognition
Activated by a cationic detergent cetyl pyridinium chloride (CPC) (PubMed:16185666, PubMed:19557749). Inhibited by phenyl thio-urea (PTU) (PubMed:16185666)
Inhibited by FMN and roseoflavin
Endocytosis and inhibition of the activated EGFR by phosphatases constitute immediate regulatory mechanisms. Moreover, inducible feedback inhibitors may constitute alternative regulatory mechanisms for the EGFR signaling
Activated by interaction with WDR20 and WDR48 through different allosteric mechanisms
Activated by phosphorylation at Tyr-216. In response to insulin, inhibited by phosphorylation at Ser-9 by PKB/AKT1; phosphorylation at this site causes a conformational change, preventing access of substrates to the active site. Inhibited by lithium (By similarity)
Inhibited by free AMP, and with lesser efficiency also by CMP, GMP, UMP, ATP and neomycin
Initially produced in an inactive form and is activated by binding to viral dsRNA, which causes dimerization and autophosphorylation in the activation loop and stimulation of function. ISGylation can activate it in the absence of viral infection. Can also be activated by heparin, pro-inflammatory stimuli, growth factors, cytokines, oxidative stress and the cellular protein PRKRA. Activity is markedly stimulated by manganese ions. Activation is blocked by the cellular proteins TARBP2, DUS2L, NPM1, NCK1 and ADAR (By similarity)
Glutamine synthetase activity is inhibited by methionine sulfoximine (MSO)
Inhibited by the serine esterase inhibitors PMSF (100%), E600 (80%) and THL (22%) (PubMed:17784850). Virtual screening identified a tautomer of ZINC13451138, known inhibitor for HIV-1 integrase, as a potential inhibitor (Probable)
Antibody-mediated surface engagement of the B-cell antigen receptor (BCR) which results in the phosphorylation of BLK on tyrosine residues, stimulates the enzymatic activity
In its inactive state, the C-terminal tail interacts with the catalytic domain and inhibits the kinase activity. Upon ligand binding, the C-terminal tail is displaced and becomes phosphorylated, thus increasing the kinase activity (By similarity)
Binds cyclosporin A (CsA). Is displaced by CsA from the mPTP leading to a lower open probability of the mPTP (By similarity)
Constitutively bound to the bcrABD promoter (PubMed:18227063, PubMed:30777814). Requires bacitracin for activation, probably through a conformational change, such as the oligomerization of inactive dimers to form active tetramers (PubMed:30777814)
In the presence of magnesium, inhibited by oxalate, potassium cyanide, manganese, silver, cadmium and to a lesser extent by succinate, glycolate, iodoacetamide, DL-penicillamine, aluminum, sodium, potassium, lithium and strontium
Stimulated by calcium/calmodulin. Inhibited by n-Nos-inhibiting protein (PIN) which may prevent the dimerization of the protein. Inhibited by NOSIP (By similarity)
Protease activity of LC inhibited by arginine hydroxamate
Stimulated by phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate, activated by the phosphokinase C-alpha, by the ADP-ribosylation factor-1 (ARF-1), and to a lesser extent by GTP-binding proteins: RHO A, RAC-1 and CDC42. Inhibited by oleate
Strongly inhibited by phenylmethylsulfonyl fluoride (PMSF)
Phospholipase activity is specifically activated upon 3',3'-cGAMP binding, which is produced by the cognate cyclic nucleotide synthase encoded in the same operon
Inactivated by bipyridine and p-chloromercuribenzoate
Activity is stimulated in the presence of Mn(2+), Ca(2+) or Mg(2+)
Inhibition of cytotoxic activity by phenylmethylsulfonyl fluoride
Activated by calcium. Autophosphorylation may play an important role in the regulation of the kinase activity (By similarity)
The cholesterol efflux is enhanced by APOA1
Activated by phosphorylation by FYN
Present in an inactive conformation in the absence of bound ligand. Binding of PDGFB and/or PDGFD leads to dimerization and activation by autophosphorylation on tyrosine residues (By similarity)
Inhibited by benzamil and quinine but not by amiloride
Inhibited by zinc and copper
Activity subject to allosteric control by arginine and citrate, which function as positive and negative effectors, respectively
Inhibited by interaction with the PCNA inhibitor TIP
Inhibited by wortmannin. Increased kinase activity upon interaction with NCS1/FREQ
Ca(2+) does not affect the enzyme activity nor the thermostability. Other cations, such as Mg(2+), Mn(2+), Cu(2+), Zn(2+), Ag(+) or Hg(2+) do not cause any serious adverse effect on the activity. Also no significant change in the activity in response to the addition of 1 mM EDTA
Activated by Ca(2+)-bound calmodulin following an increase in intracellular Ca(2+) (PubMed:16411749). At low Ca(2+) concentrations, the catalytic subunit (also known as calcineurin A) is inactive and is bound to the regulatory subunit (also known as calcineurin B) in which only two high-affinity binding sites are occupied by Ca(2+) (By similarity). In response to elevated calcium levels, the occupancy of the low-affinity sites on calcineurin B by Ca(2+) causes a conformational change of the C-terminal regulatory domain of calcineurin A, resulting in the exposure of the calmodulin-binding domain and in the partial activation of calcineurin A (PubMed:16411749). The subsequent binding of Ca(2+)-bound calmodulin leads to the displacement of the autoinhibitory domain from the active site and possibly of the autoinhibitory segment from the substrate binding site which fully activates calcineurin A (By similarity). Inhibited by immunosuppressant drug FK506 (tacrolimus) in complex with FKBP12 and also by immunosuppressant drug cyclosporin A (CsA) in complex with PPIA/cyclophilin A; the inhibition is Ca(2+)-dependent (PubMed:1715244)
Methyltransferase activity is partially inhibited (20% reduction) by phage T7 protein OCR (AC P03775, gene 0.3). Viability of cells overexpressing OCR is unaffected
Activated by phosphorylation at Ser-234
Activity is inhibited by phenylmethylsulfonyl fluoride and chymostatin
Can function alone, but full activity requires the presence of the non-peptidase homolog YmxG
Degraded by ASP after secretion and dissociation of the ASP-ORF2 complex
In liver, recruited to target gene promoters following treatment with dexamethasone and cAMP. Binding is decreased in presence of insulin
Shows pH-dependent activity
The regulatory subunit ILV6 stimulates enzymatic activity seven- to tenfold and confers sensitivity to inhibition by valine and activation by ATP
Inhibited by pepstatin
Phosphorylation at Thr-33 or Tyr-34 inactivates the enzyme
Repressor activity is regulated by binding of different sugars to TrmBL1. Binding of maltose and maltotriose results in derepression of the target genes. However, high sugar concentration results in formation of octamers with high affinity for DNA, which may prevent transcription of target genes
Inhibited by unphosphorylated OdhI, but not by phosphorylated OdhI
ATPase activity inhibited by EDTA (PubMed:26396239)
The cysteine-reactive reagent p-chloromercuribenzoic acid (pCMB) strongly decreased the ACOT activity. The serine esterase inhibitors phenylmethylsulfonyl fluoride (PMSF), diisopropylfluorophosphate (DFP) and bis-(4-nitrophenyl)phosphate (BNPP) moderately reduced the ACOT activity. The histidine-reacting reagent diethyl pyrocarbonate (DEPC) has no effect on the ACOT activity
Inhibited by 4-hydroxybenzoate, vanillate, 4-hydroxybenzaldehyde and 3-carboxymethylaminomethyl-4-hydroxybenzoic acid
Feedback inhibited by tryptophan
Inhibited by 1 mM Co(2+), Cu(2+), Zn(2+) or Fe(2+). Non-competitively inhibited by S-adenosyl-L-homocysteine. Competitively inhibited by 2'-O-methylisoliquiritigenin
Activity is inhibited by binding to OTUB1, which prevents 'Lys-63'-linked polyubiquitination (By similarity). Activity is inhibited by GPS2, leading to prevent 'Lys-63'-linked polyubiquitination (By similarity)
The metal ion affects the meta and para-regiospecificity of the enzyme as well as the enzyme activity and thermal stability
Inhibited by sodium orthovanadate and peroxovanadium compounds, and by pentamidine
Inhibited by the pyrrole-indolinone inhibitor SU11274 (K00593): intercalates between the ATP-binding Lys-65 and alpha-C glutamate (Glu-81), resulting in a partial disordering of the lysine side chain. Also specifically inhibited by erlotinib. Slightly inhibited by gefitinib (By similarity)
Inhibited by Mg(2+)
Allosterically regulated by several compounds including AMP, NAD(+), and citrate
Inhibited by sphingosine (By similarity). Activity is Ca(2+)-dependent (PubMed:17713573)
Inhibited by its anionic phospholipid end products, with phosphatidylinositol-(4,5)- bisphosphate showing the strongest inhibition
Only weakly inhibited by acifluorfen, in contrast to eukaryotic family members (PubMed:8288631, PubMed:9784236, PubMed:19944166). Weakly inhibited by methylacifluorfen (PubMed:9784236). Bilirubin, biliverdin and hemin are all competitive inhibitors (PubMed:9784236)
Contains an N-terminal autoinhibitory domain
Activated by Ser-520 phosphorylation by HOG1
Inhibited by barbituric acid
The formation of the proteasomal ATPase ARC-20S proteasome complex, likely via the docking of the C-termini of ARC into the intersubunit pockets in the alpha-rings, may trigger opening of the gate for substrate entry. Interconversion between the open-gate and close-gate conformations leads to a dynamic regulation of the 20S proteasome proteolysis activity
Stimulated about twofold by phospholipids or phorbol esters
Activated by hypophosphorylated form of ATG13 (present in nitrogen starvation conditions). Also activated by autophopsphorylation of Thr-226 and inhibited by phosphorylation of Ser-34 (By similarity)
Regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP, GTPase activating proteins (GAPs) which increase the GTP hydrolysis activity and GDP dissociation inhibitors which inhibit the dissociation of the nucleotide from the GTPase. Activated by GEFs such as ARHGEF2, ARHGEF3, ARHGEF28 and BCR. Inhibited by GAPs such as ARHGAP30. Inhibited by GDP dissociation inhibitors such as ARHGDIA
The heterotetramer and the heterodimer composed of IDH3A and IDH3G subunits can be allosterically activated by citrate (CIT) or/and ADP, and the two activators can act independently or synergistically. The heterodimer composed of IDH3A and IDH3B subunits cannot be allosterically regulated and the allosteric regulation of the heterotetramer is through the IDH3G subunit and not the IDH3B subunit. The IDH3G subunit contains the allosteric site which consists of a CIT-binding site and an ADP-binding site, and the binding of CIT and ADP causes conformational changes at the allosteric site which are transmitted to the active site in the catalytic subunit (IDH3A) through a cascade of conformational changes at the heterodimer interface, leading to stabilization of the isocitrate-binding at the active site and thus activation of the enzyme. ATP can activate the heterotetramer and the heterodimer composed of IDH3A and IDH3G subunits at low concentrations but inhibits their activities at high concentrations, whereas ATP exhibits only inhibitory effect on the heterodimer composed of IDH3A and IDH3B subunits
Inhibited by phosphorylation at Ser-219. Activated by phosphorylation on Thr-215 (By similarity)
Inhibited by Cu(2+) or Zn(2+)
Has different conformational states with differential Ca2+ affinity. The E1 conformational state (active form) shows high Ca(2+) affinity, while the E2 state exhibits low Ca(2+) affinity. Reversibly inhibited by phospholamban (PLN) at low calcium concentrations (PubMed:22971924). Inhibited by sarcolipin (SLN) and myoregulin (MRLN). The inhibition is blocked by VMP1 (By similarity). Enhanced by DWORF; DWORF increases activity by displacing sarcolipin (SLN), phospholamban (PLN) and myoregulin (MRLN) (By similarity). Stabilizes SERCA2 in its E2 state (By similarity)
Activated by mannosylphosphoryldolichol and phospholipids such as phosphatidylglycerol and phosphatidylcholine (Probable). Inhibited by natural nucleoside antibiotic tunicamycin, which acts as a structural analog and competitor of UDP-GlcNAc (PubMed:9451016, PubMed:29459785, PubMed:30388443)
Exists in an autoinhibited state in the absence of substrate protein, due to interactions of the leucine-rich repeats with NEL domain. Is activated upon binding to a substrate protein
Not inhibited by hirudin
Positively regulated by the regulatory subunit par-2/pan3
Inhibited by diphosphate
Inhibited by estradiol
Is irreversibly inactivated by the beta-lactams carbapenems via the formation of a covalent adduct resulting from enzyme acylation; imipenem is the most efficient drug for in vitro LdtMt3 inactivation
Azoreductase activity increases with salt strength
Activated by cAMP
Aromatic carboxylates are competitive inhibitors
The activity of this enzyme could be controlled by adenylation under conditions of abundant glutamine
Inhibited by 5-adeninylpentylcobalamin (AdePeCbl), a cofactor analog (PubMed:19762342). Irreversibly inhibited during catalysis by cleavage of the Co-C bond of the cobalamin coenzyme (Probable) (PubMed:19762342). Reactivated by EutA, which probably involves an ATP-dependent cobalamin exchange (PubMed:15466038)
Not inhibited by 1 uM borrelidin (BN); probably does not bind BN
Phosphorylation by KIN10 is required to positively regulates embryogenesis, seed yield, and plant growth at high temperature
Activity is regulated by phosphorylation at Ser-49 and Ser-52, which stabilizes the eIF2/GDP/eIF-2B complex and prevents the eIF-2B-mediated exchange of GDP for GTP, thereby preventing the formation of the 43S pre-initiation complex (43S PIC). This results in the global attenuation of 5' cap-dependent protein synthesis and concomitant translation of ISR-specific mRNAs that contain a short upstream open reading frame (uORF) in their 5' UTR
Activation by Thr-186 phosphorylation is calcium Ca(2+) signaling pathway-dependent; actively inactivated by dephosphorylation mediated by PPP1CA, PPM1A and PPM1B. Reversibly repressed by acetylation at Lys-44 and Lys-48 (By similarity)
Inhibited by (2-hydroxyphenyl)amino sulfinyl acetic acid 1,1-dimethylethyl ester, by DEPC and by N-ethylmaleimide
Increase of iodide influx inhibited by addition of perchlorate (NaClO(4)), a competitive inhibitor of iodide uptake catalyzed by sodium iodide symporter (NIS) (PubMed:12107270). Cotransport of monocarboxylates and nicotinate strongly inhibited by probenecid, nonsteroid anti-inflammatory drugs (ibuprofen, fenoprofen, ketprofen, naproxen) in a Na(+)-dependent manner or by prolonged exposure to external concentrations of monocarboxylates (PubMed:15090606, PubMed:16729224)
Activity is greater under oxic conditions and is regulated by the formation of a reversible disulfide-bond between Cys-291 and Cys-294
The full-length protein before cleavage is inactive: intramolecular interactions between N- and C-terminal domains mediate autoinhibition in the absence of activation signal (By similarity). The intrinsic pyroptosis-inducing activity is carried by the released N-terminal moiety (Gasdermin-E, N-terminal) following cleavage by CASP3 or granzyme B (GZMB) (By similarity). Activated by NLRP1 in the absence of GSDMD expression: NLRP1 cleaves and activates CASP8, promoting downstream activation of CASP3 and subsequent activation of GSDME (PubMed:33852854)
Taurine transport activity is inhibited by hypotaurine and beta-alanine
Inhibited by calcium-activated calmodulin (By similarity). Activated by ATP (PubMed:18937505, PubMed:17895289). Inhibited by bromoenol lactone (BEL) (PubMed:18937505, PubMed:17895289)
D-glucose and maltose competitively inhibit fructose transport. D-glucose, D-fructose and maltose inhibit deoxyglucose transport
Strongly inhibited by isoascorbic acid, 4-hydroxyacetophenone and chloromercuriphenylsulphonate. Stimulated by various salts
Allosterically regulated by ATP and dNTP
Phosphatase activity is stimulated by phosphorylation (PubMed:25535696). Inhibited by sodium molybdate, sodium orthovanadate and sodium tungstate (PubMed:10986245, PubMed:17975835). Inhibited by S-nitrosylation (PubMed:20830431, PubMed:23102706). Subjected to substrate activation, triggered by pNPP or by phosphotyrosine. Is also activated by phosphoserine, with serine being ineffective in enhancing PtpA activity (PubMed:32142609)
Each monomer binds on GSH molecule but only one subunit is catalytically active
Specifically inhibited by the pseudodipeptide CQ31 (PubMed:35165443). Inhibition by CQ31 indirectly activates the CARD8 inflammasome: dipeptide accumulation following PEPD inactivation weaky inhibit dipeptidyl peptidases DDP8 and DPP9, relieving DPP8- and/or DPP9-mediated inhibition of CARD8 (PubMed:35165443)
Phosphorylation at Thr-14 or Tyr-15 inactivates the enzyme, while phosphorylation at Thr-160 activates it. Stimulated by MYC. Inactivated by CDKN1A (p21) (By similarity)
The proteolytic activity of the heterodimer of A and B subunits requires Zn(2+) and Ca(2+) ions
Inhibited by glutamine
The dipeptidyl carboxypeptidase activity is strongly activated by chloride. The dipeptidyl carboxypeptidase activity is specifically inhibited by lisinopril, captopril and enalaprilat
Strongly inhibited by lisinopril and captopril
Inhibited by oxaloacetate
Is potently inhibited by the sulfone dapsone and the two sulfonamides sulfamethoxazole and sulfamethoxypyridazine, with Kis in the range of 12 to 32 nM. To a lesser extent, is also inhibited by p-aminosalicylate (PAS)
Inhibited by P1-(adenosine-5')-P3-(nicotinamide-riboside-5')-triphosphate (Np3AD) and P1-(adenosine-5')-P4-(nicotinamide-riboside-5')-tetraphosphate (Np4AD)
Inhibited by ancymidol and ketoconazole
Inhibited by flavonoids including apigenin, luteolin, genistein, kaempferol and quercetin and also by carbenoxolone, zearalenone, glycyrrhetinic, curcumin and flufenamic acid
Inhibited by leupeptin
Activated by Co(2+). Inhibited by EDTA and o-phenanthroline (in vitro)
Toxin complex is secreted when grown at 25 degrees Celsius or less; at higher temperatures the proteins are present intracellularly but not secreted
This alpha subunit is resistant to ouabain
Inhibited by DTT, N-bromosuccinimide and iodoacetic acid
Requires cadmium for activity
Under resting conditions, NLRP3 binds ADP and is autoinhibited (PubMed:35114687). Inactive NLRP3 forms homodecameric double-ring cages that hide pyrin domains within NACHT-LRR rings to avoid premature activation (PubMed:35114687). NLRP3 activation stimuli include extracellular ATP, nigericin, reactive oxygen species, crystals of monosodium urate or cholesterol, amyloid-beta fibers, environmental or industrial particles and nanoparticles, such as asbestos, silica, aluminum salts, cytosolic dsRNA, etc (PubMed:16407889, PubMed:18604214, PubMed:18403674, PubMed:19414800, PubMed:35114687). Activated upon human coronavirus SARS-CoV-2 infection (PubMed:33231615, PubMed:34133077). Almost all stimuli trigger intracellular K(+) efflux (By similarity). These stimuli lead to membrane perturbations that induce activation of NLRP3 (By similarity). Upon activation, NLRP3 is transported to microtubule organizing center (MTOC), where it is unlocked by NEK7, leading to its relocalization to dispersed trans-Golgi network (dTGN) vesicle membranes and recruitment of PYCARD/ASC for the formation of an active inflammasome complex (PubMed:30487600, PubMed:30612879, PubMed:36442502). NEK7-activated NLRP3 forms a disk-shaped inflammasome (PubMed:36442502). NLRP3 and PYCARD/ASC interact via their respective pyrin domains; interaction initiates speck formation (nucleation) which greatly enhances further addition of soluble PYCARD/ASC molecules to the speck in a prion-like polymerization process (PubMed:24630722, PubMed:28465465, PubMed:27432880, PubMed:35559676, PubMed:36142182, PubMed:36442502). Clustered PYCARD/ASC nucleates the formation of CASP1 filaments through the interaction of their respective CARD domains, acting as a platform for CASP1 polymerization and activation (PubMed:24630722). Active CASP1 then processes IL1B and IL18 precursors, leading to the release of mature cytokines in the extracellular milieu and inflammatory response (PubMed:24630722). NLRP3 inflammasome assembly is inhibited by IRGM, which impedes NLRP3 oligomerization (PubMed:30612879). Specifically inhibited by sulfonylurea MCC950 (also named CP-456,773, CRID3), a potent and specific small-molecule inhibitor of the NLRP3 inflammasome that acts by preventing ATP hydrolysis (PubMed:25686105, PubMed:31086327, PubMed:31086329, PubMed:34687713, PubMed:35114687, PubMed:35254907)
FtsK is required for efficient recombination
Activated following phosphorylation at Thr-182 by p38-alpha/MAPK14, p38-beta/MAPK11, ERK2/MAPK1, ERK3/MAPK6, and ERK4/MAPK4. Activated by stress-related extracellular stimuli; such as H(2)O(2), arsenite, anisomycin TNF alpha and also PMA and the calcium ionophore A23187; but to a lesser extent. In vitro, activated by SQSTM1. Inhibited by diterpenoid alkaloid noroxoaconitine
FtsK is required for recombination
Inhibited by the phenyltriazole acetic acid compound [5-(4-chlorophenyl)-1-isopropyl-1H-[1,2,4]triazol-3-yl]-acetic acid (DAS734), a bleaching herbicide
Activated by micromolar concentrations of calcium and inhibited by calpastatin
Kept in an inactive conformation by FKBP1A preventing receptor activation in absence of ligand. CD109 is another inhibitor of the receptor (By similarity)
Inhibited by FK506
Inhibited by iodoacetate, iodoacetamide and by high amounts (10 mM) of pyrrole-2-carboxylate (PYC). Not inhibited by PYC at 1 mM
Inhibited by transition metal ions including Ni(2+), Zn(2+), and Cu(2+) and by sulfhydryl-blocking agents
Inhibited by L-penicillamine. Inhibited by cilastatin
Inhibited by Cu(2+) and Zn(2+)
Regulated by a mechanism involving lumenal C-terminus region; a fine-tuned balance between photoprotective energy dissipation in high light and a maximum quantum yield in low light involves a reduced activity under high light
Inhibited by erythrose 4-phosphate and 6-phosphogluconate
Partially inhibited by concentrations of FAD above 10 uM and completely inhibited by concentrations above 50 uM
DNA-binding activates the protease activity: single-stranded DNA-binding specifically activates ability to cleave covalent DNA-protein cross-links (DPCs) (PubMed:27871366, PubMed:27871365, PubMed:30893605). In contrast, double-stranded DNA-binding specifically activates autocatalytic cleavage, and subsequent inactivation (PubMed:27852435, PubMed:27871365, PubMed:30893605)
The most important regulatory mechanism of these opposing activities is by phosphorylation and dephosphorylation of the enzyme
Inhibited by the propeptide before the second cleavage. Inhibited by ethylenediaminetetraacetic acid (EDTA), ZnSO(4) and chloroketone DEC-RVKR-CMK
Several specific inhibitors are being developed and tested (PubMed:27214403, PubMed:26741168). The inhibitor KDOAM-25 inhibits its demethylase activity, resulting to cell cycle arrest in myeloma cells (PubMed:28262558)
Ras proteins such as HRAS mediate the activation of RAF proteins such as RAF1 or BRAF which in turn activate extracellular signal-regulated kinases (ERK) through MAPK (mitogen-activated protein kinases) and ERK kinases MAP2K1/MEK1 and MAP2K2/MEK2 (PubMed:29433126). Activation occurs through phosphorylation of Ser-218 and Ser-222 (By similarity). MAP2K1/MEK1 binds KSR1 or KSR2 releasing the inhibitory intramolecular interaction between KSR1 or KSR2 protein kinase and N-terminal domains (PubMed:29433126). This allows KSR1 or KSR2 dimerization with BRAF leading to BRAF activation and phosphorylation of MAP2K1 (PubMed:29433126). MAP2K1/MEK1 is also the target of negative feed-back regulation by its substrate kinases, such as MAPK1/ERK2. These phosphorylate MAP2K1/MEK1 on Thr-292, thereby facilitating dephosphorylation of the activating residues Ser-218 and Ser-222. Inhibited by serine/threonine phosphatase 2A (By similarity). Many inhibitors have been identified including pyrrole derivatives, TAK-733 (one of a series of 8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione derivatives), CH4987655 and RDEA119/BAY 869766 (PubMed:21310613, PubMed:20621728, PubMed:19706763, PubMed:19019675, PubMed:19161339, PubMed:18951019, PubMed:17880056, PubMed:15543157)
Inhibited by L-arginine
Activated by threonine and tyrosine phosphorylation by two dual specificity kinases, MAP2K4 and MAP2K7. MAP2K7 phosphorylates MAPK10 on Thr-221 causing a conformational change and a large increase in Vmax for the enzyme. MAP2K4 then phosphorylates Tyr-223 resulting in a further increase in Vmax. Inhibited by dual specificity phosphatases, such as DUSP1 (By similarity). Inhibited by HDAC9
Inhibited by the C-terminal non-catalytic region. Activated by caspase-cleavage. Full activation also requires homodimerization and autophosphorylation of Thr-180, which are inhibited by the proto-oncogene product RAF1. Activated by RASSF1 which acts by preventing its dephosphorylation
Transport activity exhibits steep dependence on substrate concentration. Substrate concentration sensitivity of SLC16A7 arises from the strong inter-subunit cooperativity of the SLC16A7 dimer during transport. Inhibited by AR-C155858
Insensitive to pentalenolactone, an inhibitor of bacterial and eukaryotic GAPDH. Activity in vitro is significantly stabilized by potassium citrate
Activated by calcium. Upon calcium binding to the EF-hand domain 2, the C-terminus of the junction domain (J domain) undergoes a conformational change which results in the dissociation of the pseudo-substrate inhibitory motif from the catalytic domain (By similarity). This, in turn, may facilitate the autophosphorylation of the activation loop at Thr-273, which leads to the kinase activation (By similarity)
Selectively inhibited by DO264 (N-3-pyridyl-N'-(1-[3-chloro-4-{2-chloro-4-(trifluoromethoxy)phenoxy}pyridine-2-yl]piperidin-4-yl)thiourea)
Allosterically inhibited by 3'-phosphoadenosine 5'-phosphosulfate (PAPS)
Li(+) activates Na(+)/H(+) exchanger
Inhibited by the toxins okadaic acid, tautomycin and microcystin Leu-Arg. The phosphatase activity of the PPP1R15A-PP1 complex toward EIF2S1 is specifically inhibited by Salubrinal, a drug that protects cells from endoplasmic reticulum stress (By similarity)
Glycerol dehydrogenation is highly activated by NH(4+), K(+) or Rb(+), but strongly inhibited by Cu(2+), Ca(2+), the thiol reagent N-ethylmalemide, and the chelating agents 8-hydroxyquinoline and 1,10-phenanthroline (PubMed:40950). 1-amino-2-propanol oxidation by the homooctameric form is strongly inhibited by numerous divalent transition metal ions, p-mercuribenzoate and dithiodipyridine (PubMed:6365902)
ATPase activity is inhibited or reduced by lowering pH from 9.0 to 7.0, and by addition of Ca(2+), EDTA, KNO(3) or by treatment with N-ethylmaleimide (NEM)
Allosterically activated by phosphatidylserine and/or phosphatidylinositol 4-phosphate (PtdIns(4)P), and phosphatidylinositol 5-phosphate (PtdIns(5)P) (By similarity). Interaction with MTMR9 increases catalytic activity towards phosphatidylinositol 3,5-bisphosphate (By similarity)
The L-glutamate uniporter activity exhibits a biphasic dependence on chloride concentration. Chloride channel activity is allosterically activated by lumenal H(+) and Cl(-) leading to synaptic vesicles acidification. The L-glutamate transport activity is allosterically activated by lumenal H(+) and Cl(-), preventing non-vesicular L-glutamate release
Requires K(+) for maximal activity
Binds cyclosporin A (CsA). CsA mediates some of its effects via an inhibitory action on PPIase
Activated in a reduced environment which promotes the reduction of the disulfide bond between the regulatory Cys-52 and the catalytic Cys-107 residues (By similarity). Inhibited by sodium orthovanadate (PubMed:16151248)
Oxidation at Cys-197 leads to inactivation of channel activity
Activated by calcium (PubMed:22320399). Activated by protein kinase A (PKA)-mediated phosphorylation (PubMed:22320399)
The matrix-open state (m-state) is inhibited by the membrane-permeable bongkrekic acid (BKA). The cytoplasmic-open state (c-state) is inhibited by the membrane-impermeable toxic inhibitor carboxyatractyloside (CATR) (By similarity). Proton transporter activity is inhibited by ADP:ATP antiporter activity (By similarity)
Inhibited by RARRES1
Phosphorylation at Ser-462 inhibits catalytic activity. Dephosphorylation at Ser-462 by PTC7 enhances catalytic activity
Activated by phosphorylation at Ser-355 (PubMed:20008556). May be activated by svh-2-mediated phosphorylation (PubMed:23072806, PubMed:22388962)
Activated by binding to RABE1D
Resistant to pentalenolactone (PL)
Inhibited by haloxydine (3,5-dichloro-2,6-difluoro-4-haloxypyridine)
Zinc ions stimulate the exonuclease activity
Inhibited by UDP-D-galacturonate
Autophosphorylated when the cells enters mitosis
Phosphorylated and activated by cyclin-dependent kinase 1 (Cdk1/CDC28) (PubMed:19150427). Loses its lipolytic activity in cells lacking nonpolar lipids, but retains its side activity as lysophospholipid acyltransferase (PubMed:27170177)
Almost completely inhibited by paraoxon (PubMed:19225166). Inhibited by tetrahydrolipstatin (THL), a specific lipase inhibitor (PubMed:20103719)
Inhibited by poly(L-proline) only at very high concentrations
Its proteolytic activity is autoinhibited by the non-covalent binding of the propeptide to the catalytic domain. Inhibited by EGTA (By similarity)
Activated by magnesium ions
Phosphorylation at Thr-14 or Tyr-15 inactivates the enzyme, while phosphorylation at Thr-161 activates it
Serine/threonine-protein kinase activity is directly stimulated by TOPBP1. ATR kinase activity is also directly activated by ETAA1, independently of TOPBP1. Activated by DNA and inhibited by BCR-ABL oncogene. Slightly activated by ATRIP. Inhibited by caffeine, wortmannin and LY294002
Rab activation is generally mediated by a guanine exchange factor (GEF), while inactivation through hydrolysis of bound GTP is catalyzed by a GTPase activating protein (GAP)
Inhibited by GdCl3. Requires K(+) for maximal activity. K(+) greatly stimulates Na(+) binding. Thermostability depends on the binding of Mg(2+)
Inhibited by menadione and isovanillin. Not inhibited by allopurinol, a xanthine dehydrogenase potent inhibitor. Inhibited by the flavonoids quercetin, myricetin and genistein. Nitric oxide generation is inhibited by raloxifene and competitively inhibited by an increase in oxygen levels
Activated by HadI
Phosphatase activity is specifically inhibited by 5-((5-chloro-2-methoxyphenyl)sulfonamido)nicotinamide (SBI-425)
Isomerase activity is increased by sulfhydril compounds. Dithiothreitol (DTT) is most effective, followed by dihydrolipoic acid, glutathione (GSH) and 2-mercaptoethanol
Inhibited by magnesium above 10 mM and metal chelators such as 1, 10-phenanthroline and EDTA
Competitively inhibited by N-(5-(azepan-1-ylsulfonyl)-2-methoxyphenyl)- 2-(4-oxo-3,4-dihydrophthalazin-1-yl)acetamide
GTP shows a positive allosteric effect, and tetrahydrobiopterin inhibits the enzyme activity
The two-component system is activated by envelope stress such as overexpression of some (misfolded) periplasmic proteins (PubMed:7883164, PubMed:9351822). Activated by spheroplasting (which removes the periplasm) in an autoregulatory cpxA-cpxR-dependent fashion (PubMed:10972835). Cpx two-component system is activated at pH 8.0; in a degP deletion mutant activation is halved (PubMed:9473036, PubMed:16166523). The CpxA kinase activity is inhibited by periplasmic accessory protein CpxP; proteolysis of CpxP relieves inhibition (PubMed:16166523, PubMed:17259177, PubMed:25207645)
Inhibited by vanadate analogs
Both catalytic activities are inhibited by N-ethylmaleimide and are up-regulated during senescence
The activity is regulated by glucose levels. Activated by fructose-1,6-bisphosphate
Inhibited by sarcolipin (SLN), phospholamban (PLN) and myoregulin (MRLN) (By similarity). Enhanced by DWORF; DWORF increases activity by displacing sarcolipin (SLN), phospholamban (PLN) and myoregulin (MRLN) (By similarity)
DNA supercoiling is inhibited by fluoroquinolones; IC(50) 1 ug/ml for sitafloxacin (PubMed:17325221)
Not inhibited by sodium borohydride or sodium pyruvate. Unaffected by EDTA, EGTA, Mn(2+), Mg(2+) and Ca(2+)
Inhibited by divalent copper and zinc ions, but not by nickel or cobalt. Inhibited by its prosegment, but not smaller fragments. Inhibited by 4-(2-aminoethyl)benzenesulfonyl fluoride (AEBSF), a serine protease inhibitor
Interaction with DotL is critical for the export of IcmSW-dependent substrates
Activity is enhanced by binding to the pyruvate dehydrogenase subunit DLAT. Inhibited by AZD7545; this compound interferes with DLAT binding and thereby inhibits kinase activity. Inhibited by dichloroacetate and radicicol
Lipase activity is maximal at a lipid-water interface (interfacial activation), probably by an induced conformational change that results in an increased accessibility of the active site to the substrate
Inhibited by intrinsic factor and iodoacetic acid. Competitively inhibited by itaconate, mesaconate, succinate, 1-methyl-1,2-trans-clycopropane, dicarboxylate and L-malate. Non-competitively inhibited by glutaconate and 1-methyl-1,2-cis-cyclopropanedicarboxylate. Not inhibited by acrylate or by the chelating agents alpha,alpha-dipyridyl or EDTA. Not activated by Fe(2+), Mg(2+), Mn(2+) or Ca(2+). Unaffected by K(+), Na(+), NH4(+), Rb(+) or Li(+)
Allosterically inhibited by the N-terminal domain. Inhibited by phloretin
Negatively regulated by lysine acetylation
Inhibited by phenyalanine
Exhibits substrate-dependent heparin activation
Allosteric activation by glucose-6-phosphate. Phosphorylation reduces the activity towards UDP-glucose. When in the non-phosphorylated state, glycogen synthase does not require glucose-6-phosphate as an allosteric activator; when phosphorylated it does (By similarity)
Lipopolysaccharide inhibits pore-forming activity, explaining why is bactericidal for Gram-positive but not Gram-negative bacteria
Glyceraldehyde-3-phosphate dehydrogenase activity is inhibited by fumarate, via the formation of S-(2-succinyl)cysteine residues
Insensitive to inhibition by rapamycin
Loses its lipolytic activity in cells lacking nonpolar lipids, but retains its side activity as lysophospholipid acyltransferase
Inhibited strongly by 3,4-dichloroisocoumarin, bestatin and heavy metal ions. Inactivated by p-chloromercuribenzoate, but reactivated by dithiothreitol
Specifically inhibited by heterocyclic compound CBR-470-0
Homodimerization via the leucine zipper domains is required for autophosphorylation and subsequent activation (By similarity). Activated by C6-ceramide
Alpha-ketoglutarate dehydrogenase and decarboxylase activities are inhibited by unphosphorylated GarA, and allosterically activated by acetyl-CoA, the main substrate of the TCA cycle
Non-allosteric
Activated by RHOA binding. Inhibited by Y-27632
Allosteric enzyme which is feedback inhibited by dTTP and activated by a number of dNDP and dNTP
Activated by hyperosmotic stress and abscisic acid (ABA)
Conformation of the Ffh-FtsY complex and regulation of its GTPase activity are modulated by the 4.5S RNA. Formation of the FfH-FtsY complex leads to a mutual stimulation of both GTPases
Inhibited by 4-(2-aminoethyl)-benzensulfonyl fluoride. Not inhibited by antithrombin-III
Activated by magnesium and inorganic phosphate. Competitively or non-competitively inhibited by ADP, 2,3-bisphosphoglyceride or GDP (By similarity)
Inhibited by bee venom neurotoxin apamin (PubMed:9287325, PubMed:17142458). Inhibited by d-tubocurarine and tetraethylammonium (TEA) (PubMed:9287325, PubMed:17142458)
Activity is increased in the presence of K(+)or Na(+)
Allosterically inhibited by NADH
Inhibited by the VDCC blocker verapamil in yeast cells. Channel activity may be down-regulated by cytosolic Ca(2+) in rice cells. Inhibited by Al(3+) (By similarity)
Inhibited by fosmidomycin and its derivatives
Inhibited by zinc ions. Competitive inhibition of dGMP hydrolysis by GMP and 6-methylthio-GMP
In the autoinhibited state the side chain of Phe-463 inserts into a hydrophobic groove in RING-0, occluding the ubiquitin acceptor site Cys-431, whereas the REP repressor element binds RING-1 and blocks its E2-binding site. Activation of PRKN requires 2 steps: (1) phosphorylation at Ser-65 by PINK1 and (2) binding to phosphorylated ubiquitin, leading to unlock repression of the catalytic Cys-431 by the RING-0 region via an allosteric mechanism and converting PRKN to its fully-active form. According to another report, phosphorylation at Ser-65 by PINK1 is not essential for activation and only binding to phosphorylated ubiquitin is essential to unlock repression
Inhibition by zinc ions
Interaction with PknI increases the peroxidase activity by several folds
Stimulated by reducing agents such as dithiothreitol (DTT)
Activated in response to a variety of cellular stresses, including UV and gamma-irradiation, heat shock, hyperosmolarity, T-cell receptor stimulation, peroxide and inflammatory cytokines. Also activated by developmental cues. MAP2K4/MKK4 is activated by the majority of MKKKs, such as MAP3K5/ASK1, MAP3K1/MEKK1, MAP3K7/TAK1, MAP3K10/MLK2, MAP3K11/MLK3, MAP3K12/DLK and MAP3K13/LZK
ATPase activity is stimulated by microtubules, which promote homooligomerization. ATP-dependent microtubule severing is stimulated by interaction with KATNB1
Binding of cGMP results in enzyme activation
In contrast to mouse protein, not activated by anticancer molecule 5,6-dimethylxanthenone 4-acetic acid (DMXAA)
Inhibited by borate, fluoride, L-Asn and L-Asp
Activated by calcium-binding in the mitochondrial intermembrane space (PubMed:11566871). Inhibited by pyridoxal 5'-phosphate, bathophenathroline, mercurials, diethyl pyrocarbonate and N-ethylmaleimide (PubMed:11566871)
Inhibited by nickel, cobalt, calcium and magnesium
Activated by phosphorylation on Thr-807. Catalytically active only when complexed with MAP3K5, with MAP3K5 supporting the stability and the active configuration of MAP3K6 and MAP3K6 activating MAP3K5 by direct phosphorylation
Redox regulation; active in reducing conditions, inactive in oxidizing conditions. Thioredoxins f and m mediate the reversible reductive activation of oxidized CHLI1
Activated by cytosolic calcium, which is necessary for binding to membrane lipids. Activated by phosphorylation in response to mitogenic stimuli
Binding to DNA is allosterically inhibited by an effector molecule (PubMed:20047956, PubMed:21602348, PubMed:24673833, PubMed:25564531). Binding of the effector to the C-terminal domain leads to a conformational change that modulates binding to DNA and thereby regulates transcription of the target genes (PubMed:20047956, PubMed:25564531). Glucosamine-6-phosphate (GlcN6P) and/or N-acetylglucosamine-6-phosphate (GlcNAc6P) are putative effectors of NagR (PubMed:20047956, PubMed:21602348, PubMed:24673833, PubMed:25564531). Binding of GlcNAc6P may prevent the protein-protein interactions responsible for polymerization along the DNA, but not the specific DNA binding (PubMed:24673833)
Weakly inhibited by oxaloacetate, 2-oxoglutarate, and citrate. Severely inhibited by oxaloacetate plus glyoxylate
Feedback inhibition by threonine
Inhibited by chloride ions (PubMed:34116754). Inhibited by citrate (PubMed:34116754). Inhibited by oxalate (PubMed:34116754). Activated by acetate (PubMed:34116754)
Can be regulated by protein kinase C-dependent phosphorylation
Appears to be allosterically activated by the binding of pArg-containing polypeptides to the pArg-binding pocket localized in the C-terminal domain of McsB
Competitively inhibited by L-ornithine
Inhibited by hydroxylamine
When cellular nitrogen levels are high, the C-terminal adenylyl transferase (AT) of GlnE inhibits GlnA by covalent transfer of an adenylyl group from ATP to Tyr-398. Conversely, when nitrogen levels are low, the N-terminal adenylyl removase (AR) of GlnE activates GlnA by removing the adenylyl group by phosphorolysis. The fully adenylated enzyme complex is inactive
Calcium activates the enzyme, inhibited by 1,10-phenanthroline, EDTA and EGTA (PubMed:2503378). End-product inhibited by L-amino acids (PubMed:15388919). Non-competitively inhibited by NaF and NaH(2)PO(4) (PubMed:17608735)
Inhibited by chelating agents such as EDTA, 1-10 phenanthroline and pyridine-2,6-dicarboxylic acid
Inhibited by N-(2-aminoethyl)-5-chloroisoquinoline-8-sulfonamide (CKI-7)
Is specifically blocked by omega-conotoxin GVIA (By similarity). Is specifically blocked by omega-conotoxin MVIIA (ziconotide) (By similarity). Is insensitive to dihydropyridines (DHP)
Displays feedback inhibition by L-serine. Inhibited by glycine
ATPase activity is stimulated when UgpB is bound to G3P (PubMed:23013274). Transport is inhibited in vivo by increasing levels of internal phosphate (PubMed:8282692, PubMed:7836304). However, ATPase activity in proteoliposomes is neither inhibited by phosphate nor by the signal transducing protein PhoU or the phosphodiesterase UgpQ (PubMed:23013274). Activated by gluconate and inhibited by fumarate (PubMed:363686)
Activated by calcium
Taurine tranport activity is inhibited by phorbol 12-myristate 13-acetate, 3-guanidinopropionic acid, L-2,3- diaminopropionic acid, beta-alanine and hypotaurine
Allosterically activated by fructose 1,6-bisphosphate
Competitively inhibited by L-malate and NH(4)(+)
Activated by ATP, inhibited by GTP, EDTA and inorganic phosphate
Inhibited by protonophores (e.g. 2,4-dinitrophenol and carbonylcyanide m-chlorophenylhydrazone), the plasma membrane H(+)-ATPase inhibitor diethylstilbestorol, and the phosphate analog arsenate
Activated by tyrosine phosphorylation during the M phase of the meiotic cell cycle. Dephosphorylated and inactivated by DUSP1
Inhibited by 1,10-phenanthroline
Inhibited by L-aspartic acid
Feedback inhibition by L-arginine
Regulated by light/dark exposure
Inhibited by INKA1; which inhibits the serine/threonine-protein kinase activity by binding PAK4 in a substrate-like manner (PubMed:26607847)
Inhibited by Cu(2+), Ni(2+) and Co(2+)
Activated at acidic pH
Inhibited by prostaglandin E2, probably via PKA-mediated phosphorylation at Ser-379 (PubMed:15131310)
Activated by magnesium ions (PubMed:15980360). Inhibited by caspofungin and cilofungin (PubMed:15980360)
Activity is dependent on the presence of ATP and bicarbonate (PubMed:33826169). The requirement for bicarbonate may be related to allosteric activation through conformational effects, but it is also conceivable that carboxyphosphate is formed and acts as a mediator in caprolactam activation, forming carboxy- or phospholactim (PubMed:33826169)
Subject to autoinhibition, mediated by interactions between the FERM domain and the kinase domain. Activated by autophosphorylation at Tyr-397. This promotes interaction with SRC and phosphorylation at Tyr-576 and Tyr-577 in the kinase activation loop. Phosphorylation at Tyr-576 and Tyr-577 is required for maximal kinase activity. Inhibited by TAE226
E3 ubiquitin-protein ligase activity of the CRL2(APPBP2) complex is inhibited by APP
Inhibited by the product 7-methyl GDP
Activated by phosphorylation on Thr-182 (PubMed:14976552). Also activated by phosphorylation on Thr-322 in response to increases in intracellular sodium in parallel with elevations in intracellular calcium through the reversible sodium/calcium exchanger (PubMed:14976552). Inhibited by phosphorylation at Thr-473 and Ser-575, probably by PKA, which triggers interaction with 14-3-3 proteins (PubMed:29211348)
Kinase activity is activated by abscisic acid (ABA) (PubMed:26443375, PubMed:25680457). Inhibited by ABI1. Activated by SRK2E (PubMed:26443375)
Repressed by semi-carbazide, a specific and irreversible inhibitor of copper amine oxidases
Activated during mitosis by intramolecular autophosphorylation (PubMed:11864968). Activity and autophosphorylation is activated by manganese >> magnesium ions (PubMed:11864968). Sensitive to increasing concentration of detergents (PubMed:11864968). It is not cell-cycle regulated but activity is higher in G0-arrested cells (PubMed:11864968)
Resveratrol strongly inhibits the tyrosine--tRNA ligase activity
Not inhibited by the DNA gyrase inhibitor novobiocin, instead inhibited by eukaryotic topoisomerase inhibitors such as m- and o-amsacrine, ellipticine, and the quinolone CP-115,953 (PubMed:7961685)
Allosterically activated by ADP, AMP, or fructose 2,6-bisphosphate, and allosterically inhibited by ATP or citrate. GlcNAcylation by OGT overcomes allosteric regulation
Inhibited by a range of serine protease inhibitors including antipain, aprotinin, leupeptin, benzamidine and soybean trypsin inhibitor
Inhibited by N-ethylmaleimide (NEM)
Arginine lead to a slight activation. Inhibited by all nucleotide phosphates
Partially inhibited by acetaldehyde (PubMed:33677085). After incubation for 2, 4 and 6 hours in 300 mM acetaldehyde at 25 degrees Celsius, retains approximately 61.32%, 42.33% and 34.73% of the initial 2-deoxy-D-ribose-5-phosphate (DR5P) cleavage activity, respectively (PubMed:33677085)
Seems to switch between active and inactive modes in response to various stimuli (PubMed:35613257). Activated directly or indirectly by membrane phosphatidylinositol (PIs) (PubMed:35613257). Regulated by a variety of auxiliary proteins, which facilitate the maturation, cell surface expression and function of the transporter (PubMed:35613257, PubMed:25851603, PubMed:18829453). Inhibited specifically by the drug tenapanor (PubMed:24622516)
Activated by NDFIP1- and NDFIP2-binding
Inhibited by apstatin and the chelating agent 1,10-phenanthroline. Also inhibited by high concentrations of Zn(2+). Not significantly inhibited by bestatin or phosphoramidon
Constitutively activated by phosphorylation at Ser-232, Ser-372, and Ser-389 in serum-starved cells. Does not require growth factor stimulation for significant kinase activity
Activated by calcium/calmodulin binding after calcium-induced autophosphorylation
Reversely inhibited by N-(N-Sulfodiaminophosphinyl)-L-ornithine (PubMed:10747936). Zinc is an allosteric regulator of the substrate-bound enzyme and a competitive inhibitor of the free enzyme (PubMed:7048313, PubMed:2105398, PubMed:2405164)
The oxidase activity is potentiated by NOXA1 and NOXO1
The heme moiety regulates the kinase activity
Activated by phosphorylation at Ser-350, Thr-571 and Thr-690 by MAP kinases, and by further autophosphorylation of Ser-202, Ser-366 and Ser-371 by the activated C-terminal kinase domain. The active N-terminal kinase domain finally phosphorylates downstream substrates, as well as Ser-740, Ser-742 and Ser-748 in its own C-terminal region (By similarity)
Inhibited by Cu(2+) and Fe(2+), and moderately activated by divalent cations such as Co(2+), Mn(2+) and Zn(2+). Considerably activated by dithiothreitol, beta-mercaptoethanol and cysteine
Inhibited by organophosphorus esters
Activated by dual phosphorylation on Ser-207 and Thr-211 in response to a variety of cellular stresses, including UV radiation, osmotic shock, hypoxia, inflammatory cytokines, interferon gamma (IFNG), and less often by growth factors. MAP2K6/MKK6 is activated by the majority of M3Ks, such as MAP3K5/ASK1, MAP3K1/MEKK1, MAP3K2/MEKK2, MAP3K3/MEKK3, MAP3K4/MEKK4, MAP3K7/TAK1, MAP3K11/MLK3 and MAP3K17/TAOK2
The complete trimodular substrate, with carrier protein (SyrB1), covalently attached PPant cofactor, and thioester-appended amino acid, is required for substrate triggering of rapid chloroferryl intermediate formation
Regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP, GTPase activating proteins (GAPs) which increase the GTP hydrolysis activity, and GDP dissociation inhibitors which inhibit the dissociation of the nucleotide from the GTPase (By similarity). Activated in response to insulin (By similarity)
Activated by threonine and tyrosine phosphorylation by Mkk3
Reciprocal promotion of DNP-GS and E(2)17betaG uptake. E(2)17betaG uptake is also stimulated by GSH and S-methyl-glutathione (S-methyl-GS), and, to a lower extent, by GSSG and C3G-GS. Metolachlor-GS and decyl-GS slightly inhibit E(2)17betaG uptake
Two specific sites, one in the kinase domain (Thr-193) and the other in the C-terminal regulatory region (Ser-356), need to be phosphorylated for its full activation
Inhibited by zinc ions. Competitively inhibited by lysine
Strongly inhibited by diisopropyl fluorophosphate, leupeptin and (4-amidinophenyl)methanesulfonyl 1-fluoride
Inactivated by EDTA and o-phenanthroline
Function is positively regulated by phosphorylation
Probably not activated by nitric oxide (NO). Heterodimer also exhibits some stimulation, some compounds (SIN-1 and two of the NONOates) that were ineffective at stimulating Gyc-88E alone did stimulate the heterodimer
ATPase activity is enhanced upon binding to G-patch domain-containing proteins (PubMed:32179686). G-patch domain-containing proteins act like a brace that tethers mobile sections of DHX15 together, stabilizing a functional conformation with high RNA affinity, thereby promoting the ATPase activity (PubMed:32179686)
Inhibited by tyrosine
Plant MTHFRs strongly prefer NADH over NADPH. Not inhibited by methionine or S-adenosylmethionine
Inhibition of rabbit actin polymerization is reduced by phosphatidylinositol-(4,5)-P2(1,2-dipalmitoyl), a soluble form of the phospholipid phosphatidylinositol, suggesting an unknown lipid might regulate actin-profilin interaction in vivo
Synthesized as an inactive zymogen to protect the intracellular components of the bacteria from proteolytic activity during protein production (By similarity). Once secreted into the extracellular milieu, cleaved into the active protease: maturation can be mediated in cis by autocatalytic cleavage, or in trans by mature SpeB or host proteases. Protease activity is strongly inhibited by zinc and copper, which prevent its maturation into an active protease: inhibition by metal ions may be required to prevent proteolysis of streptococcal proteins (By similarity)
Phosphatase activity is enhanced by Ca(2+) and Mn(2+)
Novel PKCs (PRKCD, PRKCE, PRKCH and PRKCQ) are calcium-insensitive, but activated by diacylglycerol (DAG) and phosphatidylserine. Three specific sites; Thr-513 (activation loop of the kinase domain), Thr-656 (turn motif) and Ser-675 (hydrophobic region), need to be phosphorylated for its full activation. Inhibited by PRKCH upstream open reading frame 2 (PubMed:34593629)
Inhibited by 6,7-Dichloro-N-cyclopentyl-4-(pyridin-4-yl)phthalazin-1-amine (A-196). A-196 is competitive with the histone peptide substrate H4K20me1 but non competitive with S-adenosyl-L-methionine
Inhibited by the serine protease inhibitors DFP, PMSF and TLCK. Not inhibited by the serine protease inhibitors aprotinin, elastinal, SBTI and benzamidine, the cysteine protease inhibitors iodoacetate and E64, or the metalloprotease inhibitors EDTA and EGTA
Activated by the HgdC. Reversibly inactivated by oxidants such as 2-nitrophenol, 3-nitrophenol, 4-nitrophenol, 4-nitrobenzoate, carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP) and chloramphenicol. Irreversibly inactivated by oxidants such as hydroxylamine and nitrite
Inhibited by dipyridamole and moderately by IBMX, zaprinast and rolipram
Activated by the heterotrimeric G-protein subunits GNA12, GNA13 and GNB1-GNG2. Activated by HRAS, RAP1A, RHOA, RHOB, RHOC, RRAS and RRAS2. Activated by the G(s)-coupled GPCRs ADRB2, PTGER1 and CHRM3 through cyclic-AMP formation and RAP2B activation. Inhibited by G(i)-coupled GPCRs (By similarity)
Activated by 200-1000 micromolar concentrations of calcium and inhibited by calpastatin
Product inhibited by AP-site containing dsDNA but not by uracil
Magnesium-independent phospholipid phosphatase. Insensitive to N-ethylmaleimide
Inhibited by beta-lactam compounds such as 6-aminopenicillic acid, 7-aminocephalosporanic acid, benzylpenicillin and ampicillin. Inhibited by p-chloromercuribenzoate
Inhibited by Cu(2+), while other divalent cations such as Ca(2+), Co(2+), Fe(2+), Mn(2+) and Mg(2+) have no obvious effects on enzyme activity
Isoleucine allosterically inhibits while valine allosterically activates this enzyme
Activated by WNK1, WNK2, WNK3 and WNK4
Strictly dependent on the presence of salts for activity
Transcriptional activity is controled by regulated degradation by the ubiquitin-proteasome pathway in absence of arsenic (PubMed:17200139). Arsenic-exposure results in stabilization and increased transcriptional activity (PubMed:15147884, PubMed:17200139)
Inhibited by salicyl hydroxamate, an inhibitor of o-succinylbenzoate synthase
Inhibited by cobalt hexaammine
Allosterically activated by N-acetylglucosamine-6-phosphate (GlcNAc6P)
Inhibited by N-ethylmaleimide and high concentrations of zinc chloride
Activity is strongly promoted by Co(2+), Ni(2+) and Mn(2+) (PubMed:27322068). Activity is inhibited by EDTA (PubMed:27322068)
Is inhibited by high concentrations of Fe(2+) (> 2 mM), and by EDTA or other iron chelators in vitro
The pro-survival signaling effect of NTRK1 in neurons requires its endocytosis into signaling early endosomes and its retrograde axonal transport
Inhibited by tissue-kallikrein inhibitor TKI and trasylol. Plasma kallikrein inhibitor PKSI527 and classical inhibitors of serine-, metallo-, thiol- or aspartate-peptidases evokes a minor inhibition of the peptide digestion
Transcriptional activity at macrophage-specific genes is inhibited by interaction with GFI1, which results in the inhibition of SPI1-induced macrophage differentiation of myeloid progenitor cells, but not that of the granulocyte lineage
Inhibited by salt concentration greater than 100 mM. Uses either magnesium or manganese ions to support helicase activity. Binds strongly to single-stranded DNA in the absence of ATP but dissociates readily in the presence of 1 mM ATP
Autoinhibited by a module composed of four alpha helices (HI-1, HI-2, H4, and H5) that flank the DNA-binding ETS domain, reducing the affinity for DNA. Phosphorylation by CaMK2/CaMKII in response to calcium signaling decreases affinity for DNA
The MolBCA complex shows a decrease in affinity in the presence of increasing concentrations of substrate and nucleotide
Calcium ions and ADP stimulate, whereas ATP and NADH reduce catalytic activity
Activated by hyperosmotic stress
Activated by calcium (PubMed:20466936). Upon calcium binding to the EF-hand domains, the C-terminus of the junction domain (J domain) undergoes a conformational change which results in the dissociation of the pseudo-substrate inhibitory motif from the catalytic domain (By similarity). This, in turn, may facilitate the autophosphorylation of the activation loop at Thr-285, which leads to the kinase activation (By similarity)
Inhibited by the amidino-urea compound 1-[(2,6-diethylphenyl)-3-N-ethylcarbamimodoyl]urea (compound 8918). It acts by binding to the phosphopantetheine pocket in the active site. Inhibition by compound 8918 kills M.tuberculosis
Folding of PqsC and binding of octanoate are promoted by PqsB (PubMed:24239007). Binding of the octanoyl group probably increases the binding affinity of the complex for 2-ABA (PubMed:26811339). Activity of the complex is inhibited by 2-aminoacetophenone (2-AA) (PubMed:26811339)
Inhibited by EDTA and EGTA, but not by PMSF
Activity is strongly promoted by toluene (PubMed:34093489). Activity is promoted by magnesium, potassium, cadmium, zinc, nickel, sodium, lead and manganese ions (PubMed:34093489). Completely inhibited by IAA (cysteine protease inhibitor), PMSF (serine protease inhibitor), DEP (histidine protease inhibitor) and NAI (tyrosine protease inhibitor) (PubMed:34093489). Inhibited by ethanol, acetone, SDS, and EDTA (PubMed:34093489). Activity is strongly inhibited by mercury ions (PubMed:34093489). Also inhibited by lithium, aluminum, calcium, barium and iron ions (PubMed:34093489)
Activated by Ca(2+)/calmodulin. Binding of calmodulin results in conformational change that relieves intrasteric autoinhibition and allows autophosphorylation of Thr-287 which turns the kinase in a constitutively active form and confers to the kinase a Ca(2+)-independent activity
Ubiquitin ligase activity of the BCR(KEAP1) complex is inhibited by oxidative stress and electrophile metabolites such as sulforaphane. Electrophile metabolites react with reactive cysteine residues in KEAP1 and trigger non-enzymatic covalent modifications of these cysteine residues, leading to inactivate the ubiquitin ligase activity of the BCR(KEAP1) complex. Selective autophagy also inactivates the BCR(KEAP1) complex via interaction between KEAP1 and SQSTM1/p62, which sequesters the complex in inclusion bodies and promotes its degradation
Cellobiose inhibits xynA at high concentrations
Inhibited by RANBP9 (By similarity). Inhibited by harmine, leucettamine B and leucettine L41 (PubMed:22998443)
Inhibited by ADP-ribose and nicotinamide
Cleavage is inhibited by ubiquitin in a dosage-dependent manner (By similarity). Cleavage is blocked by ubiquitin aldehyde
Is not inhibited by lysine
Activated by phosphorylation on Ser-50 and Ser-581
Inhibited by nitrate
Serine protease inhibitors strongly inhibit activity (PubMed:15310761). Moreover, 3,4-dichloroisocoumarinshows and 2-acetyl-1,3,6,8-tetrahydroxynaphthalene act also as a strong inhibitor (PubMed:15310761)
Inhibited by both FK506 and rapamycin, but not by cyclosporin A
Allosterically activated by various compounds including ATP, 2,3-BPG/2,3-Bisphosphoglyceric acid and Ap4A/P1,P4-bis(5'-adenosyl) tetraphosphate. Binding of an allosteric activator is a prerequisiste to magnesium and substrate binding. Inhibited by inorganic phosphate
Positively regulated by the regulatory subunit pan3
Inhibited by Zn(2+), Cu(2+), and Fe(2+)
Mycophenolic acid (MPA) is a non-competitive inhibitor that prevents formation of the closed enzyme conformation by binding to the same site as the amobile flap. In contrast, mizoribine monophosphate (MZP) is a competitive inhibitor that induces the closed conformation. MPA is a potent inhibitor of mammalian IMPDHs but a poor inhibitor of the bacterial enzymes. MZP is a more potent inhibitor of bacterial IMPDH. IMP dehydrogenase subunit of E.coli contains a cysteine at the IMP binding site and is inhibited in a simple competitive manner by GMP. It does not exhibit allosteric properties as does IMP dehydrogenase from B.subtilis or S.typhimurium
Partially inhibited by 1 mM serine
Activated by MYD88
Activity is not dependent on divalent cations, but it is enhanced by Mn(2+)
Inhibited by 3-isobutyl-1-methylxanthine (IBMX)
Receptor activity is regulated by proteolytic processing. The long N-terminal has a an inhibitory effect on the constitutive signaling activity. Removal of the N-terminal region induces an increase of the receptor activity
Arachidonate 12-lipoxygenase activity is decreased when the pH decreases from 7.4 to 6.0
Inhibited by pretreatment with 1 mM 4-(hydroxymercuri)benzoate, a sulfhydryl inhibitor
Inhibited by 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS)
Irreversibly inhibited by (2S,3R,4S)-2,4-dihydroxy-3-methylhexyl-phosphonic acid and (3R,4S)-4-hydroxy-3-methyl-2-oxohexyl-phosphonic acid
Present in an inactive conformation in the absence of bound ligand. Binding of VEGFA, VEGFC or VEGFD leads to dimerization and activation by autophosphorylation on tyrosine residues. May be regulated by hydrogen sulfide (H(2)S) levels via a sensitive intracellular disulfide bond (By similarity)
Requires ATP hydrolysis for polymerization (PubMed:23235161). Polymerization is inhibited by toxins CbtA and CptA, as well as by A22 ([S-(3,4-dichlorobenzyl)isothiourea)] all of which cause cell rounding and eventual death. Inhibition by toxin CbtA is neutralized by cytoskeleton bundling-enhancing protein CbeA, inhibition by toxin CptA is neutralized by antitoxin CptB, while inhibition by A22 can be neutralized by overexpression of CbeA (PubMed:21166897, PubMed:22239607, PubMed:22515815)
The ratio of NADPH/NADP(+) may regulate enzymatic activity
Inhibited by phosphoglycolohydroxamate (PGH)
Inhibited by L-diaminobutyric acid, guvacine, cis-4-hydroxynipecotic acid, nipecotic acid, and 4,5,6,7-tetrahydroisoxazolo [4,5c]-pyridin-3-ol
The interaction with KaiA enhances its phosphorylation status, while the interaction with KaiB decreases it
Curcumin non-competitively inhibits the enzyme with respect to furfural. To a lesser extent, enzyme activity is also inhibited by indomethacin, coumarate, coumarin, and alrestatin
The chaperone activity is regulated by ATP-induced allosteric coupling of the nucleotide-binding (NBD) and substrate-binding (SBD) domains (By similarity). In the ADP-bound and nucleotide-free (apo) states, the two domains have little interaction (By similarity). In contrast, in the ATP-bound state the two domains are tightly coupled, which results in drastically accelerated kinetics in both binding and release of polypeptide substrates (By similarity). J domain-containing co-chaperones (DNAJB9/ERdj4 or DNAJC10/ERdj5) stimulate the ATPase activity and are required for efficient substrate recognition by HSPA5/BiP. Homooligomerization inactivates participating HSPA5/BiP protomers and probably act as reservoirs to store HSPA5/BiP molecules when they are not needed by the cell (By similarity)
Partially inhibited by niacin
Requires cadmium for activity. Also activated in heterologous system by AsO(4)(3-) ions, but not by Cu(2+), Zn(2+), Mn(2+) or Ni(2+) ions
By phosphorylation of various serine residues and by calcium
Phosphorylation at Thr-14 or Tyr-15 inactivates the enzyme, while phosphorylation at Thr-158 activates it
Ability to mediate liquid-liquid phase separation is regulated by ATP: moderate concentrations of ATP enhance phase separation, whereas high concentrations of ATP lead to inhibition of phase separation
Carboxypeptidase activity is insensitive to beta-lactams since it is not affected by penicillin G or ampicillin and is inhibited only by very high concentrations of cefalotin and cefoxitin
Activated by DAG and phorbol esters. Phorbol-ester/DAG-type domain 1 binds phorbol ester with low affinity. Phorbol-ester/DAG-type domain 2 binds phorbol ester with high affinity and targets the kinase to the cell periphery, enabling phosphorylation and activation by colocalized tpa-1. Both domains 1 and 2 appear to bind DAG with equal affinity so may contribute equally to translocation and activation
Inhibited by PMSF
Stimulated by DTT and Nonidet P-40
Inhibited by phosphite, moderately inhibited by phosphonic acids, the corresponding aminophosphonic acids activate the enzyme
Inhibited by sodium orthovanadate and pentamidine
Regulated by L-cysteine, which can either inhibit substrate influx or trigger substrate efflux without being transported itself
Inactivated by binding to URI1
Inhibited by ruthenium red or its derivative Ru360
Inhibited by NaCl, NADH and sulfite
The enantiomer (-)-vincadifformine acts as a competitive inhibitor
Cannot be activated without removal of the activation peptide. Activated by matrilysin
GlcN-1-P acetyltransferase activity is inhibited by divalent cations. GalN-1-P acetyltransferase activity is enhanced by Co(2+), Mg(2+) and Ca(2+), but inhibited by Zn(2+) or Mn(2+)
Under nitrogen limitation, binding of 2-oxoglutarate to the NrpRI/NrpRII complex decreases the binding affinity of NrpRI to DNA as well as the binding affinity of NrpRII to TBP and TFB, which leads to removal of the complex from the operator, RNA polymerase recruitment and initiation of transcription
Transport is inhibited by S-adenosylethionine and to a lesser extent by S-adenosylhomocysteine. Unlike eukaryotic transporters is not inhibited by sinfungin. Also inhibited by 2.4-dinitrophenol, suggesting transport is an energy-dependent process
Activated by RHOA binding. Inhibited by Y-27632 (By similarity)
Inhibited at high fructose
Autophosphorylation at His-118 increases serine/threonine protein kinase activity of the enzyme. Interaction with the SET complex inhibits the endonuclease activity
Both phosphatase and phosphodiesterase activities are competitively inhibited by low concentrations of the E.coli tRNA (10 nM). Cu(2+) stimulates the hydrolysis of pyrophosphate and ATP and completely inhibits the hydrolysis of 2'-AMP. The phosphodiesterase activity is inhibited by Zn(2+), Cu(2+) and Co(2+)
Inhibited by Li(+), Ca(2+) and Mn(2+), but also by Mg(2+) at concentrations above 3 mM
Activated by guanine nucleotide exchange factor RCC1L
Strongly inhibited by Hg (2+). Inhibited by Zn (2+). Activated by Fe (2+), Mg (2+) and Ba (2+)
Not activated by dithiothreitol (DTT) using GlcNAc-alpha-PO(3)-PO(3)-phenylundecyl (GlcNAc-PP-PhU) as acceptor substrate (PubMed:23664878, PubMed:25845842). 0.25% Triton X-100 and 0.125% NP-40 increases the activity 2.5-fold and 2-fold, respectively. 0.125% octyl glucoside has little effect on activity. Slightly increased activity with Mg(2+) and Pb(2+), while no effect with Mn(2+), Co(2+), Ni(2+), Cu(2+), Zn(2+), Ca(2+) or EDTA. Not inhibited by N-butyryl-galactosamine-alpha-benzyl or N-butyryl-glucosamine-beta-benzyl. Bis-imidazolium salts having aliphatic spacer groups with 4 or 6 carbons have little effect on activity, but spacer groups of 18-22 aliphatic carbons inhibit activity, with the most potent inhibitor being bis-imidazolium salt having a 20-carbon chain spacer length (PubMed:25845842)
Loses 93% of its activity upon incubation with 1-iodopropane and titanium(III) citrate in the dark. Subsequent exposure to light restores 80% of the original activity (PubMed:10671186). Completely inhibited by 2 mM sodium sulfite or sodium dithionite, and by 1 mM cuprous chloride (PubMed:10671186)
Competitively inhibited by low concentrations of phosphate (IC50 of 1.2 mM) and is also sensitive to Li(+) (IC50 of 15.8 mM). Also inhibited by 1 mM ATP or 50 mM KCl (60% and 20% residual activity, respectively). Slightly activated (40-50%) by the addition of 1 mM dithiothreitol in vitro
Activated by immulectin and lipopolysaccharide
Inhibited by gamma-vinyl-gamma-aminobutyrate (vigabatrin), beta-alanine and ornithine
The Rcs phosphorelay may be activated by RcsF. DjlA, LolA and OmpG might act as a regulator of the phosphorelay. Activity is probably up-regulated by YmgA/AriR, and possibly down-regulated by YcgZ, all 3 are connector proteins providing additional signal input into signaling system
Intracellular DIC accumulation is sensitive to CCCP (carbonyl cyanide-m-chlorophenylhydrazone) and DCCD (N,N-dicyclohexylcarbodiimide) and therefore likely driven by either proton potential, ATP, or both
The activity increases in the presence of K(+) ions: 15-fold with NADP and 40-fold with NAD, respectively
Inhibited by guazatine, aminoguanidine and putrescine
Allosterically activated by AdoMetDC prozyme (By similarity). Activated by putrescine (PubMed:9677309, PubMed:10413038). Inhibited by spermine and methylglyoxal-bis(guanylhydrazone) (MGBG) and slightly by spermidine (PubMed:9677309). Inhibited by 5'-([(Z)-4-amino-2-butenyl]methylamino)-5'-deoxyadenosine (MDL 73811) (PubMed:10413038)
Activated following oxidation of the conserved redox-active cysteine residue, which subsequently allows for the oxidation and activation of substrates
Inhibited by zinc
Hemagglutinating activity does not require Ca(2+) ions. Hemagglutinating activity is inhibited by porcine stomach mucin (PSM), bovine submaxillary mucin (BSM) and fetuin (Ref.2). Agglutination of V.proteolyticus bacteria is inhibited by D-galactose, but not by D-glucose. Fungal binding is inhibited by D-galactose, but not by pathogen-associated molecular patterns (PAMPs) including lipopolysaccharide (LPS), peptidoglycan and beta-glucan (PubMed:26802895)
Activity limited by low ascorbate availability. Feedback inhibition by zeaxanthin. Requires the presence of micelle-forming lipids such as monogalactosyldiacylglyceride (MGDG). Low concentration of bilayer forming lipids, such as digalactosyldiacylglyceride (DGDG) or phosphatidylcholine, supports a slower but nearly complete activity (PubMed:11891252, PubMed:14749490, PubMed:16532316). 80% of the specific activity in lumenal chloroplast fractions is lost in vitro in the presence of reduced thioredoxin (PubMed:20049866)
Activated by CHAPS at concentrations of up to 130 mM, higher concentrations reduce activity. In the presence of CHAPS, activity is stimulated by non-ionic detergents. Inhibited by the esterase inhibitors diisopropylfluorophosphate and phenylmethylsulfonyl fluoride
Activated by MRJP1 during queen determination of honeybee larvae
Autoinhibited by the N-terminal domain, containing the KxGQ motif, that completely occludes the typical substrate binding pocket. Nucleotide-binding relieves inhibition
Positively regulated by the regulatory subunit PAN3
Inhibited by EDTA in vitro
Binds cyclosporin A (CsA). CsA mediates some of its effects via an inhibitory action on PPIase (By similarity)
Inhibited by chelating agent 1,10-phenanthroline, aminopeptidase inhibitors actinonin, amastatin, and leuhistin, and to a lesser extent by puromycin
Inhibited by dideoxythymidine-triphosphate (ddTTP), but not by aphidicolin and N-ethylmaleimide
Inhibited by actinonin
Inhibited by p-chloromercuribenzoate
Activated upon translocation to the sites of synthesis of PtdIns(3,4,5)P3 in the membrane
Not stimulated by calcium/calmodulin
Both the ABR and the SH3 domains contribute to maintaining the protein in an inhibited conformation by associating with the C-terminal tail. Binding of these domains to the C-terminal tail inhibits the activity of the protein by blocking a region that is required for its GEF activity (By similarity)
Repressed by acetohydroxamic acid (AHA)
Activated by an increase in cytosolic calcium levels that induce a conformational change of the N-terminal regulatory domain, uncapping the channel and allowing transport. Inhibited by bathophenanthroline, mersalyl, p-hydroxymercuribenzoate, bromcresol purple and tannic acid
The rate-limiting step is NADH release. Catabolite repression
Phosphorylation at Tyr-2 inactivates the enzyme, while phosphorylation at Thr-148 activates it
Inhibited by metal chelator ethylenediaminetetraacetic acid (EDTA)
Inhibited by the tyrosine phosphatase inhibitor vanadate
Inhibited by histatin-3 1/24 (histatin-5). Inhibited by ECM1
Activated by calcium and magnesium ions. Inhibited by EDTA, DTT and L-cysteine. Activity is not affected by PMSF or heparin
Inhibited by the C-terminal non-catalytic region. Activated by caspase-cleavage. Full activation also requires homodimerization and autophosphorylation of Thr-183. Activated by RASSF1 which acts by preventing its dephosphorylation (By similarity)
Classical (or conventional) PKCs (PRKCA, PRKCB and PRKCG) are activated by calcium and diacylglycerol (DAG) in the presence of phosphatidylserine. Three specific sites; Thr-500 (activation loop of the kinase domain), Thr-642 (turn motif) and Ser-661 (hydrophobic region), need to be phosphorylated for its full activation. Specifically inhibited by enzastaurin (LY317615) (By similarity)
Inhibited by the iron chelator EDTA
Inhibited by serine protease inhibitors. Inhibited by N-Bromo-succinimide
Hydroxymethyltransferase is inhibited by succinylation at Lys-280
Efflux of L-methionine is inhibited by the proton ionophore carbonyl cyanide m-chlorophenylhydrazone (CCCP)
Total and irreversible inhibition by S-nitrosoglutathione (GSNO) (PubMed:21782461). Partial and reversible inhibition by oxidized glutathione (GSSG) (PubMed:21782461)
Zinc-binding negatively regulates its activity
Rubredoxin (Rd) increases the NADH consumption rate by serving as an intermediary electron-transfer shuttle between NROR and revRbr
Inhibited by mannose 6-phosphate, fructose 1-phosphate and fructose 1,6-bisphosphate. Its activity is also inhibited by Cobalt (II) ions < EDTA < nickel (II) ions < zinc (II) ions << cadmium (II) ions < copper (II) ions. Sodium and potassium ions and manganese ions show little or no effect on activity
CASP8 activity is restricted by RIPK1 (By similarity). Inhibited by the effector protein NleF that is produced by pathogenic E.coli; this inhibits apoptosis (PubMed:23516580)
Glutamine-dependent asparagine synthesis activity can be inhibited by aspartic acid analogs (such as a sulfinate derivative and (2S,3R)-2-amino-3-methylsuccinate) in vitro; the inhibition is competitive with respect to aspartate
Inhibited by RNA
Inhibited by Cu(2+), Hg(2+), Cd(2+) and Zn(2+) at 1 mM. Not inhibited by Co(2+), Mg(2+), Ca(2+), Mn(2+), Fe(3+) and EDTA. Also inhibited by sodium chloride at 1M and 2-amino-2-hydroxymethyl-1,3-propanediol (trishydroxymethylaminomethane) at 75 mM
The flippase activity is inactivated by caspase-mediated cleavage in apoptotic cells, allowing for PS exposure on the cell surface and engulfment of apoptotic cells by macrophages. The ATPase activity is up-regulated by aminophospholipids PS and PE and down-regulated by increasing intracellular Ca2+ levels
May be regulated by ROP1 through the interaction with UGT1
Inhibited by metal chelators
APOA1 is the most potent activator in plasma. Also activated by APOE, APOC1 and APOA4 (By similarity)
Subject to complex allosteric regulation. The enzyme can assume an active R-state, or an inactive T-state. Intermediate conformations may exist. AMP acts as allosteric inhibitor. AMP binding affects the turnover of bound substrate and not the affinity for substrate (By similarity)
Regulated by the nitrogen source and controlled by the circadian rhythm
MI transport activity inhibited by D-chiro-inositol (DCI), phlorizin (Pz) and sodium (Na(+)) (By similarity). Insulin increases D-chiro-inositol uptake (By similarity)
Requires potassium. Inhibition by ADP
Inhibited by Sirtinol, A3 and M15 small molecules. Inhibited by nicotinamide. Inhibited by a macrocyclic peptide inhibitor S2iL5. Inhibited by EP300-induced acetylation (By similarity)
Inhibited by propyne
Inhibited by beta-lactams containing a D-amino acid side chain
Activated by phosphorylation on Thr-182 (By similarity). Also activated by phosphorylation on Thr-322 in response to increases in intracellular sodium in parallel with elevations in intracellular calcium through the reversible sodium/calcium exchanger
Uptake is stimulated by high osmolarity. Stimulation is probably due to conformational changes
Activated by a monovalent cation that binds near, but not in, the active site (PubMed:11786021). The most likely occupant of the site in vivo is potassium (PubMed:16784868, PubMed:11786021). Also activated by ammonium ion (PubMed:16784868). Ion binding induces a conformational change that may alter substrate affinity (Probable)
Kinase activity is inhibited by phosphorylation and activated by dephosphorylation by CDC14
Negatively regulated by excess Zn(2+)
Transcriptional activity may be repressed by ESR1 and ESR2
Sphingomyelinase activity is reduced by 33 percent following addition of EDTA
The protein undergoes a dramatic conformational switch from closed to open states upon substrate-binding, which enables specific substrate recognition for the 1''-O-linkage. The glutamate flap (Glu-47) blocks substrate entrance to Mg(2+) in the unliganded closed state. In presence of substrate, Glu-47 is ejected from the active site: this closed-to-open transition significantly widens the substrate-binding channel and precisely positions the scissile 1''-O-linkage for cleavage while securing tightly 2'- and 3'-hydroxyls of ADP-ribose
Esterase and beta-lactamase activities are inhibited by the active site residue modifiers phenylmethanesulfonylflouride (PMSF) and diethylpyrocarbonate (DEPC)
Inhibited by the cysteine protease inhibitor E64 (L-trans-epoxysuccinyl-leucylamide-(4-guanido)-butane)
Both activities are inhibited by RapH
GTP shows a positive allosteric effect, and tetrahydrobiopterin inhibits the enzyme activity. Zinc is required for catalytic activity. Inhibited by Mg(2+)
Inhibited by N-ethyl-maleimide and phenylglyoxal
Present in an inactive conformation in the absence of bound ligand. KITLG/SCF binding leads to dimerization and activation by autophosphorylation on tyrosine residues. Activity is down-regulated by PRKCA-mediated phosphorylation on serine residues (By similarity)
Allosterically inhibited by lysine, but not by S-adenosyl-L-methionine (SAM). K(0.5) for lysine in the presence of physiological concentrations of substrates is 12.5 uM. No inhibition by threonine or leucine and no activation or inhibition by alanine, cysteine, isoleucine, serine, valine, methionine, glutamine, asparagine, glutamic acid or arginine
Activated by coenzyme A (CoA), aspartate, succinate and fumarate. Repressed by oxaloacetate, glucose and ATP
Binding of cAMP to kin-2 regulatory subunits induces dissociation of the heterotetramer. The released catalytic subunits are active and able to phosphorylate their substrates
Inhibited by the anti-tuberculosis drug isoxyl (ISO)
Farnesyl pyrophosphate and geranyl pyrophosphate inhibit mevalonate kinase by binding competitively at the ATP-binding site
Inhibited by cyanide, azide and antimycin A. Enzyme stability is not dependent on salt concentration
Novel PKCs (PRKCD, PRKCE, PRKCH and PRKCQ) are calcium-insensitive, but activated by diacylglycerol (DAG) and phosphatidylserine. Three specific sites; Thr-538 (activation loop of the kinase domain), Ser-676 (turn motif) and Ser-695 (hydrophobic region), need to be phosphorylated for its full activation (By similarity)
Induced by reactive oxygen species (ROS)
Allosterically regulated through the non-covalent binding of metabolites, being activated by AMP and inhibited by ATP, ADP, and glucose-6-phosphate. The activity is also controlled by post-translational modifications including phosphorylation
Adenylyltransferase activity is specifically phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2)
Activated by phosphorylation on Thr-208
Activated by nitric oxide in the presence of magnesium or manganese ions, binding of NO to the heme iron increases catalytic activity up to 400 folds
Allosterically regulated through the non-covalent binding of metabolites, being activated by AMP and inhibited by ATP, ADP, and glucose-6-phosphate. The activity is also controlled by post-translational modifications including phosphorylation and acetylation
Activated by binding small G proteins. Binding of GTP-bound CDC42 or RAC1 to the autoregulatory region releases monomers from the autoinhibited dimer, enables phosphorylation of Thr-421 and allows the kinase domain to adopt an active structure (By similarity)
Inhibited by oleoyloxyethyl phosphocholine
Inhibited by EDTA, EGTA and D/L-sphinganine D-erythro-sphingosine. L-erythro-sphingosine is a less powerful inhibitor. Stimulated by glycerophospholipids: cardiolipin is the most effective, followed by phosphatidic acid, phosphatidylethanolamine and phosphatidylglycerol, whereas phosphatidylcholine, lysophosphatidic acid and diacylglycerol are less effective
Inhibited by chemical modifications mediated by p-BPB, anhydrous acetic acid and NBSF
Strongly inhibited by biotin-YVAD-fmk (a caspase-1 inhibitor) and by Ac-DEVD-fmk
Not inhibited by EDTA, inhibited by clavulanic acid and tazobactam
EDTA is an inhibitor of catalytic activity
Stimulated by agonists such as ATP, EGF, thrombin and bradykinin as well as by cytosolic Ca(2+)
Phosphorylation results in inhibition of the kinase activity
The enzymatic reaction requires the aid of the Rab escort protein REP
Activity is competitively inhibited by the bisubstrate-type compounds TS23, JC33 and JC72, with Ki values in the low nanomolar range
Activity is inhibited by 4,4'-di-isothiocyanatostilbene-2,2'-disulfonic acid (DIDS - an inhibitor of several anion channels and transporters)
Allosteric enzyme with a cooperative mechanism; at least two neighbor subunits influence each other strongly in spastin hexamers. Microtubule binding promotes cooperative interactions among spastin subunits
Dephosphorylated and activated by CpsB
Heat shock, alkaline shift, ethanol treatment and poor nutrient availability produce increased concentrations of monoacetylated spermidine (PubMed:2061318). Inhibited by alkaline phosphatase, N(1),N(8)-bis(ethyl)spermidine (BESPD) and N(1),N(12)-bis(ethyl)spermidine (BESPM) (PubMed:8077207, PubMed:6297970)
Activated by binding to the pyruvate dehydrogenase complex subunit DLAT. Strongly activated by NADH plus acetyl-coenzyme A. Inhibited by dichloroacetate
Activated by cytochrome b5
Activated by glucose-6-phosphate. Inhibited by N-acetylglucosamine, glucosamine, mannoheptulose and ADP
Inhibited by wortmannin (PubMed:8973579). Increased kinase activity upon interaction with NCS1/FREQ (By similarity)
Proteolytic activity is blocked in the presence of EDTA
Type I PDE are activated by the binding of calmodulin in the presence of Ca(2+)
Activated, directly or indirectly, by endogenous spore dipicolinic acid released in response to nutrients. Is also activated by exogenous Ca(2+)-dipicolinic acid
Oligomerization is required for activity. May be activated by trans-autophosphorylation. Higher activity during G2/M phase and G1 phase compared to S phase
Strongly inhibited by Co(2+) and Ni(2+), and slightly inhibited by EDTA
Activity is greatly increased when AURKB is within the CPC complex. In particular, AURKB-phosphorylated INCENP acts as an activator of AURKB. Positive feedback between HASPIN and AURKB contributes to CPC localization
The enzyme is inhibited by tartrate and D-malate
Activated by ATP and maltotriose, which are both required for DNA binding
Uptake of metal ions is decreased in the presence of the ionophores FCCP or CCCP, but no clear contribution of the proton-motive force could be demonstrated (PubMed:20225068). Bicarbonate or other ions do not influence metal-uptake (PubMed:20225068)
Activated by phosphorylation at Thr-229, probably by autophosphorylation
Calcium-calmodulin exerts its inhibitory effect in cAMP sensitivity by binding to IQ-like motif of CNGA4 and preferably binds to the channel in the closed state. Inhibition by PIP3 of the CNG channel probably occurs via CGNA2 binding
Acid pH levels increase its ATPase activity
Binding of TP53BP2 to the regulatory subunit NAE1 decreases neddylation activity
Inhibited by both 1-deoxymannojirimycin (dMNJ) and kifunensine
Competitive inhibition by 3-amino-1,2,4-triazole (e.g. ATZ)
Activated by arachidonic acid
The 2Fe-2S present in the homodimer leads to inactivation of the enzyme. The 2Fe-2S may serve as a redox sensor: the presence of one-electron oxidants or reductants leading to the loss of the 2Fe-2S cluster, subsequent monomerization and activation of the enzyme. Unlike other glutaredoxins, it is not inhibited by oxidation of structural Cys residues
Inhibited by S.tuberosum metallocarboxypeptidase inhibitor
Activated by Ca(2+)/calmodulin. Regulated by a double locking mechanism, involving autophosphorylation at Ser-318, calmodulin binding, and dimerization. In the inactive state, Ser-318 is phosphorylated, and the kinase is dimeric. Activation involves: dephosphorylation at Ser-318, release-of-autoinhibition mechanism where calmodulin binding induces a conformational change that relieves the steric block of the active site by the autoinhibitory domain, and generation of the monomeric active form of the kinase
Addition of Mg(2+) or Ca(2+) increases the casein hydrolysis rate
Inhibited by phosphorylation (By similarity). Citrate promotes oligomerization of the protein into filaments that correspond to the most active form of the carboxylase (By similarity)
Inhibited by 2-bromopalmitate
Is inhibited by cyanide. Is sensitive to oxygen
Inhibited by acetazolamide
Activated by phosphorylation on Thr-524 (By similarity). Interacts with PKN2; the interaction activates PKN2 kinase activity in a MAP3K2-independent kinase activity
PA phosphatase activity not inhibited by N-ethylmaleimide
Is inhibited at high substrate concentration
Catalytic activity requires the presence of ERG27
Sensitive to heat and heavy metals
Competitive inhibition by NADPH, 3-phospho-D-glycerate and ATP
One of the zinc ions is readily exchangeable with other divalent cations such as manganese, which strongly stimulates the enzymatic activity
Inhibited by hydroxylamine or amino-oxyacetic acid
Inhibited by bulky trifluoromethyl ketones
Heparin reduces its edema-inducing activity (PubMed:11054123)
Inhibited by serine-borate
Competitively inhibited by (2S,3S)-thiahomoisocitrate in vitro
Inhibited by Hg(2+)
Activity of listeriolysin O is regulated on multiple levels. It should be high in the phagosome, thereby allowing escape of the bacteria from the phagosomal compartment. Then, once inside the host cytosol, the activity must be controlled to prevent lysis of the host plasma membrane and loss of the intracellular environment
Activated by dimerization. Not activated by EGF, TGF-alpha and amphiregulin. Interaction with PTK6 increases its intrinsic kinase activity
Allosterically activated by S-adenosyl-methionine/AdoMet. Activated by S-adenosylhomocysteine/AdoHcy. Binds non-covalently to a heme group that may control the redox sensitivity of the enzyme
Strongly inhibited by UDP
Inhibited by the antibiotic bafilomycin A1. Partially inhibited by DCCD, nigericin and FCCP
The protein undergoes a dramatic conformational switch from closed to open states upon substrate-binding, which enables specific substrate recognition for the 1''-O-linkage. The glutamate flap (Glu-35) blocks substrate entrance to Mg(2+) in the unliganded closed state. In presence of substrate, Glu-35 is ejected from the active site: this closed-to-open transition significantly widens the substrate-binding channel and precisely positions the scissile 1''-O-linkage for cleavage while securing tightly 2'- and 3'-hydroxyls of ADP-ribose
Regulated by the folate status via an increased concentration of S-adenosyl-homocysteine (AdoHcy), a potent inhibitor of most AdoMet-dependent methyltransferases
An 11-mer corresponding to the PIP-box of RfcL inhibits DNA synthesis
Activated by forskolin. Insensitive to calcium/calmodulin. Stimulated by GNAS and by the G-protein beta and gamma subunit complex
Retinyl ester hydrolase is inhibited by bis-p-nitrophenyl phosphate
Both the processed and unprocessed enzymes are catalytically active (PubMed:16802174). PCE-dependent growth and PceA activity are inhibited in the presence of high concentrations of 5,6-dimethylbenzimidazole (DMB), probably due to the formation a DMB-containing nor-B12 cofactor (PubMed:24433392). Dechlorination of PCE is stimulated by ammonium ions (PubMed:8663199, PubMed:28671181). Activity is inhibited by chlorinated methanes (PubMed:8663199)
Enzyme activity is increased by cytochrome b5 (PubMed:23821647). Enzyme activity is increased by liposomes containing anionic phospholipids, phosphatidic acid and cardiolipin. Inhibited by naringenin with an IC(50) of 5 uM (By similarity)
Isomerase activity is increased by sulfhydril compounds. Dithiothreitol (DTT) is most effective, followed by glutathione (GSH) and 2-mercaptoethanol
Does not bind cyclosporin A (CsA)
Angiopoietin binding leads to receptor dimerization and activation by autophosphorylation at Tyr-993 on the kinase activation loop
Produced as a latent enzyme which is activated by double stranded RNA (dsRNA) generated during the course of viral infection. The dsRNA activator must be at least 15 nucleotides long, and no modification of the 2'-hydroxyl group is tolerated. ssRNA or dsDNA do not act as activators. Strongly inhibited by copper, iron and zinc ions. Partially inhibited by cobalt and nickel ions
Allosterically activated by AMP and by several sugar phosphates. Belongs to type II PK
Glycine accelerates autocleavage into an alpha and beta chain
Autoinhibited by a module composed of four alpha helices (HI-1, HI-2, H4, and H5) that flank the DNA-binding ETS domain, reducing the affinity for DNA (PubMed:15591056, PubMed:15994560). Phosphorylation by CaMK2/CaMKII in response to calcium signaling decreases affinity for DNA (PubMed:15994560)
Inhibited by 10 mM EDTA
Cl(-)/HCO3(-) exchanger activity is substantially increased in response to 5 uM isoproterenol (PubMed:34585968). Cl(-)/HCO3(-) exchanger activity is increased by both forskolin and coexpression with the catalytic subunit alpha of PKA (PubMed:34585968)
Phosphorylation on Ser-45 inhibits the phosphoryl transfer from enzyme I to HPr
ATPase activity is stimulated by binding to DNA or nucleosomes, but is strongly activated by nucleosomes
Autoinhibited. In the autoinhibited state, the TPR domain interacts with the catalytic region and prevents substrate access to the catalytic pocket. Allosterically activated by various polyunsaturated fatty acids, free long-chain fatty-acids and long-chain fatty acyl-CoA esters, arachidonic acid being the most effective activator. HSP90A and probably RAC1, GNA12 and GNA13 can also release the autoinhibition by the TPR repeat. Activation by RAC1, GNA12 and GNA13 is synergistic with the one produced by fatty acids binding. Inhibited by okadaic acid
Activated by magnesium. Inhibited by succinyl acetone. Enzyme activity may depend on the oligomerization state, where the fully active octamer may dissociate and reassemble into less active lower oligomers
ARF GAP activity strongly enhanced by phosphatidylinositol 4-monophosphate (PIP) and moderately enhanced by phosphatidylinositol 4,5-bisphosphate (PIP2)
Acetylserotonin O-methyltransferase activity is inhibited by quercetin and caffeate
Strongly inhibited by 1,10-phenanthroline and phosphoramidon but relatively insensitive to EDTA. Not significantly inhibited by p-chloromercuribenzoate nor by phenylmethylsulfonyl fluoride
Chloride channel activity is allosterically activated by lumenal H(+) and Cl(-) leading to synaptic vesicles acidification. The L-glutamate transport activity is allosterically activated by lumenal H(+) and Cl(-). The allosteric requirement for H(+) efficiently prevents non-vesicular efflux across the plasma membrane (By similarity). The L-glutamate uniporter activity exhibits a biphasic dependence on chloride concentration (PubMed:11432869)
Inhibited by dicyclohexylcarbodiimide (DCDD); activity was higher at pH 5.7 than at pH 7.5
The adenosine 5'-phosphosulfate phosphorylase activity is enhanced at low pH
Inhibited by diisopropylfluorophosphate (DFP) and PMSF, and partially by soybean trypsin inhibitor, but not by EDTA
Competitively inhibited by mercaptophosphonate and pyridine carboxylate derivatives (PubMed:17307979, PubMed:20527888). Also inhibited by the binding of a second zinc ion and by chelating agents such as EDTA (PubMed:1856163, PubMed:2327760, PubMed:19651913)
Proline-mediated feedback inhibition
Phosphorylation of the transporter leads to changes in its substrate affinity, resulting in a regulation of the transport activity (PubMed:10864577). In contrast with human ortholog, ASP uptake is stimulated by protein kinase A (PKA) and C (PKC) and endogenous tyrosine kinase activation (PubMed:10864577). ASP affinity is induced by PKC-dependent phosphorylation (PubMed:10864577). Inhibited by cGMP, most likely through a cGMP-binding protein that interacts with OCT1 (PubMed:12395288)
Redox regulation; active in reducing conditions, inactive in oxidizing conditions. Thioredoxins f and m mediate the reversible reductive activation of oxidized CHLI (By similarity)
NADPH oxidase activity is stimulated by calcium ions
Zinc and calcium ions cooperatively modulate enzyme activity. The cleavage of the pro-domain is not required for protease activity. Dependence on calcium for proteolytic activity is mediated by the high affinity site
Inhibited by CST6
Completely inhibited by succinate and low-aeration conditions
Inhibited by zinc (By similarity). Inhibited by the serine proteinase inhibitor 4-(2-aminoethyl)benzenesulphonyl fluoride (AEBSF), and by di-isopropylfluorophosphate (By similarity). Specifically inhibited by isoindoline derivatives (By similarity). Inhibited by Val-boroPro (Talabostat, PT-100), a non-selective inhibitor, which triggers pyroptosis in monocytes and macrophages (PubMed:27820798, PubMed:29396289)
The CARD domain inhibits the activation of E3 ubiquitin ligase activity by preventing RING domain dimerization and E2 ubiquitin donor binding and activation. The CARD domain-mediated autoinhibition of the E3 ubiquitin-protein ligase activity suppresses cell proliferation and migration. USP19 regulates the stability of BIRC2/c-IAP1 by preventing its ubiquitination (By similarity)
Inactivated by diethyl pyrocarbonate (DEPC)
Activity is divalent cation-dependent. It is stimulated by manganese, magnesium or calcium ions and reversibly inhibited by zinc, cobalt and iron (By similarity)
Activated by free cytoplasmic calcium
Almost insensitive to rapamycin (PubMed:23963679). Strongly repressed by specific active site inhibitors (asTORis) such as AZD-8055, TORIN2 and WYE-132, and, to a lesser extent, by KU63794, WYE-354 and TORIN1, leading to impaired photoautotrophic growth and abnormally early meristematic cells differentiation (PubMed:23963679, PubMed:23524850). Repression by TORIN1 leads to impaired responses to auxin, including gravitropism (PubMed:23524850). Combined treatment with rapamycin and active-site inhibitors (e.g. Torin1 and AZD-8055) results in synergistic inhibition of activity and plant growth (PubMed:27479935). Inhibition by KU63794 leads to reduced auxin content in root tips (PubMed:27014314). AZD-8055 treatment reduces abscisic acid (ABA) levels (PubMed:26459592). In addition, inhibition by AZD-8055 leads to a strong reduction of watermelon mosaic virus (WMV) infection (PubMed:25979731)
Inhibited by magnesium, when its concentration exceeded the ATP one, and by high concentration of ATP and alpha-ketoglutarate
A head-to-tail association, of the N-terminal and C-terminal halves results in a closed conformation (inactive form) which is incapable of actin or membrane-binding
Inhibited by EGTA and apstatin, and, to some extent, by the flavonoid kaempferol
Allosterically activated by benzodiazepines (By similarity). Activated by pentobarbitol (By similarity). Inhibited by the antagonist bicuculline (By similarity). Inhibited by zinc ions (By similarity)
During activation, the N-terminal disordered prodomain is removed by cleavage. Concomitantly, double cleavage gives rise to a large 18-kDa and a small 11-kDa subunit. The two large and two small subunits then assemble to form the active CASP6 complex. Can be cleaved and activated by different caspases, depending on the context. Cleaved and activated by caspase-8 (CASP8) and subsequently by caspase-3 (CASP3). Can also undergo autoactivation by mediating autocleavage at Asp-162 and Asp-175, while it is not able to cleave its N-terminal disordered prodomain. Intramolecular cleavage at Asp-175 is a prerequisite for CASP6 self-activation. Cleaved and activated by CASP1 in neurons, possibly in the context of inflammation. Phosphorylation at Ser-239 inhibits autocleavage, preventing caspase activation
Rab activation is generally mediated by a guanine exchange factor (GEF), while inactivation through hydrolysis of bound GTP is catalyzed by a GTPase activating protein (GAP) (By similarity). That Rab is activated by the DENND4C guanine exchange factor (GEF) (Probable). That Rab is activated by the DENND4C and RABIF guanine exchange factors (GEF) (By similarity)
Activated by autophosphorylation. Prior phosphorylation at Tyr-511 by SRC inhibits ulterior autophosphorylation at Tyr-400. Activated by phorbol myristate acetate, phosphatidic acid and poly-Lys. Binding (via SH2 domain) of HCLS1 that is already phosphorylated by SYK strongly increases kinase activity
The channel activity is regulated via the N-terminal cytoplasmic region, which acts as a Mg(2+) sensor to regulate the gating of the ion-conducting pore in response to the intracellular magnesium concentration (PubMed:19798051, PubMed:25367295, PubMed:33905418). Under high-intracellular magnesium conditions, binding of magnesium to the N-terminal cytoplasmic domain stabilizes the closed conformation of the channel (PubMed:19798051, PubMed:25367295, PubMed:33905418). Under low-intracellular magnesium conditions, the channel is in equilibrium between the open and closed states (PubMed:19798051). A cation-binding site within the membrane (M1) strictly recognizes the size and geometry of the Mg(2+) hydration shells, which may be important for the selective transport of Mg(2+) over other cations (PubMed:25367295). Cation-binding sites on the periplasmic side (M2 and M3) regulate channel opening and prevent conduction of near-cognate cations (PubMed:25367295). Binding of Mn(2+) to the periplasmic sites strongly inhibits the Mg(2+) transport activity (PubMed:25367295). In addition, activity is regulated by ATP, which binds to MgtE and modulates its Mg(2+)-dependent channel gating (PubMed:28747715). ATP binding enhances the intracellular domain affinity for Mg(2+) within physiological concentrations of this divalent cation, enabling MgtE to function as an in vivo Mg(2+) sensor (PubMed:28747715). ATP dissociation from MgtE upregulates Mg(2+) influx at both high and low intracellular Mg(2+) concentrations (PubMed:28747715)
A sequential activation is proposed: autophosphorylation at consensus sites is leading to dimerization of the catalytic domain stabilized by phosphorylation at Ser-50 and activation segment exchange (producing an active confirmation of both kinase modules in trans) followed by phosphorylation at Thr-180 in the activation segment and at other regulatory sites (Probable). Phosphorylation at Thr-180, Thr-225 and Thr-265 is essential for activity. Oligomerization is required for full enzymatic activity. Inhibited by pyridone-6 (K00225), a potent, ATP-competitive inhibitor
Inhibited by S-adenosyl homocysteine
Activity is probably regulated by the inactive BbsC subunit
Inhibited by metal cations Co(2+), Cu(2+), Ni(2+), Pb(2+) and Zn(2+) (PubMed:22072709). Not inhibited by metal chelator ethylenediaminetetraacetic acid (EDTA) (PubMed:22072709)
Non-competitively inhibited by MMPA, weakly inhibited by substrate analogs dimethylsulfoniobutanoate and dimethylsulfoniopentanoate. It is used as an intracellular osmolyte
Activated by ATP (By similarity). ATP binding leads to a conformational change that promotes FAD cofactor binding and enzyme activity (By similarity). ATP binding likely occurs during acox-1.3 folding and/or dimer formation (By similarity)
Inhibited by aziridino-diaminopimelate (AziDAP)
Activated by phosphatidylserine
Inhibited by iodoacetamide and by the glutamine analogs chloroketone and DON
The cytoplasmic tail of TRAP and probably other adhesins acts as a competitive inhibitor as the binding sites of the glycolytic substrate fructose 1,6-bisphosphate and TRAP partially overlap
Two specific sites, one in the kinase domain (Thr-320) and the other in the C-terminal regulatory region (Ser-486), need to be phosphorylated for its full activation
Activated by autocatalytic cleavage (PubMed:23814066). Cleavage by CTRC inhibits autoactivation (PubMed:23814066)
Inhibited by PMSF and Prefabloc, as well as leupeptin at high concentrations (PubMed:16385448). Partially inhibited by TPCK, a chymotrypsin inhibitor and E64, a cysteine protease inhibitor (PubMed:16385448). Not affected by 4-amidinophenyl-methanesulfonyl fluoride (APMSF), pepstatin or EDTA (PubMed:16385448). Inhibited by 1-isobutyl-3-oxo-3,5,6,7-tetrahydro-2H-cyclopenta[c]pyridine-4-carbonitrile (PubMed:28726805)
Inhibited by SERPINA1, SERPINC1, SERPINE1, SERPINF2, aprotinin, soybean, trypsin inhibitor and leupeptin. Inhibited by serine protease inhibitor SPINK5. Has an autoproteolytic activity which may have a regulatory effect. Activated by citrate and inhibited by zinc and to a lower extent by manganese (By similarity)
Inhibited by divalent cations
The matrix-open state (m-state) is inhibited by the membrane-permeable bongkrekic acid (BKA) (By similarity). The cytoplasmic-open state (c-state) is inhibited by the membrane-impermeable toxic inhibitor carboxyatractyloside (CATR) (PubMed:21586654). Proton transporter activity is inhibited by ADP:ATP antiporter activity (By similarity)
The side chain of Glu-234 determines which of the two opposing activities (AMPylase or de-AMPylase) will take place. In response to endoplasmic reticulum stress, mediates de-AMPylase activity (By similarity). Adenylyltransferase activity is inhibited by the inhibitory helix present at the N-terminus: Glu-234 binds ATP and competes with ATP-binding at Arg-374, thereby preventing adenylyltransferase activity (PubMed:22266942, PubMed:25435325). In unstressed cells, disengagement of Glu-234 promotes adenylyltransferase activity (By similarity). Activation dissociates ATP-binding from Glu-234, allowing ordered binding of the entire ATP moiety with the alpha-phosphate in an orientation that is productive for accepting an incoming target hydroxyl side chain (PubMed:22266942, PubMed:25435325)
In its inactive state, the C-terminal tail interacts with the catalytic domain and inhibits the kinase activity. Upon ligand binding, the C-terminal tail is displaced and becomes phosphorylated, thus increasing the kinase activity
rRNA N6-adenosine-methyltransferase activity is inhibited by zinc
Inhibited by cellobiose
Protease activity is induced in response to various mitochondrial stress
Allosterically activated by various compounds including ATP, 2,3-BPG/2,3-Bisphosphoglyceric acid and Ap4A/P1,P4-bis(5'-adenosyl) tetraphosphate (PubMed:1659319, PubMed:10092873, PubMed:21396942). Binding of an allosteric activator is a prerequisiste to magnesium and substrate binding (PubMed:21396942). Inhibited by inorganic phosphate (PubMed:10092873)
The covalent binding to the substrate at Lys-340 of a small fraction of enolase causes inactivation of the enzyme, and possibly serves as a signal for the export of the protein
Reversibly inhibited by EDTA and free zinc ions. Enzyme is inactivated by dialysis against 1,10-phenanthroline, which is a zinc specific chelator
Inhibited by the product IMP (PubMed:12070315). Highly inhibited by nucleoside phosphonates, which are product analogs (PubMed:23927482, Ref.6)
Inhibited by the SB418011 antibiotic (PubMed:11375394). Not inhibited by cerulenin, and weakly inhibited by thiolactomycin (PubMed:11375394)
Activated by GTP and inhibited by CTP
Present in an inactive conformation in the absence of bound ligand. Ligand binding leads to dimerization and activation by autophosphorylation on tyrosine residues (By similarity)
Inhibited by brefeldin A
Activated by forskolin (PubMed:1618857, PubMed:8428899). Activated by GNAS. Activity is further increased by interaction with the G-protein beta and gamma subunit complex formed by GNB1 and GNG2 (By similarity). Is not activated by calmodulin. Inhibited by adenosine and ATP analogs. Inhibited by calcium ions, already at micromolar concentrations (PubMed:1618857). Phosphorylation by RAF1 results in its activation (By similarity)
Is inhibited by AMP; the mode of AMP inhibition is uncompetitive for both TMP and ATP
Inhibited by 3,4-dichloroisocoumarin and PMSF
Inhibited by antizyme (AZ) OAZ1 in response to polyamine levels. AZ inhibits the assembly of the functional homodimer by binding to ODC monomers and targeting them for ubiquitin-independent proteolytic destruction by the 26S proteasome
Inhibited by suramin with an IC(50) of 4.1 uM
Inhibited by cyanide and by sulfide and iron reagents such as dithioerythritol, 2,2'-dipyridyl and o-phenanthroline
Sensitive to serine proteinase inhibitors and thiol proteinase inhibitors
Inhibited by harpin, S-nitrosoglutathione (GSNO), nitric oxide, N-ethylmaleimide and 5,5'-dithiobis-(2-nitrobenzoic acid)
Inhibited by benzamidine, PMSF, leupeptin, SDS and DTT, but not by EDTA, and commercial antivenom
Inhibited by the specific serine esterase inhibitor AEBSF
Inhibited by the thiol reagents iodoacetate (IAA) and N-ethylmaleimide (NEM) (PubMed:7577935). Activity is rapidly inactivated by the histidine-modifying reagent diethylpyrocarbonate (DEPC) (PubMed:8969183)
Inhibited by cGMP
inhibited by phenylarsine oxide (PAO)
Competitive inhibition by NADH. Inhibited by ATP, ADP and AMP. Redox-regulated. Inhibited under oxydizing conditions (By similarity)
Inhibited by NaCl. Enhanced activity by NAD(+). Slightly inhibited by UDP
Inhibited by N-ethylmaleimide (PubMed:21177865). Redox-regulated during autophagy since reducing conditions activate ATG4A whereas an oxidizing environment such as the presence of H(2)O(2) inhibits its activity (PubMed:17347651). The cysteine protease activity compounds is inhibited by styrylquinoline compounds 4-28 and LV-320 (PubMed:30076329)
Inhibited by amiclenomycin. S-adenosyl-L-(2-hydroxy-4-methylthio)butyric acid and adenosine are competitive inhibitors with SAM and uncompetitive inhibitors with KAPA as substrates (PubMed:1092682). S-adenosyl-L-ethionine, adenine and 8-keto-7-aminopelargonic acid are non-competitive inhibitors with both substrates (PubMed:1092682)
Nucleosides, and particularly 2'-deoxyribonucleosides, are potent inhibitors of the phosphatase activity. The phosphatase activity is also inhibited by inorganic phosphate and EDTA in vitro
Active under anaerobic conditions
Allosterically regulated. The binding of 5-methylcytosine-containing DNA to the N-terminal parts of DNMT1 causes an allosteric activation of the catalytic domain by a direct interaction of its Zn-binding domain with the catalytic domain
Inhibited by hydrolyzation product alpha-galactopyranose and to a lesser extent by beta-galactopyranose, its mutarotational product (PubMed:26005928). Inhibited by synthetic cyclopropyl carbasugars (PubMed:27783466)
Feedback inhibition by glutathione. Inhibited by buthionine sulfoximine and cystamine
Inactivated by sulphydryl reagent
Activated by cobalt and manganese ions
Unaffected by 5,5'-dithiobis-(2-nitrobenzoic acid), 4-chloromercuribenzoate and sodium azide. Inhibited by Cu(2+), Fe(2+) and Zn(2+). Unaffected by Na(+), K(+) and Li(+)
Up-regulated by LALBA
Is inhibited by 8-nitro-benzothiazinones (BTZs) such as BTZ043; BTZs are a new class of antimycobacterial agents that block formation of both cell-wall lipoarabinomannan and arabinogalactan via inhibition of decaprenyl-phospho-arabinose (DPA) synthesis (PubMed:19299584, PubMed:22188377). BTZs are suicide inhibitors that act via covalent modification of DprE1; the essential nitro group of these compounds is reduced by DprE1 to a nitroso group, which then specifically reacts with Cys-386 of DprE1 to form an irreversible semimercaptal adduct (PubMed:22188377, PubMed:22956199). Other compounds with diverse scaffolds (dinitrobenzamides and nitrobenzoquinoxalines) also act as covalent DprE1 inhibitors (PubMed:22956199)
Inhibited by citrate, succinate and tartrate
Activity is regulated by phosphorylation at Ser-49 and Ser-52, which stabilizes the eIF2/GDP/eIF-2B complex and prevents the eIF-2B-mediated exchange of GDP for GTP, thereby preventing the formation of the 43S pre-initiation complex (43S PIC) (PubMed:15207627, PubMed:18032499). This results in the global attenuation of 5' cap-dependent protein synthesis and concomitant translation of ISR-specific mRNAs that contain a short upstream open reading frame (uORF) in their 5' UTR, such as ATF4, ATF5, DDIT3/CHOP and PPP1R15A/GADD34 (PubMed:19131336)
DNA kinase activity is inhibited by 250 mM sodium chloride whereas RNA kinase activity is unaffected
Inhibited by Zn(2+), Cu(2+) and Cd(2+)
Inhibited by N-ethyl-maleimide (NEM)
Activity is not affected by metal ions except Mn(2+), which reduces the activity by 40-50%. However, no significant change in activity in response to 1 mM EDTA
Inhibited by aminooxyacetate
Inhibited by 9-cis-, 13-cis- and all-trans-retinoic acids, with the most potent inhibitor being 13-cis-retinoic acid. Weakly inhibited by oleic acid
Ceramide synthase activity is inhibited by sphingosine-1-phosphate
In contrast to other AGC family kinases, the catalytic activity is solely regulated by the binding of substrates and ligands, not by phosphorylation of the kinase domain
Inhibited by Na(2+)
Inhibited weakly by methotrexate
Inhibited by mercury. Inhibited by Tabun. Tabun forms a covalent adduct with Ser-226 that becomes irreversible upon aging
Inhibited by the addition of an excess of H4F
Inhibited by anhydrotetracycline
Inhibited by vanadate and zinc, and slightly by calcium
Inhibited by (S)-benzylsuccinyl-CoA
Carboxylation at Lys-302 increases the catalytic activity of the enzyme
ADP-ribosyltransferase activity is regulated via an allosteric activation mechanism (PubMed:22582261, PubMed:26626479, PubMed:32358582, PubMed:26626480, PubMed:32241924). In absence of activation signal, PARP1 is autoinhibited by the PARP alpha-helical domain (also named HD region), which prevents effective NAD(+)-binding (PubMed:26626479, PubMed:26626480, PubMed:32241924). Activity is highly stimulated by signals, such as DNA strand breaks (PubMed:20388712, PubMed:32358582, PubMed:32241924). Binding to damaged DNA unfolds the PARP alpha-helical domain, relieving autoinhibition (PubMed:22582261, PubMed:26626479, PubMed:26626480, PubMed:32241924). Poly-ADP-ribosyltransferase activity is tightly regulated and PARP1 is removed from damaged chromatin following initial poly-ADP-ribosylation of chromatin to avoid prolonged residence (trapping) that has cytotoxic consequences (PubMed:34210965, PubMed:34625544, PubMed:35013556). A number of factors (VCP/p97) or post-translational modifications (auto-poly-ADP-ribosylation or ubiquitination) promote PARP1 removal from chromatin (PubMed:34210965, PubMed:34625544, PubMed:35013556). ADP-ribosyltransferase activity is inhibited by a number of PARP inhibitors (PARPi) compounds, that are used the treatment of breast or ovarian cancers that have defects in DNA repair by homologous recombination (PubMed:32358582, PubMed:29487285, PubMed:32241924). PARPi molecules can be classified in three categories: type I compounds (EB-47, UKTT15 and BAD) that promote allosteric retention of PARP1 on DNA, type II inhibitors (talazoparib and olaparib) that mediate a non-allosteric inhibition, and type III inhibitors (rucaparib, niraparib, and veliparib) that promote allosteric release from DNA (PubMed:29487285, PubMed:32241924, PubMed:33361107). Trapping to chromatin by PARPi molecules triggers activation of the cGAS-STING pathway (PubMed:32844745)
Homotetramerization is required for activity (Probable). Tetramerization results in the formation of a gated channel which is involved in substrate selection and substrate access to the catalytic sites (Probable)
Target ssDNA cleavage is inhibited by EDTA (PubMed:30337455). Activity is maximal with 5-50 mM NaCl, is less efficient at higher NaCl concentrations (PubMed:32246713, PubMed:33333018)
Activation of mTORC1 by growth factors such as insulin involves AKT1-mediated phosphorylation of TSC1-TSC2, which leads to the activation of the RHEB GTPase a potent activator of the protein kinase activity of mTORC1. Insulin-stimulated and amino acid-dependent phosphorylation at Ser-1261 promotes autophosphorylation and the activation of mTORC1. Activation by amino acids requires relocalization of the mTORC1 complex to lysosomes that is mediated by the Ragulator complex, SLC38A9, and the Rag GTPases RRAGA, RRAGB, RRAGC and RRAGD. On the other hand, low cellular energy levels can inhibit mTORC1 through activation of PRKAA1 while hypoxia inhibits mTORC1 through a REDD1-dependent mechanism which may also require PRKAA1. The kinase activity of MTOR within the mTORC1 complex is positively regulated by MLST8 and negatively regulated by DEPTOR and AKT1S1. MTOR phosphorylates RPTOR which in turn inhibits mTORC1. MTOR is the target of the immunosuppressive and anti-cancer drug rapamycin which acts in complex with FKBP1A/FKBP12, and specifically inhibits its kinase activity. mTORC2 is also activated by growth factors, but seems to be nutrient-insensitive. It may be regulated by RHEB but in an indirect manner through the PI3K signaling pathway
The channel is inhibited by clotrimazole and charybdotoxin but is insensitive to apamin
No requirement for divalent cations and insensitive to p-chloromercuribenzoate, iodoacetate, or iodoacetamide
Inhibited by dopamine with an IC(50) of 32.6 uM for the unphosphorylated form and 43.4 uM for the phosphorylated form (PubMed:21087208). Phosphorylation leads to an increase in the catalytic activity (By similarity)
Allosterically activated by fructose 2,6-bisphosphate
Cold receptor activity activated by temperatures between 10-19 degrees Celsius
Insensitive to 3'phosphoglycerate and orthophosphate
Inhibited by 4-quinoline drugs (nalidixic acid, ciprofloxacin, ofloxacin), although it is much less sensitive than the corresponding enzyme from E.coli (PubMed:8878580). GyrB intrinsic ATPase activity inhibited by aminopyrazinamide and pyrrolamide derivatives (PubMed:23268609, PubMed:24126580)
Isoform 1 is activated by phosphorylation on Tyr-464 and Tyr-471. Isoforms which lack these tyrosine residues are not regulated in this way. All catalytically active isoforms require binding to calcium and calmodulin for activation. Repressed by organometallic pyridylnaphthalimide complexes, wortmannin, ML-7 (a synthetic naphthalenesulphonyl derivative that inhibits the binding of ATP to MLCK) and ML-9
Polymerization and secretion of adiponectin is inhibited by succination of cysteine residues by the Krebs cycle intermediate fumarate, which leads to S-(2-succinyl)cysteine residues
Inactivated by the serine protease inhibitor diisopropylfluorophosphate
Partially inhibited by the serine protease inhibitor phenylmethanesulfonyl fluoride (PubMed:28124733). Inhibited by various ions, including copper, iron, sodium, potassium, magnesium and calcium (PubMed:28124733). Inhibited by the chelating agent EDTA (ethylenediaminetetraacetic acid) (PubMed:28124733). Inhibited by the surfactants sodium dodecyl sulfate and polysorbate 80 (PubMed:28124733)
Is inhibited by bromopyruvate in vitro. Activity is not affected by the presence of tellurite
The side chain of Glu-251 determines which of the two opposing activities (AMPylase or de-AMPylase) will take place. In response to endoplasmic reticulum stress, mediates de-AMPylase activity (By similarity). Adenylyltransferase activity is inhibited by the inhibitory helix present at the N-terminus: Glu-251 binds ATP and competes with ATP-binding at Arg-391, thereby preventing adenylyltransferase activity (By similarity). In unstressed cells, disengagement of Glu-251 promotes adenylyltransferase activity (By similarity). Activation dissociates ATP-binding from Glu-251, allowing ordered binding of the entire ATP moiety with the alpha-phosphate in an orientation that is productive for accepting an incoming target hydroxyl side chain (By similarity)
Subject to autoinhibition, mediated by intramolecular interactions between the SH2 domain and the C-terminal phosphotyrosine. Phosphorylation at Tyr-397 is required for optimal activity. Phosphorylated by CSK at Tyr-508; phosphorylation at Tyr-508 inhibits kinase activity. Kinase activity is modulated by dephosphorylation by PTPRC/CD45. Inhibited by Dasatinib, PP2, and SU6656
Active when the heme iron is in the ferrous state
Binding to NEK9 stimulates its activity by releasing the autoinhibitory function of Tyr-108
Sensitive to lysine inhibition. This inhibition increase in an allosteric manner with increasing concentration of the inhibitor
Activated by phosphorylation on threonine and tyrosine. Inhibited by pyridinyl-imidazole related compounds
Mycophenolic acid (MPA) is a non-competitive inhibitor that prevents formation of the closed enzyme conformation by binding to the same site as the amobile flap. In contrast, mizoribine monophosphate (MZP) is a competitive inhibitor that induces the closed conformation. MPA is a potent inhibitor of mammalian IMPDHs but a poor inhibitor of the bacterial enzymes. MZP is a more potent inhibitor of bacterial IMPDH (By similarity). Inhibited by the products XMP and NADH. Significantly inhibited in vitro by a panel of diphenyl urea-based derivatives and a series of novel classes of inhibitors, which are also potent anti-mycobacterial agents against M.tuberculosis and M.smegmatis (PubMed:21081761) (PubMed:22479467). Is also inhibited by a mycophenolic adenine dinucleotide (MAD) derivative in which a 1,2,3-triazole linker was incorporated as isosteric replacement of the pyrophosphate linker, thereby mimicking NAD (PubMed:20491506). Other inhibitors with modular structures consisting of two aromatic moieties connected by different linkers (such as urea and amide) have been identified and shown to exhibit antitubercular activity (PubMed:26440283)
Activity increased by 58%-93% in the presence of acetyl phosphate, 3-phosphoglycerate or 2,3-bisphosphoglycerate at 10 mM concentration. Inhibited by up to 25% in the presence of crotonaldehyde or formaldehyde at 10 mM concentration. Inhibited by up to 50% by sodium dithionate. 3.5-fold increase in activity observed by addition of potassium phosphate or sodium arsenate at 200 mM concentration. Activity enhanced by potassium chloride, sodium citrate or sodium sulfate at 200 mM concentration. Sensitive to oxygen
PAM activity is inhibited by EDTA, phenylglyoxal and diethyl pyrocarbonate (By similarity). PAL activity is stimulated by cadmium and inhibited by mercury (By similarity)
Activation requires autophosphorylation of Ser-332. Phosphorylation of Ser-328 also promotes increased activity (By similarity)
Activity of the enzyme is Mn(2+)-dependent and enhanced in the presence of pyrophosphate (PPi)
Inhibited by captopril stereoisomers, Hg(2+), Fe(2+), Cu(2+) and by chelating agents such as EDTA (PubMed:8141584, PubMed:26482303). This enzyme is not susceptible to inactivation by the beta-lactamase-blocking agents clavulanic acid or cloxacillin (PubMed:8141584)
The matrix-open state (m-state) is inhibited by the membrane-permeable bongkrekic acid (BKA). The cytoplasmic-open state (c-state) is inhibited by the membrane-impermeable toxic inhibitor carboxyatractyloside (CATR)
Calcium(2+)/calmodulin dependent activity (PubMed:9144159). Undergoes calcium/calmodulin-dependent intramolecular autophosphorylation, and this results in it becoming partially calcium/calmodulin-independent
MSAMO is inhibited by metal chelators (such as bathophenanthroline, bathocuprione, neocuprione, alpha-alpha-dipyridil and sodium EDTA) and by sodium azide, sodium arsenate and potassium cyanide
Activated by fructose 2,6-bisphosphate, activated by the effector in a non cooperative manner
Is inhibited by 8-nitro-benzothiazinones (BTZs) such as BTZ043 and PBTZ169; BTZs are a new class of antimycobacterial agents that kill M.tuberculosis in vitro, ex vivo, and in mouse models of tuberculosis. Is also inhibited by dinitrobenzamide derivatives (DNBs), which thus block formation of both cell-wall lipoarabinomannan and arabinogalactan via inhibition of decaprenyl-phospho-arabinose (DPA) synthesis; DNBs show high activity against intracellular growth of M.tuberculosis inside macrophages, including extensively drug resistant (XDR) strains. BTZs and DNBs are suicide inhibitors that act via covalent modification of DprE1; the essential nitro group of these compounds is reduced by DprE1 to a nitroso group, which then specifically reacts with Cys-387 of DprE1 to form an irreversible semimercaptal adduct. Many other compounds with diverse scaffolds were found to act as either covalent (e.g. nitroquinoxalines, nitroimidazoles) or non-covalent (e.g. the benzothiazole derivative TCA1, the 2-carboxyquinoxaline Ty38C, 8-pyrrole-benzothiazinones, 1,4-azaindoles, pyrazolopyridones, 4-aminoquinolone piperidine amides) DprE1 inhibitors
Sensitive to valine inhibition
Inhibited by EDTA or 1,10-phenanthroline. Not inhibited by PMSF
Addition of GM2A stimulates the hydrolysis of sulfated glycosphingolipid SM2 and the ganglioside GM2
Feedback inhibited by histidine. Also inhibited by AMP and ADP
Catalytically inactive when the propeptide is intact and associated with the mature enzyme (By similarity). The disintegrin and cysteine-rich regions modulate access of substrates to exerts an inhibitory effect on the cleavage of ADAM10 substrates (By similarity)
Nuclease activity is regulated by Rad50
Binding of a cognate ligand leads to dimerization and activation by autophosphorylation on tyrosine residues. In vitro kinase activity is increased by Mg(2+) (By similarity)
Strongly inhibited by beta-mercaptoethanol, sodium azide and potassium cyanide. Slightly repressed by 3-amino-1,2,4-triazole (3-AT). Activity is repressed proportionally to increased concentration of NaCl, KCl and MgCl(2), and, to a lower extent, of LiCl
Converted into plasmin by plasminogen activators, both plasminogen and its activator being bound to fibrin. Activated with urokinase and high concentrations of streptokinase
Inhibited by adenosine and GTP
Inactivated by phenylglyoxal by binding covalently to two arginine residues
Activated by phosphorylation on Thr-183. Binding of AMP to non-catalytic gamma subunit (PRKAG1, PRKAG2 or PRKAG3) results in allosteric activation, inducing phosphorylation on Thr-183. AMP-binding to gamma subunit also sustains activity by preventing dephosphorylation of Thr-183. ADP also stimulates Thr-183 phosphorylation, without stimulating already phosphorylated AMPK. ATP promotes dephosphorylation of Thr-183, rendering the enzyme inactive. Under physiological conditions AMPK mainly exists in its inactive form in complex with ATP, which is much more abundant than AMP. Selectively inhibited by compound C (6-[4-(2-Piperidin-1-yl-ethoxy)-phenyl)]-3-pyridin-4-yl-pyyrazolo[1,5-a] pyrimidine. Activated by resveratrol, a natural polyphenol present in red wine, and S17834, a synthetic polyphenol (By similarity)
Inhibited by p-hydroxymercuribenzoate and p-chloromercuriphenylsulfonate
Inhibited by aureobasidin A (AbA), khafrefungin and rustmicin
Isoleucine uptake is efficiently reduced in the presence of 100-fold excess valine, leucine, alanine, threonine, serine, cysteine, asparagine, and a nonproteinaceous amino acid 4-azaleucine
Inhibited by EDTA, Cu(2+) and Zn(2+)
Completely inhibited by allopurinol and significantly inhibited by adenine. Inhibited by Fe(2+), Cd(2+) and Zn(2+) and strongly inhibited by Cu(2+). Mg(2+) and Mo(2+) have no effect on activity
Inhibited by aprotinin and dithiothreitol
Inhibited by UDP
Strand annealing activity is inhibited by 150 mM NaCl (in vitro)
L-cysteine binding is slower in the presence of bcn92 and IscU (PubMed:29491838). Activation requires bcn92, IscU and fh (PubMed:29491838)
Inhibited by 1,2,3-triazole urea covalent inhibitors KT172, DH376 and DO34 (By similarity). Inhibited by p-hydroxy-mercuri-benzoate and HgCl(2), but not to PMSF. Also inhibited by RHC80267. Diacylglycerol lipase activity is inhibited by the phosphorylation of Ser-784 and Ser-810 by CAMK2A (By similarity)
(Microbial infection) Binds to viral protein RIP (AC Q3V4R7), which inhibits global transcription
Rab activation is generally mediated by a guanine exchange factor (GEF), while inactivation through hydrolysis of bound GTP is catalyzed by a GTPase activating protein (GAP). That Rab may be activated by DENND1C, a guanine exchange factor. Activated in response to insulin (By similarity)
Activated by phosphorylation at Tyr-216. In response to insulin, inhibited by phosphorylation at Ser-9 by PKB/AKT1 and RPS6KA3; phosphorylation at this site causes a conformational change, preventing access of substrates to the active site. Inhibited by lithium
Strongly inhibited by ZnCl(2) and by EDTA
Inhibited by GMP
Activated by calcium (PubMed:23252373). Autophosphorylation plays an important role in the regulation of the kinase activity (PubMed:23252373)
Activation of apourease within the UreDFG-apoprotein complex is inhibited by zinc, copper and cobalt
Is overexpressed in mecA, clpC and clpP mutants, suggesting the protein level is controlled by MecA, ClpC and ClpP (at protein level)
Inhibited by fluoride and InsP6
Hemagglutination activity is not dependent on divalent cations. Hemagglutination activity is highly inhibited by D-galactose and N-acetyl-D-galactosamine, and to a lesser extent by raffinose. Also inhibited by melibiose and alpha-lactose, but not by beta-lactose or D-glucose
Inhibited by Co(2+), Ni(2+) and Zn(2+), which may inhibit enzyme activity by replacing iron in the catalytic residues (PubMed:23391906). Inhibited by incubation with high concentrations of the iron chelators 1,10-phenanthroline and Tiron (PubMed:23391906). However, iron is not completely removed by the chelators, suggesting that iron is tightly bound to the enzyme (PubMed:23391906)
Inhibited by cerulenin by covalent binding to active site of the ketoacyl synthase (KS) region
By phosphorylation
Cholesterol O-acyltransferase activity is inhibited by nevanimibe
In contrast to the human ortholog, not activated by progesterone
Reversibly inactivated by selenide and sulfide. Not inhibited by cyanide
Specifically and significantly activated by CoCl(2). Competitively inhibited by MAPG, but not by 2-hydroxy- and 4-hydroxyacetophenone
Novel PKCs (PRKCD, PRKCE, PRKCH and PRKCQ) are calcium-insensitive, but activated by diacylglycerol (DAG) and phosphatidylserine. Three specific sites; Thr-505 (activation loop of the kinase domain), Ser-643 (turn motif) and Ser-662 (hydrophobic region), need to be phosphorylated for its full activation. Activated by caspase-3 (CASP3) cleavage during apoptosis. After cleavage, the pseudosubstrate motif in the regulatory subunit is released from the substrate recognition site of the catalytic subunit, which enables PRKCD to become constitutively activated. The catalytic subunit which displays properties of a sphingosine-dependent protein kinase is activated by D-erythro-sphingosine (Sph) or N,N-dimethyl-D-erythrosphingosine (DMS) or N,N,N-trimethyl-D-erythrosphingosine (TMS), but not by ceramide or Sph-1-P and is strongly inhibited by phosphatidylserine
Increased by calcium
Under complex allosteric control mediated by deoxynucleoside triphosphates and ATP binding to separate specificity and activation sites on the alpha subunit. The type of nucleotide bound at the specificity site determines substrate preference. It seems probable that ATP makes the enzyme reduce CDP and UDP, dGTP favors ADP reduction and dTTP favors GDP reduction. Stimulated by ATP and inhibited by dATP binding to the activity site (By similarity)
Is activated by 2,3-dimercaptopropan-1-ol
Activated by forskolin (PubMed:11055432, PubMed:25329148). After forskolin treatment, activity is further increased by calcium/calmodulin. In the absence of forskolin, calcium/calmodulin has little effect on enzyme activity (By similarity)
Has no constitutive proton transporter activity and has to be activated by long-chain fatty acids/LCFAs. Inhibited by purine nucleotides. Both purine nucleotides and LCFAs bind the cytosolic side of the transporter and directly compete to activate or inhibit it (PubMed:23063128). Activated by noradrenaline and reactive oxygen species (PubMed:27027295). Despite lacking canonical translational encoding for selenocysteine, a small pool of the protein has been observed to selectively incorporate selenocysteine at 'Cys-254' (PubMed:32358195). Selenocysteine-modified protein is highly sensitive to redox modification and may constitute a pool of protein highly sensitive to activation by elevated levels of reactive oxygen species (ROS) (PubMed:32358195)
The epoxide hydrolase activity is mildly restrained by suicide inactivation, possibly involving binding of LTA4 to Tyr-380
Inhibited by sulfhydryl reagents
Fructose-1,6-bisphosphatase II is not light-activated
Inhibited by 2-fluorogeranyl diphosphate (FGPP) and 2-fluoroneryl diphosphate (FNPP)
Protein kinase activity is inhibited by the first PAS domain: binding of an unidentified ligand desinhibits the protein kinase activity. May be activated by autophosphorylation on Thr-1221 and Thr-1225. Autophosphorylation is enhanced upon phosphatidylinositol monophosphate (phosphatidylinositol 4-phosphate) binding and inhibited upon phosphatidylinositol bi- and tri-phosphate binding. In contrast, phosphorylation of target proteins is inhibited upon all phosphatidylinositol-binding (phosphatidylinositol mono- bi- and tri-phosphate) (By similarity)
Acetyltransferase activity increases in presence of the kinase substrate, sphingosine (PubMed:29662056). In Purkinje cells, kinase activity on sphingosine increases in presence of VEGFA (PubMed:25417698). In neurons, kinase activity increases during the first 24h in presence of Amyloid-beta protein 42 to decrease after 96h (By similarity)
Catalytically inactive when the propeptide is intact and associated with the mature enzyme (By similarity). The disintegrin and cysteine-rich regions modulate access of substrates to exerts an inhibitory effect on the cleavage of ADAM10 substrates (PubMed:29224781)
Allosterically inhibited by cyclic di-GMP (c-di-GMP), which binds to Clp and abolishes its ability to bind its target gene promoter
Inhibited by PMSF, but not by heparin, hirudin and antithrombin-III
The dimers display cooperative channel gating (By similarity). The channel activity is inhibited by zinc ions
ATPase activity is stimulated 3-fold by DNA (both free and nucleosomal) binding
Inhibited by acetylation at Lys-661 and activated by deacetylation mediated by the deacetylases SIRT1 and SIRT3
Upon extracellular signal or mitogen stimulation, phosphorylated at Thr-573 in the C-terminal kinase domain (CTKD) by MAPK1/ERK2 and MAPK3/ERK1. The activated CTKD then autophosphorylates Ser-380, allowing binding of PDPK1, which in turn phosphorylates Ser-221 in the N-terminal kinase domain (NTDK) leading to the full activation of the protein and subsequent phosphorylation of the substrates by the NTKD
Inhibited by compound 1 or (5,5-Dioxido-4H-thieno[3,2-c]thiochromen-2-yl)(4-(4-methoxyphenyl)piperazin-1-yl)methanone
Undergoes competitive inhibition by its own product 1,2-diacyl-sn-glycero-3-phosphate/phosphatidic acid. The strongest inhibition being observed in vitro with 1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphate, a major intermediate in the phosphatidylinositol turnover cycle and more generally by diacylglycerols with an arachidonoyl acyl chain at the sn-2 position
Magnesium is essential for activity (PubMed:4579631). Inhibited by chloride and sulfate in the presence of 1 mM free Mg(2+). When the Mg(2+) concentration increases to 10 mM there is almost no chloride inhibition any more. Inhibited by diphosphate and AMP. Chloride strengthens the diphosphate inhibition and weakens the AMP inhibition. Chloride weakens the binding of Mg(2+) to the RNA and thereby the interaction between the enzyme and the RNA (PubMed:10572925). Acetylation at certain lysine residues could significantly impair activity (PubMed:28741290). D-tyrosine is a competitive inhibitor of L-tyrosine for the formation of tyrosyl-tRNA(Tyr) (PubMed:4292198)
The efflux inhibitor FK506 impairs the transport activity
Inhibited by micromolar concentrations of azide
Lysophospholipase D activity is stimulated by calcium. Loss of lysophospholipase D activity in presence of EDTA
Binds cobalamin (vitamin B12), but cobalamin is not required for CarA activity. Interaction with CarS prevents binding to DNA
May be regulated by molecular oxygen. Probably not activated by nitric oxide (NO) (By similarity)
ADP-ribosyltransferase activity is regulated via an allosteric activation mechanism (PubMed:34108479). In absence of activation signal, PARP2 is autoinhibited by the PARP alpha-helical domain (also named HD region), which prevents effective NAD(+)-binding (PubMed:34108479). Activity is highly stimulated by signals, which unfold the PARP alpha-helical domain, relieving autoinhibition (PubMed:34108479). Poly-ADP-ribosyltransferase activity is tightly regulated and PARP2 is removed from damaged chromatin following initial poly-ADP-ribosylation of chromatin to avoid prolonged residence (trapping) that has cytotoxic consequences (PubMed:33275888). CHD1L promotes PARP2 removal from chromatin (PubMed:33275888). ADP-ribosyltransferase activity is inhibited by a number of PARP inhibitors (PARPi) compounds, that are used the treatment of breast or ovarian cancers that have defects in DNA repair by homologous recombination (PubMed:35349716). PARPi molecules (niraparib, talazoparib, and, to a lesser extent, olaparib) also trap PARP2 at DNA damage sites (PubMed:33275888, PubMed:35349716)
Low levels of Zn(2+) ions (1 uM) increase glycine sensitivity and decrease the glycine concentration required for half-maximal channel activity (PubMed:23895467). Channel activity is strongly enhanced by ethanol (PubMed:23895467). Inhibited by picrotoxin (PubMed:23834509). Inhibited by prostaglandin E2, probably via PKA-mediated phosphorylation at Ser-379 (PubMed:15131310)
Probably regulated by oxygen tension
Beta subunit (PAFAH1B1) stimulates the acetylhydrolase activity of the alpha2/alpha2 catalytic homodimer
Strongly activated by NADPH and 2'-AMP and inhibited by NADP(+). Ca(2+) increases the activation and decreases the inhibition effect
Inhibited by aminobisphosphonate drugs (aBP), such as risedronate and alendronate
Inhibited by adenosine. Activated by GTP
Adenylyltransferase activity is inhibited by the inhibitory helix present at the C-terminus: Glu-186 binds ATP and competes with ATP-binding at Arg-118, thereby preventing adenylyltransferase activity. Activation dissociates ATP-binding from Glu-186, allowing ordered binding of the entire ATP moiety with the alpha-phosphate in an orientation that is productive for accepting an incoming target hydroxyl side chain
Inhibition by cyclosporin A with a Ki of 25 to 50 mu-mol, a concentration 1000-fold higher than that required for eukaryotic PPIases
Inhibited by aprotinin
Translocase activity is inhibited by verapamil and is sensitive to energy depletion. C1orf115 regulates drug efflux through modulation of ABCB1 localization and activity
Repressed by oxo-clomazone (keto-clomazone), a bleaching herbicide
Inhibited by divalent cations, most significantly by copper and nickel, and by diethylpyrocarbonate (DEPC)
Subject to complex allosteric regulation. The enzyme can assume an active R-state, or an inactive T-state. Intermediate conformations may exist. AMP acts as allosteric inhibitor. AMP binding affects the turnover of bound substrate and not the affinity for substrate. Fructose 2,6-bisphosphate acts as competitive inhibitor. Fructose 2,6-bisphosphate and AMP have synergistic effects (By similarity)
Regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP, GTPase activating proteins (GAPs) which increase the GTP hydrolysis activity, and GDP dissociation inhibitors which inhibit the dissociation of the nucleotide from the GTPase (Probable). Activated in response to insulin
Inhibited by the antitumor sulfonylurea LY181984, the vabilloid capsaicin, and retinoids
Inhibited by coformycin and methylthiocoformycin (MT-coformycin)
Regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP, GTPase activating proteins (GAPs) which increase the GTP hydrolysis activity, and GDP dissociation inhibitors which inhibit the dissociation of the nucleotide from the GTPase. Regulated by the GEF protein DOCK7
Requires proteolytic activation
Activated by phosphorylation on Ser-51 and Ser-555
When flavin concentration is low, activity is enhanced by the presence of the NADH-dependent flavin reductase AsuE2 (PubMed:23890006). In the presence of abundant flavin, activity of AsuE1 is not affected by AsuE2 (PubMed:23890006)
Regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP, GTPase activating proteins (GAPs) which increase the GTP hydrolysis activity, and GDP dissociation inhibitors which inhibit the dissociation of the nucleotide from the GTPase. Inhibited by GAPs such as ARHGAP44 (PubMed:24352656, PubMed:26969129)
Inhibited by E-6-bromomethylene-3-1-naphthalenyl-2H-tetrahydropyran-2-one (BEL) in vitro
The formation of the intermediates complex at the synthetase domain stimulates the glutaminase activity
Bryostatin activates PrkC activity and induces germination, whereas staurosporine inhibits PrkC and significantly reduced peptidoglycan-dependent germination. Kinase activity of isolated N-terminus stimulated by poly-L-lysine or myelin basic protein (PubMed:19246764)
Sensitive to feedback inhibition by L-cysteine
GAP activity stimulated by phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidic acid
Strongly inhibited by hydroxylamine. Modestly inhibited by EDTA
The hexamer is activated by RLP24 during pre-60S ribosomal particle maturation; RLP24 activates ATPase activity of both ATP-binding regions and increases cooperativity between AFG2 subunits (PubMed:23185031). The second ATP-binding region is inhibited by diazaborine; the inhibition requires prior ATP binding specifically to the second ATP-binding region (PubMed:24371142)
Light regulated via thioredoxin by reversible oxidation/reduction of sulfhydryl/disulfide groups
Activated by an increase in cytosolic calcium levels that induce a conformational change of the N-terminal regulatory domain, uncapping the channel and allowing transport (PubMed:22015608, PubMed:24332718, PubMed:26164100). Inhibited by bathophenanthroline, mersalyl, p-hydroxymercuribenzoate, bromcresol purple and tannic acid (PubMed:15123600)
Preincubation with the metalloprotease inhibitor 1,10-phenanthroline before injection into Anopheles or Aedes decreases toxicity
Not induced by oxidative damage (following treatment with paraquat or hydrogen peroxide). Not induced by mitomycin C. Not induced by sigma-B general stress inducers such as sodium chloride, ethanol or heat
Under conditions of nitrogen excess, the DNA-binding activity is inhibited by the formation of a stable complex with feedback-inhibited GlnA
Uptake is inhibited by protonophores such as carbonyl cyanide m-chlorophenylhydrazone (CCCP), but not by valinomycin
Inhibited by the fumagillin analog, TNP-470
Strongly inhibited by Cu(2+) and Zn(2+)
Activated by binding small G proteins (By similarity). Binding of GTP-bound CDC42 or RAC1 to the autoregulatory region releases monomers from the autoinhibited dimer, enables phosphorylation of Thr-402 and allows the kinase domain to adopt an active structure (By similarity). Following caspase cleavage, autophosphorylated PAK-2p34 is constitutively active (PubMed:9786869)
Activity is abolished upon incubation with Chelex and EDTA
Inhibited by Zn(2+) and Cu(2+)
Activated by cell stresses such as DNA damage, heat shock, osmotic shock, anisomycin and sodium arsenite, as well as pro-inflammatory stimuli such as bacterial lipopolysaccharide (LPS) and interleukin-1. Activation occurs through dual phosphorylation of Thr-180 and Tyr-182 by either of two dual specificity kinases, MAP2K3/MKK3 or MAP2K6/MKK6, and potentially also MAP2K4/MKK4, as well as by TAB1-mediated autophosphorylation. MAPK14 phosphorylated on both Thr-180 and Tyr-182 is 10-20-fold more active than MAPK14 phosphorylated only on Thr-180, whereas MAPK14 phosphorylated on Tyr-182 alone is inactive. whereas Thr-180 is necessary for catalysis, Tyr-182 may be required for auto-activation and substrate recognition. Phosphorylated at Tyr-323 by ZAP70 in an alternative activation pathway in response to TCR signaling in T-cells. This alternative pathway is inhibited by GADD45A. Inhibited by dual specificity phosphatases, such as DUSP1, DUSP10, and DUSP16. Specifically inhibited by the binding of pyridinyl-imidazole compounds, which are cytokine-suppressive anti-inflammatory drugs (CSAID). SB203580 is an inhibitor of MAPK14 (By similarity)
Reversibly inhibited by NO. Inhibited by 5,5'-dithiobis-2-nitrobenzoic acid (DTNB) and N-ethylmaleimide (NEM) (in vitro)
Activated by autophosphorylation on Thr-197
Inhibited by EDTA and EGTA
The enzyme is completely inhibited by p-chloromercuribenzoate and HgCl(2) in vitro. Thioglycollate, L-cysteine and Cu(2+) also strongly inhibit the enzyme
Stimulated by B-type cyclins
Requires phosphatidylcholine as an allosteric activator for enzymatic activity
Phosphorylation results in the activation of the kinase activity
Activated by monovalent cations, such as potassium, rubidium or ammonium
ATPase activity is inhibited by EDTA in vitro
Inhibited by isoniazid, cimetidine, clonidine, pentamidine, berenil and pentamidine
Activity is abolished by EDTA. Inhibited by Ro 48-8071, which is non-competitive with regard to DHNA and competitive with regard to the isoprenyldiphosphate substrate
Kept in an inactive conformation by FKBP1A preventing receptor activation in absence of ligand. CD109 is another inhibitor of the receptor
Activity requires salt; 100 mM potassium phosphate, potassium chloride, and sodium chloride are equally effective
Inhibited by trans-4-(N,N-dimethylamino)-cinnamaldehyde through direct binding to the catalytic zinc ion in a substrate-like geometry. Isobutyramide acts as competitive inhibitor with respect to the electron acceptor NDMA. Acetaldehyde, AMP, ADP, ATP, as well as CuSO(4), FeSO(4), HgCl(2), NiCl(2), ZnSO(4), KCN, and NaN(3) are additional inhibitors of the catalytic activity
Inhibited by the sodium/calcium exchanger inhibitor CGP-37157 (PubMed:28445457). Strongly inhibited by zinc (By similarity)
Inhibited by imidazoles (imidazole, benzimidazole, 1-benzylimidazole, 1-methylimidazole, P150/03, N-omega-acetylhistamine and 4-methylimidazole) and cysteamines (cysteamine, N-dimethylcysteamine and N-diethylcysteamine) (PubMed:17722885, PubMed:22897232). Partially inhibited by PDB50 1(3,4-dimethoxyphenyl)-3-(3-imidazol-1-ylpropyl)thiourea (PubMed:22897232)
Activated by ascorbate and magnesium ions
Activated by Ca(2+)/calmodulin. Binding of calmodulin results in conformational change that relieves intrasteric autoinhibition and allows phosphorylation of Thr-180 within the activation loop by CaMKK1 or CaMKK2. Phosphorylation of Thr-180 results in several fold increase in total activity. Unlike CaMK4, may be unable to exhibit autonomous activity after Ca(2+)/calmodulin activation (By similarity)
ATPase activity is decreased by cholesterol and ceramide. ATPase activity is stimulated by phosphatidylethanolamine. Phospholipids translocase activity is highly reduced by berylium fluoride and aluminum floride. N-ethylmaleimide inhibits phospholipid translocase activity
Activated by Ca(2+)/calmodulin. Binding of calmodulin results in conformational change that relieves intrasteric autoinhibition and allows phosphorylation of Thr-177 within the activation loop by CaMKK1 or CaMKK2. Phosphorylation of Thr-177 results in several fold increase in total activity. Unlike CaMK4, is unable to exhibit autonomous activity after Ca(2+)/calmodulin activation
Stimulated rapidly but transiently by both cell fibronectin interactions, as well as by insulin, in a PI3-K-dependent manner, likely via the binding of PtdIns(3,4,5)P3 with a PH-like domain of ILK. The protein kinase activity is stimulated by LIMD2
Inhibited by the diuretic amiloride. Inhibited by Cs(1+) ions. Inhibited by spider venom psalmotoxin-1; this locks the channel into its desensitized conformation
Inhibited by orthovanadate
Repressed by the competitive inhibitor psoralen, but not by umbelliferone, xanthotoxin, bergapten and isopimpinellin
The ATPase activity of the heterodimer is stimulated by cholate. Taurocholate, glycocholate, taurochenodeoxycholate, glycochenodeoxycholate and taurodeoxycholate also stimulate ATPase activity, but to a lower degree. Glycodeoxycholate has no significant effect on ATPase activity. ATPase activity is inhibited by vanadate and by berillium fluoride
Riboflavin transport is Na(+)-independent but moderately pH-sensitive (By similarity). Activity is strongly inhibited by riboflavin analogs, such as lumiflavin (By similarity). Weakly inhibited by flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) (By similarity)
Activated by autophosphorylation at Tyr-1163, Tyr-1167 and Tyr-1168 on the kinase activation loop; phosphorylation at all three tyrosine residues is required for optimal kinase activity. Inhibited by MSC1609119A-1, BMS-754807, PQIP, benzimidazole pyridinone, isoquinolinedione, bis-azaindole, 3-cyanoquinoline, 2,4-bis-arylamino-1,3-pyrimidine, pyrrolopyrimidine, pyrrole-5-carboxaldehyde, picropodophyllin (PPP), tyrphostin derivatives. While most inhibitors bind to the ATP binding pocket, MSC1609119A-1 functions as allosteric inhibitor and binds close to the DFG motif and the activation loop (By similarity)
Activated by autophosphorylation at tyrosines in the kinase activation loop; phosphorylation at all three tyrosine residues is required for optimal kinase activity. Inhibited by MSC1609119A-1, BMS-754807, PQIP, benzimidazole pyridinone, isoquinolinedione, bis-azaindole, 3-cyanoquinoline, 2,4-bis-arylamino-1,3-pyrimidine, pyrrolopyrimidine, pyrrole-5-carboxaldehyde, picropodophyllin (PPP), tyrphostin derivatives. While most inhibitors bind to the ATP binding pocket, MSC1609119A-1 functions as allosteric inhibitor and binds close to the DFG motif and the activation loop (By similarity)
Activated by phosphorylation at Tyr-279. In response to insulin, inhibited by phosphorylation at Ser-21 by PKB/AKT1; phosphorylation at this site causes a conformational change, preventing access of substrates to the active site. Inhibited by lithium (By similarity)
InhA activity is controlled via phosphorylation: phosphorylation on Thr-266 decreases InhA activity (5-fold reduction) and likely negatively regulates biosynthesis of mycolic acids and growth of the bacterium (PubMed:20864541, PubMed:21143326). The antitubercular pro-drug isoniazid (INH) is oxidatively activated by the catalase-peroxidase KatG and then covalently binds NAD to form an adduct that inhibits the activity of InhA (Ref.5, PubMed:14623976, PubMed:9417034). The inhibitory adduct is the isonicotinic-acyl-NADH where the isonicotinic-acyl group replaces the 4S (and not the 4R) hydrogen of NADH (PubMed:9417034). Similarly, the antitubercular pro-drugs ethionamide (ETH) and prothionamide (PTH) are activated by the flavoprotein monooxygenase EthA, and forms an adduct with NAD (ETH-NAD and PTH-NAD, respectively) that is a tight-binding inhibitor of InhA (PubMed:17227913). Is inhibited by triclosan and derivatives, pyrazole derivative Genz-8575, indole-5-amide Genz-10850, alkyl diphenyl ethers, pyrrolidine carboxamides, arylamides, pyridomycin, methyl-thiazoles, 4-hydroxy-2-pyridones, and N-benzyl-4-((heteroaryl)methyl)benzamides (PubMed:12606558, PubMed:17163639, PubMed:17034137, PubMed:17723305, PubMed:19130456, PubMed:20200152, PubMed:22987724, PubMed:24107081, PubMed:24616444, PubMed:25568071). Pyridomycin shows a unique mode of InhA inhibition by simultaneously blocking parts of the NADH and the lipid substrate-binding pocket of InhA (PubMed:24292073). Is also inhibited by thiadiazole compounds, that have very attractive antitubercular properties (PubMed:27428438)
Stimulated by clathrin
Inhibited by zinc ions
Activated by calcium and negatively charged phospholipids
Is allosterically regulated by the feedback inhibitor (S)-lysine. Is inhibited by pyruvate analogs such as 3-fluoropyruvate, 2-ketobutyrate, glyoxylate, and beta-hydroxypyruvate. Is not inhibited by its substrate, (S)-ASA
Proteolysis inhibited by 1,10-phenanthroline, captopril and EDTA (PubMed:8505288)
Present in an inactive conformation in the absence of bound ligand. Ligand binding leads to dimerization and activation by sequential autophosphorylation on tyrosine residues (By similarity)
The omega-1 hydroxylase activity is stimulated by cytochrome b5
N-bromosuccinimide completely inhibits the catalytic activity
Interaction in the cytoplasm with the NapD chaperone prevents premature export
Allosterically regulated by S-adenosylmethionine (SAM)
Activated upon phage infection
Protein kinase activity is activated following autophosphorylation at Tyr-368
TEK and vascular endothelial growth factor receptor 1 (FLT1) stimulate BMX tyrosine kinase activity (By similarity). Activated by integrins through the mediation of PTK2/FAK1. Activated by TNF through the mediation of TNFRSF1B
The ATPase activity is increased some 4-fold in the presence of RNA
ATPase activity is stimulated by both long RNAs and short oligoribonucleotides
Carboxymethylation by iodoacetic acid blocks sulfur transfer to this protein
Enhanced activity in the presence of calcium, magnesium, manganese and zinc ions, but inhibited activity in the presence of iron ion
Inhibited by tetrahydrolipstatin (THL), a specific lipase inhibitor
Enzyme activity catalyzed by the HPA decarboxylase complex is rapidly and irreversibly inactivated by oxygen. Competitively inhibited by p-hydroxyphenylacetamide. Not inhibited by m- or o-hydroxyphenyl-acetate, p-hydroxybenzoate or p-hydroxyphenylpropionate
Activated under anaerobic conditions by NrdG, a tightly associated activase (PubMed:1460049, PubMed:7852304, PubMed:9305874). Activation involves the formation of a glycyl radical at Gly-681 (PubMed:7852304, PubMed:8636106, PubMed:9305874). Exposure of the activated reductase to oxygen leads to C-terminal truncation and inactivation of the protein, by cleavage at the N-terminal side of Gly-681 (PubMed:8421692, PubMed:7826394). The presence of zinc protects the protein from proteolysis and prevents the formation of disulfide bridges within it (PubMed:19381696)
Inhibited by alpha-(methylamino)isobutyric acid (MeAIB). Inhibited by lithium, potassium, choline ions, N-methylglucamine. The pH dependence has an allosteric effect on the transport
The fibrinolytic activity is completely inhibited by PMSF, diisopropylfluorophosphate (DFP), pefabloc, dithiothreitol (DTT) and Zn(2+), but not by Pepstatin A, E64, iodoacetate, chymostatin, tosyl-Lphenylalanine chloromethyl ketone (TPCK), soybean trypsin inhibitor (SBTI), phosphoramidon, Ca(2+), Co(2+), Cu(2+), Fe(2+), Mg(2+), Mn(2+), K(+), and Na(+)
Activity is not affected by 4'-phosphopantothenate or CoA/acetyl-CoA
Subject to allosteric activation by fumarate
The ATPase activity is up-regulated by aminophospholipids PS and PE
Activated through serine, threonine and tyrosine phosphorylation, especially upon abscisic acid (ABA) treatment (PubMed:28848569, PubMed:27913741). Restricted activity by ABI1-mediated dephosphorylation (PubMed:27913741)
Inhibited by bestatin (PubMed:11175901). The epoxide hydrolase activity is restrained by suicide inactivation that involves binding of LTA4 to Tyr-379 (PubMed:7667299). 4-(4-benzylphenyl)thiazol-2-amine (ARM1) selectively inhibits the epoxide hydrolase activity (PubMed:24591641)
Mesobiliverdin acts as competitve inhibitor for flavin reduction, indicating that flavin and tetrapyrrole substrates compete for the same site
Activity enhanced by manganese ions and inhibited by p-chloromercuribenzoate
Maximum activity at KCl concentration of 0.5 M and activity decreases with increasing concentration of KCl
Activated by the non-canonical Wnt signaling pathway, in which WNT5A leads to activation of MAP3K7/TAK1 and HIPK2, which subsequently phosphorylates and activates this protein. Activated by dimerization and subsequent intermolecular autophosphorylation on Thr-298. Other cytokines such as IL6 may also activate this regulatory circuit
Regulated by a guanine nucleotide-exchange factor (GEF) and a GTPase-activating protein (GAP) and alternates between an inactive GDP-bound and an active GTP-bound form. The BLOC-3 complex composed of HPS1 and HPS4 acts as its GEF, promotes the exchange of GDP to GTP, converting it from an inactive GDP-bound form into an active GTP-bound form (By similarity). SGSM2 acts as its GAP and inactivates it by stimulating its GTPase activity (PubMed:21269460)
Down-regulated by polyamine end products putrescine and spermidine
Inhibited by Ba(2+) ions and quinidine (PubMed:8605869). Inhibited by quinine (PubMed:8605869, PubMed:21653227). Is slightly inhibited by 10 mM tetraethylammonium (TEA), and only marginally inhibited by 4-aminopyridine, charybdotoxin and dendrotoxin (PubMed:8605869). Lowering the extracellular pH to below 6.5 transiently activates the channel, and then inhibits channel activity (PubMed:15820677, PubMed:22431633). Inhibited when the intracellular pH is decreased down to pH 6.0, but this may be due to indirect effects (PubMed:8605869)
Completely inhibited by p-chloromercuribenzoate, N-ethylmaleimide, MnSO(4), MnCl(2), CoCl(2), NiCl(2), CuSO(4), CuCl(2), ZnSO(4), ZnCl(2), AgNO(3), CdCl(2), HgCl(2) and PbCl(2). Partially inhibited by FeCl(3) and Fe(NH(4))(2)(SO(4))(2). Slightly enhanced by dithiothreitol. Unaffected by LiBr, H(2)BO(3), NaCl, MgSO(4), MgCl(2), AlCl(3), KCl, CaCl(2), CrCl(3), RbCl, Na(2)MoO(4), (NH(4))(6)Mo(7)O(24), CsCl and BaCl(2). Unaffected by the chelating agents o-phenanthroline, 8-hydroxyquinoline, enthylenediaminetetraacetic acid and alpha,alpha'-dipyridyl. Not inhibited by the carbonyl reagents hydroxylamine, phenylhydrazine, hydrazine, D,L-penicillamine and D-cycloserine. Not affected by the serine protease inhibitor phenylmethanesulfonyl fluoride, the serine/cysteine protease inhibitor leupeptine or the aspartic protease inhibitor pepstatin
PDPK1 activates its transcriptional activity independently of its kinase activity
Inhibited by phosphocholine but not by choline, glycine betaine, monomethylethanolamine or dimethylethanolamine
Activated by DAG and phorbol esters. Phorbol-ester/DAG-type domains bind DAG, mediating translocation to membranes. Autophosphorylation of Ser-711 and phosphorylation of Ser-707 by PKC relieves auto-inhibition by the PH domain. Catalytic activity is further increased by phosphorylation at Tyr-718 in response to oxidative stress
6-seleno-octanoate, 8-thio-octanoate and 8-seleno-octanoate caused 100%, 50% and 63% inhibition respectively. Inhibited by Cu(2+)
Inhibited by Zn(2+)
GTPase activity is repressed by PDV2 thus increasing stability at the plastid outer envelope membranes (OEMs) periphery
Feedback inhibition by Leu
Inhibited by aprotinin, leupeptin, benzamidine, SERPINA1, SPINT1 and SPINT2
Phosphorylation of Asp-56 probably induces local conformational changes in the response regulatory domain (PubMed:22753070). These structural changes are transmitted to the adjacent EAL domain, then the signal is further transmitted down to the active site (PubMed:22753070). The phosphodiesterase activity is inhibited by Ca(2+) and Zn(2+) (PubMed:18344366). Phosphodiesterase activity is inhibited by a benzoisothiazolinone derivative that specifically inhibited RocR, but not some other phosphodiesterases (PubMed:30034764)
Activated by autophosphorylation at Thr-445
Inhibited by pyridoxal 5'-phosphate, bathophenanthroline, tannic acid, mersalyl, mercuric chloride, p-hydroxymercuribenzoate, p-hydroxymercuribenzoate sulfonate, bromocresol purple and N-ethylmaleimide
Cyclosporin A (CsA) inhibits CYPB
Interaction with ATP6AP2 results in a 5-fold increased efficiency in angiotensinogen processing
Activated by citrate
Beta-lactamase activity is inhibited by sulbactam
Inhibited to approximately 20% by EDTA
Activated by WNK3 (By similarity). Activated by isotonic conditions (PubMed:10894798). Inhibited by thiazide-type diuretics including polythiazide, metolazone, bendroflumethiazide, trichloromethiazide, hydrochlorothiazide and chlorthalidone (PubMed:10894798)
By light-reversible phosphorylation
Activated by cytochrome b5 and phosphatidylserine
Activated by zinc and cobalt ions
Phosphorylation of Thr-84 by OXSR1 inhibits activation (By similarity). Activated by binding small G proteins. Binding of GTP-bound CDC42 or RAC1 to the autoregulatory region releases monomers from the autoinhibited dimer, and enables activation by phosphorylation of Thr-422
Calprotectin (S100A8/A9) activity on TLR4 signaling is inhibited by paquinimod
The TcyJLN system is inhibited by L-cystine, L-cysteine, DL-2,6-diaminopimelic acid and L-cystathionine, and is stimulated by D-cysteine
NPM1 stimulates endodeoxyribonuclease activity on double-stranded DNA with AP sites, but inhibits endoribonuclease activity on single-stranded RNA containing AP sites
Kinase activity is inhibited by phosphorylation by cAMP-dependent protein kinase (PKA)
Inhibited by p-chlorophenyl and 1-naphthyl boronic acid derivatives
Inhibited by sodium vanadate and sodium tungstate. NaF and spermifine repress specifically phosphoserine and phosphothreonine phosphatase activity
Inhibited by drugs voriconazole and metyrapone
The side chain of Glu-252 determines which of the two opposing activities (AMPylase or de-AMPylase) will take place. In response to endoplasmic reticulum stress, mediates de-AMPylase activity (By similarity). Adenylyltransferase activity is inhibited by the inhibitory helix present at the N-terminus: Glu-252 binds ATP and competes with ATP-binding at Arg-391, thereby preventing adenylyltransferase activity (By similarity). In unstressed cells, disengagement of Glu-252 promotes adenylyltransferase activity (By similarity). Activation dissociates ATP-binding from Glu-252, allowing ordered binding of the entire ATP moiety with the alpha-phosphate in an orientation that is productive for accepting an incoming target hydroxyl side chain (By similarity)
Sensitive to oxygen
Highest activities is obtained at about 30 mM CTP and 2 mM phosphatidic acid (PA)
Present in an inactive conformation in the absence of bound ligand. Binding of VEGFC or VEGFD leads to dimerization and activation by autophosphorylation on tyrosine residues (By similarity)
Completely inhibited by the presence of 5 mM Cu(2+). Partially inhibited with 5 mM Mn(2+), Zn(2+) or EDTA
Inhibited by nicotinamide. Activated by resveratrol (3,5,4'-trihydroxy-trans-stilbene), butein (3,4,2',4'-tetrahydroxychalcone), piceatannol (3,5,3',4'-tetrahydroxy-trans-stilbene), Isoliquiritigenin (4,2',4'-trihydroxychalcone), fisetin (3,7,3',4'-tetrahydroxyflavone) and quercetin (3,5,7,3',4'-pentahydroxyflavone). MAPK8/JNK1 and RPS19BP1/AROS act as positive regulators of deacetylation activity. Negatively regulated by CCAR2
Both the ABR and the SH3 domains contribute to maintaining the protein in an inhibited conformation by associating with the C-terminal tail. Binding of these domains to the C-terminal tail inhibits the activity of the protein by blocking a region that is required for its GEF activity
Present in an inactive conformation in the absence of bound ligand. CSF1 binding leads to dimerization and activation by autophosphorylation on tyrosine residues (By similarity)
Converted into plasmin by plasminogen activators, both plasminogen and its activator being bound to fibrin. Activated with catalytic amounts of streptokinase
Inhibited by the C-terminal non-catalytic region. Activated by caspase-cleavage. Full activation also requires homodimerization and autophosphorylation of Thr-180, which are inhibited by the proto-oncogene product RAF1. Activated by RASSF1 which acts by preventing its dephosphorylation (By similarity)
Activated by 3-phosphoglycerate and inhibited by phosphate
Alternates between an inactive form bound to GDP and an active form bound to GTP (PubMed:1910037). Activated by a guanine nucleotide-exchange factor (GEF) and inactivated by a GTPase-activating protein (GAP) (PubMed:1910037)
Angiopoietin binding leads to receptor dimerization and activation by autophosphorylation at Tyr-992 on the kinase activation loop. Inhibited by staurosporine, K252a, PP2, damnacanthal, SB203580, CEP-11207, CEP-11981 and CE-245677. Inhibited by triazine, thienopyrimidine and thiazolopyrimidine derivatives
Not inhibited by an excess of substrates and common allosteric inhibitors. Inhibited by high concentrations of the reaction products, fructose 1,6-bisphosphate and ADP
During logarithmic growth and early developmental phases, the activity of GP1 is dependent on 5'AMP. It then seems to convert to an AMP independent type. This alteration in activity coincides with phosphorylation of GP1
Allosterically activated by GTP, when glutamine is the substrate (PubMed:11500486). GTP has no effect on the reaction when ammonia is the substrate. The allosteric effector GTP functions by stabilizing the protein conformation that binds the tetrahedral intermediate(s) formed during glutamine hydrolysis (By similarity). Also activated by magnesium (PubMed:11500486). Allosterically inhibited by CTP (PubMed:11500486)
Active in presence of diverse metals including Fe(2+), Zn(2+), Mn(2+) (By similarity). Also activated by Ca(2+) (By similarity). Binds two metal cations in two adjacent alpha and beta metal-binding pockets (By similarity)
Allosteric enzyme. Stimulated by magnesium ions
Inhibited by DFFA (DFF45). Interacts with HIST1H1A
Mycophenolic acid (MPA) is a non-competitive inhibitor that prevents formation of the closed enzyme conformation by binding to the same site as the amobile flap. In contrast, mizoribine monophosphate (MZP) is a competitive inhibitor that induces the closed conformation. MPA is a potent inhibitor of mammalian IMPDHs but a poor inhibitor of the bacterial enzymes. MZP is a more potent inhibitor of bacterial IMPDH. Potently inhibited by MPA and adenine dinucleotide analogs such as thiazole-4-carboxamide adenine dinucleotide (TAD)
Inhibited by cyanide; is more sensitive to cyanide than cytochrome bd-I oxidase
In the presence of Ca(2+) ions, activated by Mn(2+) or Mg(2+) ions. Inhibited by Cd(2+) or Zn(2+) ions. Inhibited by metal chelators EDTA and EGTA
Activated by calcium and magnesium and inhibited by other bivalent cations
Inhibited by phlorizin
Transactivation activity is repressed by GSK2
Creatine uptake is inhibited by carbonyl cyanide 3-chlorophenylhydrazone (CCCP) and by valinomycin
The completion of the deubiquitinase reaction is mediated by the DUSP and ubiquitin-like 1 domains which promotes the release of ubiquitin from the catalytic site enabling subsequent reactions to occur
Under complex allosteric control mediated by deoxynucleoside triphosphates and ATP binding. The type of nucleotide bound at the specificity site determines substrate preference. It seems probable that ATP makes the enzyme reduce CDP and UDP, dGTP favors ADP reduction and dTTP favors GDP reduction (By similarity)
Calcium channel activity is enhanced by MYLK, that promotes its subcellular localization at the plasma membrane
In high-amino acid conditions, activated by GTPase activating protein (GAP) FLCN that stimulates RRAGD GTPase activity to turn it into its active GDP-bound form
Constitutively activated by phosphorylation at Ser-252, Ser-392, and Ser-409 in serum-starved cells. Does not require growth factor stimulation for significant kinase activity (By similarity)
Trimethyl phosphonoacetate and DL-threose are competitive inhibitors with respect to dihydroxyacetone phosphate, and uncompetitive inhibitors with respect to DL-glyceraldehyde
Contains an N-terminal autoinhibitory domain. Activated by phosphorylation at Thr-812, inhibited by phosphorylation at Ser-924 and Ser-994 (By similarity)
Lipoproteins are powerful coactivators of PM20D1 activity in vitro and NAA biosynthesis in vivo
Inhibited by clavulanic acid, and at a low level by tazobactam and sulbactam
Under complex allosteric control mediated by deoxynucleoside triphosphates and ATP binding to separate specificity and activation sites on the M1 subunit. The type of nucleotide bound at the specificity site determines substrate preference. It seems probable that ATP makes the enzyme reduce CDP and UDP, dGTP favors ADP reduction and dTTP favors GDP reduction. Stimulated by ATP and inhibited by dATP binding to the activity site (By similarity)
Beta subunit (PAFAH1B1) inhibits the acetylhydrolase activity of the alpha1/alpha1 catalytic homodimer
EsxB binding to the third FtsK domain causes multimerization; a subsequent unknown step relieves the allosteric inhibition of linker 2 on FtsK domain 1, activating the ATPase activity; a mutant EsxB ('Ala-98') does not cause multimers to form (PubMed:25865481)
Not stimulated by addition of pyridoxal 5'-phosphate (0.1 mM), FAD, NAD(+), NADP(+) or ATP (1 mM each). EDTA (10 mM) and metal ions (1 mM) such as Ca(2+), Co(2+), Mg(2+), Ni(2+), Zn(2+) do not affect the enzyme activity
The monovalent cation sodium enhances activity but is not absolutely required
Partially inhibited by glucono-1,5-lactone, conduritol beta-epoxide and diosgenin, but not by beta-sitosterol or cholesterol
Completely inhibited by Cu(2+) and Ag(+). Partially inhibited by Cr(2+), Pb(2+) and Fe(2+). Mg(2+), Ca(2+), Mn(2+), Co(2+), Ni(2+), Zn(2+) and Cd(2+) have no effect on activity. The chelating agents EDTA, 2,2'bipyridine and o-phenanthroline have no effect on enzyme activity
Phosphorylation appears to increase the enzymatic activity
Potently inhibited by choline in the mitochondria-associated membrane (MAM). Very little inhibition by choline in the endoplasmic reticulum (ER) per se
Inhibited by Cd(2+)
Activated by pentobarbital (By similarity). Inhibited by the antagonist bicuculline (By similarity)
Inhibited by N-methyl-D-glucamine. Inhibited by choline. Allosteric regulation of sodium ions binding by pH
Citrate activates the enzyme in the oxidation of malate to oxaloacetate and inhibits it in the reverse reaction
Belongs to type I PK; fructose 1,6-bisphosphate-activated
Inhibited by 5 mM 4-aminopyridine (4-AP) (PubMed:1840649, PubMed:1722463, PubMed:9093524). Not inhibited by dendrotoxins and by tetraethylammonium (TEA) (PubMed:1722463). Inhibited by 10 mM flecainide and 20 mM quinidine (PubMed:9093524). Inhibited by the heteropodatoxins HpTx(1), HpTx(2), and HpTx(3) (PubMed:9058605)
Inhibited by dicumarol
Inhibited by N-hydroxy-N'-(4-n-butyl-2-methylphenyl formamidine)(HET0016) with an IC(50) of 38 nM
Allosterically activated by various compounds, including ATP. Activated by cAMP; the nucleotide acts as a dynamic and allosteric activator by coupling the two lobes of apo PKA, enhancing the enzyme dynamics synchronously and priming it for catalysis. Inhibited by H89 (N-[2-[[3-(4-Bromophenyl)-2-propenyl]amino]ethyl]-5-isoquinolinesulfonamide), spiroindoline, azole-based inhibitors, (3s)-amino-aminomethylbenzamide analogs, ARC-1032 (6-{[(2S,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]formamido}-N-[(1R)-4-carbamimidamido-1-carbamoylbutyl]hexanamide), ARC-1034 (6-{[(2S,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]formamido}-N-[(1R)-4-carbamimidamido-1-{[(1R)-4-carbamimidamido-1-carbamoylbutyl]carbamoyl}butyl]hexanamide), ARC-582, ARC-902 (Adc-6-aminohexanoic acid-(D-Arg)(6)-NH(2)), ARC-1012 ((2R)-6-amino-2-(6-{[(2S,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]formamido}hexanamido)-N-(5-{[(1R)-4-carbamimidamido-1-{[(1R)-4-carbamimidamido-1-carbamoylbutyl]carbamoyl}butyl]carbamoyl}pentyl)hexanamide) and ARC-1039 (6-{[(2S,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]formamido}-N-[(1R)-1-[(5-{[(1R)-4-carbamimidamido-1-{[(1R)-4-carbamimidamido-1-carbamoylbutyl]carbamoyl}butyl]carbamoyl}pentyl)carbamoyl]ethyl]he xanamide)
Activated by autophosphorylation at Tyr-434, Tyr-438 and Tyr-439 on the kinase activation loop; phosphorylation at all three tyrosine residues is required for optimal kinase activity. Inhibited by MSC1609119A-1, BMS-754807, PQIP, benzimidazole pyridinone, isoquinolinedione, bis-azaindole, 3-cyanoquinoline, 2,4-bis-arylamino-1,3-pyrimidine, pyrrolopyrimidine, pyrrole-5-carboxaldehyde, picropodophyllin (PPP), tyrphostin derivatives. While most inhibitors bind to the ATP binding pocket, MSC1609119A-1 functions as allosteric inhibitor and binds close to the DFG motif and the activation loop (By similarity)
Phosphorylated and inactivated after addition of glucose to the cell culture (repressing conditions)
Kinase activity is tightly regulated. Activated in response to signaling from a cell surface receptor. Activation probably requires binding of a substrate via the SH2 domain, plus autophosphorylation at Tyr-711. Present in an inactive form in the absence of activating stimuli (By similarity)
Inhibited by inorganic phosphate ions (PubMed:9665712, PubMed:15049687). Competitively inhibited by phosphoglycolate (PubMed:15049687). Competitively inhibited by phosphoglycolohydroxamate (PubMed:11389594)
Allosterically activated by benzodiazepines (PubMed:29950725). Allosterically activated by the anesthetic etomidate (By similarity). Inhibited by the antagonist bicuculline (PubMed:29950725)
Both beta-lactamase and RNase activities are inhibited by chaperone DnaJ2
Inhibited by 2-guanidinoethylmercaptosuccinic acid (GEMSA)
Activity is regulated by phosphorylation and moderated by concentration of metabolites and light
Activity is tightly controlled by YfiR, a small periplasmic protein, and the OmpA/Pal-like outer-membrane lipoprotein YfiB (By similarity). Diguanylate cyclase activity is inhibited by the specific interaction of YfiR with the TpbB periplasmic domain and is activated by YfiB, which releases the YfiR-mediated repression through sequestration of YfiR to the outer membrane (By similarity). Activity is also controlled by dephosphorylation of the periplasmic domain by the tyrosine phosphatase TpbA (PubMed:20946878)
Binding to rib-1 is required for GlcAT-II activity and for increasing GlcNAc-II activity in vitro
The integrated stress response (ISR) is activated in response to conditions that promote ribosome collisions: GCN1, which acts as a ribosome collision sensor, activates GCN2 (PubMed:33338396). The RQC pathway and the integrated stress response (ISR) antagonize each other: HEL2 prevents the activation of GCN2, while GCN2 suppresses RQC activation (PubMed:33338396). Ribosome stalling-induced integrated stress response prefers ribosomes with empty A sites (PubMed:33338396). The kinase activity is stimulated upon binding to uncharged tRNAs (PubMed:7623840)
Completely inhibited by ADP and ADP-glucose, and partially inhibited by ATP and NADH
Channel activity is inhibited by interaction with Ca(2+)-bound calmodulin (PubMed:27516594). Interaction of a single pore-forming alpha subunit with a calmodulin chain is sufficient to promote channel closure. Channel activity is not regulated by cyclic nucleotides. Channel activity is inhibited by binding intracellular phosphatidylinositol-3,5-bisphosphate and phosphatidylinositol-4,5-bisphosphate (PIP2), but is not inhibited by phosphatidylinositol 4-phosphate (By similarity)
The full-length protein before cleavage is inactive: intramolecular interactions between N- and C-terminal domains mediate autoinhibition in the absence of activation signal. The intrinsic pyroptosis-inducing activity is carried by the released N-terminal moiety (Gasdermin-A2, N-terminal)
Autoinhibited: in the inactive state, the enzymatic TIR domain is held apart by the autoinhibiting ARM repeats. NAD(+)-binding to ARM repeats maintains an inactive state by promoting interaction between ARM repeats and the TIR domain, thereby facilitating inhibition of the enzymatic TIR domain. Following activation, possibly by nicotinamide mononucleotide (NMN), auto-inhibitory interactions are released, allowing self-association of the TIR domains and subsequent activation of the NAD(+) hydrolase (NADase) activity. Self-association of TIR domains is facilitated by the octamer of SAM domains
Inhibited by glutathione. This inhibition is increased by NADH. Activated by adducts between glutathione and electrophiles
Inhibited by glutathione
Inhibited by the phosphatase inhibitors fluoride, molybdate and orthovanadate
Activated by phosphorylation at Ser-10 by CPK23
Insensitive to magnesium or calcium when dephosphorylated. When phosphorylated, 3-fold activation by magnesium or calcium, 2-fold activation by potassium, inhibited by ADP and AMP and insensitive to ATP or PPi
Inhibited by products of SAMS reaction (SAM, Pi, PPi), substrate analogs (cycloleucine and ethionine), and alternative nucleotides (GTP, CTP and ADP). Strongly repressed by PPPi
Amidase activity is completely suppressed by inhibitors of serine proteases (phenylmethylsulfonyl fluoride and diisopropyl fluorophosphate), partially inhibited by copper and mercury ions, but is not affected by inhibitors of aliphatic amidases (acetaldehyde and nitrophenyl disulfides) or by EDTA
ATPase activity is stimulated by lipid A, hexaacylated lipid A or Kdo(2)-lipid A (PubMed:12119303, PubMed:18344567). Inhibited by the phosphate analog vanadate (PubMed:12119303, PubMed:18344567, PubMed:28869968). ATPase activity is also modulated by the lipid-based drugs D-20133 and D-21266, along with LY335979 and leupeptin (PubMed:18344567)
Concentrations above 100 uM sulfite inhibit the reaction
The metal cations Ni(2+), K(+) and Zn(2+) show some inhibition of the activity, and Ag(+), Hg(2+) and Cu(2+) shows very significant inhibition even at relatively low ion concentrations
Activated by Mg(+) but not by K(+). Inhibited by Ca(2+)
Target RNA acts as an activator for non-specific ssRNA degradation (PubMed:28475872)
Enzymatic activity depends on membrane binding
Inhibited by diphenylene iodonium (DPI)
Activity in enhanced in the presence of K(+) and Mn(2+) and reduced by about 40% in the presence of Cu(2+)
Not regulated by MgCl(2), ruthenium red or tetramethylammonium-Cl
Inhibited by the MazE-MazF complex
Active in presence of Mn(2+), Mg(2+) and Zn(2+), but is not functional with Ca(2+) or Cu(2+). Has a higher affinity for Mn(2+) than for Mg(2+). RAN inhibits its autophosphorylation and its ability to phosphorylate histone H3 (By similarity)
Inhibited by p-hydroxymercuribenzoate and N-ethylmaleimide, but not by iodoacetate or iodoacetamide
Inhibited by peptidomimetic inhibitors such as WEHI-842
Induced by potassium ions
An iron-sulfur cluster promotes IRP2 polyubiquitination and degradation in response to both iron and oxygen concentrations
Activated by calcium and calmodulin. Autophosphorylation may play an important role in the regulation of the kinase activity (By similarity)
Inhibited by the antifolate drugs methotrexate and pemetrexed
Inhibited by sodium, potassium and ammonium ions, and by TEMED
Allosterically regulated by cAMP
Activated by Ca(2+)/calmodulin. Binding of calmodulin is thought to result in a conformational change and leads to activation through phosphorylation by CAMKK1 (By similarity)
Inhibited by 40% with 500 uM tyrosine, and a tyrosine concentration as high as 5 mM reduced activity to 5%
Not inhibited by the antitumor sulfonylurea LY181984, the vabilloid capsaicin, and retinoids
The two-component PilS2/PilR2 is required for proper assembly of T4P and regulation
K(+) transport is stimulated by Na(+)
Not inhibited by D-galactose or sucrose (Ref.1). Inhibited by pharmaceutical drug 1-deoxygalactonojirimycin (PubMed:23012371)
Activity is stimulated by ZBP1, which senses double-stranded Z-RNA structures. RIPK3-dependent necroptosis is inhibited by RIPK1: RIPK1 prevents the ZBP1-induced activation of RIPK3 via FADD-mediated recruitment of CASP8, which cleaves RIPK1 and limits TNF-induced necroptosis
Requires 4 M NaCl or KCl for maximal activity
In the resting state, through the dimerization of its C-terminal domain, HSP90 forms a homodimer which is defined as the open conformation. Upon ATP-binding, the N-terminal domain undergoes significant conformational changes and comes in contact to form an active closed conformation. After HSP90 finishes its chaperoning tasks of assisting the proper folding, stabilization and activation of client proteins under the active state, ATP molecule is hydrolyzed to ADP which then dissociates from HSP90 and directs the protein back to the resting state. Co-chaperone TSC1 promotes ATP binding and inhibits HSP90AA1 ATPase activity. Binding to phosphorylated AHSA1 promotes HSP90AA1 ATPase activity. Inhibited by geldanamycin, Ganetespib (STA-9090) and SNX-2112
Binding of Na(+) and melibiose is cooperative, the binding affinity for one substrate is increased by the presence of the other (PubMed:29054867, PubMed:34110360). With binding of one substrate (either Na(+) or melibiose), MelB favors open conformations (likely outward facing), whereas the cooperative binding of both substrates induces cavity closure. Thus, cooperative binding is the key that regulates the alternating-access process and ensures the obligatory cotransport as the core mechanism for symport (PubMed:34110360). Melibiose uptake is inhibited by valinomycin (PubMed:21148559)
Activated following phosphorylation by p38-alpha/MAPK14 following various stresses. Inhibited by ligand 5B (2'-[2-(1,3-benzodioxol-5-yl)pyrimidin-4-yl]-5',6'-dihydrospiro[piperidine-4,7'-pyrrolo[3,2-c]pyridin]- 4'(1'h)-one) and ligand P4O (2-[2-(2-fluorophenyl)pyridin-4-yl]-1,5,6,7-tetrahydro- 4h-pyrrolo[3,2-c]pyridin-4-one), 2 ATP-competitive inhibitors (By similarity)
Counter-exchange transport activity is saturable and inhibited by pyridoxal-5'-phosphate, EDTA and EGTA (PubMed:26140942). Activated by calcium Ca(2+) and manganese Mn(2+) ions, and slightly by iron Fe(2+) and zinc Zn(2+) ions (PubMed:26140942, PubMed:28695448). Repressed by copper ions Cu(2+) and slightly by magnesium Mg(2+) ions (PubMed:28695448). Magnesium Mg(2+) ions promotes slightly ATP uptake, ATP-Mg(2+) being exchanged with ATP(4-) (PubMed:26444389)
Present in an inactive conformation in the absence of bound ligand. CSF1 or IL34 binding leads to dimerization and activation by autophosphorylation on tyrosine residues. Inhibited by imatinib/STI-571 (Gleevec), dasatinib, sunitinib/SU11248, lestaurtinib/CEP-701, midostaurin/PKC-412, Ki20227, linifanib/ABT-869, Axitinib/AG013736, sorafenib/BAY 43-9006 and GW2580
Inhibited by ascorbic acid and iron ion
Inhibited by nickel (NiCl(2) and NiSO(4)) and para-chloromercuribenzoate
Substrate specificity is modulated by calcium which enhances the enzymatic activity for cleavage of acidic residues while reducing its activity with basic residues. Inhibited by aminopeptidase inhibitors amastatin and bestatin
Completely inhibited by Ag(2+), Cu(2+), Hg(2+), Mn(2+), Pb(2+) and Sn(2+). Strongly inhibited by Fe(2+) and Zn(2+). Co(2+) and Ni(2+) cause little inhibition while Ca(2+) and Mg(2+) do not affect enzyme activity, and Ba(2+) produces a small stimulating effect. Irreversibly inactivated by SDS in vitro
The calcium channel is gated following an off-response property by acid: gated open after the removal of acid stimulus, but not during acid application
Hexokinase activity is specifically inhibited by 2,6-disubstituted glucosamines
Activated by the allosteric regulator glucose-6-phosphate (By similarity). Inhibited by malate and aspartate (By similarity). Up regulated by light-reversible phosphorylation (By similarity)
Inhibited by the S-adenosyl-L-methionine analog sinefungin and by the product S-adenosyl-L-homocysteine
PAM activity is inhibited by EDTA, phenylglyoxal and diethyl pyrocarbonate (By similarity). PAL activity is stimulated by cadmium and inhibited by mercury (PubMed:19604476)
Activated following phosphorylation by p38-alpha/MAPK14 following various stresses. Inhibited by ligand 5B (2'-[2-(1,3-benzodioxol-5-yl)pyrimidin-4-yl]-5',6'-dihydrospiro[piperidine-4,7'-pyrrolo[3,2-c]pyridin]- 4'(1'h)-one) and ligand P4O (2-[2-(2-fluorophenyl)pyridin-4-yl]-1,5,6,7-tetrahydro- 4h-pyrrolo[3,2-c]pyridin-4-one), 2 ATP-competitive inhibitors
Dimerization of the C-terminal extracellular sensor domain activates kinase autophosphorylation activity
Activated by L-cysteine (PubMed:27129273). Inhibited by cysteine protease inhibitor E64 (L-trans-epoxysuccinyl-leucylamide-(4-guanido)-butane) (PubMed:25865353, PubMed:27129273). Inhibited by cysteine/serine protease inhibitor leupeptin. Not inhibited by serine protease inhibitors 4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride (AEBSF) and phenylmethanesulfonyl fluoride (PMSF), metallo protease inhibitor bestatin or aspartic protease inhibitor pepstatin A (PubMed:27129273)
Putrescine uptake is inhibited by carbonyl cyanide m-chlorophenylhydrazone (CCCP), which dissipates the proton motive force
Inhibited by alanine-alanine-phenylalanine-chloromethylketone, butabindide and phenylmethanesulfonyl fluoride (PMSF), but not by leupeptin, N-ethylmaleimide, EDTA, MG132 and lactacystin
Requires a divalent cation activator, and is inhibited by CMP. Activated by phospholipids, especially phosphatidylcholine
Slightly inhibited by salutaridine and (7S)-salutaridinol
Assembly into ribonucleoprotein complexes of high-molecular-mass (HMM) inhibits its enzymatic activity
Inhibited by calcium ion and activated by magnesium ion
3'-5' RNA exonuclease activity is inhibited by a 3' phosphate terminated RNA
Polymerizes in the presence of millimolar divalent cations in a protein concentration-dependent manner. Polymerization is favored by decreasing pH and inhibited by monovalent salts and low temperatures
Two specific sites, one in the kinase domain (Thr-256) and the other in the C-terminal regulatory region (Ser-421), need to be phosphorylated for its full activation. Phosphorylation at Ser-396 and Ser-400 are also essential for its activity. Activated by WNK1, WNK2, WNK3 and WNK4 (By similarity)
Inactivated by D- and L-beta-fluoroalanine, D- and L-beta-chloroalanine, and O-acetyl-D-serine
Inhibited by phenylhydrazine, hydroxylamine, p-chloromercuribenzoate, and HgCl(2)
Proteolysis of SNAP25 by whole toxin inhibited by dipicolinic acid, 1,10-phenanthroline and EDTA (PubMed:8294407)
Subject to complex allosteric regulation. The enzyme can assume an active R-state, or an inactive T-state. Intermediate conformations may exist. AMP acts as allosteric inhibitor. AMP binding affects the turnover of bound substrate and not the affinity for substrate. Fructose 2,6-bisphosphate acts as competitive inhibitor. Fructose 2,6-bisphosphate and AMP have synergistic effects
Acetylation of Lys-50 leads to loss of DNA nicking activity
By oxidative stress, and thioredoxin. Under oxidative stress conditions, the catalytic cysteine site is converted to a sulfenate which inhibits the MPST enzyme activity. Reduced thioredoxin cleaves an intersubunit disulfide bond to turn on the redox switch and reactivate the enzyme. Inhibited by different oxidants, hydrogen peroxide and tetrathionate
Has no constitutive proton transporter activity and has to be activated by long-chain fatty acids/LCFAs. Inhibited by purine nucleotides. Both purine nucleotides and LCFAs bind the cytosolic side of the transporter and directly compete to activate or inhibit it. Activated by noradrenaline and reactive oxygen species. Despite lacking canonical translational encoding for selenocysteine, a small pool of the protein has been observed to selectively incorporate selenocysteine at 'Cys-253'. Selenocysteine-modified protein is highly sensitive to redox modification and may constitute a pool of protein highly sensitive to activation by elevated levels of reactive oxygen species (ROS)
Inhibited by p-chloromercuribenzoate and by 3-oxoadipate, and, in a temperature-dependent manner, by manganese
Inhibited by the viral nuclear shuttle protein (NSP) that binds to the region required for oligomerization
Inhibited by GDP; less than 20 uM ppGpp stimulates the GTPase, while higher concentrations inhibit
Inhibited by ethanol
Inhibited by ADP (90%), AMP (80%), alanine (52%) and aspartate (41%) (PubMed:1973929). The activity of this enzyme could be controlled by adenylation under conditions of abundant glutamine (By similarity)
Phospholipase A1 and triacylglycerol lipase are inhibited by sphingomyelin
Chloride ions activate 4-aminobutanoate/H(+) transport
Inhibition of this enzyme by phosphorylation regulates the branch point between the Krebs cycle and the glyoxylate bypass, which is an alternate route that accumulates carbon for biosynthesis when acetate is the sole carbon source for growth
E1 activity is regulated by phosphorylation (inactivation) and dephosphorylation (activation) of the alpha subunit
Activated by Mg(2+), Co(2+), Mn(2+) and Ba(2+). Inhibited by Fe(2+), Cu(2+), Zn(2+), NaF, molybdate, arsenate, vanadate and inorganic phosphate. No effect of tartrate, Asp, Gln, glutathione, Asn, ascorbic acid and phosphite
Activated by cold via CRLK1-mediated phosphorylation and leading to elevated kinase activity towards MKK2
Inhibited by GMP, ATP, GDP-D-glucose and maltose (PubMed:2470755). Inhibited by GMP and deamidoNAD (PubMed:12135385)
Highly dependent on the characteristics of the thiol cofactors used, with some of them (coenzyme M, homocysteine, and dithiothreitol) more efficient than GSH
Cysteine residue modifying agents such as p-chloromercuribenzoate and the SH-binding metals Zn(2+), Ni(2+) and Cu(2+) completely inhibit deaminase activity, whereas Ca(2+), Mg(2+) and the histidine residue-modifying agent diethyl pyrocarbonate inhibit the activity by 23 to 50%
Inhibited by EDTA, but not by PMSF
Partially inhibited by thimerosal
In the absence of viral infection, maintained as a monomer in an autoinhibited state. Phosphorylation by TBK1 and IKBKE disrupts this autoinhibition leading to the liberation of the DNA-binding and dimerization activities and its nuclear localization where it can activate type I IFN and ISG genes. Phosphorylation and activation follow the following steps: innate adapter protein MAVS, STING1 or TICAM1 are first activated by viral RNA, cytosolic DNA and bacterial lipopolysaccharide (LPS), respectively, leading to activation of the kinases TBK1 and IKBKE. These kinases then phosphorylate the adapter proteins on their pLxIS motif, leading to recruitment of IRF3, thereby licensing IRF3 for phosphorylation by TBK1. Phosphorylated IRF3 dissociates from the adapter proteins, dimerizes, and then enters the nucleus to induce IFNs
Enzyme activity enhanced by acetylation
Inhibited by pyridoxal 5'-phosphate, N-ethylmaleimide, spermine and spermidine
Inhibited by N-ethylmaleimide and sodium orthovanadate
Activated by Ca(2+) which induces self-processing and accelerates the rate of the enzyme activity, but has no effect on Km
Resistant to triclosan
Inhibited by methyl methanethiosulfonate, phenylglyoxal, tetranitromethane and diethyl pyrocarbonate (PubMed:8812853). Inhibited by 4-oxo-1,4-dihydro-quinoline-3,7-dicarboxylic acid, 4-(benzo[d][1,3]dioxol-5-ylamino)-4-oxobutanoic acid and 1,4-diaminonaphthalene-2,6-disulfonic acid (PubMed:20496117)
Activated by phosphorylation on Thr-175
Inhibited by captopril stereoisomers and iodoacetate (PubMed:3930467, PubMed:26482303). Also inhibited by chelating agents such as EDTA (PubMed:3930467)
Inhibited by kojic acid, sodium diethyldithiocarbamate and 1,10-phenanthroline monohydrochloride
Inhibited by 4 mM Mg(2+) and acetyl-CoA, competitively inhibited by fumarate and oxaloacetate. Activated by glutamate and aspartate, glucose-6-phosphate, acetyl-phosphate and 2 mM KCl
Inhibited by potassium cyanide, menadione, benzamidine, raloxifene and norharmane
Adenylation activity is increased in the presence of the MbtH-like protein YbdZ
Enzyme activity is regulated by iron
Is salt tolerant and retains more than 50% residual activity up to 15% NaCl
Enzymatic activity is dependent on membrane association and requires the presence of lipids (PubMed:23250757). Inhibited by N-(adamantanemethyloxypentyl)-deoxynojirimycin/AMP-DNM (PubMed:26724485). Inhibited by its product sphingosine/N-acylsphing-4-enine in a feedback loop (PubMed:28258214). Also inhibited by other non-acetylated sphingoid bases and their derivatives but not by sphingosine-1-phosphate and complex sphingolipids (PubMed:28258214)
In rod outer segments, activated by light
Inhibited by reserpine, and the proton ionophore carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP)
Is active as a kinase only at high ATP concentrations or at low ATP concentrations in the presence of the allosteric activator fructose 1,6-bisphosphate (FBP). The pyrophosphate-dependent HPr phosphorylation is not stimulated by FBP. Kinase activity is inhibited by inorganic phosphate (Pi). Dephosphorylation of HPr(Ser-P) by B.subtilis HPrK/P becomes prevalent when the concentration of Pi increases. Thus, the kinase activity may prevail under conditions of good nutrient supply, whereas the phosphorylase activity is dominant if carbon and energy sources become limiting
Fructose acts as a non-competitive inhibitor with an inhibition constant of 17.2 mM. In contrast, glucose inhibits uncompetitively with an inhibition constant of 4.3 mM
GABA transport is inhibited by beta-alanine, 2,3-diaminopropionic acid and SNAP-5114
Autoinhibited by the ariadne domain, which masks the second RING-type zinc finger that contains the active site and inhibits the E3 activity (By similarity). Inhibition is relieved upon binding to neddylated cullin-RING ubiquitin ligase complexes, which activate the E3 ligase activity of ARIH1 (By similarity)
Drug-mediated inhibition leads to a delay of the oscillations with the magnitude of this effect dependent upon the timing of drug administration. Inhibited by phosphorylation (By similarity). Exhibits substrate-dependent heparin activation
Competitive inhibition is mediated by geranyl diphosphate (GPP)
Requires K(+) ions for optimum activity
Activated by free oleic acid in a dose-dependent manner and less effectively by other unsaturated fatty acids such as linoleic and linolenic acids (PubMed:11706190). Not activated by the saturated fatty acids stearic and palmitic acids (PubMed:11706190). PIP2 and Ca(2+) stimulate activity by promoting lipid substrate binding to the active site (PubMed:12397060). Activated by H(2)O(2) and by binding to GAPC (PubMed:14508007, PubMed:22589465)
Amino acid transport is sodium-dependent (By similarity). Transport of leucine, tyrosine and phenylalanine is increased by arginine binding (By similarity)
Acetyltransferase activity is increased following acute inflammatory stimulation by lipopolysaccharide (LPS). Acyltransferase activity is unchanged
The activity of AknS is substantially increased by the addition of the accessory protein AknT
Is completely inhibited by EDTA in vitro
Activity abolished by tyrosine phosphatase inhibitor sodium vanadate. Activated by rl
Activated by Triton X-100, insensitive to inhibition by adenosine and inhibited by wortmannin (By similarity). Isoform 2 is activated by detergents such as Triton X-100 and inhibited by adenosine (PubMed:7961848). The PI4K complex acts as a regulator of phosphatidylinositol 4-phosphate (PtdIns(4)P) synthesis (PubMed:23229899, PubMed:26571211). Interaction with TMEM150A regulates PtdIns(4)P synthesis (PubMed:25608530)
Inactivation of this channel is specifically inhibited by the spider toxins Hm1a and Hm1b (H.maculata, AC P60992 and AC P0DOC5) in somatosensory neurons to elicit acute pain and mechanical allodynia
The regulatory domain is involved in the regulation of cyclase activity by the carbon source. Activated by the PTS system, glucose-specific IIA component (CRR)
Autoinhibited by a module composed of four alpha helices (HI-1, HI-2, H4, and H5) that flank the DNA-binding ETS domain, reducing the affinity for DNA
Inhibited by vanadate but not by chlorogenic acid
The SRP-FtsY complex formation results in mutual stimulation of their GTP hydrolysis activity
Activity is triggered by phenol binding
Inhibited by PCNA123 and PCNA323
Allosterically regulated by a feedback inhibition loop
Probably activated by phosphorylation and inhibited by dephosphorylation
Inhibited by the serine protease inhibitors diisopropyl fluorophosphate and phenylmethanesulfonyl fluoride
Phosphorylation at Thr-17 or Tyr-18 inactivates the enzyme, while phosphorylation at Thr-166 activates it
Is competitively inhibited by (R)-HMG-CoA and lovastatin (formerly called mevinolin)
Inhibited by 4-aminopyridine (4-AP) and charybdotoxin (CTX), but not by tetraethylammonium (TEA) (PubMed:19912772). Inhibited by dendrotoxin (DTX) (By similarity). Inhibited by tityustoxin-K alpha (TsTX-Kalpha), a toxin that is highly specific for KCNA2 (By similarity). Inhibited by maurotoxin (By similarity). Inhibited by kappaM conotoxins kappaM-RIIIJ and kappaM-RIIIK; kappaM-RIIIJ has much higher affinity for channels containing KCNA2 than kappaM-RIIIK, with the exception of heterodimers formed by KCNA2 and KCNA7 where the opposite is true (PubMed:20220134)
Inhibited by the proteinase inhibitors indinavir, lopinavir, nelfinavir, isovaleryl pepstatin, ritonavir, saquinavir and tipranavir
Allosterically activated by its substrate, pyruvate
Inhibited by Hg(2+) and D-glucono-1,5-lactone
Activated by hyperosmotic shock after mannitol treatment
Two specific sites, one in the kinase domain (Thr-309) and the other in the C-terminal regulatory region (Ser-474), need to be phosphorylated for its full activation
Inhibited by the diterpenoid derivative 15-oxospiramilactone (S3)
By oxidative stress, and thioredoxin. Under oxidative stress conditions, the catalytic cysteine site is converted to a sulfenate which inhibits the MPST enzyme activity. Reduced thioredoxin cleaves an intersubunit disulfide bond to turn on the redox switch and reactivate the enzyme
Inhibited by marimastat and tripeptide hydroxamic acids
Inhibited by CoASH (IC(50)=10-15 uM). Also inhibited by cysteine-reactive agents
Kinase activity is stimulated by both birc5/survivin-binding and cell-cycle specific phosphorylation
Calcium-binding enhance the activity of the enzyme
In non-starving cells, secretion and protease activity are inhibited by formation of a cytoplasmic complex with PopD (PubMed:22404381). In response to starvation, PopD is degraded in a RelA- and FtsH(D)-dependent manner, thereby releasing pre-formed PopC for secretion (PubMed:22404381). Secreted and active during starvation, and rapidly degraded upon secretion (PubMed:18854146). Secretion is significantly and reversibly reduced by carbonyl cyanide m-chlorophenyl hydrazine (CCCP), which dissipates or reduces the proton motive force (PMF), and by nigericin, which affects the pH gradient (PubMed:30911012)
The polymerase, exonuclease and ligase activities are stimulated by Ku. Polymerase activity is inhibited by EDTA
Inhibited by plumbagin (By similarity). Activated by phorbol 12-myristate 13-acetate (PMA). Activated by insulin. Inhibited by diphenylene iodonium
Inhibited by NSC-12155 (1,3-Bis(2-methyl-4-aminoquinoline-6-yl)ure) (PubMed:14718925). Inhibited by phenoxyacetic acid bearing alpha-benzyl substituents on the C2-side chain (PubMed:22342144). Inhibited by sulfonamide hydroxamate with benzylic additions at the sulfonamide nitrogen (PubMed:25372673). Also inhibited by sulfonamide hydroxamates with alkylation at the sulfonamide nitrogen (PubMed:26492514). Inhibited by hydroxamic acid inhibitors (PubMed:26578066)
Inhibited by ammonium molybdate, sodium orthovanadate, N-ethylmaleimide and iodoacetic acid
Competitively inhibited by homoserine and by glutamine
Stimulated by calcium/calmodulin. Inhibited by n-Nos-inhibiting protein (PIN) which may prevent the dimerization of the protein. Inhibited by NOSIP
Activated by phosphorylation on Thr-211. Inhibited by phosphorylation on Thr-617 (By similarity)
The insertion of copper which activates the protein requires glutathione. This is independent of copper chaperone for SOD1 (CCS), which activates orthologs
The phosphorylation activity is calcium-independent
Activity is stimulated by low concentrations of salts and by moderate concentrations of glycine betaine. Highly tolerant to high ionic conditions. In vitro, activity is highly stimulated in the presence of proline
Competitively inhibited by acyclic nucleoside phosphonates (ANPs) with Ki values as low as 0.69 uM. Prodrugs of these compounds arrest the growth of a virulent strain of M.tuberculosis with MIC50 values as low as 4.5 uM and possess low cytotoxicity in mammalian cells (PubMed:25915781). Inhibited by pyrrolidine nucleoside bisphosphonates, which are also able to arrest the growth of virulent M.tuberculosis not only in its replicating phase but also in its latent phase, and to arrest the growth of M.tuberculosis in infected macrophages while having low cytotoxicity in mammalian cells (PubMed:30265958)
Ubiquitination of histone H2B to form H2BK123ub1 is required for efficient DOT1 methyltransferase activity on histone H3
Inhibited by PMSF and soybean trypsin inhibitor. Partially inhibited by DTT and cysteine. Not affected by EDTA
Inhibited in feedback fashion by the catecholamine neurotransmitters, especially by dopamine in competition with tetrahydrobiopterin (PubMed:15287903). Phosphorylation of several Ser/Thr residues in the N-terminus regulates the catalytic activity (PubMed:1680128, PubMed:7901013). Ser-62 and Ser-71 are readily phosphorylated to activate the catalytic activity (PubMed:1680128, PubMed:7901013). A Cysteine modification induced by N-ethylmaleimide (NEM), inhibits tyrosine 3-monooxygenase activity through the modification of the Cys-207 (PubMed:34922205)
Inhibited by K3 herbicides such as alachlor, allidochlor, anilofos, cafenstrole, fentrazamide and flufenacet (PubMed:15277688). Strongly inhibited by metazachlor (PubMed:22284369)
The side chain of Glu-222 determines which of the two opposing activities (AMPylase or de-AMPylase) will take place. In response to endoplasmic reticulum stress, mediates de-AMPylase activity (By similarity). Adenylyltransferase activity is inhibited by the inhibitory helix present at the N-terminus: Glu-222 binds ATP and competes with ATP-binding at Arg-362, thereby preventing adenylyltransferase activity (By similarity). In unstressed cells, disengagement of Glu-222 promotes adenylyltransferase activity (By similarity). Activation dissociates ATP-binding from Glu-222, allowing ordered binding of the entire ATP moiety with the alpha-phosphate in an orientation that is productive for accepting an incoming target hydroxyl side chain (By similarity)
Ca(2+)/calmodulin binding removes an autoinhibitory regulatory segment located C-terminal to the kinase domain. This releases the catalytic activity of the enzyme and makes accessible a regulatory residue Thr-284. Phosphorylation of Thr-284 by another kinase domain within the oligomeric holoenzyme keeps CaMKII active in the absence of Ca(2+)/calmodulin by preventing the rebinding of the regulatory segment to the kinase domain and by increasing the affinity of calmodulin for the enzyme. Can respond to high-frequency Ca(2+) pulses to become Ca(2+) independent (By similarity)
RNA cleavage is inhibited by the C-terminal domain of DNA topoisomerase I
Inhibited by NADH, NADPH and NADP(+)
Inhibited by quercetin, dicoumarol and some SH-reagents
Highly competitively inhibited by L-argininamide and L-arginine methyl ester. Also inhibited by alpha-difluoromethylarginine. Is not stimulated by potassium chloride as observed for other decarboxylases
Under resting conditions, NLRP3 binds ADP and is autoinhibited (By similarity). Inactive NLRP3 forms homodecameric double-ring cages that hide pyrin domains within NACHT-LRR rings to avoid premature activation. NLRP3 activation stimuli include extracellular ATP, nigericin, reactive oxygen species, crystals of monosodium urate or cholesterol, amyloid-beta fibers, environmental or industrial particles and nanoparticles, such as asbestos, silica, aluminum salts, cytosolic dsRNA, etc. Almost all stimuli trigger intracellular K(+) efflux. These stimuli lead to membrane perturbations that induce activation of NLRP3. Upon activation, NLRP3 is transported to microtubule organizing center (MTOC), where it is unlocked by NEK7, leading to its relocalization to dispersed trans-Golgi network (dTGN) vesicle membranes and recruitment of PYCARD/ASC for the formation of an active inflammasome complex. NEK7-activated NLRP3 forms a disk-shaped inflammasome. NLRP3 and PYCARD/ASC interact via their respective pyrin domains; interaction initiates speck formation (nucleation) which greatly enhances further addition of soluble PYCARD/ASC molecules to the speck in a prion-like polymerization process (By similarity). Clustered PYCARD/ASC nucleates the formation of CASP1 filaments through the interaction of their respective CARD domains, acting as a platform for CASP1 polymerization and activation. Active CASP1 then processes IL1B and IL18 precursors, leading to the release of mature cytokines in the extracellular milieu and inflammatory response (By similarity). NLRP3 inflammasome assembly is inhibited by IRGM, which impedes NLRP3 oligomerization (By similarity). Specifically inhibited by sulfonylurea MCC950 (also named CP-456,773, CRID3), a potent and specific small-molecule inhibitor of the NLRP3 inflammasome that acts by preventing ATP hydrolysis (By similarity)
Activated by threonine and tyrosine phosphorylation by the dual specificity kinase, hep. Inhibited by dual specificity phosphatase, puckered
Activated by the benzylsuccinate synthase activating enzyme BssD. Rapidly inactivated by oxygen
Homotetramerization is required for activity. Tetramerization results in the formation of a gated channel which is involved in substrate selection and substrate access to the catalytic sites
Activated by cAMP. cAMP binding causes a conformation change that leads to the assembly of an active tetramer and channel opening
Uridylyltransferase (UTase) activity is inhibited by glutamine, while glutamine activates uridylyl-removing (UR) activity. Both reactions are activated by ATP and 2-ketoglutarate, via the binding of these effector molecules to the substrates PII and PII-UMP
Inhibited by EGTA
The NAALADase activity is inhibited by beta-NAAG, quisqualic acid and 2-(phosphonomethyl)glutaric acid (PMG)
Regulated by feedback inhibition by malonyl-CoA
(Microbial infection) Activity against phage lambda cII protein is inhibited by EDTA but not by PMSF. In vitro pre-incubation of FtsH with HflKC abolishes its activity against phage lambda cII protein at the cytoplasmic side of the membrane
(Microbial infection) Inactivated by S.flexneri OspC1 and OspC3 proteins, which specifically bind the apo-form of calmodulin, thereby preventing calcium-binding and activity
Negatively regulated by the anti-sigma-I factor RsgI6 (By similarity). Binding of the polysaccharide substrate to RsgI6 may lead to the release and activation of SigI6 (By similarity)
Inhibited by phenylarsine oxide and adenosine (PubMed:11923287). Activation through membrane association is stimulated by active RAC1 (PubMed:12324459)
Inhibited by phosphorylation of Tyr-538 by leukocyte common antigen and activated by dephosphorylation of this site
Activated by GUCA1A when free calcium ions concentration is low, and inhibited by GUCA1A when free calcium ions concentration is high (By similarity). Negatively regulated by RD3; inhibits the basal and GUCA1A-stimulated guanylate cyclase activity (PubMed:21928830)
Activated by phosphorylation of Thr-236. Once activated, activity is stimulated by binding target proteins (By similarity)
Activity is potassium and sulfate-independent
Pyrrolopyrimidines inhibit both GyrB and its paralog in topoisomerase IV (parE) (PubMed:23294697)
Very slightly decreased activity with glutamine synthetase (GS) inhibitor methionine sulfoximine (MSO)
Activity is inhibited by and MTH-trp (methylthiohydantoin-DL-tryptophan), modestly inhibited by L-1MT (1-methyl-L-tryptophan) but not D-1MT (1-methyl-D-tryptophan)
Activity improves as salinity decreases
Interaction with SAMHD1 stimulates the double-strand-specific 3'-5' exonuclease activity
Stimulated by phosphatidylinositol 4-phosphate (PtdIns4P). Slightly repressed by phosphatidyl-choline (PtdCho), wortmannin and adenosine
Activated by tyrosine and threonine phosphorylation by MKK1 and MKK2
Inhibited by EDTA and N-ethylmaleimide (NEM) in vitro
Inhibited by zinc ions, carbamoylphosphate and beta,gamma-imido-ATP
Strongly inhibited by Hg(2+), Ag(+) and Fe(3+). To a lesser extent, is also inhibited by Pb(2+), Mn(2+), Sn(2+) and Cu(2+). By contrast, Ni(2+), Zn(2+), Co(2+), Ba(2+) and NH(4)(+) do not affect enzyme activity, while 10 mM Ca(2+), and Mg(2+) produce a stimulating effect. Is also strongly inhibited by chemicals such as N-bromosuccinimide and dimethyl(2-dihydroxy-5-nitrobenzyl)sulphonium bromide. Is not affected by N-acetylimidazole
Its proteolytic activity is inhibited by EDTA, TPEN, 1,10-phenanthroline, and some thiol compounds, but is enhanced by alkaline earth metal ions (Mg2+, Ca2+, Sr2+, and Ba2+). Its activity is not modulated by urea (4 M)
Binding of adenosine nucleotides results in distinct, cooperative behavior for ATP and ADP. GlnK2 is completely insensitive to 2-oxoglutarate at a low level of intracellular nitrogen
The covalent binding to the substrate at Lys-339 of a small fraction of enolase causes inactivation of the enzyme, and possibly serves as a signal for the export of the protein (PubMed:15003462). Citrate acts as a non-competitive inhibitor for both forward and reverse reactions, probably by chelating Mg(2+) (PubMed:22198292)
Slightly activated by succinate and aspartate. Repressed by fumarate, malate, oxaloacetate and glucose
Inhibited by hadacidin. Activated by fructose 1,6-bisphosphate
Inhibited by thiorphan and phosphoramidon
Inhibited by EDTA and diisopropyl fluorophosphate (DFP). Also inhibited by an excess of zinc or calcium ions
Inhibited by N-ethylmaleimide. Redox-regulated during autophagy since reducing conditions activate ATG4A whereas an oxidizing environment such as the presence of H(2)O(2) inhibits its activity. The cysteine protease activity compounds is inhibited by styrylquinoline compounds 4-28 and LV-320
Inhibited by citral, disulfiram, and cyanamide. Activated by diethylstilbestrol (PubMed:19296407). Inhibited by duocarmycin analogs (PubMed:26373694)
Inhibited by pepstatin A
GTPase activity is enhanced by Zn(2+) binding
Activated by GTP and inhibited by XMP and the IMP analogs allopurinol nucleotide and thiopurinol nucleotide
Regulated predominantly by intracellular cAMP levels. The 17,20-lyase activity is stimulated by cytochrome b5, which acts as an allosteric effector increasing the Vmax of the lyase activity
GAP activity stimulated by phosphatidylinositol 4,5-bisphosphate (PIP2)
Inhibited by phosphorylation of Tyr-531 by leukocyte common antigen and activated by dephosphorylation of this site
Inhibited by a series a OPs such as mipafox (MPX), phenyl saligenin phosphate (PSP), phenyl dipentyl phosphinate (PDPP), diisopropyl fluorophosphate and paraoxon
The RNase activity is stimulated by cA4
DHAD activity is inhibited in dose-dependent manner by 2-hydroxy-3-methylbutyric acid with an IC(50) of about 8 mM
Activated in response to stress, such as ribosomal stress, osmotic shock and ionizing radiation. Activated by phosphorylation by PKN1, followed by autophosphorylation on Thr-161 and Ser-165
Acetylation by KAT5/TIP60 stimulates the protein kinase activity (By similarity). The protein kinase activity is activated by unanchored 'Lys-63'-linked polyubiquitin chains: unanchored 'Lys-63'-linked polyubiquitin chains are catalyzed by TRIM32 in an AMBRA1-dependent manner (PubMed:31123703)
Inhibited by serpin ZX and nitric oxide through cysteine nitrosylation
The activity depends critically on the nature of the bound metal ion. Catalyzes the oxidation of 5,6-dihydroxyindole-2-carboxylic acid (DHICA) in the presence of bound Cu(2+) ions, but lacks activity in the presence of bound Zn(2+) ions
Channel activity is repressed by chloride inhibitors; strongly by niflumic acid (NFA), partially by flufenamic acid (FFA), and only slightly by meclofenamic acid (MFA), 5-Nitro-2-(3-phenylpropylamino)benzoic acid (NPPB), 4-acetamido-4'-isothiocyanato-stilben-2,2'-disulfonate (SITS), and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS)
Inhibited by nitric oxide (NO). The 2Fe-2S cluster could act as a NO sensor (By similarity)
Adopts an inactive conformation in absence of DNA damage. Binding to poly-ADP-ribosylated histones activates the ATP-dependent chromatin remodeler activity
In the absence of cGMP, PRKG1 activity is suppressed by autoinhibitory contacts
Activated by ligand-binding, leading to homodimerization and autophosphorylation
Alternates between an inactive form bound to GDP and an active form bound to GTP. Activated by guanine nucleotide-exchange factors (GEFs), and inactivated by GTPase-activating proteins (GAPs)
Inhibited by sarcolipin (SLN) and myoregulin (MRLN) (PubMed:10551848, PubMed:8428955, PubMed:29081402). Inhibited by phospholamban (PLN) (PubMed:10551848, PubMed:8428955, PubMed:29081402, PubMed:23996003). Reversibly inhibited by phospholamban (PLN) at low calcium concentrations (PubMed:10551848, PubMed:8428955, PubMed:29081402, PubMed:23996003). Dephosphorylated PLN decreases the apparent affinity of the ATPase for calcium (PubMed:10551848, PubMed:8428955). This inhibition is regulated by the phosphorylation of PLN (PubMed:10551848, PubMed:8428955). Enhanced by DWORF; DWORF increases activity by displacing sarcolipin (SLN), phospholamban (PLN) and myoregulin (MRLN) (By similarity)
Disaggregase activity is inhibited by ADP
Activated by inorganic phosphate, and to a lesser extent by sulfate ions (PubMed:21085589, PubMed:21045009). In addition to form a complex with ATP, Mg(2+) also acts as a cofactor (PubMed:21085589, PubMed:21045009). Strongly inhibited by ADP and GDP through competitive binding at the activation site and at a specific allosteric site (PubMed:21085589, PubMed:21045009, PubMed:22745722). Competitively inhibited by Ca(2+), Cu(2+) and Fe(2+) (PubMed:21085589, PubMed:21045009)
Ethylenediaminetetraacetic acid completely abolishes catalytic activity (PubMed:24415556). Catalytic activity is enhanced by complex formation with SELENOF (PubMed:24415556)
The chaperone activity is regulated by ATP-induced allosteric coupling of the nucleotide-binding (NBD) and substrate-binding (SBD) domains. In the ADP-bound and nucleotide-free (apo) states, the two domains have little interaction (PubMed:26655470). In contrast, in the ATP-bound state the two domains are tightly coupled, which results in drastically accelerated kinetics in both binding and release of polypeptide substrates (PubMed:26655470). J domain-containing co-chaperones (DNAJB9/ERdj4 or DNAJC10/ERdj5) stimulate the ATPase activity and are required for efficient substrate recognition by HSPA5/BiP (By similarity). Homooligomerization inactivates participating HSPA5/BiP protomers and probably act as reservoirs to store HSPA5/BiP molecules when they are not needed by the cell (By similarity)
Inhibited by calcium ions
Activated by interaction with the autoinducer signal molecule N-butanoyl-L-homoserine lactone (C4-HSL or BHL), the product of the RhlI synthase (PubMed:7604006, PubMed:14526008, PubMed:26732761). Is also activated by binding to rosmarinic acid (RA), a homoserine lactone mimic produced by plants, which induces a broad quorum sensing response, including the induction of all major quorum sensing controlled virulence factors. Rosmarinic acid secretion may be a plant defense mechanism to stimulate a premature quorum sensing response (PubMed:26732761, PubMed:30051572)
Allopurinol inhibits catalytic activity in a linear fashion (PubMed:363427)
Encapsulated enzyme is 7-fold more active than encapsulated enzyme
Inhibited by cadmium, copper, zinc when added cobalt when added concomitantly with manganese
Activity is strongly promoted by Co(2+), Ni(2+), Mg(2+) and Mn(2+). Activity is inhibited by EDTA
Inhibited by 2-mercaptomethyl-3-guanidinoethylthiopropanoic acid (MGTA) and guanidinoethylmercaptosuccinic acid (GEMSA). Inhibited by chelating agents such as EDTA and EGTA
Activated by Mn2+
Inhibited by dithiothreitol and stimulated by protamine
Inhibited by EDTA and o-phenanthroline. Not inhibited by PMSF, benzamidine, irreversible serine-proteinase inhibitors and cysteine proteinase inhibitor E-64
Inhibited by dicyclohexylcarbodiimide
Activated by light-induced dephosphorylation. Inhibited by dark-induced phosphorylation. Both reactions are catalyzed by PDRP1 (By similarity). Inactivated by cold due to the dissociation of the homotetramer
Binding to TXN is inhibited by hydrogen peroxide in vitro
The 5'-3' exoribonuclease activity is inhibited by adenosine 3',5'-bisphosphate
Inhibited by 12.7 nM stromatoxin 1 (ScTx1), a spider venom toxin of the tarantula S.calceata. Inhibited by 42 nM hanatoxin 1 (HaTx1), a spider venom toxin of the tarantula G.spatulata. Modestly sensitive to millimolar levels of tetraethylammonium (TEA). Modestly sensitive to millimolar levels of 4-aminopyridine (4-AP). Completely insensitive to toxins such as dendrotoxin (DTX) and charybdotoxin (CTX)
Binding to DNA is allosterically inhibited by the effector glucosamine-6-phosphate (GlcN6P). N-acetylglucosamine-6-phosphate (GlcNAc6P) and glucose-6-phosphate (Glc6P) have no effect
Is inhibited in vitro by para-hydroxymercuribenzoate, a sulfydryl inhibitor
Inactive in the absence of MgCl(2) and CaCl(2) and full activation at 10 mM concentrations of either ion (PubMed:16601675). Completely inhibited by the metal chelator orthophenanthroline, but not affected by phenylmethylsulfonyl fluoride (PMSF) or N-ethylmaleimide (NEM) (PubMed:14617063, PubMed:16601675)
Activated by multiple phosphorylations on threonine and serine residues
Inhibited by nitric oxide (NO). The 2Fe-2S cluster could act as a NO sensor
Binding to PMPCA is required for catalytic activity
Inhibited by chelating agents such as EDTA
Inhibited by antizyme (AZ) in response to polyamine levels. AZ inhibits the assembly of the functional homodimer by binding to ODC monomers and targeting them for ubiquitin-independent proteolytic destruction by the 26S proteasome
May play a role in spermatozoa-egg-interaction
Is not regulated allosterically. Activity is inhibited in the presence of high ionic strength; the inhibitory effect of KCl is slightly higher than that of NaCl
The CatSper calcium channel is indirectly activated by extracellular progesterone and prostaglandins following the sequence: progesterone > PGF1-alpha = PGE1 > PGA1 > PGE2 >> PGD2 (PubMed:21412338, PubMed:21412339, PubMed:26989199). The CatSper calcium channel is directly inhibited by endocannabinoid 2-arachidonoylglycerol (2AG) (PubMed:26989199). Indirect activation by progesterone takes place via the following mechanism: progesterone binds and activates the acylglycerol lipase ABHD2, which in turn mediates hydrolysis of 2AG inhibitor, relieving inhibition of the CatSper channel (PubMed:26989199). The primary effect of progesterone activation is to shift voltage dependence towards more physiological, negative membrane potentials; it is not mediated by metabotropic receptors and second messengers (PubMed:21412338, PubMed:21412339). Sperm capacitation enhances the effect of progesterone by providing additional negative shift. Also activated by the elevation of intracellular pH (PubMed:21412338, PubMed:21412339)
Inhibited by complexation with the proform of PRG2
Ras proteins such as HRAS mediate the activation of RAF proteins such as RAF1 or BRAF which in turn activate extracellular signal-regulated kinases (ERK) through MAPK (mitogen-activated protein kinases) and ERK kinases MAP2K1/MEK1 and MAP2K2/MEK2. Activation occurs through phosphorylation of Ser-218 and Ser-222. MAP2K1/MEK1 binds KSR1 or KSR2 releasing the inhibitory intramolecular interaction between KSR1 or KSR2 protein kinase and N-terminal domains (By similarity). This allows KSR1 or KSR2 dimerization with BRAF leading to BRAF activation and phosphorylation of MAP2K1 (By similarity). MAP2K1/MEK1 is also the target of negative feed-back regulation by its substrate kinases, such as MAPK1/ERK2. These phosphorylate MAP2K1/MEK1 on Thr-292, thereby facilitating dephosphorylation of the activating residues Ser-218 and Ser-222. Inhibited by serine/threonine phosphatase 2A (By similarity)
Potently inhibited by the serine peptidase inhibitor chymostatin. Also inhibited by antpain and PMSF
Each protein molecule can bind up to four molecules of AMP, which act as an allosteric activator to the enzyme
Optimal activity is achieved when His-310 and Lys-422 are both present to open the sugar ring, and Glu-281 catalyzes the isomerization step (PubMed:33422670). Activity is decreased in the presence of the PGI inhibitor 6-phosphogluconate (PubMed:33422670)
Binding to ERDJ3A activates the ATPase activity of BIP3
DNA supercoiling is inhibited by fluoroquinolones; IC(50) 1 ug/ml for sitafloxacin
Channel activity is activated via the interaction with PIRT and phosphatidylinositol 4,5-bisphosphate (PIP2). Both PIRT and PIP2 are required to activate channel activity. The channel is sensitized by ATP binding. Repeated stimulation with capsaicin gives rise to progressively smaller responses, due to desensitization. This desensitization is triggered by the influx of calcium ions and is inhibited by elevated ATP levels. Ca(2+) and CALM displace ATP from its binding site and trigger a conformation change that leads to a closed, desensitized channel. Intracellular PIP2 inhibits desensitization. The double-knot toxin (DkTx) from the Chinese earth tiger tarantula activates the channel and traps it in an open conformation (By similarity). The Scolopendra mutilans RhTx toxin potentiates the heat activation pathway mediated by this channel by binding to the charge-rich outer pore region (in an activated state) (By similarity)
Inhibited by serine protease inhibitors PMSF, benzamidine, leupeptin and aprotinin, as well as by copper (Cu2+) and manganese (Mn2+) ions. Not inhibited by metalloprotease inhibitors EDTA, EGTA and 1,10-phenanthroline, as well as by barium (Ba2+) and calcium ion (Ca2+)
Inactivated by diethyldithiocarbamate (PubMed:7929223). Inhibited by cyanide (PubMed:7929223)
The kinase activity is inhibited by arginine
CDC34-catalyzed polyubiquitin chain assembly activity is stimulated by the conjugation of NEDD8 to the CUL1 SCF E3 ligase complex subunit
Competitively inhibited by KAPA at concentrations above 10 uM and by amiclenomycin
Maintained in an inactive, closed conformation by an interaction between the kinase domain and the negative autoregulatory C-terminal coiled-coil region. Agonist binding to the phorbol ester binding site disrupts this, releasing the kinase domain to allow N-terminus-mediated dimerization and kinase activation by transautophosphorylation (By similarity). Inhibited by chelerythrine chloride
InhA activity is controlled via phosphorylation: phosphorylation on Thr-266 decreases InhA activity (5-fold reduction) and likely negatively regulates biosynthesis of mycolic acids and growth of the bacterium. The antitubercular pro-drug isoniazid (INH) is oxidatively activated by the catalase-peroxidase KatG and then covalently binds NAD to form an adduct that inhibits the activity of InhA. The inhibitory adduct is the isonicotinic-acyl-NADH where the isonicotinic-acyl group replaces the 4S (and not the 4R) hydrogen of NADH. Similarly, the antitubercular pro-drugs ethionamide (ETH) and prothionamide (PTH) are activated by the flavoprotein monooxygenase EthA, and forms an adduct with NAD (ETH-NAD and PTH-NAD, respectively) that is a tight-binding inhibitor of InhA. Is inhibited by triclosan and derivatives, pyrazole derivative Genz-8575, indole-5-amide Genz-10850, alkyl diphenyl/diaryl ethers, pyrrolidine carboxamides, arylamides, pyridomycin, methyl-thiazoles, 4-hydroxy-2-pyridones, and N-benzyl-4-((heteroaryl)methyl)benzamides. Pyridomycin shows a unique mode of InhA inhibition by simultaneously blocking parts of the NADH and the lipid substrate-binding pocket of InhA. Is also inhibited by thiadiazole compounds, that have very attractive antitubercular properties
Strongly inhibited (about 90% of the enzyme activity) by Ag(+), Hg(2+) and p-chloromercuribenzoic acid. Cu(2+) and Zn(2+) inhibit about 60% of the enzyme activity
Strongly inhibited in the presence of thiol modifiers, suggesting a crucial role for cysteine residues in catalysis. Slightly inhibited by EDTA
Not inhibited by phlorizin
ADP-ribosyl cyclase and cADPR hydrolase activities are both activated by Zn(2+) or Mn(2+), and inhibited by Cu(2+), while Mg(2+) and Ca(2+) do not have any significant influence
Inhibited by cyanide and 2,4-dinitrophenol, but not by arsenate
Inhibited by Zn(2+), Ca(2+), Ba(2+), Fe(2+), Co(2+), Cu(2+), Eu(2+), Eu(3+) and Mn(2+)
Strongly Inhibited by F-amidine and N-alpha-benzoyl-N5-(2-chloro-1-iminoethyl)-L-ornithine amide (Cl-amidine). These inhibitors are however not specific to PADI4 and also inhibit other members of the family
By hypertonicity. Activation requires autophosphorylation of Ser-382. Phosphorylation of Ser-378 also promotes increased activity (By similarity)
Activated by ATP (By similarity). pH-dependent and inhibited by acidic pH (PubMed:24817123)
Inactivated by cyanide
The kinase domain is activated by trans-autophosphorylation following homodimerization. Kinase activity is required for activation of the endoribonuclease domain (PubMed:25164867). Endoribonuclease activity is specifically inhibited by hydroxy-aryl-aldehydes (HAA) MKC9989, OICR464 and OICR573 (PubMed:25164867)
Negatively regulated by SpoIIID
Activated by phospholipids, Mg(2+) and Cu(+)
Inhibited by divalent cations different from calcium ions (cadmium, magnesium, manganese, zinc), since they act as competitive antagonists of this cofactor
Activated by autophosphorylation on serine and threonine residues in response to extracellular hydrogen peroxide
Allosterically activated by various compounds including ATP, 2,3-BPG/2,3-Bisphosphoglyceric acid and Ap4A/P1,P4-bis(5'-adenosyl) tetraphosphate. Binding of an allosteric activator is a prerequisiste to magnesium and substrate binding. Inhibited by inorganic phosphate (By similarity). Inhibited by inosine, guanosine, p-chloromercuribenzoate and NaF (PubMed:6060459)
Allosterically activated by ATP (By similarity). ATP binding is a prerequisite to magnesium and substrate binding. ATP binds to 2 of the subunits in the homotetramer inducing a closure of these 2 subunits and the release of the C-terminal loop, thereby activating the enzyme (By similarity)
Is specifically blocked by omega-conotoxin GVIA (By similarity). Is specifically blocked by omega-conotoxin MVIIA (ziconotide) (PubMed:34234349). Is insensitive to dihydropyridines (DHP)
Kinase activity is regulated by the redox status of the environment via the rubredoxin domain. Autophosphorylation is not essential for kinase activity, but it promotes binding to GarA. The C-terminal domain also contributes to the regulation of activity. Inhibited by a specific small molecular-weight inhibitor, the tetrahydrobenzothiophene AX20017
Inhibited by hydroxamate-type metalloproteinase inhibitors such as marimastat. Inhibited by metalloproteinase inhibitor 2 (TIMP-2) and TIMP-3 at nanomolar concentrations. Not significantly inhibited by TIMP-1 at concentrations of up to 100 nM. Not activated by PMA or ionomycin
Competitive inhibition by phenylureas
Activated by DAG and phorbol esters. Phorbol-ester/DAG-type domain 1 binds DAG with high affinity and appears to play the dominant role in mediating translocation to the cell membrane and trans-Golgi network. Phorbol-ester/DAG-type domain 2 binds phorbol ester with higher affinity. Autophosphorylation of Ser-748 and phosphorylation of Ser-744 by PKC relieves auto-inhibition by the PH domain. Phosphorylation on Tyr-469 by the SRC-ABL1 pathway in response to oxidative stress, is also required for activation. Activated by DAPK1 under oxidative stress (By similarity)
In the apo-form the DNA-binding helices form a rigid body in which their DNA recognitions helices are buried. cAMP binding causes a coil-to-helix transition, stabilizing the active DNA binding conformation by reorienting and elongating these helices, which precludes a return to the inactive state (PubMed:19359484, PubMed:19805344). Interaction with SpfP blocks activation of some, but not all, CRP-dependent genes (PubMed:35239441)
Activity unstable at KCl and NaCl concentrations lower than 2 M and activity increases with increasing concentrations of KCl or NaCl
Inhibited rather than stimulated by magnesium
ATPase activity is slightly stimulated by either circular single- or double-stranded DNA with a weak preference for double-stranded DNA
Activated by GHR1-mediated phosphorylation which is negatively regulated by ABI2 but not ABI1 (PubMed:22730405). Activation by SRK2E/OST1 and GHR1 is repressed by HT1 (PubMed:27694184)
Activated by the G protein alpha subunit (PubMed:18541530). Activated by the G protein beta and gamma subunit complex (PubMed:23229509). Activated by GNA13 and GNA12 (PubMed:18541530). Ethanol and phorbol 12,13-dibutanoate significantly potentiate adenylate cyclase activity generated in response to the activation of the prostanoid receptor by the agonist prostaglandin E1(1-) in a PKC-dependent manner (PubMed:12454008). Inhibited by lithium (By similarity)
The C-terminal iron-sulfur cluster may stabilize the structure of the C-terminal loops and may function in the regulation of the transport process
The side chain of Glu-247 determines which of the two opposing activities (AMPylase or de-AMPylase) will take place. In response to endoplasmic reticulum stress, mediates de-AMPylase activity (By similarity). Adenylyltransferase activity is inhibited by the inhibitory helix present at the N-terminus: Glu-247 binds ATP and competes with ATP-binding at Arg-386, thereby preventing adenylyltransferase activity (By similarity). In unstressed cells, disengagement of Glu-247 promotes adenylyltransferase activity (By similarity). Activation dissociates ATP-binding from Glu-247, allowing ordered binding of the entire ATP moiety with the alpha-phosphate in an orientation that is productive for accepting an incoming target hydroxyl side chain (By similarity)
Protease activity is inhibited by 3,4-dichloroisocoumarin
Inhibited by dephosphorylation by PTPN6
Inhibited by chelating agents. Calcium ions enhance its activity, they also suppress autoproteolysis, and contribute to the stability of the enzyme against pH, heating, urea and cysteine
Inhibited by diisopropylfluorophosphate (DFP)
The ATPase activity is stimulated by phosphatidylinositol 4-phosphate (PI4P)
Inhibited by several hydroxamate compounds, the most potent inhibitor is actinonin
Inhibited by a sulfonyl piperazine compound that shows antibacterial activity against E.coli; LpxH is the cellular target of this compound (PubMed:25733621). Inhibited by 0.01% (or more) Triton X-100 in vitro (PubMed:12000770)
Competitively inhibited by N-acetyl-S-trans,trans-farnesyl-l-cysteine (AFC)
Inhibited by hydrogen peroxide
AMP and XMP inhibit AICAR formyltransferase activity
Inactivated by heat (37 degrees Celsius)
Allosterically and strongly feedback inhibited by tryptophan. Addition of lysine alone slightly enhances activity. The simultaneous addition of lysine and tryptophan leads to very strong feedback inhibition of the enzyme. The feedback control by tryptophan is reduced in the presence of the compatible solutes hydroxyectoine or ectoine
Inhibited by cation hexaammines
Inhibited by the diuretic amiloride
Inhibited by zaprinast
Synergistically activated by saposin-A and saposin-C, two saposin peptides produced by proteolytic processing of prosaposin/PSAP (PubMed:9201993). Saposin-C activates GBA1 through its recruitment to membranes (PubMed:10781797, PubMed:9201993). The membrane structure and composition in anionic phospholipids are also important for the activation (PubMed:9201993, PubMed:10781797). Activated by PKC in the salvage pathway of ceramide formation (PubMed:19279011). Inhibited by conduritol B epoxide/CBE (PubMed:24211208, PubMed:26724485)
Inhibited by the beta-lactam antibiotic meropenem (PubMed:22906310). Inhibited by the non-specific inhibitor phenylmethylsulfonyl fluoride (PMSF) (Probable)
Chitinase activity is activated by high salt concentrations which cause the release of the monomer from the autoinhibited homodimer
Inhibited by N-ethylmaleimide
Inhibited by okadaic acid
Activated by cAMP, and at 10-100 times higher concentrations, also by cGMP. cAMP binding causes a conformation change that leads to the assembly of an active tetramer and channel opening. Channel activity is modulated by intracellular chloride ions and pH; acidic pH shifts the activation to more negative voltages (By similarity)
Hydrolysis of beta-cyclodextrin is inhibited by Cu(2+), Zn(2+) and Ag(+), and activated by Ca(2+), EGTA and EDTA. Activity is increased over twofold in the presence of 5 mM EDTA (PubMed:9606956). Competitively inhibited by acarbose and methyl 6-amino-6-deoxy-alpha-D-glucopyranoside by reducing the rate of the ring opening step of the reaction (PubMed:10620329)
The full-length protein before cleavage is inactive: intramolecular interactions between N- and C-terminal domains mediate autoinhibition in the absence of activation signal (By similarity). The intrinsic pyroptosis-inducing activity is carried by the released N-terminal moiety (Gasdermin-A, N-terminal) following cleavage by S.pyogenes effector protein SpeB (PubMed:35110732, PubMed:35545676)
Completely inhibited by avidin
Inhibited by Hg(2+) or Cu(2+), and by chelating agents such as EDTA and O-phenanthroline. Reduced enzymatic activity in presence of cobalt, nickel, cadmium, and manganese
Diphosphate release from FPP is inhibited by zaragozic acid
The concentration of calcium for half-maximal activity is 0.3 mM. Inhibited by calpastatin and calpeptin
Tyrosine phosphorylation of the transporter leads to activation of the transport activity. Inhibited by cGMP, most likely through a cGMP-binding protein that interacts with OCT2
Not inhibited by cystatin
Allosterically activated by ADP, AMP, or fructose 2,6-bisphosphate, and allosterically inhibited by ATP or citrate. GlcNAcylation by OGT overcomes allosteric regulation (By similarity)
Inhibited by ortho-vanadate
Cholesterol efflux is increased by extracellularly applied taurocholate
Li(+) decreases succinate transport in the presence of Na(+), by competing at one of the three cation binding sites
Specifically cleaved by the protease DegP. Cleaved ArgP can no longer interact with the oriC region in vitro. Cleavage may play an important role in the control of the protein availability
Inhibited by sulfite
Chloride channel activity is allosterically activated by lumenal H(+) and Cl(-) leading to synaptic vesicles acidification (PubMed:27133463). The L-glutamate transport activity is allosterically activated by lumenal H(+) and Cl(-) (PubMed:27133463, PubMed:32439795). The allosteric requirement for H(+) efficiently prevents non-vesicular efflux across the plasma membrane (PubMed:27133463). The L-glutamate uniporter activity exhibits a biphasic dependence on chloride concentration (PubMed:11502256, PubMed:17046815)
The kinase domain is activated by trans-autophosphorylation. Kinase activity is required for activation of the endoribonuclease domain
Inhibited by Cs(1+) and ZD7288. Is apparently not activated by cAMP
The modification by 4-hydroxy-2-nonenal (HNE) adduction in mitochondria results in loss of the oxidoreductase activity and activation of a novel function in mitochondrial oxidative stress signaling
Not inhibited by aphidicolin
N1-guanyl-1,7-diaminoheptane has a small inhibitory effect on activity
HOE642 inhibits SLC9A8 activity
Low pH triggers activation of the protease and removal of the propeptide and the KDEL motif
ADP-ribosyltransferase activity is regulated via an allosteric activation mechanism. In absence of activation signal, PARP1 is autoinhibited by the PARP alpha-helical domain (also named HD region), which prevents effective NAD(+)-binding. Activity is highly stimulated by signals, such as DNA strand breaks. Binding to damaged DNA unfolds the PARP alpha-helical domain, relieving autoinhibition. Poly-ADP-ribosyltransferase activity is tightly regulated and PARP1 is removed from damaged chromatin following initial poly-ADP-ribosylation of chromatin to avoid prolonged residence (trapping) that has cytotoxic consequences. A number of factors (VCP/p97) or post-translational modifications (auto-poly-ADP-ribosylation or ubiquitination) promote PARP1 removal from chromatin
Inhibited by O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino N-phenylcarbamate (PUGNAc) (By similarity). Inhibited by galacto-NAG-thiazoline (By similarity)
Maintained in an inactive, closed conformation by an interaction between the kinase domain and the negative autoregulatory C-terminal coiled-coil region. Agonist binding to the phorbol ester binding site disrupts this, releasing the kinase domain to allow N-terminus-mediated dimerization and kinase activation by transautophosphorylation (By similarity)
Regulates splicing of its own pre-mRNA according to its kinase activity; increased expression of the catalytically active form influences splicing to generate the catalytically inactive splicing variant lacking the kinase domain. Leucettine L41 inhibits its kinase activity and affects the regulation of alternative splicing mediated by phosphorylation of SR proteins (By similarity)
Activity is enhanced by the addition of Ba(2+) and Mg(2+), but inhibited by the addition of Al(3+), Ca(2+), Co(2+), Cu(2+), Mn(2+) and Zn(2+)
Activated by host calmodulin
Is activated by Mg(2+), Ca(2+) and Mn(2+), and inhibited by Zn(2+) and Co(2+). Is not inhibited by EDTA in vitro
Inhibited by azalanstat. Inhibited by azole antifungal agents ketoconazole, itraconazole and fluconazole
Inhibited by the ionic detergent SDS and by the serine protease inhibitor PMSF (PubMed:28164792). Inhibited by the FDA approved drugs Diosmin, Acarbose and Ouabain. These drugs remain bound in the active site pocket and could be probable drug candidates to combat TB disease (PubMed:29557724)
Inhibited by PMSF. Not inhibited by benzamidine
Allosterically activated by AMP, ADP, glucose 1-phosphate (G1P), and fructose 6-phosphate (F6P)
Highly resistant to various miscible cosolvents and tolerates high substrate concentrations
Shows highest activity at 0.5 M KCl. Does not require divalent ions for activity
Activated by blue light and repressed by red light
Glutathione may be required to regulate its activity in the endoplasmic reticulum
Binding to host ubiquitin is required to activate the phosphatidylinositol phosphate phosphatase activity (PubMed:36227980). Phosphatase activity is inhibited by sodium orthovanadate, a specific inhibitor of tyrosine phosphatases, but not by okadaic acid, an inhibitor of serine/threonine phosphatases (PubMed:10986245). Inhibition of the enzyme reduces mycobacterial survival in infected macrophages (PubMed:19240079, PubMed:20167798, PubMed:21116447, PubMed:30153005). Inhibitors also enhance killing efficacy by first-line antibiotics (PubMed:30153005)
Inhibited by ethylenediamine tetraacetic acid, ethyleneglycol (beta-aminoethyl) N,N,N',N'-tetraacetic acid, p-bromophenacyl bromide or N-bromosuccinimide, but not by iodoacetic acid or diisopropyl fluorophosphate
Allosterically regulated by UMP
Inhibited by SERPINA5 and SERPINA10
Inhibited by coumarins, sulfonamide derivatives such as acetazolamide (AZA) and Foscarnet (phosphonoformate trisodium salt)
Inhibited by pyridoxal 5'-phosphate as well as by mercurials (mersalyl, p-chloromercuribenzene sulfonate, and mercuric chloride), N-ethylmaleimide and spermine
Due to its high apparent affinity but slow transport, adenosine could act as a negative regulator of pyrimidine transport under some conditions
In normal conditions, the protein kinase activity is inhibited; inhibition is relieved by various stress conditions (By similarity). Inhibited by heme: in presence of heme, forms a disulfide-linked inactive homodimer (By similarity). Heme depletion relieves inhibition and stimulates kinase activity by autophosphorylation. Inhibited by the heme metabolites biliverdin and bilirubin. Induced by oxidative stress generated by arsenite treatment. Binding of nitric oxide (NO) to the heme iron in the N-terminal heme-binding domain activates the kinase activity, while binding of carbon monoxide (CO) suppresses kinase activity (By similarity). Protein kinase activity is also activated upon binding to the processed form of DELE1 (S-DELE1): interaction with S-DELE1 takes place in response to mitochondrial stress and triggers the integrated stress response (ISR) (By similarity)
GSS(-) is a potent inhibitor of TSTD1, since the presence of the sulfur dioxygenase (SDO) strongly increases the TSTD1 catalytic activity (PubMed:24981631)
Autophosphorylates on Ser residues. Inhibited by retinoblastoma tumor suppressor protein, RB1. Binding to TAF1 or CIITA inhibits the histone acetyltransferase activity
Is strongly inhibited by phenylmethylsulfonyl fluoride, a serine protease inhibitor, and by mercury chloride. Diethyl pyrocarbonate, a histidine modifier, also inhibits the reaction, albeit less pronounced than phenylmethylsulfonyl fluoride. EDTA and dithiothreitol have no effect on enzyme activity
Activated by growth factors and cytokine receptors through a tyrosine-kinase-dependent mechanism. Activated by RAS. IC87114 inhibits lipid kinase activity and is selective in cells at doses up to 5-10 uM. Among other effects, IC87114 reduces allergic responses, prevents the recruitment of antigen-specific T cells into target tissue, and affects natural killer cell chemotaxis
Inhibited by palmostatin-B
Under complex allosteric control mediated by deoxynucleoside triphosphates and ATP binding. The type of nucleotide bound at the specificity site determines substrate preference. It seems probable that ATP makes the enzyme reduce CDP and UDP, dGTP favors ADP reduction and dTTP favors GDP reduction (By similarity). CDP reduction is stimulated by dATP
Inhibited by 10 mM 1-butanol
Inhibited by compounds CC24201, CC27209, and MO07123 (PubMed:22943065). Inhibited by the tetraoxoanions molybdate and phosphate (PubMed:12054466). Not inhibited by EDTA or tartrate (PubMed:12054466)
Two specific sites, one in the kinase domain (Thr-256) and the other in the C-terminal regulatory region (Ser-422), need to be phosphorylated for its full activation. Phosphorylation at Ser-397 and Ser-401 are also essential for its activity. Activated by WNK1, WNK2, WNK3 and WNK4
Stimulated by phosphatidylinositol 4,5-bisphosphate and slightly activated by the ADP-ribosylation factor-1 (ARF-1)
Inhibited by quinine at micromolar levels. Modestly sensitive to millimolar levels of tetraethylammonium (TEA) and 4-aminopyridine (4-AP)
Activated in response to stress, such as ribosomal stress, osmotic shock and ionizing radiation (PubMed:11042189, PubMed:12761180, PubMed:15342622, PubMed:32289254, PubMed:32610081). Activated by phosphorylation by PKN1, followed by autophosphorylation on Thr-161 and Ser-165 (PubMed:11042189, PubMed:12220515, PubMed:12761180, PubMed:15342622, PubMed:26999302). Inhibited by nilotinib, sorafenib, dabrafenib, rebastinib and vemurafenib (PubMed:26999302). Selectively inhibited by N-(3)-((1H-Pyrazolo[3,4-b]pyridin-5-yl)ethynyl)benzenesulfonamide compound 3h (PubMed:28586211). Selectively inhibited by 1,2,3-triazole benzenesulfonamides (PubMed:31244114)
Competitively inhibited by the substrate analog azelaic acid in vitro but not in vivo
Regulated by an auto-inhibitory C-terminal domain that can be displaced by phosphorylation of Thr-947 and the subsequent binding of 14-3-3 proteins (PubMed:10353834). Negatively regulated by PKS5 (PubMed:17483306). PKS5 phosphorylates Ser-931, inhibiting interaction with the activating 14-3-3 protein (PubMed:17483306). Positively regulated by PSY1R (PubMed:25267325). PSY1R phosphorylates Thr-881, situated in the auto-inhibitory region I of the C-terminal domain, causing pump activation (PubMed:25267325). Negatively regulated by the secreted peptide RALF (PubMed:24458638). After specific binding to FERONIA, RALF causes phosphorylation at Ser-899, mediating the inhibition of proton transport (PubMed:24458638). Activated by lysophospholipids, without the involvement of phosphorylation of Thr-947 (PubMed:25971968). This activation is critically dependent on the single autoinhibitory residue Leu-919 (PubMed:25971968). Repressed by PP2C-D phosphatases (e.g. PP2C67/PP2C-D1 and PP2C64/PP2C-D5) which dephosphorylates Thr-947 (PubMed:24858935). Triggered by SAUR19 via phosphorylation of the C-terminal autoinhibitory domain (e.g. Thr-947), as a result of the inhibition of PP2C67/PP2C-D1 (PubMed:24858935)
Activated by pathogens and other damage-associated signals: activation promotes ubiquitination and degradation of the N-terminal part, releasing the cleaved C-terminal part of the protein (NACHT, LRR and PYD domains-containing protein 1a, C-terminus), which polymerizes and forms the Nlrp1a inflammasome (By similarity). Nlrp1a inflammasome is inhibited by DPP8 and DPP9, which sequester the C-terminal fragment of Nlrp1a (NACHT, LRR and PYD domains-containing protein 1a, C-terminus) in a ternary complex, thereby preventing Nlrp1a oligomerization and activation (By similarity). Nlrp1a inflammasome is strongly activated by Val-boroPro (Talabostat, PT-100), an inhibitor of dipeptidyl peptidases DPP8 and DPP9 (PubMed:31383852). Val-boroPro relieves inhibition of DPP8 and/or DPP9 by promoting disruption of the ternary complex, releasing its C-terminal part from autoinhibition (By similarity). Not activated by cleavage by B.anthracis lethal toxin (LT) endopeptidase (PubMed:20502689)
Activated by phosphorylation on Thr-172. Binding of AMP to non-catalytic gamma subunit (PRKAG1, PRKAG2 or PRKAG3) results in allosteric activation, inducing phosphorylation on Thr-172. AMP-binding to gamma subunit also sustains activity by preventing dephosphorylation of Thr-172. ADP also stimulates Thr-172 phosphorylation, without stimulating already phosphorylated AMPK. ATP promotes dephosphorylation of Thr-172, rendering the enzyme inactive. Under physiological conditions AMPK mainly exists in its inactive form in complex with ATP, which is much more abundant than AMP. Selectively inhibited by compound C (6-[4-(2-Piperidin-1-yl-ethoxy)-phenyl)]-3-pyridin-4-yl-pyyrazolo[1,5-a] pyrimidine. Activated by resveratrol, a natural polyphenol present in red wine, and S17834, a synthetic polyphenol. Salicylate/aspirin directly activates kinase activity, primarily by inhibiting Thr-172 dephosphorylation (By similarity)
Inhibited by N-ethylmaleimide, HgCl(2) and PCMB. Competitively inhibited by NAD, NMN and 3-acetylpyridine
Is inhibited by N-ethylmaleimide in vitro, but ATP affords considerable protection against the inhibitor
Subject to substrate inhibition at salutaridine concentrations higher than 20 to 30 uM
Activated by Cu(+) and Ag(+) and inhibited by vanadate. Activated by CopZ in its Cu(+)-bound form
Inhibited by its anionic phospholipid end products, with phosphatidylinositol-(4,5)- bisphosphate (PIP2) showing the strongest inhibition. Inhibition is also acyl chain specific, with 1-stearoyl-2-arachidonoyl-snphosphatidylinositol showing the strongest inhibition
Inhibited by dipyridamole, IBMX and SCH 51866. Insensitive to zaprinast, rolipram, and milrinone
Specifically inhibited by a mouse monoclonal antibody AB0023, inhibition occurs in a non-competitive manner
Inhibited by N-ethylmaleimide, dCTP, and sphingoid bases including sphinganine, sphingosine and phytosphingosine. DAG pyrophosphate, cardiolipin, CDP-DAG, and lyso-PA inhibited activity by 23-66%. Also inhibited by Ca(2+) concentrations of more than 1 mM, by addition of EDTA or EGTA at 5 mM, and by 5 mM Mn(2+) and Zn(2+). Stimulated by major membrane phospholipids including phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine, phosphatidylglycerol, and phosphatidate. Also stimulated to a maximum by addition of TritonX-100 at a concentration of 1 mM, followed by an apparent inhibition of activity at concentrations above 1 mM
Nitrogenase holoenzyme is subject to 'conformational protection' by FeSII; under oxidizing conditions FeSII binds to the holoenzyme and reversibly protects it from oxidation (PubMed:7830548)
Phosphorylation increases catalytic activity (PubMed:18054093). Ca(2+) slightly increases catalytic activity in vitro (PubMed:18054093)
Is inhibited by the anti-tuberculous drug PA-824, a bicyclic 4-nitroimidazole class compound (PubMed:24349169). Therefore, this is consistent with the finding that PA-824 inhibits the formation of K-MAs and causes an accumulation of hydroxymycolic acids (H-MAs) in M.tuberculosis (PubMed:10879539)
Ethanol and carbon monoxide-bound heme increase channel activation. Heme inhibits channel activation (By similarity)
Inhibited by magnesium, calcium, cobalt, zinc and copper
Strongly inhibited by fetuin-A/AHSG (By similarity). Inhibited by cysteine and by the metal ion chelators EDTA and 1,10-phenanthroline. Not inhibited by 3,4-dichloroisocourmarin, soybean trypsin inhibitor, or the cysteine proteinase inhibitors iodoacetic acid and E-64
Significant inhibition is seen at GGPP concentrations above 100 uM
Activated by threonine and tyrosine phosphorylation. Activated by the MAP kinase kinases MKK2, MKK3, MKK4, MKK5, MKK7 and MKK9. Activated in response to touch, wounding, low temperature, low humidity, salt stress, hydrogen peroxide, ozone, ACC (an ethylene precursor), jasmonic acid (JA), mastoparan and UVC. Activated in response to elicitors: oligogalacturonides, hexameric chitin fragments, fungal xylanase, and the bacterial flagellin and harpin. Activated upon Pseudomonas syringae pv. tomato DC3000 infection. Repressed by the protein phosphatase 2C AP2C1 and the protein-tyrosine-phosphatases MKP1 and PTP1. Repressed by DSPTP1B/MKP2-mediated dephosphorylation. Activated by polarized BASL (PubMed:27746029). Triggered by MKKK20 in response to various abiotic stresses, including osmotic stress, cold and reactive oxygen species (ROS) (PubMed:21969089). Activated by MKK5 in response to abscisic acid (ABA) (PubMed:27913741)
Not inhibited by phenylmethylsulfonyl fluoride (PMSF; serine peptidase class S1 inhibitor), clavulanic acid (beta-lactamase inhibitor) or ampicillin (penicillin-binding protein (PBP) inhibitor)
Oxidation at Cys-196 leads to inactivation of channel activity
Inhibited by mercuric chloride
Phosphorylation at Thr-14 or Tyr-15 inactivates the enzyme, while phosphorylation at Thr-160 activates it. Stimulated by MYC (By similarity). Inactivated by CDKN1A (p21) (PubMed:11506705)
Inhibited by bestatin. The epoxide hydrolase activity is restrained by suicide inactivation that involves binding of LTA4 to Tyr-379. 4-(4-benzylphenyl)thiazol-2-amine (ARM1) selectively inhibits the epoxide hydrolase activity
Inhibited by 2-fluoroinosine 5'-monophosphate (F-IMP) and by N(2)-hydroxyguanosine 5'-monophosphate (N(2)-OH-GMP)
KM and Vmax values toward ATP only are increased by m-chlorocarbonyl cyanide phenylhydrazone (CCCP). The corresponding values for ADP are not affected
Inhibition of activity is observed in the presence of a 1 mM of the divalent cations zinc, copper, and nickel
Seems to switch between active and inactive modes in response to various stimuli (By similarity). Activated directly or indirectly by membrane phosphatidylinositol (PIs) (By similarity). Regulated by a variety of auxiliary proteins, which facilitate the maturation, cell surface expression and function of the transporter. Inhibited specifically by the drug tenapanor (By similarity)
Competitively inhibited by low concentrations of phosphate (IC50 3.0 mM) and is also sensitive to Li(+) (IC50 70 mM). Slightly activated by KCl
Inhibited by Triacsin C
Is non-competitively inhibited by NADH
By phosphorylation of various serine residues
Activity is redox-regulated. Highly sensitive to inactivation by oxidation (PubMed:24560923). Strongly stimulated by potassium salts (PubMed:8380170)
Inhibited by oxalate, glycolate and ATP
Inhibited by acetylsalicylic acid (aspirin)
Activated by 3'phosphoglycerate, inhibited by orthophosphate. Allosteric regulation
Partially inhibited by MSH when MSmB is used as substrate. Competitively inhibited by the GlcNAc-cyclohexyl derivative 5-(4-chlorophenyl)-N-((2R,3R,4R,5S,6R)-2-(cyclohexylthio)-tetrahydro-4,5-dihydroxy-6-(hydroxymethyl)-2H-pyran-3-yl)furan-2-carboxamide, which also inhibits Mca
Inhibited by the 1,2,3-triazole urea covalent inhibitors KT109 and KT172 (PubMed:23103940, PubMed:31991095). Inhibited by p-hydroxy-mercuri-benzoate and HgCl(2), but not by PMSF. Also inhibited by RHC80267, a drug that blocks 2-AG formation (By similarity)
Guanosine and inosine kinase activities are both inhibited by ppGpp, a nucleotide messenger universally produced in bacteria following nutrient starvation. ppGpp binds to Gsk, and inhibits its activity by blocking conformational dynamics and inducing tetramerization. Inhibiting purine nucleotide synthesis is required during starvation to maintain levels of the metabolite 5'-phosphoribosyl-1'-diphosphate (pRpp), which is required for the synthesis of histidine and tryptophan (PubMed:32857952). Activity is slightly increased in the presence of pyrimidine nucleotides, while it is markedly inhibited by GDP and GTP (PubMed:10879466). Activity is stimulated by K(+) ions (PubMed:7665468). Guanosine and inosine kinase activities are inhibited by Cu(2+) or Zn(2+) (PubMed:7665468)
Rab activation is generally mediated by a guanine exchange factor (GEF), while inactivation through hydrolysis of bound GTP is catalyzed by a GTPase activating protein (GAP) (By similarity). Tbc-4 is a likely GAP of this rab (PubMed:23100538). Denn-4 is a putative GEF of this rab (PubMed:26633194)
In quiescent cells, maintained in an inactive state via an intramolecular interaction between the protein kinase and N-terminal domains (By similarity). Following mitogen-mediated cell activation, binds via its RGB domain to active Ras85D (GTP-bound) which releases the inhibitory intramolecular interaction between the two domains (By similarity). This allows the Dsor1/MEK1-mediated dimerization of ksr and Raf which activates Raf (PubMed:29433126)
Inhibited by p-hydroxybenzaldehyde
Inhibited by EDTA, and o-phenanthroline, but not inhibited by PMSF, pepstatin A, and aprotinin
Inhibited by various ribo- or deoxyribonucleoside 5'-triphosphates but is insensitive to nucleoside diphosphates
The enzyme has distinct binding sites for each of the allosteric effectors such as acetyl-CoA, fructose 1,6-bisphosphate, guanosine 3'-diphosphate 5'-diphosphate, long chain fatty acids, and L-aspartate
ATP and dATP inhibit nicking and closing while stimulating nucleotidyltransferase
Alternates between an inactive form bound to GDP and an active form bound to GTP
Competitively inhibited by the products cholate (CA) and deoxycholate (DCA), and by phenylacetate and 4-aminophenylacetate. Penicillin V and penicillin G show mixed inhibition (PubMed:16905539). Strongly inhibited by thiol enzyme inhibitors in vitro (PubMed:10831430)
ATP hydrolysis occurs in the polymeric state. Unlike for mammalian actin, ATP hydrolysis occurs also in the monomeric form and the release of inorganic phosphate (Pi) is more efficient
Inhibited by EDTA, Zn(2+) and by Mg(2+) plus Mn(2+); stimulated by Ca(2+) in the presence of Mg(2+)
Is inhibited by clavulanate, sulbactam and m-aminophenylboronate but not by EDTA
Activated by cytokinins to initiate phosphorelay signaling. This cytokinin-mediated activation is repressed by the trans-zeatin antagonists 6-(2-hydroxy-3-methylbenzylamino)purine (PI-55) and 6-(2,5-Dihydroxybenzylamino)purine (LGR-991)
Activity is increased markedly in macrophages and osteoblasts following pro-inflammatory stimuli
Strongly inhibited by metazachlor and mefluidide
Activated by inorganic phosphate, with a maximal activity at 190 mM. Above this concentration inorganic phosphate progressively inhibits the kinase. Completely inhibited by ADP, and partially inhibited by alpha,beta-methylene ATP (mATP). Lack of allosteric regulation
Pyruvate dehydrogenase activity is inhibited by phosphorylation of PDHA1; it is reactivated by dephosphorylation
Under physiological conditions, G3BP2 adopts a compact state that is stabilized by intramolecular interactions between the RG-rich and the acidic regions that inhibit phase separation. Upon stress, polysomes disassemble and mRNAs are released in an unfolded protein-free state. Binding of unfolded mRNA to G3BP2 outcompetes the intramolecular interactions and RNA-bound G3BP2 adopts an expanded conformation in which the RG-rich region becomes exposed to engage in protein-protein and protein-RNA interactions, allowing physical cross-linking of RNA molecules to form protein-RNA condensates, leading to liquid-liquid phase separation (LLPS)
Inhibited by equimolar N-iodoacetyl-N'-(5-sulfo-1-naphthyl)ethylenediamine
Activated by Ca(2+)
Inhibited by p-chloromercuriphenylsulfonic acid (CMPSA)
Inhibited by iodoacetamide and trans-epoxysuccinyl-L-leucylamido(4-guanidino)butane (E-64) but not by phenylmethylsulfonyl fluoride (PMSF), pepstatin-A, ethylenediamine tetra acetic acid (EDTA) or ethylene glycol tetraacetic acid (EGTA)
Feedback inhibition by heme
Allosterically regulated (By similarity); feedback inhibited by cytidine monophosphate-N-acetylneuraminic acid (CMP-Neu5Ac), the end product of neuraminic acid biosynthesis. Activity is dependent on oligomerization. The monomer is inactive, whereas the dimer catalyzes only the phosphorylation of N-acetylmannosamine, and the hexamer is fully active for both enzyme activities. Up-regulated after PKC-dependent phosphorylation
Activated when autophosphorylated at Thr-154 and inactivated when phosphorylated at Ser-261 by SnRK1.1/KIN10
Stimulated by KCl, and inhibited by the small molecules o 2',3'-dideoxythymidine 5'-triphosphate (d2TTP) and N-ethylmaleimide (NEM)
Activity of phosphorylase is controlled both by allosteric means (through the non-covalent binding of metabolites) and by covalent modification. Thus AMP allosterically activates, whereas ATP, ADP, and glucose-6-phosphate allosterically inhibit, phosphorylase B
Pantothenate exhibits uncompetitive inhibition toward both D-pantoate and ATP, and non-competitive inhibition toward beta-alanine. AMPCPP exhibits competitive inhibition toward ATP, uncompetitive inhibition toward beta-alanine, and non-competitive inhibition toward D-pantoate. The enzyme is most active in the presence of magnesium or manganese. Other divalent cations (cobalt, nickel, zinc) are less effective
Inhibited by the thiol-modifying reagent N-ethylmaleimide (NEM)
Competitively inhibited by 2-hydroxyglutarate
Classical (or conventional) PKCs (PRKCA, PRKCB and PRKCG) are activated by calcium and diacylglycerol (DAG) in the presence of phosphatidylserine. Three specific sites; Thr-514 (activation loop of the kinase domain), Thr-655 (turn motif) and Thr-674 (hydrophobic region), need to be phosphorylated for its full activation
Inhibited by 6,7-Dichloro-N-cyclopentyl-4-(pyridin-4-yl)phthalazin-1-amine (A-196) with an IC(50) of 144 nM
Activated through phosphorylation predominantly by ATR but also by ATM in response to DNA damage or inhibition of DNA replication (PubMed:11390642, PubMed:12588868, PubMed:12676583, PubMed:12676962, PubMed:15665856, PubMed:19716789). Activation is modulated by several mediators including CLSPN, BRCA1 and FEM1B (PubMed:11836499, PubMed:12766152, PubMed:16963448, PubMed:19330022). Proteolytic cleavage at the C-terminus by SPRTN during normal DNA replication activates the protein kinase activity (PubMed:31316063)
Inhibited by diisopropylphosphofluoridate (DFP)
Allosteric enzyme whose activity is greatly influenced by the end products of its metabolic pathway, dCTP and dTTP
Inhibited by thiol reagents such as p-chloromercuribenzoate and iodoacetamide
Stimulated by an intrinsic GTPase (Probably CysN)
Channel activity is inhibited by interaction with Ca(2+)-bound calmodulin. Interaction of a single pore-forming alpha subunit with a calmodulin chain is sufficient to promote channel closure (By similarity). Channel activity is not regulated by cyclic nucleotides (PubMed:19671703). Channel activity is inhibited by binding intracellular phosphatidylinositol-3,5-bisphosphate and phosphatidylinositol-4,5-bisphosphate (PIP2), but is not inhibited by phosphatidylinositol 4-phosphate (By similarity)
11-cis retinoids act as allosteric modulators of acyl-CoA retinol O-fatty-acyltransferase (ARAT) activity by suppressing esterification of 9-cis, 13-cis, or all-trans retinols concurrently increasing the enzyme specificity toward 11-cis isomer
Activity on the artificial substrate MUF tri-NAG is inhibited by 2-nitrophenylthiocyanates (NPT) compounds
Endonuclease activity is inhibited by MgCl2 on apurinic/apyrimidinic DNA but not on UV-irradiated DNA
Activated upon caspase cleavage to generate the XK-related protein 9, processed form. Does not act prior the onset of apoptosis
Taurine transport activity is inhibited by beta-alanine and gamma-aminobutyric acid (GABA) (PubMed:1435737). GABA transport activity is inhibited by taurine and beta-alanine (PubMed:18501699)
Helicase inhibited by the slowly-hydrolyzing ATP analog ATP-gamma-S (PubMed:15542859). Protein is rapidly degraded upon shifting from 20 to 30 degrees Celsius, the degradation machinery is only transiently present in cells grown at 30 degrees Celsius, is inhibited by commercial protease inhibitors and requires full-length protein expression (the N-terminal fragment does not induce proteolysis although it can be degraded by wild-type extract) (PubMed:24509313)
Activated by exposed helices in a group I intron RNA
Activity is inhibited by EDTA. Activity is abolished by Cu(2+) and shows 59% reduction in the presence of Mn(2+) (PubMed:33427933). Lactose acts as a competitive inhibitor (PubMed:33427933)
Phosphorylation at Thr-436 or Tyr-437 inactivates the enzyme, while phosphorylation at Thr-583 activates it
Inhibited at NaCl concentrations higher than 200 mM
Ca2(+)/calmodulin binding removes an autoinhibitory regulatory segment located C-terminal to the kinase domain. This releases the catalytic activity of the enzyme and makes accessible a regulatory residue Thr-284. Phosphorylation of Thr-284 by another kinase domain within the oligomeric holoenzyme keeps CaMKII active in the absence of Ca(2+)/calmodulin by preventing the rebinding of the regulatory segment to the kinase domain and by increasing the affinity of calmodulin for the enzyme. Can respond to high-frequency Ca(2+) pulses to become Ca(2+) independent
Inhibited by KCN or H(2)O(2)
Inhibited by the allylamine antimycotic drugs
Requires N-acetyl-L-glutamate (NAG) as an allosteric activator
Inhibited by carbonylcyanide m-chlorophenylhydrazone and diethylpyrocarbonate (DEPC)
Inhibited by aprotinin and PMSF, but not by EDTA
Inhibited by trehalose 6-sulfate
Allosterically activated by ATP (PubMed:8141771). ATP binding is a prerequisite to magnesium and substrate binding (By similarity). ATP binds to 2 of the subunits in the homotetramer inducing a closure of these 2 subunits and the release of the C-terminal loop, thereby activating the enzyme (By similarity)
Is completely inhibited by anacardic acid, an inhibitor of HAT activity
Inhibited by ketoconazole. May also be inhibited to a lesser extent by propiconazole
Inhibited by fructose 1,6-bisphosphate and p-chloromercuribenzoate (PCMB)
Subject to catabolite repression
Inhibited by okadaic acid, tautomycin and calyculin A. Inhibited by phosphatase inhibitor 2 (dpiA)
Rapidly inactivated in the presence of D-lysine and to a lesser extent in the absence of adenosylcobalamin (Adocbl). Activity is stable in the presence of Adocbl when D-lysine is absent. Adocbl imparts thermal stability at 37 degrees Celsius
Inhibited by the herbicide norflurazon (NFZ)
NAD-dependent protein-lysine deacetylase and deacylase activities are activated by nucleic acids. Histone deacetylase activity is activated by DNA. Protein-lysine deacylase activity is activated by RNA. H3K18Ac histone deacetylase activity is inhibited by methylation at Arg-388. H3K18Ac histone deacetylase activity is inhibited by deubiquitination by USP7
Inhibited by hydroxylamine and sodium borohydride
Requires MetW for activity
Stimulated by cytosolic Ca(2+)
Inhibited by bestatin
Inhibited by bumetanide
Activated by threonine and tyrosine phosphorylation by either of two dual specificity kinases, MAP2K4 and MAP2K7. MAP2K4 shows a strong preference for Tyr-185 while MAP2K7 phosphorylates Tyr-183 preferentially. Inhibited by dual specificity phosphatases, such as DUSP1
Regulated by bile acid salts. Up-regulated by cholate and down-regulated by taurochenodeoxycholate. Cholate-activated rate of hydrolysis is lowered by hypolipidemic drug ezetimibe
Activity toward QA is slightly repressed by phosphoribosylpyrophosphate (PRPP) in both a competitive and a non-competitive manner (PubMed:17868694). Competitively inhibited by phthalic acid (PHT) (PubMed:24038671)
Cell cycle-regulated, with maximal activity in the S-phase. Rapidly and transiently inhibited by phosphorylation following the generation of DNA double-stranded breaks during S-phase, probably by CHEK1, possibly at Ser-696. This inhibition is cell cycle checkpoint- and ATM-dependent
Activated by Mn(2+) (PubMed:7400101, PubMed:23204427). Inhibited by Ni(2+), Cd(2+), Co(2+) or Cu(2+) (PubMed:23204427)
Subject to allosteric regulation. Low glucose and high fructose-6-phosphate triggers association with the inhibitor GCKR followed by sequestration in the nucleus
Inhibited by EDTA, Mg(2+) and Ca(2+)
90% of activity is inhibited by nickel, zinc and calcium ions. Magnesium, cobalt, copper and manganese ions inhibit between 50 and 80% of activity
Activated by WNK3
A cytosolic factor (probably pyrophosphate, polytriphosphate, polyP4, polyP25, polyP45, and/or polyP65) is necessary for TRPA1 activation by irritants (PubMed:17567811). Such factor acts by keeping TRPA1 in a agonist-sensitive state (PubMed:17567811). Inhibited by the potent blocker of TRPV channels ruthenium red, A-967079, AP-18, HC-030031, and aryl sulfonamide derivative (S)-N-(4-chlorobenzyl)-1-((4-fluorophenyl)sulfonyl)pyrrolidine-2-carboxamide (ASD) (PubMed:17567811, PubMed:21873995, PubMed:21402443, PubMed:30878828, PubMed:20547126). Non-covalently activated by the scorpion wasabi receptor toxin (PubMed:31447178). Activated by benzyl isothiocyanate (BITC), iodoacetamide, sulfhydryl reactive agent MTSEA, N-methyl maleimide (NMM), N-ethylmaleimide (NEM), and 2-aminoethyldiphenylborinate (2-APB) (PubMed:17164327, PubMed:17567811, PubMed:21873995, PubMed:27241698). Also activated by hyperoxia (PubMed:21873995)
Activity increases 3-fold at pH 6.1. Inhibited by moenomycin A
Inhibited by EDTA, p-hydroxy-mercuribenzoate and iodoacetate but not by NaF
In the presence of magnesium, manganese is inhibitory
Inhibited by NH(3), heavy-metal ions, hydroxylamine and 2-bromoporphobilinogen. Not inhibited by N-ethylmaleimide
Novel PKCs (PRKCD, PRKCE, PRKCH and PRKCQ) are calcium-insensitive, but activated by diacylglycerol (DAG) and phosphatidylserine. Three specific sites; Thr-513 (activation loop of the kinase domain), Thr-656 (turn motif) and Ser-675 (hydrophobic region), need to be phosphorylated for its full activation
The enzyme activities are regulated allosterically by L-threonine
Kinase activity is activated upon binding to GTP-bound Rho1/Rac1 GTPases. Activated by caspase-3 (CASP3) cleavage during apoptosis. Activated by lipids, particularly cardiolipin and to a lesser extent by other acidic phospholipids and unsaturated fatty acids. Two specific sites, Thr-817 (activation loop of the kinase domain) and Thr-959 (turn motif), need to be phosphorylated for its full activation (By similarity)
ADP-ribosyltransferase activity is regulated via an allosteric activation mechanism. In absence of activation signal, parp1 is autoinhibited by the PARP alpha-helical domain (also named HD region), which prevents effective NAD(+)-binding. Activity is highly stimulated by signals, such as DNA strand breaks. Binding to damaged DNA unfolds the PARP alpha-helical domain, relieving autoinhibition. Poly-ADP-ribosyltransferase activity is tightly regulated and parp1 is removed from damaged chromatin following initial poly-ADP-ribosylation of chromatin to avoid prolonged residence (trapping) that has cytotoxic consequences. A number of factors or post-translational modifications (auto-poly-ADP-ribosylation) promote parp1 removal from chromatin
Activated by autophosphorylation on Ser-219
Regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP, GTPase activating proteins (GAPs) which increase the GTP hydrolysis activity, and GDP dissociation inhibitors which inhibit the dissociation of the nucleotide from the GTPase. Activated by GEFs such as DENND10
Inhibited by fluoride
Activity of this regulatory enzyme is affected by several metabolites. The non-competitive allosteric inhibition by fructose 1,6-bisphosphate (FBP) causes alterations in the quaternary structure of the enzyme. FBP inhibition requires that the enzyme exists only in a tetrameric state. Salt such as KCl reduces the affinity of the tetrameric form of the enzyme for FBP. Unphosphorylated phosphocarrier protein EIIA-Glc (III-Glc), an integral component of the bacterial phosphotransferase (PTS) system, also inhibits non-competitively and allosterically the activity. Unlike FBP, both the dimer and the tetramer appear to be fully sensitive to enzyme EIIA-Glc inhibition. Zn(+2) greatly enhances the inhibitory potency of EIIA-Glc. Both allosteric regulatory agents are strongly pH dependent, with maximal inhibition occurring at pH 6.5
Ap4A hydrolysis is inhibited by fluoride ions
Activity is decreased in the presence of the PGI inhibitor 6-phosphogluconate (PubMed:16212940, PubMed:17126561). Does not require mono- or divalent cations for activity (PubMed:16212940, PubMed:17126561)
Allosterically inhibited by NADP and activated by quinolinic acid. Strongly inhibited by HgCl(2)
Increased activity in presence of phospholipids (low concentrations) and calcium ions. Inhibited by PMSF. Not affected by EDTA and E-64
Inhibited by O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino-N-phenyl-carbamate (PUGNAc) and streptozotocin
Atypical PKCs (PRKCI and PRKCZ) exhibit an elevated basal enzymatic activity (that may be due to the interaction with SMG1 or SQSTM1) and are not regulated by diacylglycerol, phosphatidylserine, phorbol esters or calcium ions. Two specific sites, Thr-410 (activation loop of the kinase domain) and Thr-560 (turn motif), need to be phosphorylated for its full activation. Phosphatidylinositol 3,4,5-trisphosphate might be a physiological activator (Probable). Isoform 2: Constitutively active (PubMed:8378304)
Inhibited by 1-10-phenanthroline (PubMed:18937627). Inhibited by peptidomimetic isoamyl-phosphonyl-Gly-Pro-Ala, which binds to Zn(2+) (PubMed:21947205). Inhibited by broad-spectrum zinc metalloprotease inhibitor batimastat (PubMed:28820255). N-aryl mercaptoacetamide-based inhibitors have been isolated that act on clostridial collagenases with submicromolar affinity while having negligibile activity on human collagenases (PubMed:28820255)
Inhibited by pyrrolidine dione antibiotics moiramide B (CPD1) and CPD2
Activated by hyperosmotic shock after mannitol or NaCl treatment (PubMed:24503647). Activated by mechanical pressure (PubMed:30382939)
Activated by phosphorylation at Tyr-279. In response to insulin, inhibited by phosphorylation at Ser-21 by PKB/AKT1; phosphorylation at this site causes a conformational change, preventing access of substrates to the active site. Inhibited by lithium
According to some reports, it is inhibited by beta-aminopropionitrile (BAPN) (PubMed:20439985, PubMed:23319596). According to another report, it is not inhibited by beta-aminopropionitrile (BAPN) (PubMed:20306300). Specifically inhibited by a mouse monoclonal antibody AB0023, inhibition occurs in a non-competitive manner
Inhibited by mercury ions
A conditional disulfide bridge can form within the protein that dislocates a critical phosphate-coordinating arginine Arg-100 away from the active site, disabling the enzyme
Activated via binding to highly phosphorylated inositol phosphates such as inositolhexakisphosphate (InsP6) which mediates the release of an N-terminal auto-inhibitory region (PubMed:29883610). Activation requires not only RIPK3-dependent phosphorylation but also binding to highly phosphorylated inositol phosphates (PubMed:29883610). Inhibited by necrosulfonamide, a specific inhibitor of necroptosis that targets Cys-86 (PubMed:22265413)
The degree of the acp3U modification at U47 is dependent on the presence of the m7G modification at the preceding nucleotide G46. It also depends on medium conditions
The phosphomutase activity is stimulated by glucose 1,6-bisphosphate
Increases 2-fold following exposure to low pH
Highly sensitive to dioxygen
Inhibited by MK886
Fe(2+)-CDase is rapidly inactivated by H(2)O(2), whereas Mn(2+)-CDase, Co(2+)-CDase, and Zn(2+)-CDase are not inactivated by H(2)O(2). CDase is also inhibited by excess divalent cations (PubMed:8226944). Phosphonocytosine, a mimic of the tetrahedral reaction intermediate, inhibits the deamination of cytosine with a Ki of 52 nM (PubMed:21545144)
Activity is strongly inhibited by galotannin. Inhibited by P1-(adenosine-5')-P4-(nicotinic-acid-riboside-5')-tetraphosphate (Nap4AD)
Inhibited by iron ions (PubMed:35802235). Activated in presence of the surfactant polysorbate 20, while inhibited in the presence of Triton X-100 and sodium dodecyl sulfate (PubMed:35802235). Inhibited in presence of the organic solvents methanol, ethanol, propan-2-ol and acetone (PubMed:35802235)
Activity is strongly inhibited in vitro by chelating agents such as EDTA and 1,10-phenanthroline as do the reducing agent dithiothreitol and the oxidizing agent N-bromosuccinimid. Phenylmethylsulfonyl fluoride, a serine protease inhibitor has no influence on the enzyme activity. On the other hand, bestatin, an aminopeptidase inhibitor strongly inhibits the enzyme activity and leupeptin, a modified tripeptide, slightly inhibits it
Phosphorylation at Tyr-340 is necessary and sufficient for the activation of E3 activity
ATPase activity is stimulated 10-fold in the presence of Spo0J and DNA (parS, a plasmid centromere-like site or plasmid DNA itself). The first 20 residues of Spo0J stimulate ATPase by 8%
Becomes activated when its major tyrosine phosphorylation site is not phosphorylated. It can also be activated by point mutations as well as by truncations at the C-terminal end or by other mutations. Heme regulates its activity by enhancing the phosphorylation on Tyr-528 (By similarity)
Inhibited by human TIMP1 and TIMP2 and the broad MMP inhibitors BB94 (Batimastat) and CT543
Inhibited by CoA and activated by ADP
Inhibited by cephaloridine
Inhibited by the substrate analog pyrazole but not by NAD analogs such as AMP, ADP, ATP or N-methylnicotinamide chloride
Inhibited by high concentrations of substrates, and by the synthetic auxin compound 2,4-dichlorophenoxyacetate (2,4-D), which does not serve as substrate
Levodopa decarboxylation is not inhibited by carbidopa, benserazide, and methyldopa, that are three human L-dopa decarboxylase inhibitors
Found to be inhibited by cadmium, copper, zinc and mercurium divalent cations and sulfhydryl reagents (PubMed:7764365). Inhibited by the addition of unsaturated fatty acids to the culture (PubMed:7764365)
Activated by binding of S100B which releases autoinhibitory N-lobe interactions, enabling ATP to bind and the autophosphorylation of Ser-282. Thr-442 then undergoes calcium-dependent phosphorylation by STK24/MST3. Interactions between phosphorylated Thr-442 and the N-lobe promote additional structural changes that complete the activation of the kinase. Autoinhibition is also released by the binding of MOB1/MOBKL1A and MOB2/HCCA2 to the N-terminal of STK38L
Deubiquitinase activity is inhibited following interaction with PARK7
GTPase activity is stimulated by MMUT
Activity is increased following LPS stimulation and down-regulated by the anti-inflammatory glucocorticoid dexamethasone
Supercoiling activity inhibited by novobiocin and coumermycin, DNA wrapping around gyrase is not inhibited (PubMed:276855, PubMed:153201)
Inhibited by the general cysteine protease inhibitor E64 (L-trans-epoxysuccinyl-leucylamide-(4-guanido)-butane)
Inhibited by antizymes (AZs) OAZ1, OAZ2 and OAZ3 in response to polyamine levels. AZs inhibit the assembly of the functional homodimer by binding to ODC monomers. Additionally, OAZ1 targets ODC monomers for ubiquitin-independent proteolytic destruction by the 26S proteasome
Inhibited by RCVRN, which prevents the interaction between GRK1 and RHO (By similarity). Inhibition is calcium-dependent (By similarity). Inhibited by phosphorylation of Ser-21
Both phosphorylation at Thr-172 and binding of a D-type cyclin are necessary for enzymatic activity. Full activation of the cyclin-D-CDK4 complex appears to require other factors such as recruitment of the substrate via a substrate recruitment motif, and/or formation of the CDKN1B ternary complex. Inhibited by INK4 family members. In resting cells, the non-tyrosine-phosphorylated form of CDKN1B prevents phosphorylation at Thr-172 and inactivation, while, in proliferating cells, tyrosine phosphorylation of CDKN1B allows phosphorylation of Thr-172 of CDK4 and subsequent activation
When the two monomeric subunits are covalently linked by a S-S bond, the enzyme is essentially inactive. When the disulfide bond is reduced, its component sulfhydryls can associate with K-keto acids through formation of a thiohemiacetal, resulting in enzyme activation. Activated by glyoxylate, irrespective to the substitution found at Cys-127. That suggests the presence of a second activation site, possibly Cys-177
Not inhibited by 2-(2-methyl-2-hydroxypropylthio)ethanesulfonate (M-HPC), an achiral analog of both R-HPC and S-HPC
Inhibited by 3-methyl-l,2,3,4-tetrahydro[1]benzothieno[3,2-c]pyridine hydrochloride
Activity of the complex is inhibited by 2-aminoacetophenone (2-AA)
Specifically inhibited by spautin-1 (specific and potent autophagy inhibitor-1), a derivative of MBCQ that binds to usp13 and inhibits deubiquitinase activity
Glyoxalase activity is inhibited by zinc ions at pH 7.0
The C-terminus inhibits activity; it has to move for the enzyme to be active (PubMed:18988747). Activated by lipid-binding, which occurs via the C-terminus; detergents also activate the enzyme (PubMed:334770, PubMed:334771, PubMed:2663858, PubMed:18988747). Specifically activated by palmitic acid; 12 (lauric) and 14-carbon (myristic) fatty acids as well as unsaturated 16 and 18-carbon fatty acids also activate the enzyme (PubMed:6385860). Lipid affinity is increased in the presence of pyruvate plus the thiamine pyrophosphate cofactor (PubMed:334770, PubMed:334771, PubMed:2663858, PubMed:18988747)
Inhibited by p-chloromercuribenzoate, copper and nickel ions
Completely inactivated by EGTA
The protein undergoes a dramatic conformational switch from closed to open states upon substrate-binding, which enables specific substrate recognition for the 1''-O-linkage. The glutamate flap (Glu-41) blocks substrate entrance to Mg(2+) in the unliganded closed state. In presence of substrate, Glu-41 is ejected from the active site: this closed-to-open transition significantly widens the substrate-binding channel and precisely positions the scissile 1''-O-linkage for cleavage while securing tightly 2'- and 3'-hydroxyls of ADP-ribose
Activity is inhibited bythe antifunfal copmpounds PD 404,182, 6-nitroso-1,2-benzopyrone, and calmidazolium chloride with IC(50) values of 3.9 uM, 35.2 uM, and 19.2 uM, respectively (PubMed:28720735)
Competitively inhibited by 4-morpholineethanesulfonic acid (MES), SB236050 and biphenyl tetrazoles (BPTs) (PubMed:9578564, PubMed:9545432, PubMed:12019104). Also inhibited by chelating agents such as EDTA and 1,10-phenanthroline (PubMed:9712862). CcrA is not susceptible to inactivation by the beta-lactamase-blocking agents clavulanic acid or tazobactam (PubMed:2121094, PubMed:2110145)
Activity is increased in the presence of NAD(P)H (PubMed:11943208, PubMed:20178989). NADPH is not involved directly in the cyclization reaction, but must play an indirect role, e.g. as an allosteric activator (PubMed:11943208)
Extracytoplasmic function (ECF) sigma factors are held in an inactive form by a cognate anti-sigma factor (RsiW for this protein) until released by regulated membrane proteolysis (RIP). RIP occurs when an extracytoplasmic signal (envelope stress) triggers a concerted proteolytic cascade to transmit information and elicit cellular responses. The anti-sigma factor RsiW is a membrane protein, binding sigma-W in the cytoplasm. RsiW is first cut extracytoplasmically (site-1 protease, S1P, by PrsW) (PubMed:16816000), then within the membrane itself (site-2 protease, S2P, by RasP) (PubMed:15130127), while cytoplasmic proteases (predominantly ClpX-ClpP) finish degrading the regulatory protein, liberating sigma-W (PubMed:16899079)
Methylxanthine drugs surch as theophylline, caffeine and pentoxifylline, as well as the two cyclic peptide natural products argifin and argadin, act as specific inhibitors
Acetylation decreases the binding abilities to ATP and ADP and leads to inhibition of DNA replication initiation
Activated by diacylglycerol which in turn phosphorylates a range of cellular proteins
Activated by zinc, cobalt and manganese ions (PubMed:15070399). Inhibited by EDTA (PubMed:15070399)
Activity of phosphorylase is controlled both by allosteric means (through the non-covalent binding of metabolites) and by covalent modification. Thus AMP allosterically activates, whereas ATP, ADP, and glucose-6-phosphate allosterically inhibit, phosphorylase B (By similarity)
Phosphorylation of the transporter leads to changes in its substrate affinity, resulting in a regulation of the transport activity. In contrast with rat ortholog, ASP uptake is inhibited by protein kinase A (PKA) and C (PKC) activation. ASP uptake is also endogenously activated by calmodulin, the calmodulin-dependent kinase II and LCK tyrosine kinase (By similarity). Inhibited by cGMP, most likely through a cGMP-binding protein that interacts with OCT1 (By similarity)
The activity of HMG-CoA-reductase is suppressed by exogenous mevalonate
Inhibited by copper and mercury ions. Also inhibited by thiol active reagents, such as N-ethylmaleimide and hydroxymercuribenzoate. EDTA has a slight activating effect
Target of the anti-cancer drug Rocaglamide (Roc-A)
Reversibly inhibited by phospholamban (PLN) at low calcium concentrations (By similarity). Inhibited by sarcolipin (SLN) and myoregulin (MRLN) (By similarity). Enhanced by DWORF; DWORF increases activity by displacing sarcolipin (SLN), phospholamban (PLN) and myoregulin (MRLN) (By similarity)
Acyltransferase activity is inhibited by detergents such as Triton X-100 and 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS). Acyltransferase activity is inhibited by the presence of magnesium and calcium
Regulated by calcium/calmodulin
Inhibited by methotrexate
Completely inhibited by PMSF, and N-tosyl-Lphenylalanine chloromethyl ketone (TPCK) and poorly inhibited by benzamidine and derivates. Not inhibited by EDTA, heparin and hirudin
Allosterically activated by magnesium, and possibly also other divalent metal cations. Allosterically activated by ATP, ADP or GTP
Activated following phosphorylation by p38-alpha/MAPK14 following various stresses. Inhibited following sumoylation. Specifically inhibited by pyrrolopyridine inhibitors
ATPase activity is enhanced in the presence of homomeric poly(U) RNAs, but not by double-stranded DNA (dsDNA), double-stranded RNA (dsRNA) and tRNA
Inhibited by YfiR, which prevents relocation to the midcell. A reductive stress signal is required to inactivate YfiR and turn on the DGC activity of DgcN
An extracellular acidic pH inhibits chloride-sulfate and chloride-oxalate exchange activity whereas an intracellular acidic pH activates chloride-sulfate exchange with no effect on chloride-oxalate exchange activity
Serine/threonine-protein kinase activity is promoted by associated cyclins CCDN3 and CCNY and repressed by CDKN1A
Activated by forskolin. Is not activated by calmodulin. Inhibited by calcium ions, already at micromolar concentration. Activated by the G protein alpha subunit GNAS. Activated by the G protein beta and gamma subunit complex. Phosphorylation by RAF1 results in its activation (By similarity). Phosphorylation by PKC activates the enzyme (By similarity)
Malonyl-CoA decarboxylase activity does not require any cofactors or divalent metal ions. Formation of interchain disulfide bonds leads to positive cooperativity between active sites and increases the affinity for malonyl-CoA and the catalytic efficiency (in vitro)
Strongly inhibited by the polyol (sugar alcohol) phosphate D-glucitol 6-phosphate (D-sorbitol 6-phosphate) (PubMed:30240188). Also inhibited by the polyol (sugar alcohol) phosphate D-ribitol 5-phosphate (PubMed:30240188)
Inhibited by equimolar concentrations of p-chloromercuribenzoic acid, iodoacetamide or N-ethylmaleimide
Kinase activity is regulated by BUB2, CDC15 and CDC5, and is maximal during nuclear division. CDK1 kinase inhibits cellular DBF2-MOB1 kinase activity via phosphorylation of both CDC15 and MOB1
Inhibited by magnesium ions
Inhibited by diisopropylfluorophosphate (DFP), PMSF and leupeptin
Inhibited by deoxyguanosine at concentrations above 30 uM only with UTP as phosphate donor. dGTP is a potent competitive inhibitor
Inhibited by the herbicides metflurazon, difunone, fluridone and diflufenican
The complex requires PaoD for activity
Requires K(+) for maximal activity. Inhibited by the Na(+) ionophore monensin, activated by the K(+) ionophore valinomycin and unaffected by the protonophore CCCP
Stable and active over a broad range of NaCl concentrations (0.5 to 4.2 M NaCl), with maximal activity at 2.6 M NaCl. 83% and 94% of the maximum activity at 0.6 and 4.2 M NaCl, respectively. Active and stable also in KCl
Activated by threonine and tyrosine phosphorylation by either of two dual specificity kinases, MAP2K4 and MAP2K7. MAP2K4 shows a strong preference for Tyr-185 while MAP2K7 phosphorylates Tyr-183 preferentially. Inhibited by dual specificity phosphatases, such as DUSP1. Inhibited by SERPINB3
GTPase activity is stimulated in the presence of 60S subunits
Activated by Mn(2+) ions. Strongly inhibited by Cu(2+), Zn(2+), Fe(3+) and Fe(2+) ions. Moderately inhibited by Na(+) and Ca(2+) ions. Rapidly degraded at temperatures above 40 degrees Celsius
Acyltransferase and acetyltransferase activities are activated by phosphorylation and autoacetylation. Autoacetylation activates the histone acetyltransferase activity
Strongly activated by NAD. Activated by NADP. Slightly activated by NADH and NADPH. Inhibited by GDP
Toxic activity of the cleaved 40 kDa form of this subunit alone on cells of C.quinquefasciatus is decreased about 50% by chitobiose, chitotriose, N-acetylmuramic acid and N-acetylneuraminic acid
Phosphorylation of brain HDC by cAMP-dependent protein kinase leads to enzyme inactivation
MI transport activity inhibited by D-chiro-inositol (DCI), phlorizin (Pz) and sodium (Na(+)) (PubMed:17932225). Insulin increases D-chiro-inositol uptake (By similarity)
Completely inhibited by the serine protease inhibitor diisopropyl fluorophosphate (DFP) and potently inhibited by 0.5 mM ZnCl(2), 10 mM o-phenanthlorine, phenylmethanesulfonyl fluoride (PMSF) and N-tosyl-L-phenyl-alanyl chloromethyl ketone (TPCK), but not by N-tosyl-L-lysyl chloromethyl ketone (TLCK). Activity is not affected significantly by protease inhibitors, such as chymostatin, leupeptin, N-ethylmaleimide (NEM), iodoacetate (IAA), L-trans-epoxysuccinyl-leucylamido(4-guanido)butane (E64) and pepstatin A or by CoCl(2), CaCl(2) and EDTA
Isoform M2 is allosterically activated by D-fructose 1,6-bisphosphate (FBP). Inhibited by oxalate and 3,3',5-triiodo-L-thyronine (T3). The activity of the tetrameric form is inhibited by PML. Selective binding to tyrosine-phosphorylated peptides releases the allosteric activator FBP, leading to inhibition of PKM enzymatic activity, this diverts glucose metabolites from energy production to anabolic processes when cells are stimulated by certain growth factors. Glycolytic flux are highly dependent on de novo biosynthesis of serine and glycine, and serine is a natural ligand and allosteric activator of isoform M2. Acetylation at Lys-433 promotes its translocation into the nucleus and homodimerization, promoting the protein kinase activity
Undergoes calcium/calmodulin-dependent intramolecular autophosphorylation, and this results in it becoming partially calcium/calmodulin-independent
Inhibited by ATP analogs and sodium deoxycholate. Activated by choline-containing phospholipids
Inhibited by hydroxyurea, leads to dNTP depletion, replication fork arrest and genomic instability
Inhibited by DPA-S-(N-acetylcysteamine)
Diadenylate cyclase activity is inhibited by the interaction with RadA
Protein-arginine N-acetylglucosaminyltransferase activity is inhibited by 100066N compound (flavone analog) and 102644N compound (a substituted isoxazole)
Inhibited by 2-mercaptoethanol, p-chloromercuribenzoate, and iodoacetate
Inhibited by itaconate, itaconic anhydride, bromopyruvate and 3-nitropropionate (3-NP), when M.tuberculosis grows on fatty acids, but not on glucose. Succinate at 5 mM inhibits the activity to approximately 50%
Phosphorylation at Thr-437 or Tyr-438 inactivates the enzyme, while phosphorylation at Thr-584 activates it
Li(+) decreases succinate transport in the presence of Na(+)
Inhibited by (R)-2-(4-(tert-butyl)phenethyl)-2-hydroxysuccinic acid (also known as PF-06649298) (PubMed:33597751). Stimulated by Li(+) in the presence of Na(+), moreover changes stoichiometry from 4:1 to 2:1 Na(+):citrate (PubMed:12826022)
Subject to autoinhibition, mediated by intramolecular interactions involving the SH2 and SH3 domains. Kinase activity is also regulated by phosphorylation at regulatory tyrosine residues. Phosphorylation at Tyr-411 is required for optimal activity. Phosphorylation at Tyr-522 inhibits kinase activity. Inhibited by PP1 and A-770041
Protease activity is activated upon autocatalytic cleavage in response to mitochondrial depolarization
Is inhibited by 2,6-pyridine dicarboxylate (2,6-PDC or picolinate)
In the inactive state, the N terminus protrudes into the active site of the Rho-GAP domain, sterically blocking Rac binding. Phospholipid binding to the Phorbol-ester/DAG-type zinc-finger/C1 domain triggers the cooperative dissociation of these interactions, allowing the N-terminus to move out of the active site and thereby activating the enzyme (By similarity)
Phosphorylated and activated by the p38 kinases and kinases in the Erk pathway
Activated by pathogens and other damage-associated signals: activation promotes ubiquitination and degradation of the N-terminal part, releasing the cleaved C-terminal part of the protein (NACHT, LRR and PYD domains-containing protein 1a, C-terminus), which polymerizes and forms the Nlrp1a inflammasome (By similarity). Nlrp1a inflammasome is inhibited by DPP8 and DPP9, which sequester the C-terminal fragment of Nlrp1a (NACHT, LRR and PYD domains-containing protein 1a, C-terminus) in a ternary complex, thereby preventing Nlrp1a oligomerization and activation (By similarity). Nlrp1a inflammasome is strongly activated by Val-boroPro (Talabostat, PT-100), an inhibitor of dipeptidyl peptidases DPP8 and DPP9 (PubMed:31383852). Val-boroPro relieves inhibition of DPP8 and/or DPP9 by promoting disruption of the ternary complex, releasing its C-terminal part from autoinhibition (By similarity). Not activated by cleavage by B.anthracis lethal toxin (LT) endopeptidase (PubMed:20502689). Highly activated by Toxoplasma gondii (PubMed:31383852)
Phosphatidylinositol transfer activity is inhibited by N-ethylmaleimide
Activity is increased by binding phosphatidylinositol phosphates, especially phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol 4,5-bisphosphate (PubMed:17052953). Inactivated at 37 degrees Celsius by (13S)-hydroperoxy-(9Z,11E)-octadecadienoate (PubMed:8334154)
Inhibited by lithium and calcium
In the absence of the Ltp2 aldolase, ChsH1/ChsH2 can hydrate only about 30% of the 3-OPDC-CoA substrate. Complete turnover requires the presence of Ltp2
5 fold activation by the allosteric regulator glucose-6-phosphate (PubMed:24043710). Low sensitivity to inhibition by L-malate and L-aspartate (PubMed:23443546). Up-regulated by light-reversible phosphorylation (By similarity)
Stimulated by the interaction with the DNL4-LIF1 complex
Binding to c-di-GMP activates PdtaS autophosphorylation and by extension phosphotransfer to PdtaR (PubMed:33772870). At the opposite, autophosphorylation and signaling cascade are inhibited by NO, copper and zinc (PubMed:34003742). Activity is not inhibited by calcium or iron (PubMed:34003742). Full inhibition of PdtaR/PdtaS signaling cascade requires the transduction of a cell surface signal by the intramembrane protease Rip1 (PubMed:34003742)
Inhibited by the herbicide norflurazon in a non-competitive way
Cys-299 may regulate the kinetic and inhibition properties of the enzyme, but does not participate in catalysis (PubMed:8343525). Tolrestat inhibits retinal reduction (PubMed:12732097)
Inhibited by dTTP
Activated by PDK1. Repressed during osmotic stress
Interaction with Golgi matrix protein GOLGA2 leads to autophosphorylation on Thr-174, possibly as a consequence of stabilization of dimer formation. The C-terminal non-catalytic region inhibits the kinase activity (By similarity)
Activated by cardiolipin
Addition of Ca(2+), Mg(2+), Mn(2+), Ni(2+), Co(2+) or Fe(2+) decreases the catalytic activity (PubMed:15469281). Addition of Zn(2+) results in complete loss of activity (PubMed:15469281). Is potently inhibited by substrate analogs in which the hydroxy group in HMBPP is replaced by an amino or thiol group (PubMed:22012762)
Exonuclease activity is stimulated in the presence of HerA
Inhibited by 4-aminopyridine (4-AP), dendrotoxin (DTX) and charybdotoxin (CTX), but not by tetraethylammonium (TEA) (PubMed:2555158, PubMed:8495559, PubMed:18638484). Inhibited by tityustoxin-K alpha (TsTX-Kalpha), a toxin that is highly specific for KCNA2 (PubMed:8355670). Inhibited by maurotoxin (PubMed:24472174). Inhibited by kappaM conotoxins kappaM-RIIIJ and kappaM-RIIIK (By similarity)
Activity stimulated by phosphatidylinositol 4,5-bisphosphate (PIP2)
Strongly inhibited when incubated with the serine reagent phenylmethylsulfonyl fluoride. Activated by the addition of calcium to the reaction mixture. When calcium was incubated with the lipase but not added to the reaction mixture, its effect is lower but still observable. Magnesium, manganese and strontium are not able to replace calcium with full retention of activity
Competitively inhibited by valproyl-CoA
Unaffected by EDTA or Ca(2+), Co(2+), Cu(2+), Mg(2+), Mn(2+), Ni(2+) and Zn(2+)
Binding to mppA is required for catalytic activity
Activated by the ototoxic drug cisplatin (By similarity). Activated by NOXO1. Cooperatively activated by NCF1 and NCF2 or NOXA1 in a phorbol 12-myristate 13-acetate (PMA)-dependent manner. Inhibited by diphenyleneiodonium chloride
Inhibited by deoxynojirimycin
Both proenzyme processing and catalytic activity are stimulated by putrescine. Catalytic activity is inhibited by iodoacetic acid
Homodimerization regulates its activity by maintaining the kinase in an autoinhibitory conformation. NPRL2 down-regulates its activity by interfering with tyrosine phosphorylation at the Tyr-9, Tyr-376 and Tyr-379 residues. The 14-3-3 protein YWHAQ acts as a negative regulator by association with the residues surrounding the Ser-244 residue. STRAP positively regulates its activity by enhancing its autophosphorylation and by stimulating its dissociation from YWHAQ. SMAD2, SMAD3, SMAD4 and SMAD7 also positively regulate its activity by stimulating its dissociation from YWHAQ. Activated by phosphorylation on Tyr-9, Tyr-376 and Tyr-379 by INSR in response to insulin (By similarity)
Phosphorylated and activated by pdk-1
Completely inhibited by Hg(2+) and Cu(2+) ions, whereas 1 mM Zn(2+) inhibited activity by 51%
Inhibited by EDTA, EGTA and 1,10-phenanthroline. Addition of Mg(2+) or Ca(2+) increases the casein hydrolysis rate
Stimulated by reduction of the disulfide bond and the presence of pyruvate
Binding to anionic phospholipids, predominantly to cardiolipin inhibits its phosphotransfer activity
Inhibited by NaCl concentrations above 150 mM
Inhibited by Zn(2+), Cu(2+), Ca(2+) and Cd(2+)
Export of antibiotics and solvents is dramatically decreased in the presence of the protonophore carbonyl cyanide m-chlorophenylhydrazone (CCCP), therefore may be driven by a proton gradient (PubMed:8540696, PubMed:25901994). Antibiotic efflux is inhibited by pyridopyrimidine derivatives, such as ABI-PP, acting by binding to a hydrophobic pocket in MexB (PubMed:23812586)
Inhibited by 3-Cl HOPDA
Under physiological conditions, G3BP1 adopts a compact state that is stabilized by intramolecular interactions between the RG-rich and the acidic regions that inhibit phase separation. Upon stress, polysomes disassemble and mRNAs are released in an unfolded protein-free state. Binding of unfolded mRNA to G3BP1 outcompetes the intramolecular interactions and RNA-bound G3BP1 adopts an expanded conformation in which the RG-rich region becomes exposed to engage in protein-protein and protein-RNA interactions, allowing physical cross-linking of RNA molecules to form protein-RNA condensates, leading to liquid-liquid phase separation (LLPS)
Inactivated by antipain, PMSF, TPCK, leupeptin, pepstatin, EDTA, and E-64 (trans-epoxysuccinylleucylamido(4-guanidino)butane)
Regulated by PknF. Inhibited by S-adenosyl-N-decyl-aminoethyl (SADAE), thiacetazone (TAC) and dioctylamine
The NO arm of the pathway is further controlled by sequestration of PdtaR by PPE1-5', controlled by the Rip1 intramembrane protease (PubMed:34003742). PPE1-5' directly inhibits PdtaR and derepresses PdtaR targets, which are usually repressed by the PdtaR/PdtaS cascade (PubMed:34003742)
Active in presence of diverse metals including Fe(2+), Zn(2+), Mn(2+) (By similarity). Binds two metal cations in two adjacent alpha and beta metal-binding pockets (By similarity)
Inhibited by interaction with SNCAIP (isoform 2, but not isoform 1). May be inhibited by interaction with PEG10
Activated by phospholipids including cardiolipin, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol and phosphatidylserine
Activated by the phospholipids cardiolipin, phosphatidylserine, and phosphatidylethanolamine. Strongest activation with cardiolipin
Inhibited by MTSET (2-(Trimethylammonium)-ethyl-methanethiosulfonate) and E64 ([n- (l-3-trans-carboxyoxirane-2-carbonyl)-l-leucyl]-amido(4-guanido)butane) (PubMed:14725770). Inhibited by coptisine (PubMed:29690584)
Activated by magnesium and inorganic phosphate. Inhibited by ADP and GDP (PubMed:7593598)
Alternates between an inactive GDP-bound form and an active GTP-bound form (By similarity). Intrinsic GTPase activity is almost undetectable in vitro (PubMed:8954160). Activated by a guanine nucleotide-exchange factor (GEF) and inactivated by GTPase-activating protein ARFGAP1 (By similarity)
Inhibited by phlorizin and phloretin
The SgcE6-SgcC hydroxylation activity decreases in the presence of excess FAD
Exhibits two interesting properties: 'substrate synergism', in which the enzyme is most active for the catalysis of its partial reactions only when all the substrate-binding sites are occupied, and 'catalytic cooperativity' between alternating active sites in the tetramer, whereby the interaction of substrates (particularly ATP) at one site is needed to promote catalysis at the other
Inhibited by validamycin A
Activated in response to insulin. Autophosphorylation activates the kinase activity. PTPN1, PTPRE and PTPRF dephosphorylate important tyrosine residues, thereby reducing INSR activity. Inhibited by ENPP1. GRB10 and GRB14 inhibit the catalytic activity of the INSR, they block access of substrates to the activated receptor. SOCS1 and SOCS3 act as negative regulators of INSR activity, they bind to the activated INRS and interfere with the phosphorylation of INSR substrates (By similarity). Interacts with PTPRF (By similarity). Interacts with ATIC; ATIC together with PRKAA2/AMPK2 and HACD3/PTPLAD1 is proposed to be part of a signaling netwok regulating INSR autophosphorylation and endocytosis (By similarity)
Inactivated by 5-iodouracil
Na(+) extrusion is completely inhibited by the H(+) conductor carbonyl cyanide m-chlorophenylhydrazone (CCCP)
Partially inhibited by magnesium at concentration higher than 10 mM and totally inhibited at concentration higher than 250 mM. Also inhibited by tunicamycin, NaCl and KCl
Specifically inhibited by didemnin B, a natural product that triggers ribosome stalling by preventing aminoacyl-tRNA (aa-tRNA) release from EEF1A1 on the ribosome
Activated by tissue damage and upon binding to PBP1 or PBP2
Partially activated by Co(2+) and Mg(2+) has no effect (PubMed:19574214). Inhibited by 1 mM Zn(2+), Ni(2+), or Cu(2+) (PubMed:19574214). Inhibited by apstatin, a non-hydrolysable peptide analog (PubMed:27462122)
Inhibited by nisoxetine, oxaprotiline and desipramin
Inhibited by phloretin (PubMed:8958221). Activated by vasopressin, forskolin, 3-isobutyl-1-methylxanthine (IBMX) and cAMP (PubMed:16959825)
Inhibited by phloretin
Inhibited by urea analogs and phloretin and activated by forskolin
Inhibited by phloretin and activated by forskolin
Strongly inhibited by the serine protease inhibitor diisopropyl fluorophosphate (DFP), chymostatin, leupeptin, 0.5 mM ZnCl(2), 10 mM o-phenanthlorine and N-tosyl-L-phenyl-alanyl chloromethyl ketone (TPCK), but not by N-tosyl-L-lysyl chloromethyl ketone (TLCK). Activity is not affected significantly by iodoacetate (IAA), L-trans-epoxysuccinyl-leucylamido(4-guanido)butane (E64), pepstatin A and phenylmethanesulfonyl fluoride (PMSF). Activity is stimulated by addition of 0.5 mM CaCl(2), 10 mM EDTA and N-ethylmaleimide (NEM)
Activity is chloride-dependent
Stimulated by unfolded protein
Inhibited by the small molecule serine protease inhibitors phenylmethylsulfonyl fluoride (PMSF) and benzamidine
Allosterically activated by benzodiazepines and the anesthetic etomidate (By similarity). Inhibited by the antagonist bicuculline (By similarity)
Kinase activity stimulated by CENPE
Retains almost half of its activity in presence of high salt concentrations up to 100 mM NaCl (PubMed:30529567). Retains also more than 85% of its original activity in the presence of 1 mM EDTA, indicating a satisfactory resistance towards chelators, which is rare among metal-containing enzyme (PubMed:30529567). The activity drops significantly in the presence of NaN(3) or SDS (PubMed:30529567). Appears more active in the presence of methanol compared to ethanol, but acetone or DMSO addition severely affect remaining laccase activity (PubMed:30529567)
Activated by c-di-GMP
Inhibited by dithionite, sodium hydrogensulfite and tungstate
The hydrolytic product 7-methylguanosine diphosphate (m7GDP) efficiently inhibits the decapping scavenger activity and acts as a competitive inhibitor in vitro. Inhibited by 2,4-diaminoquinazoline
Inhibited by O-phenanthroline and MGTA and activated by cobalt
Subject to feedback inhibition by GMP
Is competitively inhibited by L-threo-3-hydroxyhomoserine phosphate
Inhibited by L-cycloserine
Binds iron under oxidative stress conditions, but not under conditions emulating the intracellular redox potential
Inhibited by excess substrate. Inhibited by EDTA
Inhibited by acetyl-CoA (PubMed:17825826). Inhibited by calcium hopantenate (PubMed:17379144). Activated by palmitoylcarnitine (PubMed:17825826)
Inhibited by EDTA. Inhibited by Ba(2+), Cu(+), Fe(2+) and Zn(2+) ions and, to a lesser extent, by Mn(2+) and Mg(2+) ions
Dithiothreitol increases the enzyme activity by 2.5-fold
Inhibited by K3 herbicides such as allidochlor, anilofos, cafenstrole and flufenacet (PubMed:15277688). Strongly inhibited by metazachlor (PubMed:22284369)
Acylated lysine-binding is specifically inhibited by the tripeptide XL-13m, carrying a 2-furancarbonyl side chain, preventing recruitment to chromatin
Inhibited by phosphoenolpyruvate (PEP)
Transport is inhibited by the proton uncoupler dinitrophenol (PubMed:374403). Inhibited by the nucleoside antibiotic showdomycin (PubMed:374403)
In high-amino acid conditions, activated by GTPase activating protein (GAP) FLCN that stimulates RRAGC GTPase activity to turn it into its active GDP-bound form
Inhibited by EDTA, by the reducing agents dithiothreitol and 13-mercaptoethanol, and by the divalent cation Cu(2+)
In vitro the glycolate oxidase activity is inhibited by the sulfhydryl inhibitors CuSO4 and PCMB, by KCN, but not by the metal complexing agent EDTA
Differs from archetypal CaMK members in that the kinase domain exhibits a constitutively active conformation and the autoinhibitory region does not engage in direct contact with the ATP-binding cleft, although it still binds Ca(2+)/CAM
Kinase activity is stimulated by pyrimidine nucleotides, especially CMP and CTP, and inhibited by AMP, ADP and GMP (PubMed:9357959). Activity is stimulated by potassium or ammonium ions (PubMed:9357959)
ADP-binding promotes an inactive closed conformation
Subject to allosteric regulation. Activated by ADP. Inhibited by GTP and ATP (By similarity)
Irreversibly inhibited by the fungal metabolite fumagillin, an antiangiogenic drug. Subject to product inhibition by cytosolic methionine
Inhibited by triclosan
Allosterically activated by GTP, when glutamine is the substrate; GTP has no effect on the reaction when ammonia is the substrate. The allosteric effector GTP functions by stabilizing the protein conformation that binds the tetrahedral intermediate(s) formed during glutamine hydrolysis. Inhibited by the product CTP, via allosteric rather than competitive inhibition (By similarity). Inhibited by 6-diazo-5-oxo-l-norleucine (DON) (PubMed:32507415)
Activated in a reduced environment which promotes the reduction of the disulfide bond between the regulatory Cys-53 and catalytic Cys-114 residues
Inhibited by calcium, cadmium, copper and mercury ions. Stable for 2 hours at 60 degrees Celsius but activity is decreased to less than 50 percent within 20 minutes at 80 degrees Celsius. Two folds activity enhancement in the presence of 1 mM glutathione, DTT, or 2-mercaptoethanol. Complete activity inhibition by thiol-modifying reagents such as p-chloromercuribenzoic acid or p-hydroxy-mercuribenzoic acid
Kinase activity is inhibited competitively by amlexanox
GAP activity stimulated by phosphatidylinositol 3,4,5-trisphosphate (PIP3) and, to a lesser extent, by phosphatidylinositol 4,5-bisphosphate (PIP2). Phosphatidic acid potentiates PIP2 stimulation (By similarity)
Hexokinase is an allosteric enzyme inhibited by its product D-glucose 6-phosphate. Hexokinase activity is inhibited by N-acetyl-D-glucosamine
Present in an inactive conformation in the absence of bound ligand. Ligand binding leads to dimerization and activation by autophosphorylation on tyrosine residues
Inhibited by o-phenanthroline
Inhibited by ruthenium red or its derivative Ru360; possibly by obstructing the pore
Activated by cardiolipin and dioleoyl phosphatidylethanolamine (DOPE), phospholipids found in the inner mitochondrial membrane. Inhibited by high substrate concentration
Inhibited by both ribo- and deoxyribonucleoside di- and triphosphates
cAMP does not regulate lysophospholipase activity in vitro (PubMed:18086666, PubMed:28887301). Slightly inhibited by organophosphorus (OP) compounds such as mipafox, which is likely why mice are less sensitive to distal axonophathy induced by OPs compared to humans (PubMed:18086666)
Acetylation of Lys-50 leads to loss of DNA nicking activity. Acetylation of Lys-154 has no effect
Glyoxalase activity is inhibited by zinc ions (PubMed:26678554). Active as a chaperone in both its reduced and oxidized states, and is more active in its oxidized form (PubMed:20124404)
Becomes activated when its major tyrosine phosphorylation site is not phosphorylated. It can also be activated by point mutations as well as by truncations at the C-terminal end or by other mutations. Heme regulates its activity by enhancing the phosphorylation on Tyr-527 (By similarity)
Inhibited by EDTA, calcium chloride, and zinc chloride. Enhanced by magnesium chloride (By similarity). Glycerophosphodiester phosphodiesterase activity can be modulated by G-protein signaling pathways (PubMed:12576545)
Autokinase and kinase activities depend on low (uM range) Mg(2+) concentrations. Phosphatase activity is stimulated by high (mM range) Mg(2+) concentrations and ADP at 1 mM. Autokinase inhibited by radicicol
Inhibited by uridine, CMP and dCMP
Activated by the binding of either IGP or PRFAR to the active site of HisF
Activated by phosphorylation of Thr-210 by AURKA; phosphorylation by AURKA is enhanced by BORA. Once activated, activity is stimulated by binding target proteins. Binding of target proteins has no effect on the non-activated kinase. Several inhibitors targeting PLKs are currently in development and are under investigation in a growing number of clinical trials, such as BI 2536, an ATP-competitive PLK1 inhibitor or BI 6727, a dihydropteridinone that specifically inhibits the catalytic activity of PLK1
Aminooxyacetic acid (AOAA) blocks its activity in both cytoplasm and mitochondria
Inhibited with low affinity by edelfosine
The kinase activity is positively regulated by SNF4 via sequestration of the SNF1 auto-inhibitory domain (AID) (PubMed:2557546, PubMed:17851534)
Thioesterase activity, but not pyocyanine production, is inhibited by 2-(pyridin-3-yl)benzoic acid, 2-(1H-pyrrol-1-yl)benzoic acid and 3-methylthiophene-2-carboxylic acid. Compounds bind to the active center
Up-regulated by RD3
Activated by an increase in cytosolic calcium levels that induce a conformational change of the N-terminal regulatory domain, uncapping the channel and allowing transport
Allosterically activated by GTP. Binding of GTP leads to 5-time activation of the enzyme
Platelet aggregation in inhibited by the metalloproteinase inhibitors EDTA and Batimastat. The hemorrhagic activity is not inhibited by the plasma proteinase inhibitor alpha2-macroglobulin, although the SVMP is able to cleave this plasma inhibitor, generating a 90 kDa product
Down-regulated by phosphatidylserines exposed on the cell surface
Long isoform of CD74/Ii chain stabilizes the conformation of mature CTSL by binding to its active site and serving as a chaperone to help maintain a pool of mature enzyme in endocytic compartments and extracellular space of APCs (PubMed:11483509, PubMed:12417635). IFNG enhances the conversion into the CTSL mature and active form (PubMed:11483509). Inhibited by CST6. Inhibited by the glycopeptide antibiotic teicoplanin. Inhibited by amantadine (By similarity)
Strongly inhibited by ADP
Substrate inhibition is very strong with lactaldehyde, diminishing progressively with glycolaldehyde, glyceraldehyde or methylglyoxal (PubMed:3308886). Inhibited by p-hydroxy mercuribenzoate and by some cations, including Mn(2+), Ca(2+), Cu(2+) and Zn(2+) (PubMed:3308886). Inhibited by NADH (PubMed:3275622)
Alternates between an inactive form bound to GDP and an active form bound to GTP. Inactivated by TSC1-TSC2 via the GTPase activating protein (GAP) domain of TSC2
Formation of filaments, called spirosomes, is critical for activity (PubMed:31586059, PubMed:32188856, PubMed:32523125). Filamentation is essential for substrate channeling between the ALDH and ADH domains and efficient coupling of the ALDH and ADH enzymatic activities, and for the regulation of enzyme activity (PubMed:32188856, PubMed:32523125). In the absence of ligands, the spirosomes are compact (PubMed:31586059, PubMed:32188856, PubMed:32523125). Binding of NAD(+) and Fe(2+) cofactors induces conformational changes and extension of the filaments, leading to the activation of the enzyme (PubMed:31586059, PubMed:32188856, PubMed:32523125). AdhE is inhibited in the presence of oxygen by metal-catalyzed oxidation (MCO) and by heat stress (PubMed:11917132, PubMed:19238259). The chaperone DnaK has a protective effect on AdhE activity under aerobic but not anaerobic conditions (PubMed:11917132). DnaK may protect AdhE and AdhE mutants against irreversible MCO damages and improve their ability to grow aerobically on ethanol (PubMed:11917132). IbpA and IbpB protect AdhE against thermal and oxidative inactivation during oxidative stress, providing that the enzyme remained soluble, and increase the efficiency of reactivation of heat-denatured AdhE by the DnaK system (PubMed:19238259). Acetaldehyde dehydrogenase activity is inhibited by guaiacol, which mimics an intermediate of ubiquinone synthesis (PubMed:10612730)
Inhibition by oxidized glutathione (GSSG), S-nitrosoglutathione (GSNO) and hydrogen peroxide
Is inhibited in vitro by typical serine protease inhibitors like diisopropyl fluorophosphate, Pefablock, and 3,4-dichloroisocoumarin, but not by typical cysteine class inhibitors such as E-64 or iododoacetic acid
Reversibly inhibited by O(2)
Is competitively inhibited by glycolate
Inhibited by uncouplers such as 2,4-dinitrophenol and carbonyl cyanide-m-chlorophenyl-hydrazone
Activity is strongly inhibited by riboflavin analogs, such as lumiflavin and lumichrome
Inhibited by warfarin (coumadin) (PubMed:15879509, PubMed:23772386, PubMed:23928358). Warfarin locks VKORC1 in both redox states into the closed conformation (By similarity)
Prostaglandin PGD2 synthesis is stimulated by calcium and magnesium ions. One calcium or magnesium ion is bound between the subunits of the homodimer. The interactions with the protein are for the most part mediated via water molecules. Magnesium increases the affinity for glutathione, while calcium has no effect on the affinity for glutathione
Subject to substrate inhibition by high levels of 3-dehydroecdysone
Activated by Mg(2+), but not by Ca(2+)
Excess of calcium ions significantly suppress the autoproteolysis of the enzyme
Each protein molecule can bind up to four molecules of AMP, which act as an allosteric activator to the enzyme. The enzyme is also inhibited by alpha-keto acids and other catabolites
G6PD activity is inhibited by glucosamine-6-phosphate, NADPH, and 4-(4-bromophenyl)-7-(3,4-dimethoxyphenyl)-4,6,7,8-tetrahydroquinoline-2,5(1 H,3H)-dione. G6PD and 6PGL activities can be reversibly inhibited by S-glutathionylation (in vitro)
Hemopressin, a peptide derived from hemoglobin subunit alpha (HBA1 and/or HBA2), acts as an antagonist peptide: hemopressin-binding efficiently blocks cannabinoid receptor CNR1 and subsequent signaling
Interaction with SBF1/MTMR5 increases phosphatase activity (By similarity). Increases SBF2/MTMR13 catalytic activity towards phosphatidylinositol 3,5-bisphosphate and to a lesser extent towards phosphatidylinositol 3-phosphate (PubMed:16399794)
The tetramethylammonium ion, which mimics the head group of glycine betaine, acts as a competitive inhibitor of ATRR A domain, whereas the potency decreased by three orders of magnitude with dimethylammonium (PubMed:31061132). Choline is a mixed inhibitor for both glycine betaine reductase and aldehyde reductase activity but more potent in competition against glycine betaine in the first reduction step (PubMed:31061132). Therefore, choline could act as a feedback inhibitor to regulate ATRR enzymatic activity (PubMed:31061132). The lowered binding affinity of choline to R2 favors the release of choline after glycine betaine aldehyde reduction to avoid direct product inhibition (PubMed:31061132)
Inhibited by phosphorylation at serine residues
Subject to catabolite regulation
Nicking activity (relaxase) is inhibited by bisphosphonates such as the non-competitive inhibitor imidobisphosphate (PNP), etidronic acid (ETIDRO) and clodronic acid (CLODRO). The latter 2 are competitive inhibitors, and are already used clinically to treat bone loss (marketed as Didronel and Bonefos). All 3 compounds also inhibit conjugation and kill F plasmid-containing cells. They are specific to dual tyrosine relaxases such as those found in F and related R conjugative plasmids
Not sensitive to tricolsan
Channel activity is inhibited by nM concentrations of Zn(2+)
Inhibited by calcium and zinc ions (PubMed:8740418). Inhibited by nucleoside triphosphates and diphosphates (PubMed:8740418)
Activated by calcium/calmodulin
Activated by phosphorylation at Ser-764 by CDG1
Inhibited by Cu(2+) and Zn(2+) at 0.5 mM by 93 and 87% respectively (PubMed:9148938). Not inhibited by Ca(2+), Mg(2+), Co(2+), Ni(2+), and EDTA at 0.5 mM (PubMed:9148938)
During activation, the N-terminal disordered prodomain is removed by cleavage (PubMed:12824163, PubMed:16916640). Concomitantly, double cleavage gives rise to a large Caspase-7 subunit p20 and a small Caspase-7 subunit p11 (PubMed:16916640). The two large and two small subunits then assemble to form the active CASP7 complex (PubMed:16916640). Can be cleaved and activated by different caspases, depending on the context (PubMed:16916640). Cleaved and activated by initiator caspases (CASP8, CASP9 and/or CASP10), leading to execution phase of apoptosis (PubMed:16352606, PubMed:16916640). Inhibited by XIAP, which directly binds to the active site pocket and obstructs substrate entry (PubMed:16352606, PubMed:16916640, PubMed:11257230, PubMed:11257231). Cleavage and maturation by GZMB regulates granzyme-mediated programmed cell death (By similarity). Cleavage and maturation by CASP1 regulates pyroptosis (By similarity). Phosphorylation at Ser-30 and Ser-239 by PAK2 inhibits its activity (PubMed:21555521, PubMed:27889207). Inhibited by isatin sulfonamides (PubMed:10821855). Inhibited by 2-(2,4-Dichlorophenoxy)- N-(2-mercapto-ethyl)-acetamide (DICA) and 5-Fluoro-1H-indole-2- carboxylic acid (2-mercapto-ethyl)-amide (FICA) allosteric inhibitors, which disrupt an interaction between Arg-187 and Tyr-223 (PubMed:15314233, PubMed:19581639). Specifically inhibited by DARPin D7.18 and D7.43, which specifically bind to the precursor CASP7 and prevent its processing and activation (PubMed:24779913)
Inhibited by hydrogen peroxide. Is resistant to cyanide and azide inhibition
Negatively regulated by CCAR2
Activated by forming a complex with STRAD (STRADA or STRADB) and CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta): STRADA (or STRADB)-binding promotes a conformational change of STK11/LKB1 in an active conformation, which is stabilized by CAB39/MO25alpha (or CAB39L/MO25beta) interacting with the STK11/LKB1 activation loop. Sequestration in the nucleus by NR4A1 prevents it from phosphorylating and activating cytoplasmic AMPK (By similarity)
Is inhibited by mono- and divalent cations as well as L-ascorbic acid 6-hexadecanoate
Two specific sites, one in the kinase domain (Thr-309) and the other in the C-terminal regulatory region (Ser-474), need to be phosphorylated for its full activation (PubMed:18800763, PubMed:19179070). Aminofurazans, such as 4-[2-(4-amino-2,5-dihydro-1,2,5-oxadiazol-3-yl)-6-{[(1S)-3-amino-1-phenylpropyl]oxy}-1-ethyl-1H-imidazo[4,5-c]pyridin-4-yl]-2-methylbut-3-yn-2-ol (compound 32), are potent AKT2 inhibitors (PubMed:19179070)
Strongly inhibited by sodium azide, sodium cyanide, Li(+), Sn(+), Hg(2+), and the disulfide-reducing agents beta-mercaptoethanol, dithiothreitol and thioglycolic acid. Moderately inhibited by Mn(2+) and Fe(2+), inhibition by these metal ions is stronger at 0.1 mM than at 1 mM. Moderately inhibited by Cu(2+)
GTPase-activating activity is inhibited in the folliculin complex (LFC), which stabilizes the GDP-bound state of RRAGA/RagA (or RRAGB/RagB), because Arg-164 is located far from the RRAGC/RagC or RRAGD/RagD nucleotide pocket. Disassembly of the LFC complex upon amino acid restimulation liberates the GTPase-activating activity
Inhibited by Triacsin C (PubMed:12235169). Both insulin and muscle contraction stimulate translocation to the plasma membrane in muscle, increasing fatty acid transport activity (PubMed:19527715)
Active only in complex with LYRM4
Requires cadmium for activity. Also activated in vitro or in heterologous system by Ag(+), Hg(+), Zn(2+), Cu(2+), Fe(2+) or Fe(3+) ions, but not by Co(2+) or Ni(2+) ions
Is highly and competitively inhibited by lysine that binds to the active site and competes with 2-oxoglutarate (PubMed:12095615, PubMed:19996101). Is also slightly inhibited by arginine and 2-aminoethylcysteine (PubMed:12095615)
Inhibited by amiloride
Both NAADP and cADPR synthesis are inhibited by nicotinic acid
Inhibited by protonophores (e.g. carbonyl cyanide m-chlorophenyl-hydrazone (CCCP)) and SH group inhibitors (e.g. p-chloromercuribenzene sulphonic acid (PCMBS))
Regulated by a guanine nucleotide-exchange factor (GEF) and a GTPase-activating protein (GAP) and alternates between an inactive GDP-bound and an active GTP-bound form. The BLOC-3 complex composed of HPS1 and HPS4 acts as its GEF, promotes the exchange of GDP to GTP, converting it from an inactive GDP-bound form into an active GTP-bound form. SGSM2 acts as its GAP and inactivates it by stimulating its GTPase activity (PubMed:26620560)
Feedback inhibition by ADP
Inhibited by tunicamycin
Positively regulated by SEC14. Inhibited by organophosphorus esters in the order phenyl saligenin phosphate (PSP) > phenyldipentyl phosphinate (PDPP) = diisopropyl fluorophosphate (DFP) > and paraoxon (PXN)
Allosterically inhibited by NADP, NADPH, and NADH, at concentrations lower than 0.5 mM. Completely inhibited by p-chloromercuribenzoate
Inhibited by divalent cation Mg(2+)
Activity is controlled by product inhibition
Inhibited by ethanol (By similarity)
Activity is stimulated by unphosphorylated GarA
Inhibited by serine proteinase inhibitor 4-(2-aminoethyl)-benzenesulfonyl fluoride, but not with EDTA or E-64
3-aminomethyl-p-menthane which is similar to the phomasetin substructure, dose-dependently inhibits phm7 activity in vitro and production of phomasetin in the fungus
Activated by mannosylphosphoryldolichol and phospholipids such as phosphatidylglycerol and phosphatidylcholine. Inhibited by natural nucleoside antibiotic tunicamycin, which acts as a structural analog and competitor of UDP-GlcNAc
Is inhibited by BamI, the product of its coregulated adjacent gene
Inhibited by EDTA, Zn(2+), Cd(2+), Co(2+), p-chloromercuribenzoate and L-ascorbic acid (AsA)
Subject to complex allosteric regulation. The enzyme can assume an active R-state, or an inactive T-state. Intermediate conformations may exist. AMP acts as allosteric inhibitor. Fructose 2,6-bisphosphate acts as competitive inhibitor. Strongly inhibited by Ca(2+) (By similarity)
Catalytic activity and hemolysis are inhibited by divalent ion chelators (1,10-phenanthroline, EDTA, and EGTA)
Inhibited by palmitate
At alkaline pH BPGM favors the synthase reaction; however, at lower pH the phosphatase reaction is dominant. Inhibited by citrate
Inhibited by oleic acid and sphingosine, while it is stimulated by phosphatidylcholine, phosphatidylserine and phosphatidic acid
Inhibited by Ag(+), Cu(+), Hg(2+) and Pb(2+)
Inhibited by chelating agents such as imidazole, alpha,alpha'-bipyridine, and 1,10-phenanthroline
Inhibited by NaCl. Inhibited by GDP in a concentration dependent manner, with an IC(50) value of 93 uM. Also inhibited by GMP and GTP. Inhibited by N-ethylmaleimide. Activated by poly(ethylene glycol) by enhancing the thermal stability of FUT7. Activated by Mn2+, Ca2+, and Mg2+. Both panosialin A and B inhibit activity with IC(50) values of 4.8 and 5.3 ug/ml, respectively. Inhibited by gallic acid (GA) and (-)-epigallocatechin gallate (EGCG) in a time-dependent and irreversible manner with IC(50) values of 60 and 700 nM, respectively
Activity is calcium-dependent with a more pronounced effect at higher pH
Stimulated by sodium sulfate > ammonium sulfate
Relatively insensitive to inhibition by cyclosporin A (CsA)
Inhibited by pyrimidine derivative XC11
Inhibited by phosphorylated compounds such as AMP, ADP, ATP, 3-phosphoglyceric acid and PPi. Not inhibited by orthophosphate. Activity is high in cells grown in low glucose concentrations and decreases dramatically as glucose concentration increases (By similarity)
Inhibited by EDTA and 1,10-phenanthroline, but not by PMSF
Strongly inhibited by beta-mercaptoethanol, sodium azide and potassium cyanide. Slightly repressed by 3-amino-1,2,4-triazole (3-AT). Activity is repressed proportionally to increased concentration of NaCl, KCl, LiCl and MgCl(2)
Inhibited by the pyrrole-indolinone inhibitor SU11274 (K00593): intercalates between the ATP-binding Lys-65 and alpha-C glutamate (Glu-81), resulting in a partial disordering of the lysine side chain. Also specifically inhibited by erlotinib. Slightly inhibited by gefitinib
GTPase activity is inhibited by metal binding. Activity is decreased in the presence of Co(II) or Ni(II), and is completely inhibited in the presence of Zn(II)
Inhibited by (4-[(2-butyl-6,7-dichloro-2-cyclopentyl-2,3-dihydro-1-oxo-1H-inden-5-yl)oxy]butanoic acid), which plugs the channel like a cork in a bottle by binding in the extracellular selectivity filter and sterically occluding ion conduction
Binding to the accessory protein CPAP3-A1 is essential for chitinase activity
Repressor activity is regulated by binding of different sugars to TrmB. These sugars can act as inducers or corepressors. Binding of maltose and trehalose results in derepression of the malE operon, and binding of maltotriose, larger maltodextrins and, to a minor extent, sucrose results in derepression of the mdxE operon. In contrast, binding of glucose causes stronger repression of the malE and mdxE operons. Maltose may also act as a corepressor of the mdxE operon
Inhibited by o-methylbenzoylalanine (OMBA)
Gating is voltage-dependent and repressed by decavanadate. Calmodulin-binding confers the Ca(2+) sensitivity. ATP is able to restore Ca(2+) sensitivity after desensitization. Phosphatidylinositol 4,5-bisphosphate (PIP2)-binding strongly enhances activity, by increasing the channel's Ca(2+) sensitivity and shifting its voltage dependence of activation towards negative potentials. Activity is also enhanced by 3,5-bis(trifluoromethyl)pyrazole derivative (BTP2) (By similarity)
Inactivated by binding to URI1. Activation requires multiple phosphorylation events on serine/threonine residues. Activation appears to be first mediated by phosphorylation of multiple sites in the autoinhibitory domain, which facilitates phosphorylation at Thr-412, disrupting the autoinhibitory mechanism and allowing phosphorylation of Thr-252 by PDPK1. The active conformation of the kinase is believed to be stabilized by a mechanism involving three conserved phosphorylation sites located in the kinase domain activation loop (Thr-252) and in the AGC-kinase C-terminal domain (Ser-394 in the middle of the tail/linker region and Thr-412 within a hydrophobic motif at its end). Activated by mTORC1; isoform Alpha I and isoform Alpha II are sensitive to rapamycin, which inhibits activating phosphorylation at Thr-412. Activated by PDPK1 (By similarity)
Rab activation is generally mediated by a guanine exchange factor (GEF), while inactivation through hydrolysis of bound GTP is catalyzed by a GTPase activating protein (GAP) (PubMed:20154091). That Rab is activated by the guanine exchange factors DENND1A, DENND1B and DENND1C (PubMed:20154091)
Activated under anaerobic conditions by NrdG, a tightly associated activase. Activation involves the formation of a glycyl radical at Gly-682
Inhibited by Cu(2+), Hg(2+), Mg(2+), Mn(2+), Pb(2+) and Zn(2+)
The generation of protoporphyrin IX, but not coproporphyrin III, is stimulated by heme-bound HemQ. This stimulatory effect is mediated by superoxide (PubMed:27597779). Inhibited by acifluorfen analogs (PubMed:25908396)
Enzyme activity is regulated by acetylation
Inhibited by o-phenanthroline and 8-hydroxyquinoline
Glycohydrolase activity is completely inhibited by interaction with the immunity factor for TNT (IFT) homolog. This inhibition protects M.bovis from self-poisoning
Inhibited by the copper chelator diethyl dithiocarbamate
Allosterically activated by benzodiazepines, the neuroanesthetic alphaxalone and pentobarbital (By similarity). Inhibited by the antagonist bicuculline (By similarity)
Slow activation by external aluminum
Binding of glutamate or asparatate induces a higher thermal stability of the protein structure
Inhibited by CGP57380 and staurosporine
Activated by cyclic UMP (cUMP) and to a lesser extent by cCMP
Inhibited by GPC3 and diprotin A
Fumarate hydratase activity (fumarate to L-malate) is strongly inhibited by phosphoenolpyruvate, citrate, oxaloacetate, ATP and ADP (PubMed:29688630). Malate dehydratase activity (malate to fumarate) is activated by oxaloacetate, Asn and Gln (PubMed:29688630). Malate dehydratase activity (malate to fumarate) is inhibited by citrate, succinate, ADP and ATP (PubMed:29688630)
Activated by binding of S100B which releases autoinhibitory N-lobe interactions, enabling ATP to bind and the autophosphorylation of Ser-281. Thr-444 then undergoes calcium-dependent phosphorylation by STK24/MST3. Interactions between phosphorylated Thr-444 and the N-lobe promote additional structural changes that complete the activation of the kinase. Autoinhibition is also released by the binding of MOB1/MOBKL1A and MOB2/HCCA2 to the N-terminal of STK38
Filament dynamics depend partially on MamJ
Inhibited by methyl alpha-D-glucoside, methyl beta-D-glucoside, p-nitrophenyl alpha-D-glucoside, o-nitrophenyl beta-D-glucoside and salicin, but not by 2-deoxyglucose
Weakly inhibited by oxaloacetate, 2-oxoglutarate, and citrate. Severely inhibited by oxaloacetate plus glyoxylate (By similarity)
Inhibited by GDP-fucose
In the presence of high extracellular ammonium concentrations, transport activity is inhibited by interaction with the regulatory protein GlnK. Formation of the GlnK-AmtB complex is influenced by intracellular pools of the effector molecules ATP, ADP, Mg(2+) and 2-oxoglutarate. The GlnK-AmtB interaction is also controlled by the level of intracellular glutamine and the uridylylation status of GlnK
Activation by tryptophan (a hysteretic factor)
Inhibited by Li(+) (IC(50)=10 millimolar), Na(+) (IC(50)=200 millimolar) and Ca(2+) (IC(50)=0.03 millimolar)
Repressed by coumarins
Repressed by PYR/PYL/RCAR ABA receptors in an ABA-dependent manner
Inhibited by the end product HBP
At low concentrations of ATP, a phosphorylated intermediate is formed which inhibits further hydrolysis
Activated through phosphorylation predominantly by ATR but also by ATM in response to DNA damage or inhibition of DNA replication. Activation is modulated by several mediators including CLSPN, BRCA1 and FEM1B. Proteolytic cleavage at the C-terminus by SPRTN during normal DNA replication activates the protein kinase activity
Inhibited by cyanuric acid
Activated by phosphorylation on histidine. Competitively inhibited by 3-phosphosglycerate, oxalate, malate, chloride, phosphate and sulfate ions, and uncompetitively inhibited by succinate and phosphoenolpyruvate (PEP)
GTPase is inhibited by GTP-gamma-S, which also stabilizes filaments
Local inflammatory effects are inhibited by antiserotonin drugs (cyproheptadine and methysergide), indomethacin, betamethasone, and antihistamine (chlorpheniramine)
Activated by ascorbate and inhibited by divalent metal ions such as zinc, copper and cobalt
Helicase activity toward DNA substrate is inhibited by micromolar concentrations of 5,6-dichloro-1-(beta-D-ribofuranosyl)benzotriazole (DRBT) and 4,5,6,7-tetrabromobenzotriazole (TBBT). Helicase activity toward RNA substrate is inhibited by elevated concentrations of TBBT. Inhibited by some ring-expanded nucleoside analogs
Activity is slightly inhibited by Mg(2+) and Mn(2+), and slightly increased by Cu(2+). Activity is slightly inhibited by the chelating agents 8-hydroxyquinoline, ethylenediaminetetraacetate, o-phenanthroline and 2,2'-bipyridyl
Has no response to S-adenosyl-methionine/AdoMet, unlike mammalian orthologs (PubMed:29275181). Binds non-covalently to a heme group that may control the redox sensitivity of the enzyme (By similarity)
Requires N-acetyl-L-glutamate (NAG) as an allosteric activator. N-acetyl-L-beta-phenylglutamate (Phe-NAG) can also activate CPSase I, but with an activation constant that is 2-fold higher than that for NAG
Redox-regulated enzyme; in oxidative stress conditions methionine oxidation ensure a thermodynamic and structural compensatory mechanism to guarantee H(2)O(2) peroxidase activity despite transferase activity inhibition
Inactivated by oxidation of Cys-15 to a sulfenic acid
Exists as both a dimer and a tetramer and the equilibrium between the active tetramer and inactive dimer is regulated by several allosteric effectors, including protein concentration, pH, ADP, ATP, AMP-PNP, and F6P. ADP, ATP, low pH, and AMP-PNP shift the equilibrium toward the dimer
Inhibited the trifluoromethyl compound PF-3845
Allosteric enzyme with a cooperative mechanism; at least two neighbor subunits influence each other strongly in spastin hexamers (PubMed:22637577). Microtubule binding promotes cooperative interactions among spastin subunits (PubMed:22637577). ATP-bound enzyme interacts strongly and cooperatively with microtubules; this interaction stimulates ATP hydrolysis (PubMed:23745751)
Inhibited by RANBP9
Adenylyltransferase activity is inhibited by antitoxin VbhA; which acts by competing with ATP-binding at Arg-147 and prevents productive ATP-binding
Competitively inhibited by L- and D-alanine
Phosphatase activity is strongly reduced by the protein phosphatase inhibitor 2 (I-2) (PubMed:21222654, PubMed:26943172). Phosphatase activity is strongly reduced by PYL11, an abscisic acid (ABA) receptor (PubMed:26943172)
Its inhibitory activity is greatly enhanced in the presence of glycosaminoglycans, heparin, thrombomodulin and phospholipids vesicles
Subject to allosteric activation by ADP and other diphosphonucleosides, and inhibition by phosphoenolpyruvate
Inhibited by D-alanine and D-7-keto-8-amino-pelargonic acid
Moderate substrate inhibition. Not inhibited in vitro by acylcyclohexanediones
Phosphatase activity is inhibited in vitro by low concentrations of several heavy metals (zinc chloride, sodium molybdate, magnesium chloride, and copper sulfate) and moderately high concentrations (>8 mM) of EDTA
Activated by magnesium ions (PubMed:25545638). Activated by calcium ions (PubMed:25545638). Inhibited by the serine hydrolase inhibitor phenylmethanesulfonyl fluoride (PMSF) (Probable)
Activated by phosphorylation on Thr-189 by STK11/LKB1
Completely inhibited by 2'-O-methylation on the substrate RNA
Inhibited by neomycin
Phosphorylation at Thr-14 or Tyr-15 inactivates the enzyme, while phosphorylation at Thr-160 activates it (By similarity). Activated by spdya
Inhibited by malonyl-CoA
The two-component system is activated by envelope stress such as overexpression of some (misfolded) periplasmic proteins (PubMed:7883164, PubMed:9351822). Activated by spheroplasting (which removes the periplasm) in an autoregulatory cpxA-cpxR-dependent fashion (PubMed:10972835). Cpx two-component system is induced at pH 8.0; in a degP deletion mutant induction is halved (PubMed:9473036, PubMed:16166523). The kinase activity is inhibited by periplasmic accessory protein CpxP; proteolysis of CpxP relieves inhibition (PubMed:16166523, PubMed:17259177, PubMed:25207645). Autokinase activity reconstituted in liposomes is 50% inhibited by periplasmic accessory protein CpxP, but CpxP has no effect on phosphatase activity; autokinase stimulated by KCl, NH(4)Cl, RbCl, pH 7.5 and 8.0, inhibited by sensor kinase inhibitors tetrachlorosalicylanilid and ethodin (PubMed:17259177)
Activated by growth factors and cytokine receptors through a tyrosine-kinase-dependent mechanism. Activated by RAS. IC87114 inhibits lipid kinase activity and is selective in cells at doses up to 5-10 uM. IC87114 blocks T-cell receptor signaling in naive and memory T-cells and reduces cytokine production by memory T-cells
Classic and trans-signaling are both inhibited by tocilizumab, a humanized monoclonal antibody that blocks interleukin IL6R signaling
The full-length protein before cleavage is inactive: intramolecular interactions between N- and C-terminal domains mediate autoinhibition in the absence of activation signal (By similarity). The intrinsic pyroptosis-inducing activity is carried by the released N-terminal moiety (Gasdermin-A, N-terminal) following cleavage by bacterial effector protein SpeB (PubMed:35110732)
Copper uptake is inhibited by cold temperature, silver and zinc ions (PubMed:23123662). Platinum-containing chemotherapeutic agents uptake is inhibited by cold temperature and copper (PubMed:23123662)
Active when the heme iron is in the ferrous state (PubMed:14556637). Activated by FMN, Fe(2+), Sn(2+), Na(2)SO(3), Na(2)S and vitamin K3 (PubMed:14556637)
Specifically inhibited by an endogenous cardiac glycoside, ouabain
Under non-stress conditions, Spx is degraded by ClpXP and, to a lesser extent, by ClpCP (PubMed:12057962, PubMed:12642660, PubMed:19074380). Efficient dedradation by ClpXP requires the adapter protein SpxH/YjbH (PubMed:17908206, PubMed:19074380). Binding to SpxH/YjbH reduces the overall conformational flexibility of Spx and stabilizes the C-terminal ClpX recognition region of Spx (PubMed:30982633). In addition, activity is modulated by the formation of a disulfide bound within the N-terminal Cys-X-X-Cys (CXXC) motif, which is required for the transcriptional activation of trxA and trxB, or for the activation of msrAB operon expression following paraquat oxidative stress (PubMed:15659166, PubMed:18662407). However, it seems that formation of the disulfide bound is not essential for induction of all Spx-controlled genes, as for example the case of BSH biosynthesis genes (PubMed:23894131). Similarly, induction of the Spx regulon during cell wall stress is not accompanied by oxidation of the disulfide switch, but requires Spx stabilization by the anti-adapter protein SpxO/YirB (PubMed:29271514, PubMed:30001325)
Cystathionine beta-lyase activity is inhibited by sweat components such as glycine, serine and ammonium sulfate. Inhibited by cystathionine at a concentration higher than 6 mM
Activated by dithiothreitol and p-chloromercuribenzoate. Inhibited by trimethoprim, methotrexate, sodium tetrathionate and hydroxymercuribenzoate
Inhibited by metal- and zinc-specific inhibitors, such as EDTA and 1,10-phenanthroline in vitro. Is resistant to all inhibitors of serine, cysteine and aspartic proteases
Activated by arachidonic acid (AA)
(Microbial infection) Antiviral activity is neutralized by the HIV-1 virion infectivity factor (Vif), that prevents its incorporation into progeny virions by both inhibiting its translation and/or by inducing its ubiquitination and subsequent degradation by the 26S proteasome
Analogs of L-carnitine such as D-carnitine, glycine betaine and choline, are competitive inhibitors of L-carnitine oxidation
Proteinase K-treated enzyme exhibits improved affinity for the substrate, increased activity and increased thermostability
Autoinhibited. Intramolecular binding of the interdomains A and B (also called linker region) to parts of the catalytic domain keep the catalytic center in an inactive conformation. The phosphorylation of the interdomains or the binding of the SH2 domains with dually phosphorylated ITAM domains on transmembrane proteins disrupt those intramolecular interactions allowing the kinase domain to adopt an active conformation. The phosphorylation of SYK and of the ITAM domains which is responsible for SYK activation is essentially mediated by SRC subfamily kinases, like LYN, upon transmembrane receptors engagement. May also be negatively regulated by PTPN6 through dephosphorylation (By similarity). Downstream signaling adapters and intermediates like BLNK or RHOH may mediate positive and/or negative feedback regulation. Negatively regulated by CBL and CBLB through ubiquitination and probable degradation. Phosphorylates SH3BP2 which in turn may regulate SYK through LYN (By similarity)
Activated by dithioerythritol (DTE) (in vitro)
Negatively regulated by the anti-sigma-I factor RsgI1 (PubMed:20937888). Binding of the polysaccharide substrate to RsgI1 may lead to the release and activation of SigI1 (Probable)
Inhibited by citronellyl diphosphate
Inhibited by 1 uM borrelidin (BN)
ATPase activity is slightly increased in the presence of HisM and HisQ, and strongly increased when HisJ is also present
Inhibited by NB-598 ((E)N-ethyl-N-(6,6-dimethyl-2-hepten-4-ynyl)-3-[(3,3'-bi-thiophen-5-yl)methoxy]benzene-methanamine). Contrary to fungal enzymes, the mammalian enzyme is only slightly inhibited by terbinafine (PubMed:30626872). Inhibited by tellurite, tellurium dioxide, selenite, and selenium dioxide (PubMed:10666321)
Activated by phosphatidic acid (By similarity). Inhibited by rolipram
ATPase activity is inhibited by phosphorylation at Ser-162 (PubMed:28636601, PubMed:30478378). ATPase activity is inhibited by vanadate, fluorescein isothiocyanate, N,N'-dicyclohexylcarbodiimide and N-ethylmaleimide
Allosterically activated by GTP. Can also be activated by dGTP and 3'-anthraniloyl-2'-deoxyguanosine-5'-triphosphate (Ant-dGTP). Inhibited by UTP, 5-bromo-UTP and 5-iodo-UTP
Competitively inhibited by UDP-glucose. Activated by phosphorylation, which may increase affinity for NAD(+); inhibited by dephosphorylation
Activated by AGD10
Phosphatase activity inhibited by L(+)-tartrate, and by its derivative, alpha-benzylaminobenzylphosphonic acid
Regulated by Mg(2+) ions, cytosolic Mg(2+) selectively inhibits outward current while lysosomal Mg(2+) modestly inhibits both the outward and inward currents. In the absence of Mg(2+), NAADP readily activates TPCN2, with properties similar to PI(3,5)P2 (By similarity). Na(+) current is inhibited by ATP in a MTORC-dependent manner. ATP sensitivity is independent of PI(3,5)P2 (PubMed:23394946). Both current elicited by PI(3,5)P2 as well as NAADP are inhibited by tetrandrine
Activated by Triton X-100, insensitive to inhibition by adenosine and inhibited by wortmannin (By similarity). The PI4K complex acts as a regulator of phosphatidylinositol 4-phosphate (PtdIns(4)P) synthesis. Interaction with TMEM150A regulates PtdIns(4)P synthesis (By similarity)
Activated by Ca(2+)/calmodulin. Binding of calmodulin results in conformational change that relieves intrasteric autoinhibition and allows autophosphorylation of Thr-286 which turns the kinase in a constitutively active form and confers to the kinase a Ca(2+)-independent activity
GTPase activity is increased by binding to phospholipid membranes
Non-allosteric. Competitively inhibited by PPi, Pi and fructose 1,6-bisphosphate
Inhibited by Co(2+), Zn(2+), Cd(2+) and Pb(2+) ions. Inactivated by Hg(2+) and Cu(2+) ions
Inactivated by cobalt, nickel and zinc ions
Activated by Zn(2+) ions at low concentrations (10 uM) and inhibited by Zn(2+), Fe(2+) and Ni(2+) at high concentrations (10 mM)
Activated by Co(2+) and Ni(2+) ions, however Mg(2+) ion shows almost no significant effect on the activity. Equally inhibited by ADP, CTP and GTP, while dTTP and UTP are less inhibitory
Inhibited by the phenyltriazole acetic acid compound [5-(4-chlorophenyl)-1-isopropyl-1H-[1,2,4]triazol-3-yl]-acetic acid (DAS734), a bleaching herbicide. Repressed by AMP, ADP, ATP and GTP, and slightly by GMP
Fibrinolytic and caseinolytic activities are inhibited by Cd(2+), Cu(2+) and Co(2+) ions. Not inhibited by Mg(2+), Ca(2+) and Ba(2+). Also inhibited by EDTA, EGTA and 1,10-phenanthroline (By similarity)
The 2Fe-2S present in the homodimer leads to inactivation of the enzyme. The 2Fe-2S may serve as a redox sensor: the presence of one-electron oxidants or reductants leading to the loss of the 2Fe-2S cluster, subsequent monomerization and activation of the enzyme (By similarity)
Activity is strongly promoted by Co(2+), Ni(2+), Mg(2+), Cu(2+) and Mn(2+) (PubMed:27322068). Activity is inhibited by EDTA (PubMed:27322068)
Binding to the alpha subunit is required for catalytic activity
GABA transport is inhibited by beta-alanine, L-2,4-Diaminobutyric acid, hypotaurine and nipecotic acid (PubMed:1400419, PubMed:22896705). Taurine transport is inhibited by hypotaurine, beta-alanine and nipecotic acid (PubMed:22896705)
Inhibited by zinc ions (By similarity). Enzyme purified in the absence of 1,10-phenanthroline contains on average 0.4 zinc atoms per subunit. Inhibited by 4-hydroxy-nonenal through the formation of a covalent adduct with His-173. Competitively inhibited by N(5)-iminopropyl-ornithine
Subject to high-substrate inhibition by glutathione
Strongly inhibited by manganese at concentration higher than 20 uM
Classical (or conventional) PKCs (PRKCA, PRKCB and PRKCG) are activated by calcium and diacylglycerol (DAG) in the presence of phosphatidylserine. Three specific sites; Thr-500 (activation loop of the kinase domain), Thr-642 (turn motif) and Ser-661 (hydrophobic region), need to be phosphorylated for its full activation. Specifically inhibited by enzastaurin (LY317615)
The expression of auh activity is antagonistically regulated by cyclic AMP and agmatine. In the presence of the cAMP receptor protein, cAMP represses the expression of AUH, while agmatine induces it
Inhibited by methanol and phenylmethylsulfonicfluoride (PMSF)
Tris binds the active site and may act as an inhibitor
The enzymatic activity depends on the availability of cytosolic levels of UDP-GlcUA and UDP-GlcNAc
ADGRG1 NT is proposed to inhibit receptor signaling; its interactions with extracellular ligands and /or homophilic ADGRG1 NT interactions may relieve the inhibition. Following ligand binding to the N-terminal fragment, the N-terminal fragment is released from the seven-transmembrane C-terminal fragment to unveil a new N-terminal stalk, which then stimulates G-protein-dependent signaling activity. The N-terminal stalk has also been shown to be dispensable for at least some G-protein-dependent signaling
Activity of CodY is modulated by interaction with two types of effectors: the branched-chain amino acids (BCAAs) leucine, isoleucine and valine, which are signals of the nutritional status of the cell, and GTP, which may signal the energetic status of the cell
Inhibited by EDTA and activated by calcium and magnesium (By similarity). Inhibited by laminarin sulfate and, to a lower extent, by heparin and sulfamin
Subject to allosteric regulation. Activated by ADP (PubMed:14659072). Inhibited by GTP and ATP (PubMed:14659072). ADP can occupy the NADH binding site and activate the enzyme. Inhibited by SIRT4 (By similarity). Inhibited by HADH (By similarity)
The activity is completely impaired by Ag(+), partially inhibited by Zn(2+), and enhanced by Co(2+), Ni(2+) and Cu(2+) by 22.6, 14.5 and 20.8 %, respectively (PubMed:27193267). Ca(2+), Na(+), Mg(2+), Mn(2+), urea and EDTA do not significantly affect the mannanase activity (PubMed:27193267)
Deubiquitination by USP17L2/USP17 negatively regulates the proteolytic activity toward Ras GTPases
Inhibited by p-hydroxymercurybenzoate. The inhibitory concentration 50% (IC(50)) is 13 uM. Inhibited by bestatin. The inhibitory concentration 50% (IC(50)) is 7 nM at pH 9.5
Under complex allosteric control mediated by deoxynucleoside triphosphates and ATP binding to separate specificity and activation sites on the large subunit. The type of nucleotide bound at the specificity site determines substrate preference. It seems probable that ATP makes the enzyme reduce CDP and UDP, dGTP favors ADP reduction and dTTP favors GDP reduction. Stimulated by ATP and inhibited by dATP binding to the activity site (By similarity)
In isolated subunit ATPase and 5'-3' helicase activity are inhibited by non-hydrolyzable ATP analogs and EDTA (PubMed:12815438). After reacting with DNA bearing a Chi site the holoenzyme is disassembled and loses exonuclease activity, DNA unwinding and Chi-directed DNA cleavage; RecB remains complexed with ssDNA, which may prevent holoenzyme reassembly (PubMed:10197988). High levels of Mg(2+) (13 mM MgCl(2+)) or incubation with DNase allow holoenyzme reassembly, suggesting it is DNA bound to RecB that prevents reassembly (PubMed:10197988)
(Microbial infection) RecBCD is inhibited by the lambda virus gam protein (both GamL and GamS isoforms); in vitro a short preincubation prior to adding DNA results in maximal inhibition
Inhibited by dihydropyridines (DHP), such as isradipine. Channel activity is regulated by Ca(2+) and calmodulin
Inhibited by thiolactomycin
Kinase activity is activated upon binding to Rho proteins (RHOA, RHOB and RAC1). Activated by lipids, particularly cardiolipin and to a lesser extent by other acidic phospholipids. Activated by caspase-3 (CASP3) cleavage during apoptosis. Two specific sites, Thr-774 (activation loop of the kinase domain) and Ser-916 (turn motif), need to be phosphorylated for its full activation
Strongly inhibited by asialofetuin and asialomucin
Inhibited by arginine
Activated by CHAPS (PubMed:9490062). Inhibited by chlorpyrifos oxon (IC(50)=0.21 nM), paraoxon (IC(50)=0.29 nM), or methyl paraoxon (IC(50)=49 nM) (PubMed:18762277)
Inhibited by all-trans-retinyl alpha-bromoacetate and N-boc-L-biocytinyl-11-aminoundecane chloro-methyl ketone (BACMK)
Prematurely activated/folded staphopain B is inhibited by staphostatin B (SspC), which is probably required to protect staphylococcal cytoplasmic proteins from degradation by SspB
Inhibited by the efflux inhibitor and energy decoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP)
Inhibited by the propeptide produced by autocleavage (By similarity). Long isoform of CD74/Ii chain stabilizes the conformation of mature CTSL by binding to its active site and serving as a chaperone to help maintain a pool of mature enzyme in endocytic compartments and extracellular space of APCs. IFNG enhances the conversion into the CTSL mature and active form (By similarity). Inhibited by CST6. Inhibited by the glycopeptide antibiotic teicoplanin. Inhibited by amantadine (By similarity)
Activin receptor type-2 (ACVR2A or ACVR2B) activates the type-1 receptor through phosphorylation of its regulatory GS domain
Arabinose converts the repressor form of AraC to the activator form to regulate the araBAD promoter (PubMed:2962192, PubMed:3279415). In the absence of arabinose, AraC binds to the araO2 and araI1 half-sites in the promoter region of the araBAD operon, leading to the formation of a DNA loop that blocks access of RNA polymerase to the promoter. In the presence of arabinose and the cyclic AMP receptor protein (CRP), it binds to the adjacent half-sites araI1 and araI2, leading to the binding of RNA polymerase to the promoter region and transcription of the araBAD operon (PubMed:2962192, PubMed:3279415). AraI1 acts as a switch mechanism allowing both the repressor and the activator forms of AraC protein to regulate the araBAD promoter (PubMed:2962192, PubMed:3279415). Inhibited by D-fucose, which binds competitively to the same site on the protein (PubMed:9367758)
Inhibited by zinc ions and sulfate
Norfloxacin transport is inhibited by CCCP
Allosterically activated by magnesium, and possibly also other divalent metal cations. Allosterically activated by ATP, ADP or GTP (By similarity)
The side chain of Glu-204 determines which of the two opposing activities (AMPylase or de-AMPylase) will take place. In response to endoplasmic reticulum stress, mediates de-AMPylase activity (By similarity). Adenylyltransferase activity is inhibited by the inhibitory helix present at the N-terminus: Glu-204 binds ATP and competes with ATP-binding at Arg-344, thereby preventing adenylyltransferase activity (By similarity). In unstressed cells, disengagement of Glu-204 promotes adenylyltransferase activity (By similarity). Activation dissociates ATP-binding from Glu-204, allowing ordered binding of the entire ATP moiety with the alpha-phosphate in an orientation that is productive for accepting an incoming target hydroxyl side chain (By similarity)
Farnesyl- and geranyl-pyrophosphates are competitive inhibitors. Slightly inhibited by high concentration of ATP
Inhibited in feedback fashion by the catecholamine neurotransmitters, especially by dopamine in competition with tetrahydrobiopterin. Phosphorylation of several Ser/Thr residues in the N-terminus regulates the catalytic activity. Ser-31 and Ser-40 are readily phosphorylated to activate the catalytic activity. A Cysteine modification induced by N-ethylmaleimide (NEM), inhibits tyrosine 3-monooxygenase activity through the modification of the Cys-174
The redox states are modulated by H(2)O(2)
Activity is inhibited by 4,4'-Di-isothiocyanatostilbene-2,2'-disulfonic acid (DIDS - an inhibitor of several anion channels and transporters), gluconate, and by thiosulfate
Activity is inhibited by high concentrations of phosphorylcholine, phosphorylethanolamine, choline or betaine (PubMed:2116592, PubMed:15886911, PubMed:21515416). Displays different properties depending on the substrate utilized, the pH conditions as well as the presence or absence of metal ions (PubMed:10387109, PubMed:21660097). At pH 5, activity is inhibited by Al(3+) ions. At pH 7.4, the enzyme cannot catalyze the hydrolysis of pNPP, phosphorylethanolamine is a poor substrate in either the presence or absence of divalent cations, and activity measured with phosphorylcholine is independent of divalent cations or is not inhibited by Al(3+) ions (PubMed:10387109). Mg(2+) produces identical activation at pH 5.0 and 7.4, but Zn(2+) is an activator at pH 5.0 and becomes an inhibitor at pH 7.4 (PubMed:20135339). This inhibition at pH 7.4 may be due to a transition from octahedral to tetrahedral coordination geometry, which is produced by hydrolysis of the Zn-hexacoordinated complex (PubMed:20135339)
The uptake of taurocholate is inhibited by taurolithocholate sulfate with an IC(50) of 9 uM. Pravastatin competitively inhibits the transport of taurocholic acid (PubMed:18985798). Cyclosporin A, glibenclamide, rifampicin and troglitazonestrongly competitively inhibit the transport activity of taurocholate (PubMed:18985798). The canalicular transport activity of taurocholate is strongly dependent on canalicular membrane cholesterol content. The uptake of taurocholate is increased by short- and medium-chain fatty acids. Cholesterol increases transport capacity of taurocholate without affecting the affinity for the substrate (By similarity)
Alternates between an inactive form bound to GDP and an active form bound to GTP. Activated by guanine nucleotide-exchange factor (GEF) CDC25 and inactivated by GTPase-activating proteins (GAPs) IRA1 and IRA2
Stimulated NADPH--cytochrome reductase activity in the presence of substrate. Inhibited by fatty acid substrates longer than 13 carbons and the degree of inhibition increases with increasing chain length
Inhibited by GDP
Requires magnesium or manganese for optimal activity. Inhibited by high concentrations of cobalt and by cupric phenanthroline
Activity is maximal in the presence of calcium. However, unlike phospholipases A2 whose catalytic activity is strictly calcium-dependent, this enzyme shows considerable catalytic activity on phosphatidylcholine emulsified in calcium free solution
Activated by phosphatidic acid (PA). Binding with PA stimulates the activity by promoting the binding of substrate to the catalytic site
Inhibited by manganese, zinc, and copper ions
Inhibited by salicylic acid
Inhibited by N10-(bromoacetyl)-5,8-dideazafolate
Inhibited by GTP concentrations greater than 0.3 mM and by 2-amino-5-formylamino-6-ribofuranosylamino-4(3H)-pyrimidinone 5'-phosphate (fapyGMP). Partial inhibition is observed when 2 mM GMP, dGTP, or 7-methyl-GTP was included along with 2 mM GTP
Strongly inhibited by fetuin-A/AHSG
Inhibited by sulphydryl alkylating agents, 2-nitro-5-thiocyanatobenzoate (NTCB), 5,50-dithiobis(2-nitrobenzoic acid) (DTNB) and 1,2-benzisothiazolidine 3-one (BIT) at nanomolar concentrations
Channel activity is regulated by ancillary beta subunits. Interaction with a beta subunit is required for rapid channel inactivation and rapid recovery after inactivation, and prevents decrease of channel activity in response to repetitive, high-frequency depolarizations
Activated by dephosphorylation after osmotic stress or in presence of the fludioxonil fungicide
Calcium, lithium and sodium inhibit the exonuclease activity but not the DNA binding
Acyltransferase activity is regulated by the binding of GTP and Ca(2+): inactivated by GTP, which stabilizes its closed structure, thereby obstructing the accessibility of substrates to the active sites. In contrast, Ca(2+) acts as a cofactor by inducing conformational change to the active open form. In absence of Ca(2+), Mg(2+) may bind Ca(2+)-binding sites, promoting GTP-binding and subsequent inhibition of the acyltransferase activity
Activity is slightly stimulated by oleate
Fermentation of pyruvate to lactate is inhibited when bound to folliculin FLCN, perhaps partly by FLCN preventing binding of cofactor NADH (PubMed:34381247)
90% inhibited by cyanide and 2-heptyl-4-hydroxyquinoline N-oxide, at 1 mM and 40 uM respectively
Activity is allosterically regulated by the ATP/GTP ratio in a pH-dependent manner (PubMed:35338694). At pH 7.8, GTP has only a minor positive effect and ATP only a minor negative effect on the activity, however, at lower pH values, the effects of ATP and GTP increase (PubMed:35338694). ATP-dependent inhibition can be restored by increasing GTP concentration (PubMed:35338694). IMP and XMP are competitive inhibitors (PubMed:35338694)
Inhibited by copper and tungsten
Inhibited by glycerol and zinc ions
Activated in response to insulin. Autophosphorylation activates the kinase activity. PTPN1, PTPRE and PTPRF dephosphorylate important tyrosine residues, thereby reducing INSR activity. Inhibited by ENPP1. GRB10 and GRB14 inhibit the catalytic activity of the INSR, they block access of substrates to the activated receptor. SOCS1 and SOCS3 act as negative regulators of INSR activity, they bind to the activated INRS and interfere with the phosphorylation of INSR substrates
Inhibited by lauryldimethylamine oxide (LDAO) and dodecylphosphocholine (DPC)
The phosphatase activity of the PPP1R15A-PP1 complex toward EIF2S1 is specifically inhibited by Salubrinal, a drug that protects cells from endoplasmic reticulum stress (By similarity). Inhibited by the toxins okadaic acid, tautomycin and microcystin Leu-Arg
Enzymatic activity is diminished by Cd(2+) and Hg(2+)
Inhibited by diamox
Heme binding is inhibited by dipeptide
Subject to substrate inhibition and shows allosteric regulation by acetyl-CoA
Activated by the guanine nucleotide-exchange factors RAPGEF3 and RAPGEF4 in a cAMP-dependent manner. Nucleotide exchange is also specifically stimulated by RAPGEF5, RASGEF1A and RASGEF1B (By similarity)
Down-regulated by KIN10 that controls its protein stability under a phosphorylation-dependent manner
Inhibited by phenylmethylsulfonyl fluoride
Activated by L- and D-histidine (PubMed:16807956). Activated by L- and D-phenylalanine (PubMed:16686544). Activated by L-adrenaline (PubMed:17127057). Inhibited by coumarins, sulfonamide derivatives such as acetazolamide and Foscarnet (phosphonoformate trisodium salt) (PubMed:17314045, PubMed:19186056, PubMed:19206230, PubMed:18618712). Activated by histamine (PubMed:17127057)
Inhibited by calmodulin with an IC(50) of 50 nM. Calmodulin inhibits GRK5 association with receptor and phospholipid (By similarity)
Inhibited by S-nitrosylation (PubMed:10462479, PubMed:11461922). Inhibited by antizymes (AZs) OAZ1, OAZ2 and OAZ3 in response to polyamine levels. AZs inhibit the assembly of the functional homodimer by binding to ODC monomers. Additionally, OAZ1 targets ODC monomers for ubiquitin-independent proteolytic destruction by the 26S proteasome (PubMed:17900240). Inhibited by 1-amino-oxy-3-aminopropane (APA, an isosteric analog of putrescine) (PubMed:17407445). Irreversibly inhibited by alpha-difluoromethylornithine (DFMO) (PubMed:17407445)
Activated by methionine, inhibited by glycine
Alternates between an inactive form bound to GDP and an active form bound to GTP. Activated by the G protein coupled receptor (GPCR) GPR1, which serves as a guanine nucleotide-exchange factor (GEF), and inactivated by RGS2, acting as a GTPase-activating protein (GAP) for GPA2
No activity lost during treatment with 100 mM EDTA after 2 hours, and the addition of 1 mM MgCl(2), 1 mM CaCl(2) or 1 mM MnCl(2) has no effect. However, the enzyme activity is inhibited by Zn(2+), Cu(2+), Ni(2+) and Co(2+) to different extents. Addition of Na(+) or K(+) slightly stimulates the enzyme activity at low concentrations and the optimal concentration is 250 mM. A further increase of their concentration of ions above the optimum value results in a decrease in enzyme activity. The enzyme is still active even in the presence of Na(+) or K(+) at a concentration up to 5 M
Enzymatic activity is enhanced in the presence of phosphatidylserine
Proteolytic cleavage by CASP8 or MALT1 leads to its inactivation
Is totally inhibited by EDTA in vitro
Inhibited by 3-(4-benzyloxyphenyl)-2-(R)-amino-1-propanethiol (thioamine) and N-hydroxy-N-(2-(S)-amino-3-(4-benzyloxyphenyl)propyl)-5-carboxypen-tanamide (hydroxamic acid). The aminopeptidase activity is stimulated by LTA(4)
Chloride channel activity is allosterically activated by lumenal H(+) and Cl(-) leading to synaptic vesicles acidification. The L-glutamate transport activity is allosterically activated by lumenal H(+) and Cl(-). The allosteric activation by H(+) efficiently prevents non-vesicular efflux across the plasma membrane, thereby restricting L-glutamate transport activity to acidic membranes such as synaptic vesicles
In contrast to other LDT paralogs, LdtMt5 is not inactivated by the beta-lactams carbapenems, which don't form a covalent adduct with the enzyme
Induced by interleukin IL1B
Inhibited by Ca(2+) and Zn(2+)
Activated by phosphorylation on threonine and tyrosine by dual specificity kinases, MAP2K3/MKK3 MAP2K6/MKK6, MAP2K4/MKK4 and MAP2K7/MKK7. Activation by ultraviolet radiation, hyperosmotic shock, anisomycin or by TNF-alpha is mediated by MAP2K3/MKK3. Inhibited by dual specificity phosphatase DUSP1 (By similarity)
Channel activity is regulated by the ancillary beta subunit SCN1B (PubMed:29992740). SCN1B strongly enhances the presence of the pore-forming alpha subunit at the cell surface (PubMed:29992740, PubMed:30190309). Interaction with SCN1B is required for rapid channel inactivation and rapid recovery after inactivation, and prevents decrease of channel activity in response to repetitive, high-frequency depolarizations (By similarity). The channel is inhibited by tetrodotoxin and saxitoxin (PubMed:30190309)
Allosterically activated by binding 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol 4-phosphate) (phosphatidylinositol 4-phosphate) (PubMed:24045945, PubMed:25393116, PubMed:28302728, PubMed:31243363, PubMed:31515475, PubMed:34023399). Inhibited by orthovanadate, N-ethylmaleimide, trifluoroberyllate and tetrafluoroaluminate; orthovanadate and N-ethylmaleimide inhibit phosphorylation of the active site aspartic acid (PubMed:24045945, PubMed:19805341, PubMed:25393116, PubMed:19411703). The ATPase activity is not potently stimulated by phosphatidylinositol 3-phosphate and phosphatidylinositol 5-phosphate, phosphatidylinositol 4,5-bisphosphate or phosphatidylcholine (PubMed:24045945, PubMed:19805341, PubMed:19898464). Not inhibited by azide (PubMed:19805341)
Stimulated by calcium/calmodulin. Inhibited by n-Nos-inhibiting protein (PIN) which may prevent the dimerization of the protein (By similarity). Inhibited by NOSIP
Allosterically regulated by ATP (activator) and ADP (inhibitor) (By similarity). Cold labile, it dissociates into inactive monomers at low temperature (By similarity)
Feedback inhibited by tryptophan, tyrosine, phenylalanine and chorismate
Activated by guanosine analogs including deoxyguanosine, 7-thia-8-oxoguanosine or 7-deazaguanosine in a RNA-independent manner. Activated by imiquimod (PubMed:32706371)
Requires micromolar levels of Zn(2+) for activity (PubMed:26783088). Inhibited by millimolar levels of Zn(2+) (PubMed:25288789, PubMed:26783088)
Produced as a latent enzyme which is activated by dsRNA generated during the course of viral infection. The dsRNA activator must be at least 15 nucleotides long, and no modification of the 2'-hydroxyl group is tolerated. ssRNA or dsDNA do not act as activators
Repressor activity is regulated by binding of different substrates of the LfrA multidrug efflux pump, such as acriflavine, proflavine, ethidium bromide and rhodamine 123. Binding of these ligands causes the dissociation of LfrR from the promoter, inducing lfrA expression
Strongly activated by phosphatidic acid. Inhibited by phosphatidylethanolamine (PtdEtn), phosphatidylcholine (PtdCho), sphingomyelin and phosphatidylserine (PtdSer) (By similarity)
Phosphatidylinositol 3-kinase activity is directly dependent on VPS15 protein kinase activity
Binding to alpha subunit is required for catalytic activity
Activated by binding small G proteins. Binding of GTP-bound CDC42 or RAC1 to the autoregulatory region releases monomers from the autoinhibited dimer, enables phosphorylation of Thr-402 and allows the kinase domain to adopt an active structure. Following caspase cleavage, autophosphorylated PAK-2p34 is constitutively active (By similarity)
Phosphorylation by TodS probably induces conformational changes, which allow or alter the interaction with RNA polymerase in a process assisted by the integration host factor (IHF)
Inhibited by zinc, copper and nickel ions. Activated by 2-mercaptoethanol and inhibited by EDTA in vitro
Inhibited by cyclosporin A
Several specific inhibitors are being developed and tested
Stimulated ATPase activity by MINE1
Interaction with SBF1/MTMR5 increases phosphatase activity
Inhibited by the cysteine protease inhibitors leupeptin and cystatin-C
Autophosphorylation at His-118 increases serine/threonine protein kinase activity of the enzyme. Interaction with the SET complex inhibits exonuclease activity (By similarity)
Increased nitrate reductase activity is seen under hypoxic conditions, however this seems to be due to induction of the probable nitrate/nitrite transporter narK2 rather than increased enzyme activity
Activated upon binding to double stranded DNA or nucleosomes
Inhibited by duocarmycin analogs
The activity is dependent of the presence of oxygen
Inhibited by the proton gradient disruptor carbonyl cyanide m-chlorophenylhydrazone (CCCP), but not by the sodium gradient disruptor ouabain. Both xanthine and uric acid act as competitive inhibitors of uracil transport
Constitutive activity that does not require phosphorylation. Specifically inhibited by 3-(1H-indazol-5-yl)-N-propylimidazo[1,2-b]pyridazin-6-amine (CHR-6494)
Competitively inhibited by S-adenosyl-L-homocysteine (AdoHcy) and S-adenosyl-L-homocysteine (SAH). Sinefungin is only weakly inhibitory
Thiol-modulation by raising the activation threshold of the enzyme upon oxidation of the cysteines, thereby preventing wasteful ATP-hydrolysis
The C-terminal tail exerts an inhibitory effect on ssDNA binding
Activated by phosphatidic acid
Activated by autophosphorylation and homodimerization
Is inhibited by NaCl; more than half of the enzyme activity is abolished in the presence of 10 uM of NaCl
Activated by Gram-negative bacterial lipopolysaccharides and chymotrypsin
Binding of cAMP to the PRKAR1A or PRKAR1B regulatory subunits induces dissociation of the holoenzyme heterotetramer. The released monomeric PRKX is then active and able to phosphorylate its substrates
Redox regulation; active in reducing conditions, inactive in oxidizing conditions. Thioredoxins f and m mediate the reversible reductive activation of oxidized CHLI2
By bromopyruvate, oxalate, and phosphoenolpyruvate. Malate inhibits the activity to 50% at 1 mM concentration. Glycolate inhibits only at fairly high concentrations
Inhibited by cyclopropanone ethylhemiketal. Activated by ammonia (500mM), methylamine (5mM), ethylamine (5mM), octylamine (5mM), ethanolamine (5mM) and 1-amino-2-propanol (5mM), in assays using artificial electron acceptors (PubMed:3144289). Ammonia is not needed for, nor does it stimulate, the ethanol-oxidizing activity when using the natural electron acceptor cytochrome c550 (PubMed:8380982)
Inhibited by thiol-specific reagents (p-chloromercuribenzoate and 5,5'-dithio-bis-2-nitrobenzoate)
Tyrosine phosphorylation of the transporter leads to activation of the transport activity (PubMed:26979622). TEA uptake is activated by tyrosine phosphorylation (PubMed:26979622). Inhibited by cGMP, most likely through a cGMP-binding protein that interacts with OCT2 (PubMed:12395288)
GSH stimulates the transport of MRP4 (PubMed:17959747). Urate inhibits methotrexate transport but stimulates cGMP transport (PubMed:15454390). Nonsteroidal anti-inflammatory drugs (NSAIDs) strongly suppress the transport of MRP4 substrates (PubMed:12835412)
Activated by autophosphorylation at Thr-443
Target of two classes of inhibitors, coumarins and quinolones. Coumarins bind to GyrB and are competitive inhibitors with respect to ATP. Quinolones bind DNA gyrase when the enzyme is complexed with DNA and trap the enzyme in an abortive ternary complex (By similarity)
Methylation of H3R17 (H3R17me) by CARM1 is stimulated by preacetylation of H3 'Lys-18' (H3K18ac) H3 'Lys-23' (H3K23ac) by EP300 and blocked by citrullination of H3 'Arg-17' (H3R17ci) by PADI4
When cellular nitrogen levels are high, the C-terminal adenylyl transferase (AT) of GlnE inhibits GlnA by covalent transfer of an adenylyl group from ATP to Tyr-397. Conversely, when nitrogen levels are low, the N-terminal adenylyl removase (AR) of GlnE activates GlnA by removing the adenylyl group by phosphorolysis. The fully adenylated enzyme complex is inactive (Probable)
Activated during oocyte maturation by phosphorylation on Ser-362 by cdk-1. The pseudotyrosine phosphatases egg-4 and egg-5 sequester activated mbk-2 until the meiotic divisions and inhibit mbk-2 kinase activity directly, using a mixed-inhibition mechanism that does not involve tyrosine dephosphorylation
Inhibited by EDTA and EGTA, but not by PMSF and leupeptin
Up-regulated by glycerol and no inhibition by glucose
Inhibitied by high CoA concentrations
Phosphodiesterase activity is activated by phosphorylation of the N-terminal regulatory domain. Phosphorylation triggers a conformational change of the HD-GYP domain, which renders the active site accessible
Activated by phosphorylation on Thr-524
Reversibly gated by a two-step sulfenylation-persulfidation process in cells undergoing diverse stresses
Efficiently inhibited by Cu(2+) ion, Zn(2+) ion, sodium pyrophosphate and N-ethylmaleimide, while the addition of Mg(2+), Ca(2+) or Fe(3+) ions has minimal effect. Inhibited in a competitive manner by vanadate
Only slightly inhibited by wortmannin and LY294002. Activated by clathrin and insulin (By similarity)
ATPase activity is stimulated by interaction with MacA and inhibited by vanadate
Enhanced activity by NaCl. Enhanced activity by NAD(+). Strongly inhibited by UDP
Binding to RseA is inhibited by LPS fragments; phosphorylated N-acetylglucosamine (GlcNAc) with N-linked acyl chains are minimally necessary to disrupt binding to RseA. Once RseB is no longer bound to RseA the latter is susceptible to DegS degradation. Thus if periplasmic LPS levels increase the sigma-E regulon is induced (By similarity)
Nickel/cobalt import is reduced in the presence of zinc
Is physiologically inhibited by accumulation of the reaction product 5'-deoxyadenosine (PubMed:15911379). Inhibited by the AdoMet analog S-adenosyl homocysteine
Progressively inhibited by cobalt ions at concentrations between 10-50 mM and by copper ions at any concentration between 1-50 mM
ATG12-ATG5 induces reorientation of the ATG3 structure, increasing conjugation activity of ATG3
Phosphorylation of Thr-84 by OXSR1 inhibits activation (By similarity). Activated by binding small G proteins. Binding of GTP-bound CDC42 or RAC1 to the autoregulatory region releases monomers from the autoinhibited dimer, and enables activation by phosphorylation of Thr-423 (By similarity)
Activity is stimulated by divalent cations. Highest stimulation is observed with Ca(2+)
Activated by phosphorylation. In primary B lymphocytes, is almost always non-phosphorylated and is thus catalytically inactive. Stimulation of TLR8 and TLR9 causes BTK activation. As a negative feedback mechanism to fine-tune BCR signaling, activated PRKCB down-modulates BTK function via direct phosphorylation of BTK at Ser-180, resulting in translocation of BTK back to the cytoplasmic fraction. PIN1, SH3BP5, and IBTK were also identified as BTK activity inhibitors. Interaction with CAV1 leads to dramatic down-regulation of the kinase activity of BTK. LFM-13A is a specific inhibitor of BTK. Dasatinib, a cancer drug acting as a tyrosine kinase inhibitor, also blocks BTK activity
In the absence of viral infection, maintained as a monomer in an autoinhibited state and phosphorylation disrupts this autoinhibition leading to the liberation of the DNA-binding and dimerization activities and its nuclear localization where it can activate type I IFN and ISG genes
Maintained in an autoinhibited state via homodimerization in which the CARD domain forms an extensive interaction with the adjacent linker and coiled-coil regions (PubMed:31296852). Activation downstream of T-cell receptor (TCR) by phosphorylation by PRKCB and PRKCQ triggers CARD11 homooligomerization and BCL10 recruitment, followed by activation of NF-kappa-B (By similarity)
The apolipoprotein APOC2 acts as a coactivator of LPL activity (PubMed:12032167). Ca(2+) binding promotes protein stability and formation of the active homodimer (PubMed:16179346). Interaction with GPIHBP1 protects LPL against inactivation by ANGPTL4 (PubMed:27929370, PubMed:29899144). Inhibited by NaCl (PubMed:12032167)
Completely inhibited by chemical modifiers that are specific to Cys (HgCl(2) and p-chloromercuribenzoic acid), His (diethyl pyrocarbonate) and Ser (diisopropyl fluorophosphate and phenylmethanesulfonyl fluoride). No significant effect with chemical modifiers specific to Lys (pyridoxal 5'-phosphate) and Arg (phenylglyoxal). Not inhibited by inhibitors of A-esterases (paraoxon) or C-esterases (physostigmine/eserine). Activity is also not effected by incubation with 5 mM divalent cations for 30 minutes at 30 degrees Celsius or with 10 mM EDTA for 60 minutes at 75 degrees Celsius
Activated by cytosolic calcium, which is necessary for binding to membrane lipids (PubMed:1904318). Activated by phosphorylation in response to mitogenic stimuli (PubMed:10978317). Stimulated by agonists such as ATP and thrombin (PubMed:10978317)
Activity is inhibited by iron chelators
Repressed by metal ions, zinc ions having the strongest impact, and magnesium, cobalt, nickel, manganese and calcium ions acting as partial inhibitors (PubMed:15955071). Strongly inhibited by p-chloromercuribenzoic acid (PCMB) and, to a lower extent, by dithiothreitol (PubMed:15955071)
Inhibited by Li(+)
ATP hydrolysis occurs in the polymeric state (PubMed:24743229). Unlike for mammalian actin, ATP hydrolysis occurs also in the monomeric form and the release of inorganic phosphate (Pi) is more efficient (PubMed:24743229)
Non-competitively inhibited by sulfate
Binding to dsRNA, but not CDE RNA, crosstalks with the E3 ubiquitin ligase activity and may inhibit ubiquitination
Inhibited by phosphoramidon
Inhibited by gabaculine (5-amino-1,3-cyclohexadienylcarboxylic acid)
Regulated by a guanine nucleotide-exchange factor (GEF) and a GTPase-activating protein (GAP) and alternates between an inactive GDP-bound and an active GTP-bound form. In vitro, SGSM2 acts as its GAP and inactivates it by stimulating its GTPase activity
Inhibited by L-penicillamine
Subject to allosteric regulation (PubMed:15016359). Low glucose and high fructose-6-phosphate triggers association with the inhibitor GCKR followed by sequestration in the nucleus (PubMed:10456334)
Prematurely activated/folded staphopain B is inhibited by staphostatin B (SspC), which is probably required to protect staphylococcal cytoplasmic proteins from degradation by SspB. Also inactivated by E-64 and stimulated by EDTA
Not sensitive to heparin inhibition
Oligomerization is required for catalytic activity and is metal-dependent (PubMed:33303633). The type of metal that binds the 2 metal binding sites influences catalytic activity and substrate specificity (PubMed:19931315). In vitro, activated by Co(2+), Mn(2+), Ni(2+), Mg(2+) and Zn(2+) with decreasing strength (PubMed:19931315). Occupancy of the site 2 is essential and sufficient for activating the enzyme but occupation of the 2 sites is necessary for full catalytic activity (By similarity). Inhibited by Ca(2+) (PubMed:19931315). Inhibited by fungal metabolite bestatin (PubMed:19931315, PubMed:34133730)
Inhibited by pyridine 2,4-dicarboxylate, an analog of 2-oxoglutarate
Inhibited by SERPINB3 (By similarity). Activated by threonine and tyrosine phosphorylation by either of two dual specificity kinases, MAP2K4 and MAP2K7. MAP2K4 shows a strong preference for Tyr-185 while MAP2K7 phosphorylates Tyr-183 preferentially. Inhibited by dual specificity phosphatases, such as DUSP1
Stimulated by calcium and phosphatidylserine
Heparin inhibits the neuromuscular effect, myotoxin activity and edema-inducing effects (PubMed:10860537). Bromophenacyl bromide (BPB) inhibits the neuromuscular effect, the myotoxin activity and edema-inducing effects (PubMed:10860537)
Both aliphatic amines and carboxylic acids are able to inhibit non-competitively the catalytic activity (PubMed:9193681). The inhibition depends on the non-polar moiety of the substances (PubMed:9193681). Dioxane also acts as an inhibitor of NADase activity (PubMed:9193681). Auto-ADP-ribosylation acts as a mechanism of self-inactivation by its substrate (PubMed:9787786)
Host calmodulin is an absolute requirement for its activation (PubMed:2114169, PubMed:11807546). Inhibited by ethyl 5-aminopyrazolo[1,5-a]quinazoline-3-carboxylate (PubMed:12676933)
NAD(+) hydrolase activity is strongly stimulated by c-di-GMP, weakly by 3'3'-cGAMP, very weakly by c-di-AMP and not at all by 2'3'-cGAMP. Self-association of TIR domains is required for NADase activity
ATPase activity is stimulated by microtubules, which promote homooligomerization. ATP-dependent microtubule severing is stimulated by interaction with mei-2
The reaction is stimulated by the presence of HSD17B12, the enzyme catalyzing the second step of the elongation cycle
Cleavage and activation of PanD is accelerated by PanM
Inhibited by chenodeoxycholic acid (CDCA) and its conjugated derivatives, taurochenodeoxycholic acid and glycochenodeoxycholic acid (PubMed:29378847). Inhibited by fluoride (PubMed:16185196)
Inhibition occurs with substrate concentrations above 25 uM
The acyltransferase activity is inhibited by heme
Inhibited by sodium azide, SDS and mercaptoethanol, but not by 4-hexyl resocinol, L-cysteine and dithiothreitol. Activity is inhibited by the heavy metal ions Cr, W, Sn, Ag(+) and Hg(2+), but not by Pb(2+), Fe(3+), Ni(2+), Li(2+), Co(2+) or Cd(2+)
Strongly inhibited by inositol hexakisphosphate
Binding of ATP strongly enhances the affinity of TyrR for tyrosine
Activity is inhibited by binding to OTUB1, which prevents 'Lys-63'-linked polyubiquitination (PubMed:20725033, PubMed:22325355, PubMed:22367539). Activity is inhibited by GPS2, leading to prevent 'Lys-63'-linked polyubiquitination (By similarity)
Activity stimulated by up to 40% in the presence of divalent cations such as BaCl(2), CaCl(2), MgCl(2) and MnCl(2) at 3 mM concentration, but inhibited by 82-85% in the presence of CdCl(2) and ZnCl(2) at 3 mM concentration
Inactivated by the begomovirus AL2 protein or the curtovirus L2 protein (PubMed:12671096). Activated by phosphorylation at Thr-176 by GRIK1/SNAK2 and GRIK2/SNAK1 (PubMed:19339507). Inhibited by trehalose-6-phosphate (PubMed:19193861)
Inhibited by sarcolipin (SLN), phospholamban (PLN) and myoregulin (MRLN) (PubMed:21697544, PubMed:22961106, PubMed:25640239). Reversibly inhibited by phospholamban (PLN) at low calcium concentrations (By similarity). Dephosphorylated PLN decreases the apparent affinity of the ATPase for calcium. This inhibition is regulated by the phosphorylation of PLN (By similarity). Enhanced by DWORF; DWORF increases activity by displacing sarcolipin (SLN), phospholamban (PLN) and myoregulin (MRLN) (PubMed:26816378)
Stimulated by phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate, activated by the phosphokinase C-alpha, by the ADP-ribosylation factor-1 (ARF-1), and to a lesser extent by GTP-binding proteins: RHO A, RAC-1 and CDC42
Atypical PKCs (PRKCI and PRKCZ) exhibit an elevated basal enzymatic activity (that may be due to the interaction with SMG1 or SQSTM1) and are not regulated by diacylglycerol, phosphatidylserine, phorbol esters or calcium ions. Two specific sites, Thr-412 (activation loop of the kinase domain) and Thr-564 (turn motif), need to be phosphorylated for its full activation. Might also be a target for novel lipid activators that are elevated during nutrient-stimulated insulin secretion (By similarity)
Inhibited by bicyclic azetidine BRD1389, which competes for L-phenylalanine
During the substrate-folding cycle, the two GroEL rings separate for effective substrate binding and chaperonin activity. Ring separation is triggered by ATP binding to the trans ring of the asymmetric GroEL:GroES complex and avoids formation of functionally impaired symmetric GroEL:GroES2 complexes (PubMed:29336887). Activity of the GroEL-GroES chaperonin complex requires Mg-ATP (PubMed:10532860, PubMed:9285593)
Inhibited by 3-nitropropionate (3-NP) and 3-bromopyruvate when M.tuberculosis grows on acetate, but not on glucose. Inhibition of ICL by 3-bromopyruvate is accomplished via dehalogenation of the inhibitor to form a covalent adduct with the active site Cys-191. Also inhibited by zinc and calcium ions
Pyruvate-stimulated
Allosterically activated by Mg-ATP. Inhibited by inorganic phosphate and formycin monophosphate
Not activated by inflammatory stimulation (PubMed:18285344). Inhibited by Cu(2+), Fe(2+), Ca(2+) and Mg(2+) (PubMed:18285344, PubMed:18156367). Activity is not affected by Co(2+) or Mn(2+) (PubMed:18285344)
Its activity is inhibited by trichostatin A (TSA) and butyrate, 2 well known histone deacetylase inhibitors. histone deacetylase inhibitor
Inhibited by N-phenylmaleimide (NPM) and diacetyl
Growth under standard conditions leads to moderate phosphorylation of mpkA and hppD and hmgA activities are balanced leading further to degradation of HGA and formation of 4-maleylacetoacetate (PubMed:19715768). Cell wall stress, resulting in disturbance of balanced hppD and hmgA enzyme activity, (with reduced hmgA activity), leads to HGA accumulation that polymerizes to pyomelanin (PubMed:19715768)
Inhibited by diethyl-p-nitrophenyl phosphate, diisopropyl fluorophosphate and [E]-6-[bromoethylene]-3-[1-naphthalenyl]-2H-tetrahydropyran-2-one
Inhibited by bee venom neurotoxin apamin (PubMed:8781233, PubMed:20562108). Inhibited by UCL 1684 and tetraethylammonium (TEA) (PubMed:20562108)
Phosphorylation at Ser-33 inhibits the kinase and activates the bisphosphatase
Inhibited by myricetin
In vitro inhibited by EDTA
Both the excision and insertion steps are inhibited by TnpB
Strongly inhibited by S-adenosyl-L-homocysteine and weakly by adenine and methionine
Arachidonic acid release is markedly increased by glypican, a glycosylphosphatidylinositol-anchored heparan sulfate proteoglycan
Inhibited by 4-O-alpha-D-glucopyranosylmoranoline (G1M)
Serine/threonine-protein kinase activity is inhibited by SPRED1
Inhibited by monoubiquitin and diubiquitin
Allosteric enzyme. Activity is modulated by K(+), divalent cations, UTP, and tetrahydrobiopterin. Tetrahydrobiopterin is an inhibitor of this enzyme (By similarity)
Strongly activated by phosphatidic acid. Inhibited by phosphatidylethanolamine (PtdEtn), phosphatidylcholine (PtdCho), sphingomyelin and phosphatidylserine (PtdSer)
Inhibited by inorganic arsenite such as phenylarsenoxides
Each dimer has two allosteric binding sites that can bind the regulatory effectors tryptophan or tyrosine (By similarity). Can bind either one tryptophan or one tyrosine, two tryptophan or two tyrosine or one tryptophan and one tyrosine, which differentially affect the catalytic activity (By similarity). Activated by tryptophan and subject to feedback inhibition by tyrosine (By similarity). In the presence of both tryptophan and tyrosine, the enzyme is in the activated state (By similarity)
Inhibited by the serine proteinase inhibitor 4-(2-aminoethyl)benzenesulphonyl fluoride (AEBSF), and by di-isopropylfluorophosphate (By similarity). Inhibited by Val-boroPro (Talabostat, PT-100), a non-selective inhibitor, which triggers pyroptosis in monocytes and macrophages (PubMed:27820798, PubMed:29396289). Val-boroPro inhibits activity by binding to the active site, mimicking a substrate-bound state, thereby displacing the C-terminal fragment of NLRP1, leading to activation of the NLRP1 inflammasome. In contrast, Val-boroPro does not directly displaces CARD8: it acts by promoting degradation of the N-terminal part of CARD8, leading to indirect disruption of the ternary complex (By similarity)
Activated by NDFIP1- and NDFIP2-binding (PubMed:25631046). Activated by PI4K2A-binding (PubMed:23146885). Inhibited by DTX3L-binding (PubMed:24790097). Inhibited by N4BP1 binding (By similarity)
Inhibited by the C-terminal non-catalytic region. Activated by caspase-cleavage. Full activation also requires homodimerization and autophosphorylation of Thr-185 (By similarity)
Inhibited by DFFA (DFF45)
Thr-14 and Tyr-15 are phosphorylated maximally during G2 phase, but dephosphorylated abruptly at the G2/M transition. Phosphorylation at Thr-14 and Tyr-15 inactivates the enzyme. During M phase it is also phosphorylated on Thr-161. Finally during G1 phase it is phosphorylated on Ser-277
Activated by forskolin. Activated by GNAS. Activity is further increased by interaction with the G protein beta and gamma subunit complex formed by GNB1 and GNG2 (By similarity). Is not activated by calmodulin. Inhibited by adenosine and ATP analogs. Inhibited by calcium ions, already at micromolar concentrations (By similarity). Phosphorylation by RAF1 results in its activation (By similarity)
Inactivated by EDTA (By similarity). Inhibition by zinc ions (Potential)
Allosterically regulated and controlled by phosphorylation. 5-phosphoribose 1-diphosphate is an activator while UMP is an inhibitor of the CPSase reaction (By similarity)
Strongly inhibited by fluoride ions
Activated following phosphorylation by p38-alpha/MAPK14 following various stresses. Inhibited following sumoylation. Specifically inhibited by pyrrolopyridine inhibitors (By similarity)
Competitively inhibited at the phosphate acceptor site by 3'-azido-3'-deoxythymidine monophosphate (AZT-MP) (in contrast to other TMPKs such as E.coli, in which it is a good substrate). Inhibition seems to result from the impossibility of magnesium binding
Activated by ATP and maltotriose, which are both required for DNA binding (PubMed:3305511, PubMed:2524384). Negatively regulated by MalY, MalK and Aes, which bind to MalT and block maltotriose activation (PubMed:9822819, PubMed:10692154, PubMed:11867639)
Inhibited by the antitubercular drug SQ109. Also inhibited by several other compounds such as the pyrrole derivative BM212, the adamantyl urea derivative AU1235, the benzimidazole C215, indoleamides, tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide (THPP) and N-benzyl-6',7'-dihydrospiro[piperidine-4,4'-thieno[3,2-c]pyran] (Spiro) analogs. Inhibitory effects of these compounds, including SQ109, are most likely due to their ability to dissipate the transmembrane electrochemical proton gradient
Inhibited by HgCl(2), iodoacetamide (IAA) and, to a far lesser extent, by SDS, hydrogen peroxide H(1)O(2), KCl, NaCl, ZnCl(2), AgSO(4), CdCl(2), FeCl(3), PMSF, Pepstatin A and EDTA (Ref.1, PubMed:24348183, PubMed:25043129). Repressed moderately by many organic solvents such as diethyl ether, ethy lacetate, acetophenone, butanol, trichloroethylene, tetrahydrofuran, methanol, chloroform and dichloromethane, and, to a lesser extent, by propanol, benzyl alcohol and chlorobenzene (PubMed:24348183)
Serine/threonine-protein kinase activity is directly stimulated by TOPBP1 (PubMed:16530042). ATR kinase activity is also directly activated by ETAA1, independently of TOPBP1 (PubMed:27723720, PubMed:27723717). Activated by DNA and inhibited by BCR-ABL oncogene (PubMed:10597277). Slightly activated by ATRIP (PubMed:14729973). Inhibited by caffeine, wortmannin and LY294002 (PubMed:9766667)
Inhibited by NPGB, leupeptin, aprotinin and PMSF, but not by EDTA, SBTI, heparin and hirudin
Inhibited by acetate, dimethylglycine and S-adenosyl-L-homocysteine
Inhibited by human TIMP-1 and TIMP-2 and by the peptide hydroxamate inhibitor (BB-94) (PubMed:10574937). Repressed by acetohydroxamic acid (AHA) (PubMed:24156403)
Allosteric activation by glucose-6-phosphate, and phosphorylation by a cAMP-dependent kinase
May be constitutively autocleaved; RecA is constitutively activated in this strain, leading to continuous transcription of recA
Activated by cadmium ions (PubMed:12473676). Inhibited by the metal chelator 1,10-o-phenantrolin. The inhibitory concentration 50% (IC(50)) is 5 uM
Activated by Mg(2+) or Mn(2+) and strongly inhibited by Zn(2+)
Inhibited by UDP, UTP and UDP-GlcNAc; 50 mM NaCl or KCl inhibit activity about 70%
Inhibited by bee venom neurotoxin apamin. Inhibited by d-tubocurarine and tetraethylammonium (TEA)
Activity is enhanced by ascorbate
Binding of oxidized quinones (produced as darkness falls) prevents KaiA from stimulating KaiC autophosphorylation
The catalytic activity is positively regulated by calcium via its binding to the calcium-binding site
Inhibited by putrescine. Activity is not affected by arginine and ornithine
Enhanced activation by VIK-mediated phosphorylation promoting carrier activity and consequently vacuolar sugar accumulation
Allosterically activated by benzodiazepines and pentobarbital (PubMed:1977069). Allosterically activated by the neuroanesthetic alphaxalone (By similarity). Inhibited by the antagonist bicuculline (PubMed:1977069, PubMed:1376242)
Inhibited by fluoride ions
Inhibited by isatin sulfonamides
GTPase-activating activity is inhibited in the folliculin complex (LFC), which stabilizes the GDP-bound state of rraga/RagA (or rragb/RagB), because Arg-164 is located far from the rragc/RagC or rragd/RagD nucleotide pocket. Disassembly of the LFC complex upon amino acid restimulation liberates the GTPase-activating activity
Nuclease activity is stimulated by interaction with MutL and inhibited in the presence of non-hydrolytic ATP (ADPnP). ATPase activity is stimulated by DNA
Hemagglutinating activity is slightly inhibited by alpha-methyl-D-mannopyranoside
Phosphorylation by mTORC1 stabilizes and activates GRB10 constituting a feedback pathway by which mTORC1 inhibits INSR-dependent signaling
Activity is strongly promoted by Co(2+), Ni(2+), Mg(2+) and Mn(2+) (PubMed:27322068). Activity is inhibited by EDTA (PubMed:27322068)
Activated by S-nitrosylation which promotes enzyme dimerization (PubMed:26851298). Cerulenin, a potent non-competitive pharmacological inhibitor of FAS, binds covalently to the active site of the condensing enzyme region, inactivating a key enzyme step in fatty acid synthesis (PubMed:16969344)
Not inhibited by neomycin
The xyloglucanase activity is inhibited by the binding of the host apoplastic glucanase inhibitor GIP1
Inhibited by the prolyl-hydroxylase inhibitors alpha,alpha'-dipyridyl and ethyl 3,4-dihydroxybenzoate
Is not regulated allosterically
Transglycosylase activity can be inhibited by moenomycin
Ras proteins such as HRAS mediate the activation of RAF proteins such as RAF1 or BRAF which in turn activate extracellular signal-regulated kinases (ERK) through MAPK (mitogen-activated protein kinases) and ERK kinases MAP2K1/MEK1 and MAP2K2/MEK2. Activation occurs through phosphorylation of Ser-218 and Ser-222 (By similarity). MAP2K1/MEK1 binds KSR1 or KSR2 releasing the inhibitory intramolecular interaction between KSR1 or KSR2 protein kinase and N-terminal domains (By similarity). This allows KSR1 or KSR2 dimerization with BRAF leading to BRAF activation and phosphorylation of MAP2K1 (By similarity). MAP2K1/MEK1 is also the target of negative feed-back regulation by its substrate kinases, such as MAPK1/ERK2. These phosphorylate MAP2K1/MEK1 on Thr-292, thereby facilitating dephosphorylation of the activating residues Ser-218 and Ser-222. Inhibited by serine/threonine phosphatase 2A (By similarity)
Inhibited by DFP
Inhibited by L-penicillamine. Beta-lactamase activity is inhibited by cilastatin
Activated by threonine and tyrosine phosphorylation (By similarity). Activated by the MAP kinase kinase MKK6 in vitro
Inhibited by HgCl2 and acetohydroxyamic acid slightly by EDTA, but not by boric acid or L-methionine-DL-sulfoximine
Isoleucine allosterically inhibits whereas valine allosterically activates this enzyme
Activated by pentobarbital (PubMed:2842688). Inhibited by the antagonist bicuculline (PubMed:2842688)
Inhibited by 42 nM hanatoxin 1 (HaTx1), a spider venom toxin of the tarantula G.spatulata. Inhibited by 100 nM stromatoxin 1 (ScTx1), a spider venom toxin of the tarantula S.calceata (By similarity). Modestly sensitive to millimolar levels of tetraethylammonium (TEA) and 4-aminopyridine (4-AP) (PubMed:2002364, PubMed:10414301, PubMed:15858231). Completely insensitive to toxins such as dendrotoxin (DTX) and charybdotoxin (CTX) (By similarity)
Activated through serine and threonine phosphorylation
Present in an inactive state in the absence of collagen binding and phosphorylation by SRC. Tyrosine phosphorylation enhances the affinity for ATP and the catalytic activity
Oxidation of 20-HETE is inhibited by low concentrations of N-heptylformamide (PubMed:16081420). Oxidation of 20-HETE is a decreased by 55-65% by either all-trans-retinol or all-trans-retinoic acid (PubMed:16081420). Strongly inhibited by omega-hydroxy fatty acids (PubMed:10514444)
Inhibited by EDTA and bromophenacyl bromide (BPB)
Inhibited by Hg(2+), Ag(+) and rho-chloromercuribenzoate
Both FBPase and IMPase activities are inhibited by Ca(2+). In contrast to mammalian I-1-P phosphatases, is only very weakly inhibited by Li(+) (with an IC(50) of about 290 mM)
Inhibited by methyl indoxam
Retinaldehyde reductase activity is inhibited by tolrestat
Activated by reductants such as dithiothreitol (DTT), and by thioredoxin in vivo, following exposure to light
Biotin uptake is weakly inhibited by CCCP and FCCP protonophores and by the respiratory chain blocker NaN(3)
Regulated predominantly by intracellular cAMP levels (PubMed:10720067). The 17,20-lyase activity is stimulated by cytochrome b5, which acts as an allosteric effector increasing the Vmax of the lyase activity (PubMed:9452426, PubMed:27339894)
Regulates splicing of its own pre-mRNA according to its kinase activity; increased expression of the catalytically active form influences splicing to generate the catalytically inactive splicing variant lacking the kinase domain. Leucettine L41 inhibits its kinase activity and affects the regulation of alternative splicing mediated by phosphorylation of SR proteins
Inhibited by tetrahydrofurane, acetonitrile and isopropanol
Inhibited by the C-terminal non-catalytic region. Activated by caspase-cleavage. Full activation also requires homodimerization and autophosphorylation of Thr-183. Activated by RASSF1 which acts by preventing its dephosphorylation
On oxidative stress, SENP3 degradation is blocked by inhibition of its ubiquitination, which stabilizes it as it accumulates in the nucleoplasm
Channel activity is inhibited by micromolar levels of zinc ions (PubMed:19910922). Channel activity is inhibited by ifenprodil (PubMed:19910922, PubMed:21677647)
Inhibited by the antimycobacterial compound BM212, a pyrrole derivative (PubMed:28698380). Inhibited by the antitubercular drug SQ109. Inhibited by the adamantyl urea derivative AU1235, the indole carboxamide ICA38 and rimonabant, the antagonist for the cannabinoid receptor CB1. The dissociation constant (Kd) values for SQ109, AU1235, ICA38 and rimonabant are 1.65 uM, 0.29, 0.16 and 29.5, respectively (PubMed:30682372). Inhibitory effects are due to binding of the inhibitors at the proton-transportation channel most likely dissipating the transmembrane electrochemical proton gradient needed for substrate translocation (PubMed:30682372, PubMed:32512002)
Activated by phosphorylation at Ser-360, Thr-581 and Thr-700 by MAPK1/ERK2, MAPK3/ERK1 and MAPK14/p38-alpha, and by further autophosphorylation of Ser-212, Ser-376 and Ser-381 by the activated C-terminal kinase domain. The active N-terminal kinase domain finally phosphorylates downstream substrates, as well as Ser-750, Ser-752 and Ser-758 in its own C-terminal region (By similarity)
Leucettine L41 inhibits its kinase activity and affects the regulation of alternative splicing mediated by phosphorylation of SR proteins
Enzyme activity is tightly regulated to prevent the accumulation of reactive oxygen species in the endoplasmic reticulum. Reversibly down-regulated by the formation of disulfide bonds between the active site Cys-94 and Cys-131, and between Cys-99 and Cys-104. Glutathione may be required to regulate its activity in the endoplasmic reticulum (By similarity)
Binding to mppa-1 is required for catalytic activity (PubMed:16788047). Inhibited by metal chelator ethylenediaminetetraacetic acid (EDTA) (PubMed:16788047)
Activated by phosphorylation on threonine and tyrosine
UDP-alpha-D-xylose (UDX) acts as a feedback inhibitor (PubMed:9737970). It binds at the same site as the substrate, but functions as allosteric inhibitor by triggering a conformation change that disrupts the active hexameric ring structure and gives rise to an inactive, horseshoe-shaped hexamer (By similarity)
O-acetyl-L-serine causes the CysE-CysK complex to dissociate in the absence of hydrogen sulfide
Negatively regulated by the anti-sigma-I factor RsgI7
Fenamirol efflux transporter activity is inhibited by the cyclosporin derivative PSC 833, nigericin, reserpine and valinomycin (PubMed:10954082). The effect of reserpine is transiant, while that of the cyclosporin derivative PSC 833, nigericin and valinomycin is proportional to the time of exposure (PubMed:10954082). Cyclohexinmide has inhibitory effect only when applied prior to addition of the fungicide (PubMed:10954082)
The disulfide bridge formed between Cys-33 in the propeptide and the active site residue Cys-92 may prevent activation of the zymogen through formation of a reversible covalent bond with the active site residue
Inhibited by Ca(2+). Mild inhibition by high levels of Mg(2+)(>10 mM) (PubMed:14960577)
Activated by potassium and sodium ions and inhibited by magnesium and calcium ions
The activity is strongly inhibited by riboflavin analogs, such as lumiflavin (PubMed:18632736, PubMed:20463145). Weakly inhibited by flavin adenine dinucleotide (FAD) (PubMed:18632736, PubMed:20463145)
TIMP-2 shows little inhibitory activity compared to TIMP-1. TIMP-1 seems to have less binding affinity than TIMP-2 for the short isoform
Gating is voltage-dependent and repressed by decavanadate (PubMed:15331675, PubMed:29211723). Calmodulin-binding confers the Ca(2+) sensitivity (PubMed:15590641). ATP is able to restore Ca(2+) sensitivity after desensitization (PubMed:15590641). ATP inhibits channel activity (PubMed:15331675, PubMed:14758478, PubMed:29211723). Phosphatidylinositol 4,5-bisphosphate (PIP2)-binding strongly enhances activity, by increasing the channel's Ca(2+) sensitivity and shifting its voltage dependence of activation towards negative potentials (PubMed:16186107, PubMed:16424899). Activity is also enhanced by 3,5-bis(trifluoromethyl)pyrazole derivative (BTP2) (PubMed:16407466)
Enzyme kinetics do not match Michaelis-Menten kinetics, suggesting allosteric behavior. Inhibited by high pantoate levels
Activated by forskolin (PubMed:17916776, PubMed:17110384). Inhibited by calcium ions, already at micromolar concentrations (By similarity). Inhibited by adenosine, AMP and their analogs (By similarity). Activated by GNAS (PubMed:17110384). Is further activated by the complex formed by GNB1 and GNG2 (PubMed:17110384). Phosphorylation by RAF1 results in its activation (By similarity)
Antiviral activity is neutralized by the HIV-1 virion infectivity factor (Vif), that prevents its incorporation into progeny virions by both inhibiting its translation and/or by inducing its ubiquitination and subsequent degradation by the 26S proteasome
Inhibited by EDTA (PubMed:9452493). Inhibited by 1-10-phenanthroline (PubMed:18937627). Inhibited by broad-spectrum zinc metalloprotease inhibitor batimastat (PubMed:28820255). N-aryl mercaptoacetamide-based inhibitors have been isolated that act on clostridial collagenases with submicromolar affinity while having negligibile activity on human collagenases (PubMed:28820255)
Inhibited by fosmidomycin and its derivative FT900098
The catalytic activity is inhibited by the binding of azoles clotrimazole, miconazole, fluconazole, ketoconazole, oteseconazole (VT-1161), tetraconazole, the triazole SCH39304, and the triazole derivative ICI 153066
Activated by cpn20/cpn21
The NAALADase and folate hydrolase activities are inhibited by quisqualic acid
Feedback inhibitions by L-Ser and acetyl-CoA
Inhibited by N-(6-oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide HCl (PJ34), 1,5-dihydroxyisoquinoline (DHQ) and 3-aminobenzamide (3AB)
Activated by threonine and tyrosine phosphorylation (By similarity). Activated by the MAP kinase kinase MKK2. Activated by the MAP kinase kinase MKK6 in vitro
Novel PKCs (PRKCD, PRKCE, PRKCH and PRKCQ) are calcium-insensitive, but activated by diacylglycerol (DAG) and phosphatidylserine. Three specific sites; Thr-507 (activation loop of the kinase domain), Ser-645 (turn motif) and Ser-664 (hydrophobic region), need to be phosphorylated for its full activation. Activated by caspase-3 (CASP3) cleavage during apoptosis. After cleavage, the pseudosubstrate motif in the regulatory subunit is released from the substrate recognition site of the catalytic subunit, which enables PRKCD to become constitutively activated. The catalytic subunit which displays properties of a sphingosine-dependent protein kinase is activated by D-erythro-sphingosine (Sph) or N,N-dimethyl-D-erythrosphingosine (DMS) or N,N,N-trimethyl-D-erythrosphingosine (TMS), but not by ceramide or Sph-1-P and is strongly inhibited by phosphatidylserine (By similarity). Inhibited by PRKCH upstream open reading frame 2 (PubMed:34593629)
Histone methyltransferase activity strongly stimulated by HSPCA
Activated through serine and threonine phosphorylation in response to wounding, cold, drought, salt stresses, abscisic acid (ABA), hydrogen peroxide, bacterial flagellin and laminarin beta-glucan
Its activity is inhibited by PMSF and p-nitrophenyl-p-guanidinobenzoate (NPGB)
Strongly inhibited by FK506 and L-685,818
The apoenzyme can be activated in vitro in the presence of nickel ions and carbon dioxide, which promotes carbamylation of 'Lys-217' of the UreC (alpha) subunit
Regulated by F-actin polymerization and probably by calcium
Inhibited by RCVRN, which prevents the interaction between GRK1 and RHO (PubMed:12686556, PubMed:21299498). Inhibition is calcium-dependent (PubMed:12686556)
Less sensitive to inhibition by cyclosporin A than is CYP-18
Completely inhibited by EDTA, EGTA, 1,10-phenanthroline, and partially by beta-mercaptoethanol. Is not inhibited by aprotinin and leupeptin
Carbon monoxide (CO) and the redox state of the cell can modulate the transcriptional activity of the NPAS2-BMAL1 heterodimer. NADH and NADPH enhance the DNA-binding activity of the heterodimer whereas CO binds the heme group in NPAS2 and inhibits the DNA-binding activity of the heterodimer
Requires cobalamin (vitamin B12) for repressor activity. In the dark, binding of cobalamin to CarH induces its oligomerization, which enhances binding to the DNA and repressor activity. Light causes cobalamin photolysis and disruption of the cobalamin-CarH complex, which decreases interaction with DNA and allows transcription of the carB operon. Interaction with CarS also prevents binding to DNA
Inhibited by Ca(2+) ions and by high chloride ion concentration. By contrast, low chloride concentration (up to 50 mM) slightly activate the enzyme
Inhibited by 5-aminovalerate, mercaptoacetate, 3-mercaptopropionate and 2-mercaptoethanol
Inhibited by EDTA and sulfhydryl reagents such as p-chloromercuribenzoic acid (PubMed:7766084). Both OSBS and NAAAR activities are inhibited competitively by salicylhydroxamate (PubMed:10194342)
No inhibition by the antibiotic cerulenin
Activated by homooligomerization induced by direct binding to cytosolic LPS
Not stimulated by calcium/calmodulin. Aspirin inhibits expression and function of this enzyme and effects may be exerted at the level of translational/post-translational modification and directly on the catalytic activity (By similarity)
Inhibited by PMSF and soybean trypsin inhibitor. Partially inhibited by L-cysteine and DTT. Not affected by EDTA
Inhibited by clavulanic acid
Inhibited by EDTA and DTT, and partially inhibited by EGTA, but not inhibited by PMSF and NEM
Irreversible aggregation upon several stress conditions prevents interaction with Spx and therefore leads to Spx stabilization (PubMed:25353645). Inhibited by interaction with SpxO/YuzO (PubMed:21378193)
Inhibited by Li(2+)
Methyltransferase activity is activated by RAMAC (PubMed:27422871)
Inhibited by D-Phe-Pro-Arg-chloromethyl ketone (FPRCK) (98%), PMSF (93%), benzamidine (67%), and diisopropylfluorophosphate (DFP). Is not inhibited by BPTI, antithrombin and EDTA
Strongly inhibited by isoascorbic acid, 4-hydroxyacetophenone and 4-chloromercuriphenylsulphonate. Stimulated by various salts
Reversibly inhibited by inhibited by phaseolotoxin and octicidine
Calcium ions are required for optimal activity, but do not seem to be essential since addition of EDTA causes only a 48% drop in activity
Activated by phosphatidic acid binding. Activated by hydrogen peroxide (in vitro). Activated by reactive oxygen species (ROS)
In contrast to yeast cyclase, S.pombe cyclase is not likely to be regulated by RAS proteins. Activated by git1
Displays pH dependent redox properties (PubMed:33559753). SufD is necessary for the stability of FhuF (PubMed:10322040)
Cleavage stimulated by PCNA123 and PCNA323 (PubMed:18782564) and by RadC2 (PubMed:22437993)
Activated upon amino-acid starvation
Copper(1+) transport is stimulated by extracellular acidic pH and high potassium ions concentrations (PubMed:11734551). Copper(1+) import is regulated by a copper(1+)-dependent recycling of SLC31A1 (PubMed:19740744)
Inhibited by glucose
The enzyme activity is strongly increased by double-stranded DNA (dsDNA), but not by single-stranded DNA or RNA (PubMed:23258413, PubMed:23707061, PubMed:26300263). DNA-binding induces the formation of liquid-like droplets in which CGAS is activated (PubMed:29976794, PubMed:33606975). Liquid-like droplets also create a selective environment that restricts entry of negative regulators, such as TREX1 or BANF1/BAF, allowing sensing of DNA (PubMed:33606975). A number of mechanisms exist to restrict its activity toward self-DNA (PubMed:31299200, PubMed:33051594, PubMed:32911482, PubMed:32912999, PubMed:33542149, PubMed:32792394). The nucleotidyltransferase activity is inhibited in the nucleus via its association with nucleosomes: interacts with the acidic patch of histones H2A and H2B, thereby blocking DNA-binding and subsequent activation (PubMed:31299200, PubMed:33051594, PubMed:32911482, PubMed:32912999). CGAS is also inactive when associated with mitotic chromatin (PubMed:33542149). Chromatin-bound CGAS cannot be activated by exogenous DNA in mitotic cells: phosphorylation of the N-terminal disordered part by AURKB during the G2-M transition blocks CGAS liquid phase separation and activation (PubMed:33542149). Activity toward self-DNA is inhibited by BANF1/BAF upon acute loss of nuclear membrane integrity: BANF1/BAF acts by outcompeting CGAS for DNA-binding, thereby preventing CGAS activation (PubMed:32792394). DNA-induced activation at micronuclei is also limited by TREX1, which degrades micronuclear DNA upon nuclear envelope rupture, thereby preventing CGAS activation (PubMed:33476576). Acetylation at Lys-384, Lys-394 and Lys-414 inhibits the cyclic GMP-AMP synthase activity (PubMed:30799039). Inhibited by aspirin (acetylsalicylate) drug, which acetylates CGAS (PubMed:30799039). Acetylation by KAT5 increases the cyclic GMP-AMP synthase activity by promoting DNA-binding and subsequent activation (PubMed:32817552). Phosphorylation at Ser-305 suppresses the nucleotidyltransferase activity (PubMed:26440888). Phosphorylation at Ser-435 promotes the cyclic GMP-AMP synthase activity (PubMed:32474700). Phosphorylation at Thr-68 and Ser-213 inhibits its cyclic GMP-AMP synthase activity (PubMed:33273464). Ubiquitination at Lys-173 and Lys-384 via 'Lys-27'-linked polyubiquitination enhances the cyclic GMP-AMP synthase activity (PubMed:28273161). Monoubiquitination at Lys-347 promotes oligomerization and subsequent activation (PubMed:29426904). Sumoylation at Lys-347, Lys-384 and Lys-394 prevents DNA-binding, oligomerization and nucleotidyltransferase activity (By similarity). The enzyme activity is impaired by the cleavage at Asp-140 and Asp-157 produced by CASP1 (PubMed:28314590). In addition to DNA, also activated by collided ribosomes upon translation stress: specifically binds collided ribosomes, promoting its activation and triggering type-I interferon production (PubMed:34111399). Strongly inhibited by compound PF-06928215, which is specific for human protein (PubMed:28934246, PubMed:30007416, PubMed:32459092). Inhibited by small-molecule inhibitors with a pyridoindole tricyclic core G108, G140 and G150 (PubMed:31113940)
(Microbial infection) Nucleotidyltransferase activity is inhibited by different herpesvirus tegument proteins (Herpes simplex virus 1 tegument protein VP22, herpes virus 8 protein ORF52 and herpesvirus 3 tegument protein VP22/ORF9) (PubMed:34015248, PubMed:34387695). Viral tegument proteins act by disrupting liquid-like droplets in which CGAS is activated, thereby preventing CGAS activity (PubMed:34015248, PubMed:34387695)
Oligomerization increases ATPase activity
Non-specific ssRNase activity is allosterically activated by cyclic hexaadenylate (cA6) binding to its CARF domain. cA6 is a second messenger produced by Cas10 of the ternary Csm effector complex in the presence of a cognate target RNA
Inhibited by the beta-lactam antibiotic meropenem
Inhibited by mazindol, desipramine, nomifensine and nortriptyline
ssDNase activity is inhibited by EDTA
Inhibited by 10 uM zinc, cadmium or mercury ions
Strongly inhibited by nonsteroidal anti-inflammatory drugs (NSAID) including flufenamic acid and indomethacin. Also inhibited by the flavinoid, rutin, and by selective serotonin inhibitors (SSRIs) (PubMed:14979715, PubMed:14996743, PubMed:10557352). The oxidation reaction is inhibited by low micromolar concentrations of NADPH (PubMed:14672942)
Inhibited by sodium iodide-mediated oxidation
Inhibited by L-aspartate
Allosterically activated by GTP. Probably inhibited by UTP
Activity toward plasminogen is stimulated in the presence of fibrin I
Upon extracellular signal or mitogen stimulation, phosphorylated at Thr-562 in the C-terminal kinase domain (CTKD) by MAPK1/ERK2 and MAPK3/ERK1. The activated CTKD then autophosphorylates Ser-369, allowing binding of PDPK1, which in turn phosphorylates Ser-221 in the N-terminal kinase domain (NTDK) leading to the full activation of the protein and subsequent phosphorylation of the substrates by the NTKD (By similarity)
Inhibited by mercury dichloride and diuretic drug bumetaide. Inactive in isotonic conditions
Inhibited by Co(2+) and dimethyloxalylglycine (PubMed:11595184). Inhibited by the iron chelator 2, 2'-dipyridyl (PubMed:19737748)
Following exposure to hypoxia, activated in HeLa cells but not in cardiovascular cells
Inhibited by high potassium ions-induced membrane depolarization
Phosphorylation activates zinc transport activity
Activated by phosphoenolpyruvate (PEP) and by high concentrations of monovalent cations, NH(4)(+) being most effective. Is inhibited by two types of compounds which apparently act on the enzyme at different sites. The first group consists of nucleoside monophosphates (most effective are AMP and dAMP), phosphorylated coenzymes, and denatured DNA and RNA, whose inhibition is competed by PEP. The second group, whose inhibition is not competed by PEP, consists of highly phosphorylated nucleotides (pppGpp and pppApp are most effective), nucleoside di- and triphosphates, and PPi
Phosphorylation increases DNA binding affinity
CDK kinase activated by CDKF-1. CDK kinase activity inhibited by KRP1/ICK1, KRP2/ICK2, KRP3/ICK6, KRP4/ICK7, KRP5/ICK3, KRP6/ICK4 and KRP7/ICK5. Down-regulated by phosphorylation by WEE1
ATP functions as antagonist and inhibits ADP-induced mobilization of Ca(2+) (PubMed:9038354). The P2Y1 receptor-specific antagonists A3P5PS, A3P5P and A2P5P inhibit downstream signaling mediated by mobilization of Ca(2+) from intracellular stores, and platelet shape changes in response to extracellular ADP (PubMed:9442040)
The side chain of Glu-236 determines which of the two opposing activities (AMPylase or de-AMPylase) will take place. In response to endoplasmic reticulum stress, mediates de-AMPylase activity (By similarity). Adenylyltransferase activity is inhibited by the inhibitory helix present at the N-terminus: Glu-236 binds ATP and competes with ATP-binding at Arg-375, thereby preventing adenylyltransferase activity (By similarity). In unstressed cells, disengagement of Glu-236 promotes adenylyltransferase activity (By similarity). Activation dissociates ATP-binding from Glu-236, allowing ordered binding of the entire ATP moiety with the alpha-phosphate in an orientation that is productive for accepting an incoming target hydroxyl side chain (By similarity)
Inhibited by cytochalasin B
Inhibited by vestitone concentrations above 50 uM
Inhibited by inorganic pyrophosphate and hydroxyphenylglyoxal
Interaction of the PASTA domains with peptidoglycan leads to septal and polar localization of PknB, and dimerization of the intracellular kinase domain. Dimerization activates the kinase domain via an allosteric mechanism, triggering autophosphorylation and phosphorylation of target proteins. Inhibited by mitoxantrone. Inhibition prevents mycobacterial growth
Inhibited by NaF, AgNO(3), HgCl(2), CuSO(4) and phenylmethylsulfonyl fluoride (PMSF)
Converted into plasmin by plasminogen activators, both plasminogen and its activator being bound to fibrin. Cannot be activated with streptokinase
The GTPase activity is enhanced by potassium ions as well as by DFRP1 binding
Activated by the non-canonical Wnt signaling pathway, in which WNT5A leads to activation of MAP3K7/TAK1 and HIPK2, which subsequently phosphorylates and activates this protein. Activated by dimerization and subsequent intermolecular autophosphorylation on Thr-298. Other cytokines such as IL6 may also activate this regulatory circuit (By similarity)
Activated by phosphorylation on Thr-212. Activated by phosphorylation at Ser-601 AKT1 during glucose starvation; the relevance of such activation in normal cells is however unsure (By similarity)
Activated by phosphorylation on threonine and tyrosine. MAP2K3/MKK3 and MAP2K6/MKK6 are both essential for the activation of MAPK12 induced by environmental stress, whereas MAP2K6/MKK6 is the major MAPK12 activator in response to TNF-alpha
Autoinhibited and allosterically activated by 3,5-cyclic adenosine monophosphate (cAMP). An extensive conformational rearrangement relieves this autoinhibition by means of a substrate-mimicking lid that covers the protein-substrate binding surface
Strongly inhibited by the divalent metal cations Fe(2+), Hg(2+), Co(2+), Zn(2+), Cu(2+) and Cd(2+)
ATPase activity is stimulated by interaction with RNA
Activated by phosphorylation on Thr-174 by STK11/LKB1
Inhibited by natural nucleoside antibiotics including tunicamycin, capuramycin and muraymycin. Usually the cofactor magnesium is not required for antibiotic binding
Activated by phosphorylation by specific MAP kinase kinase kinases such as MAP3K1/MEKK1, MAP3K3/MEKK3, MAP3K11/MLK3 and MAP3K12/DLK
Is completely inhibited by Ag(+) and Hg(2+) ions
Inhibited by FK506 but not by cyclosporine
Potassium antiport activity requires the presence of KhtT. Activity is also modulated by KhtS. Has higher activity at alkaline pH
Reversibly inhibited by EDTA. Stimulated by the divalent cations Mg(2+) and Mn(2+)
PPIase activity is optimal in oxidized form (S-S) and minimal in reduced form (SH). Reduction of the oxidized form is mediated by thioredoxin (TRX-M)
Inhibited by phenothiazine analogs
Inhibited strongly by Hg(2+), Cd(2+) and para-chloromercuribenzoic acid (PCMB) and weakly by Zn(2+) and iodoacetamide. Also inhibited strongly by L-xylose but not D-glucose
Inhibited by CuSO(4) and ZnCl(2)
In continuous light, by inorganic phosphate, sed7P, glycerate and ribulose 1,5-bisphosphate
Activated by cleavage by B.anthracis lethal toxin (LT) endopeptidase (PubMed:20502689). Cleavage by LT promotes ubiquitination and degradation of the N-terminal part, releasing the cleaved C-terminal part of the protein (NACHT, LRR and PYD domains-containing protein 1a, C-terminus), which polymerizes and forms the Nlrp1a inflammasome (By similarity). Nlrp1a inflammasome is inhibited by DPP8 and DPP9, which sequester the C-terminal fragment of Nlrp1a (NACHT, LRR and PYD domains-containing protein 1a, C-terminus) in a ternary complex, thereby preventing Nlrp1a oligomerization and activation (By similarity). Nlrp1a inflammasome is weakly activated by Val-boroPro (Talabostat, PT-100), an inhibitor of dipeptidyl peptidases DPP8 and DPP9 (PubMed:31383852). Val-boroPro relieves inhibition of DPP8 and/or DPP9 by promoting disruption of the ternary complex, releasing its C-terminal part from autoinhibition (By similarity). Weakly activated by Toxoplasma gondii (PubMed:31383852)
Inhibited by E64, a specific inhibitor of cysteine proteases, N-ethylmaleimide, iodacetamide, and mercury and zinc ions
Inhibited by the presence of acetyl groups on the substrate
Allosterically activated by fructose 1,6-bisphosphate (FBP). Inactivated by Mn(2+), Co(2+), Cd(2+) and Zn(2+)
Inhibited by bee venom neurotoxin apamin (PubMed:11557517, PubMed:13679367, PubMed:14657188). Inhibited by UCL 1684 and tetraethylammonium (TEA) (By similarity)
P-hydroxymercuribenzoate causes a slight inhibition (8 to 17 %). Iodoacetamide, o-iodosobenzoate and ammonium persulfate do not inhibit the enzyme activity
Inhibited by CCCP and N-ethylmaleimide
GTP hydrolysis is stimulated by unc-89
Repressed by glyphosate in a competitive inhibition manner
Inhibited by Cu(2+), and to a lesser extent by Ni(2+), Mn(2+), Co(2+), Fe(3+) and Zn(2+). Unaffected by Fe(2+) and Mg(2+)
The proteinase activity is slightly enhanced by Ca(2+) and Mg(2+), but is completely inhibited by Zn(2+). Is completely inhibited by phenanthroline and EDTA. Not inhibited by PMSF
Activated by phosphorylation on Thr-214
Threonine interaction with Gln-443 leads to inhibition of aspartate kinase activity and facilitates the binding of a second threonine on Gln-524, leading to a partial inhibition of homoserine dehydrogenase activity (25% of activity remaining at saturation with threonine). Homoserine dehydrogenase activity is also partially inhibited by cysteine (15% of activity remaining at saturation with cysteine). No synergy between threonine and cysteine for the inhibition. 13-fold activation of aspartate kinase activity by cysteine, isoleucine, valine, serine and alanine at 2.5 mM and 4-fold activation by leucine at 2.5 mM, but no activation of homoserine dehydrogenase activity
By light-reversible phosphorylation (By similarity). Activated by inorganic phosphate (Pi) deprivation and glucose 6-phosphate. Inhibited by L-malate and L-aspartate
Not inhibited by cholate, but slightly inhibited by triton X-100 and deoxycholate. Completely inhibited by PMSF (phenylmethylsulfonyl fluoride) at a concentration of 200 uM
Inhibited by the CTP analogs 5-mercuri-CTP and CTP-2',3'-dialdehyde
Inhibited by reserpine (PubMed:18156250)
Inhibited by E-64, antipain, leupeptin, heavy metal ions, iodoacetic acid, dithionitrobenzene, p-hydroxymercuri-benzoate; activated by mercaptoethanol and dithiothreitol
Inhibited by 3-isobutyl-1-methylxanthine (IBMX), zaprinast and dipyridamole. cGMP acts as an allosteric activator (By similarity)
Inhibited by Hg(2+), Co(2+), Zn(2+), Cd(2+), Cu(2+) and Pb(2+) ions. Activated slightly by Mn(2+), Ca(2+) and Mg(2+) ions
Partially inhibited by 5 mM serine
Inhibited by RTN3 and RTN4
Inhibited in feedback fashion by the catecholamine neurotransmitters, especially by dopamine in competition with tetrahydrobiopterin. Phosphorylation of several Ser/Thr residues in the N-terminus regulates the catalytic activity. Ser-31 and Ser-40 are readily phosphorylated to activate the catalytic activity. A cysteine modification induced by N-ethylmaleimide (NEM), inhibits tyrosine 3-monooxygenase activity through the modification of the Cys-177
During recombination, the heterotetrameric complex catalyzes two consecutive pairs of strand exchanges, implying that specific pairs of active sites are sequentially switched on and off in the recombinase tetramer to ensure that appropriate DNA strands will be exchanged at both reaction steps. FtsK plays a central role in this catalytic state switch that turns recombinase on and off reciprocally. The reciprocal C-terminal interaction between XerC and XerD may also participate in the enzymatic switch process
Inhibited by methyl arachidonyl fluorophosphonate (MAFP)
Suramin inhibits both myotoxic and muscle-paralyzing activities (PubMed:14505937). Chicoric acid inhibits myotoxic activity (PubMed:30251662). Zinc ions inhibits the myotoxic activity and the neuromuscular blockade (PubMed:27531710). Heparin inhibits myotoxic activity (PubMed:16197992)
UDP-alpha-D-xylose (UDX) acts as a feedback inhibitor. It binds at the same site as the substrate, but functions as allosteric inhibitor by triggering a conformation change that disrupts the active hexameric ring structure and gives rise to an inactive, horseshoe-shaped hexamer
Activated upon translocation to the sites of synthesis of PtdIns(3,4,5)P3 in the membrane. Enzymatic activity is enhanced in the presence of phosphatidylserine (By similarity)
Plant MTHFRs strongly prefer NADH over NADPH. Not inhibited by methionine or S-adenosylmethionine (By similarity)
Zinc ions inhibit enzyme activity in a dose-dependent manner (PubMed:8824626). Inhibited by KCl at concentrations above 10 mM (PubMed:21268586). Inhibited by o-oxyquinoline in vitro, suggesting that it is a metalloprotein (PubMed:3207420). Inhibited by various substrate N(8)-acetylspermidine analogs bearing different metal-binding groups such as trifluoromethylketone, thiol, or hydroxamate, and by hydroxamate analogs of short-chain acetyldiamines (PubMed:26200446)
Endocytosis and inhibition of the activated EGFR by phosphatases like PTPRJ and PTPRK constitute immediate regulatory mechanisms. Upon EGF-binding phosphorylates EPS15 that regulates EGFR endocytosis and activity. Moreover, inducible feedback inhibitors including LRIG1, SOCS4, SOCS5 and ERRFI1 constitute alternative regulatory mechanisms for the EGFR signaling. Up-regulated by NEU3-mediated desialylation of N-linked glycan at Asn-528
Feedback regulated by proline
Inhibited by Ba(2+), Zn(2+) and Fe(3+)
Inhibited by SDS and o-phenanthroline, a ferrous iron chelator (PubMed:29038259). Partially inhibited by EDTA (PubMed:29038259)
Strongly inhibited by sodium azide and sodium cyanide, and slightly inhibited by 3-amino-1,2,4-triazole
Methyl-coenzyme M reductase activity is inhibited by 3-nitrooxypropanol (3-NOP) in vitro and in vivo, by oxidation of its active site Ni(I), which stops both growth and methanogenesis (PubMed:27140643). Is also inhibited by the reaction product CoM-S-S-CoB (PubMed:3350018)
Activated by potassium ions, but not sodium ions
GTPase activity is stimulated by oxidative stress
Activated by inorganic phosphate (PubMed:3009477, PubMed:10954724). In addition to form a complex with ATP, Mg(2+) also acts as a cofactor (PubMed:9125530). Strongly inhibited by ADP through competitive binding at the activation site and at a specific allosteric site (PubMed:3009477, PubMed:6290219, PubMed:9125530). Competitively inhibited by Ca(2+) and ribose 1,5-bisphosphate (Rib-1,5-P2) (PubMed:2542328, PubMed:9125530). Less strongly inhibited by AMP, alpha,beta-methylene ATP (mATP), (2',3'-dialdehyde)-ATP (oATP) and 1-alpha,2-alpha,3-alpha-trihydroxy-4-beta-cyclopentanemethanol 5-phosphate (cRib-5-P) (PubMed:2542328, PubMed:7657655, PubMed:9125530)
Activated by phosphorylation of Thr-210 by AURKA; phosphorylation by AURKA is enhanced by BORA. Once activated, activity is stimulated by binding target proteins. Binding of target proteins has no effect on the non-activated kinase. Several inhibitors targeting PLKs are currently in development and are under investigation in a growing number of clinical trials, such as BI 2536, an ATP-competitive PLK1 inhibitor or BI 6727, a dihydropteridinone that specifically inhibits the catalytic activity of PLK1 (By similarity)
Inhibited by EDTA and EGTA in vitro
Inhibited by brefeldin A (BFA) (By similarity). Inhibited by golgicide A (GCA) (PubMed:19182783)
Pyrrolopyrimidines inhibit both GyrB and its paralog in topoisomerase IV (parE) (PubMed:23352267)
Inhibited by high levels of AMP
Shows pH-dependent activity (By similarity). The glutamate analog L-trans-pyrrolidine-2,4-dicarboxylic acid (L-PDC) blocks the uptake of glutamate by selective inhibition (PubMed:12855178)
Allosteric enzyme exhibiting negative cooperativity. Activated 2-5 fold by fatty acids
60% inhibition by 20 uM tungstate or by lack of glucose in the medium, but no inhibition by sulfate
Binds c-di-AMP (PubMed:31061098, PubMed:33619274, PubMed:35130724, PubMed:35714772). Binding of c-di-AMP to DarB inhibits the interaction with RelA and PYC (PubMed:33619274, PubMed:35130724)
Activated by forskolin (PubMed:18071070, PubMed:20466003, PubMed:20864687, PubMed:23753526, PubMed:24363043). Inhibited by calcium ions, already at micromolar concentrations (PubMed:1379717, PubMed:18071070). Inhibited by adenosine, AMP and their analogs (By similarity). Activated by GNAS. Is further activated by the complex formed by GNB1 and GNG2 (By similarity). Phosphorylation by RAF1 results in its activation (By similarity)
Activated by phosphorylation on Ser-51 and Ser-548
Inhibited competitively by nicotinic acid with a Ki of 0.49 mM. Inhibited by thiol-specific compounds p-chloromercuribenzoate, DTNB, Ag(2)SO(4), HgCl(2), CuCl(2) and N-ethylmaleimide. No inhibition by o-phenanthroline, 8-hydroxyquinoline, EDTA, disodium 4,5-dihydroxy-m-benzenedisulfonate, fluoride, azide, KCl, LiCl, NaCl, BaCl(2), MnCl(2), MgCl(2), PBCl, ZnCl(2), CoCl(2), SnCl(2), FeSO(4), FeCl(3), NiCl(2), CdCl(2), AlCl(3), iodoacetic acid, hydro-xylamine, phenylhydrazine, semicarbazide, cysteamine, alpha,alpha-dipyridyl and urea
Activation of the apo-enzyme requires the three accessory proteins LarB, LarE and LarC, that are involved in the biosynthesis of the nickel-pincer cofactor of LarA
Is strongly inhibited by 6-fluoromevalonate monophosphate but shows negligible inhibition by 6-fluoromevalonate diphosphate (a potent inhibitor of the classical mevalonate pathway)
Peptidase activity is subject to substrate inhibition by ATP
Methyltransferase activity is inhibited by BIX-01294. Efficiently inhibited by compound E72, a BIX-01294 derivative in which the diazepane ring and the benzyl are replaced with a 3-dimethylaminopropyl and a 5-aminopentyl group at sites B and C, respectively
Inhibited by metalloporphyrins such as Sn- and Zn-protoporphyrins
ATPase activity is dependent of phosphorylation by PAK1 and presence of DNA
Acylglycerol lipase activity is activated upon binding to progesterone
Competitively inhibited by oxalate, a pyruvate enolate analog
Binding to (1->3)-beta-D-glucan to alpha subunit, induces autocatalysis and activation of beta subunit (PubMed:7822328). Inhibited by intracellular coagulation inhibitor 3/LICI-3 and to a lesser extend by intracellular coagulation inhibitor 2/LICI-2 (PubMed:7822328, PubMed:8798603)
Activated by forskolin (PubMed:1719547, PubMed:22906005, PubMed:24363043). Is not activated by calmodulin (PubMed:1719547). Inhibited by calcium ions, already at micromolar concentration. Activated by the G protein alpha subunit GNAS (PubMed:1719547, PubMed:7761832, PubMed:21596131). Activated by the G protein beta and gamma subunit complex (PubMed:7761832, PubMed:21596131, PubMed:22906005). Phosphorylation by RAF1 results in its activation (By similarity). Phosphorylation by PKC activates the enzyme (PubMed:22906005)
Dephosphorylation by PTC7 leads to activation
Requires DmpM for efficient turnover. The activity of DmpLNO oxygenase is inhibited by dithiothreitol (DTT) by a mechanism apparently involving H(2)O(2) generation
By free ubiquitin: binding of free ubiquitin triggers conformational changes in the OTU domain and formation of a ubiquitin-binding helix in the N-terminus, promoting binding of the conjugated donor ubiquitin in UBE2N/UBC13 to OTUB1
Completely inhibited by Cu(2+) and Fe(2+)
Allosterically activated by alpha-keto acids and the corresponding amino acids. L-leucine, L-valine, D-valine, L-isoleucine, L-phenylalanine, D-phenylalanine, L-tyrosine and L-valine are activators (with L-leucine and L-isoleucine being the strongest activators) whereas L-tryptophan, tryptophol, phenylacetic acid and indoleacetic acid have no effect
Inhibited by monovalent metal ions
Requires the presence of IpdF
The uptake activity increases with increasing Mg(2+) concentrations. Inhibited by FCCP, TCC and nigericin
Allosterically regulated by ATP (activator) and ADP (inhibitor) (PubMed:11322891). Cold labile, it dissociates into inactive monomers at low temperature (PubMed:6136404)
Inhibited by the protonophore carbonyl cyanide m-chorophenylhydrazone (CCCP) (PubMed:8682782). Ethidium bromide efflux is inhibited by chlorpromazine, thioridazine and verapamil (PubMed:21332993)
Lysine-sensitive
Decreased activity at low temperatures (15 or 21 degrees Celsius)
Enzyme activity is increased by spermidine, EEF1A1, and when the Mg(2+) concentration is increased from 5 mM to 13 mM (in vitro), possibly by promoting the dissociation of the complex between the enzyme and its product
Activated by cAMP. cAMP binding causes a conformation change that leads to the assembly of an active tetramer and channel opening (By similarity)
Is irreversibly inactivated by the beta-lactams carbapenems via the formation of a covalent adduct resulting from acylation of the catalytic Cys
Inhibited by stilbene disulfonates, such as di-isothiocyanostilbene disulfonate(DIDS), a cross-linking reagent that forms covalent linkages with lysine groups
Substitution of the loosely bound surface exposed Mn(2+) with Mg(2+), Zn(2+), Ni(2+) or Co(2+) results in similar catalytic activity, substitution with Cd(2+) and Cu(2+) reduces catalytic activity and substitution with Hg(2+) and Ca(2+) inhibits the enzyme (PubMed:29691540). Inhibited by L-norvaline (PubMed:15053781, PubMed:29691540)
Regulated by molecular oxygen, which binds to the heme binding site. Probably not activated by nitric oxide (NO)
The fibrinogenolytic and coagulant activities of the moojenin were abolished by preincubation with EDTA, 1,10-phenanthroline and beta-mercaptoethanol
Inhibited by SERPINB1
Enzyme activity is tightly regulated to prevent the accumulation of reactive oxygen species in the endoplasmic reticulum. Reversibly down-regulated by the formation of disulfide bonds between the active site Cys-86 and Cys-123, and between Cys-91 and Cys-96. Glutathione may be required to regulate its activity in the endoplasmic reticulum (By similarity)
Calcium-independent phospholipase
The hydrolytic product 7-methylguanosine diphosphate (m7GDP) efficiently inhibits the decapping scavenger activity and acts as a competitive inhibitor in vitro
Is inhibited by Li(+) and by inorganic phosphate
Transactivation activity is enhanced by transcriptional coactivator POU2AF1
Strongly inhibited by the metal ion chelators EDTA and 1,10-phenanthroline (PubMed:11606206). Also inhibited by apstatin (PubMed:11606206, PubMed:25905034). Activity towards bradykinin is inhibited by Mn(2+) and Zn(2+) at all concentrations tested, whereas Co(2+) is inhibitory at concentrations above 100 uM and activatory at 10 uM (PubMed:11606206)
Activated by light-induced dephosphorylation. Inhibited by dark-induced phosphorylation. Both reactions are catalyzed by PDRP1 (By similarity)
Extracellular glucose and urate accelerate urate efflux (PubMed:22647630, PubMed:18842065). Intracellular urate, glucose and fructose accelerate urate influx (PubMed:22647630)
No effect of extracellular urate, glucose or fructose on urate efflux. Intracellular urate and fructose slightly accelerate urate influx
Allosterically inhibited by the N-terminal domain (PubMed:36177733). Inhibited by phloretin (PubMed:36177733, PubMed:18000046)
Redox regulation; active in reducing conditions, inactive in oxidizing conditions. Thioredoxins f1, m1, and y1 mediate the reversible reductive activation of oxidized BAM1
Beta-galactosidase activity is activated by Mg(2+) and significantly inhibited by Ca(2+), Cd(2+), Fe(2+), Ni(2+), Cu(2+) and Zn(2+) (PubMed:33584576). Inhibited by EDTA (PubMed:33584576)
Inhibited by Trichostatin A (TSA) and suberoylanilide hydroxamic acid
Allosterically inhibited by phosphoenolpyruvate
Allosterically activated by GTP. Competitively inhibited by magnesium-free UTP. Magnesium-bound UTP is unable to inhibit enzyme activity
Activated by threonine and tyrosine phosphorylation. Activated in response to bacterial and fungal pathogen-associated molecular patterns (PAMPs) including chitin, chitosan and peptidyl glycans (PGNs). Activation in response to chitin requires the CERK1, MEKK1a/b, MKK1a/b/c and MPK4a/b signaling pathway. Activated in response to necrotrophic fungus B.cinerea spores. Not activated in response to osmotic stress
Contains an allosteric site (distinct from its active site), whose occupancy by an unfolded polypeptide leads to enzyme activation
Transport is feedback inhibited by intracellular polyamines
Xylose uptake is strongly inhibited by glucose
Strongly inhibited by Hg(2+)
TG003 inhibits its kinase activity and affects the regulation of alternative splicing mediated by phosphorylation of SR proteins
Inactivated by an unknown mechanism after binding of brassinosteroids to the brassinosteroid receptor complex (Probable). Inhibited by lithium. Inhibited by dephosphorylation at Tyr-200 by BSU1 (PubMed:21855796). Competitive inhibition by KIB1 that reduces substrate (e.g. BZR1) access (PubMed:28575660). Repressed by bikinin (PubMed:22466366)
Esterase activity is down-regulated by salicylic acid (SA)
Allosterically activated by S-adenosyl-L-methionine (SAM). Activated by S-adenosyl-L-ethionine, 5'-amino-5'-deoxyadenosine, sinefungin and 5'-deoxy-5-methylthioadenosine. Inhibited by AMP
Inhibited by warfarin (coumadin) (PubMed:21367861, PubMed:23928358, PubMed:24532791). Warfarin locks VKORC1 in both redox states into the closed conformation (By similarity)
Nuclease activity is stimulated by interaction with MutL. ATPase activity is stimulated by dsDNA
Prematurely activated/folded staphopain A is inhibited by staphostatin A (ScpB), which is probably required to protect staphylococcal cytoplasmic proteins from degradation by ScpA
Responds differently to heat shock versus acid shock; degradation in response to heat shock requires sequential DegS and RseP action, whereas degradation in response to acid shock requires only RseP
Is inhibited by molecular oxygen, high salt concentrations (NaCl, KCl, or MgCl(2)), urea, and Ti(III)citrate. Activity is not affected by EDTA
Cys-11 acts as a sensor of redox state. In response to oxidative stress, monoubiquitination at Cys-11 is prevented
Inhibited by imidazoles
A sequential activation is proposed: autophosphorylation at consensus sites is leading to dimerization of the catalytic domain and activation segment exchange (producing an active confirmation of both kinase modules in trans) followed by phosphorylation at Thr-180 in the activation segment and at other regulatory sites (Probable). Phosphorylation at Thr-180, Thr-225 and Thr-265 is essential for activity. Inhibited by pyridone 6 (K00225), a potent, ATP-competitive inhibitor. Phosphorylation at Thr-180, Thr-225 and Thr-265 is essential for activity
Subject to inhibition by high substrate concentrations. Inhibited by testosterone concentrations above 10 uM. Inhibited by the primary and secondary bile acids chenodeoxycholic acid and ursodeoxycholic acid
Inhibited by salicyl-AMS, an acyl-AMP analog (PubMed:16407990, PubMed:17181146). Also inhibited by 5'-O-[(N-acyl)sulfamoyl]adenosines (PubMed:17967002)
Ethanol and carbon monoxide-bound heme increase channel activation. Heme inhibits channel activation
Strongly inhibited by bestatin, leuhistin, actinonin, amastatin, 1,10-phenanthroline, DFP, PCMBS, Zn(2+), Cd(2+), Co(2+), Cu(2+), Hg(2+), EDTA and puromycin. Not inhibited by PMSF, and only slightly inhibited by leupeptin and aprotinin. Activity is increased by Mg(2+) and Ca(2+)
Carboxylase activity of the AccA3/AccD5 complex is stimulated by interaction with the epsilon subunit AccE5 (PubMed:16354663, PubMed:16385038). Activity of the AccA3/AccD6 complex is inhibited by interaction with AccE5 and by dimethyl itaconate, C75, haloxyfop, cerulenin, and 1,2-cyclohexanedione (PubMed:17114269)
Does not require salt for activity. Not inhibited by kiwi pectin methylesterase inhibitor (PMEI)
Stimulated by Co(2+) (PubMed:3308850). Fe(2+) is also a good activator, particularly at lower concentrations, but it inhibits slightly the activity when used at concentrations over 0.1 mM (PubMed:3308850). Other divalent metals tested (Cd(2+), Ca(2+), Mn(2+), Zn(2+), Ni(2+) and Mg(2+)) are not effective activators (PubMed:3308850)
Activated by osmotic stress and by abscisic acid (ABA). Activation by NaCl is dependent on ABA
Inhibited by mecillinam and benzylpenicillin
Inhibited by sodium chloride
Rapidly activated by cAMP-dependent phosphorylation under the influence of catecholamines (PubMed:6374655). Dephosphorylation and inactivation are controlled by insulin (PubMed:6374655). cAMP stimulates its retinyl ester hydrolase activity (PubMed:9162045)
CLPS stimulates triacylglycerol lipase activity. Not inhibited by bile salts
Activated by L-lysine, L-methionine, and L-isoleucine. L-threonine, at low concentrations, is a mild activator and has a weak inhibitory effect only at concentrations over 10 mM. Strongly feedback inhibited by the concerted combination of L-lysine and L-threonine and slightly feedback inhibited by the concerted combination of L-threonine and L-methionine. Activated by the combination of L-methionine and L-lysine, L-methionine and L-isoleucine and L-lysine and L-isoleucine
Enzyme activity is completely blocked by diisopropyl-fluorophosphates, moderately by phenylmethylsulfonyl fluoride (PMSF) and 4-(2-methyl)benzenesulfonyl fluoride, and slightly by pepstatin in vitro
Activated upon caspase cleavage to generate the XK-related protein 8, processed form (PubMed:23845944). Does not act prior the onset of apoptosis (PubMed:23845944)
Regulated by pH: upon acidification, at a pH of 6.3, dinoflagellate luciferin is released from luciferin-binding protein LBP, allowing the interaction between Dinoflagellate luciferase and its substrate luciferin
The NADPH oxidase activity is calcium-dependent. Peroxidase activity is inhibited by aminobenzohydrazide (By similarity)
ATPase activity is stimulated by glutathione
Lysine-sensitive. Regulated by degradation in response to starvation of cells for various nutrients. Ammonium starvation induced the fastest aspartokinase II decline, followed by amino acid starvation and glucose limitation
The chaperone activity is regulated by ATP-induced allosteric coupling of the nucleotide-binding (NBD) and substrate-binding (SBD) domains (By similarity). In the ADP-bound and nucleotide-free (apo) states, the two domains have little interaction (By similarity). In contrast, in the ATP-bound state the two domains are tightly coupled, which results in drastically accelerated kinetics in both binding and release of polypeptide substrates (By similarity). J domain-containing co-chaperones (DNAJB9/ERdj4 or DNAJC10/ERdj5) stimulate the ATPase activity and are required for efficient substrate recognition by HSPA5/BiP (PubMed:29064368). Homooligomerization inactivates participating HSPA5/BiP protomers and probably act as reservoirs to store HSPA5/BiP molecules when they are not needed by the cell (PubMed:26473973)
The Zn(2+) uniporter activity is regulated by zinc availability (PubMed:32348750, PubMed:17202136). Extracellular acidification stimulated SLC39A4-dependent Zn(2+) uptake (PubMed:31979155)
Activated by phosphorylation on tyrosine residues
Interaction with Golgi matrix protein GOLGA2 leads to autophosphorylation on Thr-178, possibly as a consequence of stabilization of dimer formation. May also be activated by C-terminal cleavage
Inhibited by Zn(2+) and z-VAD-fmk (caspase inhibitor) but unaffected by EDTA
Amidolytic and clotting activities are completely inhibited by NPGB and PMSF, but not inhibited by EDTA
Inhibited by RC-(Rp,Sp)- and SC-(Rp,Sp)-1,2-dioctylcarbamoylglycero-3-O-p-nitrophenyl octylphosphonate (PubMed:9660188). Also inhibited by diethyl-p-nitrophenylphosphate (E600) (PubMed:1856176)
Exopolyphosphatase activity is stimulated by NH(4)(+) and K(+). Phosphotransferase activity is insensitive to the addition of K(+) or NH(4)(+) ions
The small regulatory subunit delta and PCNA1 increase POLD catalytic activity
Cerulenin, a potent non-competitive pharmacological inhibitor of FAS, binds covalently to the active site of the condensing enzyme region, inactivating a key enzyme step in fatty acid synthesis (PubMed:16969344). Another inhibitor, though less efficient, is C75, a member of the alpha-methylene-gamma-butyrolactone chemical class, also proposed as an antitumour and anti-obesity agent (PubMed:15715522)
Inhibited by azide
Divalent metal ions, such as Cu2+ and Zn2+, may inhibit the ribonucleolytic activity
Regulated by a thiol-based redox modification
Inhibited by the carbonyl reagents hydroxylamine and phenylhydrazine. Also inhibited by methionine and propargylglycine
Inhibited by the chelating agents EDTA and alpha,alpha'-dipyridyl (PubMed:7551050). Inhibited by Zn(2+) and Fe(2+) (PubMed:7551050)
Regulated by bile acid salts. Up-regulated by cholate and down-regulated by taurochenodeoxycholate
Subject to allosteric control. Substrate inhibition by ATP
Inhibited by CTP
InhA activity is controlled via phosphorylation: phosphorylation on Thr-266 decreases InhA activity and likely negatively regulates biosynthesis of mycolic acids and growth of the bacterium (PubMed:20864541) (By similarity). InhA activity is likely inhibited by activated isoniazid, hexadecynoyl-CoA and octadecynoyl-CoA, which also block the biosynthesis of mycolic acids (PubMed:10708367). The antitubercular pro-drug isoniazid (INH) is oxidatively activated by the catalase-peroxidase KatG and then covalently binds NAD to form an adduct that inhibits the activity of InhA (By similarity). The inhibitory adduct is the isonicotinic-acyl-NADH where the isonicotinic-acyl group replaces the 4S (and not the 4R) hydrogen of NADH (By similarity). Similarly, the antitubercular pro-drugs ethionamide (ETH) and prothionamide (PTH) are activated by the flavoprotein monooxygenase EthA, and forms an adduct with NAD (ETH-NAD and PTH-NAD, respectively) that is a tight-binding inhibitor of InhA (By similarity)
Strongly inhibited by 1 uM diisopropylphosphofluoridate and 10 uM p-chloromercuribenzoate but scarcely inhibited by 100 mM EDTA in vitro
When cellular nitrogen levels are high, the C-terminal adenylyl transferase (AT) of GlnE inhibits GlnA by covalent transfer of an adenylyl group from ATP to Tyr-406 (PubMed:15037612). Conversely, when nitrogen levels are low, the N-terminal adenylyl removase (AR) of GlnE activates GlnA by removing the adenylyl group by phosphorolysis (PubMed:15037612). The fully adenylated enzyme complex is inactive (Probable). Also inhibited by the diketopurine analog 1-[(3,4-dichlorophenyl)methyl]-3,7-dimethyl-8-morpholin-4-yl-purine-2,6-dione, EDTA, and by L-methionine-SR-sulfoximine (MSO) (PubMed:7937767, PubMed:12496196, PubMed:19695264)
Inhibited by Cu(2+), while other divalent cations such as Ca(2+), Co(2+), Fe(2+) and Mg(2+) have no obvious effects on enzyme activity
Allosterically activated by AMP and by several sugar phosphates. Belongs to type II PK (By similarity)
Inhibited by geldanamycin, macbecin I and radicicol, which bind to the ATP-binding pocket. Co-chaperones CDC37, SBA1 and STI1 reduce ATPase activity. Co-chaperones AHA1 and HCH1 increase ATPase activity
Not regulated by FAD or FMN
Activated by binding to the regulatory factor DNMT3L (PubMed:15671018, PubMed:17713477, PubMed:21481189). Auto-methylation at Cys-706 in absence of DNA inactivates the DNA methyltransferase activity (PubMed:21481189)
Inhibited by chelating agents
Activity is not affected by 2,3-bisphosphoglycerate
Rab activation is generally mediated by a guanine exchange factor (GEF), while inactivation through hydrolysis of bound GTP is catalyzed by a GTPase activating protein (GAP) (By similarity). That Rab is activated by DENND3, a guanine exchange factor
Inhibited by high Li(+) and restricted Mg(2+) concentrations
L,L-2,6-diaminopimelate, D,D-2,6-diaminopimelate and meso-2,5-diaminoadipate competitively inhibit the oxidation of meso-2,6-diaminopimelate. L-2-amino-6-methylene-pimelate is also a potent competitive inhibitor (5 uM) of this reaction. Glyoxylate inhibits the reductive amination of L-2-amino-6-oxopimelate about 30%. The enzyme is inhibited completely by p-chloromercuribenzoate and HgCl(2) in vitro
Inhibited by human antibodies scFvs 10FG2 and LR
Activity is regulated by pH (PubMed:12562793). Active at alkaline pH (PubMed:12562793)
Activity is higher in the enzyme containing Mn(2+) than that containing Zn(2+)
Mycophenolic acid (MPA) is a non-competitive inhibitor that prevents formation of the closed enzyme conformation by binding to the same site as the amobile flap. In contrast, mizoribine monophosphate (MZP) is a competitive inhibitor that induces the closed conformation. MPA is a potent inhibitor of mammalian IMPDHs but a poor inhibitor of the bacterial enzymes. MZP is a more potent inhibitor of bacterial IMPDH. MPA is a potent inhibitor in culture
Allosterically inhibited by lysine, but not by S-adenosyl-L-methionine (SAM). K(0.5) for lysine in the presence of physiological concentrations of substrates is 7.4 uM. No inhibition by threonine or leucine and no activation or inhibition by alanine, cysteine, isoleucine, serine, valine, methionine, glutamine, asparagine, glutamic acid or arginine
Monovalent cations such as potassium and sodium enhance activity, as well as a combined action of these cations with magnesium. However, other cations like calcium, cobalt, manganese and zinc, or the presence of EDTA, do not affect the enzymatic activity
Activity of phosphorylase is controlled both by allosteric means (through the non-covalent binding of metabolites) and by covalent modification. Thus AMP allosterically activates, whereas ATP, ADP, and glucose-6-phosphate allosterically inhibit, phosphorylase B. Activated upon phosphorylation
The 3' uridylated RNA substrate is involved in the selective incorporation of UTP; UTP binding is favored due to the constraint posed on the positioning of the NTP base by the continuous stacking interactions between Tyr-189 side chain, the bound NTP, and the terminal nucleoside base of the RNA substrate
Inhibited by sucrose
Malonyl-CoA decarboxylase activity does not require any cofactors or divalent metal ions
Inhibited by laminarin sulfate and, to a lower extent, by heparin, sulfamin and EDTA. Activated by calcium and magnesium (By similarity)
Negatively regulated by the MEKK1-MKK1-MKK2-MPK4 kinase cascade
Inhibited by divalent cations (30-100%), beta-chloromercuribenzoate (85%), iodoacetamide (40%) and N-ethylmaleamide (80%). The presence of CoA thioesters containing 12-20 carbon atoms results in inhibition of enzyme activity. The greatest degree of inhibition is observed in the presence of palmitoyl-CoA and myristoyl-CoA. The branched-chain fatty acids, isopalmitoyl-CoA and isomyristoyl-CoA are less effective inhibitors of the crotonyl-CoA reductase. Concentrations of NADPH above 200 uM lead to inhibition of enzyme activity
Homodimerization via the leucine zipper domains is required for autophosphorylation and subsequent activation
USP19 regulates the stability of BIRC3/c-IAP2 by preventing its ubiquitination
Inhibited by staurosporine
Is not activated by Mn(2+), Mg(2+), Ca(2+), Zn(2+) or Co(2+)
Activated by phytosphingosine (PHS), a sphingoid long chain base. Activated by PKH1 phosphorylation
Active at low pH (under pH 4.6): proton channel activity is activated by luminal side protons. Polyunsaturated fatty acids, such as arachidonic acid, also activate the channel activity
The reductase activity is increased by Mg(2+) (195%), Ca(2+) (169%) and slightly increased by K(+) (123%) (PubMed:22916830). The reduction activity is inhibited by Fe(2+) and Co(2+), and almost totally inhibited by Cu(2+), Mn(2+), Zn(2+) and Fe(3+) (from 3% to 9% residual activity respectively) (PubMed:22916830). The chelating agent EDTA had little effect, suggesting Mg(2+) and Ca(2+) are not determining factors, though they could promote the reductase enzyme activity (PubMed:22916830)
APOA1 is the most potent activator in plasma. Also activated by APOE, APOC1 and APOA4
Activated by forskolin (PubMed:9391159). Inhibited by calcium ions, already at micromolar concentrations (By similarity). Inhibited by adenosine, AMP and their analogs (By similarity). Activated by GNAS (PubMed:9391159, PubMed:17110384). Is further activated by the complex formed by GNB1 and GNG2 (PubMed:17110384). Phosphorylation by RAF1 results in its activation (PubMed:15385642)
Phosphorylation at Ser-56 or Tyr-57 inactivates the enzyme
Allosterically activated by its substrate, UDP-GlcNAc
Very sensitive to O(2)
Enzymatic activity may be regulated by TtuB conjugation
Activity is inhibited by D-1MT (1-methyl-D-tryptophan) and MTH-trp (methylthiohydantoin-DL-tryptophan) but not L-1MT (1-methyl-L-tryptophan)
Ni(2+), Mn(2+), Co(2+) and Fe(2+) ions greatly increase hydrolase activity. Strongly inhibited by Hg(2+), Cu(2+), Zn(2+), Pb(2+) and Fe(3+) ions, and slightly inhibited by Na(+) and K(+) ions. Beta-mercaptoethanol and 5,5'-dithiobis-(2-nitrobenzoic acid)(DTNB) cause 34% and 42% inhibition, respectively
Activated by autophosphorylation. Prior phosphorylation at Tyr-523 by SRC inhibits ulterior autophosphorylation at Tyr-412. Activated by phorbol myristate acetate, phosphatidic acid and poly-Lys. Binding (via SH2 domain) of HCLS1 that is already phosphorylated by SYK strongly increases kinase activity
Partially inhibited by ATP
Is very potently inhibited by raloxifene (PubMed:26842593). Also inhibited by estradiol, ethinyl estradiol, hydralazine, menadione, isovanillin and thioridazine. Not inhibited by allopurinol, a xanthine dehydrogenase potent inhibitor (PubMed:22031625, PubMed:22522748, PubMed:22996261, PubMed:9224775, PubMed:26322824)
Inhibited by SERPING1
Activated by guanine nucleotide-exchange factors (GEF) EPAC and EPAC2 in a cAMP-dependent manner, and GFR
Activation requires autophosphorylation of Ser-308. Phosphorylation of Ser-304 also promotes increased activity (By similarity). Kinase activity is inhibited by WNK4
Inhibited by the ATP-competitive kinase inhibitor, SP600125
Inhibited by aprotinin, ovomucoid, soybean trypsin inhibitor, benzamidine, p-aminobenzamidine, and zinc ions. Activity also inhibited by a Kazal-type proteinase inhibitor
Activity increases up to 5-6 times with Mg(2+) at 50 uM or higher ion concentration. 3-aminobenzamide (3-ABA) inhibits the activity by up to half and nicotinamide to a lesser extent. Zn(2+) inhibits the activity to half-maximal rate but at 500 uM concentration of the ion
Inhibited by high concentrations of Cu(2+) and Zn(2+). Completely inhibited by EDTA in vitro
Copper binding enhances receptor activity in response to odorant binding
Inhibited by calmodulin with an IC(50) of 50 nM. Calmodulin inhibits GRK5 association with receptor and phospholipid
Octameric ced-4 activates zymogen autoprocessing and enhances activity of processed ced-3. Zymogen autoactivation is inhibited by csp-3. csp-3 has no effect on active ced-3. Zymogen autoactivation is inhibited by csp-2. Inhibited by cysteine protease inhibitor iodoacetic acid (CH3COOI). Inhibited by benzyloxycarbonyl-DEVD-fluoro-methyl ketone (zDEVD-fmk). Inhibited by benzyloxycarbonyl-VAD-fluoro-methyl ketone (zVAD-fmk). Not inhibited by N-[N-(L-3-transcarboxirane-2-carbonyl)-leucyl]-agmatine (E-64) or by the serine and cysteine protease inhibitor L-1-chloro-3-[4-to-osylamido]-7-amino-2-heptanone (TLCK)
Repressor activity is controlled via phosphorylation on arginine residues. Unphosphorylated CtsR binds with high affinity to its DNA consensus site and inhibits transcription of downstream genes, whereas the McsB-phosphorylated CtsR repressor is not able to bind to DNA, thus allowing heat-shock gene expression (PubMed:19498169)
Transcriptional activation activity is strongly reduced by calmodulin
Maintained in an autoinhibited state via homodimerization in which the CARD domain forms an extensive interaction with the adjacent linker and coiled-coil regions (By similarity). Activation downstream of T-cell receptor (TCR) by phosphorylation by PRKCB and PRKCQ triggers CARD11 homooligomerization and BCL10 recruitment, followed by activation of NF-kappa-B (PubMed:16356855)
Inhibited by phenyl beta-GalNAc(4,6-SO(4))
The presence of the regulatory subunit Prim2 accelerates the kinetics of initiation and primer extension
Inhibited by the metal chelator ethylenediaminetetraacetic acid (EDTA)
At rest, the N- and C-terminal domains interact, as part of a larger autoinhibitory complex, with calmodulin pre-associated at the N-terminal domain. Upon a calcium rise, calmodulin becomes calcium-saturated and subsequently binds to the C-terminal domain. Fully calcium-saturated calmodulin then leaves the N-terminal domain, binding solely to the C-terminal domain, and the whole autoinhibitory complex dissociates, resulting in activation of adenylate cyclase. As local calcium concentrations decrease, the calmodulin becomes calcium free and binds once more to the N-terminal domain, whereupon the whole system returns to rest with the re-association of the autoinhibitory complex (PubMed:8163524, PubMed:8557635, PubMed:19305019). In non-excitable cells, activated by capacitative calcium entry (CCE) through store-operated channels, namely through interaction with ORAI1 and STIM1; membrane raft and caveolae localization and membrane integrity are indispensable (PubMed:19158400, PubMed:11744699, PubMed:19171672, PubMed:22494970, PubMed:20410303). CCE-mediated adenylate cyclase activity is decreased by AKAP5 and AKAP7. CCE-mediated adenylate cyclase activity is up-regulated by AKAP9 and the mitochondrially targeted AKAP1 (PubMed:20410303). In excitable cells, activated during membrane depolarization through L-type voltage-gated calcium channels (VGCC), leading to calcium entry; the L-type alpha subunit is sufficient (PubMed:24086669, PubMed:25381556). Activated via stimulation of the GLP1R (PubMed:25381556). Synergistically activated by calcium/calmodulin and GNAS (PubMed:13680124). Stimulated by forskolin (PubMed:16186630, PubMed:13680124). Inhibited by PKA directly bound to AKAP5 at membrane raft (PubMed:22976297, PubMed:21771783). Inhibition by acute activation of OPRM1 and activation by chronic activation of OPRM1 is mediated by pertussis toxin-sensitive G(i) and G(o) G alpha proteins and G beta-gamma dimer. Activity is inhibited by G beta-gamma dimer (PubMed:16186630)
Stimulated by Ca(2+) and Mg(2+)
Inhibited by Cu(2+)
Inhibited by hydroxylamine. Racemase activity is enhanced by Ca(2+), Mg(2+), Mn(2+), and is decreased by Ni(2+), Zn(2+). Hydratase activity is enhanced by Ca(2+), Mg(2+), Mn(2+), Cu(2+), Fe(2+), Ni(2+)
Inhibited by diisopropyl fluorophosphate (DFP)
Iron-sulfur clusters and prephenate are required for ho5C2501 formation
Substrate analogs 25-azalanosterol and 24(R,S),25-epiminolanosterol act as inhibitors
Inhibited by ADP and alpha-ketoglutarate
Ca(2+) does not appear to affect catalytic activity
DNA-binding activates the protease activity: single-stranded DNA-binding specifically activates ability to cleave covalent DNA-protein cross-links (DPCs). In contrast, double-stranded DNA-binding specifically activates autocatalytic cleavage, and subsequent inactivation
Inhibited by aminohydantoin compounds such as CWHM-117
5,6-dichloro-1-b-D-ribofuranosylbenzimidazole (DRB) inhibits autophosphorylation. TG003 inhibits its kinase activity and affects the regulation of alternative splicing mediated by phosphorylation of SR proteins (By similarity)
Is competitively inhibited by alpha-, beta- and gamma-cyclodextrins (cyclic maltooligosaccharides), unlike GlgE from M.tuberculosis
1 mM Hg(2+) and Ag(2+) decrease activity by 98% and 96%, respectively. 1 mM Para-chloromercuribenzoic acid (PCMB) completely inhibits enzymatic activity
Activated by the negatively charged lipid phosphatidylglycerol (PG)
Activated by threonine and tyrosine phosphorylation. Activated in response to bacterial and fungal pathogen-associated molecular patterns (PAMPs) including chitin, chitosan and peptidyl glycans (PGNs). Activation in response to chitin requires the CERK1, MEKK1a/b, MKK1a/b/c and MPK4a/b signaling pathway. Slightly activated in response to necrotrophic fungus B.cinerea spores. Not activated in response to osmotic stress
Inhibited by PMSF, but not by hirudin
Specifically inhibited by spautin-1 (specific and potent autophagy inhibitor-1), a derivative of MBCQ that binds to USP10 and inhibits deubiquitinase activity. Regulated by PIK3C3/VPS34-containing complexes (By similarity)
Conditions that promote oligomer formation increase the ATPase activity (PubMed:22834700). Chaperone activity is fundamentally influenced by the interdomain communication, even if oligomerization and the ability to recognize the substrates are retained (PubMed:26553853)
Shows decreasing activity with increasing pH (PubMed:7575431). Slightly inhibited by azide and fluoride at pH 7-8; the inhibition is drastically increased towards lower pH (PubMed:9531477)
(E(2)17G) transport activity in negatively regulated by organic anions such as oestradiol-3-sulfate, luteolin-7-O-diglucuronide-4'-O-glucuronide, glycocholate, vanadate and the sulfonylurea glibenclamide, and, to a lower extent, by bafilomycin A1, NH(4)Cl, GSH, GSSG and DNB-GS
inhibited by trifluoromethyl ketone
RNase activity inhibited by EDTA
ATPase activity is stimulated by binding to DNA. Helicase activity is stimulated by SSB
No allosteric regulation
The Zn(2+)-specific chelator 1,10-phenanthroline inhibits the enzyme activity
Inhibited by pyrrolidine dione antibiotic moiramide B (CPD1)
Activity decreases with increasing salt concentrations
No effect of calcium ions on activity
Irreversibly inactivated by 3-decynoyl-N-acetylcysteamine (DNAC) which binds to the active site and forms an adduct (PubMed:21276098)
Hydroxylation activity is abolished by NADP and increased by NADPH
Strongly inhibited by Ca(2+)
Activated by phosphorylation on threonine and tyrosine by dual specificity kinases, MAP2K3/MKK3, MAP2K6/MKK6, MAP2K4/MKK4 and MAP2K7/MKK7. Activation by ultraviolet radiation, hyperosmotic shock, anisomycin or by TNF-alpha is mediated by MAP2K3/MKK3. Inhibited by dual specificity phosphatase DUSP1
Inhibited by glucose, maltose and nigerose, and by the antibiotic deoxynojirimycin
Inhibited by serine protease inhibitors PMSF, benzamidine, leupeptin and aprotinin, as well as by copper ions (Cu2+). Not inhibited by metalloprotease inhibitors EDTA, EGTA and 1,10-phenanthroline, as well as by barium (Ba2+) and calcium ion (Ca2+)
Hemagglutinating activity is completely inhibited by methyl alpha-D-glucopyranoside or methyl alpha-D-mannopyranoside. The activity is also inhibited by maltose, glucose, galactose, mannose and lactose, but not by polygalacturonic acid, mannitol, sorbitol or sucrose
Glycosylation does not appear to be required for enzymatic activity
Specifically binds to tetracycline, which leads to a conformational change in the structure of the protein and inhibits the DNA binding activity
The affinity for the mtrCDE promoter increases 2-fold in the presence of TX-100, a known effector and substrate of the MtrCDE pump
Inhibited by 3-methylfumaryl-CoA concentrations above 0.3 mM
Binds free ubiquitin non-covalently via its RING-type zinc finger. Ubiquitin-binding leads to enhance the E3 ubiquitin-protein ligase activity by stabilizing the ubiquitin-conjugating enzyme E2 (donor ubiquitin) in the 'closed' conformation and activating ubiquitin transfer
The apoenzyme can be activated in vitro in the presence of nickel ions and carbon dioxide, which promotes carboxylation of Lys-217
During elevated serum iron levels, liver-derived hepcidin/HAMP negatively regulates cell surface SLC40A1 by inducing its ubiquitination, internalization, and degradation. Indeed, hepcidin/HAMP affinity towards ferroportin/SLC40A1 increases by 80-fold in the presence of iron
Protein kinase activity is activated following autophosphorylation at Tyr-369 (PubMed:9748265). Inhibited by harmine, an ATP competitive inhibitor (PubMed:29634919). Inhibited by small-compound GSK-626616 (PubMed:29973724)
By hypertonicity. Activation requires autophosphorylation of Ser-382, that may be regulated by calcium. Phosphorylation of Ser-378 also promotes increased activity
Feedback inhibited at very high concentrations of methionine or S-adenosylmethionine
Activity is completely abolished by Triton X-100, deoxycholate or Cu(2+), and partially inhibited by thiol reagents, rotenone and antimycin A (PubMed:6378256). The allylamine antimycotic agents naftifine and SF 86-327are potent inhibitors and show apparently non-competitive kinetics with respect to the substrate squalene (PubMed:3877503)
p-chloromercuribenzoic acid inhibits more than 95% of the GSMT activities on glycine and sarcosine, and S-adenosylhomocysteine (AdoHcy) inhibits completely GSMT activities
Activated by phosphorylation on Thr-197
Inhibited by sodium azide
Cell-cycle regulated, maximal activity in S-phase. Inactivated by phosphorylation at Ser-743, potentially by CHEK1
Weakly inhibited by AMP non-competitively to all substrates. Inhibited by IMP non-competitively with respect to GTP. Inhibited by fructose 1,6-bisphosphate competitively with respect to IMP
Homodimerization via the leucine zipper domains is required for autophosphorylation and subsequent activation (By similarity)
Activated by binding to the GTPase-activating protein RAP1GAP. Activated by guanine nucleotide-exchange factor (GEF) EPAC2 in a cAMP-dependent manner
Activated by phosphorylation on Thr-183. Binding of AMP to non-catalytic gamma subunit (PRKAG1, PRKAG2 or PRKAG3) results in allosteric activation, inducing phosphorylation on Thr-183. AMP-binding to gamma subunit also sustains activity by preventing dephosphorylation of Thr-183. ADP also stimulates Thr-183 phosphorylation, without stimulating already phosphorylated AMPK. ATP promotes dephosphorylation of Thr-183, rendering the enzyme inactive. Under physiological conditions AMPK mainly exists in its inactive form in complex with ATP, which is much more abundant than AMP. Selectively inhibited by compound C (6-[4-(2-Piperidin-1-yl-ethoxy)-phenyl)]-3-pyridin-4-yl-pyyrazolo[1,5-a] pyrimidine. Activated by resveratrol, a natural polyphenol present in red wine, and S17834, a synthetic polyphenol
Inhibited by (E)-3-(1-carboxyprop-1-enyloxy)-2-hydroxybenzoic acid (AMT), 3-(1-carboxy-2-phenylvinyloxy)-2-hydroxybenzoic acid (phenyl-AMT), 3-(1-carboxy-3-methylbut-1-enyloxy)-2-hydroxybenzoic acid, 3-(1-carboxybut-1-enyloxy)-2-hydroxybenzoic acid (ethyl-AMT), 3-(1-carboxyprop-1-enyloxy)-2-hydroxybenzoic acid (methyl-AMT), 3-(1-carboxy-2-cyclopropylethenyloxy)-2-hydroxybenzoic acid (cyclopropyl-AMT) and 3-(1-carboxy-3-methylbut-1-enyloxy)-2-hydroxybenzoic acid (isopropyl-AMT)
Inhibited by PMSF. Not or very weakly inhibited by EDTA, EGTA, beta-mercaptoethanol, benzamidine, aprotinin, iodoacetic acid, pepstatin A and SBTI
Activity is stimulated by Mn(2+), Fe(2+) Ca(2+) metal ions and DTT; and inhibited by glucose, Mg(2+), Zn(2+), Cu(2+), Hg(2+), Al(3+), and Fe(3+)
Lipoxygenase activity is activated by 13(S)-HPODE leading to an active free ferric enzyme (PubMed:20921226). The lipoxygenase and hydroperoxide isomerase activities are in competition and are reciprocally regulated by oxygen (PubMed:20923767). The oxygen reacts with an epoxyallylic radical intermediate leading to an epoxyallylic peroxyl radical, which, due to its limited reactivity within the enzyme active site, it dissociates and leaves the enzyme in the activated free ferric state (PubMed:20923767)
Inhibited by NaBH4 in the presence of FBP
Activated by Gram-negative bacterial lipopolysaccharides (PubMed:3512266). Inhibited by intracellular coagulation inhibitor 1/LICI-1 and to a lesser extent by intracellular coagulation inhibitors 2/LICI-2 and 3/LICI-3 (PubMed:8276848, PubMed:7822280, PubMed:8798603). Inhibited by the small molecule diisopropyl fluorophosphate (DFP) (PubMed:3512266)
Inhibited by okadaic acid, a specific inhibitor of serine/threonine phosphatases of types 1, 2A and 2B
Autophosphorylation is inhibited by inorganic phosphate or EDTA
Inhibited by cloxacillin and oxacillin but not by ACA derivatives or metal chelators
Kinase activity enhanced by ABA and low humidity. Repressed by PP2CA independently of its phosphatase activity. Probably inactivated by ABI1 (PubMed:12468729, PubMed:12514244, PubMed:19955427). Repressed by TOPP1 (PubMed:26943172). Negatively regulated by ABI2 (PubMed:22730405)
Specifically inhibited by spautin-1 (specific and potent autophagy inhibitor-1), a derivative of MBCQ that binds to USP10 and inhibits deubiquitinase activity. Regulated by PIK3C3/VPS34-containing complexes
When exposed to oxidative stress, Gsp amidase activity is transiently inhibited in vivo by oxidation of the catalytic Cys-59 thiol to sulfenic acid; this modification does not affect Gsp synthetase activity. Gsp amidase activity is negatively autoregulated by the Gsp synthetase domain, and is activated by the Gsp synthetase substrates, GSH and ATP-Mg(2+); the occupancy of the synthetase active site may initiate communication through the protein as manifest by the release of inhibition of the amidase activity. A tetrahedral phosphonate analog of glutathionylspermidine, designed as a mimic of the proposed tetrahedral intermediate for either reaction, inhibits the synthetase activity (Ki of 10 uM) but does not inhibit the amidase activity. Amidase activity is inhibited by iodoacetamide in vitro
Activated by Ca(2+)-bound calmodulin following an increase in intracellular Ca(2+). At low Ca(2+) concentrations, the catalytic subunit (also known as calcineurin A) is inactive and is bound to the regulatory subunit (also known as calcineurin B) in which only two high-affinity binding sites are occupied by Ca(2+). In response to elevated calcium levels, the occupancy of the low-affinity sites on calcineurin B by Ca(2+) causes a conformational change of the C-terminal regulatory domain of calcineurin A, resulting in the exposure of the calmodulin-binding domain and in the partial activation of calcineurin A. The subsequent binding of Ca(2+)-bound calmodulin leads to the displacement of the autoinhibitory domain from the active site and possibly of the autoinhibitory segment from the substrate binding site which fully activates calcineurin A
Inhibited by 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) and acetazolamide (PubMed:2371270, PubMed:12958022). Muscarinic receptor stimulation enhances activity through a Ca(2+)-dependent mechanism (PubMed:12958022)
Methyltransferase activity is activated by RAMAC
Regulated by a thiol-based redox modification; oxidation by CuCl(2) leads to a decreased activity
Is sensitive to feedback substrate inhibition by acetoacetyl-CoA. Is inactivated by hymeglusin, which also blocks the growth of E.faecalis, indicating the critical role that the mevalonate pathway plays in isoprenoid biosynthesis
Inhibited by glycerol, inorganic phosphate and arabinose 5-phosphate
Phosphorylation of severin is reduced with high concentrations of calcium ions
Catalytic activity is increase by myristoylated ARF1 (PubMed:19171150). Phosphatidic acid has no effect on catalytic activity (PubMed:19171150)
Phospholipid scramblase activity is activated upon caspase cleavage to generate the XK-related protein 4, processed form (PubMed:25231987, PubMed:33725486). Does not act prior the onset of apoptosis (PubMed:25231987)
Homodimerizes upon caspase cleavage (PubMed:33725486). Phospholipid scramblase activity is activated following interaction with the processed C-terminus of XRCC4 (protein XRCC4, C-terminus) (PubMed:33725486)
Both triacsin C and rosiglitazone inhibit arachidonoyl-CoA ligase activity
Regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP, GTPase activating proteins (GAPs) which increase the GTP hydrolysis activity, and GDP dissociation inhibitors which inhibit the dissociation of the nucleotide from the GTPase. GTP hydrolysis is stimulated by ARHGAP30
N-terminal autoinhibitory domain interacts with the C-terminal kinase domain, inhibiting kinase activity, and preventing interaction with its substrate, MAP2K6. The GADD45 proteins activate the kinase by binding to the N-terminal domain. Activated by phosphorylation on Thr-1494 (By similarity)
Inactivated by calcium and zinc ions
Inhibited by Zn(2+), Fe(3+), Cu(2+) and Ni(2+)
Activated by tyrosine and threonine phosphorylation (PubMed:9032256, PubMed:9211927, PubMed:11113180, PubMed:12455951, PubMed:12477803). Inactivated by dephosphorylation via recruitment of PTC1 to the PBS2-HOG1 complex after adaptation to osmotic stress (PubMed:14685261). PTP2 and PTP3 inactivate HOG1 by dephosphorylating Tyr-176, while the PP2Cs PTC1 and PTC2 or PTC3 dephosphorylate Thr-174 in the activation loop (PubMed:9032256, PubMed:9211927, PubMed:11113180, PubMed:12455951, PubMed:12477803)
Is allosterically regulated by the feedback inhibitor (S)-lysine
Activity is maximal in the presence of calcium. However, unlike phospholipases A2 whose catalytic activity is strictly calcium-dependent, this enzyme shows considerable catalytic activity on phosphatidylcholine emulsified in calcium free solution; the catalytic activity of VT-1 assayed in the absence of calcium ions is 18-20% of that assayed in solution containing calcium ions
Activity decreases in response to phosphate limitation
Activated upon interaction by mucunain, a cowhage (Mucuna pruriens) plant cysteine proteinase
Activity is stimulated by Mg(2+) or Mn(2+)
Activity of CodY is modulated by interaction with two types of effectors: the branched-chain amino acids (BCAAs) leucine, isoleucine and valine, which are signals of the nutritional status of the cell, and GTP, which may signal the energetic status of the cell (PubMed:11331605, PubMed:15228537, PubMed:16488888, PubMed:17993518, PubMed:18083814, PubMed:19749041, PubMed:21764931, PubMed:25645558). During growth in a nutrient-rich medium, the concentrations of these effectors are high, and CodY, once activated by binding to these effectors, shows an increased affinity for its target promoters (PubMed:11331605, PubMed:15228537, PubMed:17993518, PubMed:18083814). GTP and the BCAAs act additively to increase the affinity of CodY for DNA (PubMed:17993518, PubMed:18083814). When nutrients become limiting, the concentrations of BCAAs and GTP drop, leading to dissociation of CodY from the DNA and derepression of genes that are required for adaptation to nutrient-poor conditions (PubMed:11331605, PubMed:15228537, PubMed:17993518). Interacts specifically with GTP and dGTP; no other naturally occurring nucleotides that were tested, including ppGpp and pppGpp, result in DNA protection (PubMed:17993518). GTP hydrolysis is not required for DNA binding (PubMed:17993518)
Inhibited completely by aspartyl protease inhibitor pepstatin A, but not by the serine- or metalloproteinase inhibitors PMSF or EDTA
Channel activity inhibited by ATP via ABCB8/MITOSUR subunit
Inhibited by EDTA, calcium chloride, and zinc chloride. Enhanced by magnesium chloride (By similarity). Glycerophosphodiester phosphodiesterase activity can be modulated by G-protein signaling pathways (By similarity)
Under conditions of nitrogen excess, the DNA binding activity of GlnR is activated by a transient interaction with feedback-inhibited GlnA. Under conditions of nitrogen-limited, GlnR is autoinhibited by its C-terminal region
Activated by phosphatidylserine and tumor necrosis factor (TNF) (PubMed:25180167). Inhibited by scyphostatin (By similarity)
Compared to the defatty-acylase activity, the protein deacetylase activity is weak in vitro, and requires activation (By similarity). The histone deacetylase activity is strongly activated upon binding to nucleosomes and chromatin in vivo (By similarity). Two molecules of SIRT6 associate with the acidic patch of one nucleosome, while the C-terminal disordered region of SIRT6 associates with nucleosomal DNA, leading to efficient histone deacetylation (By similarity). The protein-lysine deacetylase activity is also activated by long-chain free fatty-acids (By similarity)
Inhibited by butan-1-ol
Inhibited by the effector protein NleF that is produced by pathogenic E.coli; this inhibits apoptosis
Atypical PKCs (PRKCI and PRKCZ) exhibit an elevated basal enzymatic activity (that may be due to the interaction with SMG1 or SQSTM1) and are not regulated by diacylglycerol, phosphatidylserine, phorbol esters or calcium ions. Two specific sites, Thr-412 (activation loop of the kinase domain) and Thr-564 (turn motif), need to be phosphorylated for its full activation (By similarity). Might also be a target for novel lipid activators that are elevated during nutrient-stimulated insulin secretion
Activity is inhibited by unphosphorylated GarA. Stimulated by manganese and magnesium
Carbonic anhydrase activity is inhibited by ethoxyzolamide, dithiothreitol, cyanide, and divalent metal chelators dipicolinic acid and nitrilotriacetic acid
Activated by ABA and Ca(2+)
Feedback inhibition by product L-ornithine, (PubMed:15843155). Inhibited by 2(S)-amino-6-boronohexanoic acid (ABH); however, with less efficiency than human ARG1 (PubMed:20527960, PubMed:21728378)
Activated by magnesium ions and thiamine diphosphate
The full-length protein before cleavage is inactive: intramolecular interactions between the N-terminal domain and the C-terminal region as well as the lipid modification, mediate autoinhibition. The pyroptosis-like-inducing activity is carried by the released N-terminal domain (Gasdermin bGSDM, N-terminus)
Requires a minimum of 0.1 mM of calcium for a significant activity. Maximal activity was observed with concentrations of calcium between 1 to 5 mM. Is 10-fold less active with the corresponding concentrations of manganese. Inhibited by NaCl at concentrations of 100 mM and higher
Inhibited by lysine
Activated by glucose up to 200 mM when p-nitrophenyl-beta-glucoside is used as the substrate. This activation by end product concentrations may be due to a transglycosylation activity of the enzyme
Pantothenate uptake is not reduced in osmotically shocked cells or by ATP depletion with arsenate, but is reduced greater than 90% by the dissipation of the membrane electrochemical gradient with 2,4-dinitrophenol
ATP hydrolysis occurs in the polymeric state (By similarity). Unlike for mammalian actin, ATP hydrolysis occurs also in the monomeric form and the release of inorganic phosphate (Pi) is more efficient (By similarity)
Activated by ATP (PubMed:27551084). ATP binding leads to a conformational change that promotes FAD cofactor binding and enzyme activity (PubMed:27551084). ATP binding likely occurs during acox-1.1 folding and/or dimer formation (PubMed:27551084)
Inhibited by sildenafil and zaprinast
Activity with myo-inositol monophosphate and D-galactose 1-phosphate is inhibited by Li(+), Ca(2+) and Mn(2+), but also by Mg(2+) at concentrations above 3 mM
Phospholipase sn-2 versus sn-1 positional specificity is affected by the phospholipid composition of membranes. Phospholipase A2 activity toward 1-hexadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine (PAPE) is enhanced in the presence of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), which promotes lipid bilayer formation (PubMed:16837646). O-acyltransferase activity is inhibited by antiarrhythmic drug amiodarone (PubMed:27993948)
Inhibited by mazindol, cocaine, desipramine, GBR 12783 dihydrochloride, GBR 12909 dihydrochloride and nomifensine
Coiled-coil-mediated oligomerization enhances the catalytic activity. Proteolytic processing of the C-terminus may release the protein from membranes and constitute a mean to regulate the enzyme. May be regulated by HSPB2, RAC1, RAF1 and G-protein second messengers
Inhibited by the antituberculosis drug isoniazid (INH)
Inhibited by 5-CH3-H4PteGlu1/5 and 5-HCO-H4PteGlu1/5 in vitro
Inhibited by captopril, lisinopril, trandolaprilat, fosinoprilat and enalaprilat
Cleavage inhibited by RadB in the absence (but not presence) of ATP
The C-terminal non-catalytic region inhibits the kinase activity, the enzyme is activated by caspase-cleavage. Homodimerization and autophosphorylation of Thr-182 is also required for full activation (By similarity)
Autoinhibited by the ariadne domain, which masks the second RING-type zinc finger that contains the active site and inhibits the E3 activity. Inhibition is relieved upon binding to neddylated cullin-RING ubiquitin ligase complexes, which activate the E3 ligase activity of ARIH1
Transcription activation is repressed by gibberellic acid GA(3) in the presence of TPR4
Activity on the artificial substrate MUF tri-NAG is inhibited by 2-nitrophenylthiocyanates (NPT) compounds. The synergistic effects on peptidoglycan degradation of RipA plus RpfB are inhibited by addition of PBP1A (ponA1)
Activated by tyrosine and threonine phosphorylation (By similarity). Inhibited by the MEK inhibitor U0126 but not by the p38 inhibitor SB203580. Cobalt abolishes kinase activity, while calcium, copper and nickel have little effect on kinase activity
Inhibited by arsenate
Dimerization of the ATPase domain is strictly required for the catalytic activity and binding to double-stranded DNA. Disrupting the interface between ATPase and the CW domains releases autoinhibition since the CW domain sterically impedes binding of the ATPase domain to DNA
Inhibited by ADP
Acyltransferase and acetyltransferase activities are activated by phosphorylation and autoacetylation (PubMed:22539723). Autoacetylation activates the histone acetyltransferase activity (By similarity)
Inhibited by cerulenin
Inhibited by fosmidomycin
Exhibits autoinhibition activity
Triacylglycerol lipase activity is inhibited by increasing bile salts concentrations and not reactivated by CLPS
In vitro inhibited by covalent binding of fosfomycin and the fungal product terreic acid in the presence of substrate UDP-N-acetylglucosamine, with an inactivation rate constant of 130 M(-1)sec(-1) for terreic acid
The acyl-AMP ligase activity is inhibited by the alkylphosphate esters of AMP, adenosine 50-dodecylphosphate (AMPC12) and eicosyl-AMP (AMPC20)
Does not have a calmodulin-binding domain
Down-regulated at acidic pH, with the exception of L-glutamate transport which is up-regulated instead
N-acetylneuraminic acid (Neu5Ac) inactivates NanR by converting NanR oligomers to monomers
Cotransport of monocarboxylates and nicotinate strongly inhibited by ibuprofen, fenoprofen and ketoprofen
Activity is inhibited by IGD1
Inhibited by ascorbate
Inhibited by CDKI-71, CR8, GPC-286199, AG-024322, flavopiridol (alvocidib), RBG-286147, anilinopyrimidine 32, arylazopyrazole 31b, indirubin 3'-monoxime, meriolin 3,P276-00, olomoucine II, pyrazolotriazine, meriolin, variolin, thiazolyl-pyrimidine, thiazolyl-pyrimidine, indirubin-30-monoxime, ZK 304709, AG-012986, AT7519, R547, RGB-286638, imidazole pyrimidine, EXEL-3700, EXEL-8647, 5,6-dichloro-1-b-ribofur-anosyl-benzimidazole (DRB), P276-00, roscovitine (seliciclib, CYC202) and SNS-032 (BMS-387032). Activation by Thr-186 phosphorylation is calcium Ca(2+) signaling pathway-dependent; actively inactivated by dephosphorylation mediated by PPP1CA, PPM1A and PPM1B. Reversibly repressed by acetylation at Lys-44 and Lys-48
Inhibited by iodoacetate and glucose 6-phosphate
Inhibited by guazatine, N-prenylagmatine and 1,12-diaminododecane
Inhibited by UDP-xylose
Channel activity is reduced by low extracellular/lumenal pH level
Activity not affected by inhibitors of phosphatases of the PPP family such as okadaic acid and cypermethrin, or by inhibitors of phosphatases of the PTP family such as sodium orthovanadate
Completely inhibited by p-chloromercuribenzoate and partially inhibited by metal chelating agents
AHBA synthase activity is activated by 3-deoxy-D-arabinoheptulosonic acid 7-phosphate (DAHP), an intermediate in the shikimate pathway, and is irreversibly inhibited by gabaculine (5-amino-1,3-cyclohexadiene-1-carboxylate)
Bound pyruvate or other intermediates in the aldol addition reaction catalyzed by BphI allosterically activates BphJ reductive deacylation activity
Threefold increase in the catalytic activity in the presence of FH (frataxin) (PubMed:22511606). 30-fold increase in the catalytic activity in the presence of SUFE1 (PubMed:16437155)
Hexose-6-phosphate dehydrogenase (H6PD) provides cosubstrate NADPH, and the glucose-6-phosphate transporter in the ER-membrane supplies the substrate for H6PDH, their activities stimulate the reduction of cortisone and abolish the oxidation of cortisol
Inhibited by lumenal H(+) and Na(+) (PubMed:18369318, PubMed:29106414). The channel pore shows dynamic behavior and undergoes spontaneous, Ca(2+)-dependent modulation when conducting Ca(2+) (PubMed:20378547)
Inhibited by dinitrophenol, 5-(2-naphthylmethyl)-D-hydantoin (D-NMH), 5-(2-naphthylmethyl)-L-hydantoin (L-NMH), 5-bromovinylhydantoin (BVH) and 5-indolylmethyl-L-hydantoin (L-IMH) (PubMed:16621827, PubMed:24952894). The affinity of benzyl-hydantoin is increased over 10-fold in the presence of 15 mM of sodium (PubMed:18927357)
The hydrolysis of TAMe (tosyl-arginine methyl ester) substrate is activated by Ca(2+), Fe(3+), Mg(2+) and Zn(2+), and inhibited by EDTA, PMSF and DTT
Inhibited by bengamide derivatives and by various metalloform-selective inhibitors
Activated upon ALKAL2 ligand-binding. ALKAL2-driven activation is coupled with heparin-binding (By similarity). Following ligand-binding, homodimerizes and autophosphorylates, activating its kinase activity (By similarity). Inactivated through dephosphorylation by receptor protein tyrosine phosphatase beta and zeta complex (PTPRB/PTPRZ1) when there is no stimulation by a ligand (By similarity)
Inhibited by Cu(2+) and Ni(2+), and to a lesser extent by EDTA, Mn(2+) and Mg(2+)
Fenoxanil inhibits arp1 scytalone dehydratase activity (PubMed:19703288)
Inhibited by phosphate. The phosphate forms a covalent bond with the active site 3-oxoalanine
Inhibited by exogenous phosphatidylserine
Strongly inhibited by dithiothreitol and high ionic strength buffers
Binding of a cognate ligand leads to dimerization and activation by autophosphorylation on tyrosine residues. In vitro kinase activity is increased by Mg(2+). Inhibited by PD153035, lapatinib, gefitinib (iressa, ZD1839), AG1478 and BIBX1382BS
Inhibited by the benzodioxole 4-[bis(1,3-benzodioxol-5-yl)-hydroxymethyl]-1-piperidinecarboxylic acid (4-nitrophenyl) ester (JZL184)
Inhibited by trichostatin A
Six- to eight-fold activated by Mn(2+). Retains residual activity after EDTA treatment in vitro. Also activated by NADH and, to a lesser extent, by NAD(+). Strongly inhibited by Zn(2+). Mg(2+) and Ca(2+) have no effect on enzymatic activity
Activated by binding of S100B which releases autoinhibitory N-lobe interactions, enabling ATP to bind and the autophosphorylation of Ser-281. Thr-444 then undergoes calcium-dependent phosphorylation by STK24/MST3. Interactions between phosphorylated Thr-444 and the N-lobe promote additional structural changes that complete the activation of the kinase. Autoinhibition is also released by the binding of MOB1/MOBKL1A and MOB2/HCCA2 to the N-terminal of STK38 (By similarity)
Can be activated without removal of the activation peptide
Inhibited by 2-hydroxy-1-naphthaldehyde and nicotinamide
Stimulated by calcium/calmodulin. Inhibited by NOSIP and NOSTRIN
Inhibited by Sirtinol, A3 and M15 small molecules (PubMed:11483616). Inhibited by nicotinamide. Inhibited by a macrocyclic peptide inhibitor S2iL5 (PubMed:24389023). Inhibited by EP300-induced acetylation (PubMed:18722353)
Inhibited by 3-amino-4-hydroxybenzensulfonic acid, 4-hydroxy-3-nitrobenzaldehyde, L-tyrosine, P-hydroxybenzaldehyde. Activated by the copper chaperone GriE
Stimulated by CHIL2 but inhibited by CHIL1
Isoform M2 is allosterically activated by D-fructose 1,6-bisphosphate (FBP) (PubMed:2813362, PubMed:15996096, PubMed:1854723, PubMed:18337815). Inhibited by oxalate and 3,3',5-triiodo-L-thyronine (T3) (PubMed:15996096). The activity of the tetrameric form is inhibited by PML (PubMed:18298799). Selective binding to tyrosine-phosphorylated peptides releases the allosteric activator FBP, leading to inhibition of PKM enzymatic activity, this diverts glucose metabolites from energy production to anabolic processes when cells are stimulated by certain growth factors (PubMed:18337815). Glycolytic flux are highly dependent on de novo biosynthesis of serine and glycine, and serine is a natural ligand and allosteric activator of isoform M2 (PubMed:23064226). Acetylation at Lys-433 promotes its translocation into the nucleus and homodimerization, promoting the protein kinase activity (PubMed:24120661)
Is completely inhibited by EDTA, N-ethylmaleimide, Cu(2+), Zn(2+), and potassium cyanide in vitro. Mg(2+) and Ca(2+) have no effect on the dehydrogenase activity, and 1 mm Mn(2+) slightly inhibit the enzyme (21% inhibition)
Moderately inhibited by staurosporine, a broad-range protein kinase inhibitor
Activated by it's association with the proteasome
Alternates between an inactive GDP-bound form and an active GTP-bound form (By similarity). Activated by a guanine nucleotide-exchange factor (GEF) and inactivated by GTPase-activating protein (GAP) (By similarity)
Redox regulation of the activity by thioredoxin TRXy1
Inhibited by L(+)-tartrate
Atypical PKCs (PRKCI and PRKCZ) exhibit an elevated basal enzymatic activity (that may be due to the interaction with SMG1 or SQSTM1) and are not regulated by diacylglycerol, phosphatidylserine, phorbol esters or calcium ions. Two specific sites, Thr-410 (activation loop of the kinase domain) and Thr-560 (turn motif), need to be phosphorylated for its full activation. Phosphatidylinositol 3,4,5-trisphosphate might be a physiological activator (By similarity). Isoform 2: Constitutively active (By similarity)
Strongly inhibited by the imidazole-modifying compound 2-bromo-4'-nitroacetophenone, by HgCl(2) and CoCl(2). Not inhibited by the thiol reagents iodoacetate and dithiothreitol
Stimulated by calcium/calmodulin
Inhibited by interaction with the metallocarboxypeptidase inhibitor (MCPI) from N.versicolor that binds to the catalytic zinc ion
ATPase activity is stimulated by DNA
Inhibited by melatonin, resveratrol and 5-hydroxytryptamine
Binds cyclic di-AMP (c-di-AMP), which may regulate the transporter activity
Exhibits substrate-dependent heparin activation. Drug-mediated inhibition leads to a delay of the oscillations with the magnitude of this effect dependent upon the timing of drug administration. Inhibited by phosphorylation. Repressed by 3-[(2,4,6-trimethoxyphenyl)methylidenyl]-indolin-2-one (IC261), N-(2-aminoethyl)-5-chloroisoquinoline-8-sulfonamide (CKI-7), 4-[4-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-5-pyridin-2-yl-1H-imidazol-2-yl]benzamide (D4476), 3,4-diaryl-isoxazoles and -imidazoles, and 4-(3-cyclohexyl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl) pyrimidin-2-ylamine (PF670462, PF670)
Activated by the negatively charged lipids phosphatidylglycerol (PG), cardiolipin (CL), dodecylphosphate-rac-glycerol (PDG), 1,2-dioleoyl-phosphatidylglycerol (DOPG) and phosphatidylserine (PS)
Activated by DAG and phorbol esters. Phorbol-ester/DAG-type domains 1 and 2 bind both DAG and phorbol ester with high affinity and mediate translocation to the cell membrane. Autophosphorylation of Ser-735 and phosphorylation of Ser-731 by PKC relieves auto-inhibition by the PH domain
Kinase activity is stimulated by cell-cycle specific phosphorylation
Is inhibited by the organophosphates paraoxon and dimethylchlorophosphate (DMCP)
Enzyme activity is inhibited by globomycin, a cyclic peptide antibiotic
Regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP, GTPase activating proteins (GAPs) which increase the GTP hydrolysis activity, and GDP dissociation inhibitors which inhibit the dissociation of the nucleotide from the GTPase. GTP hydrolysis is stimulated by ARHGAP30 and ARHGAP44
Inhibited by the serine protease inhibitor phenylmethylsulfonyl, and trypsin inhibitors soybean trypsin inhibitor and tosyllysine chloromethyl ketone. Not inhibited by dithiothreitol, a cysteine protease inhibitor
Ag(+), Co(2+), Cu(2+) and Hg(2+)
Inhibited by the not secondly cleaved propeptide. Inhibited by m-guanidinomethyl-phenylacetyl-Arg-Val-Arg-(amidomethyl)-benzamidine (m-guanidinomethyl-Phac-RVR-Amb) and 4-guanidinomethyl-phenylacetyl-Arg-Tle-Arg-4-amidinobenzylamide (MI-1148)
N-terminal region of PAH is thought to contain allosteric binding sites for phenylalanine and to constitute an 'inhibitory' domain that regulates the activity of a catalytic domain in the C-terminal portion of the molecule
ATPase activity is much induced upon complex formation with ClpQ
Serine/threonine-protein kinase activity is stimulated upon ADP-D-glycero-beta-D-manno-heptose (ADP-Heptose)-binding
Activated by insulin. Inhibited by diphenylene iodonium (By similarity). Inhibited by plumbagin. Activated by phorbol 12-myristate 13-acetate (PMA)
Inhibited by S-adenosyl-N-decyl-aminoethyl (SADAE)
Inhibited by cysteine
Activated by valinomycin and inhibited by monensin
NAD-dependent protein-lysine deacetylase and deacylase activities are activated by nucleic acids. Histone deacetylase activity is activated by DNA. Protein-lysine deacylase activity is activated by RNA. H3K18Ac histone deacetylase activity is inhibited by methylation at Arg-390. H3K18Ac histone deacetylase activity is inhibited by deubiquitination by USP7
Inhibited by the substrate analog N-acetyl tryptophan
Completely inhibited by p-chloromercuribenzoate and N-ethylmaleimide. Strongly inhibited by iodoacetate. Inhibited by Pb(2+), Fe(3+), Ag(+) and Hg(2+) and partially inhibited by several other metal ions Mn(2+), Zn(2+) and Cu(2+)
Inhibited by sarcolipin (SLN), phospholamban (PLN) and myoregulin (MRLN) (By similarity). Reversibly inhibited by phospholamban (PLN) at low calcium concentrations (By similarity). Dephosphorylated PLN decreases the apparent affinity of the ATPase for calcium. This inhibition is regulated by the phosphorylation of PLN (By similarity). Enhanced by DWORF; DWORF increases activity by displacing sarcolipin (SLN), phospholamban (PLN) and myoregulin (MRLN) (By similarity)
By phosphorylation of various serine residues. Allosteric regulation by calcium
Protonation/deprotonation of Glu-15 may play an important role in transporter function (PubMed:32636271). Cadaverin transport is inhibited in the presence of CCCP (PubMed:31416917)
Inhibited by azole drugs
By phosphorylation (By similarity). Activated by anionic lipid vesicles and by oleic acid or diacylglycerol-containing phosphatidylcholine vesicles (PubMed:7918629, PubMed:8155650)
Inhibited by (+)-catechin, quercetin and (+)- and (-)-dihydroquercetin. Not inhibited by salt. Positive cooperativity with NADPH acting as cosubstrate and modulator
Enzyme activity is tightly regulated to prevent the accumulation of reactive oxygen species in the endoplasmic reticulum. Reversibly down-regulated by the formation of disulfide bonds between Cys-150 and Cys-295
Completely inhibited by Cu(2+) and activated by Co(2+)
Inhibited by phenylthiourea
Requires dithiothreitol (DTT) for activity in vitro. Activated by Tween 20 or Tween 80 in vitro. Inhibited by UMP, UDP, UTP, 4-thio-UMP, Bio-11-UTP, and UDP-Glc but not by uridine, dUDP, dUMP, UDP-hexanolamine, and CTP. Also inhibited by EDTA
Inhibited by the wheat xylanase inhibiting protein I (XIP-I)
Produced as a latent enzyme which is activated by dsRNA generated during the course of viral infection. The dsRNA activator must be at least 15 nucleotides long, and no modification of the 2'-hydroxyl group is tolerated. ssRNA or dsDNA do not act as activators (By similarity)
Probably maintained in an inactive state via its interaction with securin ify-1 which acts as a pseudosubstrate thereby blocking access to the catalytic site. Upon ify-1 degradation at the onset of anaphase, sep-1 is likely to become active. In addition, interaction with ify-1 stabilizes sep-1
Binds four calcium ions which seem to play an important role in the thermostability of the enzyme
The direction of formate translocation depends on external pH and electron donor source
Activated by calcium ions. Inhibited by EDTA, activity is recovered by the addition of calcium ions, but not magnesium or zinc ions. Inhibited by PMSF
In the inactive state, the helix alphaC is packed against the helical, non-phosphorylated activation segment (AS) (PubMed:28545134). Upon activation, helix alphaC is displaced and the phosphorylated AS becomes disordered (PubMed:28545134). Specifically inhibited by GSK583, which blocks NOD2 signaling by interfering with XIAP binding to RIPK2 (PubMed:29452636). Specifically inhibited by CSLP37 and CSLP43, which blocks NOD2 signaling by interfering with XIAP binding to RIPK2 (PubMed:30026309)
Completely inhibited by 10 uM of nickel, copper, cadmium and mercury ions. Inhibited by zinc with an IC(50) of 1-3 uM. Metal ion inhibition may be a mechanism to control activity in vivo
Repressed by pepstatin A
PAM activity is inhibited by EDTA, phenylglyoxal and diethyl pyrocarbonate (PubMed:12699694). PAL activity is stimulated by cadmium and inhibited by mercury (By similarity)
Citrate synthase-lysine methyltransferase activity is inhibited by S-adenosylhomocysteine (AdoHcy) and oxaloacetate (OAA) (PubMed:28887308)
Activity is inhibited by 5-iodotubercidin and 5'-amino-5'-deoxyadenosine
5,6-dichloro-1-b-D-ribofuranosylbenzimidazole (DRB) inhibits autophosphorylation. TG003 inhibits its kinase activity and affects the regulation of alternative splicing mediated by phosphorylation of SR proteins
FK506, isonitrile, enniatin, RU49953, kitasatospora E420, staurosporine CGP42700, prenyl-flavonoids, D-octapeptides were found to be inhibitors in vivo. Vanadate and oligomycin were found to be inhibitors in vitro
Present in an inactive conformation in the absence of bound ligand. Binding of PDGFB and/or PDGFD leads to dimerization and activation by autophosphorylation on tyrosine residues
Inhibited by Hg(2+) ion and EDTA
Binding to PARP9 enhances DTX3L catalytic activity
Hexokinase is an allosteric enzyme inhibited by its product D-glucose 6-phosphate (PubMed:1637300). Hexokinase activity is inhibited by N-acetyl-D-glucosamine (PubMed:27374331)
Proteolysis inhibited by EDTA and captopril, and by peptides that encompass the VAMP2 cleavage site (Ala-Ser-Gln-Phe-Glu-Thr-Ser and Gln-Phe-Glu-Thr) (PubMed:1331807). Translocation of whole toxin into neurons is inhibited by toosendanin (PubMed:21925111)
Inhibited by 1,10-phenanthroline, a metalloprotease inhibitor which is a divalent metal chelator. Also inhibited by EDTA. Not inhibited by Bestatin, an aminopeptidase inhibitor, nor to a mixture of inhibitors for serine, cysteine, and aspartic proteases and aminopeptidases
Shows pH-dependent activity (PubMed:22407317, PubMed:23589309). The Glu/GABA transport activity is robust at pH 4.5 and rapidly decreases with increasing pH, with no detectable activity at pH 6.5 or above (PubMed:22407317, PubMed:23589309). The Glu analog L-trans-pyrrolidine-2,4-dicarboxylic acid (L-PDC) blocks the uptake of glutamate by selective inhibition (PubMed:12855178)
Inhibited by EDTA and at pH 6.0
Inhibited by vanadate
Inhibited by Al(3+), La(3+) and Gd(3+). Up-regulated by H(2)O(2), cryptogein, salicylic acid (SA) and cold shock
Cobalt uptake is inhibited by uncouplers (CCCP and 3,5-di-tert-butyl-4-hydroxybenzylidenemalononitrile) and by the addition of excess nickel
Inhibited by pyridoxal 5'-phosphate, bathophenanthroline, tannic acid, mersalyl, mercuric chloride and bromocresol purple
Activation requires multiple phosphorylation events on serine/threonine residues. Activation appears to be first mediated by phosphorylation of multiple sites in the autoinhibitory domain, which facilitates phosphorylation at Thr-412, disrupting the autoinhibitory mechanism and allowing phosphorylation of Thr-252 by PDPK1. The active conformation of the kinase is believed to be stabilized by a mechanism involving three conserved phosphorylation sites located in the kinase domain activation loop (Thr-252) and in the AGC-kinase C-terminal domain (Ser-394 in the middle of the tail/linker region and Thr-412 within a hydrophobic motif at its end). Activated by mTORC1; isoform Alpha I and isoform Alpha II are sensitive to rapamycin, which inhibits activating phosphorylation at Thr-412. Activated by PDPK1 (By similarity)
Repressed by withaferin A (WA)
Inhibited by ketoconazole
Contrary to classical chorismate mutases, CMU1 is not subject to allosteric regulation by tryptophan and tyrosine (PubMed:21976020, PubMed:30651637). Activity is decreased in a non-competitive and allosteric manner by the binding of the host defense kiwellin KWL1 which probably blocks substrate access to the active site of CMU1 (PubMed:30651637)
Down-regulated by phosphorylation
Not activated by classical allosteric effectors
Inhibited by methimazole
Activated by an autocatalytic mechanism
(Microbial infection) RNA cleavage activity is reduced when ADP-ribosylated
Inhibited by Mg(2+) (PubMed:15537630). Stimulated in vitro in a concentration-dependent fashion by EDF, which is able to overcome inhibition by cognate antitoxin MazE (PubMed:21419338). The TA system is antagonized by stress response kinase SrkA, but probably not by phosphorylation of MazF (PubMed:23416055)
Requires both ATP and a high membrane potential for activity. Binding of ATP causes a conformational change in KtrA, which promotes formation of the KtrAB complex. Can also bind, with lower affinity, other nucleotides such as NADH or NAD(+), but only ATP can induce a conformational change
Inhibited by retinoic acid, but phorbol ester treatment activates it
Inhibited by peptidyl-argininals wth Pro in the P2 position, diisopropyl fluorophosphate, phenylmethanesulfonyl fluoride, leupeptin, antipain, soybean trypsin inhibitor, aprotinin, ovomucoid, valyl-prolyl-arginyl-chloromethane, glycyl-valyl-arginyl-chloromethane, p-aminobenzamidine, benzamidine, zinc chloride and mercuric chloride
Inhibited by pentalenolactone (PL)
Cell-cycle regulated, maximal activity in S-phase. Inactivated by phosphorylation at Ser-743, potentially by CHEK1 (By similarity)
Repressed by 2-(2-hydroxyethylamino)-6-(3-chloroanilino)-9-isopropylpurine (DB08325)
Monomethylarsonic acid reductase activity is competitively inhibited by 1-chloro 2,4-dinitrobenzene (CDNB) and by deoxycholate
Inhibited by warfarin (coumadin) (PubMed:23928358). Warfarin locks VKORC1 in both redox states into the closed conformation (By similarity)
Strongly inhibited by FK506 but is completely resistant to cyclosporin A
Strongly inhibited by Ag(2+), Cu(2+) and cetyltrimethyl ammonium bromide (CTAB)
Feedback inhibition by L-ornithine
Inhibited by Zn2+
Its function may be negatively regulated by one of the MamGFDC proteins
The protein kinase 1 domain (also termed pseudokinase domain) mediates autoinhibition of the TYK2 kinase domain
Mycophenolic acid (MPA) is a non-competitive inhibitor that prevents formation of the closed enzyme conformation by binding to the same site as the amobile flap. In contrast, mizoribine monophosphate (MZP) is a competitive inhibitor that induces the closed conformation. MPA is a potent inhibitor of mammalian IMPDHs but a poor inhibitor of the bacterial enzymes. MZP is a more potent inhibitor of bacterial IMPDH. Subject to product inhibition by XMP and NADH. Also inhibited by ADP
Strongly inhibited by mersalyl, p-chloromercuribenzenesulfonate, mercuric chloride, N-ethylmaleimide, pyridoxal 5'-phosphate, bathophenanthroline, and tannic acid. Partially inhibited by alpha-cyanocinnamate and bromescol purple. Weakly inhibited by butylmalonate and phenylsuccinate. Not inhibited by 1,2,3-benzenetricarboxylate or carboxyatractyloside
Inhibited by different divalent cations, such as Mg(2+), Mn(2+), Fe(2+), Cu(2+) and Zn(2+)
Its proteolytic activity is blocked by a signal peptide peptidase (SPP) inhibitor, (ZLL)2-ketone (ZLL) or a gamma-secretase inhibitor, LY411,575 (PubMed:16873890). However, is not inhibited by ZLL and LY411,575 for activity on simian foamy virus envelope glycoprotein gp130 (PubMed:23132852)
Inhibited by acidic pH
Competitive inhibition by cinnamic acid (CA)
Phosphorylation by CSK at Tyr-530 inhibits kinase activity. Inhibitory phosphorylation at Tyr-530 is enhanced by heme. Further phosphorylation by CDK1 partially reactivates CSK-inactivated SRC and facilitates complete reactivation by protein tyrosine phosphatase PTPRC. Integrin engagement stimulates kinase activity. Phosphorylation by PTK2/FAK1 enhances kinase activity. Butein and pseudosubstrate-based peptide inhibitors like CIYKYYF act as inhibitors (By similarity). Phosphorylation at Tyr-419 increases kinase activity
The neuronal activity and the influx of calcium positively regulate the kinase activity and the internalization of the receptor which are both important for active signaling. Regulated by NGFR that may control the internalization of the receptor. NGFR may also stimulate the activation by BDNF compared to NTF3 and NTF4. The formation of active receptors dimers able to fully transduce the ligand-mediated signal, may be negatively regulated by the formation of inactive heterodimers with the non-catalytic isoforms (By similarity)
Activated by phosphorylation (By similarity). Activated by hyperosmotic stress
Inhibited by its reaction product N-acetylglucosamine-1-phosphate and by UDP-N-acetylmuramic acid, which is one of the first precursors specific for the peptidoglycan pathway
Activated by the small GTPase RAC1
Esterase activity of the CE2 module is inhibited when this domain binds to cellohexaose or beta-glucan
Activity is regulated by DgcM and PdeR
Inhibited by cGMP (PubMed:8695850, PubMed:8155697). Inhibited by 17beta-estradiol (PubMed:35104454). Inhibited by milrinone (PubMed:27975297)
Activated by phosphatidylserine and tumor necrosis factor (TNF). Inhibited by scyphostatin
Selectively inhibited by the enantiopure organoruthenium inhibitor 9E1. Activated following arsenic trioxide (As(2)O(3)) treatment
LTC4 transport is completely inhibited by 1 mM orthovanadate
Isoform Short: Inhibited by L-ornithine with a Ki of approximately 0.25 mm. Isoform Long: Insensitive to ornithine inhibition. This is due to the two amino acid insert which abolishes feedback inhibition of P5CS activity by L-ornithine
Activated in reducing conditions
Inhibited by bile salts, is reactivated by (pro)colipase/CLPS
Allosterically activated by magnesium, and possibly also other divalent metal cations. Allosterically activated by ATP, ADP or GTP (Potential)
The low basal catalytic activity in increased 1000-fold in the presence of UDP-MurNAc-L-Ala, the product of the preceding enzyme in the peptidoglycan biosynthesis
Regulated by the end-product isoleucine via a feedback inhibition. The binding of isoleucine has inhibitory effects on the binding of both pyruvate and acetyl-CoA. May act via conformational change of the dimer interface of the regulatory domain, leading to inhibition of the catalytic reaction
Intrinsic GTPase activity is very slow and can be stimulated by the presence of 50S ribosomal subunits or 70S ribosomes. GTPase activity is inhibited by ATP
Inhibited by acifluorfen
Regulated by a negative feedback mechanism through sterols and non-sterol metabolites derived from mevalonate (By similarity). Phosphorylation at Ser-871 down-regulates the catalytic activity (PubMed:8415689)
Its activity is inhibited by trichostatin A (TSA) and butyrate, 2 well known histone deacetylase inhibitors
ssDNase activity is activated by target RNA binding to the Csm-crRNA complex and is inhibited by EDTA
Inactivated by O(2)
Perturbation in protein folding in the endoplasmic reticulum (ER) promotes reversible dissociation from HSPA5/BIP and oligomerization, resulting in transautophosphorylation and kinase activity induction (By similarity)
Thioesterase activity is inhibited by iodoacetamide and photoactivated methylene blue, and slowly inhibited by 2,4-dinitrofluorobenzene (PubMed:4554913). Protease and lysophospholipase activities are inhibited by diisopropylfluorophosphate (DFP) (PubMed:1864840, PubMed:4945109, PubMed:238979). Lysophospholipase activity is inhibited by Fe(2+), Fe(3+) and Al(3+) ions (PubMed:238979). Diethyl p-nitrophenyl phosphate (DENP) irreversibly inhibits both the protease and thioesterase activities (PubMed:12846577)
Substrate inhibition by genkwanin (GENK) at concentrations above 10 mM
Activated by the glutamine sensor PIB2 in nutrient-rich conditions
Activity is strongly inhibited by galotannin. Inhibited by P1-(adenosine-5')-P4-(nicotinic-acid-riboside-5')-tetraphosphate (Nap4AD) (By similarity)
Activity is decreased by EGTA or EDTA
Specifically inhibited by the fungal toxin fumitremorgin C and Ko143
Inhibited by the proton ionophore carbonyl cyanide m-chlorophenylhydrazone (CCCP)
After reacting with DNA bearing a Chi site the holoenzyme is disassembled and loses exonuclease activity, DNA unwinding and Chi-directed DNA cleavage; RecB remains complexed with ssDNA, which may prevent holoenzyme reassembly (PubMed:10197988). High levels of Mg(2+) (13 mM MgCl(2+)) or incubation with DNase allow holoenyzme reassembly, suggesting it is DNA bound to RecB that prevents reassembly (PubMed:10197988)
Non-competitively inhibited by nicotinamide in vitro and in vivo, but not by nicotinic acid. Nicotinamide inhibits the deacetylation activity by reacting with a reaction intermediate
Perchlorate inhibits iodide transport activity
Inhibited by the serine protease inhibitor phenylmethylsulfonyl fluoride, the histidine reagent diethylpyrocarbonate and two sulfhydryl reagents, mercuric chloride and naphthol AS-D chloroacetate (PubMed:12039716). Not inhibited by EDTA (PubMed:12039716)
Inhibited by cadmium, copper, zinc when added activity but with less efficiency
Does not require magnesium or any other divalent metal ions for activity
Inhibited by urea analogs and phloretin
Brominating activity not inhibited by azide, peroxidase activity stimulated by bromide
Is potently inhibited by the sulfone dapsone and the two sulfonamides sulfamethoxazole and sulfamethoxypyridazine, with Kis in the range of 12 to 32 nM. Is only poorly inhibited by p-aminosalicylate (PAS) (PubMed:10542185). The inhibition of DHPS by sulfathiazole antagonizes PAS-mediated growth inhibition and therefore confers resistance to PAS (PubMed:23779105)
Inhibited by pGpG
Magnesium-independent phospholipid phosphatase (PubMed:9305923). Insensitive to N-ethylmaleimide (PubMed:9305923). Inhibited by sphingosine, zinc ions and modestly by propanolol (PubMed:9305923, PubMed:9705349). Inhibited by vanadate (PubMed:10962286)
Allosterically activated by AMP
At rest, the N- and C-terminal domains interact, as part of a larger autoinhibitory complex, with calmodulin pre-associated at the N-terminal domain. Upon a calcium rise, calmodulin becomes calcium-saturated and subsequently binds to the C-terminal domain. Fully calcium-saturated calmodulin then leaves the N-terminal domain, binding solely to the C-terminal domain, and the whole autoinhibitory complex dissociates, resulting in activation of adenylate cyclase. As local calcium concentrations decrease, the calmodulin becomes calcium free and binds once more to the N-terminal domain, whereupon the whole system returns to rest with the re-association of the autoinhibitory complex. In non-excitable cells, activated by capacitative calcium entry (CCE) through store-operated channels, namely through interaction with ORAI1 and STIM1; membrane raft and caveolae localization and membrane integrity are indispensable. CCE-mediated adenylate cyclase activity is decreased by AKAP5 and AKAP7. CCE-mediated adenylate cyclase activity is up-regulated by AKAP9 and the mitochondrially targeted AKAP1. In excitable cells, activated during membrane depolarization through L-type voltage-gated calcium channels (VGCC), leading to calcium entry; the L-type alpha subunit is sufficient. Activated via stimulation of the GLP1R. Synergistically activated by calcium/calmodulin and GNAS. Stimulated by forskolin. Inhibited by PKA directly bound to AKAP5 at membrane raft. Inhibition by acute activation of OPRM1 and activation by chronic activation of OPRM1 is mediated by pertussis toxin-sensitive G(i) and G(o) G alpha proteins and G beta-gamma dimer. Activity is inhibited by G beta-gamma dimer
Activated by divalent metal cations; Mn(2+) is the most efficient, followed by Ca(2+) and Mg(2+). In contrast to PgdA from S.pneumoniae, these ions are not absolutely required for deacetylase activity
Completely inhibited by EDTA and EGTA. Partially inhibited by serine proteinase inhibitors PMSF and benzamidine. Not inhibited by cysteine proteinase inhibitors mercury ions and E-64. Is active without cofactors, although the presence of low concentrations of calcium and zinc ions enhanced its ability to convert prothrombin (F2) into active thrombin
Allosterically activated by ADP and other diphosphonucleosides, and allosterically inhibited by phosphoenolpyruvate. The binding affinities for these effectors are decreased however, and therefore the allosteric effect becomes apparent only at high effector concentrations
Activity is strongly inhibited by riboflavin analogs, such as lumiflavin, flavin mononucleotide (FMN), flavin adenine dinucleotide (FAD), by methylene blue, and to a lesser extent by amiloride. Riboflavin transport is Na(+)-independent at low pH but significantly reduced by Na(+) depletion under neutral pH conditions
Interaction with OASA1 negatively impacts the transporter activity
Inhibited by sodium fluoride (NaF) and pyrophosphate. Strongly inhibited by manganese ion and, to a lower extent, by magnesium and calcium ions. Also inhibited by Cu(2+) ion. In an indirect manner, it is also inhibited by the zinc ion which is able to form a complex with DGPP and prevent the enzyme from removing the phosphate from the substrate. Not inhibited by N-ethylmaleimide
Inhibited by dihydropyridines (DHP), such as isradipine (By similarity). Inhibited by nifedipine (PubMed:10101289). Channel activity is regulated by Ca(2+) and calmodulin (By similarity). Binding of STAC1, STAC2 or STAC3 to a region that overlaps with the calmodulin binding site inhibits channel inactivation by Ca(2+) and calmodulin (By similarity). Binding of calmodulin or CABP1 at the same regulatory sites results in opposite effects on the channel function (By similarity). Shear stress and pressure increases calcium channel activity (By similarity)
Inhibited by S-hexylglutathione
Specific and total activity is decreased in presence of alpha-bisabolol
Activated by autophosphorylation at Thr-439
GTPase activity is strongly activated by potassium ions
Activated by autophosphorylation on Ser-220. Kinase activity is inhibited by SPRED1
Inhibited by CGP57380 and staurosporine. Activated by phosphorylation in a negative-feedback regulatory manner in response to chemotherapy (e.g. cytarabine) and thus impairs the generation of antileukemic responses
Produced as a latent enzyme which is activated by dsRNA generated during the course of viral infection. Strongly activated by long dsRNAs at least 50 nucleotides in length. ssRNA does not activate the enzyme
Activity is inhibited by binding to OTUB1, which prevents 'Lys-63'-linked polyubiquitination
Activated by GTP. Subject to allosteric product inhibition by CTP. Inhibited by p-chloromercuriphenylsulfonic acid, N-ethylmaleimide and cyclopentenylcytosine (CPEC) (By similarity)
Stability and function are regulated by the effector molecule fructose-1,6-bisphosphate (FBP). In the presence of glucose, binding of FBP to the low-affinity sugar-binding site of CggR disrupts dimer/dimer bridging interactions and triggers a tetramer to dimer transition, which leaves two physically independent dimers on the target DNA and allows transcription of the downstream coding sequences by the RNA polymerase. In addition, FBP and several other phosphorylated compounds can bind to a high-affinity binding-site and protect CggR against aggregation and proteolysis
5-fluoro-1,3-dihydro-1-hydroxy-1,2-benzoxaborole inhibits LARS1 by forming a covalent adduct with the 3' adenosine of tRNA(Leu) at the editing site, thus locking the enzyme in an inactive conformation
The C-terminal non-catalytic region inhibits the kinase activity, the enzyme is activated by caspase-cleavage. Homodimerization and autophosphorylation of Thr-183 is also required for full activation (By similarity)
Inhibited by plitidepsin, a chemical compound extracted from the ascidian Aplidium albicans
Strongly inhibited by PBD150, 1-benzylimidazole and N-omega-acetylhistamine, in a Zn(2+)-independent manner
Exists in an autoinhibited state in the absence of substrate protein, probably due to interactions of the leucine-rich repeat domain with the catalytic domain. Is activated upon binding to a substrate protein
Inhibited by EDTA, 1,10-phenanthroline, cyanide, and serum alpha2-microglobulin. Not inhibited by EGTA, PMSF, leupeptin, pepstatin and aprotinin
In contrast to classical FBPases, is resistant to inhibition by lithium
Kinase activity is activated upon binding to Rho proteins (RHOA, RHOB and RAC1). Activated by lipids, particularly cardiolipin and to a lesser extent by other acidic phospholipids. Activated by caspase-3 (CASP3) cleavage during apoptosis. Two specific sites, Thr-778 (activation loop of the kinase domain) and Ser-920 (turn motif), need to be phosphorylated for its full activation (By similarity)
Bimane-S-cysteinylglycine-hydrolyzing activity is inhibited by o-phenanthroline or bestatin, and is activated by the addition of zinc chloride
Activated by a monovalent cation that binds near, but not in, the active site. The most likely occupant of the site in vivo is potassium. Ion binding induces a conformational change that may alter substrate affinity (By similarity) (PubMed:27601466). Repressed by calcium, rubidium and sodium (PubMed:27601466). Substrate inhibition is observed in the presence of high ATP concentration (Ki=2.44 mM) (PubMed:27601466)
Competitively inhibited by glyphosate. Activated by ammonium, rubidium or potassium ions
Inactivated in response to cold stress
Completely inhibited by ZnSO(4), ZnCl(2), AgNO(3), CdCl(2) and HgCl(2). Partially inhibited by PbCl(2), NiCl(2) and CoCl(2). Unaffected by LiBr, H(2)BO(3), NaCl, MgSO(4), AlCl(3), KCl, CaCl(2), CrCl(3), MnCl(2), FeSO(4), Fe(NH(4))(2)(SO(4))(2), CuSO(4), RbCl, Na(2)MoO(4), (NH(4))(6)Mo(7)O(24), SnCl(2), CsCl and BaCl(2). Completely inhibited by phenylhydrazine, but not by the other carbonyl reagents hydroxylamine, hydrazine, D,L-penicillamine and D-cycloserine. Unaffected by the chelating agents o-phenanthroline, 8-hydroxyquinoline, enthylenediaminetetraacetic acid and alpha,alpha'-dipyridyl. Partially inhibited by the thiol reagents p-chloromercuribenzoate, iodoacetate and N-ethylmaleimide. Not affected by the serine protease inhibitor phenylmethanesulfonyl fluoride, the serine/cysteine protease inhibitor leupeptine or the aspartic protease inhibitor pepstatin
Activated by alpha-ketoglutarate and inhibited by glutamate and by RocG
Inactivated by the begomovirus AL2 protein or the curtovirus L2 protein
Rab activation is generally mediated by a guanine exchange factor (GEF), while inactivation through hydrolysis of bound GTP is catalyzed by a GTPase activating protein (GAP) (By similarity). That Rab is activated by the guanine exchange factors DENND1A, DENND1B and DENND1C (PubMed:20159556, PubMed:26774822)
Inhibited by the serine proteinase inhibitor 4-(2-aminoethyl)benzenesulphonyl fluoride (AEBSF), and by di-isopropylfluorophosphate (PubMed:12662155). Inhibited by Val-boroPro (Talabostat, PT-100), a non-selective inhibitor, which triggers pyroptosis in monocytes and macrophages (PubMed:27820798, PubMed:29967349, PubMed:32796818, PubMed:33731932, PubMed:36357533). Val-boroPro inhibits activity by binding to the active site, mimicking a substrate-bound state, thereby displacing the C-terminal fragment of NLRP1, leading to activation of the NLRP1 inflammasome (PubMed:34019797, PubMed:33731932, PubMed:36357533). In contrast, Val-boroPro does not directly displaces CARD8: it acts by promoting degradation of the N-terminal part of CARD8, leading to indirect disruption of the ternary complex (PubMed:34019797). Chemical inhibition of DPP9 by Val-boroPro in HIV-1-infected cells activates the CARD8 inflammasome, triggering cell death, offering a promising strategy for the elimination of HIV-1 reservoirs in people living with HIV-1 (PubMed:36357533)
Autoinhibited by the ariadne domain, which masks the second RING-type zinc finger that contains the active site and inhibits the E3 activity (PubMed:23707686). Inhibition is relieved upon binding to neddylated cullin-RING ubiquitin ligase complexes, which activate the E3 ligase activity of ARIH1 (PubMed:24076655, PubMed:27565346)
Inhibited by alpha-2 macroglobulin
Carpropamid acts as an efficient inhibitor of scytalone dehydratase activity
Activated by resveratrol (3,5,4'-trihydroxy-trans-stilbene), butein (3,4,2',4'-tetrahydroxychalcone), piceatannol (3,5,3',4'-tetrahydroxy-trans-stilbene), Isoliquiritigenin (4,2',4'-trihydroxychalcone), fisetin (3,7,3',4'-tetrahydroxyflavone) and quercetin (3,5,7,3',4'-pentahydroxyflavone). MAPK8/JNK1 and RPS19BP1/AROS act as positive regulators of deacetylation activity (By similarity). Inhibited by nicotinamide. Negatively regulated by CCAR2 (By similarity)
Inhibited non-competitively by borrelidin (BN, KI is 3.7 nM) which binds in a 1:1 stoichiometry, inhibiting L-thr activation (PubMed:15507440). BN binds to 4 distinct subsites in the protein, preventing binding of all 3 substrates; BN also inhibits human ThrRS, and thus it is not useful as an antibiotic (PubMed:25824639)
Is highly competitively inhibited by the fungal sesquiterpenoid aspterric acid, which is effective as a herbicide in spray applications
Magnesium increases enzyme activity with various substrates
Inhibited by sinefungin and S-adenosyl-L-homocysteine
Inhibited by canaline
Is competitively inhibited by lovastatin (formerly called mevinolin). Lovastatin also blocks the growth of H.salinarum, and this effect is reversed by addition of mevalonate, indicating the critical role that the mevalonate pathway plays in isoprenoid biosynthesis by these archaea
It is inactivated via its interaction with PDS1, which probably covers its active site. PDS1 degradation at anaphase, liberates it and triggers MCD1 cleavage
Strongly inhibited by p-chloromercuribenzoate (pCMB), iodoacetamide (IA) and EDTA
Mercaptosuccinate, pCMB, and nethylmaleimide act as inhibitors of the catalytic activity
Subject to allosteric regulation, exists in two distinct conformational states, a catalytically incompetent (or open) conformation stabilized by the binding of acetyl(acyl)-CoA, and a catalytically competent (or closed) conformation stabilized by ATP-binding (PubMed:27555321). Inhibited by acetyl-CoA and its thioesters which act as allosteric inhibitors and compete with the ATP-binding site (PubMed:30927326, PubMed:17631502, PubMed:20797618, PubMed:27555321). Inhibited by sulfonylureas and thiazolidinediones (PubMed:20797618). Activated by oleoylethanolamide, palmitoyl-carnitine and oleoyl-carnitine (PubMed:20797618)
Helicase activity is activated by temperature increase
The enzyme in complex with the DNA substrate binds a third divalent metal cation. The binding of this third divalent cation, which is coordinated by water molecules and two oxygen atoms from DNA and dNTP, is essential for catalyzing the DNA synthesis
Inhibited by p-chloromercuribenzoic acid, N-ethylmaleimide and diethyl pyrocarbonate
Stimulated by estrogen
Feedback inhibition by lysine and threonine
Protein kinase activity is inhibited by the first PAS domain: binding of an unidentified ligand desinhibits the protein kinase activity. May be activated by autophosphorylation on Thr-1161 and Thr-1165 (PubMed:11459942). The activating role of autophosphorylation at Thr-1161 is unclear: according to a report, autophosphorylation at Thr-1161 does not play a major role in activation (PubMed:20943661). Autophosphorylation is enhanced upon phosphatidylinositol monophosphate (phosphatidylinositol 4-phosphate) binding and inhibited upon phosphatidylinositol bi- and tri-phosphate binding. In contrast, phosphorylation of target proteins is inhibited upon all phosphatidylinositol-binding (phosphatidylinositol mono- bi- and tri-phosphate)
Inhibited by N-methyl-D-glucamine (PubMed:10930503). Inhibited by choline. Allosteric regulation of sodium ions binding by pH (By similarity)
Inhibited by diethylstibestrol (DES), 2,4-dinitrophenol (DNP) and carbonlycyanide m-chlorophenylhydrazone (CCCP)
Inhibited by CCCP, verapamil and reserpine
Activated by cytochrome b5. The Vmax almost doubles in the presence of cytochrome b5
Requires cysteine for activation and Ca(2+) and/or Mg(2+) for stabilization. It is stimulated by glycine-containing dipeptides. It is resistant to inhibition by proteinase inhibitors in human plasma
Inhibited by 2-deoxyglucose and methyl beta-D-glucoside, but not by methyl alpha-D-glucoside, p-nitrophenyl alpha-D-glucoside, o-nitrophenyl beta-D-glucoside and salicin
Inhibited at high temperature and by arachidonate
Inhibited by tyrosine phosphorylation
Inhibited by EDTA (PubMed:14700627, PubMed:14592712). Insensitive to phenylmethylsulfonyl fluoride (PMSF) (PubMed:14700627, PubMed:14592712)
Ca(2+) acts as an activator of the enzymatic activity and is able to promote the hydrolysis of substrates even in the absence of transition-metal ions, thus providing an effective strategy for the regulation of the enzymatic activity. Two Ca(2+) ions bind at a site different from the dinuclear transition-metal-ion binding site (PubMed:26662456). Activity is enhanced by magnesium or manganese. Activity decreases in the presence of orthovanadate and phosphotyrosine (PubMed:16313172)
Filament turnover is promoted by MamJ and/or LimJ which have overlapping function; at least one other protein is required for turnover. MamK filament dynamics are probably required for the assembly or maintenance of the magnetosome chain
Inhibited by the uncoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP)
All catalytically active isoforms require binding to calcium and calmodulin for activation
Inhibited by bestatin. Subject to suicide inhibition by leukotriene A4 (By similarity)
Not activated by ATP
8-Azaxanthine is one of the most potent competitive inhibitors of uricase activity (PubMed:17020862). Hypoxanthine has only a small inhibitor effect, and caffeine has no effect at all (PubMed:17020862). Azide not only competes with dioxygen but also competes with the substrate for its enzymatic site (PubMed:25005084)
Dissociation from BIP and oligomerization, may results autophosphorylation and kinase activity induction
Activated by Ca(2+)/calmodulin. Binding of calmodulin results in conformational change that relieves intrasteric autoinhibition
Inhibited by the proton gradient disruptor carbonyl cyanide m-chlorophenylhydrazone (CCCP), but not by the sodium gradient disruptor ouabain
Inhibited by trobenzenesulphonic acid (TNBS)
The N-terminal sequences of INSM1 and SNAI1 compete with histone H3 for the same binding site and thereby inhibit histone demethylation (in vitro)
Crenactin polymerization is inhibited by interaction with arcadin-2 (PubMed:27852434). Also significantly inhibited by elevated antibiotic A22 concentrations (PubMed:21414041)
Magnesium ions lead to a slight increase in the catalytic activity
The full-length protein before cleavage is inactive: intramolecular interactions between N- and C-terminal domains mediate autoinhibition in the absence of activation signal (PubMed:28045099, PubMed:28459430). The intrinsic pyroptosis-inducing activity is carried by the released N-terminal moiety (Gasdermin-E, N-terminal) following cleavage by CASP3 or granzyme B (GZMB) (PubMed:28459430, PubMed:32188940, PubMed:31953257, PubMed:35594856). Activated by NLRP1 in the absence of GSDMD expression: NLRP1 cleaves and activates CASP8, promoting downstream activation of CASP3 and subsequent activation of GSDME (PubMed:33852854, PubMed:35594856)
(Microbial infection) Activated upon human coronavirus SARS-CoV-2 infection, leading to lung epithelial cell death (PubMed:35594856). Activation takes place in response to (1) activation of NLRP1 and (2) inactivation of GSDMD following NLRP1 and GSDMD cleavage by the SARS-CoV-2 3C-like proteinase nsp5 (PubMed:35594856)
Inhibited by Immucillin-H and 5'-methylthio-Immucillin-H (PubMed:14982926, PubMed:24416224). Inhibited by 5'-deaza-1'-aza-2c-deoxy-1'-(9-methylene)-Immucilin-G (DADMe-ImmG) (PubMed:29440412)
Not inhibited by cyclosporin A or FK506
Present in an inactive conformation in the absence of bound ligand. Binding of PDGFA and/or PDGFB leads to dimerization and activation by autophosphorylation on tyrosine residues. Inhibited by imatinib, nilotinib and sorafenib (By similarity)
Co(2+) is a strong stimulator (100-fold increase in rate of hydrolysis). Mn(2+), Cd(2+), Ni(2+), Mg(2+) and Ca(2+) are weak stimulators; the two latter act synergistically with Co(2+)
Can alternate between a fully active homooctamer and a low-activity homohexamer. A bound magnesium ion may promote the assembly of the fully active homooctamer. The magnesium-binding site is absent in the low-activity homohexamer. Inhibited by compounds that favor the hexameric state. Inhibited by divalent lead ions. The lead ions partially displace the zinc cofactor (By similarity)
Inhibited by diethylpyrocarbonate
Inhibited by marimastat and tripeptide hydroxamic acids (PubMed:26546217). Inhibited by 1,10-phenanthroline (PubMed:25736599)
Strongly inhibited by chicken egg-white cystatin (Probable). Inhibited by iodoacetamide and the active-site-directed inhibitor E64 (L-trans-epoxysuccinyl-leucylamide-(4-guanido)-butane) (PubMed:31306685)
Inhibited by the uncoupler carbonylcyanide m-chlorophenylhydrazone (CCCP) and the ionophore monensin
Inhibited by dipyridimole. Insensitive to selective PDE inhibitor rolipram and to the non-selective inhibitor, IBMX
The pro-survival signaling effect of NTRK1 in neurons requires its endocytosis into signaling early endosomes and its retrograde axonal transport. This is regulated by different proteins including CFL1, RAC1 and SORT1. NTF3 is unable to induce this signaling probably due to the lability of the NTF3-NTRK1 complex in endosomes. SH2D1A inhibits the autophosphorylation of the receptor, and alters the recruitment and activation of downstream effectors and signaling cascades (By similarity). Regulated by NGFR (By similarity)
Activated weakly by 0.2-0.4 mM Li(+). Inhibited by bis-carboxymethyl-trithiocarbonate, ethylxanthogenacetic acid and 2,5-disulfoaniline
Allosterically regulated by zinc, which seems to regulate the activity of the catalytic GGDEF domains by impeding their mobility and thus preventing productive encounter of the two GTP substrates (PubMed:23769666). Subject to product inhibition by c-di-GMP at a KI of 44 uM (PubMed:19460094)
The chaperone activity is activated by the transition from pH 2 to 7 and inhibited by the addition of G3P
Activated by phosphorylation on Thr-175 by STK11/LKB1
Activation is generally mediated by guanine exchange factor (GEF), while inactivation through hydrolysis of bound GTP is catalyzed by GTPases activating protein (GAP). Inactivated by ACAP1 and ACAP2 (By similarity). Activated by NGF via NTRK1 (PubMed:26446845)
Inactivated by l-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) in the absence of exogenous nucleophiles (e.g. GlcNAc4, GlcNAc3 and GlcNAc2) (PubMed:1740436). Not inhibited by tetra-N-acetylchitopentaose or modified chitotetraose substrate TMG-chitotriomycin-pMP, containing a free, non-acetylated glucosaminyl residue or a N-trimethylamino glucosamine (TMG) residue at the non-reducing terminus, respectively (PubMed:24616181)
Activated by dimerization and subsequent intermolecular autophosphorylation on Thr-298 (By similarity). Activated by the non-canonical Wnt signaling pathway, in which WNT5A treatment leads to activation of MAP3K7/TAK1 and HIPK2, which subsequently phosphorylates and activates this protein. Other cytokines such as IL6 may also activate this regulatory circuit
Activated by GRB2
Activated by Ca(2+)/calmodulin. Binding of calmodulin may relieve intrasteric autoinhibition. Autophosphorylation does not alter activity or regulation by Ca(2+)/calmodulin. In part, activity is independent on Ca(2+)/calmodulin (By similarity)
Allosterically activated by phosphatidylserine and/or phosphatidylinositol 4-phosphate (PtdIns(4)P), and phosphatidylinositol 5-phosphate (PtdIns(5)P) (PubMed:19038970). Interaction with MTMR9 increases catalytic activity towards phosphatidylinositol 3,5-bisphosphate (PubMed:19038970)
Competitively inhibited by 6R-6-fluoro-EPSP
Inhibited by cyanide and azide
Stimulated by Mn(2+), Mg(2+), Co(2+) and Ca(2+), inhibited by Cu(2+), Ni(2+), Zn(2+), chymostatin and 1,10-phenanthroline
Inhibited by thiosulfate above 100 mM, particularly at low cyanide concentrations (<5 mM). Inhibited by sodium sulfate or sodium chloride at 0.25 M which gives around 50% inhibition of rhodanese activity. Addition of sodium phosphate at the same concentration results in about 65% inhibition. Sulfite strongly inhibits PspE activity (1 mM sodium sulfite resulted in more than 50% inhibition of rhodanese activity)
Is inhibited in vitro by CCPST (4-carboxy-5-(4-chlorophenyl)sulfanyl-1,2,3-thiadiazole)
Inhibited by wortmannin
Inhibited by oxygen
Activated by Ca(2+)/calmodulin (PubMed:10428833, PubMed:26725111). Binding of calmodulin results in a conformational change that generates functional binding sites for both substrate and ATP, and thus relieves autoinhibition and lowers the Km of substrate binding. Must be phosphorylated by ckk-1 to be maximally active but this does not appear to be required for activity in AFD neurons (PubMed:10428833)
Binding to poly(ADP-ribose) does not affect its activity
Inhibited by the sulfhydryl inhibitors (N-ethylmaleimide, iodoacetate, ZnCl(2) and CuCl(2))
Inhibited by prohexadione-calcium, a 2-oxoglutarate-dependent dioxygenase (2-ODD) inhibitor, thus leading to a decreased abundance of nevadensin (NEV) and absence of pilosin (PIL) production, but to the accumulation of gardenin B (GARD B) and 8-hydroxysalvigenin (8-OH-SALV)
Inhibited by EDTA (PubMed:6368264). Stimulated by Ca(2+), Mn(2+) and Co(2+) (PubMed:6368264). Not inhibited by flavomycin (PubMed:8772200)
Inhibited by histatin-3 1/24 (histatin-5)
Transcriptional activity at macrophage-specific genes is inhibited by interaction with GFI1, which results in inhibition of SPI1-induced macrophage differentiation of myeloid progenitor cells, but not that of the granulocyte lineage
Inhibited by cadmium, cobalt, manganese, magnesium, calcium and nickel ions
Inhibited by bee venom neurotoxin apamin
Activated by Ca(2+)/calmodulin. Must be phosphorylated to be maximally active. Activated by CAMKK1
Activity is chloride-dependent (PubMed:18375752). Inhibited by AMP-PNP, gammaS-ATP, diadenosine triphosphate, 4,4'- diisothiocyanatostilbene-2,2'-disulfonate (DIDS) and Evans blue (PubMed:18375752)
Inhibited by EDTA and p-bromophenacyl bromide (BPB)
Inhibited by morin and p-BPB
CASP8 activity is restricted by RIPK1
Binding of cAMP to the PRKAR1A or PRKAR1B regulatory subunits induces dissociation of the holoenzyme heterotetramer. The released monomeric PRKX is then active and able to phosphorylate its substrates (By similarity)
Specifically inhibited by spautin-1 (specific and potent autophagy inhibitor-1), a derivative of MBCQ that binds to USP13 and inhibits deubiquitinase activity. Regulated by PIK3C3/VPS34-containing complexes. The weak deubiquitinase activity in vitro suggests the existence of some mechanism that activates the enzyme
Inhibited by Al(3+)
Activity increases in the presence of Mg(2+) (PubMed:28978920). RNA-binding is heat stable (PubMed:12614195)
Inhibited by cysteine protease inhibitors ICP1 and ICP2 (PubMed:16979632). Inhibited by leupeptin and such inhibitors of cysteine proteinases as L-transepoxysuccinyl-L-leucylamido-(4-guanidino)butane, peptidyldiazomethanes, iodoacetic acid and chicken cystatin
The L-glutamate uniporter activity exhibits a biphasic dependence on chloride concentration (PubMed:12388773). Chloride channel activity is allosterically activated by lumenal H(+) and Cl(-) leading to synaptic vesicles acidification (PubMed:27133463). The glutamate transport activity is allosterically activated by lumenal H(+) and Cl(-), preventing non-vesicular L-glutamate release (PubMed:27133463)
Formation of the GlnK-AmtB complex is influenced by intracellular pools of the effector molecules ATP, ADP, Mg(2+) and 2-oxoglutarate. The GlnK-AmtB interaction is also controlled by the level of intracellular glutamine and the uridylylation status of GlnK
Autoinhibited. Activated by diacylglycerol and calcium binding, which induces a conformational change releasing the autoinhibitory state. Regulated by DGKA. Regulated by DGKZ. Regulated by PLC gamma and F-actin polymerization (By similarity)
Allosterically regulated and controlled by phosphorylation. 5-phosphoribose 1-diphosphate is an activator while UMP is an inhibitor of the CPSase reaction
Inhibited by both clorgyline (selective MAOA inhibitor) and deprenyl (selective MAOB inhibitor)
Zinc-binding is required for catalytic activity
Activated by cAAA and to a lesser extent cAA and cAAG; cAAA and cAA are products of its cognate CD-NTase. Cyclic nucleotide binding causes hexamerization (PubMed:31932165). Cyclic nucleotide binding causes a series of shifts that enclose the cAAA molecule, enable hexamer formation and juxtapose pairs of active sites to allow dsDNA cleavage (PubMed:31932164)
Addition of 5 mM Mg(2+), Ca(2+) or Mn(2+) slightly enhances catalysis (about 100-120%) (PubMed:20722388). Significant reduction of enzyme activity (2%-35%) is observed with Cu(2+), Zn(2+), Fe(2+), or Sn(2+) (5 mM) (PubMed:20722388)
Inhibited by the tyrosine phosphatase inhibitor sodium vanadate
Heparin and wedelolactone inhibit the myotoxic activity (PubMed:9920492). The PLA2 inhibitor, para-bromophenacyl bromide (BPB), inhibits enzymatic and myotoxic activities (PubMed:9028014, PubMed:9920492)
Inhibited by adenosine 3',5'-bisphosphate (PAP)
Activated by cAMP, and at 10-100 times higher concentrations, also by cGMP. cAMP binding causes a conformation change that leads to the assembly of an active tetramer and channel opening. Channel activity is modulated by intracellular chloride ions and pH; acidic pH shifts the activation to more negative voltages
Sensitive to oxidants such as superoxide or hydrogen peroxide
Its activity is inhibited by diisopropylfluorophosphate (DFP) and PMSF, whereas EDTA has no effect on it
Erythritol may act as an inducer, probably by binding to EryD and inhibiting its repressor activity
Strongly inhibited by PMSF and slightly inhibited by EDTA and soybean trypsin inhibitor
Activity repressed by anti-sigma-G factor Gin (csfB) and Lon protease during the early stages of forespore development (PubMed:17921305). When both Gin and sigma-G are expressed in E.coli Gin inhibits sigma-G activity, strongly suggesting Gin inhibits by direct physical interaction (PubMed:19497328)
Inhibited by the regulatory subunits VHS3 and SIS2
Stimulated by the polynucleotide FII (physiological activator), and by chondroitin sulfate (CS) and heparin. Activation by the polyanion is inhibited by high salt concentration as well as by high concentrations of mononucleoside phosphates
Activated by tyrosine and threonine phosphorylation by skh1/pek1
Alternates between an inactive GDP-bound form and an active GTP-bound form (PubMed:10022920, PubMed:15107860, PubMed:10102276). Intrinsic GTPase activity is almost undetectable in vitro (PubMed:10022920, PubMed:15107860). Activated by guanine nucleotide-exchange factors (GEFs) and inactivated by GTPase-activating proteins (GAPs) (PubMed:10022920, PubMed:15107860, PubMed:10102276)
Catalytic activity is enhanced by complex formation with SELENOF
Inhibited by serinamide, unlike type-1 M.barkeri SerRS
Inhibited by BSH
Exhibits homotropic positive cooperativity for PEP (PubMed:3711058). Allosterically activated by ribose-5-phosphate, AMP and other nucleoside monophosphates but not by fructose-1,6-bisphosphate (PubMed:3711058)
Substrate identity influences both the ground-state and transition-state energies for the conformational exchange process, emphasizing the coupling between substrate binding and transport
Inhibited by high concentrations of the substrates fructose 6-phosphate and ATP, and by the reaction products, fructose 1,6-bisphosphate and ADP. Allosterically inhibited by phosphoenolpyruvate (PEP), guanosine diphosphate (GDP) and citrate
Oxidation at Cys-195 leads to inactivation of channel activity
Inhibited by INK4 proteins (CDKN2C/p18-INK4c), aminopurvalanol, PD0332991, 4-(Pyrazol-4-yl)-pyrimidines and fisetin, a flavonol inhibitor. Activated by Thr-177 phosphorylation and Tyr-24 dephosphorylation (By similarity). Stimulated by cyclin from herpesvirus saimiri (V-cyclin/ECLF2). Rapidly down-regulated prior to cell differentiation (e.g. erythroid and osteoblast)
Inhibited by GTP
Oligomerization, which is mediated by phosphorylation, is required for chaperone activity. Lower oligomeric GroELs possess substrate binding activity but are inefficient in promoting refolding (PubMed:19717599). The binding of copper protects GroEL1 from destabilization and increases its ATPase activity (PubMed:32812602)
Inhibited by dTTP, which binds to the active site and stabilizes the inactive form of the enzyme (PubMed:17651436). Inhibited by inorganic phosphate (PubMed:15539408)
1D-myo-inositol hexakisphosphate activates protein-acetyltransferase activity via an allosteric mechanism: 1D-myo-inositol hexakisphosphate-binding induces a conformational rearrangement that stimulates the interaction with acetyl-CoA
Inhibited by mersalyl
Dephosphorylated and activated by wzb
Single stranded DNA (ssDNA) hydrolase activity does not depend upon, but is stimulated by the presence of Ca(2+) and Mn(2+) (By similarity). MIGA1 and MIGA2 increase PLD6 self-association affinity and affects the homodimer conformation facilitating its phospholipase activity over the nuclease activity. MYC induces its expression and stimulates its phospholipase activity (By similarity)
GTPase activity is coupled to stimulation of the rate of APS formation
S-adenosylhomocysteine is an extremely powerful competitive inhibitor of the uroporphyrinogen III methylation. SUMT exhibits a substrate inhibition phenomenon at uroporphyrinogen III concentrations above 2 uM; this property might play a regulatory role in cobalamin biosynthesis. The enzyme activity is completely insensitive to feedback inhibition by cobalamin and corrinoid intermediates
Activated by ATP (PubMed:10092647). Inhibited by calcium-activated calmodulin (By similarity). Inhibited by bromoenol lactone (BEL) (By similarity)
ATPase activity is inhibited by derivatives of thiazolidinone, benzamide and furan in vitro
Inhibited by N,N,-dimethylsphingosine; this inhibitor increases sensitivity to cisplatin
Present in an inactive conformation in the absence of bound ligand. Binding of VEGFA, VEGFB or PGF leads to dimerization and activation by autophosphorylation on tyrosine residues
Hemagglutinating activity is inhibited by galactose and structurally related sugars
Synthesized as an inactive form which is proteolytically cleaved to generate an active enzyme. Processing at the upstream site is particularly important for activation of the proenzyme, whereas processing at the boundary between the pro-domain and the catalytic domain does not appear to be essential (PubMed:25795784). Inhibited by hydroxamic acid-based inhibitors (PubMed:9920899)
Inhibited by 5,5'-dithiobis-2-nitrobenzoic acid (DTNB) and N-ethylmaleimide (NEM) (in vitro)
Activated by external aluminum. The enhancement of malate transport is not due to alteration in the selectivity properties but is due to an increased anion permeability
Inhibited by the nonsteroidal anti-inflammatory drugs aspirin, naproxen, diclofenac, meclofenamic acid, indomethacin and their analogs
XP620 is a selective DGAT1 inhibitor
The chaperone activity is regulated by ATP-induced allosteric coupling of the nucleotide-binding (NBD) and substrate-binding (SBD) domains. In the ADP-bound and nucleotide-free (apo) states, the two domains have little interaction. In contrast, in the ATP-bound state the two domains are tightly coupled, which results in drastically accelerated kinetics in both binding and release of polypeptide substrates. J domain-containing co-chaperones stimulate the ATPase activity and are required for efficient substrate recognition by HSPA5/BiP
Activated by forming a complex with STRAD (STRADA or STRADB) and CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta): STRADA (or STRADB)-binding promotes a conformational change of STK11/LKB1 in an active conformation, which is stabilized by CAB39/MO25alpha (or CAB39L/MO25beta) interacting with the STK11/LKB1 activation loop. Sequestration in the nucleus by NR4A1 prevents it from phosphorylating and activating cytoplasmic AMPK
Slightly activated by Mg(2+) and inhibited by both Ca(+) and Mn(2+). EDTA ha no effect on activity in vitro
Potently inhibited by benzbromarone and 3',3'',5',5''-tetrabromophenolphthalein (TBPP)
Activity abolished by 1 mM Cu(2+). 0.1 mM Cu(2+) reduces trehalose phosphorolysis to 76% and trehalose synthesis to 48% of maximum activity. 1 mM Zn(2+) abolishes trehalose synthesis, and reduces trehalose phosphorolysis to 40% of maximum activity. Unaffected by EDTA
ZBP1-dependent necroptosis is normally inhibited by RIPK1: RIPK1 inhibits the ZBP1-induced activation of RIPK3 via FADD-mediated recruitment of CASP8, which cleaves RIPK1 and limits TNF-induced necroptosis
Desumoylase activity is inhibited by zinc ions, and inhibition is released by nitric oxide or calcium-activated calmodulin
ATPase activity is stimulated by microtubules, which promote homooligomerization. ATP-dependent microtubule severing is stimulated by interaction with katnb1
Inhibited by Ca(2+) and other cations such as Ni(2+), Co(2+) and Zn(2+). The inhibition by o-phenanthroline and salicylhydroxamic acid suggests the presence of a metal cofactor besides FAD in the enzyme. The L-arginine-stimulated O(2) consumption involving slr0782 is inhibited by inhibitors of the respiratory electron transport chain, such as KCN and 2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone, which indicates a participation of the cytochrome b6/f complex and of a cytochrome oxidase
Activated by citrate at pH 5. Allosterically activated by fructose 1,6-bisphosphate (FBP) at pH from 5.8 to 7.2
Inhibited by 3-octylthio-1,1,1-trifluoro-2-propanone (OTFP), a specific inhibitor of juvenile hormone esterase (JHE), but not by diisopropyl fluorophosphate (DFP), a serine enzyme inhibitor
AmhT alone exhibits antiport activity, but interaction with AmhM confers different properties, such as higher KM for potassium
Its proteolytic activity is blocked by a signal peptide peptidase (SPP) inhibitor, (ZLL)2-ketone (ZLL) or a gamma-secretase inhibitor, LY411,575
Activated by GAP1
Activated by manganese or magnesium ions. In the presence of magnesium ions, the enzyme is activated by bicarbonate. Calcium mildly increases the enzyme activity, also in the presence of magnesium ions
The monomer has very low activity by itself. Activated several thousandfold by formation of a complex with PyrB aspartate carbamoyltransferase (ATCase)
Activated by calcium which induces conformational changes and interaction between the N-terminal regulatory region and the C-terminal catalytic region. Inhibited by diphenylene iodonium
The matrix-open state (m-state) is inhibited by the membrane-permeable bongkrekic acid (BKA) (PubMed:24474793). The cytoplasmic-open state (c-state) is inhibited by the membrane-impermeable toxic inhibitor carboxyatractyloside (CATR) (PubMed:24474793)
Non-specific ssRNase activity is stimulated about 1000-fold by cyclic oligoadenylate (cOA), a second messenger produced by Cas10 of the ternary Csm effector complex in the presence of a cognate target RNA
Activity is increased by monovalent cations such as K(+), Rb(+) or Cs(+)
Inhibited by pyridoxal 5'-phosphate, 4,7-diphenyl-1,10-phenanthroline, tannic acid, and mercurials (mercury dichloride, mersalyl acid, p-hydroxymercuribenzoate)
Inhibited by EDTA, EGTA and 1,10-phenanthroline, partially inhibited by beta-mercaptoethanol and not inhibited by serine protease inhibitors (leupeptin and aprotinin). Also inhibited by an excess of zinc, mercury and magnesium ions. Extracts of the plant Casearia mariquitensis neutralizes the decrease of platelets and plasma fibrinogen induced by the protease. The same extracts also partially inhibit Bbeta chain cleavage, but not Aalpha chain cleavage
Repressor activity requires the presence of the Integration Host Factor (IHF), which binds to sequences located between FarR binding sites A and C. IHF binding to the promoter region stabilizes the binding of FarR to its binding sites A and C and as a consequence, enhances repression of the farAB operon
Activated by ATP (PubMed:18937505, PubMed:9111008). Inhibited by calcium-activated calmodulin (PubMed:11118454, PubMed:18937505). Inhibited by bromoenol lactone (BEL) (PubMed:18937505)
The heme-bound form can bind gaseous signaling molecules such as CO and nitric oxide (NO) and NO can reverse its transcriptional repressor activity
Inhibited by ADP and EDTA
Inactivated by oxidation of Cys-110 to a sulfenic acid
Inhibited by the protonophore 2,4-dinitrophenol
Inhibited by metal ions such as Co(2+), Zn(2+), Cu(2+) or Ni(2+). Is also inhibited by EDTA or diethylpyrocarbonate (DEPC) in vitro. Unlike the procollagen-proline cis-3- and trans-4-hydroxylases from mammals, does not necessarily require L-ascorbate for activity although it does increase the activity of the enzyme
Requires Mg2(+) for activity in vitro (PubMed:2679883). Inhibited by 3-n-dodecylmercapto-2-hydroxy-1,4-naphthoquinone (PubMed:7009604). The quinone-dependent Cu(2+) reduction is partially inhibited by superoxide dismutase (PubMed:10510271)
Unlike for mammalian OATs, activity is increased by TRX1-mediated reduction of the disulfide bond between Cys-154 and Cys-163. Binding to TRX1 may also induce conformational changes that facilitate substrate binding
Inhibited by clavulanic acid, sulbactam, tazobactam, and imipenem
Inhibited by citrate and under aerobic conditions
Stimulated by MgCl2
Inhibited by phenylmethanesulfonyl fluoride (PMSF) and diethyl pyrocarbonate (DEPC), but not by benzamidine
Inhibited by the diuretic amiloride. Inhibited by Cs(1+) ions. Inhibited by the spider venom psalmotoxin-1; this locks the channel into its desensitized conformation. Channel activity is increased by the heterodimeric snake venom neurotoxin composed of MitTx-alpha and MitTx-beta; this slows channel closure and increases the magnitude of the steady-state current that is triggered by low pH
PA phosphatase activity is magnesium ion-independent and potently inhibited by N-ethylmaleimide. Also inhibited by phenylglyoxal and propranolol
Phosphorylation at Tyr-102 inactivates the enzyme
The translocation ATPase activity is stimulated by SecY and a precursor protein such as proOmpA
Inhibited by 2-(1-ethyl-2-hydroxyethylamino)-6-benzylamino-9-isopropylpurine (roscovitine), 1-isopropyl-4-aminobenzyl-6-ether-linked benzimidazoles, resveratrol, AT-7519 and olomoucine. Activated by CDK5R1 (p35) and CDK5R2 (p39) during the development of the nervous system; degradation of CDK5R1 (p35) and CDK5R2 (p39) by proteasome result in down regulation of kinase activity, during this process, CDK5 phosphorylates p35 and induces its ubiquitination and subsequent degradation. Kinase activity is mainly determined by the amount of p35 available and subcellular location; reversible association to plasma membrane inhibits activity. Long-term inactivation as well as CDK5R1 (p25)-mediated hyperactivation of CDK5 triggers cell death. The pro-death activity of hyperactivated CDK5 is suppressed by membrane association of CDK5, via myristoylation of p35. Brain-derived neurotrophic factor, glial-derived neurotrophic factor, nerve growth factor (NGF), retinoic acid, laminin and neuregulin promote activity. Neurotoxicity enhances nuclear activity, thus leading to MEF2 phosphorylation and inhibition prior to apoptosis of cortical neurons. Repression by GSTP1 via p25/p35 translocation prevents neurodegeneration (By similarity)
Activated by mechanical pressure
Histone demethylase activity is inhibited by fumarate
Inhibited by the metal chelator 1,10-phenanthroline
Inhibited by the following metal ions: Cd(2+), Cu(2+), Fe(2+), Hg(2+) and Zn(2+). Activity is strongly inhibited by CoA-SH and partially inhibited by acetyl-CoA, caffeic acid and bisdemalonylsalvianin
Inhibited by fumonisin B1
Imidazole acts as a reversible inhibitor via the formation of an imidazole-prenyl-FMN adduct (PubMed:33763291). Activity is light sensitive (PubMed:33763291)
Inhibited by AMP and ADP with 25% and 35% of activity remaining, respectively, at saturating conditions. Activated 5-fold by diadenosine polyphosphates(Ap[n]A) with n>2 (Ap3A, Ap4A, Ap5A, Ap6A) at saturating conditions
Insensitive to stilbene derivatives
Completely inhibited by Cu(2+) and partially inhibited by Co(2+) and Ba(2+)
Repressed by the active-site-directed cysteine protease inhibitor E64 (L-trans-epoxysuccinyl-leucylamide-(4-guanido)-butane) produced by Aspergillus japonicus
Activated by DAG and phorbol esters. Phorbol-ester/DAG-type domain 1 binds DAG with high affinity and appears to play the dominant role in mediating translocation to the cell membrane and trans-Golgi network. Phorbol-ester/DAG-type domain 2 binds phorbol ester with higher affinity. Autophosphorylation of Ser-742 and phosphorylation of Ser-738 by PKC relieves auto-inhibition by the PH domain. Phosphorylation on Tyr-463 by the SRC-ABL1 pathway in response to oxidative stress, is also required for activation. Activated by DAPK1 under oxidative stress
Requires the monovalent cation K(+) for optimal activity
Competitively inhibited by alpha-D-galactose-1-phosphate
Is activated by phosphates
Activated by phosphorylation on Thr-168, potentially by autophosphorylation
Inhibited by N-ethylmaleimide (NEM). Not affected by leupeptin or trans-epoxysuccinyl-l-leucylamido-(4-gianidino) butane (E64)
Inhibited by homocysteine sulfonamide
Inhibited by glycerol-3-P (G3P)
Activated by phosphorylation on Thr-174, potentially by autophosphorylation
Inhibited by dichloroisocoumarin (DCI) and N-p-tosyl-L-phenylalanine chloromethyl ketone (TPCK), but not by other serine protease inhibitors such as sulfonyl fluoride PMSF and 4-(2-aminoethyl)benzenesulfonyl fluoride (AEBSF)
Completely inhibited by HgCl(2) and iodoacetamide. Stimulated by dithiothreitol
Phosphorylation leads to an increase in the catalytic activity
Inhibited by Fe(3+) ion
Strongly inhibited by reserpine. Also inhibited to a lesser extent by ketanserin and fenfluramine. Not significantly inhibited by tetrabenazine
Inhibited by pyrrole-2-carboxylate in vitro
Inhibited by excess phenol (PubMed:4146224). Heavy metals such AsCuSO(4), AgNO(3), or HgCl(2) severely inhibit activity (PubMed:4146224)
Inhibited by pyrrolidine dione antibiotic moiramide B (CPD1); in vivo the effects are not seen unless the efflux MexAB-OprM system is inactive
Inhibited by cadaverin or RNase A
Activity is stimulated by zinc, potassium, lithium, cobalt, sodium, calcium, iron, manganase, magnesium and mercury ions at a concentration of 1 mM, but inhibited by copper ions at a concentration of 1 mM. Activity is inhibited by potassium, sodium and magnesium ions at a concentration of 1 M. Activity is inhibited by urea, EDTA, dithiothreitol, p-CMB, PSF, natrium lauryl sulfate and N-bromosuccinimide
Inhibited by the inhibitory protein CpiA
Inhibited by Fe(2+) and DTT. Slightly inhibited by SDS and Zn(2+). Activity is slightly increased by Mn(2+)
Activated by Mn(2+)
Inhibited by the protonophore uncouplers 2,4-dinitrophenol and carbonyl cyanide m-chlorophenylhydrazone (CCCP), and by valinomycin (PubMed:15513740, PubMed:374403). Inhibited by the nucleoside antibiotic showdomycin (PubMed:374403)
Inhibited by 4-chloro-3-hydroxyanthranilate. Mechanism of inactivation involves the oxidation of the catalytic active site Fe(2+) to the catalytically inactive Fe(3+) oxidation state, superoxide production, and formation of two disulfide bonds between Cys-125 and Cys-128, and Cys-162 and Cys-165. Enzyme can be reactivated under reducing conditions
Inhibited by Cu(2+) or Zn(2+) and to a lesser extent Ni(2+) ions
Enzyme activity is not stimulated by phosphate. Phosphate increases kcat, but decreases substrate affinity, resulting in unchanged enzyme activity
TAFI/CPB2 is unique among carboxypeptidases in that it spontaneously inactivates with a short half-life, a property that is crucial for its role in controlling blood clot lysis. The zymogen is stabilized by interactions with the activation peptide. Release of the activation peptide increases a dynamic flap mobility and in time this leads to conformational changes that disrupt the catalytic site and expose a cryptic thrombin-cleavage site present at Arg-324
Active in alkaline conditions
Strand exchange activity is enhanced by fatty acid synthase (stimulatory factor P190/210)
Activated by various stressors, including oxidative stress, endoplasmic reticulum stress, and calcium overload, as well as by receptor-mediated inflammatory signals, such as the tumor necrosis factor (TNF) and lipopolysaccharide (LPS). Homophilic association of MAP3K5/ASK1 through the C-terminal coiled-coil domains and the heteromeric complex formation of MAP3K5/ASK1 with the reduced form of thioredoxin (TXN), constitutes an inactive form of the kinase. Upon ROS-induced dissociation of TXN from MAP3K5/ASK1, TRAF2 and TRAF6 are reciprocally recruited to MAP3K5/ASK1 and form the active MAP3K5/ASK1 signalosome, in which TRAF2 and TRAF6 appear to facilitate the active configuration of MAP3K5/ASK1. MAP3K5/ASK1 activity is also regulated through several phosphorylation and dephosphorylation events. Thr-845 is an activating phosphorylation site that is autophosphorylated and phosphorylated by MAP3K6/ASK2 and dephosphorylated by PPP5C. Ser-90 and Ser-1040 are inactivating phosphorylation sites, the former of which is phosphorylated by AKT1. Phosphorylation of Ser-973 induces association of MAP3K5/ASK1 with the 14-3-3 family proteins, which suppresses MAP3K5/ASK1 activity. Calcium/calmodulin-activated protein phosphatase calcineurin (PPP3CA) has been shown to directly dephosphorylate this site. SOCS1 binds to ASK1 by recognizing phosphorylation of Tyr-725 and induces MAP3K5/ASK1 degradation in endothelial cells. Also dephosphorylated and activated by PGAM5. Contains an N-terminal autoinhibitory domain
Inhibited by strychnine (PubMed:2155780, PubMed:15302677). Inhibited by picrotoxin (PubMed:15302677). Channel activity is potentiated by 10-100 uM Zn(2+) (PubMed:15302677, PubMed:16144831, PubMed:23895467). Channel activity is marginally increased by 50 mM ethanol; it is strongly increased by a combination of 0.5 uM Zn(2+) and 50 mM ethanol (PubMed:23895467). Channel activity is inhibited by 100-1000 uM Zn(2+) (PubMed:15302677)
Activity is increased by Mn(2+) and Mg(2+)
Partially inhibited by berberine; higher inhibitory effects are observed with longer chain polyester substrates
Activated in presence of the surfactant polysorbate 20, while inhibited in the presence of polysorbate 40, polysorbate 60, polysorbate 80, Triton X-100 and sodium dodecyl sulfate (PubMed:31234557). Inhibited by the metal chelator ethylenediaminetetraacetic acid (EDTA) (PubMed:31234557). Inhibited by iron and cobalt ions (PubMed:31234557)
The side chain of Glu-251 determines which of the two opposing activities (AMPylase or de-AMPylase) will take place. In response to endoplasmic reticulum stress, mediates de-AMPylase activity (By similarity). Adenylyltransferase activity is inhibited by the inhibitory helix present at the N-terminus: Glu-251 binds ATP and competes with ATP-binding at Arg-390, thereby preventing adenylyltransferase activity (By similarity). In unstressed cells, disengagement of Glu-251 promotes adenylyltransferase activity (By similarity). Activation dissociates ATP-binding from Glu-251, allowing ordered binding of the entire ATP moiety with the alpha-phosphate in an orientation that is productive for accepting an incoming target hydroxyl side chain (By similarity)
Regulated by phosphoenolpyruvate substrate and allosteric effectors such as fructose 1,6 diphosphate and magnesium
Inhibited at greater than 500 mM NaCl
Inhibited by phenol, paracetamol, 2,4,6-trimethylphenol, resveratrol, furfuryl mercaptan, 2-thiophenthiol, phenylhydrazine, and hydroxyurea
Activated by cAAA and to a lesser extent cAA; cAAA binding promotes hexamerization which is probably necessary for nuclease activation
Calcium, magnesium and manganese cations reduce peptidase activity to 20.3-51.3 percent. The metal ion chelating reagent EDTA almost completely inhibits activity. The protease inhibitor bacitracin and the aminopeptidase B inhibitor bestatin, as well as DTT and beta-mercaptoethanol act also as lap A inhibitorsD
Hydroproxyproline dehydrogenase activity is inhibited by THFA,(1R,3R)3-OH-cyclopentane-COOH and 5-OH-1H-pyrazole-3-COOH
ADP and vanadate (ABC transporters inhibitor) inhibit the ATP-dependent abscisic acid (ABA) uptake
Subject to competitive inhibition by phosphate. Inhibited by manganese. Magnesium mildly increases enzyme activity when the zinc concentration is suboptimal. Optimal activity is dependent on the presence of 0.01-2% Triton X-100. Triton X-100 at a concentration of 0.05% increases the activity about fivefold relative to that in its absence. The enzyme is even active in Triton X-100 concentrations up to 80%. 50% inhibition by 4 mM EDTA and 50% inhibition by 48 mM sodium citrate
Activated by calcium/calmodulin. Activated by forskolin. Activated by the G protein alpha subunit GNAS. Inhibited by the G protein beta and gamma subunit complex. Inhibited by the ATP analogs adenosine, 2'-deoxyadenosine and 2'-deoxy-3'-AMP
Inhibited by reagents such as p-chloromercuribenzoate, and by coformycin, a structural analog of inosine
DNA binding depends on WhiB
Under complex allosteric control mediated by deoxynucleoside triphosphates and ATP binding to separate specificity and activation sites on the M1 subunit. The type of nucleotide bound at the specificity site determines substrate preference. It seems probable that ATP makes the enzyme reduce CDP and UDP, dGTP favors ADP reduction and dTTP favors GDP reduction. Stimulated by ATP and inhibited by dATP binding to the activity site, the dATP inhibition is mediated by AHCYL1 which stabilizes dATP in the site (By similarity)
Activated by calcium (By similarity). Upon calcium binding to the EF-hand domain 2, the C-terminus of the junction domain (J domain) undergoes a conformational change which results in the dissociation of the pseudo-substrate inhibitory motif from the catalytic domain (By similarity). This, in turn, may facilitate the autophosphorylation of the activation loop at Thr-271, which leads to the kinase activation (By similarity)
Allosterically activated by fructose 1,6-bisphosphate (FBP). The improvement in affinity for substrate occurs in two steps; the binding of fructose 1,6-bisphosphate (FBP) to the dimer, and the dimer to tetramer conversion
Inhibited by tetrahydrofolate concentrations above 40 uM
Mn(2+) and Co(2+) strongly enhance prenylation activity (PubMed:23150454)
Activated in response to stimuli that lead to increased intracellular Ca(2+) levels; this activation is indirect and may be mediated by calcium-mediated production of reactive oxygen species (ROS). Activated by autophosphorylation at Tyr-402; this creates a binding site for SRC family kinases and leads to phosphorylation at additional tyrosine residues. Phosphorylation at Tyr-402, Tyr-579 and Tyr-580 is required for optimal kinase activity (By similarity)
Cleavage of PPAF2 is Ca(2+)-independent (PubMed:12185078). Inhibited by heparin (PubMed:17287215)
MYC stimulates its phospholipase activity (PubMed:26678338). MIGA1 and MIGA2 increase PLD6 self-association affinity and affects the homodimer conformation facilitating its phospholipase activity over the nuclease activity (PubMed:26711011). Single stranded DNA (ssDNA) hydrolase activity does not depend upon, but is stimulated by the presence of Ca(2+) and Mn(2+) (By similarity)
Activated by magnesium ions (PubMed:25545638). Activated by calcium ions (PubMed:25545638). Inhibited by the serine hydrolase inhibitor phenylmethanesulfonyl fluoride (PMSF) (PubMed:18658138)
Activated by ethanol. Inhibited strongly by EDTA and more weakly by other divalent ions chelators 1,10-phenanthroline, EGTA and dipicolinic acid. Inhibited also by nucleosides, inorganic phosphate and Ca(2+). Unaffected by F(-)
Inhibited by NADPH at concentrations above 200 uM, by MgCl (30%), by ZnCl(2) (55%), and by CoCl, MnCl and CaCl (100%). Also inhibited by iodoacetamide, N-ethylmaleamide, the thiol group inhibitor beta-chloromercuribenzoate, palmitoyl-CoA and myristoyl-CoA
Binding of 2-keto-3-deoxy-6-phosphogluconate (KDPG) to HexR releases the repressor from its target sequences
Acyltransferase and acetyltransferase activities are activated by phosphorylation and autoacetylation (PubMed:20100829, PubMed:30704899). Autoacetylation activates the histone acetyltransferase activity (PubMed:20100829, PubMed:25865756, PubMed:30704899)
Inhibited by nitric oxide
Converted into plasmin by plasminogen activators, both plasminogen and its activator being bound to fibrin. Cannot be activated with streptokinase (By similarity)
Activity may be regulated by the intramolecular thiol-disulfide exchange or disulfide bond switching
Activity of the enzyme is enhanced about 20-fold in the presence of ATP
The complex is activated by an osmotic gradient or by low temperature
IP3K is activated by calcium and calmodulin. Form B is much more sensitive to calcium/calmodulin than form A
Stimulated by dithiothreitol (DTT) in vitro. Totally inhibited by EDTA
TRIB1 competes with substrates for RFWD2 binding
Aryl sulfonamide anticancer drugs change the substrate specificity of DCAF15 by acting as a molecular glue that promotes binding between DCAF15 and weak affinity interactors, such as RBM39
95% inhibition by diisopropyl fluorophosphate (DFP) and 30% by phenylmethylsulfonyl fluoride (PMSF)
In the presence of 0.2 M NaCl, 2.0 mM sodium cholate (bile salts) decreases expression from the ompC promoter; how this is mediated is unknown
Allosteric enzyme with positive cooperativity toward the substrate N-carbamoyl-beta-alanine at low substrate concentrations (below 12 nM). Displays no cooperativity at substrate levels above 12 nM
Activated by a monovalent cation that binds near, but not in, the active site. The most likely occupant of the site in vivo is potassium. Also activated by ammonium ion. Ion binding induces a conformational change that may alter substrate affinity
Requires phospholipid, a metal ion, dithiothreitol and at least one other so far unidentified soluble cofactor for maximal activity. Inhibited by EDTA
Inhibited by sulfanilamide
Inhibited by thiol reagent and N-ethylmaleimide, but not by ubiquitin aldehyde, pepstatin A or benzamidine HCl
Inhibited by EDTA, but not PMSF and beta-mercaptoethanole
Allosterically inhibited by L-aspartate and L-malate. PEPC activity is not affected by allosteric activators of E.coli PEPC such as glucose 6-phosphate, fructose 1,6-bisphosphate, and acetyl coenzyme A
Inhibited by SERPINA1, SERPINC1, SERPINE1, SERPINF2, aprotinin, soybean, trypsin inhibitor and leupeptin. Inhibited by serine protease inhibitor SPINK5. Has an autoproteolytic activity which may have a regulatory effect. Activated by citrate and inhibited by zinc and to a lower extent by manganese
Inhibited by phlorizin. Inhibited by diabetic drugs that lower blood sugar levels, including empagliflozin and dapagliflozin
Inhibited by phenylmethylsulfonyl flouride
ATP binding enhances channel sensitivity to agonists. Ca(2+)-calmodulin prevents the ATP-mediated increased sensitivity to agonists
Inhibited by lumenal H(+) and Na(+). The channel pore shows dynamic behavior and undergoes spontaneous, Ca(2+)-dependent modulation when conducting Ca(2+)
Strongly inhibited by ADP, ATP and other NTPs
Negatively regulated by hyperphosphorylation during mitosis. The hyperphosphorylated form does not associate with CCNB1-CDC2 complexes. The PLK1 protein kinase may be required for mitotic phosphorylation
In resting state, adopts an open conformation, anion-binding promoting the inactive configuration (By similarity). Upon aromatic amino acid-binding, the groove in the extracellular venus flytrap module is closed, thereby inducing the formation of a novel homodimer interface between subunits (By similarity). Calcium ions stabilize the active state by enhancing homodimer interactions between membrane-proximal domains to fully activate the receptor (By similarity). In contrast to human protein, not activated by AMG 416, a D-amino acid-containing peptide agonist: this is probably due to the absence of a Cys residue at position 482, which forms a disulfide bond with the AMG 416 peptide agonist in human and that is replaced by a Tyr residue in pig (PubMed:26290606)
Inhibited by oxalate and by alpha-ketoglutarate. In vitro, the enzyme is stimulated by reducing agents such as dithiothreitol (DTT), reduced glutathione and 2-mercaptoethanol
Inhibited by phenylmethylsulfonyl fluoride and O-phenanthroline
Sensitive to thiol reagents and oxidizing reagents, but is not influenced by chelators or reducing reagents
Activity is markedly stimulated by KCl (PubMed:10833389). Reversibly inhibited by fructose-1,6- bisphosphate and ADP. Irreversibly inhibited by phenylmethanesulfonyl fluoride (PMSF) (Ref.6)
Inhibited by 2-(3-carbamimidoylsulfanylmethyl-benzyl)-isothiourea
Enzyme activity is tightly regulated to prevent the accumulation of reactive oxygen species in the endoplasmic reticulum. Reversibly down-regulated by the formation of disulfide bonds between the active site Cys-94 and Cys-131, and between Cys-99 and Cys-104. Glutathione may be required to regulate its activity in the endoplasmic reticulum
Activated by phosphorylation on Thr-530
Inhibited by various metalloform-selective inhibitors
Non-competitively inhibited by high concentrations of NAD(+) and L-malate. Also inhibited by CoA, acetyl-phosphate, palmitoyl-CoA, and oxaloacetate. Activated by aspartate
Channel activity is controlled by multiple regulatory mechanisms in different subcellular compartments. Channel function is transiently modulated by changes in Ca(2+), and inhibited by a reduction of pH; pH changes modify the aggregation state of unitary channels; a negative cooperativity between extracellular/lumenal Ca(2+) and H(+) is suggested. Regulated by phosphoinositides in a compartment-specific manner: in lysosomes activated by PtdIns(3,5)P2 (Phosphatidylinositol 3,5-bisphosphate) and at the plasma membrane inhibited by PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate)
Inhidited by the small peptide uracil-DNA-glycosylase inhibitor (Ugi)
Inhibited by methylepoxypropane (PubMed:9405410). Inhibited by the zinc chelator 4-(2-pyridylazo)resorcinol (PAR), in the presence of p- (hydroxymercuri)benzenesulfonic acid (PMPS), and by EDTA (PubMed:11939797). Not inhibited by the coenzyme M analog 2-bromoethanesulfonate (BES) (PubMed:20551308)
Inhibited by EDTA, EGTA, 1,10-phenanthroline and DTT. Not inhibited by PMSF and SBTI
Interaction with Golgi matrix protein GOLGA2 leads to autophosphorylation on Thr-174, possibly as a consequence of stabilization of dimer formation. The C-terminal non-catalytic region inhibits the kinase activity
Its activity is completely inhibited by PMSF, and almost not inhibited by EDTA
Novel PKCs (PRKCD, PRKCE, PRKCH and PRKCQ) are calcium-insensitive, but activated by diacylglycerol (DAG) and phosphatidylserine. Three specific sites; Thr-566 (activation loop of the kinase domain), Thr-710 (turn motif) and Ser-729 (hydrophobic region), need to be phosphorylated for its full activation. Inhibited by PRKCH upstream open reading frame 2 (PubMed:34593629)
Inhibited by 2beta-deoxy-Kdo
Activated upon interaction with the KU heterodimer. Not stimulated by ATP
Negatively regulated by phosphorylation in the M-phase
Inhibited by 12.7 nM stromatoxin 1 (ScTx1), a spider venom toxin of the tarantula S.calceata (PubMed:14565763). Inhibited by 42 nM hanatoxin 1 (HaTx1), a spider venom toxin of the tarantula G.spatulata (PubMed:14565763). Modestly sensitive to millimolar levels of tetraethylammonium (TEA) (PubMed:8081723, PubMed:1283219). Modestly sensitive to millimolar levels of 4-aminopyridine (4-AP). Completely insensitive to toxins such as dendrotoxin (DTX) and charybdotoxin (CTX) (By similarity)
The cyclic peptide natural product argifin acts as a specific inhibitor
Phosphoenolpyruvate carboxykinase activity is regulated by acetylation and glucose levels (By similarity). The anaplerotic conversion of phosphoenolpyruvate to oxaloacetate is improved by PCK1 acetylation on Lys-91 (K91ac), Lys-473 (K473ac) and Lys-521 (K521ac) (By similarity). High glucose concentrations favor PCK1 anaplerotic activity by triggering acetylation on Lys-91 (K91ac). At low glucose levels, SIRT1-mediated deacetylation of Lys-91 promotes the cataplerotic conversion of oxaloacetate to phosphoenolpyruvate. Phosphorylation at Ser-90 reduces the binding affinity to oxaloacetate and converts the enzyme into an atypical protein kinase using GTP as donor (By similarity)
Activated by threonine and tyrosine phosphorylation. Activated by MAP kinase kinases MKK4, MKK5, MKK7 and MKK9. Activated in response to hydrogen peroxide, ozone, salt stress and flagellin bacterial elicitor. Triggered by Agrobacterium upon T-DNA transfer. Repressed by DSPTP1B/MKP2-mediated dephosphorylation
Phosphorylation of the N-terminal regulatory domain activates the methylesterase activity
Stabilized in the inactive form by an association between the SH3 domain and the SH2-TK linker region, interactions of the N-terminal cap, and contributions from an N-terminal myristoyl group and phospholipids. Activated by autophosphorylation as well as by SRC-family kinase-mediated phosphorylation. Activated by RIN1 binding to the SH2 and SH3 domains (By similarity). Inhibited by imatinib mesylate (Gleevec). Phosphatidylinositol 4,5-bisphosphate (PIP2), a highly abundant phosphoinositide known to regulate cytoskeletal and membrane proteins, inhibits the tyrosine kinase activity
Inhibited by metal ions such as Co(2+), Zn(2+), Ni(2+) or Cu(2+). Is also inhibited by EDTA in vitro
Inhibited by bacterial PC-phospholipase C inhibitor D609
Requires potassium. Inhibition by ADP (By similarity)
Rab activation is generally mediated by a guanine exchange factor (GEF), while inactivation through hydrolysis of bound GTP is catalyzed by a GTPase activating protein (GAP). That Rab is activated by DENND3, a guanine exchange factor (By similarity)
Galactosylgalactosylglucosylceramidase activity is stimulated by saposin B and ammonium chloride
ECF sigma-E is held in an inactive form by its cognate anti-sigma factor (RseA) until released by regulated intramembrane proteolysis (RIP). RIP occurs when an extracytoplasmic signal (periplasmic stress and excess LPS) triggers a concerted proteolytic cascade to transmit information and elicit cellular responses. The anti-sigma factor RseA is an inner membrane protein, binding sigma-E in the cytoplasm and RseB in the periplasm. RseA is first cut extracytoplasmically (site-1 protease, S1P, by DegS), then within the membrane itself (site-2 protease, S2P, by RseP), while cytoplasmic proteases (predominantly ClpX-ClpP) finish degrading the regulatory protein, liberating sigma-E. Degradation of RseA requires 2 signals to activate DegS; an outer membrane protein (OMP) signal activates DegS, while an LPS signal causes release of RseB from RseA, freeing RseA to be cleaved (By similarity)
Inhibited by caspase-1 inhibitor YVAD-FMK and the pan-caspase inhibitor VAD-FMK
Cleavage is inhibited by ubiquitin in a dosage-dependent manner. Cleavage is blocked by ubiquitin aldehyde
Methyltransferase activity is regulated by miRNAs via a sequence pairing mechanism (By similarity). Methyltransferase activity is inhibited by sumoylation (PubMed:29506078)
Significantly inhibited by divalent metal ions such as Cu(2+), Cd(2+) or Ca(2+)
Potently inhibited by the nonsteroidal anti-inflammatory drugs (NSAID)
Under resting conditions, NLRP3 binds ADP and is autoinhibited (By similarity). Inactive NLRP3 forms homodecameric double-ring cages that hide pyrin domains within NACHT-LRR rings to avoid premature activation (PubMed:30518920, PubMed:34861190, PubMed:35254907). NLRP3 activation stimuli include extracellular ATP, nigericin, reactive oxygen species, crystals of monosodium urate or cholesterol, amyloid-beta fibers, environmental or industrial particles and nanoparticles, such as asbestos, silica, aluminum salts, cytosolic dsRNA, etc (PubMed:16407889, PubMed:18403674, PubMed:19362020). Almost all stimuli trigger intracellular K(+) efflux (PubMed:23809161). These stimuli lead to membrane perturbations that induce activation of NLRP3 (PubMed:34861190). Upon activation, NLRP3 is transported to microtubule organizing center (MTOC), where it is unlocked by NEK7, leading to its relocalization to dispersed trans-Golgi network (dTGN) vesicle membranes and recruitment of PYCARD/ASC for the formation of an active inflammasome complex (PubMed:26814970, PubMed:26642356, PubMed:28716882, PubMed:30487600, PubMed:34615873, PubMed:34861190). NEK7-activated NLRP3 forms a disk-shaped inflammasome (By similarity). NLRP3 and PYCARD/ASC interact via their respective pyrin domains; interaction initiates speck formation (nucleation) which greatly enhances further addition of soluble PYCARD/ASC molecules to the speck in a prion-like polymerization process (PubMed:24630723). Clustered PYCARD/ASC nucleates the formation of CASP1 filaments through the interaction of their respective CARD domains, acting as a platform for CASP1 polymerization and activation (By similarity). Active CASP1 then processes IL1B and IL18 precursors, leading to the release of mature cytokines in the extracellular milieu and inflammatory response (By similarity). NLRP3 inflammasome assembly is inhibited by IRGM, which impedes NLRP3 oligomerization (By similarity). Specifically inhibited by sulfonylurea MCC950 (also named CP-456,773, CRID3), a potent and specific small-molecule inhibitor of the NLRP3 inflammasome that acts by preventing ATP hydrolysis (PubMed:35254907)
ATPase activity is inhibited by N-ethylmaleimide (NEM) but not by sodium azide
Inhibited by L-buthionine-S-sulfoximine (L-S-BSO)
Maintained in an autoinhibited state via homodimerization in which the CARD domain forms an extensive interaction with the adjacent linker and coiled-coil regions (By similarity). Activation downstream of C-type lectin receptors, by phosphorylation by PRKCD and/or ubiquitination by TRIM62, triggers disruption of the CARD domain-coiled coil interface, CARD9 homooligomerization and BCL10 recruitment, followed by activation of NF-kappa-B and MAP kinase p38 pathways (By similarity). Zinc-binding inhibits activation by stabilizing the CARD ground-state conformation and restricting its capacity to form BCL10-nucleating filaments (By similarity)
Autoproteolysis is stimulated by exogenous substrates or peptides that bind to its PDZ domains; may be stimulated by an environmental cue in vivo. Protease activity is tightly regulated; increasing its activity decreases substrate levels and disturbs biomineralization
Activated by dual phosphorylation on Ser-218 and Thr-222
Activated by DAG and phorbol esters. Phorbol-ester/DAG-type domains 1 and 2 bind both DAG and phorbol ester with high affinity and mediate translocation to the cell membrane. Autophosphorylation of Ser-734 and phosphorylation of Ser-730 by PKC relieves auto-inhibition by the PH domain
Subject to competitive inhibition by 3-phenylpropionate for the conversion of L-phenylalanine to phenylpyruvate. Subject to competitive inhibition by D-phenylalanine for the conversion of phenylpyruvate to L-phenylalanine
Each activity is inhibited by the substrate(s) of the other
Down-regulated by YKP1 phosphorylation. This effect is counteracted in the presence of mannosyl-inositolphosphorylceramide (MIPC)
Regulated by a redox-switch modulation. Reversibly inactivated by oxidative stress through the disulfide bond formation between two catalytic residues, Cys-88 and Cys-378, which enables the enzyme to protect its active site from oxygen radicals and be reactivated upon switching back to a reducing condition
Oxidation of meso-2,3-butanediol is enhanced in the presence of Fe(2+) (PubMed:23666479). Reduction of diacetyl and (3S/3R)-acetoin is slightly enhanced in the presence of Mg(2+) and Mn(2+) (PubMed:23666479). Activity is inhibited by several metal ions, particularly Fe(3+) for reduction of diacetyl and acetoin (PubMed:23666479)
Activated by ascorbate. Inhibited by N-oxalylglycine, fumarate and succinate
Induced by glucose excess, the induction may be mediated by CcpA transcriptional regulator
Nuclease activity partially inhibited by CasE (PubMed:21219465)
The GPCAT activity is sensitive to N-ethylmaleimide, phenanthroline, and divalent cations including Ca(2+), Mg(2+), Mn(2+) and Zn(2+) (PubMed:18430972). The activity is also inhibited by glycerol-3-phosphate (G3P) (PubMed:27758859)
Strongly inhibited by iodoacetate and potassium cyanide (KCN). Weakly inhibited by 2-mercaptoethanol, dithiothreitol (DTT), menadione, estradiol, 4'-(9-acridinylamino)methanesulfon-m-anisidine (mAMSA), allopurinol and tritonX-100. Not affected by p-chloromercuribenzoate
Completely inhibited by 10 mM p-coumaric acid, this inhibition is rapid, reversible and non-competitive. Completely inhibited by 0.1 mM Cu(2+), 0.1 mM Hg(2+) and 10 mM caffeic acid. Partially inhibited by 5 mM N-ethylmaleimide, 1 mM diethylpyrocarbonate and 1 mM acetyl-CoA
Inhibited by Zn(2+) and Ni(2+)
Weakly inhibited by triclosan
Inhibited in the presence of the protonophore carbonyl cyanide m-chlorophenyl hydrazone
Inhibited by dihydropyridines (DHP), such as isradipine (By similarity). Inhibited by nifedipine (By similarity). Channel activity is regulated by Ca(2+) and calmodulin (PubMed:15140941). Binding of STAC1, STAC2 or STAC3 to a region that overlaps with the calmodulin binding site inhibits channel inactivation by Ca(2+) and calmodulin (By similarity). Binding of calmodulin or CABP1 at the same regulatory sites results in opposite effects on the channel function (PubMed:15140941). Shear stress and pressure increases calcium channel activity (By similarity)
Two specific sites, one in the kinase domain (Thr-256) and the other in the C-terminal regulatory region (Ser-422), need to be phosphorylated for its full activation. Phosphorylation at Ser-397 and Ser-401 are also essential for its activity. Activated by WNK1, WNK2, WNK3 and WNK4 (By similarity)
Activity is inhibited by 2-nitroresorcinol (2-NR)
Inhibited by SERPINA5. Activity is strongly inhibited by Zn2+, 100 times more abundant in semen than in serum. This inhibition is relieved by exposure to semenogelins, which are avid zinc binders (By similarity)
Feedback inhibited by histidine. Also inhibited by AMP and PR-ATP
Somewhat inhibited by MgCl(2) and spermidine, strongly inhibited by MnCl(2)
In normal conditions, the protein kinase activity is inhibited; inhibition is relieved by various stress conditions (PubMed:12767237, PubMed:14752110). Inhibited by heme: in presence of heme, forms a disulfide-linked inactive homodimer (By similarity). Heme depletion relieves inhibition and stimulates kinase activity by autophosphorylation (PubMed:12767237, PubMed:14752110). Inhibited by the heme metabolites biliverdin and bilirubin (PubMed:16893190). Induced by oxidative stress generated by arsenite treatment (PubMed:12767237). Binding of nitric oxide (NO) to the heme iron in the N-terminal heme-binding domain activates the kinase activity, while binding of carbon monoxide (CO) suppresses kinase activity (PubMed:14752110). Protein kinase activity is also activated upon binding to the processed form of DELE1 (S-DELE1): interaction with S-DELE1 takes place in response to mitochondrial stress and triggers the integrated stress response (ISR) (By similarity)
Rab activation is generally mediated by a guanine exchange factor (GEF), while inactivation through hydrolysis of bound GTP is catalyzed by a GTPase activating protein (GAP). That Rab may be activated by DENND1C, a guanine exchange factor. Activated in response to insulin
Activated by magnesium
Activated in vitro by very low concentrations of spermidine, but inhibited at spermidine concentrations higher than 4 uM. The activating effect of low spermidine concentrations may be mediated by N(8)-acetylspermidine produced by KAT2B/P/CAF itself acting as a positive feedback loop
Inhibited by copper, mercury and iron ions
Negatively regulated by R-spondin proteins such as RSPO1: interaction with RSPO1 induces the indirect association between ZNRF3 and LGR4, promoting membrane clearance of ZNRF3
Inhibited by p-chloromercuribenzoate (pCMB), EDTA, Zn(2+) ions, and under aerobic conditions
Inhibited upon FCER1A triggering
Activated by phytosphingosine (PHS), a sphingoid long chain base. Activated by PKH2 phosphorylation. Kinase activity is regulated by TOR2 via direct phosphorylation of Ser-641 and Thr-659
Uncompetitive inhibition by micromolar concentrations of lithium. Competitive inhibition by inositol 1,4-bisphosphate
Inhibited by psoralen, a major downstream product
Activity is weakly pH-dependent
Inhibited by metal ions such as Co(2+), Zn(2+), Ni(2+) or Cu(2+). Is also inhibited by EDTA in vitro. Unlike the procollagen-proline cis-3- and trans-4-hydroxylases from mammals, does not necessarily require L-ascorbate for activity although it does increase the activity of the enzyme
Na(+) current is inhibited by ATP in a MTORC-dependent manner. ATP sensitivity is independent of PI(3,5)P2 (By similarity). Probably regulated by Mg(2+) ions, cytosolic Mg(2+) selectively inhibits outward current while lysosomal Mg(2+) modestly inhibits both the outward and inward currents. In the absence of Mg(2+), NAADP readily activates TPCN2, with properties similar to PI(3,5)P2 (By similarity). Both current elicited by PI(3,5)P2 as well as NAADP are inhibited by tetrandrine (By similarity)
Binding to DNA is inhibited by zinc ions
Inhibited by kaempferol, quercetin, genistein and myristic acid
Strongly inhibited by the serine protease inhibitor diisopropyl fluorophosphate
Inhibited by ethoxyzolamide and dithiothreitol (in crude extracts upon expression in E.coli)
Activated by forskolin (PubMed:24700542). Activated by GNAS. Activity is further increased by interaction with the G-protein beta and gamma subunit complex formed by GNB1 and GNG2 (PubMed:26206488). Is not activated by calmodulin. Inhibited by adenosine and ATP analogs. Inhibited by calcium ions, already at micromolar concentrations (By similarity). Phosphorylation by RAF1 results in its activation (PubMed:15385642)
Inhibited by both galactose-6-phosphate and ATP
Regulated by a negative feedback mechanism through sterols and non-sterol metabolites derived from mevalonate (By similarity). Phosphorylation at Ser-871 down-regulates the catalytic activity (By similarity)
Inhibited strongly by tannic acid, bromocresol purple, mercuric chloride, mersalyl, p-hydroxymercuribenzoate, S-adenosylhomocysteine, S-adenosylcysteine and adenosylornithine, and to a lesser extent by N-ethylmaleimide, bathophenanthroline and pyridoxal-5'-P
Activated by calcium (PubMed:19307175, PubMed:19666141). Upon calcium binding to the EF-hand domains, the C-terminus of the junction domain (J domain) undergoes a conformational change which results in the dissociation of the pseudo-substrate inhibitory motif from the catalytic domain (PubMed:19307175). This, in turn, may facilitate the autophosphorylation of the activation loop at Thr-234, which leads to the kinase activation (PubMed:19307175). Intracellular calcium increase is triggered by xanthurenic acid (XA), a small mosquito molecule that induces the differentiation of specialized transmission stages, the gametocytes, into male and female gametes (Probable). Activated by a decrease in temperature (20 degrees Celsius) and an increase in pH (7.6) occurring when the parasite is ingested by in the mosquito (PubMed:19666141)
Inhibited by the chelating agents 1,10-phenanthroline and EDTA. Inhibited by the thiol-containing compounds 2-mercaptoethanol and dithiothreitol. Also inhibited by apstatin, captopril and p-(ch1oromercuri)benzenesulfonic acid. Weakly inhibited by D,L-2-mercaptomethyl-3-guanidinoethylthiopropanoic acid and N-[l-(R,S)-carboxy-(2-phenylethyl)]-Ala-Ala-Phe-p-aminobenzoate. Inhibited by ramiprilat and enalaprilat, in a Mn(2+)-dependent manner. Metal ions have a complex substrate- and concentration-dependent effect on activity. Activity towards Arg-Pro-Pro and Gly-Pro-Hyp is stimulated by Mn(2+) ion concentrations of 10-100 uM and then inhibited at Mn(2+) concentrations of 1-2 mM. Mn(2+) concentrations in excess of 2 mM stimulate activity towards Gly-Pro-Hyp but inhibit activity towards Arg-Pro-Pro. Zn(2+) and Co(2+) ions also inhibit activity towards Arg-Pro-Pro at high concentrations. Activity towards bradykinin is inhibited by Mn(2+) concentrations in excess of 1 mM
The protease activity is completely inhibited by the serine inhibitor PMSF but is not affected by thiol group inhibitors and in the presence of dithiothreitol (PubMed:6750031). In the presence of high concentrations of o-phenanthroline the protease activity is only partially inhibited (PubMed:6750031). The pro-region plays an inhibitory role and may provide a mechanism for preventing premature activation in the secretory pathway (PubMed:2649495)
Can bind 1 iron ion per dimer. Iron binding seems to decrease LDLR degradation activity
Regulated by metabolites. Post-translationally inactivated by cysteine-mediated redox modification via the ferredoxin-thioredoxin system in the light and this avoids futile cycles with photosynthetic CO2 fixation
The activation of GTP-binding proteins is generally mediated by a guanine exchange factor (GEF), while inactivation through hydrolysis of bound GTP is catalyzed by a GTPase activating protein (GAP). The GATOR1 complex functions as a GAP and stimulates RRAGA GTPase activity to turn it into its inactive GDP-bound form
Inhibited by nmolar levels of AMP and GMP
The guanine nucleotide exchange factor (GEF) activity is autoinhibited. Autoinhibition may be the result of intramolecular interaction between the DENN domain and the C-terminus, which is disrupted upon phosphorylation. Activation is regulated by Akt activation
Insensitive to calcium/calmodulin, forskolin and somatostatin. Stimulated by beta-adrenergic receptor activation (PubMed:9628827). Activity is down-regulated by calcium/calcineurin (PubMed:10987815)
Inhibited by copper chloride, mercury chloride, ammonium molybdate and para-chloromercuribenzoate
Loss of hemagglutinating activity by EDTA treatment. The activity is fully recovered by the addition of 5 mM Ca(2+) ions, but not with Mg(2+) and Mn 2(+). Hemagglutination activity is inhibited by maltose and its derivatives, with maltopentaose and maltohexaose being the best inhibitors followed by maltose and iso maltose. Not inhibited by glycoproteins
Inhibited by ethanol, acetone, acetonitrile and 2-propanol (65 to 70% inhibition) and to a lesser extent by methanol and dimethyl formamide (26 and 49 % inhibition respectively). No effect of glycerol or DMSO
In vitro, requires PhzS for activity
Inhibited by N-ethylmaleimide, p-bromophenacylbromide, 2,4- dinitrofluorobenzene and divalent cations such as such as Mn(2+), Mg(2+) and Zn(2+) (PubMed:9989261). Inhibition by p-bromophenacylbromide is strongly pH dependent and is highest at alkaline conditions (PubMed:9989261)
Activated by phosphorylation on Thr-215. Inhibited by phosphorylation at Ser-219
The kinase domain is activated by trans-autophosphorylation. Kinase activity is required for activation of the endoribonuclease domain (By similarity)
Oxidation of 20-HETE is inhibited by low concentrations of N-heptylformamide. Oxidation of 20-HETE is a decreased by 55-65% by either all-trans-retinol or all-trans-retinoic acid. Strongly inhibited by omega-hydroxy fatty acids
No activity is lost during treatment with 20 or 100 mM EDTA in Z buffer for 3 hours at 0 degrees Celsius, nor is activity greatly stimulated by the addition of cations. Inhibited by 1 mM zinc and 1 mM copper, the levels of activity decrease to 10% of the untreated control. Nickel, cobalt and manganese at concentrations of 10 mM decrease enzyme activity to either 40% (for nickel and cobalt) or 60% (for manganese) of the activity in untreated controls. No change in enzyme activity in the presence of calcium and magnesium at concentrations up to 50 mM. EDTA-treated enzyme exhibits a slight increase in relative specific activity when it is assayed in the presence of 50 mM NaCl or 50 mM KCl, it does not exhibit enhanced activity at concentrations greater than 250 mM. Maintains between 20 and 40% of activity in the presence of 4 M NaCl or 4 M KCl, and it is more active in the presence of KCl than in the presence of NaCl. Retains 50% of activity in the presence of 3 M KCl or 2.5 M NaCl
Allosterically activated by (2R,4S)-DAP. Negatively regulated by AKP, and by both acetyl-CoA and D-alanine
Enzyme activity is enhanced by acetylation
Activated by both the alpha and the beta-gamma G proteins following stimulation of G protein-coupled receptors (GPCRs). Activation by GPCRs is assisted by the regulatory subunit PIK3R5 leading to the translocation from the cytosol to the plasma membrane and to kinase activation; the respective activation involving PIK3R6 requires HRAS for membrane recruitment. Wortmannin sensitive in nM range. Inhibited by AS252424
Activated by Ca(2+)-bound calmodulin following an increase in intracellular Ca(2+). At low Ca(2+) concentrations, the catalytic subunit (also known as calcineurin A) is inactive and is bound to the regulatory subunit (also known as calcineurin B) in which only two high-affinity binding sites are occupied by Ca(2+). In response to elevated calcium levels, the occupancy of the low-affinity sites on calcineurin B by Ca(2+) causes a conformational change of the C-terminal regulatory domain of calcineurin A, resulting in the exposure of the calmodulin-binding domain and in the partial activation of calcineurin A. The subsequent binding of Ca(2+)-bound calmodulin leads to the displacement of the autoinhibitory domain from the active site and possibly of the autoinhibitory segment from the substrate binding site which fully activates calcineurin A. Inhibited by immunosuppressant drug FK506 (tacrolimus) in complex with FKBP12 and also by immunosuppressant drug cyclosporin A (CsA) in complex with PPIA/cyclophilin A; the inhibition is Ca(2+)-dependent (PubMed:26248042)
Activated by threonine and tyrosine phosphorylation (By similarity). Activated in response to hydrogen peroxide, salicylic acid, jasmonic acid, ethylene, fungal elicitor and infection with rice blast fungus (M.grisea)
Inhibited by L-proline as part of a negative feedback loop. Also inhibited by L-proline analogs 3,4-dehydro-L-proline, L-azetidine-2-carboxylic acid and L-4-thiazolidine carboxylic acid
Oxyphenbutazone (OPB), anisic acid and atropine inhibit the enzymatic activity by binding at the substrate-binding site (PubMed:15544328, PubMed:16596639). P-coumaric acid, resveratrol, spermidine, corticosterone and gramine derivative inhibit the enzymatic activity by binding at the substrate-binding site (PubMed:25541253)
The activity is thought to be regulated mainly by the availability of decarboxylated S-adenosylmethionine. Inhibited by dicyclohexylamine, S-adenosyl-1,8-diamino-3-thiooctane (AdoDATO), sulfonium-deaminated analogs of S-adenosyl(5')-3-methylthiopropylamine, p-hydroxymercuribenzoate and N-ethylmaleimide
Inhibited by iodoacetate. Appears to be regulated by the fur protein, but this effect is not mediated at the transcriptional level
ATPase activity is inhibited by EDTA, N-ethylmaleimide (NEM) and p-chloromercuriphenyl-sulfonic acid (PCMS) in vitro
Activated by a monovalent cation that binds near, but not in, the active site. The most likely occupant of the site in vivo is potassium. Ion binding induces a conformational change that may alter substrate affinity (By similarity). Competitively inhibited by phosphonoacetic acid, etidronate, 2-carboxethylphosphonic acid, N-(phosphonomethyl)glycine, N-(phosphonomethyl)iminodiacetic acid and clodronate (PubMed:17585908)
Enzyme activity is tightly regulated to prevent the accumulation of reactive oxygen species in the endoplasmic reticulum. Reversibly down-regulated by the formation of disulfide bonds between the active site Cys-94 and Cys-130, and between Cys-99 and Cys-104. Glutathione may be required to regulate its activity in the endoplasmic reticulum (By similarity)
The receptor is strongly activated by gamma-linolenic acid, while myristate gives a lower response. It is also activated by phytanic acid and pristanic acid (PubMed:21570468). Is also activated by synthetic agonists, such as TAK-875 (fasiglifam); this compound is a partial agonist and potentiates the activity of the endogenous ligand gamma-linolenic acid (PubMed:24130766)
Inhibited by PMSF, disodium-EDTA, S(Dm) and soybean trypsin inhibitor (SBTI). SBTI and S(Dm) (the anti-hemorrhagic protein) acts as non-competitive inhibitors that decrease the enzymatic activity
Deoxyadenosine inhibits deoxycytidine phosphorylation and deoxycytidine inhibits deoxyadenosine phosphorylation. Deoxyadenosine/deoxycytidine kinase is inhibited by both dATP and dCTP
Potently inhibited by sphingolipids, in particular, the sphingoid bases sphinganine and sphingosine and ceramide-1-phosphate. Inhibited by concentrations of Mg(2+) and Mn(2+) above their optimums and by Ca(2+), Zn(2+), N-ethylmaleimide and propranolol
Inhibited by diethylstilbestrol, N,N'-dicyclohexylcarbodiimide, carbonyl cyanide m-chlorphenyl-hydrazone and 2,4-dinitrophenol. Competitive inhibition of adenine transport by isopentenyladenine, cytosine, cytidine, hypoxanthine, kinetin, zeatin, nicotine and caffeine, but not by zeatin riboside or kinetin riboside
Activated by fructose 6-phosphate. Inorganic phosphate inhibits the synthase activity in the complex, but activates the synthase activity in the free monomeric form
Strongly inhibited by the thiol reagents p-chloromercuribenzoate and N-ethylmaleimide. Partially inhibited by o-phenanthroline and 2,2'-dipyridyl. Competitively inhibited by L-tryptophan and indolmycin
Not inhibited by dithiothreitol, N-ethylmaleimide, phenylmethane sulfonyl fluoride, ascorbate, L-galactose and L-galactonolactone
Acetyl-CoA acts as a non-competitive inhibitor of the PhoQ autokinase activity. Feedback inhibited by MgrB, which seems to bind PhoQ, altering its activity and that of downstream effector PhoP
FBPase activity is inhibited by Ca(2+), ATP, ADP and phosphoenolpyruvate
Inhibited by conduritol B epoxide/CBE
Activated by Na(+) or K(+). Inhibited by silver
Regulated in response to catabolite repression
Strongly inhibited by p-chloromercuribenzoate (PCMB). Potassium cyanide (KCN) strongly inhibits activity towards 7,8-dihydropterin but has almost no effect on activity towards guanine. Pterin inhibits activity towards guanine but has little effect on activity towards 7,8-dihydropterin
Inhibited by KCN
Stabilized in the inactive form by an association between the SH3 domain and the SH2-TK linker region, interactions of the N-terminal cap, and contributions from an N-terminal myristoyl group and phospholipids. Activated by autophosphorylation as well as by SRC-family kinase-mediated phosphorylation (By similarity). Activated by RIN1 binding to the SH2 and SH3 domains. Also stimulated by cell death inducers and DNA-damage (By similarity). Phosphatidylinositol 4,5-bisphosphate (PIP2), a highly abundant phosphoinositide known to regulate cytoskeletal and membrane proteins, inhibits also the tyrosine kinase activity. Inhibited by imatinib mesylate (Gleevec)
The ATPase activity of IrtAB is stimulated more than 38-fold in the presence of Fe-MBT, and more than 10-fold in the presence of Fe-cMBT
Inactivated by zinc
Competitively inhibited by a four-residue peptide derived from the C-terminus of serine acetyltransferase (CysE). This suggests that CysK1 may associate with CysE in vivo to form a bi-enzyme complex, in which the OASS activity is down-regulated
The disulfide bridge formed between Cys-35 in the propeptide and the active site residue Cys-94 may prevent activation of the zymogen through formation of a reversible covalent bond with the active site residue
Activated by autophosphorylation of the T-loop at Thr-167 and Ser-171: in contrast to other members of the SNF1 subfamily, phosphorylation at Thr-167 is not mediated by STK11/LKB1 but via autophosphorylation instead. Inhibited by calcium-binding. Kinase activity is also regulated by reducing agents: dithiothreitol (DTT) or reduced glutathione are required for kinase activity in vitro; such dependence is however not due to the presence of disulfide bonds
Regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP. Regulated by the MON1-CCZ1 complex which serves as a link between Rab5 and Rab7 protein families in PVCs and mediates PVC maturation
Phosphorylation at Thr-14 or Tyr-15 inactivates the enzyme, while phosphorylation at Thr-160 activates it
Inhibited by 1,2,3-triazole urea covalent inhibitor KT172, DH376 and DO34 (PubMed:23103940, PubMed:26668358). Inhibited by p-hydroxy-mercuri-benzoate and HgCl(2), but not to PMSF. Also inhibited by RHC80267. Diacylglycerol lipase activity is inhibited by the phosphorylation of Ser-784 and Ser-810 by CAMK2A (By similarity)
Inhibited by diethylpyrocarbonate. Competitively inhibited by S-(2-oxo)pentadecyl-CoA, a non hydrolysable myristoyl-CoA analog, and by SC-58272, a peptidomimetic derived from the N-terminal sequence of a natural substrate
Activated in response to insulin. Three specific sites, one in the kinase domain (Thr-309) and the two other ones in the C-terminal regulatory region (Ser-474 and Tyr-475), need to be phosphorylated for its full activation
Strong, mutual inhibition of uptake by tyrosine, phenylalanine, and tryptophan. Transport is also inhibited by the aromatic analogs p-fluorophenylalanine, beta-2-thienylalanine and 5-methyltryptophan
Strongly inhibited by aprotinin, moderately inhibited by secretory leukoprotease inhibitor (SLPI), leupeptin, benzamidine, and phenylmethanesulfonyl fluoride (PMSF), weakly inhibited by urinary trypsin inhibitor, and Kunitz-type soybean trypsin inhibitor and not inhibited by EDTA and alpha-1 protease inhibitor
In vitro ADP-ribosylation is enhanced by dithiotheritol
Activity is modulated by phosphorylation (PubMed:21423706). Phosphorylated phosphatase is more active than its unphosphorylated equivalent (PubMed:21423706). Inhibited partially by NaF and cyclosporine (PubMed:14575702). Also inhibited by zinc ions and inorganic phosphate (PubMed:21423706)
Activated by 5mM MnCl(2) and MgCl(2). No significant effect on activity by 5 mM ethylenediaminetetraacetic acid (EDTA), 0.125-0.5% Triton X-100 or dithiothreitol (DTT). Inhibited by 5 mM Zn-acetate
The N-terminal RlmL activity is enhanced by the C-terminal RlmK activity
Phosphorylation at Thr-14 or Tyr-15 inactivates the enzyme, while phosphorylation at Thr-176 activates it
Binding of acidic phospholipids inhibits the Rho GAP activity and promotes the Rac GAP activity
Active in presence of diverse metals including Fe(2+), Zn(2+), Mn(2+) (By similarity). Also activated by Ca(2+) (PubMed:2435736). Binds two metal cations in two adjacent alpha and beta metal-binding pockets (By similarity)
Inhibited by formycin B, partially inhibited by purine analog ara-A
Activity requires divalent metal cations
Completely inhibited by HgCl(2), CoCl(2) and CaCl(2)
Inhibited by carbonyl cyanide m-chlorophenylhydrazone (CCCP), which dissipates the proton motive force
Rab activation is generally mediated by a guanine exchange factor (GEF), while inactivation through hydrolysis of bound GTP is catalyzed by a GTPase activating protein (GAP). YPT7 is activated by GEFs MON1-CCZ1 complex (MC1) and VAM6/VPS39, and inactivated by GAPs GYP7 and GYP1
Inhibited by sphingosine (PubMed:12783875). Inhibited by Mn(2+), Zn(2+), and Cu(2+) in a dose-dependent manner (PubMed:12783875). Slightly activated by Ca(2+) in a dose-dependent manner (PubMed:12783875)
Activated by various stressors, including oxidative stress, endoplasmic reticulum stress, and calcium overload, as well as by receptor-mediated inflammatory signals, such as the tumor necrosis factor (TNF) and lipopolysaccharide (LPS). Homophilic association of MAP3K5/ASK1 through the C-terminal coiled-coil domains and the heteromeric complex formation of MAP3K5/ASK1 with the reduced form of thioredoxin (TXN), constitutes an inactive form of the kinase (PubMed:17210579, PubMed:9564042). Upon ROS-induced dissociation of TXN from MAP3K5/ASK1, TRAF2 and TRAF6 are reciprocally recruited to MAP3K5/ASK1 and form the active MAP3K5/ASK1 signalosome, in which TRAF2 and TRAF6 appear to facilitate the active configuration of MAP3K5/ASK1 (PubMed:9774977, PubMed:10688666, PubMed:11920685). MAP3K5/ASK1 activity is also regulated through several phosphorylation and dephosphorylation events. Thr-838 is an activating phosphorylation site that is autophosphorylated and phosphorylated by MAP3K6/ASK2 and dephosphorylated by PPP5C (PubMed:11689443). Ser-83 and Ser-1033 are inactivating phosphorylation sites, the former of which is phosphorylated by AKT1 (PubMed:11154276, PubMed:15094778). Phosphorylation of Ser-966 induces association of MAP3K5/ASK1 with the 14-3-3 family proteins, which suppresses MAP3K5/ASK1 activity (PubMed:10411906, PubMed:14688258). Calcium/calmodulin-activated protein phosphatase calcineurin (PPP3CA) has been shown to directly dephosphorylate this site (PubMed:14749717). SOCS1 binds to ASK1 by recognizing phosphorylation of Tyr-718 and induces MAP3K5/ASK1 degradation in endothelial cells (PubMed:16407264). Also dephosphorylated and activated by PGAM5. Contains an N-terminal autoinhibitory domain. Once activated targeted for proteasomal degradation by RC3H2-mediated ubiquitination (PubMed:24448648)
Slightly inhibited by phenylmethylsulfonyl fluoride (PMSF)
Activated by calcium/calmodulin (PubMed:12747803). Inhibited by high concentrations of the substrate Ins(1,2,4)P3, and allosterically activated by the product Ins(1,3,4,5)P4
Salts and glycerol enhance the enzymatic activity in vitro towards pNP-esters, while detergents and organic solvents reduce the enzymatic activity
NADP(+) is a potent inhibitor of both the NADPH- and NADH-linked xylose reduction, whereas NAD(+) showS strong inhibition only with the NADH-linked reaction
Inhibited in a dose dependent manner by opiorphin (PubMed:17101991). Activated by K49-P1-20, a twenty-residue synthetic peptide shortened from the snake B.asper myotoxin II (PubMed:26931059)
Inhibited by 1-(1-acetylpiperidin-4-yl)-3-(4-(trifl uoromethoxy)phenyl)urea (TPAU), 1-cyclohexyl-3-dodecylurea (CDU), 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA), 1-((3S, 5S, 7S)-adamantan-1-yl)-3-(5-(2-(2-ethoxyethoxy) ethoxy)pentyl)urea (AEPU), N-adamantyl-N[']-cyclohexyl urea (ACU), 4-(((1S, 4S)-4-(3-((3S, 5S, 7S)-adamantan-1-yl) ureido)cyclohexyl)oxy)benzoic acid (c-AUCB), 4-(((1R, 4R)-4-(3-((3S, 5S, 7S)-adamantan-1-yl)ureido)cyclohexyl)oxy)benzoic acid (t-AUCB), 4-(((1R, 4R)-4-(3-(4(trifluoromethoxy)phenyl)ureido)cyclohexyl)oxy)benzoic acid (t-TAUCB) and to a lesser extent by 8-(3-((3S, 5S, 7S)-adamantan-1-yl)ureido) octanoic acid (AUOA)
This reaction is tightly coupled to the Na(+) pumping activity and specifically requires Na(+) for activity. Inhibited by korormicin and 2-N-heptyl-4-hydroxyquinoline N-oxide (HQNO)
Inhibited by zinc. Inhibited by the serine proteinase inhibitor 4-(2-aminoethyl)benzenesulphonyl fluoride (AEBSF), and by di-isopropylfluorophosphate. Specifically inhibited by isoindoline derivatives (PubMed:11012666, PubMed:12662155, PubMed:15664838). Inhibited by Val-boroPro (Talabostat, PT-100), a non-selective inhibitor, which triggers pyroptosis in monocytes and macrophages (PubMed:27820798, PubMed:29967349, PubMed:32796818)
Is inactivated by oxygen, due to oxidation of the Fe-S cluster to its [3Fe-4S] form. Both the fumarase and the isomerase reactions are competitively inhibited by 3-hydroxy-2-nitropropionate. The isomerase reaction is also inhibited by fumarate and malate
Irreversibly inhibited by phenylhydrazine, hydroxylamine, semicarbazide, hydrazine and aminoguanidine. Reversibly inhibited by isonicotinic acid hydrazide (isoniazid) and isonicotinic acid 2-isopropyl hydrazide (iproniazid)
Inhibited by carbonylcyanide m-chlorophenylhydrazone and 2,4-dinitrophenol
Subject to autoinhibition, mediated by intramolecular interactions involving the SH2 and SH3 domains. Kinase activity is also regulated by phosphorylation at regulatory tyrosine residues. Phosphorylation at Tyr-409 is required for optimal activity. Phosphorylation at Tyr-520 inhibits kinase activity (By similarity)
Alternates between an inactive form bound to GDP and an active form bound to GTP. Activated by the G protein coupled receptors (GPCRs) STE2 and STE3, which serve as guanine nucleotide-exchange factors (GEFs), and inactivated by SST2, probably acting as a GTPase-activating protein (GAP)
Single stranded DNA (ssDNA) hydrolase activity does not depend upon, but is stimulated by the presence of Ca(2+) and Mn(2+) (PubMed:23064227). MIGA1 and MIGA2 increase PLD6 self-association affinity and affects the homodimer conformation facilitating its phospholipase activity over the nuclease activity. MYC induces its expression and stimulates its phospholipase activity (By similarity)
Inhibited 16-fold better by the beta-lactamase inhibitor clavulanic acid than by tazobactam
Phenylalanine transport is inhibited by mercury, L-alanine and charged amino acids
Activity doubles within 5 hours of elicitor treatment and continues to increase for at least 80 hours
Inhibited by novobiocin
Forms a stable complex with CAR1 in the presence of ornithine and arginine. In this complex CAR1 retains activity, but ARG3 activity is inhibited
Uptake is completely abolished by carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) or nigericin
Secreted in a disulfide-oxidized form and apo-pools of secreted SOD5 can readily capture extracellular copper for rapid induction of enzyme activity
Allosterically activated by GTP, when glutamine is the substrate; GTP has no effect on the reaction when ammonia is the substrate (PubMed:4550559). The allosteric effector GTP functions by stabilizing the protein conformation that binds the tetrahedral intermediate(s) formed during glutamine hydrolysis (PubMed:11336655). Also activated by magnesium; the enzyme requires more Mg(2+) for full catalytic activity than required simply to complex the nucleotide substrates (PubMed:8385490). Inhibited by the product CTP, via allosteric rather than competitive inhibition (PubMed:8385490, PubMed:16216072). Also inhibited by divalent metal ions such as copper and zinc (PubMed:8385490). Is potently inhibited by the intermediate analog inhibitor glutamate gamma-semialdehyde (PubMed:11336655)
Inhibited by the monovalent cation Li(+) with an inhibition constant of 140 uM. Also inhibited by AMP and phosphoenolpyruvate and to a lesser extent by phosphate, fructose 6-phosphate, fructose 2,6-bisphosphate, and UDP. ATP and ADP have no significant effects on FBPase activity
Inhibited by itaconyl-CoA, a metabolite that inactivates the coenzyme B12 cofactor
Inhibited by EDTA and 1,10-phenanthroline (PubMed:8193588). Is also inhibited by endogenous tripeptide inhibitors pyroGlu-Asn-Trp, pyroGlu-Gln-Trp, and pyroGlu-Lys-Trp (PubMed:9703966)
ATPase activity inhibited by N-ethylmaleimide but not by vanadate
Competitively inhibited by cinnamyl and coniferyl alcohols and by isoeugenol
Strongly inhibited by ZnCl(2)
Strongly inhibited by leupeptin, puromycin, NEM, and divalent cations
Activated by threonine and tyrosine phosphorylation by two dual specificity kinases, MAP2K4 and MAP2K7. MAP2K7 phosphorylates MAPK10 on Thr-221 causing a conformational change and a large increase in Vmax for the enzyme. MAP2K4 then phosphorylates Tyr-223 resulting in a further increase in Vmax. Inhibited by dual specificity phosphatases, such as DUSP1. Inhibited by HDAC9 (By similarity)
Inhibited by dicyclohexylcarbodiimide; the enzyme is protected from inhibition by Na(+) in a pH-dependent manner
Activated by GUCA1B when free calcium ions concentration is low, and inhibited by GUCA1B when free calcium ions concentration is high (PubMed:15772651). Inhibited by RD3 (PubMed:29515371)
Treatment with N-ethylmaleimide inhibits sulfur transfer. Activated by ThiI and TusA
Activated in response to insulin. Autophosphorylation activates the kinase activity. PTPN1, PTPRE and PTPRF dephosphorylate important tyrosine residues, thereby reducing INSR activity. Inhibited by ENPP1. GRB10 and GRB14 inhibit the catalytic activity of the INSR, they block access of substrates to the activated receptor. SOCS1 and SOCS3 act as negative regulators of INSR activity, they bind to the activated INRS and interfere with the phosphorylation of INSR substrates (By similarity)
Not inhibited by (+)-menthofuran
Phosphorylation at Thr-18 or Tyr-19 inactivates the enzyme, while phosphorylation at Thr-169 activates it
Stimulated by GTF2F1. Inhibited by beryllofluoride anions
DNA-binding activity may be regulated by fatty acids
Is highly activated in the presence of AMP, with an increase of >40-fold in activity levels. Among other nucleotides, isomerase activity is slightly increased in the presence of GMP, but CMP, UMP, TMP, and NAD(+) have no effect; therefore, AMP is likely the major activator of R15P isomerase in vivo. To a lesser extent, various compounds with an adenosyl moiety, such as dAMP, adenosine, or methylthioadenosine, can also act as activators. The regulation of this enzyme by AMP prevents excess degradation of intracellular AMP by the archaeal AMP degradation pathway
Activated by tyrosine phosphorylation by a wide range of cytokine stimulations. When T-cells or B-cells receptors are activated, a series of phosphorylation leads to the recruitment of TEC to the cell membrane, where it is phosphorylated at Tyr-519. Also activated in response to SCF. Integrin engagement induces tyrosine phosphorylation of TEC in platelets. STAP1 participates in a positive feedback loop by increasing the activity of TEC. SOCS1 is an inhibitor of TEC kinase activity
In the absence of inducing signals, ExsE interacts with and inhibits ExsC activity
Unaffected by known inhibitors of amidohydrolases: PMSF, p-hydroxymercuribenzoate, p-chloromercuribenzoate and EDTA
Stimulated by a long-lived interaction with RsbT
Intracellular choline sensor. Binding to choline induces conformational changes and relieves the repressing effects of GbsR on expression
Activated by Ca(2+)/calmodulin. Binding of calmodulin may relieve intrasteric autoinhibition. Partially inhibited upon phosphorylation by PRCAKA/PKA (By similarity). May be regulated through phosphorylation by CAMK1 and CAMK4
Inhibited by Immucillin-H (PubMed:11707439, PubMed:30602534). Inhibited by antimalaria drugs quinine and mefloquine (PubMed:30602534)
Binding to DNA is inhibited by nickel and cobalt ions
Dysidenin and perchlorate inhibit iodide transport activity
Inhibited by high concentrations of magnesium
Endocytosis and inhibition of the activated EGFR by phosphatases like PTPRJ and PTPRK constitute immediate regulatory mechanisms. Upon EGF-binding phosphorylates EPS15 that regulates EGFR endocytosis and activity. Moreover, inducible feedback inhibitors including LRIG1, SOCS4, SOCS5 and ERRFI1 constitute alternative regulatory mechanisms for the EGFR signaling
Activated by calcium/calmodulin (PubMed:2022671, PubMed:19029295). Activated by forskolin (PubMed:2472670). Activated by the G protein alpha subunit GNAS (PubMed:2022671). Inhibited by the G protein beta and gamma subunit complex (PubMed:2022671). Inhibited by the ATP analogs adenosine, 2'-deoxyadenosine and 2'-deoxy-3'-AMP (PubMed:2022671)
Activated by Ca(2+)-bound calmodulin following an increase in intracellular Ca(2+) (PubMed:1322410, PubMed:24018048). At low Ca(2+) concentrations, the catalytic subunit (also known as calcineurin A) is inactive and is bound to the regulatory subunit (also known as calcineurin B) in which only two high-affinity binding sites are occupied by Ca(2+) (PubMed:1322410, PubMed:24018048). In response to elevated calcium levels, the occupancy of the low-affinity sites on calcineurin B by Ca(2+) causes a conformational change of the C-terminal regulatory domain of calcineurin A, resulting in the exposure of the calmodulin-binding domain and in the partial activation of calcineurin A (PubMed:1322410, PubMed:24018048). The subsequent binding of Ca(2+)-bound calmodulin leads to the displacement of the autoinhibitory domain from the active site and possibly of the autoinhibitory segment from the substrate binding site which fully activates calcineurin A (PubMed:1322410, PubMed:24018048). Inhibited by immunosuppressant drug FK506 (tacrolimus) in complex with FKBP12 and also by immunosuppressant drug cyclosporin A (CsA) in complex with PPIA/cyclophilin A; the inhibition is Ca(2+)-dependent (By similarity)
The full-length protein before cleavage is inactive: intramolecular interactions between N- and C-terminal domains mediate autoinhibition in the absence of activation signal. The intrinsic pyroptosis-inducing activity is carried by the released N-terminal moiety (Gasdermin-C, N-terminal)
Competitively inhibited by pyrophosphate
E3 ubiquitin-protein ligase activity of CeBCD complexes occurs at DNA damage sites. Following DNA damage, E3 ubiquitin-protein ligase activity is reduced by caffeine treatment (inhibitor of ATM and ATK kinase activity)
The rate of DNA-strand exchange is stimulated by RadA
Inhibited by AEBSF (4-(2-aminoethyl)benzenesulfonyl fluoride, Pefabloc SC), ampicillin and AMP(hyd) (ampillicin-derived penicilloic acid)
Is inhibited by sulbactam, tazobactam, and clavulanate. Sulbactam inhibits the enzyme competitively and reversibly with respect to nitrocefin. Tazobactam inhibits the enzyme in a time-dependent manner, but the activity of the enzyme reappears due to the slow hydrolysis of the covalently acylated enzyme. In contrast, clavulanate reacts with the enzyme quickly to form hydrolytically stable, inactive forms of the enzyme, via irreversible acylation of the catalytic serine residue. Clavulanate has potential to be used in combination with approved beta-lactam antibiotics to treat multi-drug resistant (MDR) and extremely drug resistant (XDR) strains of M.tuberculosis. Is also irreversibly inhibited by NXL104, which forms an extremely stable carbamoyl adduct with the enzyme but shows an inhibition efficiency more than 100-fold lower than that of clavulanate. Is inhibited by carbapenems, that are very poor substrates for the enzyme
Autoinhibited. Activated by diacylglycerol and calcium binding, which induces a conformational change releasing the autoinhibitory state (PubMed:23908768). Regulated by DGKA (PubMed:11919165). Regulated by DGKZ (PubMed:11257115). Regulated by PLC gamma and F-actin polymerization (PubMed:12839994)
Regulated by molecular oxygen, which binds to the heme binding site. Probably not activated by nitric oxide (NO) (By similarity)
Gelatinase activity is inhibited by serine-protease inhibitors, such as phenylmethylsulfonyl fluoride (PMSF), 4-(2-aminoethyl)-benzenesulfonyl fluoride hydrochloride (AEBSF), 4-amidino phenylsulfonyl fluoride (APSF) and diisopropyl fluorophosphate (DFP), N-ethylmaleimide (NEM) and phenylmethylsulfonyl fluoride (PMSF). Dipeptidyl peptidase activity is inhibited by 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid), diisopropylfluorophosphate (DFP). Prolyl endopeptidase activity is inhibited by the boronic acid peptide Ac-Gly-BoroPro, Ac-Gly-Pro-chloromethyl ketone and Thr-Ser-Gly-chloromethyl ketone
Activity is competitively inhibited by substituted ribitylpurinetrione compounds such as 3-(1,3,7,9-tetrahydro-9-D-ribityl-2,6,8-trioxopurin-7-yl)propane 1-phosphate, with inhibition constants in the 4-5 nM range
Activity is dependent on magnesium
In the absence of viral infection, maintained as a monomer in an autoinhibited state (PubMed:16846591, PubMed:16979567, PubMed:20049431). Phosphorylation by TBK1 and IKBKE disrupts this autoinhibition leading to the liberation of the DNA-binding and dimerization activities and its nuclear localization where it can activate type I IFN and ISG genes (PubMed:25636800). Phosphorylation and activation follow the following steps: innate adapter protein MAVS, STING1 or TICAM1 are first activated by viral RNA, cytosolic DNA and bacterial lipopolysaccharide (LPS), respectively, leading to activation of the kinases TBK1 and IKBKE (PubMed:25636800). These kinases then phosphorylate the adapter proteins on their pLxIS motif, leading to recruitment of IRF3, thereby licensing IRF3 for phosphorylation by TBK1 (PubMed:25636800). Phosphorylated IRF3 dissociates from the adapter proteins, dimerizes, and then enters the nucleus to induce IFNs (PubMed:25636800, PubMed:27302953)
(Microbial infection) Activated upon coronavirus SARS-CoV-2 infection
Ca(2+), Mg(2+) and EDTA have little effect on enzyme activity at 1-10 mM. Zn(2+) at 3, 5, 7 or 10 mM inhibits activity by 20%, 30%, 40% and 65%, respectively
Binding of effector molecule SA, or its structural analog PAS, to the binding pocket of Rv2887 induces conformational change in its DNA binding domain, preventing binding to the promoter region of htm, triggering the expression of this SAM-dependent methyltransferase
Is strongly inhibited by hydroxylamine and EDTA in vitro
Activated in the presence of substrate at low pH (PubMed:28812349). Specific activity fluctuates during fruit ripening, starting at immature-green stage, reaching a peak at the breaker stage, followed by a sharp decrease until the half-ripe stage to remain stable during the following development stages (PubMed:10198084). Triggered by CuSO(4) and by low concentrations of SDS. Repressed by several inhibitors including 4-hexylresorcinol, ascorbic acid, benzoic acid, kojic acid, glutathione (reduced form), L-cysteine and sodium metabisulfite. Inhibited by various salt such as FeSO(4), KCl, NaCl, CaCl(2), MnCl(2), NiCl(2) and AlCl(3). Spontaneously activated during storage at 4 degrees Celsius (PubMed:28812349)
Inhibited by phenylmethanesulfonyl fluoride (PMSF) and p-chloromercuribenzoate (PCMB)
Is inhibited by the substrate analog pyrrole-2-carboxylate, but not by N-formylphenylalanine
Coiled-coil-mediated oligomerization enhances the catalytic activity. Proteolytic processing of the C-terminus may release the protein from membranes and constitute a mean to regulate the enzyme. May be regulated by HSPB2, RAC1, RAF1 and G-protein second messengers (By similarity)
ATP hydrolysis is inhibited by Mg(2+), already at a concentration of 0.4 mM
Activated by GUCA1B when free calcium ions concentration is low, and inhibited by GUCA1B when free calcium ions concentration is high (PubMed:9571173). Inhibited by RD3 (By similarity)
Alternates between an inactive form bound to GDP and an active form bound to GTP. Activated by the guanine nucleotide-exchange factor (GEF) TRAPP complex, and inactivated by GTPase-activating protein (GAP) GYP3
Activated by pro-inflammatory cytokines and in response to physical and chemical stresses, including osmotic stress, oxidative stress, arsenic and ultraviolet light irradiation. Activated by 'Lys-63'-linked polyubiquitination and by autophosphorylation. Association with TAB1/MAP3K7IP1 and TAB2/MAP3K7IP2 promotes activation through autophosphorylation, whereas PPM1B/PP2CB, PP2A and PPP6C dephosphorylation leads to inactivation. Ceramides are also able to activate MAP3K7/TAK1
Increased activity at pH 6.0 (PubMed:31356773). sulfate/sulfate exchange activity is inhibited strongly by pyridoxal 5'-phosphate, bathophenanthroline and the organic mercurials mersalyl, p-chloromercuribenzoate and HgCl2 (PubMed:31356773)
Inhibited by HQNO, a quinone derivative
Increased activity in the presence of dithiothreitol (DTT) in vitro. Inhibited by 1 mM potassium phosphate and potassium chloride. Inhibited by L-alpha-ornithine, D,L-alpha-lysine, L-beta-lysine (50%-60%), L-alpha-lysine (26%) and by delta-amino-n-valeric acid to a lesser extent. Significant decrease in activity is observed in the presence of 0.2 mM p-chloromercuribenzoate, N-ethylmaleimide and also by 2 mM iodoacetate to a lesser extent but not inhibited by arsenite
Stimulated by lipoic acid. Inhibited in presence of methylamine
Inhibited by PMSF, L-cysteine and partially by SBTI and leupeptin
Inhibited by the multi-targeted cancer drugs imatinib and ponatinib
Transcriptionally activated by IRE1 in response to endoplasmic reticulum (ER) stress. IRE1 cleaves a 20-bp fragment causing a frameshift of the mRNA transcript, leading to a nuclear isoform of the BZIP50 activator
Inhibited by Z-VAD-fmk, a well-known caspase inhibitor. Also inhibited by Man9GlcNAc2-iodoacetoamide. Both molecules inhibit enzyme activity through covalent binding of the carbohydrate to the single Cys-191 residue
Inhibited by L-penicillamine (By similarity). Inhibited by cilastatin (PubMed:8823187, PubMed:8045301)
Stimulated by calcium and phosphatidylserine (By similarity). Activated by sphingosine (PubMed:22627129)
Phosphatidate (1,2-diacyl-sn-glycero-3-phosphate, PA) can positively regulate phospholipase A1 activity
Inhibited by semicarbazide, hydroxylamine, aminooxyacetate, sodium borate or phenylhydrazine (PubMed:19249065). Racemase activity is enhanced by Ca(2+), Mg(2+) and is decreased by ATP, Cu(2+), Zn(2+) (PubMed:19249065, PubMed:20564571). Hydratase activity is enhanced by ATP and is decreased by Ca(2+), Mg(2+), Co(2+), Cu(2+), Ni(2+), Zn(2+) (PubMed:19249065, PubMed:20564571)
Activated through serine and threonine phosphorylation by MEKK1. Inhibited through phosphorylation by GSK3/Shaggy-like kinase ASKs
Not inhibited by (+)-marmesin, psoralen, 5- or 8-methoxypsoralen and angelicin
The enzyme activity is specifically activated by double-stranded RNA (dsRNA)
Cellobiose-6'-phosphate and 6-phospho-beta-D-glucopyranoside are not substrates but competitive inhibitors of GlvA
Inhibited by 42 nM hanatoxin 1 (HaTx1), a spider venom toxin of the tarantula G. spatulata (PubMed:7576642). Inhibited by 100 nM stromatoxin 1 (ScTx1), a spider venom toxin of the tarantula S. calceata (PubMed:12065754). Modestly sensitive to millimolar levels of tetraethylammonium (TEA) and 4-aminopyridine (4-AP) (PubMed:2770868, PubMed:1875913, PubMed:8083226, PubMed:9362476). Completely insensitive to toxins such as dendrotoxin (DTX) and charybdotoxin (CTX) (PubMed:9362476)
Miglitol is an effective inhibitor at 1 mM
Inhibited by wortmannin and adenosine (PubMed:11277933). Increased kinase activity upon interaction with NCS1/FREQ (By similarity)
(Microbial infection) Activated by Aichi virus protein 3A, this activation is sensitized by ACBD3
Is competitively inhibited by aspterric acid in vitro, which is thus a potential new lead compound for the design of novel anti-TB drugs
Kinase activity is activated upon binding to GTP-bound Rho/Rac GTPases. Activated by lipids, particularly cardiolipin and to a lesser extent by other acidic phospholipids and unsaturated fatty acids. Two specific sites, Thr-809 (activation loop of the kinase domain) and Thr-951 (turn motif), may be needed to be phosphorylated for its full activation (By similarity)
Has c-di-GMP PDE activity in both Fe(2+) and Fe(3+)-bound forms; this activity is increased 6-7 fold by binding of O(2) and CO (PubMed:15995192) and NO (PubMed:17535805). Has cAMP PDE activity only when the heme is in the Fe(2+) form. cAMP PDE activity is inhibited by oxidation of the heme iron and by binding of external ligands such as CO and NO. Also strongly inhibited by etazolate hydrochloride, a selective cAMP PDE inhibitor. PDE activity is inhibited in the absence of oxygen
Fibrinolytic and caseinolytic activities are inhibited by Cd(2+), Cu(2+) and Co(2+) ions. Not inhibited by Mg(2+), Ca(2+) and Ba(2+). Also inhibited by EDTA, EGTA and 1,10-phenanthroline
Inhibited by calcium concentrations higher than 1 mM
Inhibited by glycolohydroxamate at concentration above 0.1 mM
Allosterically activated by S-adenosyl-methionine (SAM)
Subject to inhibition by high substrate concentrations. Inhibited by testosterone concentrations above 10 uM (PubMed:18407998). Inhibited by the primary and secondary bile acids chenodeoxycholic acid and ursodeoxycholic acid (PubMed:21255593)
Inhibited by both 1-deoxymannojirimycin and kifunensine
Folding, maturation and production of the active form of the protease by the cell requires a protein (ORF2), encoded just downstream of asp, which acts as a chaperone (PubMed:11092244, PubMed:12446656, PubMed:25784551). Formation of a complex with ORF2 in the periplasm also inactivates the protease activity and likely protects ASP from intrinsic proteases (PubMed:25784551). In vitro, protease activity is inhibited by human alpha-2-macroglobulin, suggesting that this inhibitor can impede ASP virulence activities in A.sobria infection sites (PubMed:23089609). However, slow ASP inhibition by alpha-2-macroglobulin in plasma may indicate insufficient ASP control in vivo (PubMed:23089609). Activity is inhibited by serine protease inhibitors such as 4-(2-aminoethyl)-benzenesulfonyl fluoride (AEBSF) and diisopropyl fluorophosphate (DFP) (PubMed:11092244, PubMed:12153115). Not inhibited by metallo-protease inhibitors and cysteine protease inhibitors (PubMed:12153115). The treatment with reagents to modify sulfhydryl group do not reduce the activity (PubMed:12153115)
Activated by glutamine (PubMed:34535752, PubMed:29698392). May also be activated by cysteine (PubMed:34535752)
The activity can be inhibited by the 18 kDa competence-specific protein nin
The formation of the complex with AroG activates the chorismate mutase activity
Allosterically activated and regulated via the combined actions of GTP and dNTPs (dATP, dGTP, dTTP and dCTP): Allosteric site 1 binds GTP, while allosteric site 2 binds dNTP (PubMed:25288794, PubMed:25267621, PubMed:25760601). Allosteric activation promotes the formation of highly active homotetramers (PubMed:22056990, PubMed:24141705, PubMed:24217394, PubMed:25288794, PubMed:25267621, PubMed:25760601). Phosphorylation at Thr-592 impairs homotetramerization, thereby inhibiting dNTPase activity, leading to reduced ability to restrict infection by viruses (PubMed:23602554, PubMed:23601106, PubMed:26294762, PubMed:26431200, PubMed:29610582, PubMed:29670289)
Inactivated by phenylmethylsulfonylfluorid (PMSF), a specific inhibitor of serine esterases
Inhibited by 4-aminopyridine (4-AP), tetraethylammonium (TEA) and dendrotoxin (DTX), but not by charybdotoxin (CTX)
Activated by Ser and Thr phosphorylation
Completely inhibited by EDTA, EGTA, 1,10-phenanthroline, and partially by beta-mercaptoethanol. Is not inhibited by aprotinin and leupeptin. Conserves its activity upon fibrinogen when incubated with cobalt, magnesium ions up to 40 mM, but loses the proteolytic activity when incubated with manganese, fer, zinc or calcium ions
In non-stressed conditions, mainly remains soluble (PubMed:32117138). Forms aggregates in response to different environmental stresses such as heat shock, oxidative stress and antibiotic treatment, and cannot assist Spx degradation (PubMed:32117138)
Activated by the G protein alpha subunit. Activated by the G protein beta and gamma subunit complex. Activated by GNA13 and GNA12. Ethanol and phorbol 12,13-dibutanoate significantly potentiate adenylate cyclase activity generated in response to the activation of the prostanoid receptor by the agonist prostaglandin E1(1-) in a PKC-dependent manner (By similarity). Inhibited by lithium (PubMed:18205980)
In quiescent cells, maintained in an inactive state via an intramolecular interaction between the protein kinase and N-terminal domains. Following mitogen-mediated cell activation, binds via its RGB domain to active HRAS (GTP-bound) which releases the inhibitory intramolecular interaction between the two domains. This allows the MAP2K1-mediated dimerization of KSR1 or KSR2, and BRAF which activates BRAF
Significantly inhibited by the addition of sodium dodecyl sulfate (SDS), but not by EDTA, urea, 2-mercaptoethanol or Triton X-100. Strongly inhibited by Cu2(+) ions, in case of which the activity is decreased by 70%. No significant inhibition with Al(3+), Fe(3+), Ca(2+), Cd(2+), Mg(2+), Mn(2+), Ni(2+) and Zn(2+) ions. Strongly inhibited by PugNAc (O-(2-acetamido-2-deoxy-D-glucopyranosylideneamino) N-phenylcarbamate) in the sub-micromolar concentration range. PugNAc at a concentration of 0.5 mM decreases the activity by 50% and the addition of 1 mM PugNAc fully inhibits the enzyme. No significant reduction in the activity by alkylation using N-ethylmaleimide or 2-iodoacetamide
Clotting activity on human plasma is not abrogated by the plasma proteinase inhibitors alpha(2) macroglobulin and murinoglobulin
Inhibited by amino-NADP(+)
Inhibited by small molecule methimazole (MMZ)
Regulated by metabolites
Allosteric enzyme. Stimulated by magnesium ions (By similarity)
Novel PKCs (PRKCD, PRKCE, PRKCH and PRKCQ) are calcium-insensitive, but activated by diacylglycerol (DAG) and phosphatidylserine. Three specific sites; Thr-505 (activation loop of the kinase domain), Ser-643 (turn motif) and Ser-662 (hydrophobic region), need to be phosphorylated for its full activation. Activated by caspase-3 (CASP3) cleavage during apoptosis. After cleavage, the pseudosubstrate motif in the regulatory subunit is released from the substrate recognition site of the catalytic subunit, which enables PRKCD to become constitutively activated. The catalytic subunit which displays properties of a sphingosine-dependent protein kinase is activated by D-erythro-sphingosine (Sph) or N,N-dimethyl-D-erythrosphingosine (DMS) or N,N,N-trimethyl-D-erythrosphingosine (TMS), but not by ceramide or Sph-1-P and is strongly inhibited by phosphatidylserine (By similarity)
Calcium ions inhibit the GTPase activity and promote the polymerization of FtsZ
Is inhibited by Ag(+) and Hg(2+) in vitro. EDTA and other metal cations such as Na(+), K(+), Ca(2+), Cu(2+), Mg(2+), Fe(3+), and Zn(2+) have no effect on catalytic activity
Phosphorylation of GltR induces its dissociation from DNA leading to transcriptional activation
Allosterically activated and regulated via the combined actions of GTP and dNTPs (dATP, dGTP, dTTP and dCTP): Allosteric site 1 binds GTP, while allosteric site 2 binds dNTP. Allosteric activation promotes the formation of highly active homotetramers
Activated by threonine and tyrosine phosphorylation (By similarity). Activated in response to hydrogen peroxide. Activation is triggered by MAPKKK17 and MAPKKK18 in a MKK3-dependent manner (PubMed:25720833)
Competitively inhibited by 6-hydroxynicotinaldehyde
Activated by Pb(2+) and Hg(2+) ions
No change in activity after supplementation with 10 mM glucose. However, activity decreases significantly when glucose concentration is higher than 50 mM and almost all activity is lost with 200 mM glucose. Activity is significantly increased after treatment with 10 mM and 50 mM ATP. However, activity drops significantly with 200 mM ATP. Inhibited by 10-200 mM alpha-ketoglutarate. No change in activity after incubation with 10-200 mM L-citrulline, L-ornaline or glycerol
Phosphorylation at Thr-14 or Tyr-15 inactivates the enzyme, while phosphorylation at Thr-159 activates it
Inhibited by menadione and isovanillin. Not inhibited by allopurinol, a xanthine dehydrogenase potent inhibitor
The phosphatase activity of the PPP1R15A-PP1 complex toward EIF2S1 is specifically inhibited by Salubrinal, a drug that protects cells from endoplasmic reticulum stress
Inhibited by tetrahydrolipstatin (THL), a specific lipase inhibitor, and by derivatives of THL (PubMed:19169353, PubMed:20656688, PubMed:21384024). Inhibited by high concentrations of paraoxon (PubMed:19225166). Also inhibited by a Furan-based urea derivative, 1-(3,5-difluorophenyl)-3-(furan-2-ylmethyl)urea (PubMed:31741730)
CARD8 inflammasome is inhibited by DPP8 and DPP9, which sequester the C-terminal fragment of CARD8 (Caspase recruitment domain-containing protein 8, C-terminus) in a ternary complex, thereby preventing CARD8 oligomerization and activation. CARD8 inflammasome is activated by Val-boroPro (Talabostat, PT-100), an inhibitor of dipeptidyl peptidases DPP8 and DPP9. Val-boroPro relieves inhibition of DPP8 and/or DPP9 by inducing the proteasome-mediated destruction of the N-terminal part of CARD8, releasing its C-terminal part from autoinhibition
The NAALADase activity is inhibited by beta-NAAG, quisqualic acid, 2-(phosphonomethyl) pentanedioic acid (PMPA) and EDTA. Activated by cobalt
Dimerization causes loss of catalytic activity (By similarity). Inhibited by pepstatin A (PubMed:11782538)
Inhibited by zinc. Inhibited by heparin and proteolysis by plasmin
Calcium-binding enhances the activity of the enzyme
Inhibited by chlorate (PubMed:9576487). The kinase activity is subject to inhibition by the substrate adenylyl sulfate (PubMed:17540769)
Subject to competitive inhibition by NADP. Not inhibited by proline
In normal conditions, the protein kinase activity is inhibited; inhibition is relieved by various stress conditions (By similarity). Inhibited by heme: in presence of heme, forms a disulfide-linked inactive homodimer (PubMed:2722851). Heme depletion relieves inhibition and stimulates kinase activity by autophosphorylation. Inhibited by the heme metabolites biliverdin and bilirubin. Induced by oxidative stress generated by arsenite treatment. Binding of nitric oxide (NO) to the heme iron in the N-terminal heme-binding domain activates the kinase activity, while binding of carbon monoxide (CO) suppresses kinase activity (By similarity). Protein kinase activity is also activated upon binding to the processed form of DELE1 (S-DELE1): interaction with S-DELE1 takes place in response to mitochondrial stress and triggers the integrated stress response (ISR) (By similarity)
RAN inhibits its autophosphorylation and its ability to phosphorylate histone H3
Allosterically activated by AMP and inhibited by ATP
Activated by GTP and inhibited by ATP and IMP. Mycophenolic acid (MPA) is a competitive inhibitor of the enzyme with respect to NADPH
Activity of CodY is modulated by interaction with two types of effectors: the branched-chain amino acids (BCAAs) leucine, isoleucine and valine, which are signals of the nutritional status of the cell, and GTP, which may signal the energetic status of the cell (PubMed:20363936, PubMed:27116338, PubMed:29357354). GTP and the BCAAs act additively to increase the affinity of CodY for DNA (PubMed:20363936). Isoleucine could be a major signal for CodY regulation in comparison to other BCAAs (PubMed:19251851, PubMed:29357354)
Inhibited by KAPA at concentrations higher than 0.05 mM
Inhibited by 1-(1-acetylpiperidin-4-yl)-3-(4-(trifl uoromethoxy)phenyl)urea (TPAU), 1-cyclohexyl-3-dodecylurea (CDU), 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA), 1-((3S, 5S, 7S)-adamantan-1-yl)-3-(5-(2-(2-ethoxyethoxy) ethoxy)pentyl)urea (AEPU) and to a lesser extent by 8-(3-((3S, 5S, 7S)-adamantan-1-yl)ureido) octanoic acid (AUOA)
Constitutively active protein kinase whose activity is not directly affected by phosphorylation. Seems to be regulated by level of expression and localization
Inhibited by tryptophan, indole-3-pyruvic acid, 3-indolepropionic acid, DL-indole-3-lactic acid, indole-3-acetic acid (IAC), amino-oxyacetate (AOAA), aminooxy-phenylpropionic acid (AOPP) and Tris
DNA binding is affected significantly by increasing the NaCl concentration
Inhibited by cyanide and therefore dependent of an energy source (PubMed:18270315). Inhibited by DIDS/4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid, an inhibitor hydrogencarbonate-dependent transporters (PubMed:18270315)
By arginine and urea
Partially inhibited by Na(+), Ca(2+) or Mn(2+) at concentrations of 5 mM. Presence of 5 mM of Zn(2+), Hg(2+) or EDTA results in more than 95% inhibition
By divalent metal ions. Fe(2+), Zn(2+), Cu(2+), Pb(2+) and Sn(2+) inhibit 52, 76.6, 85.3, 100 and 100% of the enzyme activity, respectively. Other metal cations and EDTA do not inhibit this enzyme. Thiol reagents 2-mercaptoethanol and dithiothreitol have no effect on the activity. Sulfhydryl group-blocking reagents p-chloromercuribenzoic acid and iodoacetic acid inhibit 86.2 and 74% of the enzyme activity, respectively
Specifically inhibited by sinefungin derivatives. N-propyl sinefungin (Pr-SNF) interacts preferentially with SETD2
Inhibited by N-ethylmaleimide, hydroxymercuribenzoate, methyl mercury iodide and heavy metals such as Hg2+, Cu2+, and Ag2+
Not regulated by feedback inhibition by CoA and its thioesters as described for many other pantothenate kinases. Competitively inhibited by N-pentylpantothenamide (N5-Pan) and N-heptylpantothenamide (N7-Pan), although these compounds can also act as substrates, being converted to inactive CoA analogs which inhibit a number of cellular targets, especially fatty acid biosynthesis
The enzyme in complex with the DNA substrate binds a third divalent metal cation (PubMed:27284197). The binding of this third divalent cation, which is coordinated by water molecules and two oxygen atoms from DNA and dNTP, is essential for catalyzing the DNA synthesis (PubMed:27284197)
Inhibited by delta-N-phosphonoacetyl-L-ornithine
Activated by ATP (By similarity). Inhibited by calcium-activated calmodulin (PubMed:29472584). Inhibited by bromoenol lactone (BEL) (By similarity)
Inhibited by antizymes (AZs) in response to polyamine levels. AZs inhibit the assembly of the functional homodimer by binding to ODC monomers and targeting them for ubiquitin-independent proteolytic destruction by the 26S proteasome
Inhibited by EDTA, butyrate and citrate
It is inactivated via its interaction with cut2, which probably covers its active site. Cut2 degradation at anaphase, liberates it and triggers rad21 cleavage
Methyltransferase activity is autoinhibited by the K-loop region that blocks S-adenosyl-L-methionine-binding. Upon activation, K-loop changes conformation, allowing S-adenosyl-L-methionine-binding and subsequent methyltransferase activity. mRNA N6-adenosine-methyltransferase activity is inhibited by zinc
Its activity is inhibited by trichostatin A (TSA), suberoylanilide hydroxamic acid (SAHA), 3-(1-methyl-4-phenylacetyl-1H-2-pyrrolyl)-N-hydroxy-2-propenamide (APHA), 4-dimethylamino-N-(6-hydroxycarbamoyethyl)benzamide-N-hydroxy-7-(4-dimethylaminobenzoyl)aminoheptanamide (MS-344), 5-(4-methyl-benzoylamino)-biphenyl-3,4'-dicarboxylic acid 3-dimethylamide 4'-hydroxyamide (CRA-A) and butyrate
NADPH is a strong modulator that switches activity from a pyruvate-producing malic enzyme to a lactate-generating malolactic enzyme
Is potentially allosterically regulated by GTP/GDP, which enhances its affinity for AdoCbl by 5-fold. Binds cob(II)alamin weakly in the absence of ATP. The presence of ATP (but not GTP or GDP) increases the affinity of cob(II)alamin for the enzyme, and stoichiometric binding is observed. GTP blocks the transfer of cob(II)alamin to IcmF from ATR, thus averting its reconstitution with inactive cofactor
The very low intrinsic ATPase activity is increased upon interaction with liposomes
Expression inhibited by androgens such as testosterone
Binds heme b (PubMed:24669201, PubMed:24865947). The redox state of the heme b modulates the activity of the enzyme (PubMed:24865947). Activity is stimulated by sodium dithionite (PubMed:24865947)
The side chain of Glu-261 determines which of the two opposing activities (AMPylase or de-AMPylase) will take place. In response to endoplasmic reticulum stress, mediates de-AMPylase activity (By similarity). Adenylyltransferase activity is inhibited by the inhibitory helix present at the N-terminus: Glu-261 binds ATP and competes with ATP-binding at Arg-400, thereby preventing adenylyltransferase activity (By similarity). In unstressed cells, disengagement of Glu-261 promotes adenylyltransferase activity (By similarity). Activation dissociates ATP-binding from Glu-261, allowing ordered binding of the entire ATP moiety with the alpha-phosphate in an orientation that is productive for accepting an incoming target hydroxyl side chain (By similarity)
Activated by binding small G proteins. Binding of GTP-bound CDC42 or RAC1 to the autoregulatory region releases monomers from the autoinhibited dimer, enables phosphorylation of Thr-436 and allows the kinase domain to adopt an active structure (By similarity)
Phosphorylated at multiple sites in response to pheromone
Inhibited by leupeptin and bis(5-amidino-2-benzimidazolyl)methane (BABIM)
The aminobutyraldehyde dehydrogenase activity is negatively regulated by ethanol in vivo
Activated by GUCA1A when free calcium ions concentration is low, and inhibited by GUCA1A when free calcium ions concentration is high (By similarity). Negatively regulated by RD3; RD3 inhibits the basal and GUCA1A-stimulated guanylate cyclase activity (By similarity)
Methyltransferase activity is autoinhibited by the K-loop region that blocks S-adenosyl-L-methionine-binding (PubMed:30197297). Upon activation, K-loop changes conformation, allowing S-adenosyl-L-methionine-binding and subsequent methyltransferase activity (PubMed:30197297). mRNA N6-adenosine-methyltransferase activity is inhibited by zinc (PubMed:33428944)
Activation may be calcium-dependent. Inhibited by the non-covalent interaction with the cleaved propeptide
Inhibited by GBR 12909 dihydrochloride, amphetamine and cocaine
Inhibited by Zn(2+), Fe(2+) and Cu(2+), but not by EDTA
Efflux is inhibited by FCCP
Present in an inactive conformation in the absence of bound ligand. Binding of VEGFA, VEGFB or PGF leads to dimerization and activation by autophosphorylation on tyrosine residues (By similarity)
Allosterically activated by fructose-1,6-bisphosphate (F16BP), hexanediol 1,6-bisphosphate, NADPH and pyridoxal phosphate. Inhibited by AMP and by high concentrations of MgCl(2)
Inhibited by divalent metal cations
Inhibited by ATP, but not by fructose 1,6-bisphosphate or 2-phosphoglycerate
Adopts an inactive conformation in absence of DNA damage (PubMed:33357431, PubMed:34486521, PubMed:34874266). Binding to poly-ADP-ribosylated histones activates the ATP-dependent chromatin remodeler activity (PubMed:34486521, PubMed:34874266)
The activity is calcium-dependent (PubMed:7809169). Requires phosphatidylserine for maximal activity (By similarity)
Inhibited by sodium vanadate
Affinity and transport activity are regulated by a phosphorylation switch state at Ser-274 and Ser-297; increasing of affinity and amino acid transport activity via dephosphorylation at Ser-274 and phosphorylation at Ser-297
Activated by oxidation of Cys-199 resulting in the alternative formation of cystine, sulfenic acid, S-nitroso- or glutathione-bound cysteine
The activity of this enzyme is not inhibited by terbinafine, an established inhibitor of the conventional flavoprotein squalene epoxidase
Is activated by sulfite ions
The formation of the proteasomal ATPase ARC-20S proteasome complex, likely via the docking of the C-termini of ARC into the intersubunit pockets in the alpha-rings, may trigger opening of the gate for substrate entry. Interconversion between the open-gate and close-gate conformations leads to a dynamic regulation of the 20S proteasome proteolysis activity. In vitro, chymotryptic and tryptic activities of the proteasome are both completely inhibited by epoxomicin and by the peptidyl boronate inhibitor MLN-273. Also inhibited by Mg(2+), Ca(2+) and SDS. It was also shown that certain oxathiazol-2-one compounds can act as selective suicide-substrate inhibitors of the M.tuberculosis proteasome by irreversibly cyclocarbonylating its active site threonine. Proteasome activity is potently inhibited by fellutamide B (Ki=6.8 nM), a lipopeptide aldehyde that forms a reversible bond with the beta-OH of the active site threonine (PubMed:20558127)
Activated by metal ions such as Mg(2+), Na(+) and K(+)
Activated by MTM1
Inhibited by Cu(2+), Ag(+) and Hg(+), but not by other cations such as Mg(2+), Ca(2+), Mn(2+) and Co(2+). Inhibited by 1-amino-1-deoxy-D-glucose and p-chloromercuribenzoic acid, but not by EDTA or dithiothreitol. Inhibited by the disaccharides sucrose, lactose and cellobiose. The monosaccharides D-fructose, D-mannose, D-xylose and D-glucose increase the beta-D-fucosidase activity, but not the beta-D-glucosidase activity. D-glucose inhibits the beta-D-glucosidase activity, but promotes the beta-D-fucosidase activity. D-fucose inhibits the beta-D-glucosidase activity and does not significantly affect the beta-D-fucosidase activity
The activity of this enzyme is not inhibited by butyrate, a well-known histone deacetylase inhibitor
Autophosphorylation of CAMK2 plays an important role in the regulation of the kinase activity
Activated by the cyclic di-AMP (c-di-AMP) receptor DarB in the absence of c-di-AMP (PubMed:35130724). Allosterically activated by acetyl-CoA (PubMed:4146915, PubMed:35130724). Inhibited by the biotin-complexing protein avidin (PubMed:4146915)
Zofenoprilat inhibits Cys-Gly hydrolysis activity
Its activity is inhibited by trichostatin A (TSA), a known histone deacetylase inhibitor
Inhibited by the protonophore 3,3',4',5-tetrachlorosalicylanilide (TCS). Not activated by osmolarity
The rate of urea conduction is increased by hypotonic stress
Inhibited by 3,5-dichlorocatechol, chlorohydroquinone and 4,5-dibromocatechol
Mg(2+) is absolutely required for DNA restriction
Inhibited by alendronate (ALN), orthovanadate, and phenylarsine oxide (PAO)
Cholesterol transport is inhibited by vanadate and by beryllium fluoride
Inhibited by zinc and copper ions (PubMed:16782809). Repressed by 4-bromo-cinnamyl acetate (PubMed:16782809)
Prematurely activated/folded staphopain A is inhibited by staphostatin A (ScpB), which is probably required to protect staphylococcal cytoplasmic proteins from degradation by ScpA. Also inactivated by heavy metal ions such as Hg(2+) or Ag(+), iodoacetamide, E-64 and human plasma
Phosphodiesterase (PDE) inhibited by Zn(2+), Ca(2+) inhibits in the presence of Mg(2+) but not Mn(2+); c-di-AMP PDE activity is competitively inhibited by ppGpp (PubMed:19901023). Heme binding (by Fe(2+) or Fe(3+) heme) inhibits PDE, activity is partially restored by KCN or NO only for Fe(2+) heme (PubMed:21257773). Binding of NO to Fe(2+) heme switches from hexa- to pentacoordination (PubMed:21257773). Heme binding inhibits the ATPase activity (PubMed:21257773)
Inhibited by adenosine(5')pentaphospho(5')adenosine (Ap5A), Ap6A and to a much lower extent by Ap4A
The higher affinity of RsbW for RsbV than for sigma-B, rather than a difference in the concentrations of RsbV and sigma-B, is the driving force that is responsible for the switch of RsbW to non-phosphorylated RsbV. The kinase activity of RsbW is directly regulated by changes in the ATP/ADP ratio
Its proteolytic and hemorrhagic activities are inhibited by EDTA, but not by PMSF
Activated by calcium/calmodulin (PubMed:9662407). Activated by forskolin. Activated by the G protein alpha subunit GNAS. Inhibited by the G protein beta and gamma subunit complex. Inhibited by the ATP analogs adenosine, 2'-deoxyadenosine and 2'-deoxy-3'-AMP
Inhibited by quinolone antibiotic ciprofloxacin and coumarin antibiotic novobiocin, but at much higher concentrations than is usual for DNA gyrase/topoisomerase
Lysyl hydroxylase activity is strongly inhibited by imidazole
Activated by Ca(2+) (PubMed:11580282). Activated by NCALD in a Ca(2+)-dependent fashion (PubMed:11580282)
Myo-inositol causes the dissociation of the IpsA-DNA complex in vitro
Inhibited by N-ethylmaleimide and iodoacetamide
Glucose and fructose transport are inhibited by the flavonoid apigenin
Inhibited by endo-oxabicyclic diacid resembling to the conformation of the transition state
Inhibited by triclosan and its diphenyl ether analgues
Phosphatase activity requires amyloid-like aggregation on the membrane
Inhibited by low micromolar concentrations of Gd(3+) and high micromolar concentrations of verapamil. Insensitive to tetrodotoxin (TTX) and potentiated by low external Ca(2+) concentration
Completely inhibited at 50 mM ATP, but not inhibited at high fructose concentration
Completely inhibited by phenylmethylsulfonyl fluoride (PMSF) and partially by leupeptin
When cellular nitrogen levels are high, the C-terminal adenylyl transferase (AT) of GlnE inhibits GlnA by covalent transfer of an adenylyl group from ATP to Tyr-406 (PubMed:15037612). Conversely, when nitrogen levels are low, the N-terminal adenylyl removase (AR) of GlnE activates GlnA by removing the adenylyl group by phosphorolysis (PubMed:15037612). The fully adenylated enzyme complex is inactive (Probable)
Upon extracellular signal or mitogen stimulation, phosphorylated at Thr-570 in the C-terminal kinase domain (CTKD) by MAPK1/ERK2 and MAPK3/ERK1. The activated CTKD then autophosphorylates Ser-377, allowing binding of PDPK1, which in turn phosphorylates Ser-218 in the N-terminal kinase domain (NTDK) leading to the full activation of the protein and subsequent phosphorylation of the substrates by the NTKD
Inhibited by the protonophore carbonyl cyanide m-chlorophenylhydrazone (CCCP), but not by valinomycin
Not inhibited by 13-cyclopropylidene or 16-methylidenegeranylgeranyl diphosphate. The copalyl diphosphate synthase activity is not susceptible to magnesium-dependent inhibition
In vitro, can be activated by reagents that attack Cys-50 sulfhydryl, such as N-ethylmaleimide and via nitration of Tyr-93 by peroxynitrite
The presence of the regulatory subunit PRIM2/p58 accelerates the kinetics of initiation and primer extension (By similarity). Inhibited by arabinose nucleoside derivatives such as fludarabine and vidarabine (PubMed:31479243)
DNA polymerase is inhibited by replication protein A (RPA), while 3'-5' exonuclease activity is not. Polymerase inhibition can be overcome by replication factor C (RFC) and PCNA
Activation requires autophosphorylation of Ser-335. Phosphorylation of Ser-331 also promotes increased activity (By similarity)
Each dimer has two allosteric binding sites that can bind the regulatory effectors tryptophan or tyrosine (PubMed:10428795). Can bind either one tryptophan or one tyrosine, two tryptophan or two tyrosine or one tryptophan and one tyrosine, which differentially affect the catalytic activity (By similarity). Activated by tryptophan and subject to feedback inhibition by tyrosine (PubMed:10428795). In the presence of both tryptophan and tyrosine, the enzyme is in the activated state (By similarity)
Inhibited by econazole, clotrimazole and miconazole
Amino acid transport activity is increased by sodium (PubMed:29872228). Transport of L-glutamine, leucine and tyrosine is increased by arginine binding (By similarity)
Inhibited by bestatin (By similarity). The epoxide hydrolase activity is restrained by suicide inactivation that involves binding of LTA4 to Tyr-379 (PubMed:9287304). 4-(4-benzylphenyl)thiazol-2-amine (ARM1) selectively inhibits the epoxide hydrolase activity (By similarity)
The LKR activity is stimulated by NaCl
Inhibited by piperine, verapamil and verapamil analogs
Activation of CDK1, appears to be an upstream event of AURKA activation. Phosphatase inhibitor-2 (PPP1R2) and TPX2 act also as activators. Inactivated by the G2 checkpoint. Inhibited by GADD45A and p53/TP53, and through dephosphorylation by protein phosphatase type 1 (PP1). MLN8054 is also a potent and selective inhibitor. Activated during the early phase of cilia disassembly in the presence of PIFO. Inhibited by the small molecule inhibitor VX-680 (PubMed:28218735)
Activated by Ca(2+)/calmodulin
The full-length protein before cleavage is inactive: intramolecular interactions between the N-terminal domain and the C-terminal region as well as the lipid modification, mediate autoinhibition (Probable). The pyroptosis-like-inducing activity is carried by the released N-terminal domain (Gasdermin bGSDM, N-terminus) (By similarity)
In bacteria displays feedback inhibition by L-serine
Inhibited by vanadate and calcium
Inhibited by 5-methyltetrahydrofolate monoglutamate and by 5-methyltetrahydrofolate pentaglutamate, inhibition is much more effective by the pentaglutamate form than by the monoglutamate form (PubMed:3838667). Two molecules of 5-methyltetrahydrofolate are bound per tetramer. The binding sites are localized between subunits. Inhibitor binding may preclude movements of the polypeptide chain that are necessary for enzyme activity
Inhibited by acyl-CoA
(Microbial infection) Cleavage by S.pyogenes cysteine protease SpeB promotes its activation independently of CASP1 (PubMed:28331908, PubMed:32719155). SpeB-mediated maturation of IL1B plays a dual role depending on infection site: while IL1B inflammatory response prevents bacterial growth during invasive skin infections, it promotes streptococcal infection of the nasopharynx by disrupting colonization resistance mediated by the microbiota (PubMed:28331908, PubMed:32719155)
Inhibited by NaF, sodium orthovanadate, propanolol, and N-ethylmaleimide
Requires cadmium for activity. Also activated in vitro by Zn(2+), Cu(2+), Fe(2+) or Fe(3+) ions, but not by Co(2+) or Ni(2+) ions
Activity is optimum in the presence of Mg(2+) and K(+)
Autoinhibited by the C-terminal PH domain which folds back and binds to the surface of the DH domain, blocking binding of RHOA to the catalytic center of the DH domain (PubMed:31888991). The 2nd BRCT domain is also involved in inhibition, probably by helping to impede RHOA binding (PubMed:31888991). Allosterically activated by binding of activated GTP-bound RHOA to the PH domain which stimulates the release of PH inhibition and promotes the binding of substrate RHOA to the catalytic center (PubMed:31888991). Binding of phosphorylated RACGAP1 to the N-terminal BRCT domain-containing region also releases autoinhibition (PubMed:25068414)
platelet-activating factor hydrolysis is inhibited by higher amount of sphingomyelin (PubMed:16255717). The hydrolysis of platelet-activating factor and sphingomyelin can be inhibited by the presence of sphingomyelin and platelet-activating factor respectively, the inhibition of platelet-activating factor hydrolysis by sphingomyelin being stronger (PubMed:16255717). PAF hydrolysis is dose-dependently increased by both taurocholate (TC) and taurodeoxycholate (TDC) (PubMed:16255717). Hydrolase activity against PAF is inhibited by EDTA and stimulated by 0.1-0.25 mM Zn2+ (PubMed:16255717)
Is also activated by synthetic agonists, such as AM-8182, AM-6331 and TAK-875 (fasiglifam). AM-8182 is a full agonist, while AM-6331 and TAK-875 (fasiglifam) are partial agonists that potentiate the activity of the endogenous ligands, such as alpha-linolenic acid and gamma-linolenic acid
Ferroxidase activity inhibited by Zn(2+); mutants at Glu-31, Glu-34 and Trp-38 are also inhibited by Zn(2+)
Inhibited by EDTA and EGTA. Inhibited by serum and antihemorrhagic factors Da2-I and Da2-II from D.albiventris. Not inhibited by PMSF or SBT-I
Allosterically activated by ADP and other diphosphonucleosides, and allosterically inhibited by phosphoenolpyruvate. Strongly inhibited by diphosphate, triphosphate and polyphosphate
Allosterically activated by intracellular ATP
Inhibited by (S)-alpha-fluoromethyltryptophan
Carbonic anhydrase (CA) activity is probably under redox control to remain inactive in the cytoplasm. CA activity of full-length protein inhibited by ethoxyzolamide, and for both full-length and CcmM 1-209 construct by reducing agents
Homodimerization via the leucine zipper domains is required for autophosphorylation of multiple sites in the activation loop and subsequent activation. Autophosphorylation at Thr-305 is the key step in activation of MAP3K9/MLK1 and is required for full phosphorylation. Autophosphorylation at Thr-297 and Ser-301 have been shown to be of secondary importance in the activation of MAP3K9/MLK1
The PI3K inhibitor LY294002 affects phosphatidylinositol 3-phosphate (PI3P) levels and triggers a decrease in proline, hydrophobic and aromatic amino acids, and sugars (e.g. raffinose) accumulation in response to salt treatment correlated with lower P5CS1 expression and higher ProDH1 expression, genes involved in proline biosynthesis and catabolism, respectively
Inhibited by Cu(2+) and, to a lesser extent, by Zn(2+) and Ba(2+). Not inhibited by Ca(2+) and Mg(2+)
Inhibited by long-chain acyl-CoA thioesters, oleoyl-CoA (an analog of acetyl-CoA) and tyrosol (an analog of tyramine)
Inhibition by ornithine increases at higher pH
Calcium ions are required for optimal activity, but do not seem to be essential since addition of EDTA causes only a 30% drop in activity
Strongly stimulated by ascorbate
Interaction with MTMR9 increases phosphatase activity
Completely inhibited by the A-type carboxypeptidase inhibitor benzylsuccinic acid. Inhibited by the leech carboxypeptidase inhibitor and the potato carboxydase inhibitor. Inhibited by the chelating agent 1,10-phenanthroline. Partial inhibition by preincubation with the chelating agent EDTA is reversed by addition of Zn(2+). Not inhibited by the cysteine protease inhibitors L-carboxy-trans-2,3-epoxypropyl-leycylamido (4-guanidino) butane, E-64 and cystatin, the aspartic protease inhibitor pepstatin, or the serine protease inhibitors Pefabloc, soybean trypsin-chymotrypsin inhibitor, soybean trypsin inhibitor and aprotinin
Activated by cell derived metabolites including itaconate and fumarate
(Microbial infection) Transcription factor activity on antioxidant target genes is significantly inhibited by SARS coronavirus-2/SARS-COV-2
Activity enhanced by Fe(2+) and Mg(2+) ions. Divalent cations such as Ca(2+), Cr(2+), Co(2+), and Mn(2+) show moderate inhibition of the enzyme, whereas heavy metal ions such as Ag(+), Cu(2+), Pb(2+), Hg(2+), Ni(2+) and Zn(2+) severely inhibit the activity
Inhibited by ferricyanide and EDTA
Inhibited by iodoacetate
Activity depends on Ca(2+) concentration
Activated by the LcdC protein
The reductase activity is completely inhibited by quercetin (a common inhibitor of mammalian oxidoreductases) and p-chloromercuribenzoate, but not by iodoacetimide, N-ethylmaleimide and pyrrazole
The activation of GTP-binding proteins is generally mediated by a guanine exchange factor (GEF), while inactivation through hydrolysis of bound GTP is catalyzed by a GTPase activating protein (GAP) (PubMed:25936802). The GATOR1 complex functions as a GAP and stimulates RRAGA GTPase activity to turn it into its inactive GDP-bound form (PubMed:25936802, PubMed:23723238)
Isoform 1 is inhibited by ionizing radiation in the presence of PPP1CA. Its catalytic activity is inhibited by the inhibitor CCT241950. In the presence of this inhibitor, displays an autoinhibited conformation: Tyr-70 side chain points into the active site, interacts with the activation loop, and blocks the alphaC helix
Is inhibited by EDTA, N-ethylmaleimide, diethylpyrocarbonate, and 1-cyclohexyl-N-(2-morpholinoethyl)carbodiimide in vitro
Alternates between an inactive GDP-bound form and an active GTP-bound form (By similarity). Activated by guanine nucleotide-exchange factors (GEFs) and inactivated by GTPase-activating proteins (GAPs) (By similarity)
Competitively inhibited by L,L-DAP, D,L-DAP, 2-carboxyethylphosphonic acid (CEPA) and 5-mercaptopentanoic acid (MSPA). Succinate is a poor inhibitor
Target RNA acts as an activator for non-specific ssRNA degradation (PubMed:28475872, PubMed:28408723)
Peroxidase activity is inhibited by aminotriazole and azide
Inhibited by mercuric ions, PNP-beta-Glc, PNP-beta-Gal, PNP-alpha-GlcNAc, and PNP-beta-S-GlcNAc
The activity of this protein is inhibited by an intracellular protein inhibitor
TpbB/YfiN repression is released through an YfiB-dependent sequestration of YfiR to the outer membrane (PubMed:22719254). Binds vitamin B6 (VB6) or L-Trp at the periphery of the dimer, and both VB6 and L-Trp are able to reduce biofilm formation induced by YfiB L43P mutant (PubMed:27113583). However, VB6 or L-Trp alone may have little effects in interrupting the YfiB-YfiR interaction (PubMed:27113583). GMP enhances the binding affinity between YfiB and YfiR (PubMed:28870806)
Activated by calcium ions (PubMed:22183084). Activated by magnesium ions (PubMed:22183084). Activated by manganese ions (PubMed:22183084). Inhibited by the serine hydrolase inhibitor phenylmethanesulfonyl fluoride (PMSF) (PubMed:22183084). Inhibited by the chelator ethylenediaminetetraacetic acid (EDTA) (PubMed:22183084). Inhibited by iron ions (PubMed:22183084). Inhibited by aluminum ions (PubMed:22183084). Inhibited by rubidium ions (PubMed:22183084). Inhibited by lithium ions (PubMed:22183084)
Is inhibited by EDTA in vitro
Inhibited by nitric oxide (NO)
Completely inhibited by Zn(2+) and Cu(2+)
Appears to be allosterically activated by the binding of pArg-containing polypeptides to the pArg-binding pocket localized in the C-terminal domain of McsB (By similarity). The McsB kinase is inhibited in nonstressed cells by direct interaction with ClpC; upon heat exposure, the interaction of McsB with ClpC is dramatically decreased, leading to McsB release and activation during heat stress. Its kinase activity is counteracted by the protein-arginine-phosphatase YwlE in vivo. Requires McsA for full kinase activity
Inhibited by natural nucleoside antibiotic tunicamycin, which acts as a structural analog and competitor of UDP-GlcNAc
Magnesium-independent phospholipid phosphatase. Insensitive to N-ethylmaleimide. Inhibited by sphingosine, zinc ions and modestly by propanolol
Inhibited by diphenylene iodinium (DPI)
Partial loss of activity with the combination Mn(2+) and chelating agents. Activity is lost in presence of 0.5 mM dithiothreitol
Weakly inhibited by the wheat xylanase inhibiting protein I (XIP-I)
Completely inhibited by propionic anhydride and by cystamine. Irreversibly inhibited by the mercapto reagents iodoacetate and iodoacetamide. Unaffected by hydroxylamine
Activation requires autophosphorylation of Ser-307. Phosphorylation of Ser-303 also promotes increased activity. Kinase activity is inhibited by WNK4 (By similarity)
Inhibited by N-bromosuccinimide, diethyl pyrocarbonate, and some metal ions such as Co(2+), Fe(2+) and Cu(2+)
Inhibited by serine protease inhibitors PMSF and 4-(2-aminoethyl)benzenesulfonyl fluoride, but not by EDTA
Inhibited by iodoacetamide in a pH-dependent manner
Activated by tyrosine and threonine phosphorylation. Activated in response to hyperosmolarity, hydrogen peroxide, and epidermal growth factor (EGF) (By similarity)
Two specific sites, one in the kinase domain (Thr-305) and the other in the C-terminal regulatory region (Ser-472), need to be phosphorylated for its full activation. IGF-1 leads to the activation of AKT3, which may play a role in regulating cell survival
Activated by autophosphorylation at Tyr-1165, Tyr-1161 and Tyr-1166 on the kinase activation loop; phosphorylation at all three tyrosine residues is required for optimal kinase activity. Inhibited by MSC1609119A-1, BMS-754807, PQIP, benzimidazole pyridinone, isoquinolinedione, bis-azaindole, 3-cyanoquinoline, 2,4-bis-arylamino-1,3-pyrimidine, pyrrolopyrimidine, pyrrole-5-carboxaldehyde, picropodophyllin (PPP), tyrphostin derivatives. While most inhibitors bind to the ATP binding pocket, MSC1609119A-1 functions as allosteric inhibitor and binds close to the DFG motif and the activation loop
Is inhibited by the product PPi
Present in an inactive conformation in the absence of bound ligand. CSF1 or IL34 binding leads to dimerization and activation by autophosphorylation on tyrosine residues (By similarity)
Inhibited by S-adenosyl-L-homocysteine. Negatively regulated by CCAR2
Strongly inactivated by diisopropylfluorophosphate (DFP) and phenylmethanesulfonyl fluoride (PMSF), and to a lesser extent by tosyl-L-lysine chloromethyl ketone (TLCK)
Deacetylase activity is stimulated by hydroxylation on Pro-179 (PubMed:28333455). Inhibited by CuCl(2) and ZnCl(2) (PubMed:15961396). Inhibited by the hydroxamate N-hydroxy-4-(naphthalene-1-yl)benzamide (NHNB) (PubMed:29983281)
Translocation activity is inhibited by the ATPase inhibitor vanadate and the calcium channel blocker verapamil (PubMed:7912658). Translocation activity is enhanced by the addition of the bile salt taurocholate (PubMed:7592705)
Phosphorylation triggers an intra-molecular protein closure, which blocks the FHA binding site and interaction with target enzymes, and switches off the regulatory function of GarA
Is activated by 2-fold in the presence of high concentrations of sodium and potassium ions. Is almost completely inhibited by a high concentration of pyruvate (10 mM)
Inhibited by p-chloromercuribenzoate and iodoacetate by modification of the active site cysteine residue. Inhibited by diethyl pyrocarbonate by modification of histidine residues. Inhibited by pyridoxal 5'-phosphate by modification of an essential lysine residue
Competitively inhibited by glyphosate, (R)-difluoromethyl and (R)-phosphonate analogs of the tetrahedral reaction intermediate
Activated when phosphorylated and inactivated when dephosphorylated
(Microbial infection) Inhibited by baculovirus p35 protein P35
Tricyclazole and pyroquilon inhibit arp2 hydroxynaphtalene reductase activity (PubMed:19703288)
Inhibited by the CDK inhibitor (CKI) PHO81 in response to phosphate starvation
ATPase activity is negatively regulated by YscL/SctL
Is completely inhibited by low concentrations of heavy metal ions, while Ca(2+) and Mg(2+) or chelating agents such as EDTA neither inhibit nor activate the enzyme to any significant extent
Not inhibited by 3,3-difluoroxaloacetate
Activated by GUCA1B when free calcium ions concentration is low, and inhibited by GUCA1B when free calcium ions concentration is high (By similarity). Inhibited by RD3 (By similarity)
Reversibly inhibited by Ni(2+) ions
Inhibited by 3,4-DCI, but no significant effect on enzyme activity by pepstatin A, E-64, 1,10-phenanthroline or EDTA
The metalloproteases inhibitors EDTA and 1.10-phenanthroline both inhibit the activity, whereas bestatin, an inhibitor of most aminopeptidases, does not affect enzyme activity
Binding to NEK9 stimulates its activity by releasing the autoinhibitory function of Tyr-97
Calcium transport is inhibited by Na(+), K(+), Li(+), Mg(2+) or Mn(2+)
Stimulated by rubredoxin at pH 7.6 but not ferredoxin
Inhibited by 2,4-dinitrophenyl-2-fluoro-2-deoxy-beta-D-glucopyranoside
Phosphorylation at Ser-15 or Tyr-16 inactivates the enzyme, while phosphorylation at Thr-160 activates it
Leucine export is inhibited by the proton ionophore carbonyl cyanide m-chlorophenylhydrazone (CCCP)
Alpha-ketoglutarate dehydrogenase and decarboxylase activities are inhibited by unphosphorylated GarA, and allosterically activated by acetyl-CoA, the main substrate of the TCA cycle. Both the phosphoadenosine and acetyl moieties of acetyl-CoA are important for activation because neither CoA nor the synthetic compound S-(2-acetamidoethyl)-ethanethioate (which mimics the terminal acetyl-phosphopantetheine group of acetyl-CoA) has an activation effect
Interaction with host calmodulin (CALM1, CALM2 and/or CALM3) is required to mediate arginine ADP-riboxanation of host caspases
Allosterically regulated; feedback inhibited by cytidine monophosphate-N-acetylneuraminic acid (CMP-Neu5Ac), the end product of neuraminic acid biosynthesis. Activity is dependent on oligomerization. The monomer is inactive, whereas the dimer catalyzes only the phosphorylation of N-acetylmannosamine, and the hexamer is fully active for both enzyme activities. Up-regulated after PKC-dependent phosphorylation (By similarity)
Under conditions of nitrogen excess, the DNA binding activity of GlnR is activated by a transient interaction with feedback-inhibited GlnA (Probable). Under conditions of nitrogen-limited, GlnR is autoinhibited by its C-terminal region (By similarity)
Inhibited by chloroquine, cibacron blue, ferriprotoporphyrin IX (hemin) and S-hexylglutathione
Activated by 3'phosphoglycerate, inhibited by orthophosphate. Allosteric regulation. Inhibited by inorganic phosphate (Pi)
Preincubation with heparin slightly increase the enzymatic activity
Not stimulated by calmodulin (CaM)
When cellular nitrogen levels are high, the C-terminal adenylyl transferase (AT) of GlnE inhibits GlnA by covalent transfer of an adenylyl group from ATP to Tyr-406. Conversely, when nitrogen levels are low, the N-terminal adenylyl removase (AR) of GlnE activates GlnA by removing the adenylyl group by phosphorolysis. The fully adenylated enzyme complex is inactive
Inhibited by strychnine (PubMed:1716350, PubMed:2483325, PubMed:3037383). Inhibited by picrotoxin (PubMed:2483325)
Activation of CDK1, appears to be an upstream event of AURKA activation (By similarity). Phosphatase inhibitor-2 (PPP1R2) and TPX2 act also as activators (By similarity). Inactivated by the G2 checkpoint (By similarity). Inhibited by GADD45A and p53/TP53, and through dephosphorylation by protein phosphatase type 1 (PP1) (By similarity). MLN8054 is also a potent and selective inhibitor (By similarity). Activated during the early phase of cilia disassembly in the presence of PIFO (By similarity). Inhibited by the small molecule inhibitor VX-680 (By similarity)
Inhibited by L-phenylalanine and L-tyrosine
Activity is decreased by HgCl(2) and maltose. Activity is stimulated by Na(2)SeO(4), BaCl(2), MgCl(2), chondroitin 6-sulfate and phenylmethylsulfonyl fluoride
Autophosphorylation activates the kinase activity (By similarity). Interaction with shc-1 may inhibit its activity (PubMed:18832074)
p54 and probably p47 forms are inhibited by the non-covalent interaction with the cleaved propeptide (PubMed:12764150). Inhibited by subtilisin propeptide-like protein SUB1-ProM (By similarity)
Activity is inhibited by the serine modifier phenylmethylsulfonyl fluoride (PMSF)
Inhibited by CTP (PubMed:19876400, PubMed:21731728). CTP strongly binds the enzyme at a site overlapping that of the leading substrate, dephosphocoenzyme A. Binding of CTP probably prevents interaction with dephosphocoenzyme A and oligomeric transformation to the active form, which limits the catalytic efficiency of the enzyme (PubMed:21731728)
Inhibited by high concentrations of paraoxon (PubMed:19225166). Inhibited by tetrahydrolipstatin (THL), a specific lipase inhibitor (PubMed:20103719)
MI transport activity stimulated five-fold under 24 hour hypertonic shock conditions. MI inward currents were gradually inhibited as increasing amounts of phlorizin were added to the superfusion medium. When sodium is replaced by potassium, MI uptake is dramatically reduced and in the presence of L-fucose or D-chiro-inositol (DCI), the specific accumulation of tracer amounts of MI is also reduced
Channel activity is activated via the interaction with PIRT and phosphatidylinositol 4,5-bisphosphate (PIP2). Both PIRT and PIP2 are required to activate channel activity (By similarity). The channel is sensitized by ATP binding. Repeated stimulation with capsaicin gives rise to progressively smaller responses, due to desensitization. This desensitization is triggered by the influx of calcium ions and is inhibited by elevated ATP levels. Ca(2+) and CALM displace ATP from its binding site and trigger a conformation change that leads to a closed, desensitized channel. Intracellular PIP2 inhibits desensitization. The double-knot toxin (DkTx) from the Chinese earth tiger tarantula activates the channel and traps it in an open conformation (By similarity). The Scolopendra mutilans RhTx toxin potentiates the heat activation pathway mediated by this channel by binding to the charge-rich outer pore region (in an activated state) (By similarity)
Up-regulated by calmodulin binding at physiological pH
Activated by Ca(2+)/calmodulin (PubMed:10336483, PubMed:10428833). Binding of calmodulin may relieve intrasteric autoinhibition (By similarity)
Shows little dependence on metals
Up-regulated by TNFAIP6. In a transesterification reaction, TNFAIP6 cleaves the ester bond between the heavy chain and the chondroitin sulfate chain in I-alpha-I complex and potentiates the antiprotease function of I-alpha-I complex through release of free bikunin
Inhibited by the quinone analog 2-heptyl-4-hydroxyquinolone N-oxide (HQNO). Inactivated by iodoacetamide treatment. Inhibited by KCN
GDP-loaded state of HypB enhances HypA-HypB complex formation and nickel transfer
Quinone binding to the enzyme accelerates the reaction with superoxide
Catabolite repressed
Atrazine dechlorination rates are reduced by aminoatrazine but dechlorination is not inhibited by either melanine or CAAT (2-chloro-4,6-diamino-s-triazine)
Phosphorylation results in activation of its activity (By similarity). Glucose 6-phosphate, fructose 6-phosphate, fructose 2,6-bisphosphate, ribulose 5-phosphate, and fructose 1,6-bisphosphate also act as activators (By similarity)
Activated by tyrosine and threonine phosphorylation catalyzed by MAP kinase kinase kinases
Up-regulated by KIN10, by S1-bZIP specific dimers, and also by C/S1 bZIP heterodimers
Inhibited by the metal chelator dipicolinate (PubMed:17128965). Inhibited by N-formimino-L-aspartate and N-guanidino-L-glutaric acid (PubMed:25559274)
ADP inhibits the peptide cleavage activity of LonTk, but the enzyme retains 57% activity in comparison to the condition with the addition of ATP
Has different conformational states with differential Ca2+ affinity. The E1 conformational state (active form) shows high Ca(2+) affinity, while the E2 state exhibits low Ca(2+) affinity. Reversibly inhibited by phospholamban (PLN) at low calcium concentrations. Inhibited by sarcolipin (SLN) and myoregulin (MRLN). The inhibition is blocked by VMP1 (By similarity). Enhanced by DWORF; DWORF increases activity by displacing sarcolipin (SLN), phospholamban (PLN) and myoregulin (MRLN) (By similarity). Stabilizes SERCA2 in its E2 state (By similarity)
Is inhibited in vitro by diethyl pNP-phosphate (E600), but not by EDTA
The activity is enhanced 5-7 times by ammonium and potassium
Maintained as a monomer in an autoinhibited state (PubMed:25326418, PubMed:18836453, PubMed:22412986). Phosphorylation and activation follow the following steps: innate adapter protein TASL recruits IRF5, thereby licensing IRF5 for phosphorylation by IKBKB (PubMed:32433612). Phosphorylated IRF5 dissociates from the adapter proteins, dimerizes, and then enters the nucleus to induce IFNs (PubMed:25326418, PubMed:32433612)
Activated by histamine, imidazole, L-adrenaline, L- and D-histidine, and L- and D-phenylalanine. Inhibited by coumarins, sulfonamide derivatives such as acetazolamide, benzenesulfonamide and derivatives (4-carboxyethylbenzene-sulfonamide, 4-carboxyethylbenzene-sulfonamide ethyl ester, 4-(acetyl-2-aminoethyl)benzene-sulfonamide, 4-aminoethylbenzene-sulfonamide), and 'prong inhibitors' BR15, BR17, BR22 and BR30. Activated by a short exposition to Foscarnet (phosphonoformate trisodium salt), but inhibited by a long one. Esterase activity weakly reduced by cyanamide
Inhibited by tetcyclcis, but not by metyrapone
The full-length protein before cleavage is inactive: intramolecular interactions between N- and C-terminal domains mediate autoinhibition in the absence of activation signal. The intrinsic pyroptosis-inducing activity is carried by the released N-terminal moiety (Gasdermin-E, N-terminal) following cleavage by CASP3 or granzyme B (GZMB). Activated by NLRP1 in the absence of GSDMD expression: NLRP1 cleaves and activates CASP8, promoting downstream activation of CASP3 and subsequent activation of GSDME
Citrate synthase-lysine methyltransferase activity is inhibited by S-adenosylhomocysteine (AdoHcy) and oxaloacetate (OAA)
Completely inhibited by the metal chelator orthophenanthroline
The presence of a 5'-monophosphate on substrate RNA accelerates its cleavage by catalytically activating the enzyme (PubMed:15197283). Binding to the membrane stabilizes protein structure and increases affinity for the substrate
Inhibited by dipyridimole. Insensitive to selective PDE inhibitors including rolipram and milrinone as well as to the non-selective inhibitor, IBMX. Unaffected by cGMP
Activated by chloride. Inhibited by captopril and lisinopril, and to a lesser extent by delaprilat
Activity is maximal in the presence of calcium. However, unlike phospholipases A2 whose catalytic activity is strictly calcium-dependent, this enzyme shows considerable catalytic activity on phosphatidylcholine emulsified in calcium free solution; the catalytic activity of VT-2a assayed in the absence of calcium ions is 18-20% of that assayed in solution containing calcium ions
Exhibits synergistic gating by Ca(2+) and voltage. Inhibited by some non-specific cation channel blockers such as: ruthenium red, 2-aminoethyl diphenylborinate (2APB), gadolinium and cadmium ions
Inhibited by PUGNac (O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino-N-phenylcarbamate)
Inhibited by excess of arginine and by the bisubstrate delta-N-phosphonoacetyl-L-ornithine (PALO)
Binding of GTP stimulates kinase activity
Inhibition of KLK7 is enhanced by heparin
Inhibited by Co(2+), Cu(2+), Ni(2+), Zn(2+), beta-mercaptoethanol, and non-competitively by imidazole
Inhibited by AgNO(3), HgCl(2), p-chloromercuribenzoic acid and NiCl(2)
Binding of human antimicrobial peptide LL-37 decreases the catalytic activity, which leads to the decrease of cell adhesion
Activity on pectate is nearly completely inhibited by ethyleneglycol-bis-(P-aminoethyl ether) N,N'-tetraacetic acid (EGTA), EDTA or nitrilotriacetic acid. Activity is specifically restored by the addition of Ca(2+)
Inhibited by N-ethylammeline, N-hydroxyethylammeline, N-isopropylammeline, ammeline and 2-amino-4hydroxy-1,3,5-s-triazine
The complex formed with CadA represents a possible means of regulating RavA activity in response to acid stress conditions. This interaction results in an increase in RavA ATPase activity
Inhibited by AgNO(3) at a concentration of 0.1 mM. Strongly inhibited by CdCl(2), ZnCl(2) and FeCl(3) and moderately by CoCl(2), CuSO(4) and NiCl(2) at 10 mM concentration. CaCl(2), MgCl(2), MnSO(4) and KI also have a slight inhibitory effect of 20%-25% at 10 mM concentration. Activated to a small extent by MgCl(2) at 0.1 mM concentration but inhibited with increasing concentration. Not affected by carbohydrates such as fucose, galactose and glucose but displays a slight decrease in activity up to 25% with lactose, alpha-mannose and N-acetyl-galactosamine (GalNAc)
Regulated by cyclic AMP receptor 1 through a guanine nucleotide binding protein and protein CRAC. Both positively and negatively regulated by extracellular cAMP; this regulation is part of the mechanism that establishes the oscillatory cAMP waves during aggregation
Inhibited by vanadate and sodium pyrophosphate. Not inhibited by sodium fluoride
Inhibited by 2-mercaptomethyl-3-guanidinoethylthiopropanoic acid (MGTA) and guanidinoethylmercaptosuccinic acid (GEMSA). Inhibited by chelating agents such as EDTA and EGTA (By similarity)
Inhibited by protonophores (e.g. dinitrophenol and carbonyl cyanide m-chlorophenyl-hydrazone (CCCP)) and SH group inhibitors (e.g. N-ethylmaleimide (NEM) and p-chloromercuriphenyl sulphonic acid (PCMPS))
Divalent ions have no significant effect on activity
Channel activity is modulated by zinc ions. The activity of the heterotetramer with grin2b is stimulated by micromolar levels of Zn(2+) (PubMed:19524674). The activity of the heterotetramer with grin2a is inhibited by nanomolar levels of Zn(2+) (Ref.11)
Up-regulated by K(+) and NH(4+), down-regulated by Zn(2+), Cu(2+), Fe(2+) and Fe(3+)
IMPase activity is inhibited by Ca(2+) and Zn(2+). In contrast to mammalian I-1-P phosphatases, is not inhibited by Li(+) up to 100 mM
Inhibited by carbenoxolone and phenyl arsenoxide
L-lactate oxidation is competitively inhibited by glycolate, D-lactate, oxalate and 2-hydroxybutanoate
The full-length protein before cleavage is inactive: intramolecular interactions between N- and C-terminal domains mediate autoinhibition in the absence of activation signal (PubMed:26375003, PubMed:26375259, PubMed:26611636, PubMed:29576317, PubMed:31097341). The intrinsic pyroptosis-inducing activity is carried by the released N-terminal moiety (Gasdermin-D, N-terminal) following cleavage by inflammatory caspases CASP1, CASP4/CASP11 or CASP8 (PubMed:26375003, PubMed:26375259, PubMed:26611636, PubMed:30361383, PubMed:30381458, PubMed:32554464, PubMed:32553275). Cleavage at Asp-88 by CASP3 or CAPS7 inactivates the ability to mediate pyroptosis (By similarity)
Proteolysis activated by calcium and cobalt
Inhibited by KNI derived compounds KNI-10333 and to a lesser extent KNI-10743
Activated by AMP. Probably promotes oligomerization of the enzyme
Is subject to substrate inhibition. Is regulated by L-arginine, which stimulates enzymatic activity at 0.1-1 mM while inhibits activity at higher concentrations, and has pronounced effects on the optima for pH and temperature and on the Km for L-ornithine. Is not inhibited by L-proline
The active site contains a binuclear metal center, with a fully occupied alpha-metal ion site, and partially occupied beta-metal ion site (PubMed:17306828, PubMed:18678932, PubMed:18831553). The presence of substrate promotes the formation of a catalytically competent binuclear center by significantly enhancing the binding affinity of one of the metal ions in the active site (PubMed:18831553)
Activated by threonine and tyrosine phosphorylation by either of two dual specificity kinases, MAP2K4 and MAP2K7. MAP2K4 shows a strong preference for Tyr-185 while MAP2K7 phosphorylates Tyr-183 preferentially. Inhibited by dual specificity phosphatases, such as DUSP1. Inhibited by SERPINB3 (By similarity). Inhibited by IFN-gamma-induced S-nitrosylation
Enzymatically inactive by itself, and become active following phosphorylation by PKA
The gelatinase activity is inhibited by EDTA
Activated by certain divalent metal cations, such as cobalt, manganese, nickel or magnesium. Zinc or iron ions do not affect activity
Inhibited by reserpine, ketanserin and tetrabenazine. Not significantly inhibited by vesamicol
Inhibited by the pseudosugar allosamidin A
Its activity is inhibited in vitro by geranyl pyrophosphate (GPP) and farnesyl pyrophosphate (FPP) that bind competitively at the ATP-binding site on the enzyme
The sterol 14-alpha demethylase activity is inhibited by azole compounds (PubMed:15142553, PubMed:15855543, PubMed:9184358, PubMed:26459890). Activity is inhibited by the novel and long-acting fungicidal azole, PC1244 (PubMed:29439966)
Inhibited by L-phenylalanine but not by L-tyrosine or L-tryptophan
Activated by cytosolic Ca(2+) in the presence of cardiolipin. Activated by phosphoinositides. Inhibited by electrophilic ketone inhibitors
The covalent binding to the substrate causes inactivation of the enzyme, and possibly serves as a signal for the export of the protein (By similarity). Inhibited by fluoride and phosphate
Inhibited by wheat xylanase inhibiting protein I (XIP-I)
Phospholipid scramblase activity is activated upon caspase cleavage to generate the XK-related protein 4, processed form (By similarity). Does not act prior the onset of apoptosis (By similarity)
Homodimerizes upon caspase cleavage (By similarity). Phospholipid scramblase activity is activated following interaction with the processed C-terminus of XRCC4 (protein XRCC4, C-terminus) (PubMed:33725486)
Activated by heparin. Inhibited by its chaperone crotapotin
Inhibited by Ca(2+), Li(+), and Na(+) and activated by K(+)
Completely inhibited by Cu(2+), Hg(2+) and N-bromosuccinimide. Strongly inhibited by Ag(+), Zn(2+) and Pb(2+). Moderately inhibited by Fe(3+), Al(3+), Mn(2+), dithiothreitol and p-chloromercuribenzoic acid. Slightly activated by Mg(2+) and Ca(2+). Unaffected by Na(+), K(+), Ba(2+), EDTA, iodoacetic acid and N-ethylmalaimide
The phosphatase domain is activated by the anti-sigma factor kinase domain
ATPase activity is 15-fold stimulated by single-stranded DNA (ssDNA). ATP-dependent DNA helicase activity requires divalent cations (Mg(2+), Ca(2+) or Mn(2+)) but is not detected in the presence of Zn(2+) (PubMed:12748189). Reduction of the [4Fe-4S] cluster reversibly switches off helicase activity. Remains fully active after exposure to 100-fold excess of hydrogen peroxide, but the [4Fe-4S] cluster can be efficiently modified by nitric oxide (NO), forming the DinG-bound dinitrosyl iron complex with the concomitant inactivation of helicase activity (PubMed:19074432)
Strongly inhibited by 1 mM isoleucine
Activated by GSTU20/FIP1
Ca(2+) ions inhibit the phosphotransfer from MtrB to MtrA
Activated by Ca(2+)/calmodulin. Regulated by a locking mechanism, involving autophosphorylation at Ser-308 and calmodulin binding. In the inactive state, Ser-308 is phosphorylated. Activation involves its dephosphorylation and a release-of-autoinhibition mechanism where binding of calmodulin induces a conformational change that relieves the steric block of the active site by the autoinhibitory domain. Activity is modulated by UNC5B and NTN1. UNC5B activates it by inhibiting the phosphorylation at Ser-308, whereas NTN1 inhibits UNC5B-mediated activation of DAPK1. Endoplasmic-stress activates by causing Ser-308 dephosphorylation
CDP reduction is stimulated by dATP
The uptake of 2-deoxyglucose is inhibited by cytochalasin B. Fructose transport is inhibited by the flavonoids epigallocatechin gallate and apigenin but not quercetin (PubMed:29548810)
Inhibited by the sulfhydryl reagent N-ethylmaleimide, but not by the ionophore carbonyl cyanide m-chlorophenylhydrazone (CCCP)
Positively regulated by CK2
Inhibited by TH588
The RNase activity is stimulated by cOA
Ubiquitin ligase activity of the BCR(KEAP1) complex is inhibited by oxidative stress and electrophile metabolites such as sulforaphane (PubMed:12193649, PubMed:14764894, PubMed:22014577). Electrophile metabolites react with reactive cysteine residues in KEAP1 and trigger non-enzymatic covalent modifications of these cysteine residues, leading to inactivate the ubiquitin ligase activity of the BCR(KEAP1) complex (PubMed:20498371, PubMed:22014577). Selective autophagy also inactivates the BCR(KEAP1) complex via interaction between KEAP1 and SQSTM1/p62, which sequesters the complex in inclusion bodies and promotes its degradation (PubMed:20421418, PubMed:20173742, PubMed:24011591)
Inhibited by glibenclamide, verapamil and vanadate (ABC transporters inhibitors)
Activated by Co(2+) (PubMed:17720817, PubMed:22709581). Inhibited by high concentrations (>1mM) of Zn(2+) (PubMed:22709581)
Activated by phosphorylation at Ser-360, Thr-581 and Thr-700 by MAPK1/ERK2, MAPK3/ERK1 and MAPK14/p38-alpha, and by further autophosphorylation of Ser-212, Ser-376 and Ser-381 by the activated C-terminal kinase domain. The active N-terminal kinase domain finally phosphorylates downstream substrates, as well as Ser-750, Ser-752 and Ser-758 in its own C-terminal region
The full-length protein before cleavage is inactive: intramolecular interactions between N- and C-terminal domains mediate autoinhibition in the absence of activation signal. The intrinsic pyroptosis-inducing activity is carried by the released N-terminal moiety (Gasdermin-C2, N-terminal)
Produced as a single polypeptide precursor and is activated by proteolytic cleavage (PubMed:14769868). The LGOX precursor is an active enzyme, but it exhibits lower catalytic efficiency and lower thermostability compared with the mature hexameric LGOX (PubMed:14769868). The mature form is strongly inhibited by p-chloromercuribenzoate, but not by CuCl(2), EDTA and diethyldithiocarbamate (Ref.2)
Activated by phosphorylation of Thr-239. Once activated, activity is stimulated by binding target proteins (By similarity)
Is stable during exponential growth and degraded in stationary phase by the essential FtsH protease. Degradation is influenced by the alarmone (p)ppGpp, but not by inorganic polyphosphate (polyP), RpoS, RcsB or PpiD
EDTA completely blocks the reaction
Inhibited preferentially by rapamycin over FK506
Inhibited by the translational inhibitors neomycin and alpha-sarcin, which suppress the ATPase activity
Is inhibited by high concentrations of NADH
Inhibited by serpin SRPN2
Acyltransferase activity is regulated by the binding of GTP and Ca(2+): inactivated by GTP, which stabilizes its closed structure, thereby obstructing the accessibility of substrates to the active sites (PubMed:2879844). In contrast, Ca(2+) acts as a cofactor by inducing conformational change to the active open form (PubMed:2879844). In absence of Ca(2+), Mg(2+) may bind Ca(2+)-binding sites, promoting GTP-binding and subsequent inhibition of the acyltransferase activity (By similarity)
Cleavage occurs in the presence of magnesium, but is much more pronounced with manganese
Inhibited by EDTA, but not by PMSF. Pre-incubation with 2 mM DTT completely abolishes activity
DAC activity is stimulated about 20-fold in E.coli by coexpression with CdaR (PubMed:23192352)
Inhibited by EDTA but not by EGTA
The enzymatic reaction requires the aid of a Rab escort protein (also called component A)
Active in presence of diverse metals including Fe(2+), Zn(2+) and Mn(2+) (PubMed:35459748). Binds two metal cations in two adjacent alpha and beta metal-binding pockets (PubMed:35459748). The activity is the highest with Fe(2+) bound to the 2 metal-binding sites (PubMed:35459748). Activity is low with Zn(2+) and Mn(2+) (PubMed:35459748)
Strongly activated in response to phosphatidic acid (PA) and xylanase in a OXI1- and PDK1-dependent manner, and, to a lesser extent, by hydrogen peroxide and flagellin in a OXI1-dependent manner
Allosterically and strongly feedback inhibited by tryptophan. The presence of either 650 mM NaCl or KCl reduces the inhibition by tryptophan
DNA supercoiling is inhibited by the coumarin antibiotic novobiocin (PubMed:8574396). Also inhibited by the fluoroquinolones ciprofloxacin and moxifloxacin (PubMed:12000834)
ATPase activity is inhibited by MgATP with an IC(50) of 1.03 mM and up-regulated by coporphyrin III> hemin > protoporphyrin IX (PubMed:23792964). ATPase activity for hemin is up-regulated by glutathione (PubMed:33007128). The ATPase activity is impaired by increasing copper concentrations (0-300 uM) (PubMed:33007128). The ATPase activity is stimulated in presence of glutathione for increasing copper concentrations (0-300 uM) (PubMed:33007128)
Inhibited by 2-(4-amino-4-carboxybutyl)aziri-dine-2-carboxylate (aziDAP) and iodoacetamide
In the presence of high extracellular ammonium concentrations, transport activity is inhibited by interaction with the regulatory protein GlnK (PubMed:11847102, PubMed:14668330, PubMed:16864585). Ammonium transport through AmtB is required for GlnK sequestration (PubMed:14668330). Formation of the GlnK-AmtB complex is influenced by intracellular pools of the effector molecules ATP, ADP, Mg(2+) and 2-oxoglutarate (PubMed:16864585, PubMed:20639578). The rapid drop in the 2-oxoglutarate pool upon ammonium influx and a simultaneous, but transient, change in the ATP/ADP ratio promotes AmtB-GlnK complex formation (PubMed:20639578). The GlnK-AmtB interaction is also controlled by the level of intracellular glutamine and the uridylylation status of GlnK (PubMed:14668330). Inhibited by imidazole and thallium, which likely act by competitive binding to the periplasmic ammonium binding site (PubMed:18362341). Transport activity is independent of the membrane potential and of ATP hydrolysis (PubMed:15876187)
Inhibited by EDTA, zinc, silver, copper, and activated by magnesium and calcium. A competitive inhibition is observed with NAD at concentrations higher than 5.6 mM, and with trilostane (3,17-dihydroxy-4,5-epoxyandrost-2-ene-2-carbonitrile)
Inhibited by 4-aminopyridine (4-AP) (PubMed:8415758). Inhibited by dendrotoxin (DTX) and charybdotoxin (CTX), but not by tetraethylammonium (TEA) (By similarity). Inhibited by tityustoxin-K alpha (TsTX-Kalpha), a toxin that is highly specific for KCNA2 (By similarity). Inhibited by maurotoxin (By similarity). Inhibited by kappaM conotoxins kappaM-RIIIJ and kappaM-RIIIK (By similarity)
Activated by calcium (By similarity). Upon calcium binding to the EF-hand domains, the C-terminus of the junction domain (J domain) undergoes a conformational change which results in the dissociation of the pseudo-substrate inhibitory motif from the catalytic domain (By similarity). This, in turn, may facilitate the autophosphorylation of the activation loop at Thr-278, which leads to the kinase activation (By similarity)
Has no constitutive proton transporter activity and has to be activated by long-chain fatty acids/LCFAs. Inhibited by purine nucleotides. Both purine nucleotides and LCFAs bind the cytosolic side of the transporter and directly compete to activate or inhibit it. Activated by noradrenaline and reactive oxygen species. Despite lacking canonical translational encoding for selenocysteine, a small pool of the protein has been observed to selectively incorporate selenocysteine at 'Cys-254'. Selenocysteine-modified protein is highly sensitive to redox modification and may constitute a pool of protein highly sensitive to activation by elevated levels of reactive oxygen species (ROS)
Activity is improved in the presence of Mn(2+), Mg(2+) and Ca(2+), and inhibited by Ni(2+), Zn(2+) and Cu(2+)
Phosphorylation at Thr-14 or Tyr-15 inactivates the enzyme, while phosphorylation at Thr-167 activates it
Activity is partially inhibited by the competence and sporulation stimulating factor (CSF), encoded by phrC (PubMed:9238025). Phosphatase activity is abolished in the presence of EDTA (PubMed:11923303). Insensitive to vanadate (PubMed:9843420)
Thiol-based regulation. Inactivation after dimerization under oxidizing conditions
Inhibited by benzylpenicillin, cephaloridine, ampicillin and cetiofur
The reverse reaction is inhibited by Zn(2+) and Cu(2+) (PubMed:11278489). Inhibited by cardiolipin and phosphatidic acid (PubMed:11278489)
Inhibited by 90 uM 3-phosphonooxypyruvate, but not by Ser, Thr, Val, Gly Trp, O-acetyl-L-Ser and Cys
Strongly inhibited by antipain, PMSF and aprotinin. Inhibited by benzamidine by 49%. Little or no inhibition by EDTA, E-64, iodoacetic acid, leupeptin and FUT-175
The enzyme activity is strongly increased by double-stranded DNA (dsDNA), but not by single-stranded DNA or RNA. DNA-binding induces the formation of liquid-like droplets in which CGAS is activated. Liquid-like droplets also create a selective environment that restricts entry of negative regulators, such as TREX1 or BANF1/BAF, allowing sensing of DNA (By similarity). A number of mechanisms exist to restrict its activity toward self-DNA. The nucleotidyltransferase activity is inhibited in the nucleus via its association with nucleosomes: interacts with the acidic patch of histones H2A and H2B, thereby blocking DNA-binding and subsequent activation (By similarity). CGAS is also inactive when associated with mitotic chromatin (By similarity). Chromatin-bound CGAS cannot be activated by exogenous DNA in mitotic cells: phosphorylation of the N-terminal disordered part by AURKB during the G2-M transition blocks CGAS liquid phase separation and activation (By similarity). Activity toward self-DNA is inhibited by BANF1/BAF upon acute loss of nuclear membrane integrity: BANF1/BAF acts by outcompeting CGAS for DNA-binding, thereby preventing CGAS activation (By similarity). DNA-induced activation at micronuclei is also limited by TREX1, which degrades micronuclear DNA upon nuclear envelope rupture, thereby preventing CGAS activation. Acetylation at Lys-375, Lys-385 and Lys-405 inhibits the cyclic GMP-AMP synthase activity. Acetylation by KAT5 increases the cyclic GMP-AMP synthase activity by promoting DNA-binding and subsequent activation (By similarity). Phosphorylation at Ser-294 suppresses the nucleotidyltransferase activity. Phosphorylation at Ser-426 promotes the cyclic GMP-AMP synthase activity (By similarity). Phosphorylation at Ser-202 inhibits its cyclic GMP-AMP synthase activity. Ubiquitination at Lys-375 via 'Lys-27'-linked polyubiquitination enhances the cyclic GMP-AMP synthase activity (By similarity). Monoubiquitination at Lys-338 promotes oligomerization and subsequent activation. Sumoylation at Lys-338, Lys-375 and Lys-385 prevents DNA-binding, oligomerization and nucleotidyltransferase activity. The enzyme activity is impaired by the cleavage by CASP1 (By similarity). In addition to DNA, also activated by collided ribosomes upon translation stress: specifically binds collided ribosomes, promoting its activation and triggering type-I interferon production (By similarity)
Activated by guanosine 5'-3-O-(thio)triphosphate (GTPgammaS) (PubMed:11522784, PubMed:11777934). Inhibited by calcium (PubMed:11777934)
ATPase activity is inhibited by EDTA, N-ethylmaleimide (NEM) and sodium azide
The full-length protein before cleavage is inactive: intramolecular interactions between N- and C-terminal domains mediate autoinhibition in the absence of activation signal (PubMed:25825937, PubMed:26100518, PubMed:26375003). The intrinsic pyroptosis-inducing activity is carried by the released N-terminal moiety (Gasdermin-A3, N-terminal) (PubMed:26100518, PubMed:26375003)
Inhibited by the fungicide flutolanil
Weakly inhibited by phosphate and completely inhibited by iodoacetate
Inhibited by a range of serine protease inhibitors including soybean trypsin inhibitor, benzamidine and serpins. Activated by a range of glycosaminoglycans including chondroitin sulfate, dermatan sulfate, heparan sulfate and heparin
Inhibited by apilimod and YM201636
Inhibited by PhrF, which prevents RapF-ComA interaction (PubMed:15968044, PubMed:16816200, PubMed:22215984, PubMed:23526880). Interaction with PhrF induces a conformational change in RapF, which is propagated to the ComA binding site and causes the dissociation of ComA from RapF (PubMed:22215984, PubMed:23526880)
Insensitive to dehydroascorbate, p-isoascorbate, inorganic phosphate, glutamate, ATP, p-aminohippuric acid or tetraethylammonium
Activated by threonine and tyrosine phosphorylation (By similarity). Activated in response to low temperature (12 degrees Celsius) treatment (PubMed:12177502, PubMed:12615946). Activated by phosphorylation at Thr-14 and Thr-32 by CPK18 (PubMed:25035404)
Activity is potentiated by the SL-1 transporter MmpL8. Inhibited by the lipase inhibitor tetrahydrolipstatin (THL)
Inhibited by emetine, quinidine and verapamil. The IC(50) of emetine is 4.2 uM. Not inhibited by valproic acid. Transport of (R)-carnitine is stimulated by cholesterol in the plasma membrane
Synthesized as a precursor protein (p25), which is cleaved after secretion to generate the mature active C-signal (p17) (PubMed:12923062). The p25 precursor purified from M.xanthus cells does not display C-signal activity (PubMed:12923062)
Inhibited by 4-hydroxybenzoate, but not by pyruvate
Subject to product inhibition by pyrophosphate
Activated by Ca(2+)/calmodulin. Binding of calmodulin may relieve intrasteric autoinhibition
Competitively inhibited by both D- and L-5-(methylthioethyl)hydantoin. Strongly inhibited by Cu(2+), Hg(2+), Pb(2+) and Zn(2+). The activity is twofold lower in the presence of Mn(2+), Co(2+) and Ni(2+)
The SRP-FtsY complex formation results in mutual stimulation of their GTP hydrolysis activity (PubMed:29361248). GTPase activity is stimulated by Mg(2+) or a high concentration of Mn(2+). Increasing Mg(2+) decreases the activity (PubMed:33412199). GDP acts as an inhibitor (PubMed:33412199)
Activated by autocatalytic cleavage
Strongly inhibited by glutathione, and moderately inhibited by PMSF, acetate iodine and glutamic acid. Is also inhibited by Zn(2+) ions, but not by Ca(2+), Mg(2+) and Mn(2+)
Resistant to alkali and organic solvents such as methanol, ethanol and acetone. Resistant to EDTA, which might be explained by the spatial protection of copper ions in the active sites. Inhibited by DMSO. Strongly inhibited by Fe(2+) and DTT
Strongly inhibited in vitro by CyC17, a monocyclic enol phosphate analog to Cyclipostins, which binds covalently to the catalytic Ser-104 residue leading to a total loss of enzyme activity (PubMed:30292819). Methyl arachidonyl fluorophosphonate (MAFP) inhibits esterase activity but it only reduces by approximately 50% thioesterase activity with palmitoyl-CoA as substrate (PubMed:31388991). Thioesterase activity is inhibited by tetrahydrolipstatin (THL) (PubMed:31388991)
Inhibited by N-methylmaleimide (NEM), but not by E64, benzamidine, aprotinin, leupeptin, pefabloc, pepstatin A, EGTA, EDTA and 1,10-phenanthroline
Inhibited by TIMP2
Inhibited by 3-(4-Aroyl-1-methyl-1H-pyrrol-2-yl)-N-hydroxy-2-propenamides. 3-(1-methyl-4-phenylacetyl-1H-pyrrol-2-yl)-N-hydroxy-2-propenamide 1b and 3-[1-methyl-4-(3-phenyl-2-propenoyl)-1H-pyrrol-2-yl]-N-hydroxy-2-propenamide 1c are very potent inhibitors
The activity of this enzyme is not controlled by adenylation
Strongly inhibited by protease inhibitors diisopropyl fluorophosphate, phenylmethanesulfonyl fluoride and SBTI
ATP-pyrophosphate exchange is inhibited in vitro by nonhydrolyzable acylsulfamate analogs that mimic the AsbC-bound intermediate 3,4-dihydroxybenzoyl-AMP
Inhibited by imidazole
Activated by autocatalytic cleavage (By similarity). Cleavage by CTRC inhibits autoactivation (By similarity)
Partially inhibited by divalent metal cations such as Co(2+), Cu(2+) and Ni(2+)
Activity is stimulated by Fe(2+) in autotrophically grown cells
Cannot be activated without removal of the activation peptide
Activated by phosphorylation of Thr-208 by AURKA; phosphorylation by AURKA is enhanced by BORA. Once activated, activity is stimulated by binding target proteins. Binding of target proteins has no effect on the non-activated kinase. Several inhibitors targeting PLKs are currently in development and are under investigation in a growing number of clinical trials, such as BI 2536, an ATP-competitive PLK1 inhibitor or BI 6727, a dihydropteridinone that specifically inhibits the catalytic activity of PLK1 (By similarity)
Inhibited by oxalate
Present in an inactive conformation in the absence of bound ligand. Binding of PDGFA and/or PDGFB leads to dimerization and activation by autophosphorylation on tyrosine residues (By similarity)
During catalysis, accumulation of oxidized inactive cofactor hydroxocobalamin (OH2Cbl) leads to loss of MMUT activity (PubMed:21138732, PubMed:28943303). Interaction with MMAA decreases the rate of OH2Cbl formation and promotes the replacement of OH2Cbl by the active cofactor adenosylcobalamin (AdoCbl), thereby restoring MMUT activity (PubMed:21138732, PubMed:28943303). Inhibited by itaconyl-CoA, a metabolite that inactivates the coenzyme B12 cofactor (PubMed:29056341). Inhibited at high concentration of substrate (PubMed:28943303)
Binding to DNA is inhibited by nickel and, to some extent, cobalt ions
Converted into plasmin by plasminogen activators, both plasminogen and its activator being bound to fibrin. Activated with catalytic amounts of streptokinase (By similarity)
The protein is a cosubstrate rather than a true enzyme and is left in an inactive state after a single turnover (PubMed:32967910, PubMed:36122239). Inactive under anaerobic conditions (PubMed:32967910)
Specifically inhibited by the intercalating agent amsacrine
GTPase activity is inhibited by GDP but not by UTP, CTP, ATP, GMP or cGMP
Inhibited by vanadate and tungstate
Strongly activated by glucose-6-phosphate, ribose-5-phosphate and fructose-6-phosphate. Weak activator AMP and weak inhibitor fructose-1,6-bisphosphate can act as strong inhibitors in the presence of strong activators
Activated by GAS6-binding and subsequent autophosphorylation
Activity toward p-nitrophenyl acetate inhibited by N-ethylmaleimide, 10-(fluoroethoxyphosphinyl)-N-(biotinamidopentyl)decanamide (FP-biotin), iodoacetamide, CuCl(2) and ZnSO(4), but not by phenylmethylsulfonyl fluoride, EDTA, Mg(2+), Mn(2+), Ca(2+) or paraoxon, an organo-phosphate inhibitor of serine hydrolases
Low intrinsic peptidase activity is stimulated by ATP-binding subunits ClpC, ClpE and ClpX. Activity is disregulated by acyldepsipeptides (ADEP) antibiotics, which negate the need for ATP-binding subunits for activation and which makes it into an unregulated protease. Each ClpP subunit binds 1 ADEP molecule, which prevents binding of ClpX. ADEP binding causes conformational shifts that open the gated pore of the ring (PubMed:20305655). Protease activity is inhibited by diisopropylfluoro-phosphate (PubMed:22080375). Protease activity is inhibited by bortezomib, an oncology drug originally designed to work on the human proteasome (PubMed:31155236)
Activated by the non-canonical Wnt signaling pathway, in which WNT5A leads to activation of MAP3K7/TAK1 and HIPK2, which subsequently phosphorylates and activates this protein. Activated by dimerization and subsequent intermolecular autophosphorylation on Thr-305. Other cytokines such as IL6 may also activate this regulatory circuit (By similarity)
Subject to complex allosteric regulation. The enzyme can assume an active R-state, or an inactive T-state. Intermediate conformations may exist. AMP acts as allosteric inhibitor. Fructose 2,6-bisphosphate acts as competitive inhibitor. Strongly inhibited by Ca(2+)
KL001 (N-[3-(9H-carbazol-9-yl)-2-hydroxypropyl]-N-(2-furanylmethyl)-methanesulfonamide) binds to CRY1 and stabilizes it by inhibiting FBXL3- and ubiquitin-dependent degradation of CRY1 resulting in lengthening of the circadian periods
GAP activity stimulated by phosphatidylinositol 3,4,5-trisphosphate (PIP3) and, to a lesser extent, by phosphatidylinositol 4,5-bisphosphate (PIP2). Phosphatidic acid potentiates PIP2 stimulation
Uptake of D-serine is inhibited by carbonyl cyanide m-chlorophenylhydrazone (CCCP), and at high concentrations of D-threonine, stimulated by D-cycloserine and not affected by D-alanine or glycine
Activated by linoleic acid, linolenic acid, oleic acid, and arachidonic acid (AA)
Each protein molecule can bind up to four molecules of AMP, which act as an allosteric activator to the enzyme. The enzyme is inhibited by alpha-keto acids and other catabolites
In vitro, inhibited by acetylene
Calcium is required for the activity of the heterotrimer
Does not bind DNA in the presence of high glucose or glycerol
Exists in an autoinhibited state in the absence of substrate protein, due to interactions of the leucine-rich repeats with NEL domain (PubMed:20831869, PubMed:31216343, PubMed:33303953). Is activated upon binding to a substrate protein (PubMed:20831869, PubMed:31216343, PubMed:33303953)
The full-length protein before cleavage is inactive: intramolecular interactions between N- and C-terminal domains mediate autoinhibition in the absence of activation signal (PubMed:26375003, PubMed:28928145, PubMed:29576317, PubMed:32109412). The intrinsic pyroptosis-inducing activity is carried by the released N-terminal moiety (Gasdermin-D, N-terminal) following cleavage by caspases CASP1, CASP4, CASP5 or CASP8 (PubMed:26375003, PubMed:26375259, PubMed:27418190, PubMed:29898893, PubMed:32109412). Cleavage at Asp-87 by CASP3 or CAPS7 inactivates the ability to mediate pyroptosis (PubMed:28392147)
Strongly inhibited by swainsonine. Also inhibited to a lesser extent by deoxymannojirimycin (DMM)
Is potently inhibited by immucillin A and immucillin ACAP, which are transition state inhibitors
Not strictly dependent on divalent cations, but the presence of Mn(2+), Ca(2+), Mg(2+) or Co(2+) stimulates activity
Is not inhibited by methylcellulose
Inhibited by the cysteine modifiers iodoacetamide, N-ethylmaleimide and 5,5'-dithiobis(2-nitrobenzoic acid)
Helicase activity is inhibited by Hjc (PubMed:18296528) and by PCNA123 and PCNA323 (PubMed:18782564)
The acyl-AMP ligase activity is inhibited by the alkylphosphate ester of AMP, adenosine 50-dodecylphosphate (AMPC12) (PubMed:23364516, PubMed:26900152). Also inhibited by eicosyl-AMP (AMPC20) (PubMed:26900152)
Inhibited by oxaloacetate, a substrate analog
Activated by phosphorylation on Thr-212 by STK11 in complex with STE20-related adapter-alpha (STRAD alpha) pseudo kinase and CAB39
Inhibited by (S)-6-hydroxynicotine (PubMed:5849820, PubMed:4965794, PubMed:4628374). Inhibited by high concentrations of phenanthroline (PubMed:4628374)
Inhibited by rolipram, cilomilast, Ro 20-1724, roflumilast and denbufylline
Inhibited by rolipram
Inhibited by rolipram and cilomilast
Activated by Ca(2+)-bound calmodulin following an increase in intracellular Ca(2+) (By similarity). At low Ca(2+) concentrations, the catalytic subunit (also known as calcineurin A) is inactive and is bound to the regulatory subunit (also known as calcineurin B) in which only two high-affinity binding sites are occupied by Ca(2+) (PubMed:12221132). In response to elevated calcium levels, the occupancy of the low-affinity sites on calcineurin B by Ca(2+) causes a conformational change of the C-terminal regulatory domain of calcineurin A, resulting in the exposure of the calmodulin-binding domain and in the partial activation of calcineurin A (PubMed:12221132). The subsequent binding of Ca(2+)-bound calmodulin leads to the displacement of the autoinhibitory domain from the active site and possibly of the autoinhibitory segment from the substrate binding site which fully activates calcineurin A (By similarity). Inhibited by immunosuppressant cyclosporin A (CsA) (PubMed:12221132)
Completely inhibited by EDTA. Activated by 0.5 mM MgCl(2), slightly activated by 0.5 mM BaCl(2) and 0.5 mM MnCl(2). Partially inhibited by 0.5 mM CoCl(2), 0.5 mM NiCl(2) and 0.5 mM ZnCl(2). Activity is maximal in the presence of 0.5 mM CaCl(2), and decreases gradually at higher concentrations
Inhibited by carbonyl cyanide m-chlorophenylhydrazone (CCCP) and by the human glucose transport inhibitors cytochalasin B, phloretin, and forskolin
Lipoamide reduction and the NADH -> NAD reaction are both completely inhibited by copper and cadmium ions
Although it can bind simultaneously with SLBP to the 3'-end of histone mRNA, the presence of SLBP prevents the exonuclease activity
Binds cyclosporin A (CsA). Is displaced by CsA from the mPTP leading to a lower open probability of the mPTP
Inhibited by ddTTP
Hexokinase is an allosteric enzyme inhibited by its product D-glucose 6-phosphate
Activity is tightly controlled by YfiR, a small periplasmic protein, and the OmpA/Pal-like outer-membrane lipoprotein YfiB (PubMed:20300602, PubMed:22719254). Diguanylate cyclase activity is inhibited by the specific interaction of YfiR with the TpbB periplasmic domain and is activated by YfiB, which releases the YfiR-mediated repression through sequestration of YfiR to the outer membrane (PubMed:20300602, PubMed:22719254). Release of repression leads to a conformational shift in TpbB/YfiN that propagates through the PAS and transmembrane domains to switch the cytoplasmic HAMP domain from an inactive to an active conformation and activate the C-terminal catalytic GGDEF domain (PubMed:22719254, PubMed:24278422). Thus, TpbB/YfiN appears to function by switching between discrete inactive and active functional states depending on the presence or absence of bound YfiR (PubMed:22719254). Activity is also controlled by dephosphorylation of the periplasmic domain by the tyrosine phosphatase TpbA (By similarity). These two mechanisms of regulation could in principle work in parallel or as part of the same regulatory pathway (PubMed:20300602). Does not undergo product feedback inhibition (PubMed:24278422)
Allosteric enzyme. Activity is modulated by K(+), divalent cations, UTP, and tetrahydrobiopterin. Tetrahydrobiopterin is an inhibitor of this enzyme
Binding of biotin and ATP significantly increases the thermal stability of BirA and leads to the formation of a high affinity holoenzyme complex
Activated by VAC14 and VAC7. VAC14 acts as a specific osmotic response regulator
Inhibited by metal chelators ciclopirox olamine and mimosine, both of which also significantly inhibit growth. Kojic acid has no effect on activity
Down-regulated by nonsteroidal anti-inflammatory drugs diclofenac, indomethacin and niflumic acid
The side chain of Glu-234 determines which of the two opposing activities (AMPylase or de-AMPylase) will take place. In response to endoplasmic reticulum stress, mediates de-AMPylase activity (By similarity). Adenylyltransferase activity is inhibited by the inhibitory helix present at the N-terminus: Glu-234 binds ATP and competes with ATP-binding at Arg-374, thereby preventing adenylyltransferase activity (By similarity). In unstressed cells, disengagement of Glu-234 promotes adenylyltransferase activity (By similarity). Activation dissociates ATP-binding from Glu-234, allowing ordered binding of the entire ATP moiety with the alpha-phosphate in an orientation that is productive for accepting an incoming target hydroxyl side chain (By similarity)
Kinase activity is inhibited by C24:1-ceramide during hypoxia (e.g. submergences)
Not inhibited by O-phenanthroline or EDTA
Binding of FadR to DNA is specifically inhibited by long chain acyl-CoA compounds, but not by long chain fatty acids (PubMed:1569108). Long chain acyl-CoA binds directly to the protein preventing it from binding DNA, which derepresses genes for beta-oxidation and prevents activation of genes for unsaturated fatty acid biosynthesis (PubMed:7836365, PubMed:19854834)
Repressed by the active-site-directed cysteine protease inhibitor E64 (L-trans-epoxysuccinyl-leucylamide-(4-guanido)-butane) produced by Aspergillus japonicus (PubMed:1860874). Inhibited by the inhibitor of cysteine proteases from Trypanosoma brucei (TbICP, rhodesain) and Colocasia esculenta cv. Kaohsiung no. 1 (CeCPI, tarocystatin) (PubMed:16754967, PubMed:21416241). Repressed by leupeptin, a peptidic cysteine, serine and threonine protease inhibitor (PubMed:8416808)
Phosphorylated by MAP2K1/MEK1 and MAP2K2/MEK2 on Thr-185 and Tyr-187 in response to external stimuli like insulin or NGF. Both phosphorylations are required for activity. This phosphorylation causes dramatic conformational changes, which enable full activation and interaction of MAPK1/ERK2 with its substrates. Phosphorylation on Ser-29 by SGK1 results in its activation by enhancing its interaction with MAP2K1/MEK1 and MAP2K2/MEK2. Dephosphorylated and inactivated by DUSP1, DUSP3, DUSP6 and DUSP9. Inactivated by pyrimidylpyrrole inhibitors
Unlike most bacteria, is not activated by GTP. UTP acts as a competitive inhibitor against both substrates. High concentration of UMP abolishes the inhibition of UTP at low ATP concentrations, indicating that UTP binds to the acceptor site (UMP site)
Inhibited by phosphatidic acid
The kinase domain is activated by trans-autophosphorylation following homodimerization (PubMed:12637535, PubMed:9637683). Kinase activity is required for activation of the endoribonuclease domain (PubMed:12637535, PubMed:9637683). Endoribonuclease activity is specifically inhibited by hydroxy-aryl-aldehydes (HAA) (By similarity)
Catabolite repression by gluconate
Hemagglutinating activity is most inhibited by methyl alpha-mannopyranoside. This activity is inhibited to a less extent (about a third of the inhibition of that of methyl alpha-mannopyranoside) by methyl alpha-glucoside, other alpha-glucosides, such as maltose, isomaltose, panose or palatinose, and alpha-glucosides modified at the second position, such as methyl 2-deoxy-alpha-arabinoglucopyranoside or methyl 2-acetamido-2-deoxy alpha-glucopyranoside. Mildly inhibited by free monosaccharides, with glucose presenting at least 20-fold less inhibitory effect on hemagglutinating activity than mannose. Glycoproteins are somewhat inhibitory, the best being asialothyroglobulin and ovomucoid. Not inhibited by isomaltitol, sucrose or trehalose
Activated by TLR ligands such as LPS, bacterial DNA and peptidoglycan
The uptake of taurocholate is inhibited by taurolithocholate sulfate with an IC(50) of 9 uM (PubMed:16332456). Pravastatin competitively inhibits the transport of taurocholic acid (PubMed:18985798, PubMed:15901796). Cyclosporin A, glibenclamide, rifampicin and troglitazonestrongly competitively inhibit the transport activity of taurocholate (PubMed:18985798, PubMed:32203132). The canalicular transport activity of taurocholate is strongly dependent on canalicular membrane cholesterol content (PubMed:19228692). The uptake of taurocholate is increased by short- and medium-chain fatty acids (PubMed:20398791). Cholesterol increases transport capacity of taurocholate without affecting the affinity for the substrate (PubMed:24711118)
Is inhibited by Cu(2+)
The full-length protein before cleavage is inactive: intramolecular interactions between N- and C-terminal domains mediate autoinhibition in the absence of activation signal. The intrinsic pyroptosis-inducing activity is carried by the released N-terminal moiety (Gasdermin-C3, N-terminal)
The 3',5'-cyclic-AMP phosphodiesterase activity is stimulated by 3',5'-cyclic GMP (By similarity). Specifically inhibited by Bay 60-7550. When repressed, protected from ionomycin- but not staurosporin-induced cell death
May be regulated by cyclin-dependent kinase A
Inhibited by 6,7-Dichloro-N-cyclopentyl-4-(pyridin-4-yl)phthalazin-1-amine (A-196)
Strongly inhibited by erythrose 4-phosphate
Inhibited by aureobasidin A (AbA)
Exhibits positive cooperativity. It may be the result of acetyl-CoA binding to two distinct sites, or the result of subunit interactions
Activated by PDK1
Inhibited by 3,4-epoxy-3-methylbutyl diphosphate (EIPP)
Inhibited by quinolone antibiotic ciprofloxacin and coumarin antibiotic novobiocin, but at much higher concentrations than is usual for DNA gyrase/topoisomerase (PubMed:16313624)
Inhibited by phloretin and para-chloromercuribenzene sulfonate
Inhibited by 1,10-phenanthroline (PubMed:8218204). Phosphorylation of Ser-239 by HipA inhibits aminoacylation of tRNA(Glu) (PubMed:24095282, PubMed:24343429)
Competitively inhibited by L-norvaline (NVA)
The cysteine desulfurase activity is stimulated over 40-fold upon complex formation with SUFE1 (PubMed:16437155, PubMed:16455656)
Once phosphorylated no longer has kinase activity
Inhibited by oxygen. Activated by cyanide except in the prolonged presence of excess cyanide, where the enzyme is inactivated
Completely inhibited by HgCl(2), CuCl, CuCl(2) and AgNO(3). Partially inhibited by ZnCl(2) and SnCl(2). Almost completely inhibited by the reducing reagent DTT. Partially inhibited by phenylhydrazine. Moderately inhibited by phenanthroline and 8-hydroxyquinoline. Completely inhibited by the thiol-specific inhibitors N-ethylmaleimide and p-chloromercuribenzoate. Not inhibited by the carbonyl-specific inhibitors aminoguanidine and semicarbazide, the chelating agents alpha,alpha'-dipyridyl, KCN, diethyldithiocarbamate and EDTA, or the oxidizing reagents and serine-modifying reagents such as H(2)O(2), ammonium persulfate, phenylmethanesulfonyl fluoride and diisopropyl fluorophosphates
Activated by threonine and tyrosine phosphorylation (PubMed:11875070, PubMed:16336213, PubMed:19166846). Inhibited by dual specificity phosphatases, such as DUSP1 (By similarity). Phosphorylation and activation in response to DNA damaging agents, serum stimulation (PubMed:11875070, PubMed:16336213, PubMed:19166846). Constitutively activated when phosphorylated on Tyr-177. Activity depends on the relative rates of MAPK15 autophosphorylation and dephosphorylation by PTPN1 (PubMed:16336213)
Substrate inhibition is observed at high concentrations of oxaloacetate
The xyloglucanase activity is inhibited by the binding of the host apoplastic glucanase inhibitor GIP2
ECF sigma-E is held in an inactive form by its cognate anti-sigma factor (RseA) until released by regulated intramembrane proteolysis (RIP). RIP occurs when an extracytoplasmic signal (periplasmic, acid or heat stress) triggers a concerted proteolytic cascade to transmit information and elicit cellular responses. In S.typhimurium there are 2 cascades, the heat shock response which depends on DegS and RseP, and acid response which depends only on RseP. The anti-sigma factor RseA is an inner membrane protein, binding sigma-E in the cytoplasm and RseB in the periplasm. RseA is first cut extracytoplasmically (site-1 protease, S1P, by DegS), then within the membrane itself (site-2 protease, S2P, by RseP), while cytoplasmic proteases (predominantly ClpX-ClpP) finish degrading the regulatory protein, liberating sigma-E. Degradation of RseA requires 2 signals to activate DegS; an outer membrane protein (OMP) signal activates DegS, while an LPS signal causes release of RseB from RseA, freeing RseA to be cleaved. OMP stress can be abrogated by overexpression of the sRNA rybB
Inhibited under hypotonic conditions
Inhibited by warfarin (coumadin) (By similarity). Warfarin locks VKORC1 in both redox states into the closed conformation (By similarity)
The disulfide bridge formed between Cys-34 in the propeptide and the active site residue Cys-93 may prevent activation of the zymogen through formation of a reversible covalent bond with the active site residue
Inhibited by propranolol (PubMed:18930839). Not inhibited by N-ethylmaleimide or bromoenolactome (PubMed:18930839)
Threonine dehydratase 2 biosynthetic, chloroplastic: Strongly inhibited by 1 mM isoleucine (PubMed:21436043). Processed threonine dehydratase 2: Not inhibited by isoleucine (PubMed:21436043, PubMed:17416643)
Competitively inhibited by oxalate
Prolactin stimulates its activity
Activated by ATP (By similarity). ATP binding leads to a conformational change that promotes FAD cofactor binding and enzyme activity (By similarity). ATP binding likely occurs during acox-1.4 folding and/or dimer formation (By similarity)
Subject to autoinhibition, mediated by intramolecular interactions between the SH2 domain and the C-terminal phosphotyrosine. Phosphorylation at Tyr-397 is required for optimal activity. Phosphorylated by CSK at Tyr-508; phosphorylation at Tyr-508 inhibits kinase activity. Kinase activity is modulated by dephosphorylation by PTPRC/CD45
Activated by phosphorylation on Thr-181
Inhibited by metalloproteinase inhibitor 3 (TIMP-3), but not by TIMP-1, TIMP-2 and TIMP-4
Chloride channel activity is allosterically activated by lumenal H(+) and Cl(-) leading to synaptic vesicles acidification. The L-glutamate transport activity is allosterically activated by lumenal H(+) and Cl(-). The allosteric requirement for H(+) efficiently prevents non-vesicular efflux across the plasma membrane. The L-glutamate uniporter activity exhibits a biphasic dependence on chloride concentration
Redox-regulated. Inhibited under oxydizing conditions. Inhibited by hydrogen peroxide H(2)O(2)
Rab activation is generally mediated by a guanine exchange factor (GEF), while inactivation through hydrolysis of bound GTP is catalyzed by a GTPase activating protein (GAP). That Rab is activated by the DENND4C guanine exchange factor (GEF) (By similarity)
Hydrolysis of liposomal sphingomyelin is stimulated by incorporation of diacylglycerol (DAG), ceramide and free fatty acids into the liposomal membranes. Phosphatidylcholine hydrolysis is inhibited by incorporation of cholesterol, ceramide, DAG, monoacylglycerol and fatty acids
Not inhibited by lithium (PubMed:11243884). Partial allosteric regulation on ions sodium binding (By similarity)
Inhibited by nSMase inhibitor GW4869. Binding of anionic phospholipids (APLs) such as phosphatidylserine (PS) and phosphatidic acid (PA) increases enzymatic activity (PubMed:21550973)
Only has nuclease activity when bound to both gRNAs (crRNA plus tracrRNA), which results in conformational changes in the protein and formation of a central channel which binds target DNA (PubMed:24505130). Also requires interaction with PAM to trigger catalytic activity (PubMed:24476820). Nuclease activity is inhibited by EDTA (PubMed:26841432)
Activity is inhibited by 5-aminovalerate
Inhibited by Cu(2+), SDS and DTT. Activity is slightly increased by Fe(2+), Mn(2+), triton X-100 and EDTA
Competitively inhibited by N,N-dimethyl-2-amino-1-ethyl diphosphate (NIPP) and isopentyl diphosphate
Inhibited by curcumin, 3-(2-naphthyloxy)-4-oxo-2-(trifluoromethyl)-4H-chromen-7-yl 3-chlorobenzoate, butyl 2-{[3-(2-naphthyloxy)-4-oxo-2-(trifluoromethyl)-4H-chromen-7-yl]oxy}propanoate, 2-({2-[(2-{[2-(2,3-dimethylanilino)-2-oxoethyl]sulfanyl}-1,3-benzothiazol-6-yl)amino]-2-oxoethyl}sulfanyl)-N-(2-naphthyl)acetamide, and maesaquinone diacetate
Glutamate binding triggers a rapidly reversible current, while the anti-helmintic drug ivermectin triggers a permanently open channel configuration (PubMed:8702744, PubMed:11095718). Inhibited by picrotoxin (PubMed:31535971)
Inactivated by binding to URI1. The phosphatase activity of the PPP1R15A-PP1 complex toward EIF2S1 is specifically inhibited by Salubrinal, a drug that protects cells from endoplasmic reticulum stress
Inhibited by amphetamine, bupropion, cocaine and ritalin
Activated by insulin (By similarity). Only slightly inhibited by wortmannin and LY294002. Activated by clathrin
Inhibited by the antibiotics imipenem, penicillin G, and ceftriaxone
Inhibited in response to H(2)O(2)
Allosterically activated by the C-terminus of exposed OMP peptides (consensus Tyr-X-Phe-COOH); cleavage only occurs in the presence of peptides. Inhibited when RseB is bound to RseA
Maintained in an inactive, closed conformation by an interaction between the kinase domain and the negative autoregulatory C-terminal coiled-coil region. Agonist binding to the phorbol ester binding site disrupts this, releasing the kinase domain to allow N-terminus-mediated dimerization and kinase activation by transautophosphorylation. Inhibited by chelerythrine chloride (By similarity)
Inhibited by AMP and slightly innibited by hydrogen peroxyde
Activity increases in response to increased acetyl-CoA and NADH levels and upon binding to the pyruvate dehydrogenase subunit DLAT. Inhibited by ADP and pyruvate; these compounds interfere with DLAT binding and thereby inhibit kinase activity. Inhibited by dichloroacetate. Inhibited by AZD7545; this compound interferes with DLAT binding and thereby inhibits kinase activity. Reactive oxygen species cause the formation of disulfide bonds, and thereby inhibit the enzyme
Stimulated by sulfite, ethanol, glycerol, magnesium and zinc ions
Allosterically activated by calcium. It may represent the only case of a monomeric, allosteric enzyme
Is not inhibited by leucine
Activated by Ca(2+)/calmodulin. Binding of calmodulin results in conformational change that relieves intrasteric autoinhibition and allows autophosphorylation of Thr-287 which turns the kinase in a constitutively active form and confers to the kinase a Ca(2+)-independent activity (By similarity)
Activation is generally mediated by a guanine exchange factor (GEF), while inactivation through hydrolysis of bound GTP is catalyzed by a GTPase activating protein (GAP). Activated by ASAP3. Inactivated by ACAP1 and ACAP2. Activated by NGF via NTRK1 (By similarity)
Inhibited by cysteine and TLCK. Inhibited by high concentration of thiourea and thio-L-citrulline
Present in an inactive conformation in the absence of bound ligand. Binding of vegfc or vegfd leads to dimerization and activation by autophosphorylation on tyrosine residues (By similarity)
Inhibition by cyclosporin A with a Ki of 21 mu-mol
Activity is strongly reduced by pyoluteorin, an antifungal compound produced by the bacterium
Activated by Mn(2+). Inhibited by bis-carboxymethyl-trithiocarbonate, ethylxanthogenacetic acid and 2,5-disulfoaniline. Not affected by Li(+) within 0.05-40 mM concentration range
Partially inhibited by 0.1 mM pyridoxal phosphate
Mainly exists in a closed and catalytically competent conformation but a closed-to-open switch allows substrate entry into the catalytic chamber (PubMed:24931469). Substrate binding induces closure and dimerization (PubMed:24931469). A disulfide bond may lock the enzyme in a closed conformation preventing substrate entry into the catalytic chamber, participating in redox regulation of the enzyme (Probable). Inhibited by metal-chelating agents (PubMed:10360838). Inhibited by nickel and zinc excess, and slightly activated by manganese (PubMed:19196155)
Completely inhibited by glutamine and partially inhibited by glycine, alanine and AMP (PubMed:4149044, PubMed:24158439). Also inhibited by L-methionine-SR-sulphoximine (Met-Sox) (PubMed:8093698, PubMed:24158439)
Target RNA acts as an activator for non-specific ssRNA cleavage; the target RNA and complementary crRNA must both be at least 20 nucleotides long to activate the HEPN-like catalytic pocket for RNase activity (PubMed:28757251)
Inhibited by Ag(2)+, Hg(2+), Zn(2+), p-chloromercuribenzoate (pCMB) and 1-deoxygalactonojirimycin
Slightly inhibited by Pb(2+), Hg(+) and Cu(2+)
ATPase activity is enhanced upon binding to G-patch domain-containing proteins. G-patch domain-containing proteins act like a brace that tethers mobile sections of DHX15 together, stabilizing a functional conformation with high RNA affinity, thereby promoting the ATPase activity
Stable for 2 hours at 60 degrees Celsius but activity is decreased to less than 50 percent within 15 minutes at 70 degrees Celsius
By K-252a
DNA cleavage is inhibited by EDTA
Heterotrimeric PCNA stimulates the nuclease activity without altering cleavage specificity
The protein undergoes a dramatic conformational switch from closed to open states upon substrate-binding, which enables specific substrate recognition for the 1''-O-linkage. The glutamate flap (Glu-27) blocks substrate entrance to Mg(2+) in the unliganded closed state. In presence of substrate, Glu-27 is ejected from the active site: this closed-to-open transition significantly widens the substrate-binding channel and precisely positions the scissile 1''-O-linkage for cleavage while securing tightly 2'- and 3'-hydroxyls of ADP-ribose
DNase activity is activated upon ligand binding. Inhibited by EDTA
Activated by magnesium ions and inhibited by manganese ions. Inhibited by dipyridamole, moderately sensitive to IBMX and inhibited by vinpocetine (By similarity)
Toxin internalization is inhibited by azide or dinitrophenol or at 4 degrees Celsius (PubMed:6694738). Dynamin (DNM) inhibitors abolish toxin uptake (PubMed:21832053)
ATPase activity is inhibited by orthovanadate and activated by the cancer drugs doxorubicin and vinblastine
Activated by calcium/calmodulin and G protein
Activated by homooligomerization induced by direct binding to cytosolic LPS, in a TLR4-independent manner (PubMed:25119034, PubMed:29520027). In addition to LPS, CASP4/CASP11 may also be activated by oxidized phospholipid 1-palmitoyl-2-arachidonoyl- sn-glycero-3-phosphorylcholine, an oxidized phospholipid (oxPAPC), in dendritic cells, promoting adaptive immunity (By similarity). The role of oxPAPC is however unclear and another report suggests that oxPAPC competes with LPS-binding and inhibits the non-canonical inflammasome in macrophages (PubMed:29520027)
Inhibited by 4-aminopyridine (4-AP), but not by tetraethylammonium (TEA) and charybdotoxin (CTX)
Uptake of inorganic carbon by cells in the presence of thiosulphate is fully inhibited by the uncouplers carbonyl cyanide m-chlorophenyl hydrazone (CCCP), carbonyl cyanide p-trifluoromethoxyphenyl hydrazone (FCCP), S13 or SF6847. Not inhibited by the ATPase inhibitor N,N-dicyclohexylcarbodiimide (DCCD) (Ref.2). Inorganic carbon uptake is inhibited by the ionophore CCCP, suggesting uptake is coupled to a cation gradient (PubMed:31406332)
Inhibited by koningic acid through the interaction of cysteine residues with koningic acid even at very low concentrations
Inhibited by EDTA, DTT and high concentrations of zinc ions (>2 mM). Weakly inhibited by TLCK. Not inhibited by PMSF. Activated by calcium ions
Inhibited by quercetin and diphenylhydantoin
Activated by divalent cations. Activated by bile acids
Inhibited by Cu(2+), Hg(2+) and Zn(2+). No effect with Ca(2+), Mg(2+), Mn(2+) or excess EDTA (10 mM)
Is physiologically inhibited by accumulation of the reaction product 5'-deoxyadenosine
Inhibited by the NADH analogs tetrahydro-NADH and hexahydro-NADH
In the absence of inducing signals such as low Ca(2+) or host cell contact, the T3SS/injectisome is expressed at a low basal level and exists in a quiescent state due to ExsA sequestration by ExsD in a 1:1 complex (PubMed:19369699, PubMed:20008065). Upon host cell contact, this interaction is disrupted by the anti-antiactivator protein ExsC leading to ExsA activation (PubMed:15225323)
Inhibited in vitro by juglone
Anhydrotetracycline, a poor substrate, prevents tetracycline degradation in vitro
Activity of listeriolysin O is regulated on multiple levels. It should be high in the phagosome, thereby allowing escape of the bacteria from the phagosomal compartment. Then, once inside the host cytosol, the activity must be controlled to prevent lysis of the host plasma membrane and loss of the intracellular environment. Multiple regulatory mechanisms include translational repression, which is required to minimize levels of listeriolysin O in the host cytosol. In addition, cytolytic activity is pH-dependent. Activity is high in the acidic environment of the phagosome and is turned off in the neutral pH of the cytosol. Listeriolysin O is also ubiquitinated and rapidly degraded by host proteasome in cytosol. The lytic activity is activated by reducing agents and suppressed by oxidation. Also inhibited by very low amounts of cholesterol
The proteolytic activity requires Zn(2+) and Ca(2+) ions. The alpha-fibrinogenase activity is completely inhibited by EDTA, but not by PMSF
In the presence of 10 mM allantoin, the activity is reduced more than 25%
Weakly inhibited by D-tryptophan
Tetraethylammonium (TEA) and tetrabutylammonium (TBA) inhibit the proton-activated currents in a dose- and voltage-dependent manner in vitro, whereas the blocker of acid sensing ion channels, amiloride, has no effect. Channel current of GLIC can be inhibited by inhaled and intravenous general anesthetics at and below concentrations used clinically. Ion conduction is also inhibited by lidocaine and by divalent transition metal ions such as cadmium ions
Specific activity for chondroitin sulfate substrates increases moderately (2-fold) while an increase of 25-fold is observed for dermatan sulfate as substrate upon addition of Ca(2+) or Mg(2+) ions (PubMed:18227125). Increasing the concentration of Na(+), K(+) or Cs(+) chloride from 0 to 0.1 M, increases the activity against all substrates. Further increases in salt concentration reduces the activity dramatically, with 50% inhibition occurring at 0.15 M and nearly complete inhibition at 0.4 M salt. The addition of 10 mM Ca(2+) or Mg(2+) ions increases the activity against chondroitin 4- and 6-sulfates by 2-3-fold, while the activity against dermatan sulfate increases much more significantly by 50-fold (PubMed:18512954). Addition of Mn(2+) and Zn(2+) reduces activity against chondroitin sulfate substrates, but increases the activity against dermatan sulfate. Increasing the concentration of CaCl(2) with both chondroitin 4- and 6-sulfates from 0 to 0.04 M increases the activity. A further increase reduces activity, with 50% inhibition at 0.065-0.085 M and a complete inhibition of the reaction at 0.2 M. In case of dermatan sulfate, the addition of low concentration of CaCl(2) dramatically increases the activity from the basal level. The maximal activity is reached at 0.01 M CaCl(2)
Activated by GUCA1A when free calcium ions concentration is low, and inhibited by GUCA1A when free calcium ions concentration is high (By similarity). Negatively regulated by RD3; inhibits the basal and GUCA1A-stimulated guanylate cyclase activity (By similarity)
Inhibited by PAK5; inhibition is independent of the kinase activity of PAK5. Activated by phosphorylation on Thr-208. Inhibited by phosphorylation at Ser-212 and Thr-593. Inhibited by hymenialdisine (By similarity)
Completely inhibited by Hg(2+). Cu(2+) and zinc have no effect on enzyme activity. Lithium, potassium, manganese, Ni(2+), calcium, magnesium and EDTA have no significant effect on enzyme activity. Enzyme requires presence of detergents such as Triton X-100 and Lubrol PX for the hydrolysis of glycosphingolipids. Taurodeoxycholate strongly inhibits the enzyme activity and SDS completely inhibits the enzyme activity
ATP-depletion almost completely abolishes SLC9A5 activity. Inhibited by amiloride compounds
Fumarate hydratase activity (fumarate to L-malate) is strongly inhibited by phosphoenolpyruvate, citrate, oxaloacetate, ATP and ADP (PubMed:29688630). Malate dehydratase activity (malate to fumarate) is activated by oxaloacetate, pyruvate, Asn and Gln (PubMed:29688630). Malate dehydratase activity (malate to fumarate) is inhibited by citrate, succinate, ADP, ATP, glucose-6P and phosphoenolpyruvate (PubMed:29688630)
Inhibited by 5'-deaza-1'-aza-2c-deoxy-1'-(9-methylene)-Immucilin-G (DADMe-ImmG)
Activity is susceptible to product inhibition
ADP-ribosyltransferase activity is regulated via an allosteric activation mechanism. In absence of activation signal, PARP2 is autoinhibited by the PARP alpha-helical domain (also named HD region), which prevents effective NAD(+)-binding. Activity is highly stimulated by signals, which unfold the PARP alpha-helical domain, relieving autoinhibition. Poly-ADP-ribosyltransferase activity is tightly regulated and PARP2 is removed from damaged chromatin following initial poly-ADP-ribosylation of chromatin to avoid prolonged residence (trapping) that has cytotoxic consequences. CHD1L promotes PARP2 removal from chromatin
Environmental stimuli such as light and salt stress suppress activity through stimulation of calmodulin (CaM) that binds BEA2 and probably impairs its dimerization
KL001 (N-[3-(9H-carbazol-9-yl)-2-hydroxypropyl]-N-(2-furanylmethyl)-methanesulfonamide) binds to CRY1 and stabilizes it by inhibiting FBXL3- and ubiquitin-dependent degradation of CRY1 resulting in lengthening of the circadian periods. KL001-mediated CRY1 stabilization can inhibit glucagon-induced gluconeogenesis in primary hepatocytes
Activated by diarachidonoyl phosphatidic acid (DAPA), when 1,2-dipalmitoyl-PI4P is used as a substrate
The acetate and butyrate conversion reactions are inhibited in vitro by physiological levels of acetone and butanol
Inhibited in the presence of NADH and NADPH. When Mg(2+) is present, Cu(2+), Hg(2+) and Zn(2+) inhibit the enzyme activity in some extent
Interaction with gamma-glutamyl phosphate reductase (proA) seems necessary for kinase activity. Requires free Mg(2+). Inhibited by proline and ADP
2,6-dichloro-4-dicyanovinylphenol (PC16) and antimycin A inhibit ubiquinol oxidation activity more selectively than the ubiquinone reductase activity
Activated by GUCA1A when free calcium ions concentration is low, and inhibited by GUCA1A when free calcium ions concentration is high (PubMed:21598940). Negatively regulated by RD3; RD3 inhibits the basal and GUCA1A-stimulated guanylate cyclase activity (By similarity)
The side chain of Glu-273 determines which of the two opposing activities (AMPylase or de-AMPylase) will take place. In response to endoplasmic reticulum stress, mediates de-AMPylase activity (By similarity). Adenylyltransferase activity is inhibited by the inhibitory helix present at the N-terminus: Glu-273 binds ATP and competes with ATP-binding at Arg-414, thereby preventing adenylyltransferase activity (By similarity). In unstressed cells, disengagement of Glu-273 promotes adenylyltransferase activity (By similarity). Activation dissociates ATP-binding from Glu-273, allowing ordered binding of the entire ATP moiety with the alpha-phosphate in an orientation that is productive for accepting an incoming target hydroxyl side chain (By similarity)
The presence of the regulatory subunit PRIM2/p58 accelerates the kinetics of initiation and primer extension
Down-regulated by YWHAE
Activated by the heterotrimeric G-protein subunits GNA12, GNA13 and GNB1-GNG2. Activated by HRAS, RAP1A, RHOA, RHOB, RHOC, RRAS and RRAS2. Activated by the G(s)-coupled GPCRs ADRB2, PTGER1 and CHRM3 through cyclic-AMP formation and RAP2B activation. Inhibited by G(i)-coupled GPCRs
Activated by threonine and tyrosine phosphorylation (By similarity). Inhibited by dual specificity phosphatases, such as DUSP1 (By similarity). Phosphorylation and activation in response to DNA damaging agents, serum stimulation. Constitutively activated when phosphorylated on Tyr-178. Activity depends on the relative rates of MAPK15 autophosphorylation and dephosphorylation by PTPN1 (By similarity)
Inhibited by sulfite, metabisulfite and dithonite
The phosphatase activity is constitutive and the kinase activity is regulated by the presence or absence of AI-1. At low cell density the kinase activity overrides the phosphatase activity
Irreversibly inhibited by the synthetic inhibitor cyc-SeCN-amidine, which inactivates the enzyme by inducing disulfide bond formation between the two active site cysteine residues Cys-9 and Cys-14
Does not appear to require metal ions or other cofactors for catalysis (PubMed:15613473). The reaction is insensitive to heptyl-4-hydroxyquinoline-N-oxide (HOQNO), a typical inhibitor of single electron reduction reactions (PubMed:15613473)
Erythrocytes hemolysis is inhibited by cholesterol
Inhibited by Gd(3+), Ruthenium Red, and Zn(2+) and partially inhibited by 2-aminoethoxydiphenyl borate
The DNA binding ability is drastically reduced in the presence of ATP. Tyrosine further reduces the binding affinity of TyrR in the presence of ATP
The activity is stimulated two- to fourfold by divalent cations but is unaffected by K(+) ions
The enzyme activity is strongly increased by double-stranded DNA (dsDNA), but not by single-stranded DNA or RNA (PubMed:23722159). DNA-binding induces the formation of liquid-like droplets in which CGAS is activated. Liquid-like droplets also create a selective environment that restricts entry of negative regulators, such as TREX1 or BANF1/BAF, allowing sensing of DNA (By similarity). A number of mechanisms exist to restrict its activity toward self-DNA. The nucleotidyltransferase activity is inhibited in the nucleus via its association with nucleosomes: interacts with the acidic patch of histones H2A and H2B, thereby blocking DNA-binding and subsequent activation (By similarity). CGAS is also inactive when associated with mitotic chromatin (By similarity). Chromatin-bound CGAS cannot be activated by exogenous DNA in mitotic cells: phosphorylation of the N-terminal disordered part by AURKB during the G2-M transition blocks CGAS liquid phase separation and activation (By similarity). Activity toward self-DNA is inhibited by BANF1/BAF upon acute loss of nuclear membrane integrity: BANF1/BAF acts by outcompeting CGAS for DNA-binding, thereby preventing CGAS activation (By similarity). DNA-induced activation at micronuclei is also limited by TREX1, which degrades micronuclear DNA upon nuclear envelope rupture, thereby preventing CGAS activation. Acetylation at Lys-359, Lys-369 and Lys-389 inhibits the cyclic GMP-AMP synthase activity. Acetylation by KAT5 increases the cyclic GMP-AMP synthase activity by promoting DNA-binding and subsequent activation (By similarity). Phosphorylation at Ser-278 suppresses the nucleotidyltransferase activity. Phosphorylation at Ser-410 promotes the cyclic GMP-AMP synthase activity (By similarity). Phosphorylation at Ser-188 inhibits its cyclic GMP-AMP synthase activity. Ubiquitination at Lys-359 via 'Lys-27'-linked polyubiquitination enhances the cyclic GMP-AMP synthase activity (By similarity). Monoubiquitination at Lys-322 promotes oligomerization and subsequent activation. Sumoylation at Lys-322, Lys-359 and Lys-369 prevents DNA-binding, oligomerization and nucleotidyltransferase activity. The enzyme activity is impaired by the cleavage by CASP1 (By similarity). In addition to DNA, also activated by collided ribosomes upon translation stress: specifically binds collided ribosomes, promoting its activation and triggering type-I interferon production (By similarity)
Activated by ethanol. Also activated by Co(2+), Zn(2+) and glycerol. Inhibited by EDTA, inorganic phosphate, nucleosides and Ca(2+). Unaffected by fluoride and tartrate
The GATase domain is allosterically activated by the binding of substrates, ATP and XMP, to the ATPPase domain, thus ensuring that glutamine hydrolysis occurs only when the ATPPase domain is primed to receive ammonia (PubMed:17868038, PubMed:32358899). Inhibited by Na(2+) (PubMed:17868038). Inhibited by the reaction product GMP (PubMed:17868038)
Subject to product inhibition by geranylgeranyl diphosphate
Subject to competitive inhibition by sulfite
ADP inhibits the formation of nebramycin 5'
4-guanidinobutyrate and guanidinoethyl sulfonate inhibit the transport activity
Not sensitive to pyruvate. Is in a constitutively active state. When the two monomeric subunits are covalently linked by a S-S bond, the enzyme is essentially inactive
Inhibited by Ras, probably via the interaction between RAS2 and ERI1
Lithium ions exhibits the highest inhibition (97%). To a lesser extent (5-20%), potassium, sodium, and ammonium ions also inhibit PuuC activity. Transition metals, such as copper and zinc ions inhibit PuuC activity by more than 90%. The presence of heavy metals (mercury, silver) or sodium hydrogensulfite in the reaction mixture completely inactivate PuuC; in contrast, disulfide reductants such as DTT and 2-mercaptoethanol significantly increase its activity by 75% and 27%, respectively
Inhibited by sorbitol-6-phosphate (S6P) and activated by CsrA
Partially inhibited by POA but not by PZA or nicotinamide, probably also inhibited by calcium pantothenate
Present in an inactive conformation in the absence of bound ligand. Ligand binding leads to dimerization and activation by autophosphorylation on tyrosine residues. Inhibited by SU5402
Activated by rho-1 binding
CLPS stimulates triacylglycerol lipase activity (PubMed:21382969, PubMed:2302735). Triacylglycerol lipase activity is not inhibited by increasing bile salt concentration (PubMed:21382969)
Regulation is a highly complex process involving membrane recruitment, protein-protein interactions, dimerization, and phosphorylation/dephosphorylation events. Ras-GTP recruits RAF1 to the membrane, thereby promoting its activation. The inactive conformation of RAF1 is maintained by autoinhibitory interactions occurring between the N-terminal regulatory and the C-terminal catalytic domains and by the binding of a 14-3-3 protein that contacts two phosphorylation sites, Ser-259 and Ser-621. Upon mitogenic stimulation, Ras and PPP2R1A cooperate to release autoinhibition and the subsequent phosphorylation of activating sites: Ser-338, Tyr-341, Thr-491, and Ser-494, yields a fully active kinase. Through a negative feedback mechanism involving MAPK1/ERK2, RAF1 is phosphorylated on Ser-29, Ser-43, Ser-289, Ser-296, Ser-301 and Ser-642 by MAPK1/ERK2, which yields an inactive, desensitized kinase. The signaling-competent conformation of RAF1 is finally re-established by the coordinated action of PIN1, a prolyl isomerase that converts pSer and pThr residues from the cis to the trans conformation, which is preferentially recognized and dephosphorylated by PPP2R1A. Activated by homodimerization and heterodimerization (with BRAF). Also regulated through association with other proteins such as KSR2, CNKSR1/CNK1, PEBP1/RKIP, PHB/prohibitin and SPRY4. PEBP1/RKIP acts by dissociating RAF1 from its substrates MAP2K1/MEK1 and MAP2K2/MEK2. PHB/prohibitin facilitates the displacement of 14-3-3 from RAF1 by activated Ras, thereby promoting cell membrane localization and phosphorylation of RAF1 at the activating Ser-338. SPRY4 inhibits Ras-independent, but not Ras-dependent, activation of RAF1. CNKSR1/CNK1 regulates Src-mediated RAF1 activation (By similarity)
Inhibited by phenothiazine analogs (PubMed:15767566). Inhibited by 2-mercapto-quinazolinones (PubMed:29522317). Not inhibited by classic inhibitors of type I NADH dehydrogenase, such as rotenone, piericidin A and pyridaben (PubMed:15767566)
The neuronal activity and the influx of calcium positively regulate the kinase activity and the internalization of the receptor which are both important for active signaling. Regulated by NGFR that may control the internalization of the receptor. NGFR may also stimulate the activation by BDNF compared to NTF3 and NTF4. SH2D1A inhibits the autophosphorylation of the receptor, and alters the recruitment and activation of downstream effectors and signaling cascades. The formation of active receptors dimers able to fully transduce the ligand-mediated signal, may be negatively regulated by the formation of inactive heterodimers with the non-catalytic isoforms
Inhibited by L-tetrahydro-2-furoic acid (THFA), L-mandelate and L-lactate (PubMed:17344208). Inhibited by N-propargylglycine (PubMed:18426222)
Inhibited by pyridoxal 5-phosphate, bathophenanthroline, mersalyl, p-hydroxymercuribenzoate and tannic acid
Activated by EGF. Arachidonic acid conversion is inhibited by (13S,14S)-epoxy-(4Z,7Z,9E,11E,16Z,19Z)-docosahexaenoate (13S,14S-epoxy-DHA) (By similarity). Arachidonate 12-lipoxygenase activity is decreased when PH decreases from 7.4 to 6 (PubMed:11256953)
Fructose uptake is inhibited by mercury ions (PubMed:26416735). Fructose uptake is only slightly inhibited by cytochalasin B (PubMed:8333543, PubMed:9820812)
Chloride channel activity is allosterically activated by lumenal H(+) and Cl(-) leading to synaptic vesicles acidification (PubMed:27133463). The L-glutamate transport activity is allosterically activated by lumenal H(+) and Cl(-) (PubMed:27133463, PubMed:19169251). The allosteric activation by H(+) efficiently prevents non-vesicular efflux across the plasma membrane, thereby restricting L-glutamate transport activity to acidic membranes such as synaptic vesicles (PubMed:27133463)
Mainly exists in a closed and catalytically competent conformation but a closed-to-open switch allows substrate entry into the catalytic chamber. Substrate binding induces closure and dimerization. A disulfide bond may lock the enzyme in a closed conformation preventing substrate entry into the catalytic chamber, participating in redox regulation of the enzyme. Inhibited by metal-chelating agents. Inhibited by nickel and zinc excess, and slightly activated by manganese
Activated by calcium (PubMed:29716996, PubMed:18768477, PubMed:23204525, PubMed:17123645, PubMed:32484216). Upon calcium binding to the EF-hand domains, the C-terminus of the junction domain (J domain) undergoes a conformational change which results in the dissociation of the pseudo-substrate inhibitory motif from the catalytic domain (Probable) (PubMed:23204525). This, in turn may facilitate the autophosphorylation of the activation loop at Thr-231, which leads to the kinase activation (PubMed:19307175). May be negatively regulated by PKA-mediated phosphorylation (PubMed:28680058). Inhibited by purfalcamine (PubMed:23204525, PubMed:29716996)
Novel PKCs (PRKCD, PRKCE, PRKCH and PRKCQ) are calcium-insensitive, but activated by diacylglycerol (DAG) and phosphatidylserine. Three specific sites; Thr-566 (activation loop of the kinase domain), Thr-710 (turn motif) and Ser-729 (hydrophobic region), need to be phosphorylated for its full activation
In the resting state, through the dimerization of its C-terminal domain, HSP90 forms a homodimer which is defined as the open conformation. Upon ATP-binding, the N-terminal domain undergoes significant conformational changes and comes in contact to form an active closed conformation. After HSP90 finishes its chaperoning tasks of assisting the proper folding, stabilization and activation of client proteins under the active state, ATP molecule is hydrolyzed to ADP which then dissociates from HSP90 and directs the protein back to the resting state. Co-chaperone TSC1 promotes ATP binding and inhibits HSP90AA1 ATPase activity. Binding to phosphorylated AHSA1 promotes HSP90AA1 ATPase activity. Inhibited by Ganetespib (STA-9090) and SNX-2112
The lipolytic activity of the full-length protein is regulated/inhibited by the presence of the C-terminal adenylate cyclase domain (PubMed:33960821). Lipolytic activity of the full-length protein decreases in the presence of ATP, but ATP does not affect activity of the N-terminal domain in the absence of the C-terminal cyclase domain (PubMed:33960821). Lipolytic activity is inhibited by the serine modifier phenylmethylsulfonyl fluoride (PMSF) (PubMed:33960821)
Allosterically activated by DHSp. Inhibited by spermididine analog N1-guanyl-1,7-diamineoheptane (GC7)
Inhibited by micromolar Cu(2+)
Phosphorylation of Thr-84 by OXSR1 inhibits activation (By similarity). Activated by binding small G proteins. Binding of GTP-bound CDC42 or RAC1 to the autoregulatory region releases monomers from the autoinhibited dimer, and enables activation by phosphorylation of Thr-422 (By similarity)
Inhibited by the chelating agent EDTA. Divalent metal ions have substrate- and concentration-dependent effects on activity. Activity towards bradykinin is inhibited with increasing Mn(2+) concentration. Activity towards substance P is stimulated by low Mn(2+) concentrations (in the range 10 uM-1 mM) but inhibited by Mn(2+) concentrations in excess of 1 mM. Ca(2+), Mg(2+) and Co(2+) stimulate activity towards substance P at concentrations of 10-100 uM but are inhibitory at concentrations of 1 mM. Zn(2+), Ni(2+) and Cu(2+) strongly inhibit activity towards substance P at concentrations of 1 mM
Competitively inhibited by several inositol 1-phosphate analogs, including the phosphonate analog 1-deoxy-1-phosphonomethyl-myo-inositol (Ino-C-P) (By similarity). This leads to inhibition of M.smegmatis growth (PubMed:23225597)
Up-regulated by CLPS in the presence of increasing concentrations of bile salts
Completely inhibited by NPGB, PMSF, diisopropylfluorophosphate (DFP), benzamidine and soybean trypsin inhibitor. Not inhibited by EDTA
Activated by proton donors such as imidazole and the dipeptide histidylhistidine (PubMed:16042381). Inhibited by coumarins and sulfonamide derivatives such as acetazolamide (PubMed:18618712, PubMed:19186056, PubMed:19206230)
Stimulated by estrogen. Repressed by 5-iodotubercidin (DB04604)
Inhibited by N-hydroxy-N-isopropyloxamate (IpOHA)
Inhibited by rolipram. Activated by phosphatidic acid
Inhibited by pyrophosphate and polyphosphates. Also competitively inhibited by validoxylamine and castanospermine, but not by trehazolin
Activated when MTREX is incorporated into NEXT complex an the nuclear RNA exosome complex
Protease activity is inhibited by the metal chelating reagents 1,10-phenanthroline and EDTA
Activated by phosphorylation on Thr-183. Binding of AMP to non-catalytic gamma subunit (PRKAG1, PRKAG2 or PRKAG3) results in allosteric activation, inducing phosphorylation on Thr-183. AMP-binding to gamma subunit also sustains activity by preventing dephosphorylation of Thr-183. ADP also stimulates Thr-183 phosphorylation, without stimulating already phosphorylated AMPK. ATP promotes dephosphorylation of Thr-183, rendering the enzyme inactive. Under physiological conditions AMPK mainly exists in its inactive form in complex with ATP, which is much more abundant than AMP. AMPK is activated by antihyperglycemic drug metformin, a drug prescribed to patients with type 2 diabetes: in vivo, metformin seems to mainly inhibit liver gluconeogenesis. However, metformin can be used to activate AMPK in muscle and other cells in culture or ex vivo (PubMed:11602624). Selectively inhibited by compound C (6-[4-(2-Piperidin-1-yl-ethoxy)-phenyl)]-3-pyridin-4-yl-pyyrazolo[1,5-a] pyrimidine. Activated by resveratrol, a natural polyphenol present in red wine, and S17834, a synthetic polyphenol
Inhibited by Zn2+ and Cu2+ at low micromolar concentrations. Inhibited by SERPINA12 (By similarity)
Inhibited by olomoucine and 3-isobutyl-1-methylxanthine
Inhibited by CCCP
Inhibited by kifunensine and 1-deoxymannojirimycin, but not by swainsonine
Activated by the binding of calmodulin-like protein 1 (CML1) in the presence of Ca(2+)
Activated by light-induced dephosphorylation. Inhibited by dark-induced phosphorylation. Both reactions are catalyzed by PDRP1
Inhibited by the inhibitor JF0064
Inhibited by 10 mM Co(2+), Mn(2+) and Ni(2+), and by 1 mM Cu(2+) and Hg(2+)
Inhibition of RapA requires a free carboxylate group at the C-terminal end of the PhrA pentapeptide (PubMed:11587784). A free C-terminal carboxylic acid PhrA pentapeptide inhibits RapA phosphatase activity at a 1:1 ratio and is approximately 200 fold more active than a C-terminal amide peptide (PubMed:11587784)
Uncompetitive inhibition by micromolar concentrations of lithium. Competitive inhibition by inositol 1,4-bisphosphate. Inhibited by calcium ions
Its proteolytic activity is autoinhibited by the non-covalent binding of the propeptide to the catalytic domain. Inhibited by EGTA
Channel activity is inhibited by mercury ions and phloretin
ATPase activity is stimulated by various thiol compounds (PubMed:24958725). The presence of heme leads to a further enhancement of thiol-stimulated ATPase activity, although a large excess of heme inhibits activity (PubMed:24958725). Glutathione transport is inhibited by sodium orthovanadate, an inhibitor of ABC-type transport systems, but not by the proton ionophore carbonyl cyanide m-chlorophenylhydrazone (CCCP) (PubMed:16040611)
ATPase activity is strongly stimulated by single-stranded DNA (PubMed:11751861). Presence of ATP and Mg cofactor are required for helicase activity allowing to unwind duplex oligonucleotides up to 60-70-mer (PubMed:11751861). This helicase activity is stimulated by replication protein A (RPA/RP-A) complex that binds to unwound regions and inhibits re-annealing (PubMed:11751861)
Autophosphorylation is induced in vitro by dithiothreitol (DTT)
Active at low pH (under pH 4.6): proton channel activity is activated by luminal side protons. Polyunsaturated fatty acids, such as arachidonic acid, also activate the channel activity. Channel activity is activated following interaction with AKT (AKT1, AKT2 or AKT3): interaction promotes activation from closed to an open state. Activation by AKT is independent of AKT serine/threonine-protein kinase activity
Inhibited by the hydroxamate N-hydroxy-4-(naphthalene-1-yl)benzamide (NHNB)
Phosphatase activity repressed by oxidized ATGPX3, free fatty acids (e.g. arachidonic acid (20:4) and Linolenic acid (18:3)) and by H(2)O(2). Repressed by PYR/PYL/RCAR ABA receptors in an ABA-dependent manner
A Cys to Ala mutation in SufU (Cys-41-Ala) has been described to be a competivie inhibitor of SufS activity and a non-competitive inhibitor (PubMed:21236255, PubMed:24321018)
Triazaspirodimethoxybenzoyls are high-nanomolar inhibitors of M.tuberculosis Lpd and are non-competitive versus NADH, NAD(+), and lipoamide and >100-fold selective compared to human Lpd
3'-5' nuclease activity is stimulated in presence of pcna
The activity decreases with increasing concentration of H(2)O(2). Has 68% and 43% of activity remaining upon treatment with 0.1 and 0.2 mM H(2)O(2) for 30 minutes, respectively. Inhibited significantly by 2 mM Zn(2+), Cu(2+) and Ag(+), moderately by Co(2+), Mn(2+), Sn(2+) and Mg(2+), and only slightly by Ba(2+). Slightly activated by Fe(2+) and Ca(2+). No effect on activity by metal chelators EDTA and 8-hydroxyquinoline at 2 mM or by dithiothreitol, 2-mercaptoethanol or phenylmethanesulfonyl fluoride
Inhibited by p-chloromercuribenzoic acid and alkyliodines
Calcium efflux is tightly regulated by intracellular pH
Activated by threonine and tyrosine phosphorylation by the dual specificity kinase, MKK3
Inhibited by n-butylic acid and S-adenosyl-L-homocysteine
Inhibited by 0.1 mM diisopropyl fluorophosphate (DFP), phenylmethanesulfonyl fluoride (PMSF), chymostatin and elastatinal. Not inhibited by N-alpha-p-tosyl-L-lysine chloromethylketone (TLCK), N-tosyl-L-phenylalanyl chloromethyl ketone (TPCK) or N-carbobenzoxy-L-phenylalanine chloromethylketone (ZPCK)
Activated by manganese and, to a lesser extent, by calcium
RuvA inhibits the RuvC resolution reaction by binding junction DNA and preventing cleavage. RuvA binds to cruciform DNA in the presence of RuvC
Completely inhibited by the serine protease inhibitor diisopropyl fluorophosphate (DFP) and moderately by N-tosyl-L-phenyl-alanyl chloromethyl ketone (TPCK). Somewhat inhibited by phenylmethanesulfonyl fluoride (PMSF). Activity is not affected by thiol- or metalloprotease inhibitors, such as iodoacetate (IAA), EDTA, N-tosyl-L-lysyl chloromethyl ketone (TLCK), o-phenanthlorine, N-ethylmaleimide (NEM) or dithiothreitol (DTT)
The GTPase activity is stimulated in the presence of ribosomes, particularly of the 60S subunit
Inhibited by flavonoids (quercetin and genistein), cetylpyridium chloride, phenylhexane and valproic acid. Low inhibition is observed with fatty acids (myristic acid and lauric acid). No significant inhibition is observed with barbital, dicumarol, indomethacin, metyrapone, ethacrynic acid, disulfiram, hexestrol and benzodiazepines (diazepam and nitrazepam)
Inhibited by tacrolimus/FK506
Inhibited by RANBP9 (PubMed:14500717). Inhibited by harmine, leucettamine B and leucettine L41 (PubMed:22998443)
Uncompetitively inhibited by high concentration of 3-OCS-CoA
Inhibited by sodium vanadate and peroxide
Cu(2+), zinc, manganese, calcium, magnesium and EDTA have no significant effects on enzyme activity. Enzyme requires presence of detergents such as Triton X-100 and Lubrol PX for the hydrolysis of glycosphingolipids. Taurodeoxycholate strongly inhibits the enzyme activity
Inhibited by divalent metal cations, including Mg(2+), Mn(2+), Ca(2+) and Zn(2+). Mildly inhibited by 0.01 % SDS and 0.1% dodecyl-beta-D-maltoside. Activity is nearly abolished by 1 % SDS
Subject to autoinhibition, mediated by interactions between the FERM domain and the kinase domain. Activated by autophosphorylation at Tyr-397. This promotes interaction with SRC and phosphorylation at Tyr-576 and Tyr-577 in the kinase activation loop. Phosphorylation at Tyr-576 and Tyr-577 is required for maximal kinase activity. Inhibited by TAC544, TAE226, PF-573,228 and PF-562,271
Transport of iron ions is inhibited by zinc ions
Clofazimine, a drug being evaluated for XDR and MDR tuberculosis, inhibits SerB2 phosphatase activity and reverses the various functional effects described above and interactions with host proteins (PubMed:26984196). Is inhibited by known PSP inhibitors such as chlorpromazine, DL-AP3 and sodium orthovanadate, but not by okadaic acid (PubMed:25037224, PubMed:25521849). By binding to the ACT domains, amino-acids have various effects on enzyme activity: L-serine and L-glycine act as inhibitors, whereas L-lysine, L-tyrosine and L-phenylalanine are activators (PubMed:25521849). High throughput screen has been performed to identify specific PSP inhibitors with activity against intracellular bacteria; the two best hits identified in this screen, clorobiocin and rosaniline, are bactericidal and kill bacteria in infected macrophages in a dose-dependent manner (PubMed:25037224)
Phenylglyoxal and propranolol inhibit activity in dose-dependent manners with IC(50) values of 1.3 mM and 0.2 mM, respectively
Inhibited by cloxacillin and clavulanic acid
Activated during mitosis by intramolecular autophosphorylation. Activity and autophosphorylation is activated by manganese >> magnesium ions. It is not cell-cycle regulated but activity is higher in G0-arrested cells
Feed-back regulated by NAD. A high level of NAD causes NadR to lose enzymatic activity and repress several NAD synthetic genes; conversely, a low NAD level activates the assimilatory enzymatic activities and leads to derepression of biosynthetic genes
Inhibited by globomycin
Could be inhibited during sporulation by acidification of the forespore, thus allowing accumulation of the spore's large depot of 3-phosphoglyceric acid
Both the ceramide and diacylglycerol kinase activities are inhibited by sphingosine and stimulated by cardiolipin (PubMed:15252046). Both activities are stimulated by calcium when magnesium concentrations are low but inhibited by calcium when magnesium concentrations are high (PubMed:15252046)
Interaction with F1P may induce a structural change in the DNA spacer region between the -35 and -10 elements, thereby facilitating RNAP binding to the promoter to trigger the transcriptional activation of the fru operon. Interaction with F1P does not release FruR from its binding sequence
Inhibited by putrescine and by the substrate analog arginine. Inactive when the purified enzyme is incubated with dithiothreitol followed by excess iodoacetic acid or N-ethylmaleimide
Sodium cyanoborohydride, N-ethylmaleimide, hydroxylamine, phenyhydrazin and EDTA are inhibitors of the catalytic activity
Inhibited by kifunensine
Inhibited by rolipram. Activated by phosphatidic acid (By similarity)
Activated upon translocation to the sites of synthesis of PtdIns(3,4,5)P3 in the membrane. Enzymatic activity is enhanced in the presence of phosphatidylserine
Compared to the defatty-acylase activity, the protein deacetylase activity is weak in vitro, and requires activation (PubMed:24052263, PubMed:23892288, PubMed:21362626, PubMed:23552949). The histone deacetylase activity is strongly activated upon binding to nucleosomes and chromatin in vivo (PubMed:23892288, PubMed:27043296, PubMed:33067423). Two molecules of SIRT6 associate with the acidic patch of one nucleosome, while the C-terminal disordered region of SIRT6 associates with nucleosomal DNA, leading to efficient histone deacetylation (PubMed:33067423). The protein-lysine deacetylase activity is also activated by long-chain free fatty-acids (PubMed:24052263). The histone deacetylase activity is specifically repressed by long non-coding RNA lncPRESS1, which binds to SIRT6 and prevents chromatin-binding, thereby promoting stem cell pluripotency (PubMed:27912097). Due to its essential role as tumor suppressor and involvement in DNA repair and life span, extensive research is made for the identification of small compound regulators of SIRT6 (PubMed:27990725, PubMed:30395713, PubMed:30374165, PubMed:31844103, PubMed:33214841, PubMed:33649599, PubMed:33649600). Nitro-fatty acids (nitro-oleic acid and nitro-conjugated linoleic acid) strongly stimulate the protein-lysine deacetylase activity by forming a covalent Michael adduct formation with Cys-18 (PubMed:33122195). Activated by UBCS039 (4-(pyridin-3-yl)-4,5- dihydropyrrolo[1,2-a]quinoxaline) (PubMed:27990725). Inhibited by non-selective hydroxamate trichostatin A inhibitor (PubMed:30395713). Deacetylase activity is activated by fluvastatin and quercetin-based compounds (PubMed:31844103, PubMed:33214841). The protein-lysine deacetylase activity, but not the defatty-acylase activity, is specifically activated by MDL-800 and MDL-801 activators in vivo, enhancing the histone deacetylase and tumor suppressor activities (PubMed:30374165, PubMed:33649599, PubMed:33649600). MDL-800 and MDL-801 selectively activate SIRT6 and not other members of the sirtuin family (PubMed:30374165). The binding-mode of MDL-801 is however subject to discussion (PubMed:30374165, PubMed:33649599, PubMed:33649600)
Activity towards dsRNAs such as hairpin dsRNAs, short dsRNAs and microRNAs, is inhibited by inorganic phosphate (PubMed:21419681, PubMed:24488111, PubMed:29550490). Binding to inorganic phosphate may function in substrate discrimination by blocking the enzyme from binding to nonphysiological substrates, as the presence of inorganic phosphate at physiological concentrations inhibits processing of the inappropriate substrates microRNAs (pre-miRNAs) and short dsRNAs but does not affect cleavage of long dsRNAs (PubMed:21419681, PubMed:24488111, PubMed:29550490). In the presence of inorganic phosphate, interaction with loqs (isoform PD) enables the enzyme to process blunt-end hairpin RNA substrates and produce endo-siRNAs, likely by increasing binding affinity of the enzyme to the hairpin dsRNAs (PubMed:29550490)
Inhibited by EDTA, calcium chloride, and zinc chloride (PubMed:18227059, PubMed:25596343). Enhanced by magnesium chloride (PubMed:18227059, PubMed:25596343). Glycerophosphodiester phosphodiesterase activity can be modulated by G-protein signaling pathways (By similarity)
Histone acetyltransferase activity stimulated by the presence of ADA2 proteins
Allosterically activated by calcium
Stimulated by FeSO(4) up to a concentration of 1 mM, whereas higher concentrations inhibited the ectoine hydroxylase. Also inhibited by ascorbate
Not activated by calcium. Autophosphorylation may play an important role in the regulation of the kinase activity. Stimulated by magnesium ions (optimum at 10-15 mM) and manganese ions
Inhibited by CuCl(2), monoiodoacetate and diethylpyrocarbonate (PubMed:15466039). Inhibited by 2,3-dihydroxybenzaldehyde, which is an analog of the substrate 2,3-dihydroxybenzoate (PubMed:16963440)
Inhibited by N-ethylmaleimide, p-chloromercuriphenyl sulfonate, cobalt and copper ions
The apolipoprotein APOC2 acts as a coactivator of LPL activity (PubMed:10727238). Ca(2+) binding promotes protein stability and formation of the active homodimer (PubMed:16179346). Interaction with GPIHBP1 protects LPL against inactivation by ANGPTL4 (PubMed:27929370)
Not inhibited by Kunitz-type trypsin inhibitors
Inhibited by strychnine (PubMed:10762330)
Specifically inhibited by spautin-1 (specific and potent autophagy inhibitor-1), a derivative of MBCQ that binds to USP13 and inhibits deubiquitinase activity. Regulated by PIK3C3/VPS34-containing complexes. The weak deubiquitinase activity in vitro suggests the existence of some mechanism that activates the enzyme (By similarity)
Binding of domain III of RuvA to a single subunit of the RuvB hexamer activates the ATPase 2 subunits away and nucleotide exchange in the adjacent subunit
Inhibited by NADH
Binding of Ca(2+) to PE_PGRS33 induces conformational changes and increases affinity for TLR2
Inhibited by 1,4-dideoxy-1,4-imino-d-mannitol (DIM) and EDTA
Compared to the defatty-acylase activity, the protein deacetylase activity is weak in vitro, and requires activation. The histone deacetylase activity is strongly activated upon binding to nucleosomes and chromatin in vivo. Two molecules of SIRT6 associate with the acidic patch of one nucleosome, while the C-terminal disordered region of SIRT6 associates with nucleosomal DNA, leading to efficient histone deacetylation. The protein-lysine deacetylase activity is also activated by long-chain free fatty-acids
Enzyme activity is markedly inhibited by TLCK and PMSF, and moderately by SBTi. Platelet aggregating activity is strongly inhibited by TLCK
Inhibited by p-chloromercuribenzoate (10 mM), HgCl2 (10 mM), or 5,5-dithiobis(2-nitrobenzoate) (100 mM)
Inhibited by 5 mM of zinc, copper and iron. Unaffected by low concentrations of detergents and irreversibly inactivated by 2% ethanol, isopropanol or dimethyl sulfoxide
Inhibited by millimolar levels of tetraethylammonium (TEA). Contrary to other channels, inhibited only by millimolar levels of 4-aminopyridine (4-AP). Inhibited by Stichodactyla helianthus peptide ShK
Competitively inhibited by methylglyoxal bis-guanylhydrazone. Inactivated by treatment with the imine reductant NaCNBH(3) only in the presence of substrate
Activity stimulated by beta-mercaptoethanol
Inhibited by PhrK, which prevents RapK-ComA interaction
Uptake is inhibited by the proton ionophore nigericin, which dissipates the proton gradient, and by the potassium ionophore valinomycin, which dissipates the membrane potential
Competively inhibited by 6-phosphogluconate and erythrose 4-phosphate
The pro-survival signaling effect of NTRK1 in neurons requires its endocytosis into signaling early endosomes and its retrograde axonal transport. This is regulated by different proteins including CFL1, RAC1 and SORT1. NTF3 is unable to induce this signaling probably due to the lability of the NTF3-NTRK1 complex in endosomes (By similarity). SH2D1A inhibits the autophosphorylation of the receptor, and alters the recruitment and activation of downstream effectors and signaling cascades. Regulated by NGFR (By similarity)
Activated by calcium. Upon calcium binding to the EF-hand domains, the C-terminus of the junction domain (J domain) undergoes a conformational change which results in the dissociation of the pseudo-substrate inhibitory motif from the catalytic domain. This, in turn may facilitate the autophosphorylation of the activation loop at Thr-230, which leads to the kinase activation
Hydrolysis of both phloretin and MAPG is competitively inhibited by DAPG
Activated by phosphorylation by CDKF-1
Inhibited by phloretin (PubMed:12217874). Activated by forskolin, 3-isobutyl-1-methylxanthine (IBMX) and cAMP (PubMed:12217874)
Inhibited by phloretin (PubMed:11029290). Activated by forskolin, 3-isobutyl-1-methylxanthine (IBMX) and cAMP (PubMed:12217874)
Activity is influenced by intracellular pools of the effector molecules ATP, ADP and 2-oxoglutarate. It senses the cellular nitrogen status through 2-oxoglutarate, and the energy level of the cell by binding both ATP and ADP with different affinities. ATP and 2-oxoglutarate prohibit binding to Amt3. ADP promotes the complex formation
Stimulated by the presence of a monovalent cation (PubMed:11948193). Acetylation leads to decreased substrate binding and decreased catalytic activity (PubMed:26847092)
Activity is stimulated by ZBP1, which senses double-stranded Z-RNA structures (By similarity). RIPK3-dependent necroptosis is inhibited by RIPK1: RIPK1 prevents the ZBP1-induced activation of RIPK3 via FADD-mediated recruitment of CASP8, which cleaves RIPK1 and limits TNF-induced necroptosis (By similarity)
Activated by Ca(2+)/calmodulin. Binding of calmodulin may relieve intrasteric autoinhibition. Partially inhibited upon phosphorylation by PRCAKA/PKA. May be regulated through phosphorylation by CAMK1 and CAMK4
Inhibited by dipyridimole. Insensitive to selective PDE inhibitors including rolipram and zaprinast as well as to the non-selective inhibitor, IBMX. Unaffected by cGMP
Triggered by EIN3
Inhibited by calcium, cadmium, mercury, and copper ions
Not inhibited by iron, calcium, mercury, manganese, zinc or EDTA
Activated by binding of S100B which releases autoinhibitory N-lobe interactions, enabling ATP to bind and the autophosphorylation of Ser-282. Thr-442 then undergoes calcium-dependent phosphorylation by STK24/MST3. Interactions between phosphorylated Thr-442 and the N-lobe promote additional structural changes that complete the activation of the kinase. Autoinhibition is also released by the binding of MOB1/MOBKL1A and MOB2 to the N-terminal of STK38L (By similarity)
Binding of DSF to the sensor region causes allosteric change, which facilitates RpfC autophosphorylation
Phosphorylation leads to a decrease in the catalytic activity
Activated by phosphorylation by specific MAP kinase kinase kinases such as MAP3K1/MEKK1, MAP3K3/MEKK3, MAP3K11/MLK3 and MAP3K12/DLK. Isoforms 3 and 4 have lower basal activity but a higher level of inducible activation, than isoforms 2, 6, 7 and 8
Inhibited by propargylglycine, trifluoroalanine and aminoethoxyvinylglycine
Under neutral conditions, the reaction is stimulated 4-fold by fructose 1,6-bisphosphate (FBP), however the L-lactate dehydrogenase is a nonallosteric enzyme. Calcium and zinc ions at 1 mM stimulate the activity almost 2-fold. Weakly inhibited by cadmium, cobalt and copper ions
Allosterically activated by tryptophan but not by tyrosine and phenylalanine
Activated by ATP (PubMed:27477609). pH-dependent and inhibited by acidic pH (By similarity)
Allosterically activated by metal cations, which are absolutely required for activity. The presumed physiological activator is Mg(2+), but can also be activated in vitro by other divalent cations such as Mn(2+), Fe(2+) and Ca(2+), by the monovalent cation Li(+), and by trivalent cations such as Eu(3+), Tb(3+) and Gd(3+). Competitively inhibited by methylglyoxal bis-guanylhydrazone. Also inhibited by Zn(2+), inhibition may be due to interaction with the active site cysteine. Inactivated by treatment with the imine reductant NaCNBH(3) only in the presence of substrate
Activated by iron and manganese
Inhibited in the presence of EDTA (PubMed:33737179). Resistant to inhibition by sodium azide (PubMed:33737179)
3,4-epoxy-l-butenyl diphosphate and 3-(fluoromethyl)-3-butenyl diphosphate (FIPP) act as specific active site-directed inhibitors of IP Pisomerase
Activated by phosphatidylinositol 4,5-bisphosphate (PIP2) (PubMed:29745897). Although PIP2 is essential for the channel activation, its contribution to the level of channel activity is minimal (PubMed:29745897). Also activated by diphosphate ribose-2'-phosphate (PubMed:27333281). Upon binding to ADPR, channel activation requires only a short initial cytosolic Ca(2+) increase, then the activation is sustained by the uptake of extracellular Ca(2+) (PubMed:29745897, PubMed:25620041). Activated by 2-aminoethyl diphenylborinate (2-APB) in a Ca(2+)-dependent manner (PubMed:28775320). 2-APB prevents the inactivation of the channel (PubMed:28775320)
Activity is divalent cation-dependent. It is stimulated by manganese, magnesium or calcium ions and reversibly inhibited by zinc, cobalt and iron
When length of the acyl-CoA aliphatic chain is increased, it begins to occupy the binding site for the amine substrate, leading to non-productive amine binding which results in a decrease in the rate of catalysis (PubMed:26476413). Inhibited by tyrosol (an analog of tyramine) (PubMed:26476413). Tyramine or octopamine are not substrates when the acyl acceptor is oleoyl-CoA (PubMed:24444601)
Activated by 3'cADPR. 3'cADPR activates the NADase function of ThsA by binding to the SLOG domain, which changes its tetramer organization, probably allowing NAD(+) to access the active site
Strongly inhibited by CuSO(4), FeCl(3), K(3)[Fe(CN)(6)], AgNO3, HgCl(2) and MnCl(2)
The 3-oxoacetyl-CoA thiolase activity is inhibited by acetyl-CoA while the acetyl-CoA hydrolase activity is inhibited by acetoacetyl-CoA
Negatively regulated through phosphorylation by the MAPK module (PubMed:19008449). Activity is constrained by polarized BASL in stomatal lineage ground cells (SLGCs) undergoing ACD (PubMed:27746029)
The presence of the regulatory subunit accelerates the kinetics of initiation and primer extension
Inhibited by 8-bromoadenosine phosphate (8-Br-AMP)
Synthesis is increased during S and G2 phases, presumably by an increase in transcription; activity is decreased by phosphorylation during m phase. Protein levels fall in M phase as a result of decreased synthesis combined with degradation. Activity seems to be negatively regulated by phosphorylation upon entry into mitosis, although N-terminal phosphorylation might also regulate the protein stability via protection from proteolysis or might regulate the subcellular location
Activity is inhibited by sulfhydryl-reactive compounds, acriflavine, o-phenanthroline and EDTA
The L-glutamate uniporter activity exhibits a biphasic dependence on chloride concentration. Chloride channel activity is allosterically activated by lumenal H(+) and Cl(-) leading to synaptic vesicles acidification. The glutamate transport activity is allosterically activated by lumenal H(+) and Cl(-), preventing non-vesicular L-glutamate release
Strongly inhibited by E-64 (L-trans-epoxysuccinylleucylamido(4-guanidino)butane), Leupeptin, and N-alpha-p-tosyl-L-lysine chloromethyl ketone
Binding to the yetM cis sequence is clearly inhibited by kaempferol, morin, apigenin and luteolin, slightly inhibited by quercetin and galangin, but no inhibition is observed with the other flavonoids (PubMed:19329649). Flavonoid binding may induce conformational changes and modulate interaction with DNA (PubMed:35367827)
GABA transport is inhibited by beta-alanine
(S)-alpha-fluoromethyltyrosine (AFMT) specifically inhibits microbial L-dopa decarboxylase activity, including in Parkinson's disease patient microbiotas. AFMT shows potential to block degradation of L-dopa by E.faecalis in mice. Blocking bacterial L-dopa decarboxylase activity in patients with Parkinson's disease, with knowledge of the abundance of this enzyme in an individual, could personalize and potentially improve L-dopa therapies. In contrast, L-dopa decarboxylation by E.faecalis is not inhibited by carbidopa, a commonly used human L-dopa decarboxylase inhibitor
Redox-regulated. Inhibited under oxydizing conditions (By similarity)
Binding of TP53BP2 to the regulatory subunit NAE1 decreases activity
Competitively inhibited by pyridine-2,4-dicarboxylate (PubMed:8546682). Inhibited by diethyl pyrocarbonate (DEPC), 3,4-dihydroxybenzoate, pyridine-2,5-dicarboxylate, alpha,alpha'-dipyridyl, and some metal ions such as Co(2+) and Zn(2+) (PubMed:6324794, PubMed:8546682)
Activated in response to hydrogen peroxide and cellulase elicitor. Activated by PDK1 in a phosphatidic acid dependent manner
Inhibited by EDTA and Zn(2+)
Inhibited by carbon monoxide (CO)
Inhibited by quinine at micromolar levels (PubMed:9612272). Modestly sensitive to millimolar levels of tetraethylammonium (TEA) and 4-aminopyridine (4-AP) (PubMed:9612272)
Inhibited by arsenite, iodoacetate and cyanide
Activated by Ca(2+)/calmodulin. Binding of calmodulin results in conformational change that relieves intrasteric autoinhibition and allows phosphorylation of Thr-180 within the activation loop by CaMKK1 or CaMKK2. Phosphorylation of Thr-180 results in several fold increase in total activity. Unlike CaMK4, may be unable to exhibit autonomous activity after Ca(2+)/calmodulin activation
Activated upon ALKAL2 ligand-binding (PubMed:34646012, PubMed:34819673). ALKAL2-driven activation is coupled with heparin-binding (PubMed:25605972, PubMed:34646012). Following ligand-binding, homodimerizes and autophosphorylates, activating its kinase activity (PubMed:16317043, PubMed:17681947, PubMed:34646012, PubMed:34819673). Inactivated through dephosphorylation by receptor protein tyrosine phosphatase beta and zeta complex (PTPRB/PTPRZ1) when there is no stimulation by a ligand (PubMed:17681947). Staurosporine, crizotinib and CH5424802 act as inhibitors of ALK kinase activity (PubMed:21575866)
Oxamate, fructose-1,6-diphosphate and L-lactate act as non-competitive inhibitors, whereas succinate, citrate and tartrate isomers produce a competitive inhibition
Competitively inhibited by NAD(+). Inhibited by mercurials such as p-chloromercuribenzoate (PCMB) and HgCl(2). Enzymatic activity increases under anaerobic conditions (By similarity)
Activated by binding to the regulatory factor DNMT3L. Auto-methylation at Cys-706 in absence of DNA inactivates the DNA methyltransferase activity
Inhibited by the 1,2,3-triazole urea covalent inhibitors KT109 and KT172 (By similarity). Inhibited by p-hydroxy-mercuri-benzoate and HgCl(2), but not by PMSF. Also inhibited by RHC80267, a drug that blocks 2-AG formation (By similarity)
In vitro, inhibited by hexaamminecobalt(3+)
Oligomerization increases ATPase activity (PubMed:26947936, PubMed:27770024, PubMed:29595954, PubMed:31978132). Monomeric forms exhibit low-level ATPase activity by forming short-lived oligomers with active site contributions from at least two protomers. In contrast, oligomers exhibit enhanced ATP hydrolysis rates that likely result from multiple preformed active sites within the oligomeric complex (PubMed:31978132). Oligomerization is important for both enzyme activation and T3SS function (PubMed:31978132). Activity is regulated by MxiN/SctL, which differentially regulates the activity of the monomer and the oligomer: it up-regulates the ATPase activity of the monomer, while it down-regulates the activity of the oligomer (PubMed:29595954)
Inhibited by tolrestat and epalrestat
In the famine mode, FL11 forms dimers and acts as a repressor, leading to growth arrest. In the feast mode, in the presence of high concentrations of lysine or arginine, four dimers assemble into an octamer and cover the fl11 and lysine biosynthesis promoters. This leads to the inhibition of fl11 expression and lysine biosynthesis, decrease of the FL11 concentration in the cell, derepression of the target genes and activation of the metabolism
Inhibited by divalent cations such as Ca(2+) and Mg(2+)
Inhibited by excess of Ca(2+) and Cd(2+), Mn(2+), and Zn(2+)
Activated by ATP (PubMed:9016352). pH-dependent and inhibited by acidic pH (By similarity)
Strongly inhibited by gardenin B (GARD B)
Has been suggested to require either an unsaturated acyl carrier protein or unsaturated acyl-CoA (but not their saturated equivalents) for DNA-binding (PubMed:19854834). Another group suggests that unsaturated thioesters are not essential but act instead to enhance DNA-binding (PubMed:21276098)
Activated by calcium and calmodulin. Autophosphorylation may play an important role in the regulation of the kinase activity
Activity of CodY is modulated by interaction with the branched-chain amino acids (BCAAs) leucine, isoleucine and valine, which are signals of the nutritional status of the cell (PubMed:18024519). Whereas both BCAA and GTP are CodY effectors in B.subtilis, S.pneumoniae CodY responds to the intracellular BCAA concentrations, but not to physiological fluctuations in intracellular GTP (PubMed:18024519)
Strongly inhibited by tannic acid and Bromocresol Purple
Higher dietary salt intake stimulates transcription (PubMed:18579702). Chorionic gonadotropin stimulates expression in the ovaries (PubMed:27169804)
Competitively inhibited by 2-deoxy-glucose
Maintained as a monomer in an autoinhibited state (By similarity). Phosphorylation and activation follow the following steps: innate adapter protein TASL recruits IRF5, thereby licensing IRF5 for phosphorylation by IKBKB (By similarity). Phosphorylated IRF5 dissociates from the adapter proteins, dimerizes, and then enters the nucleus to induce IFNs (By similarity)
Activated by cleavage by B.anthracis lethal toxin (LT) endopeptidase: cleavage by LT promotes ubiquitination and degradation of the N-terminal part, releasing the cleaved C-terminal part of the protein (NACHT, LRR and PYD domains-containing protein 1b, C-terminus), which polymerizes and forms the Nlrp1b inflammasome (PubMed:19124602, PubMed:19651869, PubMed:19949100, PubMed:22536155, PubMed:23818853, PubMed:24492532, PubMed:24935976, PubMed:31383852, PubMed:30872531). Activated by S.flexneri IpaH7.8, an E3 ubiquitin ligase that mediates ubiquitination and degradation of the N-terminal part, releasing the cleaved C-terminal part of the protein, which polymerizes and forms the Nlrp1b inflammasome (PubMed:30872533). Nlrp1b inflammasome is inhibited by DPP8 and DPP9, which sequester the C-terminal fragment of Nlrp1b (NACHT, LRR and PYD domains-containing protein 1b, C-terminus) in a ternary complex, thereby preventing Nlrp1b oligomerization and activation (PubMed:29396289, PubMed:31525884). Nlrp1b inflammasome is activated by Val-boroPro (Talabostat, PT-100), an inhibitor of dipeptidyl peptidases DPP8 and DPP9 (PubMed:29396289, PubMed:31525884, PubMed:31383852, PubMed:30872531). Val-boroPro relieves inhibition of DPP8 and/or DPP9 by promoting disruption of the ternary complex, releasing its C-terminal part from autoinhibition (By similarity). Activated by metabolic inhibitors, such as 2-deoxy-D-glucose and sodium azide, by nutrient deprivation and hypoxia, possibly due to a decrease in cytosolic ATP (PubMed:24935976, PubMed:23230290). Also activated by Toxoplasma gondii (PubMed:24218483). Not activated by muramyl dipeptide, nor by full-length bacterial peptidoglycan (PubMed:22753929). Contrary to its human ortholog, not activated by positive-strand RNA virus such as Semliki Forrest virus or long dsRNA (PubMed:33243852)
Resistant to pentalenolactone
Serine-threonine kinase activity is inhibited by linear polyubiquitination ('Met-1'-linked) by the LUBAC complex (By similarity). Inhibited by necrostatins, including necrostatin-1, necrostatin-3 and necrostatin-4 (PubMed:23473668)
Inhibited by propargylglycine
Negatively regulated by the anti-sigma-I factor RsgI
Inhibited by DEPC and HgCl(2)
Allosterically activated by magnesium, and possibly also other divalent metal cations. Allosterically activated by ATP, ADP or GTP. Competitively inhibited by malonate
GTPase is competitively inhibited by GDP but not by ADP, ATP, CTP or UTP
Inhibited by HIV protease inhibitors, such as lopinavir, tipranavir and nelfinavir, leading to defects in lamin A/LMNA maturation and accumulation of prelamin-A/C precursors in cells (PubMed:17652517, PubMed:27462105). This causes defecs in nuclear envelope integry and release of DNA in the cytosol, activating the AIM2 inflammasome (PubMed:27462105)
Inhibited by Fe(2+) and to a lesser extent by Mn(2+)
Competitively inhibited by adenosine 5'-(3-thio)triphosphate and beta,gamma-methylene-ATP
Activated by DAG and phorbol esters. Phorbol-ester/DAG-type domain 1 binds phorbol ester with high affinity and mediates accumulation at the cell periphery. Phorbol-ester/DAG-type domain 2 binds phorbol ester with low affinity but may mediate initial contact, resulting in a conformational change allowing previously occluded domain 1 to anchor the kinase. Phosphorylation on Thr-626 is then also required for activation and may also result in a further conformational change (By similarity)
Adenine transport is strongly inhibited by decynium-22
6-mercaptopurine-transport is inhibited by 6-thioguanine, 6-methylmercaptopurine and decynium-22
Inhibited by excess of Ca(2+)
Weakly inhibited by citrate, but not by asparagine
Ni(2+) and Co(2+) ions greatly increase hydrolase activity
Ihnhibited by hemin
The activity is calcium-dependent (By similarity). Requires phosphatidylserine for maximal activity (By similarity)
Inhibited by maleic acid, iodoacetamide, iodoacetate and, most particularly, pyrrole-2-carboxylic acid
Inhibited by SERPINA1, SERPINC1 and SERPING1
Inactive below 20 degrees Celsius and pH 6.0. Inhibited by divalent cations
Activated by calcium/calmodulin. Inhibited by high concentrations of the substrate Ins(1,2,4)P3, and allosterically activated by the product Ins(1,3,4,5)P4
Inhibited by isovalerate, pyruvate, 3-methyl-2-butanone, and valine. Partially inhibited by formaldehyde and tetrahydrofolate below or near the KM value. Also inhibited by later intermediates pantoate, pantothenate and coenzyme A
Inhibited by the serine protease inhibitor PMSF, but not by benzamidine, alpha 1-antitrypsin, alpha 1-antichymotrypsin. Not inhibited by metalloprotease inhibitors such as EDTA and orthophenanthroline
Uptake is activated by hyperosmotic stress (PubMed:7642496, PubMed:9446558, PubMed:10625602, PubMed:15134432, PubMed:19262666, PubMed:21364531, PubMed:24141878). Osmoresponsive activation is triggered by a change in the internal K(+) concentration (PubMed:11574473, PubMed:15063732). In addition, shows a pronounced chill stimulation, at temperatures around 10 degrees Celsius (PubMed:15995189, PubMed:17693504). Chill activation may be influenced by the membrane lipid composition (PubMed:17693504). Uptake is completely abolished by the uncoupler CCCP, and to a different extent by the ionophores valinomycin and nigericin (PubMed:7642496)
Inhibited by Zn(2+), whereas Ni(2+), Fe(2+), and Cu(2+) have little or no effect on activity
Activated by K(+) (Probable). Activity is increased in the presence of Na(+) (By similarity)
Directly inhibited by buparvaquone and juglone anti-parasite drugs. Inhibited at lesser degree by the non-quinone inhibitor dipentamethylene thiuram monosulphide (DTM)
Its activity is increased by calorie restriction, which slows the pace of aging and increases maximum lifespan. Activated by resveratrol (3,5,4'-trihydroxy-trans-stilbene), which is found in red wine
Repressed by steroid (4-MA, VG106, PD91, PD17, Finasteride) and non-steroid (AS601811, AFA27, AFA76, AFA131, AFA192) inhibitors; steroid inhibitors are generally more efficient
Mono-ADP-ribosyltransferase activity of PARP3 is selectively inhibited by ME0328 compound; ME0328 does not inhibit other ARTD/PARP enzymes, such as PARP1 (PubMed:23742272). Mono-ADP-ribosyltransferase is strongly inhibited by KU0058948 compound (PubMed:19354255)
Uptake is inhibited by carbonyl cyanide m-chlorophenylhydrazone (CCCP)
The 5'-3' ssDNA and dsDNA exonuclease and ssDNA endonuclease activities are inhibited by SSB
Up-regulated by calmodulin which increases the affinity of the pump for Ca(2+) ions
Phospholipase activity is specifically activated upon 3',3'-cGAMP binding. Is not activated by the other cyclic dinucleotides 3',3'-cUAMP, 3',3'-c-diAMP and 3',3'-c-diGMP. Therefore, is specifically activated by only the nucleotide synthesized from its adjacently encoded nucleotidyltransferase (DncV)
Maintained as a monomer in an autoinhibited state (PubMed:25326420). Phosphorylation and activation follow the following steps: innate adapter protein TASL recruits IRF5, thereby licensing IRF5 for phosphorylation by IKBKB (By similarity). Phosphorylated IRF5 dissociates from the adapter proteins, dimerizes, and then enters the nucleus to induce IFNs (PubMed:25326420)
Phosphorylation at Thr-14 or Tyr-15 inactivates the enzyme, while phosphorylation at Thr-180 activates it
Regulated by a negative feedback mechanism through sterols and non-sterol metabolites derived from mevalonate (By similarity). Phosphorylation at Ser-869 down-regulates the catalytic activity (By similarity)
Inhibited by aminooxyacetate (in vitro)
Cell cycle-regulated, with maximal activity in the S-phase (PubMed:10523312, PubMed:20016786). Rapidly and transiently inhibited by phosphorylation following the generation of DNA double-stranded breaks during S-phase, probably by CHEK1, possibly at Ser-750 (PubMed:12660173, PubMed:12955071). This inhibition is cell cycle checkpoint- and ATM-dependent (PubMed:12955071)
Regulated by circadian protein CLOCK (Circadian Locomotor Output Cycles Kaput)
Inhibited by Sirtinol, A3 and M15 small molecules. Inhibited by nicotinamide (By similarity)
Phosphorylation by CSK at Tyr-530 inhibits kinase activity. Inhibitory phosphorylation at Tyr-530 is enhanced by heme. Further phosphorylation by CDK1 partially reactivates CSK-inactivated SRC and facilitates complete reactivation by protein tyrosine phosphatase PTPRC. Integrin engagement stimulates kinase activity. Phosphorylation by PTK2/FAK1 enhances kinase activity. Butein and pseudosubstrate-based peptide inhibitors like CIYKYYF act as inhibitors. Phosphorylation at Tyr-419 increases kinase activity
Inhibited by the toxins okadaic acid, tautomycin and microcystin Leu-Arg (By similarity). The phosphatase activity of the PPP1R15A-PP1 complex toward EIF2S1 is specifically inhibited by Salubrinal, a drug that protects cells from endoplasmic reticulum stress
Is activated by the monovalent cation potassium
Polyethylene glycol (PEG) stimulates whereas glycerol inhibits the aquaporin activity
Is specifically blocked by omega-conotoxin GVIA (Probable) (PubMed:10938268). Is specifically blocked by omega-conotoxin MVIIA (ziconotide) (By similarity). Is insensitive to dihydropyridines (DHP)
Acetylation inhibits the helicase activity
Phosphorylation at Thr-172 is necessary for enzymatic activity
Regulated by autophosphorylation, can both activate or decrease activity. Heme regulates its activity by enhancing the phosphorylation on Tyr-1007 and Tyr-1008
Ethanol and carbon monoxide-bound heme increase channel activation. Heme inhibits channel activation (By similarity). Phosphorylation of Thr-139 leads to inhibition of channel activity by ethanol
The structure reveals a short flexible hairpin turn that partially occludes the active site and may be involved in autoregulation
Inhibited by hesperadin
Inactivated by interferon-induced RSAD2. This inactivation may result of disruption of lipid rafts at the plasma membrane, and thus have an antiviral effect since many enveloped viruses need lipid rafts to bud efficiently out of the cell (By similarity)
Inhibited by phosphorylated compounds such as AMP, ADP, ATP, 3-phosphoglyceric acid and PPi. Not inhibited by orthophosphate. Activity is high in cells grown in low glucose concentrations and decreases dramatically as glucose concentration increases
Stimulated by calcium/calmodulin. Inhibited by L-NAME. Not activated by tetrahydrobiopterin (BH4), FAD, FMN, or heme
Activity is inhibited by both beta-cyclodextrin or amylose that block the access to the active site
Inhibited by benzamidine, (4-amidino-phenyl)-methane-sulfonyl (APMSF), N-p-tosyl-L-lysine chloromethylketone (TLCK), gabexate, mesylate, BABIM and trypsin soybean inhibitor (TSI)
Repressed by sodium carbonate, sodium bicarbonate and K-phosphate
The protein undergoes a dramatic conformational switch from closed to open states upon substrate-binding, which enables specific substrate recognition for the 1''-O-linkage (By similarity). The glutamate flap (Glu-33) blocks substrate entrance to Mg(2+) in the unliganded closed state (By similarity). In presence of substrate, Glu-33 is ejected from the active site: this closed-to-open transition significantly widens the substrate-binding channel and precisely positions the scissile 1''-O-linkage for cleavage while securing tightly 2'- and 3'-hydroxyls of ADP-ribose (By similarity). Activity is inhibited by calcium (PubMed:30472116)
Shows high stability to high concentrations of acetaldehyde
Autorepressed by intramolecular binding of the C-terminus which dissociates following phosphorylation by NEK2. Activated in response to DNA damage. Inhibited by zinc
Strongly inhibited by EDTA (PubMed:33603127). Not inhibited by E-64 and PMSF, broad-spectrum cysteine and serine protease inhibitors (PubMed:33603127)
The deacetylase activity is specifically inhibited by N-Ethylmaleimide (PubMed:8483907). The sulfotransferase activity is specifically inhibited by 3',5'-ADP (PubMed:8483907)
Rab activation is generally mediated by a guanine exchange factor (GEF), while inactivation through hydrolysis of bound GTP is catalyzed by a GTPase activating protein (GAP). That Rab may be activated by DENND1C, a guanine exchange factor (By similarity). Activated in response to insulin
Inhibited by aprotenin. Not inhibited by EDTA, PMSF or leupeptin
DNA restriction requires S-adenosyl-L-methionine and Mg(2+), and is inhibited by S-adenosyl-homocysteine (PubMed:8451198). SAM may be a cofactor for DNA restriction (Probable)
Inhibited by EDTA, and O-phenanthrolene
Allosterically activated by benzodiazepines and the anesthetic alphaxalone (PubMed:30266951, PubMed:29950725). Allosterically activated by pentobarbital (By similarity). Inhibited by the antagonist bicuculline (PubMed:29950725)
Inhibited by L-methionine
Nitrite transport mediated by system 1 is very sensitive to inhibition by nitrate
Inhibited by calcium but not affected by chloride ions. Inhibited by amastatin and to a lower extent by bestatin. Weakly inhibited by puromycin
Activated by EGF. Arachidonic acid conversion is inhibited by (13S,14S)-epoxy-(4Z,7Z,9E,11E,16Z,19Z)-docosahexaenoate (13S,14S-epoxy-DHA) (By similarity). Arachidonate 12-lipoxygenase activity is decreased when PH decreases from 7.4 to 6 (By similarity)
Histone acetyltransferase activity is inhibited by GMNN in the context of a complex with CDT1, inhibiting histone H4 acetylation and DNA replication licensing (PubMed:20129055). Selectively inhibited by WM-3835 (N'-(4-fluoro-5-methyl-[1,1'-biphenyl]-3-carbonyl)-3- hydroxybenzenesulfonohydrazide) inhibitor (PubMed:31827282)
Hygromycin B inhibits RbbA ATPase activity and releases RbbA from 70S ribosomes
Phenyl isothiocyanate inhibits anion transport in vitro
The uptake of glucose is inhibited by cytochalasin B. Glucose uptake is increased in response to phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment: TPA-induced glucose uptake requires phosphorylation at Ser-226
The protein undergoes a dramatic conformational switch from closed to open states upon substrate-binding, which enables specific substrate recognition for the 1''-O-linkage (PubMed:29907568, PubMed:34321462). The glutamate flap (Glu-41) blocks substrate entrance to Mg(2+) in the unliganded closed state (PubMed:30045870, PubMed:29907568, PubMed:34321462). In presence of substrate, Glu-41 is ejected from the active site: this closed-to-open transition significantly widens the substrate-binding channel and precisely positions the scissile 1''-O-linkage for cleavage while securing tightly 2'- and 3'-hydroxyls of ADP-ribose (PubMed:30045870, PubMed:29907568, PubMed:34321462)
PPIase activity is inhibited by binding of nickel ions to the C-terminal metal-binding region and/or the C-terminal part of the PPIase domain. Folding activity is inhibited by FK506 and by permanently unfolded proteins, irrespective of their proline content
Activated by Ca(2+), Mg(2+) and Na(+) cations (PubMed:12764132). Inhibited by Zn(2+) (PubMed:12764132). Phosphatidylserine and phosphatidic acid stimulate while cardiolipin, phosphatidylcholine, lysophosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol and sphingomyelin inhibit the reverse ceramide synthase activity (PubMed:12764132). Phosphatidic acid, phosphatidylinositol and C16-ceramide inhibit the ceramidase/hydrolase activity (PubMed:12764132)
Autophosphorylation activates the kinase activity
Binding to DNA is abolished in the presence of high concentration of iron. Specifically binds to tetracycline, which leads to a conformational change in the structure of the protein and inhibits the DNA binding activity
Inhibited by 6-azido-6-deoxy-alpha,alpha-trehalose (ADT)
Allosterically inhibited by tyrosine and phenylalanine (PubMed:10564818). According to another report, seems not to be repressed by tyrosine and phenylalanine (PubMed:25160622). Activated by tryptophan, cysteine and histidine (PubMed:10564818, PubMed:25160622)
Pronounced pH dependence with sodium as substrate (PubMed:8496184). Ca(2+)/H(+) and Na(+)/H(+) antiporter activities are both inhibited by magnesium (PubMed:8496184). Ca(2+)/H(+) activity is inhibited by the proton ionophore carbonyl cyanide m-chlorophenylhydrazone (CCCP) (PubMed:8496184)
Activated by the guanine nucleotide-exchange factors RAPGEF3 and RAPGEF4 in a cAMP-dependent manner. Nucleotide exchange is also specifically stimulated by RAPGEF5, RASGEF1A and RASGEF1B
In the autoinhibited state the side chain of Phe-462 inserts into a hydrophobic groove in RING-0, occluding the ubiquitin acceptor site Cys-430, whereas the REP repressor element binds RING-1 and blocks its E2-binding site. Activation of PRKN requires 2 steps: (1) phosphorylation at Ser-65 by PINK1 and (2) binding to phosphorylated ubiquitin, leading to unlock repression of the catalytic Cys-430 by the RING-0 region via an allosteric mechanism and converting PRKN to its fully-active form. According to another report, phosphorylation at Ser-65 by PINK1 is not essential for activation and only binding to phosphorylated ubiquitin is essential to unlock repression
Inhibited by SCH 51866 and moderately, by zaprinast. Specifically inhibited by PF-04447943 (6-[(3S,4S)-4-methyl-1-(pyrimidin-2-ylmethyl)pyrrolidin-3-yl]-1-(tetrahydro-2H-pyran-4-yl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one) (PubMed:22328573)
Activated upon caspase cleavage to generate the XK-related protein 8, processed form. Does not act prior the onset of apoptosis
Allosterically activated by benzodiazepines (By similarity). Activated by pentobarbitol (PubMed:2561970). Inhibited by the antagonist bicuculline (PubMed:2561970). Inhibited by zinc ions (By similarity)
Inhibited by 3,4-dichloroisocoumarin and tetrahydrolipstatin in the absence of substrate, but by phenylmethylsulfonyl fluoride (PMSF) only in the presence of substrate. Several water-miscible solvents enhance the lipase hydrolytic activity in vitro. Tetrahydrofuran and N,N-dimethylformamide (both 50%) inactivate the enzyme with t1/2 of 5 minutes and t1/2 of 2 hours, respectively
Activity requires salt; 100 mM sodium or potassium salts of chloride, phosphate or sulfate are equally effective. Inactivated by O(2)
Inhibited bye p-chloromercuribenzoate and salicylaldehyde. Activated by salicylate
Is inhibited by phenylmethylsulfonyl fluoride and 3,4-dichloroisocoumarin. EDTA and iodoacetate (1 to 5 mM) have only little effect on the enzyme activity
Activated by bile salts such as sodium taurocholate
Inhibited by NSC95397
Inhibited by heparin, and to a lesser extent by DTT, Fe(3+) and Cu(2+). Not inhibited by reduced glutathione, L-cysteine, EDTA, Ca(2+) or Mg(2+)
Lysophospholipase D activity is increased by magnesium and manganese and inhibited by calcium in a concentration dependent manner (By similarity). Loss of lysophospholipase D activity by addition of EDTA (PubMed:25596343)
Inhibited by pyrimidine
Inhibited by NaF, molybdate and vanadate
Activated by low temperature of 18 degrees Celsius in ASER neuron
Inhibited by dipyridamole and moderately by IBMX. cGMP acts as an allosteric activator
Aldehydes with apolar groups are the most effective inhibitors. N-Methylated compounds are also inhibitory, but to a much lesser degree than the aldehydes. The alcohols are more inhibitory than the corresponding acids, and the inhibitory effect increases with the degree of methylation from ethanolamine to choline
Inhibited by Ag(+), Cu(2+), Hg(2+), Mn(2+), Pb(2+), Zn(2+) and p-chloromercuric benzoic acid
Activated by Ca(2+)/calmodulin. Binding of calmodulin results in conformational change that relieves intrasteric autoinhibition and allows phosphorylation of Thr-196 within the activation loop by CaMKK1 or CaMKK2. Phosphorylation of Thr-196 results in a 10-20-fold increase in total activity to generate Ca(2+)/calmodulin-independent activity. Autophosphorylation of the N-terminus Ser-11 and Ser-12 is required for full activation. Inactivated by protein phosphatase 2A (PPP2CA/PPP2CB) which dephosphorylates Thr-196, thereby terminating autonomous activity and helping to maintain the enzyme in its autoinhibited state
p54 and probably p47 forms are inhibited by the non-covalent interaction with the cleaved propeptide (PubMed:19214190). Inhibited by subtilisin propeptide-like protein SUB1-ProM (PubMed:31942933). Inhibited by small molecule MRT12113 (PubMed:18083098)
Strongly inhibited by p-chloromercuribenzoate. Also inhibited by N-ethylmaleimide and o-phenanthroline
Inhibited by diisopropylfluorophosphate (DFP), but not by hirudin
Flavin concentrations greater than 15 uM do not inhibit the NADH oxidation activity of the reductase component C1 but do affect the hydroxylation activity of the C1-C2 complex. Maximal reductase activity is achieved only upon HPA binding to the reductase component C1 before interaction with NADH. HPA stimulates the rates of both the reduction of FMN and release of reduced FMN from the reductase component
Inhibited by Mn(2+) and Ca(2+) ions. Maintains 17% and 60% of its enzymatic activity with Mn(2+) and Ca(2+), respectively. No significant change in activity by the addition of Na(+), K(+) and Mg(2+) ions
Is inhibited by 2-aminooxyacetate (AOA), a mimic of beta-alanine and a known inhibitor of aminotransferases
Inhibited by plitidepsin, a chemical compound extracted from the ascidian Aplidium albicans (PubMed:33495306). Specifically inhibited by didemnin B, a natural product that triggers ribosome stalling by preventing aminoacyl-tRNA (aa-tRNA) release from EEF1A1 on the ribosome (PubMed:26651998, PubMed:36264623). Specifically inhibited by ternatin-4, a small-molecule inhibitor that triggers ribosome stalling by traping EEF1A1 on the ribosome and preventing aminoacyl-tRNA (aa-tRNA) accommodation (PubMed:26651998, PubMed:36264623, PubMed:36123449, PubMed:36638793). Ribosome stalling by ternatin-4 causes ubiquitination and degradation of EEF1A1 (PubMed:36638793). Specifically inhibited by ternatin SR-A3, which differs from ternatin-4 by the addition of a single oxygen atom into the side chain of N-Me-Leu (PubMed:36123449). Inhibition by ternatin-4 can be reversed, while it is not the case for didemnin B (PubMed:36264623)
Inhibited by glucose and lactose
Inhibited by O-phenanthroline, but not by EDTA
Inhibited by pyridoxal 5'-phosphate, 4,7-diphenyl-1,10-phenanthroline, tannic acid, and mercurials (mercury dichloride, Mersalyl acid, p-hydroxymercuribenzoate)
The enzyme is subject to substrate inhibition by adenosine and is competitively inhibited by the adenosine analog iodotubercidin. Unlike other adenosine kinases it is not stimulated by inorganic phosphate. Activity is stimulated in the presence of potassium. Is inhibited by a series of 7-(het)aryl-7-deazaadenine ribonucleosides bearing small and bulky substituents in position 7; some of them display micromolar antimycobacterial activity and low cytotoxicity
Hydroxyisobutyrylation on Lys-121 (K121hib) decreases the DNA-binding activity of H-NS, promotes the expression of acid-resistance genes and enhances bacterial survival under extreme acid stress
The dehydrogenase activity is inhibited by 3',3'',5',5''-tetraiodophenolphthalein, phenolphthalein, genistein, quercetin, zearalenone and diethylstilbestrol
Inhibited by GDP and FAD
Activated by threonine and tyrosine phosphorylation by Mkk3 in response to environmental stress
Not inhibited by proline
Allosteric regulation by both substrate and reaction products
Inhibited by S-adenosylhomocysteine, adenosylornithine and products
Present in an inactive conformation in the absence of bound ligand. Binding of VEGFA, VEGFC or VEGFD leads to dimerization and activation by autophosphorylation on tyrosine residues (By similarity)
Inhibited by naringenin
Inhibited by hydrogen peroxide H(2)O(2) and FMN (PubMed:9862135). Completely repressed activity by Hg(2+) (PubMed:9862135)
In normal conditions, the protein kinase activity is inhibited; inhibition is relieved by various stress conditions (By similarity). Inhibited by heme: in presence of heme, forms a disulfide-linked inactive homodimer (By similarity). Heme depletion relieves inhibition and stimulates kinase activity by autophosphorylation. Inhibited by the heme metabolites biliverdin and bilirubin (By similarity). Induced by oxidative stress generated by arsenite treatment. Binding of nitric oxide (NO) to the heme iron in the N-terminal heme-binding domain activates the kinase activity, while binding of carbon monoxide (CO) suppresses kinase activity (By similarity). Protein kinase activity is also activated upon binding to the processed form of DELE1 (S-DELE1): interaction with S-DELE1 takes place in response to mitochondrial stress and triggers the integrated stress response (ISR) (PubMed:32132706, PubMed:32132707)
A sequential activation is proposed: autophosphorylation at consensus sites is leading to dimerization of the catalytic domain and activation segment exchange (producing an active confirmation of both kinase modules in trans) followed by phosphorylation at Thr-180 in the activation segment and at other regulatory sites (Probable). Phosphorylation at Thr-180, Thr-225 and Thr-265 is essential for activity. Inhibited by pyridone 6 (K00225), a potent, ATP-competitive inhibitor. Phosphorylation at Thr-180, Thr-225 and Thr-265 is essential for activity (By similarity)
Inhibited by thiosulfate, selenate, molybdate, tungstate, citrate and succinate
Efflux activity is inhibited by carbonyl cyanide m-chlorophenylhydrazone (CCCP) and reserpine, but not by o-vanadate or chlorpromazine (CPZ)
Strongly inhibited by p-chloromercuribenzoate (PCMB). Partially inhibited by bis-p-nitrophenylphosphate (BNPP). Not inhibited by DFP, PMSF, eserine or EDTA
Inhibited by azide and hydrazine
Inhibited by the sodium/calcium exchanger inhibitor CGP-37157 (PubMed:24898248). Strongly inhibited by zinc (PubMed:15060069)
Inhibited by LiCl or CaCl(2). Not inhibited by ascorbate
Subject to product inhibition by UDP
Inhibited by isoniazid metabolites. The prodrug isoniazid is metabolized to isoniazid-NADP adducts that inhibit the enzyme at subnanomolar concentration
Inactive in absence of double-stranded DNA (dsDNA) (By similarity). Homooligomerizes upon binding to dsDNA, dsDNA serving as an oligomerization platform (By similarity). AIM2 requires large dsDNA to generate a structural template that couples dsDNA ligand-binding and homooligomerization (By similarity). Homooligomerization is followed by recruitment of PYCARD/ASC to initiate speck formation (nucleation) (By similarity). AIM2 and PYCARD/ASC homooligomer filaments assemble bidirectionally and the recognition between AIM2 and PYCARD/ASC oligomers occurs in a head-to-tail manner (By similarity). Clustered PYCARD/ASC nucleates the formation of CASP1 filaments through the interaction of their respective CARD domains, acting as a platform for CASP1 polymerization and activation (By similarity). Active CASP1 then specifically processes protein precursors, such as gasdermin-D (GSDMD), IL1B and IL18, leading to the release of mature cytokines in the extracellular milieu or pyroptosis, depending on cell type (PubMed:27846608, PubMed:32350463). AIM2 can be activated in response to events that cause genomic DNA (HIV protease inhibitor nelfinavir) or mitochondrial DNA release in the cytoplasm (such as Perfluoroalkyl substance pollutants or cholesterol overload) (PubMed:27462105, PubMed:29033131, PubMed:34006824). Activation of the AIM2 inflammasome is inhibited by IFI202 (PubMed:19131592, PubMed:23850291). Activation of the AIM2 inflammasome is inhibited by TRIM11, which promotes autophagy-dependent degradation of AIM2 (By similarity)
Activated by phosphatidic acid (PA) and in response to the fungal elicitor xylanase
Inhibited by acetate and propionate. Irreversibly inhibited by cycloserine
The uptake of taurocholate is inhibited by taurolithocholate sulfate with an IC(50) of 9 uM. Pravastatin competitively inhibits the transport of taurocholic acid. Cyclosporin A, glibenclamide, rifampicin and troglitazonestrongly competitively inhibit the transport activity of taurocholate (By similarity). The canalicular transport activity of taurocholate is strongly dependent on canalicular membrane cholesterol content (By similarity) (PubMed:19228692). The uptake of taurocholate is increased by short- and medium-chain fatty acids. Cholesterol increases transport capacity of taurocholate without affecting the affinity for the substrate (By similarity)
Inhibited by SERPING1 and A2M
Inhibited by human histatin-3 1/24 (histatin-5)
Activity is high with beta-5 type stilbene and minimal with beta-1 type stilbene. A 4-hydroxyl group and trans-stilbene structure is essential for the binding of substrates to the enzyme
Reaction is unaffected by the ionophores valinomycin, valinomycin plus nigericin, and carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP)
Uptake is activated by osmotic stress (PubMed:16239220). Inhibited by CCCP (PubMed:9811661)
Inhibited by NADP(+) and weakly by dicoumarol
Negatively regulated by the anti-sigma-I factor RsgI4 (By similarity). Binding of the polysaccharide substrate to RsgI4 may lead to the release and activation of SigI4 (By similarity)
Exhibits an elevated basal enzymatic activity and is not regulated by diacylglycerol, phosphatidylserine, phorbol esters or calcium ions. Two specific sites, Thr-404 (activation loop of the kinase domain) and Thr-556 (turn motif), need to be phosphorylated for its full activation (By similarity)
Transacylase activity is inhibited by MJ33
Subject to product inhibition by NADP and GDP-fucose
Activated by LiCl and NH(4)Cl. Inhibited by dimethylsulfoniopropionate (DMSP). MMPA concentrations above 2 mM relieve the DMSP inhibition and 80% of activity is regained at an MMPA concentration of 8 mM
Activated by EGF (PubMed:8912711). Arachidonic acid conversion is inhibited by (13S,14S)-epoxy-(4Z,7Z,9E,11E,16Z,19Z)-docosahexaenoate (13S,14S-epoxy-DHA) (PubMed:23504711). Arachidonate 12-lipoxygenase activity is decreased when PH decreases from 7.4 to 6 (By similarity)
Inhibited by 1-(1-acetylpiperidin-4-yl)-3-(4-(trifl uoromethoxy)phenyl)urea (TPAU), 1-cyclohexyl-3-dodecylurea (CDU), 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA), 1-((3S, 5S, 7S)-adamantan-1-yl)-3-(5-(2-(2-ethoxyethoxy) ethoxy)pentyl)urea (AEPU), N-adamantyl-N[']-cyclohexyl urea (ACU), 4-(((1S, 4S)-4-(3-((3S, 5S, 7S)-adamantan-1-yl) ureido)cyclohexyl)oxy)benzoic acid (c-AUCB), 4-(((1R, 4R)-4-(3-((3S, 5S, 7S)-adamantan-1-yl)ureido)cyclohexyl)oxy)benzoic acid (t-AUCB), 4-(((1R, 4R)-4-(3-(4(trifluoromethoxy)phenyl)ureido)cyclohexyl)oxy)benzoic acid (t-TAUCB) and to a lesser extent by 8-(3-((3S, 5S, 7S)-adamantan-1-yl)ureido) octanoic acid (AUOA) (PubMed:21217101). Phosphatase activity is inhibited by dodecyl-phosphate, phospholipids such as phospho-lysophosphatidic acids and fatty acids such as palmitic acid and lauric acid (By similarity)
Kinase activity is tightly regulated. Activated in response to signaling from a cell surface receptor. Activation probably requires binding of a substrate via the SH2 domain, plus autophosphorylation at Tyr-713. Present in an inactive form in the absence of activating stimuli
Regulated by at least two independent mechanisms. First, it is inactivated via its interaction with securin/PTTG1, which probably covers its active site. The association with PTTG1 is not only inhibitory, since PTTG1 is also required for activating it, the enzyme being inactive in cells in which PTTG1 is absent. PTTG1 degradation at anaphase, liberates it and triggers RAD21 cleavage. Second, phosphorylation at Ser-1126 inactivates it. The complete phosphorylation during mitosis, is removed when cells undergo anaphase. Activation of the enzyme at the metaphase-anaphase transition probably requires the removal of both securin and inhibitory phosphate
Inhibited by the morpholine antifungal drug fenpropimorph
Regulated by calcium/calmodulin. Aspirin inhibits expression and function of this enzyme and effects may be exerted at the level of translational/post-translational modification and directly on the catalytic activity (By similarity)
Activated by phosphorylation at Thr-175 by GRIK1/SNAK2 and GRIK2/SNAK1 (PubMed:19339507). Inactivated by dephosphorylation at Thr-175 (PubMed:24179127). Inhibited by trehalose-6-phosphate (PubMed:19193861). Down-regulated by SR45 by affecting its stability (PubMed:27436712). Reduced kinase activity in response to H(2)O(2) treatment. The redox-state of Cys-177 seems to directly influence its kinase activity (PubMed:28940407). Down-regulated by FLZ6 and FLZ10 (PubMed:29406622)
The side chain of Glu-250 determines which of the two opposing activities (AMPylase or de-AMPylase) will take place. In response to endoplasmic reticulum stress, mediates de-AMPylase activity (By similarity). Adenylyltransferase activity is inhibited by the inhibitory helix present at the N-terminus: Glu-250 binds ATP and competes with ATP-binding at Arg-389, thereby preventing adenylyltransferase activity (By similarity). In unstressed cells, disengagement of Glu-250 promotes adenylyltransferase activity (By similarity). Activation dissociates ATP-binding from Glu-250, allowing ordered binding of the entire ATP moiety with the alpha-phosphate in an orientation that is productive for accepting an incoming target hydroxyl side chain (By similarity)
Stimulated by cytosolic Ca(2+) (PubMed:27399000, PubMed:29447909). Stimulated by anionic phospholipids such as phosphatidylserine (PubMed:29447909)
GAP activity is stimulated by phosphatidylinositol 4,5-bisphosphate (PIP2) and, to a lesser extent, by phosphatidylinositol 3,4,5-trisphosphate (PIP3). Phosphatidic acid potentiates PIP2 stimulation
Inhibited by EDTA and ADP
Down-regulated by Zn(2+), Cu(2+) and Fe(3+). No effect of K(+), NH(4+), Na(+), Ca(2+), Mg(2+), Mn(2+) and Fe(2+)
Phosphorylation at Thr-20 or Tyr-21 inactivates the enzyme, while phosphorylation at Thr-162 activates it
Subject to complex allosteric regulation. The enzyme can assume an active R-state, or an inactive T-state. Intermediate conformations may exist. AMP acts as allosteric inhibitor (PubMed:33977262). Fructose 2,6-bisphosphate acts as competitive inhibitor. Strongly inhibited by Ca(2+)
Optimal transglycosylase/glycosyltransferase (GT) activity in the presence of 30-40% dimethylsulfoxide and 0.002% Triton X-100. High GT activity in the presence of CHAPS, Triton X-100 and n-dodecyl-beta-D-maltopyranoside (DDM) detergents, and to a lesser extent in the presence of Cymal-5 (PubMed:22487093). GT activity is inhibited by moenomycin (PubMed:12867450, PubMed:22487093). 50% inhibition of the GT activity with 2.8 uM moenomycin. No effect on GT activity detected with 2.8 uM vancomycin, but complete inhibition with 28 uM vancomycin (PubMed:12867450). No GT activity in the presence of n-octyl-beta-D-glucopyranoside, Cymal-3 and Cymal-4 detergents (PubMed:22487093)
Strongly inhibited by carbonyl cyanide m-chlorophenylhydrazone (CCCP), and by spermidine via its interaction with the C-terminus. Also inhibited by N-ethylmaleimide and p-chloromercuribenzoic acid. Partially inhibited by KCN
Slightly inhibited by Ca(2+) and Mg(2+). Strongly inhibited by Zn(2+), Ni(2+) and Co(2+)
Not inhibited by adenosine, potently inhibited by MT-DADMe-immucillin A
Stimulated by phosphatidylinositol 4,5-bisphosphate. Is not responsive to either ADP-ribosylation factor-1 (ARF-1) or GTP-binding proteins such as RHOA
Completely inhibited by Hg(2+), Cu(2+) Ag(2+), and partially inhibited by Zn(2+), imidazole and EDTA. Activated by Ca(2+), Co(2+), Ni(2+)
Allosterically inhibited by isoleucine. Strain GM11b is isoleucine feedback insensitive and is resistant to the antimetabolite L-O-methylthreonine
Activated by phosphorylation at Tyr-493 in the activation loop. Inhibited by staurosporine
Inhibited by strychnine
Alanine--glyoxylate aminotransferase activity is inhibited by 1 mM (aminooxy)acetic acid by 97.5%
Activated by phosphorylation at Ser-359, Thr-645 and Thr-764 by MAPK1/ERK2, MAPK3/ERK1 and MAPK14/p38-alpha, and by further autophosphorylation of Ser-211, Ser-375 and Ser-380 by the activated C-terminal kinase domain. The active N-terminal kinase domain finally phosphorylates downstream substrates, as well as Ser-814, Ser-816 and Ser-822 in its own C-terminal region
Inhibited by intracellular coagulation inhibitor 2/LICI-2 and to a lesser extent by intracellular coagulation inhibitor 3/LICI-3
ssDNase activity is inhibited by the divalent cation chelator EDTA and the reducing agent DTT (PubMed:22506810). Divalent metal ions (e.g. Ca(2+), Mg(2+) and Zn(2+)) and DTT represses RNase activity (PubMed:22506810, PubMed:25157844). RNase activity is enhanced by EDTA (PubMed:22506810). Also repressed by vanadate (VO(4)(3-)) and phosphate (PO(4)(3-)) by occupying the active site (PubMed:25157844)
Inhibited by EDTA and 2-mercaptoethanol. Inhibited by 1 mM zinc ion and to a lesser extent by 1 mM calcium ion
CASK plays a role in regulation of CaMKII autophosphorylation. When complexed with CASK and in the presence Ca[2+]/CaM, autophosphorylation of Thr-287 causes constitutive activation of the kinase. In the absence of Ca[2+]/CaM, autophosphorylation of Thr-306 causes inactivation of the kinase
RNA helicase activity is inhibited by EDTA
Activated by histamine, L-adrenaline, L- and D-histidine, and L- and D-phenylalanine. Inhibited by coumarins, saccharin, sulfonamide derivatives such as acetazolamide (AZA) and Foscarnet (phosphonoformate trisodium salt)
Inhibited by 6-diazo-5-oxo-L-norleucine (DON). The inhibition is competitive with glutamine, but uncompetitive with chorismate
Inhibited by pyrophosphate
Calcium-independent and PIP2-dependent
Strongly inhibited by Antipain, E64 and Leupeptin, and weakly inhibited by iodoacetic acid (IAA) and phenylmethylsulfonyl fluoride (PMSF). Requires the presence of dithiothreitol (DTT) for activity
Calcium-calmodulin exerts its inhibitory effect in cAMP sensitivity by binding to IQ-like motif of CNGA4 and preferably binds to the channel in the closed state. Inhibition by PIP3 of the CNG channel probably occurs via CGNA2 binding (By similarity)
Activated by Ca(2+)/calmodulin. Binding of calmodulin may relieve intrasteric autoinhibition. Autophosphorylation does not alter activity or regulation by Ca(2+)/calmodulin. In part, activity is independent on Ca(2+)/calmodulin
Inhibited by DFP, and Hg(Cl)2
Activated by chelators like citrate, malate, and oxalate specially at alkaline pH
Inhibited by deprenyl
Inhibited by azide and cyanide. Subject to competitive inhibition by sulfite
Activated by calcium (PubMed:27923926). Upon calcium binding to the EF-hand domains, the C-terminus of the junction domain (J domain) undergoes a conformational change which results in the dissociation of the pseudo-substrate inhibitory motif from the catalytic domain. This, in turn may facilitate the autophosphorylation of the activation loop at Thr-231, which leads to the kinase activation (By similarity)
After binding to 2-5A (5'-phosphorylated 2',5'-linked oligoadenylates) the homodimerization and subsequent activation occurs. Inhibited by RNASEL inhibitor ABCE1/RLI, a cytoplasmic member of the ATP-binding cassette (ABC) transporter family
Benzyl triethylammonium cation (BTAC) acts as a competitive inhibitor of trichodiene synthase reaction in the presence of pyrophosphate (PPi) (PubMed:17678871)
Inhibited by glycyrrhetinic acid, carbenoloxone, 11-alpha-OH-progesterone and 11-beta-OH-progesterone
Mycophenolic acid (MPA) is a non-competitive inhibitor that prevents formation of the closed enzyme conformation by binding to the same site as the amobile flap. In contrast, mizoribine monophosphate (MZP) is a competitive inhibitor that induces the closed conformation. MPA is a potent inhibitor of mammalian IMPDHs but a poor inhibitor of the bacterial enzymes. MZP is a more potent inhibitor of bacterial IMPDH. Subject to product inhibition by XMP and NADH (PubMed:7903306). Also inhibited by ADP
The inhibitor KDOAM-25 and others inhibit its demethylase activity, resulting to cell cycle arrest in myeloma cells
H(2)O(2) activates the 3-hydroxylation and oxidative cyclization of tetrahydroxychalcone but inhibits reaction with pentahydroxychalcone. Inhibited by phenylthiourea
Inhibited by Stichodactyla helianthus peptide ShK (By similarity). Inhibited by millimolar levels of tetraethylammonium (TEA). Contrary to other channels, inhibited only by millimolar levels of 4-aminopyridine (4-AP) (PubMed:2367536, PubMed:1879548, PubMed:7643197, PubMed:10482766, PubMed:10414303)
Activated by autophosphorylation of its activation loop
Inhibited by citral, perillyl alcohol, geraniol, farnesol and geranyl geraniol
3'-5' exonuclease activity is activated by sodium and manganese (By similarity). 3'-5' exonuclease and 3'-phosphodiesterase activities are stimulated in presence of PCNA (By similarity)
Activated by a monovalent cation that binds near, but not in, the active site. The most likely occupant of the site in vivo is potassium. Ion binding induces a conformational change that may alter substrate affinity. Competitively inhibited by phosphonoacetic acid, etidronate, 2-carboxethylphosphonic acid, N-(phosphonomethyl)glycine, N-(phosphonomethyl)iminodiacetic acid and clodronate (By similarity)
Activated by calcium and phospholipids
Is completely inhibited by phenylmethanesulphonylfluoride (PMSF) in vitro
Tightly binds to CoA, which is presumably a feedback inhibitor (PubMed:21527250). Potently inhibited by D-amethopterin, which simultaneously occupies the 4'-phosphopantetheine- and ATP-binding sites; following treatment with D-amethopterin, H.pylori exhibits morphological characteristics associated with cell death, showing that D-amethopterin displays antimicrobial activity (PubMed:24040220)
Inactivated by low concentrations of cyanide in vitro
Activated by Ca(2+)/calmodulin. Binding of calmodulin results in a conformational change that generates functional binding sites for both substrate and ATP, and thus relieves autoinhibition and lowers the Km of substrate binding. Must be phosphorylated by ckk-1 to be maximally active but this does not appear to be required for activity in AFD neurons
rNTP addition and end joining activities are stimulated by Ku homodimer
Channel activity is blocked by dihydropyridines (DHP), phenylalkylamines, and by benzothiazepines
Could be activated by protein kinase C (By similarity). Strongly induced by calcium. Blocked by barium, tetraethylammonium (TEA), quinine and quinidine
Inhibited by phosphorylation (By similarity). Citrate promotes oligomerization of the protein into filaments that correspond to the most active form of the carboxylase (PubMed:20952656)
Beta-alanine uptake is inhibited by carbonyl cyanide m-chlorophenylhydrazone (CCCP), which dissipates the proton motive force
Classical (or conventional) PKCs (PRKCA, PRKCB and PRKCG) are activated by calcium and diacylglycerol (DAG) in the presence of phosphatidylserine. Three specific sites; Thr-497 (activation loop of the kinase domain), Thr-638 (turn motif) and Ser-657 (hydrophobic region), need to be phosphorylated for its full activation
3'-phosphoadenosine 5'-phosphate (pAp) is an inhibitor of KEM1. Sodium-induced GCN4 expression reduces pAp accumulation by activating HAL2 expression, and therefore maintains mRNA degradation capacity which is likely to be important for the accurate and rapid adaptation of gene expression to salt stress
Subject to complex allosteric regulation. The enzyme can assume an active R-state, or an inactive T-state. Intermediate conformations may exist. Activated by three-carbon carboxylic acids, phosphorylated three-carbon carboxylic acids and sulfate. Strongly activated by phosphoenolpyruvate and citrate. Inhibited by AMP, which affects the turnover of bound substrate and not the affinity for substrate. Allosterically inhibited by glucose 6-phosphate. AMP and glucose 6-phosphate act synergistically as allosteric inhibitors. Phosphoenolpyruvate antagonizes inhibition by AMP and glucose 6-phosphate. Fructose 2,6-bisphosphate acts as competitive inhibitor
Gyrase is the target of many classes of inhibitors, including coumarins, cyclothialidines, pyrrolopyrimidines, pyrazolthiazoles and (fluoro)quinolones. Coumarins bind to GyrB and are competitive inhibitors of its ATPase activity (PubMed:7811004). Cyclothialidines also bind GyrB and are ATPase competitive inhibitors; they seem to act differently from coumarins (PubMed:7811004, PubMed:8635474). Pyrrolopyrimidines inhibit both GyrB and its paralog in topoisomerase 4 (parE) (PubMed:23294697, PubMed:23352267, PubMed:24386374). Pyrazolthiazoles also inhibit the ATPase activity of GyrB (PubMed:20356737). Quinolones bind GyrA when the enzyme is complexed with DNA and trap the enzyme in a covalent reaction intermediate with DNA (PubMed:3031051, PubMed:12051842, PubMed:337300). Acriflavine inhibits DNA supercoiling and DNA-stimulated ATPase activity (PubMed:9148951). DNA supercoiling activity is protected from fluoroquinolone inhibition by QnrB4; QnrB4 has no effect on supercoiling activity alone (PubMed:19060136)
Inhibited by inositol hexakisphosphate and benzene tri-, tetra- and hexacarboxylates
Is markedly activated by the monovalent cations K(+), NH(4)(+), and Rb(+). Is significantly inhibited by ADP, AMP, p-chloromercuribenzoate, N-ethylmaleimide, pyrophosphate, and EDTA
Competitively inhibited by D-alanine, 8-amino-7-hydroxy-8-phosphonononanoic acid and 2-amino-3-hydroxy-2-methylnonadioic acid
Activity is inhibited by p-chloromercuribenzoate (pCMB), monoiodoacetamide, H(2)O(2), ATP, ADP, NADH, NADPH, Hg(2+) and Zn(2+)
Substrate inhibited by S-adenosyl-L-homocysteine
Inhibited by O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino N-phenylcarbamate (PUGNAc) (By similarity). Inhibited by galacto-NAG-thiazoline (PubMed:27149221)
Strongly inhibited by the cysteine protease inhibitor E64 (L-trans-epoxysuccinyl-leucylamide-(4-guanido)-butane). Not inhibited by the serine protease inhibitor PMSF, the aspartic protease inhibitor pepstatin A, or by the metal ion chelator 1,10-phenanthroline
Inhibited by palladium ions
Inhibited by N-acetylcastanospermine, 2-acet-amido-1,2-dideoxynojirimycin and PUGNAc
Activated by light-induced dephosphorylation. Inhibited by dark-induced phosphorylation. Both reactions are catalyzed by PDRP1. Inactivated by cold due to the dissociation of the homotetramer. Independent of circadian regulation (PubMed:24710069)
Enzyme activity is increased by phosphate, due to increased kcat and increased substrate affinity
Phosphate transport activity is competitively inhibited by vanadate and arsenate
Insensitive to calcium/calmodulin, forskolin and somatostatin. Stimulated by beta-adrenergic receptor activation. Activity is down-regulated by calcium/calcineurin
The ligand-induced conformational reorganization of the protein could be an important regulatory mechanism
Inhibited by AKT1, AKT2 and AKT3. Activated by oleic acid and arachidonic acid (PubMed:24892992)
Completely inhibited by Hg(2+), unaffected by EDTA
Inhibited by oxygen when heated in air at 80 degrees Celsius. The enzyme is reactivated by addition of dithionite
Inhibited by millimolar concentrations of warfarin
Competitively inhibited by the product (S)- or (R)-carvone
Activated by PDPK1/PDK1
Uncompetitive inhibition by micromolar concentrations of lithium. Competitive inhibition by inositol 1,4-bisphosphate (By similarity)
Activated by small peptides (By similarity). Activated by ATP and GTP, and to a lesser extent by CTP, TTP and PPPi (PubMed:17613531). Inhibited by bacitracin (PubMed:17055432, PubMed:17613531). In vitro modification of Cys residues impairs enzyme activity (PubMed:18986166)
Transport is inhibited by the sulfhydryl-specific modifier N-ethylmaleimide
Activated by chorismate and inhibited by dihydrofolate and methotrexate
Phosphorylation at Thr-162 is required for enzymatic activity. The association of p53/TP53 to the CAK complex in response to DNA damage reduces kinase activity toward CDK2 and RNA polymerase II repetitive C-terminal domain (CTD), thus stopping cell cycle progression (By similarity)
Up-regulated upon treatment with streptozotocin
Phosphatase activity repressed by oxidized GPX3 and phosphatidic acid (PA). PA is produced by PLD alpha 1 in response to ABA. Repressed by PYR/PYL/RCAR ABA receptors in an ABA-dependent manner
Inhibited by bathophenanthroline sulfonate, o-phenanthroline, 8-hydroxyquinoline, 2,2'-dipyridyl and p-chlormercuribenzoate. Also inhibited by Hg(2+), Cu(2+), Co(2+) and Fe(3+) ions
Kinase activity is stimulated by calcium/calmodulin, but blocked by chlorpromazine
The activity of TylM2 is substantially increased by the addition of the accessory protein TylM3
Inhibited by inorganic phosphate (Pi)
After binding to 2-5A (5'-phosphorylated 2',5'-linked oligoadenylates) the homodimerization and subsequent activation occurs. Inhibited by RNASEL inhibitor ABCE1/RLI, a cytoplasmic member of the ATP-binding cassette (ABC) transporter family (By similarity)
Activity is decreased by glutathione and ammonium ion
Activated in response of some unknown stimulus (PubMed:29924997). Not activated in response to L-monocytogenes infection (PubMed:29924997)
Partially inhibited by 1-10-phenanthroline; inactivation is irreversible (PubMed:18937627, PubMed:23703618). Partially inhibited by EDTA; inactivation is reversible (PubMed:23703618). Inhibited by broad-spectrum zinc metalloprotease inhibitor batimastat (PubMed:28820255). N-aryl mercaptoacetamide-based inhibitors have been isolated that act on clostridial collagenases with submicromolar affinity while having negligibile activity on human collagenases (PubMed:28820255)
Inhibited by 3-phosphoglycerate, 6-phosphogluconate, phosphoenolpyruvate (PEP), fructose 1,6-bisphosphate, glycolate, oxalate, and itaconate
Activity is high with beta-1 type stilbene and minimal with beta-5 type stilbene. A 4-hydroxyl group and trans-stilbene structure is essential for the binding of substrates to the enzyme. Inhibited by N-benzylideneaniline-hydroxy and -methoxy derivatives and N-(4-hydroxybenzyl)-3-methoxyaniline but not N-benzylideneaniline. Fluorinated olefin (Z)-1-fluoro-1(4-hydroxyphenyl)-2-phenylethylene is also a potent inhibitor. Imine linkage instead of ethylene bridge in the substrate enhances the inhibitory activity
Disulfiram reverses CDR1-mediated drug resistance by interaction with both ATP and substrate-binding sites of the transporter and may be useful for antifungal therapy
Inhibited by copper, mercury, UDP, UTP and partially by calcium, cadmium, iron and UMP. Not affected by cobalt, magnesium, manganese, zinc, nickel, tin, uridine, sadium malonate and glucose
Inhibited by 1-(2,5-dichlorophenyl)-3-(dimethylamino)propan-1-one (MD3)
Binding to mpp is required for catalytic activity (PubMed:2967109). Inhibited by metal chelator ethylenediaminetetraacetic acid (EDTA) (PubMed:2967109)
Enzymatic activity of DncV is inhibited by folate-like molecules, such as 5-methyltetrahydrofolate di-glutamate and 5-methyltetrahydrofolate, suggesting the existence of a signaling pathway that links folate-like metabolism cofactors to the regulation of cyclic dinucleotide second messenger synthesis (PubMed:25201413). Lacks a regulatory loop and is constitutively activated (PubMed:25131990)
Activated by calcium. Inhibited by the serine protease inhibitors 4-(2-aminoethyl)benzenesulphonyl fluoride (AEBSF), PMSF, di-isopropyl phosphofluoridate (DFP) and soybean trypsin inhibitor (SBTI). Not inhibited by benzamidine or iodoacetamide. Leupeptin and pepstatin A have a minor inhibitory action
Strongly inhibited by oxalate
Strongly inactivated by diisopropylfluorophosphate (DFP) and to a lesser extent by tosyl-L-lysine chloromethyl ketone (TLCK)
Retinol oxidation is inhibited by the detergent Tween 80. Ethanol inhibits both all-trans-retinol and 9-cis-retinol oxidation. 13-cis-retinol is an effective competitive inhibitor of the 9-cis-retinol oxidation. All-trans-retinoic acid is a powerful inhibitor of all-trans-retinol oxidation. 13-cis-retinoic acid is a powerful inhibitor of all-trans-retinol oxidation. Cimetidine competitively inhibited ethanol oxidation
Arsenate, pyrophosphate and polyphosphates up to 15 residues long inhibit phosphate binding, while organic phosphates do not
Has no constitutive proton transporter activity and has to be activated by long-chain fatty acids/LCFAs. Inhibited by purine nucleotides. Both purine nucleotides and LCFAs bind the cytosolic side of the transporter and directly compete to activate or inhibit it (PubMed:26038550). Activated by noradrenaline and reactive oxygen species. Despite lacking canonical translational encoding for selenocysteine, a small pool of the protein has been observed to selectively incorporate selenocysteine at 'Cys-252'. Selenocysteine-modified protein is highly sensitive to redox modification and may constitute a pool of protein highly sensitive to activation by elevated levels of reactive oxygen species (ROS) (By similarity)
Inhibited by aminoguanidine, amiloride and beta-aminopropionitrile
Inhibited by phenylmethanesulfonyl fluoride (PMSF) and butabindide, but not by peptidase inhibitor pepstatin, EDTA, nor bestatin
The enzyme is subject to substrate inhibition by adenosine and is competitively inhibited by the adenosine analog iodotubercidin. Unlike other adenosine kinases it is not stimulated by inorganic phosphate. Activity is stimulated in the presence of potassium, resulting in a 13- and 300-fold increase in the catalytic efficiency with adenosine and methyl-Ado as substrate, respectively; the stimulatory effects are not observed in the presence of NaCl or LiCl
Phosphorylation both activates and inactivates the enzyme depending on the site of phosphorylation
Inhibited by adenosine 3',5'-bisphosphate
Atypical PKCs (PRKCI and PRKCZ) exhibit an elevated basal enzymatic activity (that may be due to the interaction with SMG1 or SQSTM1) and are not regulated by diacylglycerol, phosphatidylserine, phorbol esters or calcium ions. Two specific sites, Thr-411 (activation loop of the kinase domain) and Thr-563 (turn motif), need to be phosphorylated for its full activation (By similarity). Might also be a target for novel lipid activators that are elevated during nutrient-stimulated insulin secretion
Activity is regulated by phosphorylation at Ser-49 and Ser-52, which stabilizes the eIF2/GDP/eIF-2B complex and prevents the eIF-2B-mediated exchange of GDP for GTP, thereby preventing the formation of the 43S pre-initiation complex (43S PIC). This results in the global attenuation of 5' cap-dependent protein synthesis and concomitant translation of ISR-specific mRNAs that contain a short upstream open reading frame (uORF) in their 5' UTR, such as ATF4, ATF5, DDIT3/CHOP and PPP1R15A/GADD34
Activated by phosphorylation; inhibited by dephosphorylation
Activity enhanced by Mg(2+) ion but inhibited by Zn(2+) ion
Rosmarinic acid inhibits the myotoxic activity (PubMed:22205953). Bromophenacyl bromide (BPB) inhibits the myotoxic activity through a covalent binding (PubMed:19616648). Caffeic acid and aristolochic acid, two plant compounds used in folk medicine used to treat envenomation, inhibit the myotoxic activity (PubMed:26192963)
Pyrazolthiazoles inhibit the ATPase activity of GyrB (PubMed:20356737)
DNA-binding activity is increased in the presence of L-arabinose and inhibited by the small molecule I-OMe-Tyrphostin
Activity is enhanced by Co(2+), Mn(2+) and Sr(2+), and decreased by Cu(2+)
Its enzymatic activities is reduced when it is exposed to Ca(2+), Zn(2+), Al(3+), Cu(2+) or Ni(2+) salts
Inhibited by warfarin (coumadin) (PubMed:33154105). Warfarin locks VKORC1 in both redox states into the closed conformation (PubMed:33154105)
Completely inhibited by Hg(2+), partially inhibited by Mn(2+), Cu(2+) and Pb(2+). Unaffected by Ca(2+), Mg(2+) and EDTA
Activated by the binding of calmodulin in the presence of Ca(2+)
Activity is presumably regulated by its sequestration in vesicles before egg fertilization. After fertilization and upon NADase release, it could then be regulated via its potential phosphorylation sites
Inhibited by leucyl-ethionine
Serine transport is strongly inhibited by KCN, an inhibitor of the respiratory chain, or by CCCP
The GTPase activity is stimulated in the presence of the 60S ribosomal subunit
Not inhibited by cAMP (PubMed:18590734). Inhibited by zaprinast (PubMed:16038615, PubMed:18590734)
Allosterically regulated; subject to end product regulation by purine nucleotides
AMP and XMP inhibit AICAR formyltransferase activity (By similarity). AICAR formyltransferase activity is competitively inhibited by 2-[5-hydroxy-3-methyl-1-(2-methyl-4-sulfo-phenyl)-1H-pyrazol-4-ylazo]-4-sulfo-benzoic acid (326203-A) (PubMed:15355974). FAICAR cyclization is competitively inhibited by 1,5-dihydroimidazo[4,5-c][1,2,6]thiadiazin-4(3H)-one-2,2-dioxide and the corresponding nucleoside and nucleoside monophosphate (PubMed:17324932)
Is inhibited by the anti-epileptic drug valpromide (Ki value of about 100 uM)
Competitively inhibited by the key pollutants 1,2-dichloroethane (1,2-DCE) and 1,2-dichloropropane (1,2-DCP)
Partially inhibited by magnesium ions and completely inhibited by zinc ions These divalent cations may act as competitive antagonists of the cofactor
Is not inhibited by (S)-lysine, in contrast to E.coli DapA
Activated by Cu(2+) and to a lesser extent by Ag(+) and Cu(+)
Methyltransferase activity is inhibited by BIX-01294. Efficiently inhibited by compound E72, a BIX-01294 derivative in which the diazepane ring and the benzyl are replaced with a 3-dimethylaminopropyl and a 5-aminopentyl group at sites B and C, respectively (By similarity)
Inhibited by calcium and magnesium ions and spermidine. Enhanced by KCl, NaCl and NH(4)Cl in concentrations from 0.1-0.25 M. Concentrations of more than 0.3 M are inhibitory
In contrast to nucleotidases from other families, is not inhibited by ribo- and deoxyribonucleoside di- and triphosphates
The efflux and influx of formate are mechanistically distinct processes that are controlled by the interplay between the conserved pore residues Thr-91 and His-209 (PubMed:35390794). The direction of formate translocation depends on external pH and electron donor source (PubMed:30247527). Interaction with PflB is important for optimal translocation of formate by FocA (PubMed:24887098). The N-terminal domain may also have a role in gating formate access (PubMed:33169422)
Activated by phosphorylation of Thr-31
Resistant to treatment with 5% SDS, 8 M urea, 10% Triton X-100 or 10% Tween-20. Fully active although less stable in the presence of 10 mM EDTA. Activity not affected by the absence or presence of 10 mM CaCl(2). Unstable in the presence of 2 M or over GdnHCl and loses 35% and 99% of its activity upon incubation with 2 and 4 M GdnHCl, respectively, for 1 hour at 55 degrees Celsius. Nearly fully loses activity upon incubation at pH 2.0
Activated by X-ray, histamine, L-adrenaline, L- and D-phenylalanine, L- and D-histidine, L-His-OMe and beta-Ala-His (carnosine). Competitively inhibited by saccharin, thioxolone, coumarins, 667-coumate, celecoxib (Celebrex), valdecoxib (Bextra), SC-125, SC-560, diclofenac, acetate, azide, bromide, sulfonamide derivatives such as acetazolamide (AZA), methazolamide (MZA), ethoxzolamide (EZA), dichlorophenamide (DCP), brinzolamide, dansylamide, thiabendazole-5-sulfonamide, trifluoromethane sulfonamide and N-hydroxysulfamide, fructose-based sugar sulfamate RWJ-37497, and Foscarnet (phosphonoformate trisodium salt). Repressed strongly by hydrogen sulfide(HS) and weakly by nitrate (NO(3)). Esterase activity weakly reduced by cyanamide. N-hydroxyurea interfers with zinc binding and inhibit activity
Oxygen is necessary for cyanogenesis. Activated by succinate, glycine methyl ester, glucose and D,L-methionine in addition to glycine. Phenazine methosulfate, methylene blue, 2,6-dichlorophenolindophenol (DCIP) and ferricyanide can replace oxygen for the reaction. Inhibited by pyrrolnitrin and acriflavine at 1 mM concentration
Shows preference for transcripts carrying a monophosphate group at the 5' end
Efflux is inhibited by reserpine
Homodimerization or heterodimerization is required for the choline and ethanolamine kinase activities
Its platelets aggregating activity is inhibited by chlorpromazine, theophylline mepacrine. Its platelet aggregating activity and its amidolytic activity are inhibited by PMSF, TPCK, TLCK and soybean trypsin inhibitors. Is unaffected by hirudin or by antithrombin-III in the presence of heparin
Inhibited by glycerol
Stimulated by ZDP (PubMed:22325353). Stimulated by XRCC1 (PubMed:23316050)
Putrescine and N(8)-acetylspermidine are competitive inhibitors of spermidine acetylation
DNA supercoiling inhibited by (fluoro)quinoline antibiotics such as sparfloxacin and levofloxacin, which usually act on GyrA subunit (PubMed:15047530). DNA supercoiling inhibited by the coumarin antibiotic novobiocin which acts on GyrB (PubMed:16876125). Quinolones lead to gyrase-mediated dsDNA cleavage while preventing reclosure (PubMed:15047530, PubMed:16876125, PubMed:23869946). DNA supercoiling activity inhibited by aminopyrazinamide and pyrrolamide derivatives, probably via effects on the GyrB subunit (PubMed:23268609, PubMed:24126580). DNA relaxation inhibited by ATP and its analogs (PubMed:16876125). DNA supercoiling, relaxation, decatenation and quinolone-promoted DNA cleavage are inhibited by MfpA (50% inhibition occurs at 2 uM), inhibition of gyrase activities is enhanced in a concentration-dependent manner by MfpA (PubMed:19060136)
Competitively inhibited by NAD(+). Inhibited by mercurials such as p-chloromercuribenzoate (PCMB) and HgCl(2). Enzymatic activity increases under anaerobic conditions
Activated by the AGRIN-induced phosphorylation which is mediated by MUSK
Inhibited by alpha(2)-macroglobulin, diisopropylfluorophosphate (DFP) and PMSF. Low inhibition by tosyl-L-lysine chloromethyl ketone
Autoinhibited. Intramolecular binding of the interdomains A and B (also called linker region) to parts of the catalytic domain keep the catalytic center in an inactive conformation. The phosphorylation of the interdomains or the binding of the SH2 domains with dually phosphorylated ITAM domains on transmembrane proteins disrupt those intramolecular interactions allowing the kinase domain to adopt an active conformation. The phosphorylation of SYK and of the ITAM domains which is responsible for SYK activation is essentially mediated by SRC subfamily kinases, like LYN, upon transmembrane receptors engagement. Downstream signaling adapters and intermediates may mediate positive and/or negative feedback regulation (By similarity)
Ca(2+) increases protease activity
Inhibited by triclosan and acrylamide
Inhibited by S-adenosyl-L-homocysteine (SAH)
Inhibited by aristolochic acid
Binding to RseA is inhibited by LPS fragments; phosphorylated N-acetylglucosamine (GlcNAc) with N-linked acyl chains are minimally necessary to disrupt binding to RseA. Once RseB is no longer bound to RseA the latter is susceptible to DegS degradation. Thus if periplasmic LPS levels increase the sigma-E regulon is induced
Inhibited by sarcosine
Inhibited by sodium orthovanadate
Probably not activated by nitric oxide (NO). Homodimer is slightly stimulated by the NO donor sodium nitroprusside (SNP) but not the NO donor DEA-NONOate or the NO-independent activator YC-1. Heterodimer also exhibits some stimulation, some compounds (SIN-1 and two of the NONOates) that were ineffective at stimulating Gyc-88E alone did stimulate the heterodimer
Strongly inhibited by alpha2-plasmin inhibitor and DFP. Partially inhibited by benzamidine, leupeptin and PCMB
Competitively inhibited by glyphosate (PubMed:12430021, PubMed:6229418). Inhibited by (S)- and (R)-phosphonates analogs (PubMed:15736934). Inhibited by (R)-difluoromethyl analogs of the tetrahedral reaction intermediate (PubMed:16225867). Inhibited by bromopyruvate (PubMed:1899181)
Unaffected by EDTA, Mg(2+), Mn(2+), Fe(2+), Ca(2+), Co(2+) and Zn(2+)
Channel activity is regulated by phosphorylation. Channel activity is regulated by intracellular Ca(2+)
Hydrolysis of liposomal sphingomyelin is stimulated by incorporation of diacylglycerol (DAG), ceramide and free fatty acids into the liposomal membranes (PubMed:25339683). Phosphatidylcholine hydrolysis is inhibited by incorporation of cholesterol, ceramide, DAG, monoacylglycerol and fatty acids (PubMed:25339683). Antidepressants, namely amitriptyline, imipramine, desipramine, fluoxetine, sertraline, escitalopram, and maprotiline inhibit sphingomyelin phosphodiesterase activity (PubMed:33163980, PubMed:22573858)
(Microbial infection) The secretory form is activated by P. aeruginosa, this activation results in the release of ceramide in the outer leaflet of the plasma membrane
(Microbial infection) The secretory form is activated by human coronavirus SARS-CoV-2, this activation results in the release of ceramide in the outer leaflet of the plasma membrane
Strongly inhibited by antipain and PMSF. Inhibited by benzamidine and aprotinin by 80% and 17% respectively. Little or no inhibition by EDTA, E-64, iodoacetic acid, leupeptin and FUT-175
Allosterically inhibited by dimers of the product c-di-GMP
Inhibited by 4-aminopyridine (4-AP) and by tetraethylammonium (TEA) (PubMed:2539643). Inhibited by kaliotoxin (KTX) (PubMed:23725331)
Strongly inhibited by 10% dimethyl sulfoxide
The tumor necrosis factor (TNF), as well as endotoxins and pro-inflammatory stimuli such as polyinosine-polycytidine (poly(IC)), lipopolysaccharides (LPS), peptidoglycan (PGN), flagellin, or lipid A activate MAP4K2 by promoting its autophosphorylation
Inhibited by borate, fluoride, L-Asn and L-Asp, but not by phenylphosphorodiamidate
Is prone to inactivation during catalytic turnover due to the occasional loss of the 5'-deoxyadenosine moiety and formation of the inactive cob(II)alamin cofactor in its active site. The GTPase activity of IcmF powers the ejection of the inactive cofactor and requires the presence of an acceptor protein, adenosyltransferase (ATR), for receiving it. ATR, in turn, catalyzes an adenosylation reaction converting cob(II)alamin in the presence of ATP and a reductant to the active AdoCbl cofactor. The repaired cofactor is then reloaded onto IcmF in a GTPase-gated step, regenerating active enzyme. The GTPase activity of IcmF is significantly decreased in the presence of excess of AdoCbl or cob(II)alamin and is higher in the apoenzyme state, indicating that the G-domain senses the presence and identity of the cofactor in the mutase active site
Inactivated by oxygen
Requires calcium ions (PubMed:19014349). Inhibited by exogenous phosphatidylserine (PubMed:24241535)
Hemagglutination activity is inhibited by lactose (MIC=2.5 mM), galactose (MIC=10 mM), and raffinose (Ref.5, PubMed:16309723, PubMed:28003128). Is very weakly or not inhibited by gentamicin, kanamycin, glucose and sucrose (PubMed:16309723, PubMed:28003128)
Activated by 1,2-diacyl-sn-glycero-3-phosphate/phosphatidic acid irrespective of its acyl chain composition
Inhibited, in a time-dependent manner, by phenyl phosphorodiamidate, which forms a covalently modified Ser-189
Exists in an autoinhibited state in the absence of substrate protein, due to interactions of the leucine-rich repeat domain with the catalytic domain. Is activated upon binding to a substrate protein (By similarity)
In the resting state, through the dimerization of its C-terminal domain, HSP90 forms a homodimer which is defined as the open conformation (By similarity). Upon ATP-binding, the N-terminal domain undergoes significant conformational changes and comes in contact to form an active closed conformation (By similarity). After HSP90 finishes its chaperoning tasks of assisting the proper folding, stabilization and activation of client proteins under the active state, ATP molecule is hydrolyzed to ADP which then dissociates from HSP90 and directs the protein back to the resting state (By similarity). Co-chaperone TSC1 promotes ATP binding and inhibits HSP90AA1 ATPase activity (PubMed:29127155). Binding to phosphorylated AHSA1 promotes HSP90AA1 ATPase activity (PubMed:29127155). Inhibited by geldanamycin, Ganetespib (STA-9090) and SNX-2112 (By similarity)
Activated by Pb(2+) and Hg(2+) ions (PubMed:23659204, PubMed:29748552). Phosphorylation at Thr-161 by PKC/PKCD increases its phospholipid scramblase activity during both cell stimulation and apoptosis (PubMed:10770950)
Peroxidase activity is inhibited by aminobenzohydrazide
The formation of the proteasomal ATPase ARC-20S proteasome complex, likely via the docking of the C-termini of ARC into the intersubunit pockets in the alpha-rings, may trigger opening of the gate for substrate entry. Interconversion between the open-gate and close-gate conformations leads to a dynamic regulation of the 20S proteasome proteolysis activity (By similarity). PPS auto-regulates its own activity via pupylation and degradation of its components (PubMed:24986881). Peptidolytic activity is inhibited by N-acetyl-Leu-Leu-norleucinal (Ac-LLnL) in vitro (PubMed:9282749)
Activated by cell stresses such as DNA damage, heat shock, osmotic shock, anisomycin and sodium arsenite, as well as pro-inflammatory stimuli such as bacterial lipopolysaccharide (LPS) and interleukin-1. Activation occurs through dual phosphorylation of Thr-180 and Tyr-182 by either of two dual specificity kinases, MAP2K3/MKK3 or MAP2K6/MKK6, and potentially also MAP2K4/MKK4, as well as by TAB1-mediated autophosphorylation. MAPK14 phosphorylated on both Thr-180 and Tyr-182 is 10-20-fold more active than MAPK14 phosphorylated only on Thr-180, whereas MAPK14 phosphorylated on Tyr-182 alone is inactive. whereas Thr-180 is necessary for catalysis, Tyr-182 may be required for auto-activation and substrate recognition. Phosphorylated at Tyr-323 by ZAP70 in an alternative activation pathway in response to TCR signaling in T-cells. This alternative pathway is inhibited by GADD45A. Inhibited by dual specificity phosphatases, such as DUSP1, DUSP10, and DUSP16. Specifically inhibited by the binding of pyridinyl-imidazole compounds, which are cytokine-suppressive anti-inflammatory drugs (CSAID). SB203580 is an inhibitor of MAPK14
Inhibited by ionic detergents SDS (anions) and CTAB (cationic). Strongly inhibited by Zn(2+)
Competitively inhibited by piericidin A, non-competitively inhibited by 2-n-heptyl-4-hydroxyquinoline N-oxide, NaN(3) and KCN; 50% inhibition occurs at 2 uM, 2 uM, 15 mM and 10 uM, respectively. Inhibited by Zn(2+) and Cd(2+)
Not inhibited by lithium (By similarity). Partial allosteric regulation on ions sodium binding (By similarity)
Activated through phosphorylation by atr or atm in response to DNA damage or inhibition of DNA replication
Inhibited by O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino N-phenylcarbamate (PUGNAc). Inhibited by galacto-NAG-thiazoline (By similarity)
Compounds that react with thiol groups, such as Ag+, p-chloromercuribenzoate, and iodoacetamide show a strong inhibitory effect on cyanamide hydratase activity. The enzymatic activity is also sensitive to chelating agents such as EDTA or o-phenanthroline, as well as to reagents containing structural elements of cyanamide, such as urea, dicyandiamide, azide, hydroxylamine, thiocyanate, or cyanate
Phosphorylated by MAP2K1/MEK1 and MAP2K2/MEK2 on Thr-185 and Tyr-187 in response to external stimuli like insulin or NGF. Both phosphorylations are required for activity. This phosphorylation causes dramatic conformational changes, which enable full activation and interaction of MAPK1/ERK2 with its substrates. Phosphorylation on Ser-29 by SGK1 results in its activation by enhancing its interaction with MAP2K1/MEK1 and MAP2K2/MEK2. Dephosphorylated and inactivated by DUSP1, DUSP3, DUSP6 and DUSP9. Inactivated by pyrimidylpyrrole inhibitors (By similarity)
Inhibited by Stichodactyla helianthus peptide ShK (PubMed:15709110). Inhibited by millimolar levels of tetraethylammonium (TEA). Contrary to other channels, inhibited only by millimolar levels of 4-aminopyridine (4-AP) (By similarity)
Displays maximal in vitro activity at high salt levels
Repressor activity is controlled via phosphorylation on arginine residues. Unphosphorylated CtsR binds with high affinity to its DNA consensus site and inhibits transcription of downstream genes, whereas the McsB-phosphorylated CtsR repressor is not able to bind to DNA, thus allowing heat-shock gene expression (By similarity)
The transfer reaction from maltose-1-P to glycogen is inhibited by micromolar amounts of inorganic phosphate or arsenate but is only slightly inhibited by millimolar concentrations of glucose-1-P, glucose-6-P, or inorganic pyrophosphate. Is also inhibited by ATP, by 1,4-dideoxy-1,4-imino-D-arabinitol (DIA), but not by isofagomine
Activity is not affected by addition of 10 mM Ca(2+) or removal of Ca(2+)
p54 and probably p47 forms are inhibited by the non-covalent interaction with the cleaved propeptide (By similarity). Inhibited by subtilisin propeptide-like protein SUB1-ProM (By similarity)
Activated by Mg(2+) and Mn(2+)
Is inhibited by clavulanate
Inhibited by palmostatin-B, leading to impair depalmitoylating of Ras
Inhibited by divalent cations. Inhibition decreases in the order zinc, lead, cadmium, nickel, mercury
Inhibited by phlorizin (PubMed:20980548, PubMed:34880492). Possibly modulated by cholesterol binding (PubMed:34880492)
Inhibited by HgCl(2), AgNO(3), CuCl(2), phenylhydrazine, 8-hydroxyquinoline, R-cycloserine and p-chloromercuribenzoic acid
Binding of ferrichrome or colicin M enhances the interaction between FhuA and TonB (PubMed:9353297). TonB activates FhuA through interaction with the beta-barrel (PubMed:12427941)
Translocation activity is inhibited by the ATPase inhibitor vanadate and the calcium channel blocker verapamil. Translocation activity is enhanced by the addition of the bile salt taurocholate
Regulated by a negative feedback mechanism through sterols and non-sterol metabolites derived from mevalonate (By similarity). Phosphorylation at Ser-872 down-regulates the catalytic activity (By similarity)
DNA polymerase activity strongly inhibited by uracil-containing oligonucleotides
Channel activity is controlled by multiple regulatory mechanisms in different subcellular compartments. Channel function is transiently modulated by changes in Ca(2+), and inhibited by a reduction of pH; pH changes modify the aggregation state of unitary channels; a negative cooperativity between extracellular/lumenal Ca(2+) and H(+) is suggested (PubMed:12459486, PubMed:28112729). Regulated by phosphoinositides in a compartment-specific manner: in lysosomes activated by PtdIns(3,5)P2 (Phosphatidylinositol 3,5-bisphosphate) and at the plasma membrane inhibited by PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) (PubMed:22733759, PubMed:29019983)
Inhibited by (2R)-2-methyl-3-dehydroquinic acid
Inhibited by NAD and NADP
TEK and vascular endothelial growth factor receptor 1 (FLT1) stimulate BMX tyrosine kinase activity. Activated by integrins through the mediation of PTK2/FAK1 (By similarity). Activated by TNF through the mediation of TNFRSF1B (By similarity)
Competitively inhibited by xanthine
Inhibited by Ni(2+) and to a lesser extent by Mn(2+) and Cu(2+)
Inhibited by magnesium, cadmium and manganese ions. Also inhibited by crotapotin
Inhibited by LL-aziridino (LL-AziDAP), DL-aziridino (DL-AziDAP) (PubMed:16723397). Also inhibited by (2S,3R,6S)-2,6-diamino-3-fluoropimelate (L,L-3-fluoro-DAP) and (2R,3S,6S)-2,6-diamino-3-fluoropimelate (D,L-3-fluoro-DAP) (Ref.3)
Inhibited by laminarin sulfate and, to a lower extent, by heparin and sulfamin (By similarity). Activated by calcium and magnesium. Inhibited by EDTA
Phosphorylation decreases the condensing activity of KasB and leads to the production of shorter mycolic acids, which is associated to dramatic phenotype changes, such as loss of acid-fastness, increase of cell wall permeability, severe attenuation in infected mice and defect in macrophage colonization
GTPase inhibited by GTP-gamma-S, which also stabilizes filaments
Inhibited by DFP, Z-Pro-prolinal and poststatin, but not by PMSF, SBTI, EDTA, leupeptin, E-64 and pepstatin
Inhibited by Hg(2+) and Mn(2+). Not affected by EDTA in vitro
Inhibited by warfarin (coumadin) (PubMed:15879509, PubMed:16270630, PubMed:22923610, PubMed:33154105). Warfarin locks VKORC1 in both redox states into the closed conformation (PubMed:33154105). Inhibited by warfarin analogs phenindione, brodifacoum and chlorophacinone (PubMed:33154105)
The protein undergoes a dramatic conformational switch from closed to open states upon substrate-binding, which enables specific substrate recognition for the 1''-O-linkage. The glutamate flap (Glu-42) blocks substrate entrance to Mg(2+) in the unliganded closed state. In presence of substrate, Glu-42 is ejected from the active site: this closed-to-open transition significantly widens the substrate-binding channel and precisely positions the scissile 1''-O-linkage for cleavage while securing tightly 2'- and 3'-hydroxyls of ADP-ribose
Totally inhibited by EDTA, EGTA, and 1,10-phenanthroline. Strongly inhibited by divalent cations such as Cu(2+), Cd(2+), Co(2+) and Mn(2+). Partially inhibited by the reducing agents 2-mercaptoethanol and dithiothreitol
The E3 ubiquitin-protein ligase activity is stimulated by PEX12/prx-12
Ligase activity stimulated by PCNA heterotrimer
Inhibited by bis-peroxovanadates and hydrogen peroxide
Activated by lipids
Inhibited by exposure to molecular oxygen
Inhibited by phosphorylation at Ser-219 (By similarity). Activated by phosphorylation on Thr-215
Accumulates in an inactive autophosphorylated state (PubMed:26134396). The presence of spermine results in a dose-dependent reduction in autophosphorylation (PubMed:31996848)
Uridylyltransferase (UTase) activity is inhibited by glutamine, while glutamine likely activates uridylyl-removing (UR) activity
Is allosterically feedback inhibited by lysine; the N.meningitidis enzyme is significantly more sensitive to lysine than the E.coli enzyme. Shows substrate inhibition by (S)-ASA, with a Ki of 1.7 mM
Activated by phosphorylation on Tyr-478. Isoforms which lack this tyrosine residue are not regulated in this way. All catalytically active isoforms require binding to calcium and calmodulin for activation
Magnesium-independent phospholipid phosphatase (PubMed:10359651, PubMed:8663293). Insensitive to N-ethylmaleimide (PubMed:10359651)
The exchange activity is regulated by phosphorylation in a cyclic AMP signaling-dependent way (PubMed:22031603, PubMed:23661805). Temperature-sensitive, reduction or elevation of the temperature significantly decreases or increases its activity respectively (PubMed:18367447)
Interaction with the sulfate transporter SULTR1;2 enhances its catalytic activity
Activated by AGD7 and AGD10
Export of the fluoroquinolone antibiotic norfloxacin is inhibited by the proton ionophore carbonyl cyanide m-chlorophenylhydrazone (CCCP) (PubMed:36282241). Nickel may influence the extrusion of antibiotics possibly by facilitating the proton motive force-dependent efflux process (PubMed:36282241)
P-bromophenacyl bromide (BPB) completely inhibits the catalytic and edematogenic activities (PubMed:25365526). Enzymatic activity is also diminished by EDTA, heparin and crotapotins F2 and F3 from C.d.collilineatus (PubMed:25365526). Inhibited by divalent cations different from calcium ions (cadmium, magnesium, manganese, zinc), since they act as competitive antagonists of this cofactor (PubMed:25365526)
Inhibited by PhrG
Inhibited by galvestine-1
Phosphorylation at Thr-169 is required for enzymatic activity
Stimulated by magnesium ions
Inhibited by D-arginine and D-lysine at high concentration
Activity is modulated by PCNA. PCNA increases the binding affinity of NucS towards ssDNA as well as branched DNA substrates carrying either 3' or 5' flaps. PCNA is also required for optimal loading of NucS on its substrates and to direct activity towards ss/dsDNA junction
Maintained in an inactive, closed conformation by an interaction between the kinase domain and the negative autoregulatory C-terminal coiled-coil region. Agonist binding to the phorbol ester binding site disrupts this, releasing the kinase domain to allow N-terminus-mediated dimerization and kinase activation by transautophosphorylation. Inhibited by chelerythrine chloride
Inhibited by dithiothreitol, partially inhibited by acetatzolamide and cyanide
Inhibited by heavy metal ions such as Zn(2+) or Ni(2+), iodoacetamide, N-ethylmaleimide, leupeptin, SDS and E-64. Also inhibited by chloromethylketones TPCK and TLCK and by human plasma inhibitor alpha-2-macroglobulin. Stimulated by L-cysteine
Inhibited by 2.5 mM Ca(2+)
Binding to mas2 is required for catalytic activity
Binding of zinc or nickel in the G-domain decreases GTPase activity (PubMed:21544686). Once GTP hydrolysis is triggered, probably via a GTPase activating protein, the GDP-loaded state may enhance HypA-HypB complex formation and reduces the affinity of HypB for nickel, which is then transferred to HypA (PubMed:27951644). In contrast to nickel, zinc reduces the formation of complexes with HypA (PubMed:27951644)
Counteracted by the antibiotic cefotaxime during responses to light stress
Inhibited by 2-pyridone derivatives such as PT172 and PT173
Phosphorylation at Thr-14 or Tyr-15 inactivates the enzyme, while phosphorylation at Thr-158 activates it (By similarity). Activated by cyclin cyc-1 in vitro (By similarity). Activated by cyclin cyc-3 in vitro (By similarity)
Transport activity exhibits steep dependence on substrate concentration (PubMed:32415067). Substrate concentration sensitivity of SLC16A7 arises from the strong inter-subunit cooperativity of the SLC16A7 dimer during transport (PubMed:32415067). Inhibited by AR-C155858 (PubMed:32415067)
Activity is inhibited by ammonium ions (PubMed:12902251). Photoreversibly inactivated by 1-iodopropane (PubMed:8636034, PubMed:12902251)
The pro-survival signaling effect of NTRK1 in neurons requires its endocytosis into signaling early endosomes and its retrograde axonal transport. This is regulated by different proteins including CFL1, RAC1 and SORT1. NTF3 is unable to induce this signaling probably due to the lability of the NTF3-NTRK1 complex in endosomes. SH2D1A inhibits the autophosphorylation of the receptor, and alters the recruitment and activation of downstream effectors and signaling cascades. Regulated by NGFR
Taurine transport activity is stimulated by thyrotropin (PubMed:8382624). Taurine transport activity is inhibited by GABA, hypotaurine and beta-alanine (PubMed:8010975, PubMed:8654117)
Activity is stimulated by high salt concentrations with different efficiencies depending on the kind of salt. In vitro, inhibited by glucose
Autoinhibited by the C-terminal PH domain which folds back and binds to the surface of the DH domain, blocking binding of RHOA to the catalytic center of the DH domain. The 2nd BRCT domain is also involved in inhibition, probably by helping to impede RHOA binding. Allosterically activated by binding of activated GTP-bound RHOA to the PH domain which stimulates the release of PH inhibition and promotes the binding of substrate RHOA to the catalytic center. Binding of phosphorylated RACGAP1 to the N-terminal BRCT domain-containing region also releases autoinhibition
Inhibited by the sodium/calcium exchanger inhibitor CGP-37157
Zinc acts as a coregulator and is required for DNA-binding activity
Carboxylation at Lys-302 increases the catalytic activity of the enzyme (PubMed:20695527). Is potently inhibited by N(alpha)-acetyl-N(delta)-phosphonoacetyl-L-ornithine (PALAO) (PubMed:16585758)
During activation, the N-terminal disordered prodomain is removed by cleavage. Concomitantly, double cleavage gives rise to a large 18-kDa and a small 11-kDa subunit. The two large and two small subunits then assemble to form the active CASP6 complex. Can be cleaved and activated by different caspases, depending on the context. Cleaved and activated by caspase-8 (CASP8) and subsequently by caspase-3 (CASP3). Can also undergo autoactivation by mediating autocleavage at Asp-179 and Asp-193, while it is not able to cleave its N-terminal disordered prodomain. Intramolecular cleavage at Asp-193 is a prerequisite for CASP6 self-activation. Cleaved and activated by CASP1 in neurons, possibly in the context of inflammation. Phosphorylation at Ser-257 inhibits autocleavage, preventing caspase activation
Thiocyanate inhibits the formation of 3-bromotyrosine
Channel activity is potentiated by nanomolar concentrations of Zn(2+); half-maximal activation is observed with 37 nM Zn(2+) (PubMed:16144831). Inhibited by higher Zn(2+) levels; haf-maximal inhibition occurs at 20 uM Zn(2+) (PubMed:16144831). Inhibited by strychnine (PubMed:2155780, PubMed:16144831, PubMed:25445488). Inhibited by lindane (PubMed:25445488). Inhibited by picrotoxin (PubMed:22715885, PubMed:23994010, PubMed:25730860). Strychnine binding locks the channel in a closed conformation and prevents channel opening in response to extracellular glycine (By similarity)
By autophosphorylation on threonine
Increased activation in hypoxia. Hydroxylation of the C-terminal ODD domain (CODD) proline of HIF1A is activated by cyclosporin A (CsA)
The hypobromous acid formation is activated by increasing nitrite concentrations and inhibited by increasing urate concentrations
Inhibited by the microbial peptide pepstatin
L-amino-acid oxidase activity toward phenylalanine (Phe) is specfically inhibited by a number of Phe derivatives, such as Cp3 (ethyl 3-(2,6-dichlorophenyl)-2-(piperidin-1-yl)propanoate) or Cp2-SO4 (PubMed:31812258). Cp3 is a very potent inhibitor for activity toward phenylalanine but is toxic (PubMed:31812258). In contrast, Cp2-SO4 is less efficient but not toxic and is able to reverse immunosuppressive action of IL4I1 in vitro (PubMed:31812258)
The presence of FadD32 is necessary for the transfer of the acyl chain from the AMP carrier onto Pks13
The efflux inhibitor FK506 does not impair the transport activity
Activated for cAAA synthesis by Cap7 (also called HORMA2) and by Cap7:Cap8 (HORMA2:HORMA3). Does not require dsDNA for activity. The CdnD:Cap7:Cap8 complex (also called CdnD:HORMA2:HORMA3) is deactivated by Cap6 (also called Trip13)
Inhibited by bumetanide (PubMed:7629105, PubMed:32081947). Activated by WNK3 (PubMed:21613606)
Inhibited by barium (PubMed:9003761). Activated by volatile general anesthetics such as chloroform, diethyl ether, halothane and isoflurane (PubMed:10321245)
Inhibited by phosphorylation of Tyr-528 by leukocyte common antigen and activated by dephosphorylation of this site
Insensitive to okadaic acid. Deubiquitination by WDR48-USP12 complex positively regulates PHLPP1 stability
Inhibited by the cathepsin B inhibitors Ac-LVK-CHO, CA-074 and Z-FA-FMK, and the caspase-3 inhibitor Z-DEVD-CHO
Inhibited by 5-methyltetrahydrofolate monoglutamate and by 5-methyltetrahydrofolate pentaglutamate, inhibition is much more effective by the pentaglutamate form than by the monoglutamate form. Two molecules of 5-methyltetrahydrofolate are bound per tetramer. The binding sites are localized between subunits. Inhibitor binding may preclude movements of the polypeptide chain that are necessary for enzyme activity
Activated by GTP. Subject to allosteric product inhibition by CTP. Inhibited by p-chloromercuriphenylsulfonic acid, N-ethylmaleimide and cyclopentenylcytosine (CPEC)
Resistant to a number of clinically useful HIV-1 PR inhibitors. Inhibited by cyclic urea SD146
Activated by threonine and tyrosine phosphorylation by the dual specificity kinase, MKK6
Antimicrobial activity depends on the dehydration degree and integrity of flavucin
Mycophenolic acid (MPA) is a non-competitive inhibitor that prevents formation of the closed enzyme conformation by binding to the same site as the amobile flap. In contrast, mizoribine monophosphate (MZP) is a competitive inhibitor that induces the closed conformation. MPA is a potent inhibitor of mammalian IMPDHs but a poor inhibitor of the bacterial enzymes. MZP is a more potent inhibitor of bacterial IMPDH. Potently inhibited by MPA. Inhibited by XMP and GMP
Stimulated by anionic phospholipids
NLRP1 inflammasome is activated by cleavage by the Protease 3C from various human enteroviruses and rhinoviruses (EV68, EV71, Coxsackievirus B3, HRV-14 and HRV-16): cleavage promotes ubiquitination and degradation of the N-terminal part, releasing the cleaved C-terminal part of the protein (NACHT, LRR and PYD domains-containing protein 1, C-terminus), which polymerizes and forms the NLRP1 inflammasome (PubMed:33093214, PubMed:33410748). NLRP1 inflammasome is also activated by cleavage by the 3C-like proteinase nsp5 from human coronavirus SARS-CoV-2 (PubMed:35594856). Activated double-stranded RNA: positive-strand RNA viruses such as Semliki forest virus and long dsRNA activate the NLRP1 inflammasome (PubMed:33243852). In contrast to its mouse ortholog, not activated by Bacillus anthracis lethal toxin (PubMed:19651869). NLRP1 inflammasome is inhibited by DPP8 and DPP9, which sequester the C-terminal fragment of NLRP1 (NACHT, LRR and PYD domains-containing protein 1, C-terminus) in a ternary complex, thereby preventing NLRP1 oligomerization and activation (PubMed:30291141, PubMed:31525884, PubMed:33731929, PubMed:33731932). NLRP1 inflammasome is activated by Val-boroPro (Talabostat, PT-100), an inhibitor of dipeptidyl peptidases DPP8 and DPP9 (PubMed:30291141, PubMed:33731929, PubMed:33731932). Val-boroPro relieves inhibition of DPP8 and/or DPP9 by promoting disruption of the ternary complex, releasing its C-terminal part from autoinhibition (PubMed:33731929, PubMed:33731932). ATPase activity is activated by dsRNA-binding but not dsDNA-binding (PubMed:33243852)
(Microbial infection) The NLRP1 inflammasome is activated by human herpes virus 8/HHV-8 protein ORF45, which interacts with the N-terminal part of NLRP1 and promotes its translocation into the nucleus, relieving autoinhibition and leading to activation
Allosterically activated by AdoMetDC prozyme. Activated by putrescine and to a lesser extent by spermidine, norspermidine and spermine. Inhibited by 5'-([(Z)-4-amino-2-butenyl]methylamino)-5'-deoxyadenosine (MDL 73811)
Inhibited by EDTA, 4-hydroxymercuribenzoic acid (PHMB), mercury and zinc ions at a concentration of 2 mM
Binds cyclosporin A (CsA) (PubMed:1702215). CsA mediates some of its effects via an inhibitory action on PPIase (PubMed:1702215)
Activated by the negatively charged lipid dioleoylphosphatidylglycerol (DOPG) and inhibited by N-(n-nonyl)deoxygalactonojirimycin (C9J)
Inhibited by MPK4 and MPK12
Cu(2+) and Zn(2+) completely inhibit the xanthine dioxygenase activity, whereas Co(2+), Mn(2+), and Ni(2+) partially inhibit the activity. The inactive metal ions are presumed to compete for the Fe(2+)-binding site (PubMed:17429948). N-oxalylglycine (NOG), a known inhibitor of several Fe(2+)/alpha-ketoglutarate-dependent dioxygenase family members, competes with alpha-ketoglutarate and provides a Ki of 0.12 uM for inhibition (PubMed:17429948). 6,8-dihydroxypurine acts as a slow-binding competitive inhibitor (PubMed:18036331). The thiol-specific inhibitors 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) and iodoacetamide, inhibit also the catalytic activity (PubMed:18036331)
Proteolysis is inhibited by Wag31; when Wag31 is non-functional oxidative stress increases proteolysis
Export is inhibited by vanadate (PubMed:10639134). Phosphorylation is inhibited by vanadate and sensitive to KOH and hydroxylamine; it is not inhibited by azide (PubMed:12351646). Phosphorylation is Cu(+) not Cu(2+)-dependent (PubMed:12351646). ATPase activity is inhibited by bathocuproindisulfonate (BCDS), which chelates Cu(+) but not Cu(2+), and stimulated 3-4-fold by Cu(+) (PubMed:12351646, PubMed:25899340). ATPase activity is inhibited by Cu(2+) plus DTT or Ag(+) (PubMed:12351646)
Regulated by autoinhibition via interaction of the N-terminal and the C-terminal domains. Autoinhibition may prevent NusG from interacting prematurely with other components of the transcription complex or non-specific interactions with other cellular components
p-chloromercuribenzoate acid inhibits 23% of the SDMT activities on sarcosine and dimethylglycine, and S-adenosylhomocysteine (AdoHcy) inhibits completely GSMT activities
Detected in exponentially growing cells as many processing products, protein disappears upon entry into stationary phase with the concomitant appearance of smaller products. The large products persist in the absence of the extracellular serine protease Epr (PubMed:11987133)
Inhibited by barium, but not by tetraethylammonium
Inhibited by RCVRN, which prevents the interaction between GRK1 and RHO (By similarity). Inhibition is calcium-dependent (By similarity)
Seems to switch between active and inactive modes in response to various stimuli (By similarity). Activated directly or indirectly by membrane phosphatidylinositol (PIs) (PubMed:20736165). Regulated by a variety of auxiliary proteins, which facilitate the maturation, cell surface expression and function of the transporter. Inhibited specifically by the drug tenapanor (By similarity)
Nuclease activity requires the presence of HerA
Is inbibited by tetrahydrolipstatin, a specific lipase inhibitor and RHC 80267, a diacylglycerol lipase inhibitor, but not by phenylglyoxal and iodoacetate
Transcription of the aapA1 gene generates a full-length transcript whose folding impedes translation. Processing of the 3' end of the aapA1 message generates a shorter transcript that becomes translatable after a structural rearrangement. The processing also makes it more susceptible to forming dsRNA with IsoA1 which leads to duplex RNA degradation by RNase 3 (rnc)
Inhibited by thioguanine, GMP and, to a lesser extent, by thioxanthine, azaxanthine and azaguanine (PubMed:3886014). Highly inhibited by nucleoside phosphonates, which are product analogs (PubMed:23927482)
Subject to allosteric regulation. Activated by ADP. Inhibited by GTP and ATP. ADP can occupy the NADH binding site and activate the enzyme. Inhibited by SIRT4 (By similarity). Inhibited by HADH (By similarity)
Type I PDE are activated by the binding of calmodulin in the presence of Ca(2+) (PubMed:15673286). Inhibited by zaprinast and sildenafil (PubMed:15673286)
Inhibited by salicylic acid, acetylsalicylic acid, 2,6-dichrolo-4-nitrophenol, N-ethylmaleimide and iodoacetamide
Cytoplasmic zinc binding may trigger movements of two electrically repulsive cytoplasmic domains and reorient transmembrane helices, thereby modulating coordination geometry of the active site for zinc transport. It may modulate activity in response to cytoplasmic metal fluctuations
Has no constitutive proton transporter activity and has to be activated by long-chain fatty acids/LCFAs. Inhibited by purine nucleotides. Both purine nucleotides and LCFAs bind the cytosolic side of the transporter and directly compete to activate or inhibit it (PubMed:22952235). Activated by noradrenaline and reactive oxygen species. Despite lacking canonical translational encoding for selenocysteine, a small pool of the protein has been observed to selectively incorporate selenocysteine at 'Cys-254'. Selenocysteine-modified protein is highly sensitive to redox modification and may constitute a pool of protein highly sensitive to activation by elevated levels of reactive oxygen species (ROS) (By similarity)
Inhibited by AMPCPP (alpha,beta-methyleneadenosine triphosphate)
Inhibited in a dose dependent manner by ATP, imidazole, orthovanadate and zinc ion. Not inhibited by ADP, AMP and EDTA
Subject to substrate inhibition. Alternate orientations for binding of steroid substrates to SULT2A1 may play a role in substrate inhibition
Autoinhibited in apo-primosome, where the zinc motif of POLA1 and oligonucleotide/olicosaccharide-binding domain of POLA2 are placed into the active site blocking RNA:DNA duplex entry
Requires high levels of phosphatidylserine to be activated. The presence of the C2 domain lowers the affinity of protein kinase C activators for the C1 domains and this inhibition can be removed by phosphatidylserine. Phosphatidic acid, however, is much more potent than phosphatidylserine in reducing C2 domain-mediated inhibition, suggesting that phosphatidic acid may be a required cofactor for the activation of APL II
Activated by phosphorylation in response to hyperosmotic stress within 5 minutes
The formation of the proteasomal ATPase ARC-20S proteasome complex, likely via the docking of the C-termini of ARC into the intersubunit pockets in the alpha-rings, may trigger opening of the gate for substrate entry. Interconversion between the open-gate and close-gate conformations leads to a dynamic regulation of the 20S proteasome proteolysis activity (By similarity). Peptidolytic activity is completely inhibited by lactacystin, and to a lesser extent, by N-acetyl-Leu-Leu-norleucinal (Ac-LLnL) and benzoyloxycarbonyl-Leu-Leu-Leu-vinylsulfone (Z-LLL-VS) in vitro
Strongly inhibited by the sulfhydryl-modifying reagents N-ethylmaleimide and iodoacetamide (PubMed:21897878). Inhibited by the substrate analog N-carbamoyl aspartic acid (PubMed:29425231)
In the inactive state, the helix alphaC is packed against the helical, non-phosphorylated activation segment (AS). Upon activation, helix alphaC is displaced and the phosphorylated AS becomes disordered
Inhibited by small molecule 49c (PubMed:29074775). Inhibited by small molecule WM382 (PubMed:32109369)
Protein kinase activity is activated following autophosphorylation at Tyr-349
Subject to substrate inhibition by pyruvate for the reverse reaction but not for the forward reaction of the tauropine dehydrogenase activity
Activity is stimulated by high osmolarity
Inhibited by nSMase inhibitor GW4869. Binding of anionic phospholipids (APLs) such as phosphatidylserine (PS) and phosphatidic acid (PA) increases enzymatic activity
Stabilized in the inactive form by an association between the SH3 domain and the SH2-TK linker region, interactions of the N-terminal cap, and contributions from an N-terminal myristoyl group and phospholipids. Activated by autophosphorylation as well as by SRC-family kinase-mediated phosphorylation. Activated by RIN1 binding to the SH2 and SH3 domains. Inhibited by imatinib mesylate (Gleevec) which is used for the treatment of chronic myeloid leukemia (CML). Phosphatidylinositol 4,5-bisphosphate (PIP2), a highly abundant phosphoinositide known to regulate cytoskeletal and membrane proteins, inhibits the tyrosine kinase activity (By similarity)
Completely inhibited by the serine protease inhibitor phenylmethylsulfonyl fluoride. Partially inhibited by the serine protease inhibitor Pefabloc. Not inhibited by cysteine proteinase-specific or metalloproteinase-specific inhibitors. Not inhibited by prolinal or its derivatives. EDTA and EGTA both partially inhibit this enzyme (PubMed:14519127). EDTA has no effect on activity (PubMed:15598885)
Regulated by feedback inhibition by coenzyme A (CoA). CoA acts by competing with NAD(P)H (PubMed:23941541, PubMed:26757028). A disulfide bond is formed between CoA and Cys-84, which indicates an irreversible inhibition upon binding of CoA (PubMed:26757028)
Strongly inhibited by bestatin, leuhistin, actinonin, amastatin, 1,10-phenanthroline, DFP, PCMBS, Zn(2+), Cd(2+), Co(2+), Cu(2+), Hg(2+), EDTA and puromycin. Not inhibited by PMSF, and only slightly inhibited by leupeptin and aprotinin. Activity is increased by Mg(2+) and Ca(2+) (By similarity)
Phosphate is a competitive inhibitor
Stimulated by extracellular acidic pH
Both coagulant and amidolytic activities are inhibited by PMSF. Amidolytic activity is partially inhibited by DTT, chymostatin, SBTI and TLCK, but not by heparin and EDTA
Activated by cyclic AMP
Inhibited by various carbonyl reagents, such as p-nitrophenylhydrazine (pNPH), 2,4-dinitrophenylhydrazine, semicarbazide and hydroxylamine
Inhibited by diisopropylfluorophosphate (DFP) and diazoacetyl-D,L-norleucine methyl ester (DAN)
Loses its lipolytic activity in cells lacking nonpolar lipids
Binding of citrate to the ligand-binding domain reduces the chemotaxis towards the strong attractants such as malate and succinate. However, in physiologically relevant niches, citrate is mostly complexed with magnesium or calcium ions, and does not bind McpS
Repressed by sodium ions Na(+)
Feedback inhibition by phosphatidylcholine and also by S-adenosylhomocysteine
Channel activity is regulated by the ancillary beta subunit SCN1B (PubMed:28012039). SCN1B strongly enhances the presence of the pore-forming alpha subunit at the cell surface (By similarity). Interaction with SCN1B is required for rapid channel inactivation and rapid recovery after inactivation, and prevents decrease of channel activity in response to repetitive, high-frequency depolarizations (PubMed:28012039). Potently inhibited by tetrodotoxin and saxitoxin (PubMed:16303569, PubMed:23077250)
Inhibited by 0.1 mM Cu(2+)
Autoinhibited. Intramolecular binding of the interdomains A and B (also called linker region) to parts of the catalytic domain keep the catalytic center in an inactive conformation. The phosphorylation of the interdomains or the binding of the SH2 domains with dually phosphorylated ITAM domains on transmembrane proteins disrupt those intramolecular interactions allowing the kinase domain to adopt an active conformation. The phosphorylation of SYK and of the ITAM domains which is responsible for SYK activation is essentially mediated by SRC subfamily kinases, like LYN, upon transmembrane receptors engagement (By similarity). May also be negatively regulated by PTPN6 through dephosphorylation (By similarity). Downstream signaling adapters and intermediates like BLNK or RHOH may mediate positive and/or negative feedback regulation (By similarity). Negatively regulated by CBL and CBLB through ubiquitination and probable degradation (By similarity). Phosphorylates SH3BP2 which in turn may regulate SYK through LYN
Inhibited by crotonyl-CoA, 2-octenoyl-CoA and 2-hexadecenoyl-CoA
Phosphorylated and unphosphorylated forms are both active and have different functions. A low concentration of phospho-DegU is sufficient to activate transcription of flagellar genes, but a higher concentration of phospho-DegU is required for transcription of other genes. Phosphorylated DegU is stabilized by DegR
Inhibited by CP-166,572, an inhibitor that is competitive with fructose (PubMed:12962626). Also competitively inhibited by phenanthroline and 4-methylpyrazole in vitro (PubMed:3365415)
Kinase activity is activated upon binding to GTP-bound Rho1/Rac1 GTPases. Activated by caspase-3 (CASP3) cleavage during apoptosis. Activated by lipids, particularly cardiolipin and to a lesser extent by other acidic phospholipids and unsaturated fatty acids. Two specific sites, Thr-815 (activation loop of the kinase domain) and Thr-957 (turn motif), need to be phosphorylated for its full activation (By similarity)
Irreversibly inhibited by the fungal metabolite fumagillin and the fumagillin analog TNP470, antiangiogenic drugs
The enzyme in complex with the DNA substrate binds a third divalent metal cation. This binding is essential for catalyzing the DNA synthesis
Inhibited by 1-deoxygalactonojirimycin. Not inhibited by stachyose. Strong inhibition of the hydrolytic activity by sucrose
Allosterically activated by GTP. Inhibited by CTP and UMP in combination
Inhibited by the herbicides chlorimuron ethyl, chlorsulfuron and imazapyr
DNA synthesis is stimulated by PCNA heterotrimers
Autoinhibited: in the inactive state, the enzymatic TIR domain is held apart by the autoinhibiting ARM repeats (PubMed:27671644, PubMed:31278906, PubMed:32755591, PubMed:33053563). NAD(+)-binding to ARM repeats maintains an inactive state by promoting interaction between ARM repeats and the TIR domain, thereby facilitating inhibition of the enzymatic TIR domain (PubMed:33053563). Following activation, possibly by nicotinamide mononucleotide (NMN), auto-inhibitory interactions are released, allowing self-association of the TIR domains and subsequent activation of the NAD(+) hydrolase (NADase) activity (PubMed:27671644, PubMed:31128467, PubMed:32755591). Self-association of TIR domains is facilitated by the octamer of SAM domains (PubMed:31278906, PubMed:31439792). NAD(+) hydrolase activity is inhibited by nicotinamide (PubMed:28334607). Specifically inhibited by berberine chloride and zinc chloride (PubMed:32828421)
Activity is stimulated by ZBP1, which senses double-stranded Z-RNA structures (PubMed:32200799, PubMed:32296175). RIPK3-dependent necroptosis is inhibited by RIPK1: RIPK1 prevents the ZBP1-induced activation of RIPK3 via FADD-mediated recruitment of CASP8, which cleaves RIPK1 and limits TNF-induced necroptosis (PubMed:24813849, PubMed:24813850, PubMed:24557836, PubMed:27321907, PubMed:27819681, PubMed:27819682, PubMed:32296175). Inhibited by type II inhibitor 1-(4-fluorophenyl)-N-[3-fluoro-4-(1H-pyrrolo[2,3-b]pyridin-4-yloxy)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxamide (PubMed:32184955)
Activity decreased by 80% by addition of 0.01 M calcium, zinc or magnesium. Activity only decreased by 17% by addition of ammonium, and by 2% by addition of sodium
Reversibly inactivated by post-translational acetylation by Pat in a cAMP-dependent manner and reactivated by Sir2 deacylase
Activated by Ca(2+) and inhibited by Zn(2+)
Phosphorylation of exogenous substrates activated by Dfp1
Enzymatic activity is activated by HTRA2 in dopaminergic cells upon mitochondrial stress
Activated by acidifying treatment at pH 3.0
Is totally inhibited by 4-aminobenzylcyanide in vitro
Is irreversibly inactivated by the beta-lactams carbapenems via the formation of a covalent adduct resulting from acylation of the catalytic Cys; ertapenem and imipenem are the most efficient drugs for in vitro LdtMt1 inactivation. Cephalosporins (cefotaxime, cephalothin, and ceftriaxone) also form covalent adducts with LdtMt1, although the acylation reaction was 7- to 1,000-fold slower and leads to elimination of one of the drug side chains. A high drug concentration (360 uM) of ceftriaxone is required for full inhibition of enzyme activity. Is not inhibited by ampicillin
Inhibited by KCl
Inhibited by mercaptoethanol and dithiothreitol
Inhibited by apstatin and the metal ion chelator EDTA (PubMed:8870669). Potently inhibited by the converting enzyme inhibitors cilazaprilat; enalaprilat; L155,212; ramiprilat and YS 980 (PubMed:1312513). Also inhibited to a lesser extent by indolaprilat; quinaprilat; spiraprilat; captopril and zofenoprilat (PubMed:1312513)
Amidase activity is inhibited by metal chelators such as EDTA, dipicolinic acid or 1,10-phenanthroline
50% inhibited by vanadate; it has been suggested that vanadate fully inhibits the dimer but not the monomer (PubMed:15766260). Activated by 15 uM reserpine then inhibited by higher concentrations
Enzyme activity is tightly regulated to prevent the accumulation of reactive oxygen species in the endoplasmic reticulum. Reversibly down-regulated by the formation of disulfide bonds between the active site Cys-90 and Cys-129, and between Cys-95 and Cys-100. Glutathione may be required to regulate its activity in the endoplasmic reticulum (By similarity)
Specifically inhibited by alpha-alkylidene-beta-lactone KC01 ((Z)-6-(2-Oxo-4-tridecyloxetan-3-ylidene)hexanamide)
DNA binding is efficiently suppressed in the presence of ADP-ribose (ADPR) or phospho-ADPR (PubMed:20926389). Accumulation of ADPR resulting from NAD degradation may be interpreted by the cell as a signal to activate recycling of nicotinamide (PubMed:20926389)
Assembly into ribonucleoprotein complexes of high-molecular-mass (HMM) inhibits its enzymatic activity. Antiviral activity is neutralized by the simian immunodeficiency virus (SIV-mac) virion infectivity factor (VIF), that prevents its incorporation into progeny virions by both inhibiting its translation and/or by inducing its ubiquitination and subsequent degradation by the 26S proteasome
The inhibitors KDOAM-25, CPI-455 and others inhibits its demethylase activity, resulting to cell growth arrest in cancer cells
Regulation is a highly complex process involving membrane recruitment, protein-protein interactions, dimerization, and phosphorylation/dephosphorylation events. Ras-GTP recruits RAF1 to the membrane, thereby promoting its activation. The inactive conformation of RAF1 is maintained by autoinhibitory interactions occurring between the N-terminal regulatory and the C-terminal catalytic domains and by the binding of a 14-3-3 protein that contacts two phosphorylation sites, Ser-259 and Ser-621. Upon mitogenic stimulation, Ras and PPP2R1A cooperate to release autoinhibition and the subsequent phosphorylation of activating sites: Ser-338, Tyr-341, Thr-491, and Ser-494, yields a fully active kinase. Through a negative feedback mechanism involving MAPK1/ERK2, RAF1 is phosphorylated on Ser-29, Ser-43, Ser-289, Ser-296, Ser-301 and Ser-642 by MAPK1/ERK2, which yields an inactive, desensitized kinase. The signaling-competent conformation of RAF1 is finally re-established by the coordinated action of PIN1, a prolyl isomerase that converts pSer and pThr residues from the cis to the trans conformation, which is preferentially recognized and dephosphorylated by PPP2R1A. Activated by homodimerization and heterodimerization (with BRAF). Also regulated through association with other proteins such as KSR2, CNKSR1/CNK1, PEBP1/RKIP, PHB/prohibitin and SPRY4. PEBP1/RKIP acts by dissociating RAF1 from its substrates MAP2K1/MEK1 and MAP2K2/MEK2. PHB/prohibitin facilitates the displacement of 14-3-3 from RAF1 by activated Ras, thereby promoting cell membrane localization and phosphorylation of RAF1 at the activating Ser-338. SPRY4 inhibits Ras-independent, but not Ras-dependent, activation of RAF1. CNKSR1/CNK1 regulates Src-mediated RAF1 activation
Inhibited by vanadate and chlorogenic acid
Activity is not inhibited by EDTA in vitro, nor enhanced by the addition of Mg(2+)
Activated by threonine and tyrosine phosphorylation. Activated by the MAP kinase kinases MKK1 and MKK2. Activated in response to touch, wounding, low temperature, low humidity, salt stress and the bacterial elicitors flagellin and harpin. Activated upon Pseudomonas syringae pv. tomato DC3000 infection. Repressed by the protein phosphatase 2C AP2C1. Repressed by DSPTP1-mediated dephosphorylation. Activated by the MAP kinase kinase MKK6 in vitro
Allosterically activated by benzodiazepines (By similarity). Allosterically activated by the anesthetic etomidate (PubMed:17093081). Inhibited by the antagonist bicuculline (By similarity)
Rab activation is generally mediated by a guanine exchange factor (GEF), while inactivation through hydrolysis of bound GTP is catalyzed by a GTPase activating protein (GAP). That Rab is activated by the guanine exchange factors DENND1A, DENND1B and DENND1C (By similarity)
Antiviral activity is neutralized by the HIV-1 virion infectivity factor (VIF), that prevents its incorporation into progeny virions by both inhibiting its translation and/or by inducing its ubiquitination and subsequent degradation by the 26S proteasome
Activated by divalent metal ions. Inhibited by certain thiol reagents
Activated by citrate. Inhibited by NaBH(4). Activity is independent of divalent metal cations
Regulated by a guanine nucleotide-exchange factor (GEF) and a GTPase-activating protein (GAP) and alternates between an inactive GDP-bound and an active GTP-bound form. The BLOC-3 complex composed of HPS1 and HPS4 acts as its GEF, promotes the exchange of GDP to GTP, converting it from an inactive GDP-bound form into an active GTP-bound form. SGSM2 acts as its GAP and inactivates it by stimulating its GTPase activity
Inhibited by EDTA and EGTA. Not inhibited by PMSF, antipain, pepstatin, and iodoacetamide
Inhibited by alpha-(methylamino)isobutyric acid (MeAIB) (PubMed:10660562, PubMed:11692272). Inhibited by lithium, potassium, choline ions, N-methylglucamine (PubMed:11692272). The pH dependence has an allosteric effect on the transport (PubMed:11692272)
Uptake is activated by hyperosmotic stress (PubMed:15327991). Shows a small but significant chill stimulation around 15 degrees Celsius (PubMed:15995189)
Subject to allosteric regulation. Activated by ADP. Inhibited by GTP and ATP. ADP can occupy the NADH binding site and activate the enzyme. Inhibited by SIRT4 (By similarity). Inhibited by HADH (PubMed:20670938)
Coformycin and 2'-deoxycoformycin, whose structures mimic the transition state of the deamination reaction, are potent competitive inhibitors
Inhibited by chloral hydrate
Inhibited by phenylmethylsulfonyl fluoride and Pefabloc
Substrate inhibition is not observed with any alcohols, and the enzyme-NADH dissociation is not considered to be a rate-limiting step
Activity increases following DNA damage
Binds the effectors ADP and ATP. Also binds AMP with high affinity, raising the possibility that AMP could be an important PII effector, at least in archaea. The change in the ATP/AMP ratio may be more relevant for describing the energy status in the cells than the ATP/ADP ratio alone
Inhibited by p-chloromercuribenzoate, iodoacetate and N-ethylmaleimide
30S ribosomal subunit binding to Shine-Dalgarno sequences blocks exonuclease activity
Activated by ascorbate (By similarity). Inhibited by N-oxalylglycine, fumarate and succinate (By similarity). RNA N(6)-methyladenosine demethylase activity is inhibited by fluorescein derivatives (PubMed:26457839). RNA N(6)-methyladenosine demethylase activity is selectively inhibited by meclofenamic acid; inhibition is specific to FTO and meclofenamic acid does not inhibit ALKBH5 (PubMed:25452335). Specifically inhibited by R-2-hydroxyglutarate (R-2HG), an oncometabolite that also exerts a broad antileukemic activity (PubMed:29249359). Inhibition by R-2HG leads to increased level of N(6)-methyladenosine-containing transcripts, leading to down-regulate expression of MYC and CEBPA transcripts (PubMed:29249359)
Inhibited by 1-(1-acetylpiperidin-4-yl)-3-(4-(trifl uoromethoxy)phenyl)urea (TPAU), 1-cyclohexyl-3-dodecylurea (CDU), 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA), 1-((3S, 5S, 7S)-adamantan-1-yl)-3-(5-(2-(2-ethoxyethoxy) ethoxy)pentyl)urea (AEPU), N-adamantyl-N[']-cyclohexyl urea (ACU), 4-(((1S, 4S)-4-(3-((3S, 5S, 7S)-adamantan-1-yl) ureido)cyclohexyl)oxy)benzoic acid (c-AUCB), 4-(((1R, 4R)-4-(3-((3S, 5S, 7S)-adamantan-1-yl)ureido)cyclohexyl)oxy)benzoic acid (t-AUCB), 4-(((1R, 4R)-4-(3-(4(trifluoromethoxy)phenyl)ureido)cyclohexyl)oxy)benzoic acid (t-TAUCB) and to a lesser extent by 8-(3-((3S, 5S, 7S)-adamantan-1-yl)ureido) octanoic acid (AUOA) (By similarity). Phosphatase activity is inhibited by dodecyl-phosphate, phospholipids such as phospho-lysophosphatidic acids and fatty acids such as palmitic acid and lauric acid (PubMed:21217101)
Transport of D-lactate and pyruvate stimulated by alpha-cyano-4-hydroxycinnamic acid, but inhibited by the short-chain fatty acids acetate, propionate and butyrate
Activated by phosphorylation on Thr-220
The side chain of Glu-231 determines which of the two opposing activities (AMPylase or de-AMPylase) will take place (PubMed:27918543). In response to endoplasmic reticulum stress, mediates de-AMPylase activity (PubMed:27918543). Adenylyltransferase activity is inhibited by the inhibitory helix present at the N-terminus: Glu-231 binds ATP and competes with ATP-binding at Arg-371, thereby preventing adenylyltransferase activity (By similarity). In unstressed cells, disengagement of Glu-231 promotes adenylyltransferase activity (PubMed:27918543). Activation dissociates ATP-binding from Glu-231, allowing ordered binding of the entire ATP moiety with the alpha-phosphate in an orientation that is productive for accepting an incoming target hydroxyl side chain (By similarity)
StkP is activated continuously during growth and its activity is inhibited upon growth arrest. Inhibited by staurosporine, a known protein kinase inhibitor
Inhibited by cefmetazole
Inhibited by columbianetin
Inhibited by Ca(2+)
Activated by phosphorylation on Thr-172. Binding of AMP to non-catalytic gamma subunit (PRKAG1, PRKAG2 or PRKAG3) results in allosteric activation, inducing phosphorylation on Thr-172. AMP-binding to gamma subunit also sustains activity by preventing dephosphorylation of Thr-172. ADP also stimulates Thr-172 phosphorylation, without stimulating already phosphorylated AMPK. ATP promotes dephosphorylation of Thr-172, rendering the enzyme inactive. Under physiological conditions AMPK mainly exists in its inactive form in complex with ATP, which is much more abundant than AMP. Selectively inhibited by compound C (6-[4-(2-Piperidin-1-yl-ethoxy)-phenyl)]-3-pyridin-4-yl-pyyrazolo[1,5-a] pyrimidine. Activated by resveratrol, a natural polyphenol present in red wine, and S17834, a synthetic polyphenol. Salicylate/aspirin directly activates kinase activity, primarily by inhibiting Thr-172 dephosphorylation
At rest, the N- and C-terminal domains interact, as part of a larger autoinhibitory complex, with calmodulin pre-associated at the N-terminal domain. Upon a calcium rise, calmodulin becomes calcium-saturated and subsequently binds to the C-terminal domain. Fully calcium-saturated calmodulin then leaves the N-terminal domain, binding solely to the C-terminal domain, and the whole autoinhibitory complex dissociates, resulting in activation of adenylate cyclase. As local calcium concentrations decrease, the calmodulin becomes calcium free and binds once more to the N-terminal domain, whereupon the whole system returns to rest with the re-association of the autoinhibitory complex (PubMed:14585998). In non-excitable cells, activated by capacitative calcium entry (CCE) through store-operated channels, namely through interaction with ORAI1 and STIM1; membrane raft and caveolae localization and membrane integrity are indispensable. CCE-mediated adenylate cyclase activity is decreased by AKAP5 and AKAP7. CCE-mediated adenylate cyclase activity is up-regulated by AKAP9 and the mitochondrially targeted AKAP1. In excitable cells, activated during membrane depolarization through L-type voltage-gated calcium channels (VGCC), leading to calcium entry; the L-type alpha subunit is sufficient. Activated via stimulation of the GLP1R. Synergistically activated by calcium/calmodulin and GNAS. Stimulated by forskolin. Inhibited by PKA directly bound to AKAP5 at membrane raft. Inhibition by acute activation of OPRM1 and activation by chronic activation of OPRM1 is mediated by pertussis toxin-sensitive G(i) and G(o) G alpha proteins and G beta-gamma dimer. Activity is inhibited by G beta-gamma dimer (By similarity)
Activity is enhanced by binding to the pyruvate dehydrogenase subunit DLAT. Inhibited by ADP and pyruvate; these compounds interfere with DLAT binding and thereby inhibit kinase activity. Inhibited by dichloroacetate. Inhibited by AZD7545; this compound interferes with DLAT binding and thereby inhibits kinase activity
Inhibited by thiazolidinedione-type compounds: inhibited by furan- and pyridone- thiazolidinediones
Inhibited by substrate levels above 8 mM
Feedback inhibited by MgrB, which seems to bind PhoQ, altering its activity and that of downstream effector PhoP. PhoP-regulated transcription is redox-sensitive, being activated when the periplasm becomes more reducing (deletion of dsbA/dsbB, or treatment with dithiothreitol). MgrB acts between DsbA/DsbB and PhoP/PhoQ in this pathway
Inhibited by substituted imidazole inhibitors TH27, KK96 and KK71
Inhibited by pyridoxal phosphate
Phosphorylation at Thr-14 or Tyr-15 inactivates the enzyme, while phosphorylation at Thr-160 activates it (PubMed:1396589). Inhibited by 1,25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)), AG-024322, N-(4-Piperidinyl)-4-(2,6-dichlorobenzoylamino)-1H-pyrazole-3-carboxamide (AT7519), R547 (Ro-4584820), purine, pyrimidine and pyridine derivatives, 2-aminopyrimidines, paullones, thiazo derivatives, macrocyclic quinoxalin-2-one, pyrazolo[1,5-a]-1,3,5-triazine, pyrazolo[1,5-a]pyrimidine, 2-(1-ethyl-2-hydroxyethylamino)-6-benzylamino-9-isopropylpurine (roscovitine, seliciclib and CYC202), SNS-032 (BMS-387032), triazolo[1,5-a]pyrimidines, staurosporine and olomoucine. Stimulated by MYC. Inactivated by CDKN1A (p21)
Stimulated rapidly but transiently by both cell fibronectin interactions, as well as by insulin, in a PI3-K-dependent manner, likely via the binding of PtdIns(3,4,5)P3 with a PH-like domain of ILK. The protein kinase activity is stimulated by LIMD2 (PubMed:24590809)
Inhibited by FK506 but not cyclosporin
Contrary to classical chorismate mutases, is not subject to allosteric regulation by tryptophan or tyrosine (PubMed:33010586). Also not regulated by phenylalanine (PubMed:33010586)
Inhibited by fructose 1,6-bisphosphate
Stimulated by PKA-dependent PLIN phosphorylation
No effect on activity with glutamine synthetase (GS) inhibitor methionine sulfoximine (MSO)
Dehydrogenase activity is increased by ammonium ions
SELENOF decreases the retinol dehydrogenase activity
Phosphorylation by SenX3 stimulates binding to the target promoters (PubMed:21698211). Activation of the SenX3-RegX3 two-component system is inhibited by PhoY1 and PhoY2 when phosphate is readily available (PubMed:28698272). Overexpression of the kinase domain of PknB (PknB-KDMtb) inhibits the transcriptional activity of RegX3 by phosphorylating Thr-100, Thr-191 and Thr-217 (PubMed:31160336). Phosphorylation at Thr-191 and Thr-217 abolishes the DNA-binding ability of RegX3 and phosphorylation at Thr-100 likely prevents RegX3 from being activated through conformational changes induced by SenX3-mediated phosphorylation (PubMed:31160336)
Phosphorylation on Ser-202 and Ser-204 induces 'Lys-63'-specific deubiquitinase activity
In vitro, inhibited by acetylene (PubMed:19453274). In fact, acetylene is oxidized to ketene which binds irreversibly to His-191 of ammonia monooxygenase alpha subunit (AmoA) (PubMed:19118368)
Completely inhibited by EDTA and 1,10-phenanthroline. Moderately inhibited by the phosphonocarboxylic acids phosphonoformate and 3-phosphonopropionate and the phosphonate herbicide glyphosate. Partially inhibited by the reducing agents sodium sulfide and dithiotheitol and the chelating agent iminodiacetate. Nonphosphonate analogs of phosphonoacetate, such as arsonoacetate, sulfonoacetate and malonate are poor inhibitors. Inorganic phosphate, acetate and the known phosphonotase inhibitor phosphite have little effect on activity. Not inhibited by the alkylphosphonic acids methylphosphonate and ethylphosphonate, or the aminoalkylphosphonates 2-aminoethylphosphonate, 3-aminopropylphosphonate and 4-aminobutylphosphonate. Fe(3+), Ca(2+), Mg(2+) and Cs(+) have no effect on activity. Activity is slightly increased by the aminoalkylphosphonates 1-aminoethylphosphonate, 1-aminobutylphosphonate, 2-amino-4-butylphosphonate. Activity is increased by Zn(2+), Mn(2+) and Co(2+), these 3 metal ions also allow recovery of activity after EDTA treatment
Supercoiling activity inhibited by novobiocin and coumermycin, DNA wrapping around gyrase is not inhibited (PubMed:153201, PubMed:276855)
Is inhibited by Zn(2+), Ni(2+), Fe(2+) and Cu(2+)
Inactivated by di-isopropylfluorophosphate and phenylmethylsulfonylfluorid (PMSF), a specific inhibitor of serine esterases
At physiological pH, allosterically activated by ATP (PubMed:32591529). ATP binding is a prerequisite to magnesium and substrate binding (PubMed:32591529). ATP binds to 2 of the subunits in the homotetramer inducing a closure of these 2 subunits and the release of the C-terminal loop, thereby activating the enzyme (PubMed:32591529). In this conformation, the enzyme can bind IMP and magnesium which ultimately leads to the release of ATP (PubMed:32591529). At pH 5, ATP does not have an allosteric role and is dispensable for magnesium and substrate binding (PubMed:32591529). Inhibited by phosphocholine and D-myo-inositol-4-phosphate (PubMed:32591529)
The enzyme activity is enhanced by Mg(2+), Fe(2+), Mn(2+) and Ca(2+). No stimulation is observed with Cu(2+) and Zn(2+)
Activity is increased by ascorbate. Inhibited by myristoyl-CoA
Inhibited by nSMase inhibitor GW4869 (PubMed:10823942). Binding of anionic phospholipids (APLs) such as phosphatidylserine (PS) and phosphatidic acid (PA) increases enzymatic activity (By similarity)
Selectively inhibited by DO264 (N-3-pyridyl-N'-(1-[3-chloro-4-{2-chloro-4-(trifluoromethoxy)phenoxy}pyridine-2-yl]piperidin-4-yl)thiourea) (PubMed:30420694, PubMed:30720278). Reversibly inhibited by triterpenoids, but with rather low potency (PubMed:24879289)
Inhibited by sulfate and phosphate ions
Inhibited by ATP
In the famine mode, FL11 forms dimers and acts as a repressor, leading to growth arrest (PubMed:18073105). In the feast mode, in the presence of high concentrations of lysine or arginine, four dimers assemble into an octamer and cover the fl11 and lysine biosynthesis promoters (PubMed:18073105, PubMed:19004003). This leads to the inhibition of fl11 expression and lysine biosynthesis, decrease of the FL11 concentration in the cell, derepression of the target genes and activation of the metabolism (PubMed:18073105)
Inhibited by carbonyl reagents such as hydrazine, hydroxylamine, phenylhydrazine and semicarbazide
Increased GTPase activity in the presence of phosphatidic acid
Inactivated by interferon-induced RSAD2. This inactivation may result of disruption of lipid rafts at the plasma membrane, and thus have an antiviral effect since many enveloped viruses need lipid rafts to bud efficiently out of the cell
Strongly inhibited by mercury chloride and KCN
Inhibited by a high concentration of pyrophosphate
During sporulation, is negatively regulated by MciZ, which binds to FtsZ and inhibits its polymerization and the formation of the Z ring
Strongly inhibited by PMSF and moderately inhibited by leupeptin. Not inhibited by EDTA, aprotinin, pepstatin, and bestatin
Zinc and calcium ions cooperatively modulate enzyme activity. The cleavage of the pro-domain is not required for protease activity. Dependence on calcium for proteolytic activity is mediated by the high affinity site (By similarity)
ATP and calmodulin are essential for its activation. Channel activity is inhibited by CFTR protein and by chloride inhibitors such as niflumic acid (NFA) and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS). Activated by heat with activation seen at temperatures above 44 degrees Celsius (By similarity). Activated by BDNF in radial glial cells (By similarity)
Specifically inhibited by ZT-12-037-01 (1a) (N2-cyclopropyl-N4-(1-isopropylpiperidin-4-yl)- 6,7-dimethoxyquinazoline-2,4-diamine) (PubMed:30712867). Inhibition by ZT-12-037-01 (1a) blocks oncogenic NRAS-driven melanocyte malignant transformation and melanoma growth (PubMed:30712867)
Inhibited by nipecotic acid and thiazolidine-2-carboxylic acid
Inhibited by 1-(1-acetylpiperidin-4-yl)-3-(4-(trifl uoromethoxy)phenyl)urea (TPAU), 1-cyclohexyl-3-dodecylurea (CDU), 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA), 1-((3S, 5S, 7S)-adamantan-1-yl)-3-(5-(2-(2-ethoxyethoxy) ethoxy)pentyl)urea (AEPU), N-adamantyl-N[']-cyclohexyl urea (ACU), 4-(((1S, 4S)-4-(3-((3S, 5S, 7S)-adamantan-1-yl) ureido)cyclohexyl)oxy)benzoic acid (c-AUCB), 4-(((1R, 4R)-4-(3-((3S, 5S, 7S)-adamantan-1-yl)ureido)cyclohexyl)oxy)benzoic acid (t-AUCB), 4-(((1R, 4R)-4-(3-(4(trifluoromethoxy)phenyl)ureido)cyclohexyl)oxy)benzoic acid (t-TAUCB) and to a lesser extent by 8-(3-((3S, 5S, 7S)-adamantan-1-yl)ureido) octanoic acid (AUOA). Phosphatase activity is inhibited by dodecyl-phosphate, phospholipids such as phospho-lysophosphatidic acids and fatty acids such as palmitic acid and lauric acid (PubMed:22217705, PubMed:22387545)
Not inhibited by sucrose
Is potently inhibited by 5-fluoro-2'-deoxyuridine 5'-monophosphate (FdUMP), but in contrast to ThyA, is not inhibited by the folate-based 1843U89 (PubMed:18493582). A 5-alkynyl dUMP analog has been shown to highly inhibit ThyX (IC(50) value of 0.91 uM), while lacking activity against the classical mycobacterial thymidylate synthase ThyA, and therefore is a selective mycobacterial FDTS inhibitor (PubMed:21657202)
Inhibited by quinolones
Activated by chloride ions. Inhibited by acarbose. Not inhibited by wheat alpha-amylase inhibitors 1 (WI-1, the tetrameric form) or 3 (WI-3, the monomeric form) and bean alpha-amylase inhibitor 1 (alphaAI-1)
Phosphoenolpyruvate carboxykinase activity is regulated by glucose levels (By similarity). Phosphorylation at Ser-90 reduces the binding affinity to oxaloacetate and converts the enzyme into an atypical protein kinase using GTP as donor (By similarity)
Inhibited in vitro by p-hydroxymercuribenzoate, EDTA, l,l0-phenanthroline and N-ethylmaleimide
Inhibited by S-adenosyl-L-methionine (SAM) and lysine in a synergistic manner. No inhibition by threonine, leucine or SAM alone, and no activation or inhibition by alanine, cysteine, isoleucine, serine, valine, methionine, glutamine, asparagine, glutamic acid or arginine
The integrated stress response (ISR) is activated in response to conditions that promote ribosome collisions: gcn1, which acts as a ribosome collision sensor, activates gcn2. The RQC pathway and the integrated stress response (ISR) antagonize each other: hel2 prevents the activation of gcn2, while gcn2 suppresses RQC activation. Ribosome stalling-induced integrated stress response prefers ribosomes with empty A sites. The kinase activity is stimulated upon binding to uncharged tRNAs
Strongly inhibited by Fe(2+), Fe(3+), K(3)[Fe(CN)(6)], Ag(+), and Cu(2+)
Requires the presence of NTP, preferentially ATP rather than dATP, UTP, CTP and GTP, respectively, to mediate ribonucleotide 5'-phosphorylation
Subject to competitive inhibition by dicoumarol, nicotinic acid and acetate with respect to NADH. Subject to uncompetitive inhibition by dicoumarol, nicotinic acid and acetate with respect to nitrofurazone and nitrofurantoin
Inhibited by protoporphyrinogen-IX, by metal chelator (EGTA) and by low concentrations of heavy metal ions
Low feedback inhibition by lysine and threonine. The decreased sensitivity of C.flavum, as compared to C.glutamicum, is probably due to the Asp-345-Gly sequence difference
Signaling is inhibited by the antagonist LY341495. The LY341495 binding site partially overlaps with the glutamate binding site. Signaling is also inhibited by synthetic allosteric regulators, such as FITM (4-fluoro-N-(4-(6-(isopropylamino)pyrimidin-4-yl)thiazol-2-yl)-N-methylbenzamide) that bind in a pocket between the transmembrane helices
Completely inhibited by ZnCl(2) and CuCl(2)
Free GntR fails to recognize gluconate and 6-phosphogluconate, whereas the GntR/DNA complexes recognize both ligands. It is therefore likely that GntR DNA binding induces structural changes that permit GntR to recognize effectors
Only has nuclease activity when bound to both gRNAs (crRNA plus tracrRNA)
Activated by phosphorylation on Thr-211. Inhibited by phosphorylation on Thr-564 (By similarity)
Activated by autophosphorylation of the T-loop at Thr-169 and Ser-173: in contrast to other members of the SNF1 subfamily, phosphorylation at Thr-169 is not mediated by STK11/LKB1 but via autophosphorylation instead
Its activity is inhibited by trichostatin A (TSA), a well known histone deacetylase inhibitor. Cytosolic activity is refractory to inhibition by TSA, while the nuclear activity is inhibited completely
Inhibited by D-Phe-Pro-Arg-chloromethyl ketone (FPRCK) (97%), PMSF (76%), and benzamidine (50%). Is not inhibited by BPTI, antithrombin and EDTA
Is inhibited by a series of cycloalkyl pyrimidines, which also show suppression of bacterial growth
Inhibited by CuCl(2) and ZnCl(2)
In contract to the MetAP 2 isoform, is not inhibited by the fungal metabolite fumagillin, an antiangiogenic drug
Activated by phosphorylation on Thr-207, potentially by autophosphorylation
Inhibited by N-hydroxyhydantoin carbamate JJH260 and beta-lactone KC01
Regulated at the post-translational level in response to alterations of the sphingolipid and the sterol biosynthetic pathways
Inhibited by 1,10-phenanthroline, EDTA and bestatin (PubMed:12166515, PubMed:21659511, PubMed:34133730, PubMed:19196988). Inhibited by (Benzyl)Tyr-Ala (BTA) (PubMed:21844374). Activity is not affected by phosphoramidin, PMSF, leupeptin, iodoacetamide or pepstatin (PubMed:12166515, PubMed:19196988)
The proton transporter activity is activated by fatty acids (in vitro) (PubMed:11171965). The proton transporter activity is inhibited by ATP and ADP (in vitro) (PubMed:11171965). The effect of Ubiquinone/coenzyme Q10 on the proton transporter activity in reconstituted membranes is unclear (in vitro) (PubMed:11171965, PubMed:12734183)
Autophosphorylation is stimulated by the presence of C4-dicarboxylates such as fumarate or succinate (PubMed:12167640). DcuB is required for converting DcuS to the sensory competent state (PubMed:27318186)
Inhibited by Zn(2+), Cd(2+) and Hg(2+), but not by Co(2+), Ni(2+), Mn(2+), Sr(2+), Mg(2+), or Fe(3+). Inhibited by pyrrole-2-carboxylate and its derivative 2-thiophenecarboxylate, but not by trans-aconitate, fluorocitrate and oxalomalate, which are typical inhibitors of the aconitase enzymes
Inhibited by the not secondly cleaved propeptide (By similarity). Inhibited by m-guanidinomethyl-phenylacetyl-Arg-Val-Arg-(amidomethyl)-benzamidine (m-guanidinomethyl-Phac-RVR-Amb) and 4-guanidinomethyl-phenylacetyl-Arg-Tle-Arg-4-amidinobenzylamide (MI-1148) (By similarity). Inhibited by Decanoyl-Arg-Val-Lys-Arg-chloromethylketone (decanoyl-RVKR-CMK) (PubMed:9252368). Inhibited by heparin/heparan sulfate-binding (By similarity)
IRS4 and TAX4 are both positive regulator of INP51 activity and phosphatidylinositol 4,5-bisphosphate turnover
Inhibited by iodoacetate, p-chloromercuribenzoate, HgCl(2), cupric sulfate and ammonium sulfate
Inhibited by serine hydrolase inhibitor FP-biotin and by antipain
Inhibited by high concentrations of FMN
Activated by tyrosine phosphorylation by a wide range of cytokine stimulations. When T-cells or B-cells receptors are activated, a series of phosphorylation leads to the recruitment of TEC to the cell membrane, where it is phosphorylated at Tyr-518. Also activated in response to SCF. Integrin engagement induces tyrosine phosphorylation of TEC in platelets. STAP1 participates in a positive feedback loop by increasing the activity of TEC. SOCS1 is an inhibitor of TEC kinase activity
Alternates between an inactive GDP-bound form and an active GTP-bound form (By similarity). Intrinsic GTPase activity is almost undetectable in vitro (By similarity). Activated by a guanine nucleotide-exchange factor (GEF) and inactivated by GTPase-activating protein ARFGAP1 (By similarity)
Inhibited by disulfiram
Allosterically activated by N-acetylglucosamine 6-phosphate (GlcNAc6P). Competitively inhibited by 2-amino-2-deoxy-D-glucitol-6-phosphate (GlcN-ol-6P)
RNA triphosphatase activity is inhibited by vanadate, iodoacetate and magnesium
Activated by phosphorylation on Thr-175 (By similarity). Inhibited by phosphorylation at Ser-343, Ser-358, Thr-484 and/or Ser-587, probably by PKA, which triggers interaction with 14-3-3 proteins (PubMed:29211348)
Inhibited by hydroxylamine, aminooxyacetate, phenylhydrazine and sodium borohydride
Activity is completely inhibited by the addition of 0.5 mM Mn(2+), Ni(2+), or Co(2+) and partially inhibited by 0.5 mM Zn(2+)
Interaction with SpoIIAB inhibits sigma-F activity throughout the cell before the formation of the asymmetric septum; after septation the interaction is confined to the mother cell, and sigma-F activity is released in the prespore (PubMed:8358793). Fin, a second, forespore-specific anti-sigma factor is induced in 2 successive waves by sigma-F and sigma-G, by antagonizing sigma-F it allows the switch to sigma-G factor and progression to the late sporulation development stages (PubMed:21037003)
Activated by interaction with DLAT. Inhibited by AZD7545, dichloroacetate and radicicol
Inhibited by the pore blockers saxitoxin and tetrodotoxin
Kinase activity is activated upon binding to GTP-bound Rhoa/Rac1 GTPases. Activated by caspase-3 (CASP3) cleavage during apoptosis. Activated by lipids, particularly cardiolipin and to a lesser extent by other acidic phospholipids and unsaturated fatty acids. Two specific sites, Thr-816 (activation loop of the kinase domain) and Thr-958 (turn motif), need to be phosphorylated for its full activation
Upon extracellular signal or mitogen stimulation, phosphorylated at Thr-577 in the C-terminal kinase domain (CTKD) by MAPK1/ERK2 and MAPK3/ERK1. The activated CTKD then autophosphorylates Ser-386, allowing binding of PDPK1, which in turn phosphorylates Ser-227 in the N-terminal kinase domain (NTDK) leading to the full activation of the protein and subsequent phosphorylation of the substrates by the NTKD (By similarity)
Strongly inhibited by puromycin and DAMPAQ-22
Detected in exponentially growing cells, the 50 and 30 kDa processing products disappear upon entry into stationary phase with the concomitant appearance of a 20 kDa products. The 50 kDa form persists in the absence of extracellular proteases (PubMed:11987133)
Inhibited by L-leucine, EDTA and heat
Activity is significantly decreased by addition of divalent cations such as Mg(2+), Mn(2+), Zn(2+), Ca(2+), Co(2+), Cu(2+), and Ni(2+); while Fe(2+) has little effect
Kinase activity is slightly activated by fructose 1,6-bisphosphate (FBP) at low ATP concentrations, and is inhibited by inorganic phosphate (Pi). Moreover, FBP, phosphoenolpyruvate and 2-phosphoglycerate, but not fructose 1-P, fructose 6-P, and ribulose 1,5-bisphosphate protect kinase activity against inhibition by Pi. Dephosphorylation of P-Ser-HPr by S.salivarius HPrK/P is strictly dependent on the presence of Pi, and is inhibited by FBP. FBP seems to modulate HPrK/P activities by enhancing affinity of the active site for ATP and, conversely, lowering the affinity for Pi
Inhibited by alpha-ethyl-N-4-pyridinyl-benzeneacetamide (EPBA) and 4,4'-dihydroxybenzophenone (DHBP)
TAFI/CPB2 is unique among carboxypeptidases in that it spontaneously inactivates with a short half-life, a property that is crucial for its role in controlling blood clot lysis. The zymogen is stabilized by interactions with the activation peptide. Release of the activation peptide increases a dynamic flap mobility and in time this leads to conformational changes that disrupt the catalytic site and expose a cryptic thrombin-cleavage site present at Arg-323 (By similarity)
Requires high salt concentrations for activity and thermostability; 1.5-1.8 M KH(2)PO(4) stimulates activity while stabilizing the enzyme
Has no constitutive proton transporter activity and has to be activated by long-chain fatty acids/LCFAs (PubMed:28781081). Inhibited by purine nucleotides (PubMed:28781081). Both purine nucleotides and LCFAs bind the cytosolic side of the transporter and directly compete to activate or inhibit it (PubMed:28781081). Activated by noradrenaline and reactive oxygen species. Despite lacking canonical translational encoding for selenocysteine, a small pool of the protein has been observed to selectively incorporate selenocysteine at 'Cys-254'. Selenocysteine-modified protein is highly sensitive to redox modification and may constitute a pool of protein highly sensitive to activation by elevated levels of reactive oxygen species (ROS)
Transport activity inhibited by 1-N-naphthylphthalamic acid (NPA), cyclopropyl propane dione (CPD), cyclosporin A, verapamil and quercetin
Inhibited by AIM-100 (4-amino-5,6-biaryl-furo[2,3-d]pyrimidine), which suppresses activating phosphorylation at Tyr-284. Repressed by dasatinib
Strongly inhibited by S-adenosyl-1,8-diamino-3-thiooctane
Inhibited by diisopropyl fluorophosphate and diethyl-P-nitrophenyl phosphate
Negatively regulated by ATP. Not redox-regulated. The formation of intramolecular disulfide bonds does not alter enzymatic activity
Inhibited by the adenylate analogs, 5'-O-[N-(salicyl)sulfamoyl]adenosine (Sal-AMS) and 5'-O-[N-(2,3-dihydroxybenzoyl)sulfamoyl]adenosine (DHB-AMS). Adenylation of 2,3-dihydroxybenzoate (DHB) is enhanced by a protein-protein interaction between the EntA and EntE
Inhibited by cyclosporin A (CsA) (PubMed:20676357). Is displaced by CsA from the mPTP leading to a lower open probability of the mPTP
Inhibited by adenosine 5'-(alpha,beta-methylene)-diphosphate (AMPCP)
Inhibited by aminoalkyl phosphinate analogs
Inhibited by aminooxyacetate and beta-chloro-L-alanine, but not by p-hydroxymercuribenzoate
Activated by dual phosphorylation at Thr-256 and Tyr-258 (PubMed:20624915). May be inactivated by lip-1-mediated dephosphorylation (PubMed:21901106)
DNase activity is activated upon ligand binding
Inhibited by 1-[2-cyano-3,12-dioxooleana-1,9(11)- dien-28-oyl]ethylamide (CDDO-EA) with an IC(50) of 60 uM (PubMed:28134508). Inhibited by Fe3+ and Cu2+ and the O-acyltransferase activity is completely blocked over 5 mM Fe3+ and 0.5 mM Cu2+ (PubMed:19501572)
Levels are regulated by proteolytic cleavage by PepD to help maintain cell envelope homeostasis
Activated by GTP. Inhibited by CDP-diacylglycerol and by phosphatidylglycerol 4,5-bisphosphate (PPI2)
ATPase activity is influenced by KaiB1 and KaiB3 in vitro; ATPase is reduced 35% by the KaiB1 tetramer and 55% by the KaiB3 monomer but not affected by KaiA or the KaiB3 tetramer
Inhibited by antizyme (AZ) in response to polyamine levels. AZ inhibits the assembly of the functional homodimer by binding to ODC monomers and targeting them for ubiquitin-independent proteolytic destruction by the 26S proteasome (By similarity). Inhibited by 1-amino-oxy-3-aminopropane (APA, an isosteric analog of putrescine) (PubMed:17407445). Irreversibly inhibited by alpha-difluoromethylornithine (DFMO, a curative agent of West African sleeping sickness) (PubMed:3098971, PubMed:17407445)
Inhibited by beta-lactone-based lipid inhibitors, such as beta-lactone palmostatin-B
Partially inhibited by N-(2-aminoethyl)-5-chloroisoquinoline-8-sulfonamide (CKI-7)
Activity is stimulated by YcdY
Both ssDNase and ssRNase are inhibited by EDTA
Reversibly inhibited by nordihydroguaiaretic acid (NDGA) and irreversibly by salicylic acid
Phosphate uptake is dependent on the presence of divalent cations, which form soluble metal phosphate (MeHP04) complexes (PubMed:8110778, PubMed:10713426). In Mg(2+)-limiting conditions, the PhoQP-regulated small protein MgtS and sRNA MgrR both regulate the PitA transporter, leading to increased intracellular Mg(2+) (PubMed:30276893). Metal phosphate uptake is inhibited at low internal pH (PubMed:8110778). Inhibited by the uncoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP) (PubMed:328484). Is also inhibited by the energy uncoupler 2,4-dinitrophenol and the sulfhydryl reagent N-ethylmaleimide (PubMed:6998957)
Activated by calcium (PubMed:8440720, PubMed:8142371, PubMed:7808482). Upon calcium binding to the EF-hand domains, the C-terminus of the junction domain (J domain) undergoes a conformational change which results in the dissociation of the pseudo-substrate inhibitory motif from the catalytic domain (By similarity). This, in turn may facilitate the autophosphorylation of the activation loop at Thr-231, which leads to the kinase activation (By similarity). Inhibited by calmodulin antagonists such as calmidazolium, trifluoperazine, N-[6-aminohexyl]-5-chloro-1-naphthalene-sulfonamide, and ophiobolin A (PubMed:7808482)
Autophosphorylates on Tyr-356 and Tyr-358
CARD8 inflammasome is activated by HIV-1 protease activity: HIV-1 protease cleaves CARD8, promoting ubiquitination and degradation of the N-terminal part, releasing the cleaved C-terminal part of the protein (Caspase recruitment domain-containing protein 8, C-terminus), which polymerizes and forms the CARD8 inflammasome (PubMed:33542150). CARD8 inflammasome is inhibited by DPP8 and DPP9, which sequester the C-terminal fragment of CARD8 (Caspase recruitment domain-containing protein 8, C-terminus) in a ternary complex, thereby preventing CARD8 oligomerization and activation (PubMed:29967349, PubMed:31525884, PubMed:32796818, PubMed:34019797). CARD8 inflammasome is activated by Val-boroPro (Talabostat, PT-100), an inhibitor of dipeptidyl peptidases DPP8 and DPP9 (PubMed:29967349, PubMed:31525884, PubMed:32796818, PubMed:33053349, PubMed:32840892, PubMed:34019797, PubMed:36357533). Val-boroPro relieves inhibition of DPP8 and/or DPP9 by inducing the proteasome-mediated destruction of the N-terminal part of CARD8, releasing its C-terminal part from autoinhibition (PubMed:29967349, PubMed:31525884, PubMed:32796818, PubMed:34019797, PubMed:36357533). Indirectly activated by the pseudodipeptide CQ31 (PubMed:35165443). CQ31 directly inactivates the peptidases PEPD and XPNPEP1, leading to an accumulation of dipeptides that weaky inhibit DDP8 and DPP9, relieving DPP8- and/or DPP9-mediated inhibition of CARD8 (PubMed:35165443)
Is inactivated in vitro by the mechanism-based inactivator 5-fluoro-beta-L-idopyranosyl fluoride (5FIdoF) that yields a covalent glycosyl-enzyme complex with the active site nucleophile Asp-405
Phosphorylation at Thr-14 or Tyr-15 inactivates the enzyme, while phosphorylation at Thr-181 activates it
Leucine uptake is inhibited by the proton ionophore carbonyl cyanide m-chlorophenylhydrazone (CCCP)
Inhibited by zinc. Stimulated by calcium and bacitracin
Isoform Short: Inhibited by L-ornithine with a Ki of approximately 0.25 mm. Isoform Long: Insensitive to ornithine inhibition. Thus, the two amino acid insert in the long isoform abolishes feedback inhibition of P5CS activity by L-ornithine
Activated during dark in short day conditions
Inhibited in a dose dependent manner by sialorphin
Actin binding is enhanced by calcium Ca(2+)
Activated by divalent cations (PubMed:16527816). Activated by bile acids and their conjugates, except for lithocholic acid which is rather inhibitory. Binding of deoxycholic acid favors the selective release of anandamide and likely other unsatured long FAEs (PubMed:27571266, PubMed:25684574). Inhibited by phosphatidylethanolamines (PubMed:25684574)
Activated by inorganic phosphate, and to a lesser extent by sulfate ions (PubMed:2169413). In addition to form a complex with ATP, Mg(2+) also acts as a cofactor (PubMed:2169413). Strongly inhibited by ADP through competitive binding at the activation site and at a specific allosteric site (PubMed:2169413, PubMed:16008562). Less strongly inhibited by alpha,beta-methylene ATP (mADP), AMP, GDP, GMP and UTP (PubMed:2169413, PubMed:16008562)
Inhibited by high concentrations of magnesium (>10 mM) and by EDTA in vitro
Is irreversibly inactivated by the beta-lactams carbapenems via the formation of a covalent adduct resulting from acylation of the catalytic Cys; imipenem is the most efficient drug for in vitro LdtMt2 inactivation
During activation, the N-terminal disordered prodomain is removed by cleavage. Concomitantly, double cleavage gives rise to a large Caspase-7 subunit p20 and a small Caspase-7 subunit p11. The two large and two small subunits then assemble to form the active CASP7 complex. Can be cleaved and activated by different caspases, depending on the context (By similarity). Cleaved and activated by initiator caspases (CASP8 and/or CASP9), leading to execution phase of apoptosis (By similarity). Cleavage and maturation by GZMB regulates granzyme-mediated programmed cell death. Cleavage and maturation by CASP1 regulates pyroptosis (By similarity). Inhibited by XIAP, which directly binds to the active site pocket and obstructs substrate entry. Phosphorylation at Ser-30 and Ser-239 by PAK2 inhibits its activity (By similarity)
In the inactive state, the N terminus protrudes into the active site of the Rho-GAP domain, sterically blocking Rac binding. Phospholipid binding to the Phorbol-ester/DAG-type zinc-finger/C1 domain triggers the cooperative dissociation of these interactions, allowing the N-terminus to move out of the active site and thereby activating the enzyme
Requires the presence of IpdC
Activated by glycerol, not effected by dimethyl sulfoxide and inhibited by high concentration of monovalent salts, UDP-xylose, UDP-arabinose or UDP
Negatively regulated by the anti-sigma-I factor RsgI. Upon exposure to heat, SigI is released from RsgI and activated. Transient heat activation of SigI may depend upon DnaK chaperone
Activated by lipids, particularly cardiolipin and to a lesser extent by other acidic phospholipids and unsaturated fatty acids. Two specific sites, Thr-1022 (activation loop of the kinase domain) and Thr-1164 (turn motif), may be needed to be phosphorylated for its full activation (By similarity). Kinase activity is activated upon binding to GTP-bound Rho/Rac GTPases
Inhibited by 5-fluoro-2'-deoxyuridine 5'-monophosphate (FdUMP)
Inhibited by the phytotoxin cyperin and the synthetic antimicrobial compound triclosan
Acyltransferase activity is regulated by the binding of GTP and Ca(2+): inactivated by GTP, which stabilizes its closed structure, thereby obstructing the accessibility of substrates to the active sites (PubMed:2903073, PubMed:7592956, PubMed:18092889, PubMed:31991788). In contrast, Ca(2+) acts as a cofactor by inducing conformational change to the active open form (PubMed:2903073, PubMed:18092889, PubMed:31991788). In absence of Ca(2+), Mg(2+) may bind Ca(2+)-binding sites, promoting GTP-binding and subsequent inhibition of the acyltransferase activity (PubMed:31991788). Specifically inhibited by compound VA4 ((S)-Benzyl (6-Acrylamido-1-(4-((5-(dimethylamino)naphthalen-1-yl)sulfonyl)piperazin-1-yl)-1-oxohexan-2-yl)carbamate), which specifically abolishes both the transamidation and GTP-binding activities (PubMed:28858494)
Inhibited by ADP but not significantly by other nucleotides, inhibited by diphosphate and less well by triphosphate
Synthesis is increased during S and G2 phases, presumably by an increase in transcription; activity is decreased by phosphorylation during m phase. Protein levels fall in M phase as a result of decreased synthesis combined with degradation. Activity seems to be negatively regulated by phosphorylation upon entry into mitosis, although N-terminal phosphorylation might also regulate the protein stability via protection from proteolysis or might regulate the subcellular location (By similarity)
Significantly inhibited by Cu(2+), Fe(3+) and Co(2+). Partially inhibited by Mg(2+), Ca(2+) and Mn(2+). Also inhibited by ATP, ADP, dATP, TTP and GTP
Inhibited by PhrI
Phosphoenolpyruvate carboxykinase activity is regulated by acetylation and glucose levels (PubMed:30193097). The anaplerotic conversion of phosphoenolpyruvate to oxaloacetate is improved by PCK1 acetylation on Lys-91 (K91ac), Lys-473 (K473ac) and Lys-521 (K521ac) (PubMed:30193097). High glucose concentrations favor PCK1 anaplerotic activity by triggering acetylation on Lys-91 (K91ac). At low glucose levels, SIRT1-mediated deacetylation of Lys-91 promotes the cataplerotic conversion of oxaloacetate to phosphoenolpyruvate (By similarity). Phosphoenolpyruvate carboxykinase activity is inhibited by 3-mercaptopicolinate (PubMed:26322521). Phosphoenolpyruvate carboxykinase activity is inhibited by 3-[(carboxymethyl)thio]picolinate (CMP), which acts as a competitive inhibitor at the oxaloacetate/phosphoenolpyruvate-binding site (PubMed:31461616). Phosphorylation at Ser-90 reduces the binding affinity to oxaloacetate and converts the enzyme into an atypical protein kinase using GTP as donor (By similarity)
Complete inhibition by 4-(2-aminoethyl)-benzenesulfonyl fluoride (AEBSF), N-tosyl-L-phenylalanine chloromethylketone (TPCK), Hg(2+) and diethyl-pyrocarbonate (DEPC) (PubMed:15110860). 50% inhibition by N-(N-(L-3-trans-carboxirane-2-carbonyl)-L-leucyl)-agmanitine (E-64), N-alpha-p-tosyl-L-lysine chloromethylketone (TLCK) and phenylmethylsulfonyl fluoride (PMSF) (PubMed:15110860)
Exhibits higher affinity for 1-butanol compared to 1,2-propanediol but inhibited by 10 mM 1-butanol
nlrp1 inflammasome is activated by pathogens and other damage-associated signals: activation promotes ubiquitination and degradation of the N-terminal part, releasing the cleaved C-terminal part of the protein (NACHT, LRR and PYD domains-containing protein 1, C-terminus), which polymerizes and forms the nlrp1 inflammasome
Feed-back regulated by NAD. A high level of NAD causes NadR to lose enzymatic activity and repress several NAD synthetic genes; conversely, a low NAD level activates the assimilatory enzymatic activities and leads to derepression of biosynthetic genes (By similarity)
Pre-incubation with heparin markedly reduces the neurotoxicity of this toxin
Inhibited in feedback fashion by the catecholamine neurotransmitters, especially by dopamine in competition with tetrahydrobiopterin. Phosphorylation of several Ser/Thr residues in the N-terminus regulates the catalytic activity. Ser-31 and Ser-40 are readily phosphorylated to activate the catalytic activity. A Cysteine modification induced by N-ethylmaleimide (NEM), inhibits tyrosine 3-monooxygenase activity through the modification of the Cys-170
Inhibited by phenylmethanesulfonyl fluoride, 3,4,dichloroisocoumarin, diisopropyl fluorophosphate (DFP) and diethyl p-nitrophenyl phosphate (DENP)
During activation, the N-terminal disordered prodomain is removed by cleavage. Concomitantly, double cleavage gives rise to a large Caspase-7 subunit p20 and a small Caspase-7 subunit p11. The two large and two small subunits then assemble to form the active CASP7 complex. Can be cleaved and activated by different caspases, depending on the context (By similarity). Cleaved and activated by initiator caspases (CASP8 and/or CASP9), leading to execution phase of apoptosis (By similarity). Cleavage and maturation by GZMB regulates granzyme-mediated programmed cell death. Cleavage and maturation by CASP1 regulates pyroptosis (By similarity)
Inhibited by the C-terminal non-catalytic region. Activated by caspase-cleavage. Full activation also requires homodimerization and autophosphorylation of Thr-179 (By similarity)
Alternates between an inactive form bound to GDP and an active form bound to GTP. Activated by a guanine nucleotide-exchange factor (GEF) and inactivated by a GTPase-activating protein (GAP) (By similarity)
Inhibited by GdCl(3), but not by verapamil
Inhibited by dithiotreitol (DTT)
Inhibited by pyridoxal- 5'-phosphate, bathophenanthroline, tannic acid, bromocresol purple, butylmalonate and phenylsuccinate
Inhibited by lithium. Lithium inhibition is competitive with respect to magnesium but non-competitive with respect to the peptide substrate
Activated by ATP (By similarity). ATP binding leads to a conformational change that promotes FAD cofactor binding and enzyme activity (By similarity). ATP binding likely occurs during acox-1.5 folding and/or dimer formation (By similarity)
Inhibited by nonsteroidal the anti-inflammatory drugs (NSAID) flufenamic (PubMed:14672942). The oxidation reaction is inhibited by low micromolar concentrations of NADPH (PubMed:14672942)
2-ketogluconate acts as a molecular effector and causes dissociation of PtxS from its target promoter (PubMed:33529626). Glucose negatively affects the molecular binding of PtxS and 2KGA, and gluconic acid inhibits the PtxS-2KGA binding reaction (PubMed:33529626)
Inactivated by EDTA
Produced as a latent enzyme which is activated by dsRNA generated during the course of viral infection. The dsRNA activator must be at least 15 nucleotides long, and no modification of the 2'-hydroxyl group is tolerated (PubMed:34581622). ssRNA or dsDNA do not act as activators
Phosphorylation leads to a decrease of the catalytic activity
Kinase activity is activated by topbp1
Inhibited by several divalent cations, including Zn(2+)
Competitively inhibited by riboflavin (Ki of 17 uM)
Strongly inhibited by glucose. No activity is lost during treatment with 100 mM EDTA after 2 hours. Activity not considerably affected by metal ions (5 mM), including Na(+), K(+), Mg(2+), Co(2+) and Ca(2+). Completely inhibited by Cu(2+) and Zn(2+) (5 mM) and is strongly inhibited by Mn(2+) (11%), Fe(2+) (25%) and Ni(2+) (38%) in comparison with the activity in the absence of cations (100%). Activity not affected by dithiothreitol, beta-mercaptoethanol and L-cysteine whereas reduced glutathione almost completely inactivates it. With ONPG as substrate, the addition of ethanol up to 20% still slightly stimulates activity. The activity increases up to 120% in the presence of 8% v/v ethanol at pH 5.5
No metal dependence, but Mn(2+) increases the activity with alpha-cyclodextrin as substrate. No effect on the activity with presence or absence of Ca(2+), Zn(2+), Tween-20 or EDTA
Potently inhibited by L-vesamicol, reserpine and tetrabenazine
Specifically inhibited by a compound named 3r ((R)-2-((1-cyclopentyl-4-hydroxy-1H-pyrazolo[3,4-d]pyrimidin-6- yl)amino)-N-(4-methoxyphenyl)propanamide); the inhibitor forms a hydrogen bond with Tyr-484, Ala-512 and Gln-513
Strongly inhibited by FK506
Present in an inactive conformation in the absence of bound ligand. Binding of PDGFA and/or PDGFB leads to dimerization and activation by autophosphorylation on tyrosine residues. Inhibited by imatinib, nilotinib and sorafenib
Inhibited by micromolar concentrations of guanidinium chloride. Inhibits the ATPase activity, but does not dissociate the hexameric protein
Inhibited by NB-598 ((E)N-ethyl-N-(6,6-dimethyl-2-hepten-4-ynyl)-3-[(3,3'-bi-thiophen-5-yl)methoxy]benzene-methanamine). Contrary to fungal enzymes, the mammalian enzyme is only slightly inhibited by terbinafine
The dipeptidyl carboxypeptidase activity is strongly activated by chloride (PubMed:7683654, PubMed:11432860, PubMed:15615692, PubMed:12540854, PubMed:16476442). The dipeptidyl carboxypeptidase activity is specifically inhibited by lisinopril, captopril and enalaprilat (PubMed:6270633, PubMed:6208535, PubMed:1320019, PubMed:7876104, PubMed:8609242, PubMed:12540854, PubMed:16476442)
Inhibited by suramin. NAD-dependent lysine desuccinylase activity is inhibited by physiological nicotinamide concentrations, while deacetylase activity is not. In contrast, resveratrol activates deacetylase activity, while inhibiting desuccinylase activity
Inhibited by cyanide
The enzyme is subject to end product inhibition by NADPH and 2-oxoglutarate
Competitively inhibited by pyrrolidine dione antibiotic moiramide B (CPD1)
Activated via binding to highly phosphorylated inositol phosphates such as inositolhexakisphosphate (InsP6) which mediates the release of an N-terminal auto-inhibitory region (By similarity). Activation requires not only RIPK3-dependent phosphorylation but also binding to highly phosphorylated inositol phosphates (By similarity)
Inhibited by 2,4-dinitrophenol
Phosphorylation affects GTPase activity as well as polymerization ability
Inhibited by hygromycin and streptomycin, but not by gentamycin or kanamycin
Activated by cAMP, and at 10-100 times higher concentrations, also by cGMP. cAMP binding promotes tetramerization and formation of an active channel. Compared to other family members, cAMP has less stimulatory effect on HCN1 because part of the molecules already contain bound cAMP and form homotetramers when cAMP levels are low. Inhibited by Cs(1+), zatebradine, capsazepine and ZD7288
Active in zinc-limited cells and repressed in replete cells. Zinc controls ZAP1 DNA binding activity
GABA transport is inhibited by beta-alanine, taurine, hypotaurine, beta-guanidinopropionic acid and 2,3-diaminopropionic acid (PubMed:8420981). Beta-alanine transport is inhibited by GABA (PubMed:8420981)
Activity can be regulated by an intermolecular trans association between the zinc-binding domain and the catalytic core domain of two different primase molecules
Inhibited by umbelliferone, 8-anilinonaphthalenesulfonate, a range of metal-chelating agents, and Hg(2+), Cd(2+) and Pb(2+) ions
Phosphorylation at Tyr-341 is necessary and sufficient for the activation of E3 activity
Protease activity is inhibited by PMSF
Inhibited by antimycin A
Inhibited by low concentration of 4-fluoro-7-nitrobenzofurazan (NBD-F)
Inhibited by sphingomyelin
Inhibited by diisopropyl fluorophosphate
Taurine transport activity is inhibited by L-alanine, guanidinoethane sulfonate, homotaurine and phorbol 12-myristate 13-acetate (PubMed:11118543). Taurine transport activity is stimulated by hypertonic stress (PubMed:11118543)
Ca(2+) binding promotes protein stability and formation of the active homodimer
Activated by cytokinins to initiate phosphorelay signaling. This cytokinin-mediated activation is repressed by the trans-zeatin antagonists 6-(2-hydroxy-3-methylbenzylamino)purine (PI-55) and 6-(2,5-dihydroxybenzylamino)purine (LGR-991)
Inhibited by PMSF and EDTA. Slightly inhibited by Cu(2+) and Zn(2+). Not inhibited by aprotinin, SBTI, Ca(2+), Mg(2+), Na(+) and K(+)
Efflux activity is inhibited by carbonyl cyanide m-chlorophenylhydrazone (CCCP) and verapamil
Activated by insulin. Inhibited by diphenylene iodonium. Inhibited by plumbagin. Activated by phorbol 12-myristate 13-acetate (PMA) (By similarity)
Inhibited by Na(3)BO(3) and KCN. No inhibition by sodium dodecyl sulfate, even at high concentration
Activated by Ca(2+)-bound calmodulin following an increase in intracellular Ca(2+) (PubMed:26794871). At low Ca(2+) concentrations, the catalytic subunit (also known as calcineurin A) is inactive and is bound to the regulatory subunit (also known as calcineurin B) in which only two high-affinity binding sites are occupied by Ca(2+) (PubMed:26794871). In response to elevated calcium levels, the occupancy of the low-affinity sites on calcineurin B by Ca(2+) causes a conformational change of the C-terminal regulatory domain of calcineurin A, resulting in the exposure of the calmodulin-binding domain and in the partial activation of calcineurin A (PubMed:26794871). The subsequent binding of Ca(2+)-bound calmodulin leads to the displacement of the autoinhibitory domain from the active site and possibly of the autoinhibitory segment from the substrate binding site which fully activates calcineurin A (PubMed:26794871). Inhibited by immunosuppressant drug FK506 (tacrolimus) in complex with FKBP12 and also by immunosuppressant drug cyclosporin A (CsA) in complex with PPIA/cyclophilin A; the inhibition is Ca(2+)-dependent (By similarity)
Strongly inhibited by Ba(2+). To a lesser extent, is also inhibited by Sn(2+), Mg(2+) and Ag(+). Inhibited by EDTA in vitro
Inhibited by 3'-dATP
Specifically and competitively inhibited by 2-thiomalate, which coordinates with the catalytic [4Fe-4S] cluster (PubMed:30645090). Weakly inhibited by malonate (PubMed:27528683)
Allosterically activated by various compounds including ATP, 2,3-BPG/2,3-Bisphosphoglyceric acid and Ap4A/P1,P4-bis(5'-adenosyl) tetraphosphate (PubMed:9371705, PubMed:8031149). Binding of an allosteric activator is a prerequisiste to magnesium and substrate binding (By similarity). Inhibited by inorganic phosphate (By similarity)
The nuclease activity shows a general salt dependency with a clear reduction by magnesium and sulfate ions
Strongly inhibited by PMSF, and moderately by benzamidine and soybean trypsin inhibitor
The relative activities of the inhibitory tyrosine-protein kinase CSK and the activating tyrosine-protein phosphatase PTPRC/CD45 determine the level of LCK activity. These interactions allow rapid and efficient activation of LCK in response to TCR stimulation
Activity increases by approximately two-fold in the presence of GCBP
Alternates between an inactive form bound to GDP and an active form bound to GTP. Activated by a guanine nucleotide-exchange factor (GEF) and inactivated by a GTPase-activating protein (GAP). Interaction with SOS1 promotes exchange of bound GDP by GTP
Strongly inhibited by eserin, NaF, HgCl2, SDS and Triton X-100
Activated by cytosolic calcium, which is necessary for binding to membrane lipids (PubMed:12672805). Activated by phosphorylation in response to mitogenic stimuli (PubMed:8381049). Activated by ceramide-1-phosphate. Binding (via C2 domain) to ceramide-1-phosphate increases the affinity for membrane lipids (PubMed:17472963). Can be activated by phosphoinositides in the absence of calcium (PubMed:12672805). Inhibited by ANXA5 in a calcium- and substrate-dependent way (PubMed:9425121)
Nearly completely inhibited by 0.5 mM ZnCl(2), 0.1 mM N-tosyl-L-lysyl chloromethyl ketone (TLCK) and 0.1 mM leupeptin. Strongly inhibited by 0.5 mM CoCl(2) and 0.1 mM chymostatin. Activity is hardly affected by general serine protease inhibitors phenylmethanesulfonyl fluoride (PMSF), diisopropyl fluorophosphate (DFP) and N-tosyl-L-phenyl-alanyl chloromethyl ketone (TPCK) or by aspartyl protease inhibitor pepstatin A or by CaCl(2) and EDTA. Cysteine protease inhibitors, such as N-ethylmaleimide (NEM), iodoacetic acid and L-trans-epoxysuccinyl-leucylamido(4-guanido)butane (E-64) have no effect on activity
ATP-binding allows dimerization and subsequent antagonistic effect against FleQ
Activated by clathrin (By similarity). Only slightly inhibited by wortmannin and LY294002. Activated by insulin
Inhibited by serine/threonine phosphatase 2A
Activated by fructose 2,6-bisphosphate, activated by the effector in a cooperative manner
SsDNA cleavage is inhibited by MazF4
Active when the heme iron is in the ferrous state (PubMed:12773527). Is very sensitive to AgNO(3), is also inhibited by hydroxylamine and phenylhydrazine, and hardly inhibited by thiol reagents (PubMed:12773527). Not sensitive to chelating agents and serine-modifying reagents (PubMed:12773527)
ECF sigma-E is held in an inactive form by its cognate anti-sigma factor (RseA) until released by regulated intramembrane proteolysis (RIP). RIP occurs when an extracytoplasmic signal (periplasmic stress and excess LPS) triggers a concerted proteolytic cascade to transmit information and elicit cellular responses. The anti-sigma factor RseA is an inner membrane protein, binding sigma-E in the cytoplasm and RseB in the periplasm. RseA is first cut extracytoplasmically (site-1 protease, S1P, by DegS), then within the membrane itself (site-2 protease, S2P, by RseP), while cytoplasmic proteases (predominantly ClpX-ClpP) finish degrading the regulatory protein, liberating sigma-E (PubMed:15371343). Degradation of RseA requires 2 signals to activate DegS; an outer membrane protein (OMP) signal activates DegS, while an LPS signal causes release of RseB from RseA, freeing RseA to be cleaved (PubMed:23687042). The rate-limiting step in this protease cascade is the first signal-sensing cleavage (half-life about 1 minute) (PubMed:17210793)
Requires Ca(2+) for stability (PubMed:2116590). Activity is inhibited by phenylmethylsulfonyl fluoride (PMSF) and EDTA (PubMed:2116590, PubMed:3142851)
Activated by guanosine analogs including deoxyguanosine, 7-thia-8-oxoguanosine or 7-deazaguanosine in a RNA-independent manner
Is inhibited by H(2)O(2). 1,10-phenanthroline inhibits the activity slightly, but other metal cation chelators such as EDTA or tiron have no effect on the activity. Divalent metal cations and hydroxylamine have also no effect on the activity. Due to the relationship of the protein with glutamine synthetases, glutamate and glutamine were tested as inhibitors; neither preincubation of the compounds with the enzyme nor their addition to the assay buffer affected 3HAP mutase activity
Highly susceptible to inhibition by indole-3-pyruvate (PubMed:24835098). Activity is not affected by the presence of metal ions, EDTA, KCl or DMSO (PubMed:24835098)
Inhibited by 3-isobutyl-1-methylxanthine (IBMX), zaprinast and dipyridamole. cGMP acts as an allosteric activator. Weakly inhibited by Sildenafil (Viagra) and Tadalafil (Cialis); however, the fact that the protein is probably absent from testis, suggests that it is not biologically relevant and is not related with erectile dysfunction
The presence of cobalamin does not affect the ATPase activity
Inhibited by pepstatin A (PubMed:29943906). Inhibited by KNI derived compounds (KNI-10742, 10743, 10395, 10333, and 10343) (PubMed:29943906)
Sulfate could be an allosteric effector of the enzyme that is responsible for stabilizing substrate binding. In addition, this anion effector may act as a counterion during enzyme-mediated catalysis
Binds heme and heme binding inhibits DNA binding
Its casein hydrolytic activity is inhibited almost completely by a chelating agent (EDTA), whereas neither diisopropyl fluorophosphate nor phenylmethylsulfonyl fluoride inhibit the proteolytic activity in vitro
Exopolyphosphatase activity is inhibited by ppGpp alarmones produced during the bacterial stringent response
Inhibited by Ag(+), Cu(2+), Fe(2+), Hg(2+), V(3+) and phenylmethylsulfonyl fluoride (PMSF)
Gyrase is the target of many classes of inhibitors, including coumarins, cyclothialidines, pyrrolopyrimidines, pyrazolthiazoles and (fluoro)quinolones. Quinolones bind GyrA when the enzyme is complexed with DNA and trap the enzyme in a covalent reaction intermediate with DNA (PubMed:3031051, PubMed:12051842). Coumarins bind to GyrB and are competitive inhibitors of its ATPase activity (PubMed:7811004). Cyclothialidines also bind GyrB and are ATPase competitive inhibitors; they seem to act differently from coumarins (PubMed:7811004). Pyrrolopyrimidines inhibit both GyrB and its paralog in topoisomerase IV (parE) (PubMed:23294697). Pyrazolthiazoles also inhibit the ATPase activity of GyrB (PubMed:20356737). DNA supercoiling and relaxation are both inhibited by oxolinic acid (PubMed:337300). Acriflavine inhibits supercoiling activity and DNA-stimulated ATPase activity (PubMed:9148951). DNA supercoiling activity is protected from fluoroquinolone inhibition by QnrB4; QnrB4 has no effect on supercoiling activity alone (PubMed:19060136)
Inhibited by pentalenolactone
Inhibited by the herbicide acifluorfen
Shows highest activity at 4 M KCl. Does not require divalent ions for activity
Inhibited by CCCP and valinomycin
Inhibited by the sodium/calcium exchanger inhibitor CGP-37157. Strongly inhibited by zinc
Regulated by autophosphorylation, can both activate or decrease activity (PubMed:8343951, PubMed:20304997, PubMed:21726629). Heme regulates its activity by enhancing the phosphorylation on Tyr-1007 and Tyr-1008 (By similarity)
Inhibited in a dose-dependent manner by non-specific trypsin-like serine protease inhibitors including benzamidine
Activated by tyrosine and threonine phosphorylation (By similarity). Activated in response to hyperosmolarity, hydrogen peroxide, and epidermal growth factor (EGF)
Activated by EGF, NRG1 and IGF1. Inhibited by SOCS3 to phosphorylate STAT3. Stabilized in the inactive form by an association between the SH3 domain and the SH2-TK linker region. Interaction between Trp-184 within SH2-TK linker region and the catalytic domain appears essential for positive regulation of kinase activity
Activated by high osmotic strength
DNA-binding activates the protease activity: single-stranded DNA-binding specifically activates ability to cleave covalent DNA-protein cross-links (DPCs) (By similarity). In contrast, double-stranded DNA-binding specifically activates autocatalytic cleavage, and subsequent inactivation (By similarity)
Inhibited by the proton ionophore carbonyl cyanide m-chlorophenylhydrazone (CCCP) (PubMed:2115866, PubMed:9498571). Partially inhibited by the respiratory chain inhibitor KCN (PubMed:2115866). Activity is Na(+) independent (PubMed:2115866, PubMed:9498571)
Activity depends on O(2)-binding and heme redox state: the Fe(III), Fe(II)-O(2), and Fe(II)-CO complexes of DosC are active forms, whereas Fe(II) and Fe(II)-NO complexes are inactive forms
Weakly inhibited by thiocyanate (SCN(-))
Inhibited by chelating agents like EDTA, TPEN and 1,1-phenanthroline, as well as NEM, free cysteine and DTT
In the absence of bound tRNA, ATP is bound in a non-productive mode, and the enzyme cannot activate amino acids
Activity is sensitive to salt concentration, a high concentration of KCL (500 mM) is needed for complete inactivation
Activated by phosphorylation at Thr-175
Strongly inhibited by diisopropyl fluorophosphate and Pefabloc. Weakly inhibited by 3,4-dichloroisocumarin. Not inhibited by phenylmethylsulfonyl fluoride, leupeptin, antipain or prolinal. Activated by iodoacetamide
Shows aldolase activity only when expressed and copurified with HsaG. This arrangement probably prevents the deleterious formation and release of toxic aldehydes in the absence of the partner dehydrogenase
Inhibited by spermidine (PubMed:116850). Inhibited by N-(phosphonoacetyl)-putrescine (PubMed:17028272, PubMed:4621632, PubMed:22363663). Inhibited by N-(phosphonoacetyl)-L-ornithine (PubMed:22363663)
Inhibited by SERPINA5. Activity is strongly inhibited by Zn2+, 100 times more abundant in semen than in serum. This inhibition is relieved by exposure to semenogelins, which are avid zinc binders
Inhibited by excess pyrophosphate as well as excess Mg(2+). Inhibition by ATP, GTP, and CTP is reversed by increasing the Mg(2+) concentration. This suggests that the substrate is a particular metal complex such as MgPPi(2-). Modification of Asp-283 with DCCD abolishes pyrophosphatase activity
Hemagglutination activity requires divalent cations such as Ca(2+) (PubMed:31769916, PubMed:33328520). Hemagglutination activity is weakly inhibited by monosaccharides such as D-Gal (25 mM), D-GalNAc (25 mM) and D-Fuc (25 mM) and by disaccharides such as melibiose (25 mM) and lactose (25 mM). Hemagglutination activity is inhibited by bovine submaxillary mucin, but not by porcine stomach mucin or fetuin (PubMed:31769916)
6-phosphofructo-2-kinase activity is activated by pyruvate. 6-phosphofructo-2-kinase activity is inhibited by PPi, phosphoenolpyruvate and 2-phosphoglycerate. Fructose-2,6-bisphosphatase activity is inhibited by pyruvate, fructose 1,6-bisphosphate and 6-phosphogluconate
Isoform 1 and isoform 2 are differently regulated by calcium and DAG
NADH, NADPH or ATP do not increase activity
Activated by homooligomerization induced by direct binding to cytosolic LPS, in a TLR4-independent manner (PubMed:22002608, PubMed:23348507, PubMed:23887873, PubMed:24031018, PubMed:25119034). In addition to LPS, CASP4/CASP11 may also be activated by oxidized phospholipid 1-palmitoyl-2-arachidonoyl- sn-glycero-3-phosphorylcholine, an oxidized phospholipid (oxPAPC), in dendritic cells, promoting adaptive immunity (PubMed:27103670). The role of oxPAPC is however unclear and another report suggests that oxPAPC competes with LPS-binding and inhibits the non-canonical inflammasome in macrophages (PubMed:29520027)
Inhibited by 2-aminopentanoic acid (norvaline). Activated by phosphate and nucleoside monophosphates such as AMP, GMP, CMP, UMP. Allosterically inhibited by the polyamines such as spermidine and putrescine
Under complex allosteric control mediated by deoxynucleoside triphosphates and ATP binding to separate specificity and activation sites on the R1 subunit. The type of nucleotide bound at the specificity site determines substrate preference. It seems probable that ATP makes the enzyme reduce CDP and UDP, dGTP favors ADP reduction and dTTP favors GDP reduction. Stimulated by ATP and inhibited by dATP binding to the activity site. Inhibited by SML1
Specifically inhibited by remodelin (4-[2-(2-cyclopentylidenehydrazinyl)-4-thiazolyl]-benzonitrile, monohydrobromide), a hydrobromide salt molecule (PubMed:24786082). Remodelin can improve nuclear architecture, chromatin organization and fitness of cells from patients suffering from Hutchinson-Gilford progeria syndrome (HGPS); molecular mechanisms explaining the relation between NAT10 activity and nuclear architecture are however unclear (PubMed:24786082)
Binding of a wide range of cationic hydrophobic compounds to SCO4008 causes a decrease in DNA-binding, probably via allosteric conformational change of SCO4008
Phosphorylation on Ser-47 inhibits the phosphoryl transfer from enzyme I to HPr
Specifically feedback inhibited by tyrosine with 50% inhibition observed at 9 microM tyrosine, pH 7.0
Inhibited by the anti-tuberculous drug Q203, an optimized imidazopyridine amide (IPA) compound. Q203 triggers a rapid ATP depletion in M.tuberculosis grown under an aerobic or anaerobic atmosphere (PubMed:23913123). Also inhibited by LPZS (lansoprazole sulfide), a metabolite of LPZ (lansoprazole) generated by intracellular sulfoxide reduction into the host cytoplasm; LPZS is a potent anti-mycobacterial agent that inhibits growth of intracellular M.tuberculosis with good activity against drug-resistant isolates. The inhibition of QcrB by LPZS leads to disruption of the mycobacterial respiratory chain and massive and rapid ATP depletion (PubMed:26158909). Both compounds target the same active site in QcrB (the ubiquinol oxidation QP site), but they have distinct drug-binding mechanisms (PubMed:26158909)
Inhibited by EDTA, 1,10 phenanthroline and batimastat (a peptidomimetic MMP inhibitor)
1D-myo-inositol hexakisphosphate activates protein-acetyltransferase activity via an allosteric mechanism: 1D-myo-inositol hexakisphosphate-binding induces a conformational rearrangement that stimulates the interaction with acetyl-CoA (PubMed:27525589). Acetyltransferase activity is activated by phytic acid (PubMed:22319451)
Alternates between an inactive GDP-bound form and an active GTP-bound form. Intrinsic GTPase activity is almost undetectable in vitro. Activated by guanine nucleotide-exchange factors (GEFs) and inactivated by GTPase-activating proteins (GAPs)
Under non-stress conditions, Spx is degraded by ClpXP (PubMed:16788195). Efficient degradation by ClpXP requires the adapter protein SpxH/YjbH (PubMed:32117138). Function, levels and solubility of Spx are affected by SpxH/YjbH aggregation and stress conditions (PubMed:32117138)
Inhibited by 5'-methylthiotubercin and 5'-chloroformycin
Slightly inhibited by oxalate
Sphingoid base activates kinase activity
Phosphorylation decreases the condensation activity
Strongly inhibited by N-ethylmaleimide, inactivated by MgCl(2) or MgSO(4)
Competitively inhibited by phosphate
DNA-binding ability is not susceptible to zinc, nickel, cobalt, cadmium, lead, copper and manganese ions
Specifically inhibited by spautin-1 (specific and potent autophagy inhibitor-1), a derivative of MBCQ that binds to USP13 and inhibits deubiquitinase activity
Activated by pathogens and other damage-associated signals: activation promotes ubiquitination and degradation of the N-terminal part, releasing the cleaved C-terminal part of the protein (NACHT, LRR and PYD domains-containing protein 1b, C-terminus), which polymerizes and forms the Nlrp1b inflammasome (By similarity). Nlrp1b inflammasome is inhibited by DPP8 and DPP9, which sequester the C-terminal fragment of Nlrp1b (NACHT, LRR and PYD domains-containing protein 1b, C-terminus) in a ternary complex, thereby preventing Nlrp1b oligomerization and activation (By similarity). Nlrp1b inflammasome is activated by Val-boroPro (Talabostat, PT-100), an inhibitor of dipeptidyl peptidases DPP8 and DPP9 (PubMed:31383852). Val-boroPro relieves inhibition of DPP8 and/or DPP9 by promoting disruption of the ternary complex, releasing its C-terminal part from autoinhibition (By similarity). May be activated by Toxoplasma gondii, although at a lower extent than allele 1 (PubMed:24218483). Not activated by cleavage by B.anthracis lethal toxin (LT) endopeptidase (PubMed:16429160, PubMed:21170303, PubMed:24492532, PubMed:31383852). May be activated by muramyl dipeptide (MDP), a fragment of bacterial peptidoglycan, in a NOD2-dependent manner (PubMed:18511561)
Is feedback inhibited by lysine. Is competitively inhibited by 2-oxobutyrate with respect to pyruvate
Activation is generally mediated by a guanine exchange factor (GEF), while inactivation through hydrolysis of bound GTP is catalyzed by a GTPase activating protein (GAP) (By similarity). May be activated by Efa6 (PubMed:28607459)
The activation of GTP-binding proteins is generally mediated by a guanine exchange factor (GEF), while inactivation through hydrolysis of bound GTP is catalyzed by a GTPase activating protein (GAP). The GATOR1 complex functions as a GAP and stimulates RRAGB GTPase activity to turn it into its inactive GDP-bound form
c-di-AMP hydrolysis inhibited by ppGpp, without altering c-di-AMP binding
Phosphorylation at Thr-463 may be important for modulating interactions with other cell division proteins, thus regulating the cell division process
Present in an inactive conformation in the absence of bound ligand. Binding of VEGFA, VEGFC or VEGFD leads to dimerization and activation by autophosphorylation on tyrosine residues. Inhibited by the small molecule PTK inhibitor SU5614 ((3Z)-5-Chloro-3-[(3,5-dimethyl-1H-pyrrol-2-yl)methylene]-1,3-dihydro-2H-indol-2-one). May be regulated by hydrogen sulfide (H(2)S) levels via a H(2)S-sensitive intracellular disulfide bond
Inhibited by carbonyl cyanide m-chlorophenylhydrazone (CCCP)
Activated by autophosphorylation in response to salt stress
Magnesium-independent phospholipid phosphatase (PubMed:1334090). Insensitive to N-ethylmaleimide (PubMed:1334090)
Stimulated by sodium sulfate > ammonium sulfate and is sensitive to inactivation by 5'AMP
Activated by autophosphorylation on Thr-1381 and Thr-1393 following oligomerization
Strongly inhibited at high fructose concentration
S-adenosyl-L-homocysteine acts as a competitive inhibitor (PubMed:12957890). Also strongly inhibited by low concentrations of several metal ions, such as Cu(2+), Hg(2+), Zn(2+), and Ag(+), and to a lesser extent by p-chloromercuribenzoic acid, but it is not significantly affected by several thiols or other thiol reagents (PubMed:12957890)
Activated by glycine and taurine. Inhibited by strychnine (PubMed:10188956, PubMed:26344198). Allosterically activated by ivermectin (PubMed:26344198). Inhibited by picrotoxinin (PubMed:26344198). Strychnine binding locks the channel in a closed conformation and prevents channel opening in response to extracellular glycine (PubMed:26344198). Can also be activated by GABA and inhibited by bicuculline, but this requires heterologous expression in human cells (PubMed:10188956)
Inhibited by 6,7-Dichloro-N-cyclopentyl-4-(pyridin-4-yl)phthalazin-1-amine (A-196) with an IC(50) of 25 nM. A-196 is competitive with the histone peptide substrate H4K20me1 but non competitive with S-adenosyl-L-methionine
Stimulated by PCNA and inhibited by aphidicolin
Stimulated by magnesium, inhibited by zinc
Subject to autoinhibition, mediated by intramolecular interactions involving the SH2 and SH3 domains. Kinase activity is also regulated by phosphorylation at regulatory tyrosine residues. Phosphorylation at Tyr-389 is required for optimal activity. Phosphorylation at Tyr-500 inhibits kinase activity (By similarity)
Activated by divalent cations (PubMed:17655883). Activated by bile acids (By similarity). Activated by membrane phospholipids such as phosphatidylethanolamines (PubMed:17655883)
Myotoxic activity is inhibited by suramin and rosmarinic acid (PubMed:26457430, PubMed:30679550). Cytotoxic and myotoxic activities are inhibited by pre-incubation with varespladib (PubMed:31748642). Suramin inhibits this myotoxin by (i) direct blockage of the MDoS and MDiS, preventing the toxin/membrane interaction and disruption and (ii) formation of an oligomeric complex, resulting in a tetrameric configuration for which both MDoS and MDiS becomes physically inaccessible, thus avoiding any possibility of toxin-membrane interaction or disruption (PubMed:26457430). Heparin completely inhibits the cytotoxic and bactericidal activities, but only partially the myotoxic, edema-inducing and lethal effects (PubMed:9637370)
The polymerization activity is inhibited in the presence of 2'-3'-dideoxynucleoside 5'-triphosphate (ddNTP)
Inhibited by farnesylthioacetic acid (FTAA) and N-acetyl-S-trans, trans-farnesyl-l-cysteine (AFC)
The presence of GTP-bound RAS2 protein is required in order to elicit a magnesium-dependent adenylyl cyclase activity
Not inhibited by the anti-tuberculosis drug ethambutol (EMB)
Inhibited by N-ethylmaleimide but not by vanadate
Stimulated by DMS3
Probably regulated via interaction with FhaA
Activated by fry
Inhibited by borrelidin (BN, IC 50 is 7 nM), which binds to 4 distinct subsites in the protein, preventing binding of all 3 substrates (PubMed:25824639)
By catabolite repression
Negatively regulated by integrin, bsk and Src/Src64B
Stimulated by DTT (PubMed:11463796, PubMed:22860206). Stimulated by nonionic detergent of the polyoxyethylenep-t-octylphenylether type (Triton X-100 or Nonidet P-40) whereas 3-[(3-cholamidopropyl)dimethylammonio]propane-1-sulfonate (CHAPS) and octyl alpha-D-glucopyranoside decrease the N-(long-chain-acyl)ethanolamine deacylase activity (PubMed:22860206). Polysorbate 20 (Tween 20) is inhibitory (PubMed:11463796). Stimulated by endogenous phospholipids such as choline- or ethanolamine-containing phospholipids, and dihydrolipoic acid (PubMed:22860206)
Inhibited by dimethylglycine and methylthioacetate
Enhanced by the presence of ethylamine or NH4(+) ions
In vitro, is slightly activated in the presence of Ca(2+), but inhibited by Zn(2+)
Inhibited by acyl-CoA and 1-acylglycerol-3-phosphate
Inhibited by its product oxalate (PubMed:17669354). Inhibited by high concentrations of dichlorophenolindophenol (DCIP) in vitro (PubMed:17669354)
Feedback inhibited by histidine. Also inhibited by AMP
Activated by phosphorylation of Thr-201
Inhibited by 3-[(carboxyethenyl)oxy]-6-hydroxy-1-benzoic acid and 3-[(carboxyethenyl)oxy]benzoic acid
Partly inhibited by interleukin 10
The NAALADase activity is inhibited by quisqualic acid, beta-NAAG and 2-(phosphonomethyl) pentanedioic acid (PMPA). Ethanol ingestion decreases the folate hydrolase activity by 50%
EsxB binding to the second FtsK domain of EccCb1 causes multimerization; a subsequent unknown step relieves the allosteric inhibition of linker 2 on FtsK domain 1 (this subunit), activating the ATPase activity (PubMed:25865481)
C-di-GMP interaction leads to active site obstruction, hexameric ring destabilization thus relieving DNA bending and activating gene transcription
Inhibited by Li(+) and Na(+)
Diaminopimelate-sensitive
Inhibited by Mn(2+) ions. Inhibited by phosphatidylethanolamine (PE) (PubMed:27405756)
The side chain of Glu-274 determines which of the two opposing activities (AMPylase or de-AMPylase) will take place. In response to endoplasmic reticulum stress, mediates de-AMPylase activity (By similarity). Adenylyltransferase activity is inhibited by the inhibitory helix present at the N-terminus: Glu-274 binds ATP and competes with ATP-binding at Arg-415, thereby preventing adenylyltransferase activity (By similarity). In unstressed cells, disengagement of Glu-274 promotes adenylyltransferase activity (By similarity). Activation dissociates ATP-binding from Glu-274, allowing ordered binding of the entire ATP moiety with the alpha-phosphate in an orientation that is productive for accepting an incoming target hydroxyl side chain (By similarity)
Catalytic activity is inhibited competitively by 4-deoxypyridoxine, and is also inhibited by the benzodiazepine receptor ligands 1012S and ethyl-beta-carboline-3-carboxylate (PubMed:9099727). Inhibited by ginkgotoxin, theophylline, lamotrigine, enprofylline, theobromine, and caffeine (PubMed:22879864). Activity is increased in the presence of K(+)or Na(+) (PubMed:17766369)
Inhibited by 100 mM KCl
By phosphorylation. The catalytic activity is inhibited by soraphen A, a polyketide isolated from the myxobacterium Sorangium cellulosum and a potent inhibitor of fungal growth
Inhibited by phosphorylation of Ser-36
Inhibited by orthovanadate, beryllium trifluoride, Ca(2+) and EDTA
AIM-100 (4-amino-5,6-biaryl-furo[2,3-d]pyrimidine) suppresses TNK2-mediated phosphorylation at Tyr-269. Inhibits the binding of the Tyr-269 phosphorylated form to androgen-responsive enhancers (AREs) and its transcriptional activity
The azo reduction activity is inhibited by dicoumarol
Strongly repressed by loganin and slightly by S-adenosyl-L-homocysteine
The chaperone activity is regulated by ATP-induced allosteric coupling of the nucleotide-binding (NBD) and substrate-binding (SBD) domains (By similarity). In the ADP-bound and nucleotide-free (apo) states, the two domains have little interaction (By similarity). In contrast, in the ATP-bound state the two domains are tightly coupled, which results in drastically accelerated kinetics in both binding and release of polypeptide substrates (By similarity). J domain-containing co-chaperones (dnajb9/ERdj4 or dnajc10/ERdj5) stimulate the ATPase activity and are required for efficient substrate recognition by hspa5/BiP. Homooligomerization inactivates participating hspa5/BiP protomers and probably act as reservoirs to store hspa5/BiP molecules when they are not needed by the cell (By similarity)
Inhibited in the presence of 100 mM KCl, NaCl or NH(4)Cl
Up-regulated by bile acids such as deoxycholate (PubMed:9442065, PubMed:9442064). Inhibited by diisopropyl fluorophosphate (PubMed:9442065, PubMed:9442064)
Phospholipase activity is specifically activated upon 3',3'-cUAMP binding. Is not activated by the other cyclic dinucleotides 3',3'-cGAMP, 3',3'-c-diAMP and 3',3'-c-diGMP. Therefore, is specifically activated by only the nucleotide synthesized from its adjacently encoded nucleotidyltransferase (CdnE)
Uptake is activated by NaCl, KCl or mannose gradients across the cell membrane. Inhibited by the protonophore 3,3',4',5-tetrachlorosalicylanilide (TCS)
Completely inhibited by DEPC, HgCl(2), ammonium sulfate and glucosamine. Inhibited by 1,10-phenanthroline at concentrations as low as 1 mM. Glycine hydroxamate, Zn(2+), Hg(2+) and EDTA inhibit the activity at 10 mM. Sodium chloride (NaCl) and potassium chloride (KCl) inhibit protease activity at 100 mM
Inhibited by micromolar concentrations of copper and zinc ions
Alternates between an inactive form bound to GDP and an active form bound to GTP. Activated by the guanine nucleotide-exchange factors (GEFs) ROM1, ROM2 and TUS1, and inactivated by GTPase-activating proteins (GAPs) BAG7, BEM2, LRG1, and SAC7, and the Rho GDP-dissociation inhibitor RDI1. The different GAPs regulate RHO1 in a target-specific manner
The synergistic effects on peptidoglycan degradation of RipA plus RpfB are inhibited by addition of PBP1A (ponA1)
Activity is increased about twofold by 10 mM manganese. ADP, at 10 mM concentration, inhibits the formation of trehalose-P by 70% with either UDP-glucose or GDP-glucose as substrate, but GDP, also at 10 mM, only inhibits the reaction with UDP-glucose (50%) but not with GDP-glucose
Nlrp1a inflammasome is activated by pathogens and other damage-associated signals: activation promotes ubiquitination and degradation of the N-terminal part, releasing the cleaved C-terminal part of the protein (NACHT, LRR and PYD domains-containing protein 1a, C-terminus), which polymerizes and forms the Nlrp1a inflammasome (By similarity). Nlrp1a inflammasome is inhibited by DPP8 and DPP9, which sequester the C-terminal fragment of Nlrp1a (NACHT, LRR and PYD domains-containing protein 1a, C-terminus) in a ternary complex, thereby preventing Nlrp1a oligomerization and activation (By similarity). Nlrp1a inflammasome is activated by Val-boroPro (Talabostat, PT-100), an inhibitor of dipeptidyl peptidases DPP8 and DPP9 (PubMed:31383852). Val-boroPro relieves inhibition of DPP8 and/or DPP9 by promoting disruption of the ternary complex, releasing its C-terminal part from autoinhibition (By similarity)
Magnesium-independent phospholipid phosphatase (PubMed:9705349). Insensitive to N-ethylmaleimide (PubMed:9705349). Inhibited by sphingosine, zinc ions and modestly by propanolol (PubMed:9705349, PubMed:9607309)
Activated by dithiothreitol and inhibited by SH-reactive compounds
Inhibited by Li(+) (IC(50)=10 mM), Na(+) (IC(50)=50 mM) and Ca(2+) (IC(50)=0.06 mM)
Inhibited by NaF, Zn(2+), Ca(2+), Mn(2+) and EDTA
Inhibited by phenylmethanesulfonyl fluoride (PMSF) and diisopropyl fluorophosphate (DFP)
Transport process is modulated by three forces: the membrane potential, the chemical potential of lysine, and the proton gradient (PubMed:1657604). Strongly inhibited by CCCP and valinomycin (PubMed:1657604)
The isomerase activity is inhibited by S-methylglutathione (GSMe)
Decreased activity upon treatment with hydrogen peroxide
Inhibited by c8-acylated ghrelin mimetic peptide with an IC(50) of 22 nM (PubMed:25562443). Inhibited by 1-[2-cyano-3,12-dioxooleana-1,9(11)- dien-28-oyl] (CDDO) derivatives such as CDDO-imidazole (CDDO-Im), CDDO-methyl ester (CDDO-Me), CDDO-ethylamide (CDDO-EA), CDDO-trifluoroethylamide (CDDO-TFEA) with an IC(50) of 38 uM, 6uM, 8 uM and 44 uM respectively (PubMed:28134508). Inhibited by cyclohexenone derivatives such as 2-cyano-2-cyclohexanone and 2-bromo-2-cyclohexanone (PubMed:28134508). Inhibited by steroid derivatives such as alpha-cyanoenone steroid (PubMed:28134508)
Up-regulated by K(+) ions in a dose-dependent way
Inhibited at high ER lumenal peptide concentrations
(Microbial infection) Inhibited by herpes simplex virus US12/ICP47 protein, which blocks the peptide-binding site of TAP1-TAP2
(Microbial infection) Inhibited by human cytomegalovirus US6 glycoprotein, which binds to the lumenal side of TAP1-TAP2 complex and inhibits peptide translocation by specifically blocking ATP-binding and preventing TAP1-TAP2 conformational rearrangement induced by peptide binding
Inhibited by pembrolizumab (also named MK-3475 or lambrolizumab), a monoclonal antibody that prevents the interaction with CD274/PDCD1L1 (PubMed:27734966, PubMed:27325296). Inhibited by nivolumab (also named ONO-4538, BMS-936558 or Opdivo), a monoclonal antibody that prevents the interaction with CD274/PDCD1L1 (PubMed:28165004). The interaction with nivolumab is not dependent on glycosylation and depends on a loop at the N-terminus (N-terminal loop, corresponding to residues 25-34) (PubMed:28165004). Targeting the interaction between PDCD1 and CD274/PDCD1L1 with pembrolizumab and nivolumab antibodies has demonstrated great promise as a strategy for controlling and eradicating cancer (PubMed:22658127, PubMed:25034862, PubMed:25399552). Pembrolizumab and nivolumab are used for treatment of patients with advanced melanoma (PubMed:25034862, PubMed:25399552). These antibodies are also effective against other cancers, such as non-small cell lung cancer, renal cell carcinoma, bladder cancer and Hodgkin's lymphoma (PubMed:25034862)
Inhibited by adenosine 5'-diphosphate (ADP)
Efflux activity is inhibited by carbonyl cyanide m-chlorophenylhydrazone (CCCP)
Inhibited by acylsulfamoyl (acyl-AMS) analogs
Inhibited by dihydropyridines (DHP), such as isradipine (PubMed:14609949, PubMed:21216955). Inhibited by nifedipine. Channel activity is regulated by Ca(2+) and calmodulin. Binding of STAC1, STAC2 or STAC3 to a region that overlaps with the calmodulin binding site inhibits channel inactivation by Ca(2+) and calmodulin (By similarity). Binding of calmodulin or CABP1 at the same regulatory sites results in opposite effects on the channel function. Shear stress and pressure increases calcium channel activity (By similarity)
Inhibited by phosphorylation of Tyr-531 by leukocyte common antigen and activated by dephosphorylation of this site (By similarity). Relatively inactive in the unfertilized oocyte, undergoes rapid activation immediately following fertilization. Total activity increases progressively during later development and remains elevated during sphere and epiboly stage
Amylosucrase favors hydrolysis at low sucrose concentrations, and polymerization at high sucrose concentrations. Competitively inhibited by fructose
Inhibited by 5'-ADP
Completely inhibited by p-chloromercuribenzoate (p-ClHgBzO) and acetyl-CoA, and partially inhibited by N-ethylmaleimide
Uptake of inorganic carbon by cells in the presence of thiosulphate is fully inhibited by the uncouplers carbonyl cyanide m-chlorophenyl hydrazone (CCCP), carbonyl cyanide p-trifluoromethoxyphenyl hydrazone (FCCP), S13 or SF6847. Not inhibited by the ATPase inhibitor N,N-dicyclohexylcarbodiimide (DCCD) (Ref.2). Inorganic carbon uptake is inhibited by the ionophore carbonyl cyanide m-chlorophenyl hydrazone (CCCP), suggesting uptake is coupled to a cation gradient (PubMed:31406332)
Inhibited by hymenialdisine (By similarity). Activated by phosphorylation on Thr-208 by STK11/LKB1 and TAOK1. Inhibited by phosphorylation at Ser-212 or Thr-539. Inhibited by PAK5; inhibition is independent of the kinase activity of PAK5
Activated by high pH or also by potassium ions when the medium pH is low
Activated by archease, which accelerates both the RNA 3'-P guanylylation and ligation steps (PubMed:24435797). Archease also expands the NTP specificity of RtcB, enabling the efficient use of dGTP, ATP or ITP (PubMed:24435797)
Inhibited by 2,2,2-trifluoroethanol and pyrazole
Full activity requires coexpression with the neighboring gene ymdB
Competitively inhibited by 5-methylthioadenosine, 5-methylthiotubercidin, S-adenosyl(5)-3-thiopropylamine and S-adenosyl-3-thio-l,8-diaminooctane
Activated by autophosphorylation on Ser-215. Kinase activity is inhibited by SPRED1
Stimulated by magnesium ions; inhibited by N-bromosuccinimide and 2-hydroxy-5-nitrobenzyl bromide
AMP phosphorolysis is allosterically regulated by the substrate AMP
The triglyceride lipase activity is inhibited by BEL ((E)-6-(bromomethylene)-3-(1-naphthalenyl)-2H-tetrahydropyran-2-one), a suicide substrate inhibitor
Inhibited by aprotinin, leupeptin, benzamidine and soybean trypsin inhibitor. Partially inhibited by PMSF and DFP
Under conditions of nitrogen excess, the DNA binding activity of GlnR is activated by a transient interaction with feedback-inhibited GlnA (PubMed:18331450). Under conditions of nitrogen-limited, GlnR is autoinhibited by its C-terminal region (PubMed:25691471)
Inhibited by reducing agents and activated during exposure to oxidative stress
Activated by phosphorylation on Ser-52 and Ser-588
Cleavage of host complement factor C3 is inhibited by PMSF
Inhibited by chymostatin, Boc-Glu(NHO-Bz)-Pyrrolidide, Z-Pro-L-prolinal dimethyacetal and the peptide H-H-L-P-P-P-V-OH
Maintained latent until the signal peptide is removed by signal peptidase
Inhibited by TDP-L-rhamnose, the sugar donor that most closely structurally resembles the natural substrate dTDP-beta-L-noviose
Inhibited by acetylation at Lys-635 and activated by deacetylation mediated by the deacetylase SIRT3
Insensitive to oxygen. Decarboxylation and carboxylation are inhibited by AgNO(3) and by diethyl pyrocarbonate, a histidine residue-specific inhibitor. Decarboxylation is also inhibited by HgCl(2) and activated by MgCl(2)
Stimulated by lipoic acid. Inhibited in presence of methylamine (By similarity)
Active at low pH (under pH 4.6): proton channel activity is activated by luminal side protons (By similarity). Polyunsaturated fatty acids, such as arachidonic acid, also activate the channel activity (By similarity). Channel activity is activated following interaction with AKT (AKT1, AKT2 or AKT3): interaction promotes activation from closed to an open state (PubMed:33505021). Activation by AKT is independent of AKT serine/threonine-protein kinase activity (PubMed:33505021)
Inhibited by dihydropyridines (DHP), such as isradipine (PubMed:2474130, PubMed:9278523). Inhibited by nifedipine (PubMed:23145875). Channel activity is regulated by Ca(2+) and calmodulin (PubMed:7491499, PubMed:29363593). Binding of STAC1, STAC2 or STAC3 to a region that overlaps with the calmodulin binding site inhibits channel inactivation by Ca(2+) and calmodulin (PubMed:29363593). Binding of calmodulin or CABP1 at the same regulatory sites results in opposite effects on the channel function (By similarity). Shear stress and pressure increases calcium channel activity (By similarity)
Phospholipase A1 and lysophospholipase activities are inhibited by annexin II
Activated by calcium (Probable). Upon calcium binding to the EF-hand domain 2, the C-terminus of the junction domain (J domain) undergoes a conformational change which results in the dissociation of the pseudo-substrate inhibitory motif from the catalytic domain (Probable). This, in turn, may facilitate the autophosphorylation of the activation loop at Thr-279, which leads to the kinase activation (By similarity)
In the autoinhibited state the side chain of Phe-463 inserts into a hydrophobic groove in RING-0, occluding the ubiquitin acceptor site Cys-431, whereas the REP repressor element binds RING-1 and blocks its E2-binding site (PubMed:23727886, PubMed:23770887). Activation of PRKN requires 2 steps: (1) phosphorylation at Ser-65 by PINK1 and (2) binding to phosphorylated ubiquitin, leading to unlock repression of the catalytic Cys-431 by the RING-0 region via an allosteric mechanism and converting PRKN to its fully-active form (PubMed:24660806, PubMed:25474007, PubMed:24784582, PubMed:25527291). According to another report, phosphorylation at Ser-65 by PINK1 is not essential for activation and only binding to phosphorylated ubiquitin is essential to unlock repression (PubMed:24751536)
Specifically and competitively inhibited by 2-thiomalate, which coordinates with the catalytic [4Fe-4S] cluster
Allosterically inhibited by arginine
Activated by phosphorylation in the activation loop
Regulated by metabolites. Post-translationally inactivated by cysteine-mediated redox modification via the ferredoxin-thioredoxin system in the light and this avoids futile cycles with photosynthetic CO2 fixation (By similarity)
Allosterically activated by S-adenosyl-methionine/AdoMet. Activated by S-adenosylhomocysteine/AdoHcy (PubMed:20506325). Binds non-covalently to a heme group that may control the redox sensitivity of the enzyme (PubMed:11483494, PubMed:12173932, PubMed:22738154)
By BTG1, BTG2 and ILF3
Stimulated by phosphatidylinositol 4,5-bisphosphate and phosphatidylethanolamine. Inhibited by phosphatidylserine and by oleate. Is not responsive to ADP-ribosylation factor 1 (ARF1), nor to GTP-binding protein RhoA
Inhibited by zinc, calcium or copper ions
Allosterically inhibited by isoleucine
Autophosphorylation is inhibited by Na(+) but not by Cl(-) (PubMed:26904089). Reducing agents dithionite, duroquinol and decyl-plastoquinone, but not NADPH or ferredoxin inhibit autophosphorylation. Oxidation of the Fe-S cluster (with potassium ferricyanide) induces a conformational change that is conducive to its autophosphorylation activity (PubMed:31925322)
Activated by threonine and tyrosine phosphorylation (Probable). Inactivated by phosphatase PHS1
Inhibited by beta-lactam antibiotics such as penicillin, moenomycin, macarbomycin, furazlocillin and piperacillin. Antibiotics inhibit the activity by binding to the catalytic serine
Is inhibited by PMSF and by NaF in vitro, which is consistent with the catalytic nucleophile being a serine
Inhibited by 6-methoxynicotinamide (JBSNF-000088)
Activated by ATP, other nucleotide triphosphates and small peptides (PubMed:14527953, PubMed:21731629, PubMed:22049080). Inhibited by bacitracin (PubMed:12941771)
Inhibited by diethylpyrocarbonate, hydroxylamine and phenylglyoxal
Transport is inhibited by the protonophores 2,4-dinitrophenol (DNP) and carbonyl cyanide m-chlorophenyl hydrazone (CCCP), but not by ionophores such as valinomycin, nonactin and nigericin
Histone H3K4me1 and H3K4me2 demethylase activity is inhibited by DNA, this inhibition is released in complex with GLYR1
Completely inhibited by hydroxylamine hydrochloride
Magnesium-independent phospholipid phosphatase (PubMed:9705349). Insensitive to N-ethylmaleimide (PubMed:9705349). Inhibited by sphingosine, zinc ions and modestly by propanolol (PubMed:9705349)
Competitively inhibited by several inositol 1-phosphate analogs, including the phosphonate analog 1-deoxy-1-phosphonomethyl-myo-inositol (Ino-C-P)
Activated by CDP-diacylglycerol especially in the presence of Triton X-100 (0.1% w/v) at concentrations where micelles are formed. Maximal activation by Triton X-100 at 0.2% w/v, but higher concentrations become inhibitory. Inhibited by EDTA and high concentrations of choline
Inhibited by EDTA and 2,3-bisphosphoglycerate
Glytamylation catalyzed by SidJ requires host calmodulin and can be regulated by intracellular changes in Ca2+ concentrations. Requires also ATP
Activated by magnesium ions (PubMed:25545638). Activated by calcium ions (PubMed:25545638)
Activated by Ca(2+)/calmodulin. Binding of calmodulin is thought to result in a conformational change and leads to activation through phosphorylation by CAMKK1
Inhibited by K3 herbicides such as alachlor, allidochlor, anilofos, cafenstrole and flufenacet (PubMed:15277688). Strongly inhibited by metazachlor and mefluidide (PubMed:22284369)
ATPase activity is slightly stimulated by either circular single- or double-stranded DNA with a weak preference for double-stranded DNA (PubMed:18243819). Helicase activity is stimulated by Mre11 (PubMed:18243819)
Not inhibited by DHEAS or warfarin
SNAP25 proteolysis is inhibited by 1,10-phenanthroline and 2,2'-dipyridyl but not EDTA (PubMed:8103915). Inhibited by hydroxamate compounds with halogenated benzene-containing arms which directly bind the zinc ion (PubMed:21434688)
Cys-11 acts as a sensor of redox state (PubMed:24118911). In response to oxidative stress, monoubiquitination at Cys-11 is prevented (PubMed:24118911)
Inhibited by EDTA and 1,10-phenanthroline (PubMed:27443638)
Competitive inhibition of L-kynurenine transamination by glutamine, methionine and histidine but not by tyrosine and phenylalanine (PubMed:15556614). Cysteine concentration between 0.31-2.5 mM increases L-kynurenine transamination while concentration above 2.5 mM inhibits L-kynurenine transamination (PubMed:15556614). Keto-acids as amino acceptors modulate the transamination activity toward L-kynurenine (PubMed:15556614)
Regulated by phosphoenolpyruvate substrate and is allosterically activated by ribose-5-phosphate, AMP and other nucleoside monophosphates but not by fructose-1,6-bisphosphate
Inhibited by apstatin and the metal ion chelators EDTA and 1,10-phenanthroline (PubMed:11106490). Partially inhibited by dithiothreitol. Not inhibited by enalaprilat or amastatin (PubMed:11106490). Specifically inhibited by the pseudodipeptide CQ31 (PubMed:35165443). Inhibition by CQ31 indirectly activates the CARD8 inflammasome: dipeptide accumulation following PEPD inactivation weaky inhibit dipeptidyl peptidases DDP8 and DPP9, relieving DPP8- and/or DPP9-mediated inhibition of CARD8 (PubMed:35165443)
Activation is generally mediated by a guanine exchange factor (GEF), while inactivation through hydrolysis of bound GTP is catalyzed by a GTPase activating protein (GAP). Activated by ASAP3. Inactivated by ACAP1 and ACAP2 (By similarity). Activated by NGF via NTRK1 (By similarity)
Strongly inhibited by anti-hypertensive drugs losartan, candesartan, valsartan, irbesartan, telmisartan, eprosartan, olmesartan and azilsartan, most of which share a common biphenyl-tetrazole scaffold
Esterase activity is significantly inhibited by the serine modifier phenylmethylsulfonyl fluoride (PMSF). Completely inhibited by diethyl pyrocarbonate
Glucan synthesis by GTF-S is independent of primer glucan unlike GTF-I
Inhibited by flavonoids such as datiscetin, naringenin, marein and phloretin
Activated by nucleotides, including ATP, GTP, CTP, UTP, and ADP (PubMed:35997162). Activated by copper, manganese, calcium and magnesium ions; copper and manganese restore activity following inactivation by EDTA (ethylenediaminetetraacetic acid) (PubMed:35997162). Inhibited by metal chelators including EDTA, EGTA (ethylene glycol bis(2-aminoethyl)tetraacetic acid), and 1,10-phenanthroline (PubMed:35997162). Inhibited by copper, zinc, and iron ions (PubMed:35997162). Also inhibited by dithiothreitol p-mercuribenzenesulfonic acid, N-ethylmaleimide, protoporphyrin, hemin, protamine and triarginine (PubMed:35997162)
In males, activity increases in an age-dependent fashion, maybe derived from the induction by sex-hormones
Inhibited by vanadate (PubMed:27268273). Inhibited by micromolar levels of bile salts, such as tauroursodeoxycholate. Not inhibited by taurodeoxycholate. Not inhibited by hydroxysterols, such as 7-hydroxycholesterol, testosterone, dexamethasone and prednisolone (PubMed:27075612). Inhibited by EDTA and EGTA (PubMed:12354767)
Inhibited by AKT1, AKT2 and AKT3. Activated by oleic acid and arachidonic acid
Inhibited in vitro by the competence and sporulation stimulating factor (CSF), encoded by phrC (PubMed:23526881). However, CSF has at least three targets (RapB, RapC, and RapJ) and the physiological importance of RapJ inhibition by CSF is unknown (PubMed:23526881). Interaction with CSF induces a conformational change in RapJ (PubMed:23526881)
dTTP inhibits both the combined reaction and the dUTPase reaction
Inhibited by imidazoles (imidazole, benzimidazole, 1-benzylimidazole, 1-methylimidazole, P150/03 and N-omega-acetylhistamine) and cysteamines (cysteamine and N-dimethylcysteamine) (PubMed:17722885, PubMed:22897232). Inhibited by PDB50 1(3,4-dimethoxyphenyl)-3-(3-imidazol-1-ylpropyl)thiourea (PubMed:22897232)
Nuclease activity is inhibited by EDTA
Completely inhibited by phenylmethylsulfony fluoride (PMSF) and partially inhibited by benzamidine hydrochloride, leupeptin, and pepstatin A
Inhibited by inositol hexakisphosphate
Not activated by fructose-1,6-bisphosphate
Inhibited by N-acetylcastanospermine
Inhibited by orthovanadate, molybdate and spermidine
Inhibited by 4-aminopyridine (4-AP), dendrotoxin (DTX) and charybdotoxin (CTX), but not by tetraethylammonium (TEA) (By similarity). Inhibited by tityustoxin-K alpha (TsTX-Kalpha), a toxin that is highly specific for KCNA2 (By similarity). Inhibited by maurotoxin (PubMed:12527813). Inhibited by kappaM conotoxins kappaM-RIIIJ and kappaM-RIIIK (By similarity)
ATP hydrolysis occurs at the interface between the nucleotide-binding domains of subunits A and B (Probable). ATP hydrolysis triggers a conformational change in the subunits D and F, which induces a shift of subunit d (Probable). The c-ring is subsequently rotated and results in a continuous proton translocation across the membrane (Probable). The V-ATPase is inhibited by bafilomycin A (PubMed:32764564)
Feedback inhibition by phosphatidylcholine
Maintained in an autoinhibited state via homodimerization in which the CARD domain forms an extensive interaction with the adjacent linker and coiled-coil regions (PubMed:31296852). Activation downstream of C-type lectin receptors, by phosphorylation by PRKCD and/or ubiquitination by TRIM62, triggers disruption of the CARD domain-coiled coil interface, CARD9 homooligomerization and BCL10 recruitment, followed by activation of NF-kappa-B and MAP kinase p38 pathways (PubMed:26488816, PubMed:31296852). Zinc-binding inhibits activation by stabilizing the CARD ground-state conformation and restricting its capacity to form BCL10-nucleating filaments (PubMed:30206119)
May be activated by autophosphorylation or phosphorylation by a separate activating kinase
Activity is increased in the presence of Mn(+) and Mg(2+). Inhibited by thiol compounds
Completely inhibited by serine protease inhibitors such as chymostatin, diisopropylfluorophosphate and phenylmethylsulfonyl fluoride, but not by p-tosyl-L-phenylalanine chloromethyl ketone, p-tosyl-L-lysine chloromethyl ketone, pepstatin, E-64, EDTA or o-phenanthroline. Also inhibited by lima bean trypsin inhibitor, soy bean trypsin inhibitor and human plasma alpha1-antichymotrypsin
Divalent metals such as nickel and iron have a similar negative effect on YqjI DNA-binding activity
Inhibited by protonophores and ionophores, but is insensitive to the thiol reagent N-ethylmaleimide or cytochalasin B
Activity is reduced by the addition of 0.1 mM of various metal ions, including Ca(2+) (16%), Mn(2+) (20%), K(+) (30%), Zn(2+) (64%) and Cu(2+) (83%). However, the addition of 0.1 mM Mg(2+) enhances activity by 16%
Activated by cell stresses such as DNA damage, heat shock, osmotic shock, anisomycin and sodium arsenite, as well as pro-inflammatory stimuli such as bacterial lipopolysaccharide (LPS) and interleukin-1. Activation occurs through dual phosphorylation of Thr-180 and Tyr-182 by either of two dual specificity kinases, MAP2K3/MKK3 or MAP2K6/MKK6, and potentially also MAP2K4/MKK4, as well as by TAB1-mediated autophosphorylation. MAPK14 phosphorylated on both Thr-180 and Tyr-182 is 10-20-fold more active than MAPK14 phosphorylated only on Thr-180, whereas MAPK14 phosphorylated on Tyr-182 alone is inactive. whereas Thr-180 is necessary for catalysis, Tyr-182 may be required for auto-activation and substrate recognition. Phosphorylated at Tyr-323 by ZAP70 in an alternative activation pathway in response to TCR signaling in T-cells. This alternative pathway is inhibited by GADD45A. Inhibited by dual specificity phosphatases, such as DUSP1, DUSP10, and DUSP16. Specifically inhibited by the binding of pyridinyl-imidazole compounds, which are cytokine-suppressive anti-inflammatory drugs (CSAID). Isoform Mxi2 is 100-fold less sensitive to these agents than the other isoforms and is not inhibited by DUSP1. Isoform Exip is not activated by MAP2K6. SB203580 is an inhibitor of MAPK14
Interaction with Golgi matrix protein GOLGA2 leads to autophosphorylation on Thr-178, possibly as a consequence of stabilization of dimer formation. May also be activated by C-terminal cleavage (By similarity)
The holdase activity is activated by HOCl, via the reversible chlorination of several residues in the TPR domain. Chorination probably increases the hydrophobicity of CnoX and enables it to bind a variety of substrates. Reduced glutathione (GSH) is required to resolve CnoX-substrate complexes
The choline uptake activity is completely inhibited by the protonophore carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP)
Inhibited by Cu(2+) and Hg(2+), coformycin, deoxycoformycin (dCF), 2-deoxyadenosine, 6-methylaminopurine riboside, 2-3-iso-propylidene-adenosine and erythro-9-(2-hydroxy-3-nonyl)adenine
Inhibited by formycin B
Phosphorylation is inhibited by EGTA and vanadate. ATPase activity is stimulated by Sr(2+). Inhibited by very high concentrations of cyclopiazonic acid (CPA)
ADGRG1 NT is proposed to inhibit receptor signaling; its interactions with extracellular ligands and /or homophilic ADGRG1NT interactions may relieve the inhibition (PubMed:21708946, PubMed:24949629, PubMed:25918380). Following ligand binding to the N-terminal fragment, the N-terminal fragment is released from the seven-transmembrane C-terminal fragment to unveil a new N-terminal stalk, which then stimulates G-protein-dependent signaling activity (PubMed:25918380). The N-terminal stalk has also been shown to be dispensable for at least some G-protein-dependent signaling (PubMed:26710850)
Light exposure induces a conformational change in the C-terminal domain CCT1 required for activity
Inhibited by mannose 6-phosphate, fructose 1-phosphate and fructose 1,6-bisphosphate
Inhibited by active site inhibitors: edrophonium, trimethyl-(m-acetamidopheny1)-ammonium iodide, and trimethyl-(p-acetarnidopheny1)-ammonium iodide (PubMed:4197660, PubMed:9187246). Inhibited by both active and peripheral site inhibitors: decamethonium, and BW284c51 (PubMed:8662867, PubMed:9187246). Inhibited by peripheral site inhibitors: snake acetylcholinesterase fasciculin-2, propidium, gallamine, D-tubocurarine, and tacrine (PubMed:8662867, PubMed:9187246, PubMed:25411244). Also inhibited by antibodies Elec410 and Fab410 (PubMed:25411244)
Inhibited by heavy metal such as Hg(2+) and by p-chloromercuribenzoate
Inhibited by the bisubstrate delta-N-phosphonoacetyl-L-ornithine (PALO)
The uptake of taurocholate is inhibited by taurolithocholate sulfate with an IC(50) of 52.9 uM (PubMed:16332456). Pravastatin competitively inhibits the transport of taurocholic acid (PubMed:15901796, PubMed:18985798). Cyclosporin A, glibenclamide, rifampicin and troglitazonestrongly competitively inhibit the transport activity of taurocholate (PubMed:18985798). The canalicular transport activity of taurocholate is strongly dependent on canalicular membrane cholesterol content. The uptake of taurocholate is increased by short- and medium-chain fatty acids. Cholesterol increases transport capacity of taurocholate without affecting the affinity for the substrate (By similarity)
In contrast to mammalian I-1-P phosphatases, is only weakly inhibited by Li(+), since 50% inhibitory concentration for Li(+) is about 100 mM, and the Li(+) concentration required to totally abolish I-1-Pase activity is 1 M
Inhibited by N-[4,4-Diphenyl-3-butenyl]-nipecotic acid (SKF-89976-A), L-2,4-diamino-n-butyric acid, guvacine and nipecotic acid
Allosterically regulated; feedback inhibited by cytidine monophosphate-N-acetylneuraminic acid (CMP-Neu5Ac), the end product of neuraminic acid biosynthesis. Activity is dependent on oligomerization. The monomer is inactive, whereas the dimer catalyzes only the phosphorylation of N-acetylmannosamine; the hexamer is fully active for both enzyme activities (By similarity). Up-regulated after PKC-dependent phosphorylation
Inhibited by PAK5; inhibition is independent of the kinase activity of PAK5 (By similarity). Activated by phosphorylation on Thr-208. Inhibited by phosphorylation at Ser-212 and Thr-596. Inhibited by hymenialdisine. Specifically inhibited by the H.pylori CagA peptide FPLKRHDKVDDLSK that mimics host substrates and binds to the kinase substrate-binding site
Does not require magnesium. Completely inhibited by 5 mM of either NiSO4 or p-chloromercuribenzoate (pCMB). Acetylserotonin O-methyltransferase activity is inhibited by caffeate (PubMed:25039887)
Two specific sites, one in the kinase domain (Thr-313) and the other in the C-terminal regulatory region (Ser-478), need to be phosphorylated for its full activation
Glutathione-conjugate transport is inhibited by decyl-glutathione and, to a lower extent, by GS-GS, but not by GSH. All transports are inhibited by vanadate
Inhibited by diazaborines, triclosan (5-chloro-2-2,4-dichlorophenoxyphenol), 1,4-disubstituted imidazoles, 1,4-benzodiazepine derivatives, naphthyridinone derivatives, luteolin and curcumin (PubMed:10398587, PubMed:10493822, PubMed:11514139, PubMed:12109908, PubMed:12699381, PubMed:19959361, PubMed:8119879, PubMed:8953047, PubMed:9707111). The antibiotic diazaborine interferes with the activity by binding to the protein and NAD (PubMed:8119879)
Inhibited by pyridoxal 5'-phosphate (PLP)
Activated by phosphorylation at Tyr-492 in the activation loop
Inhibited in feedback fashion by the catecholamine neurotransmitters, especially by dopamine in competition with tetrahydrobiopterin. Phosphorylation of several Ser/Thr residues in the N-terminus regulates the catalytic activity. Ser-31 and Ser-40 are readily phosphorylated to activate the catalytic activity. A Cysteine modification induced by N-ethylmaleimide (NEM), inhibits tyrosine 3-monooxygenase activity through the modification of the Cys-177
Cleavage activities for 'Lys-48'- and 'Lys-63'-linked ubiquitin (UB) tetramers is inhibited by UB aldehyde and N-ethylmaleimide but not by the metalloprotease inhibitors 1,10-phenanthroline and EDTA, and the serine protease inhibitor phenylmethylsulfonyl fluoride
Inhibited by Zn2+ and Cu2+ at low micromolar concentrations. Inhibited by SERPINA12
Strongly inhibited by 2,2'-anhydro-5-ethyluridine, a competitive inhibitor
Inhibited by chloride and sulfate ions
Inhibited by EDTA and EGTA. Not inhibited by PMSF, antipain, pepstatin, and iodoacetamide (By similarity)
Activated by threonine and tyrosine phosphorylation by either of the dual specificity kinases, jkk-1 and mek-1
Activated by peroxide
Specifically inhibited by sinefungin derivatives
Is completely inhibited by the metal cation chelators 1,10-phenanthroline and EDTA, but PMSF, pepstatin A and E-64 have no effect on activity
Inhibited by hydroxylamine, phenylhydrazine, sodium borohydride, D-cycloserine, hydrazine, semicarbazine and succinic dehydrazine. L-glutamate, succinate, oxaloacetate, L-serine, L-cysteic acid, beta-hydroxy-DL-aspartate, and D-serine are competitive inhibitors
Inhibited by S-methyl-L-cysteine sulfoxide in vitro, via the formation of a covalently bound cysteine at the active site Cys-134
Competitively inhibited by 3-(2-carboxyethyl)benzoate
Repressed by various protease inhibitors including p-chloromercuribenzene sulfonic acid (PCMBS), N-ethylmaleimide, kininogen, elastatinal, cystatin EW and leupeptin
Transacylase activity is completely inhibited by Triton X-100 and partially inhibited by heparin. Moderately activated by Mg(2+) and Ca(2+)
Inhibited by Li(+) (PubMed:8002619, PubMed:10747806) (Probable). Li(+) binds to Asp-84, Asp-87 and Asp-212 (PubMed:22384802)
Activity can be increased by one order of magnitude by adding bovine serum albumin in vitro. This result suggests that the enzyme is activated in vivo by protein-protein or interactions with other cellular components
Potassium may regulate kinase activity
The kinase activity is stimulated upon binding to uncharged tRNAs
PceT is required as a chaperone for prePceA maturation (PubMed:22961902, PubMed:24814779). In the absence or presence of exogenous vitamin B12, the intracellular corrinoid level decreases in fumarate-grown cells and the PceA precursor forms catalytically inactive, corrinoid-free multiprotein aggregates (PubMed:22961902). Exogenous vitamin B12 is not incorporated into the PceA precursor, even though it affects the transposition of the pce gene cluster (PubMed:22961902)
Inhibited by reduction with NaBH(4), and by Cu(2+) ions, p-chloromercuribenzoate and N-bromosuccinimide (PubMed:1646603). Co(2+), Mn(2+) and Ni(2+) stimulate activity, perhaps by enhancing the opening of the substrate Neu5Ac (PubMed:33895133)
Inhibited by metal chelator o-phenanthroline
Inhibited by 2,6-dichloro-4-nitrophenol but not by triethylamine or tetra-n-butyl-ammonium chloride
IgM cleavage is inhibited by iodoacetamide but not by AEBSF, bestatin, E-64, Z-LVG-CHN(2), or EDTA
Inhibited by the mycotoxin fumonisin B(1), a sphingosine analog mycotoxins produced by pathogenic fungi (PubMed:26276842, PubMed:26635357). Repressed by divalent cation such as magnesium Mg(2+), copper Cu(2+), zinc Zn(2+), manganese Mn(2+), calcium Ca(2+) and cobalt Co(2+) (PubMed:26635357)
Inhibited by L-aminoethoxyvinylglycine (AVG) (PubMed:12228256). Inhibited by L-vinylglycine (L-VG) (PubMed:10704193). Inhibited by S-methylmethionine through a L-VG ketimine intermediate (PubMed:14678788)
ATPase activity is inhibited by interaction with PspA. Under inducing conditions, the interaction is disrupted, allowing activation of psp transcription
Phosphatase activity is inhibited by the phosphatase regulator PhrE
Inhibited by O-aryl carbamates and alpha-keto heterocycles (PubMed:17015445). Inhibited by trifluoromethyl ketone (PubMed:9122178)
Inhibited by (GlcNAc)4, (GlcNAc)5, (GlcNAc)6, and PNP-(GlcNAc)3
Can be inhibited by an excess of zinc
Inhibited by 4-quinoline drugs (nalidixic acid, ciprofloxacin, ofloxacin), although it is much less sensitive than the corresponding enzyme from E.coli (PubMed:8878580)
Allosterically activated and regulated via the combined actions of GTP and dNTPs (dATP, dGTP, dTTP and dCTP): Allosteric site 1 binds GTP, while allosteric site 2 binds dNTP. Allosteric activation promotes the formation of highly active homotetramers. Isoform 1: Phosphorylation at Thr-634 impairs homotetramerization, thereby inhibiting dNTPase activity, leading to reduced ability to restrict infection by viruses
Activated by N,N'-dicyclohexylcarbodiimide (DCCD) thus leading to increased ginsenosides accumulation
Activated by cpn20/cpn21 (in vitro)
Activated by JAR1/FIN219
Inhibited by quinolones, such as levofloxacin
Transport is inhibited by 6-deoxy-D-glucose
Inhibited by nucleoside 3', 5'-bisphosphates
Pyruvate uptake inhibited by 2-oxobutyrate, 2-oxovalerate, 2-oxoisovalerate, 2-oxoisocaproate and 2-oxo-3-methylvalerate
Activated by forskolin. Inhibited by calcium ions, already at micromolar concentrations. Inhibited by adenosine, AMP and their analogs (PubMed:1528892). Activated by GNAS (PubMed:17110384). Is further activated by the complex formed by GNB1 and GNG2 (PubMed:17110384). Phosphorylation by RAF1 results in its activation (By similarity)
Is inhibited by 8-nitro-benzothiazinones (BTZs) such as BTZ043 and PBTZ169; BTZs are a new class of antimycobacterial agents that kill M.tuberculosis in vitro, ex vivo, and in mouse models of tuberculosis (PubMed:20828197, PubMed:19299584, PubMed:22733761, PubMed:24500695). Is also inhibited by dinitrobenzamide derivatives (DNBs), which thus block formation of both cell-wall lipoarabinomannan and arabinogalactan via inhibition of decaprenyl-phospho-arabinose (DPA) synthesis; DNBs show high activity against intracellular growth of M.tuberculosis inside macrophages, including extensively drug resistant (XDR) strains (PubMed:19876393). BTZs and DNBs are suicide inhibitors that act via covalent modification of DprE1; the essential nitro group of these compounds is reduced by DprE1 to a nitroso group, which then specifically reacts with Cys-387 of DprE1 to form an irreversible semimercaptal adduct (PubMed:20828197, PubMed:22733761, PubMed:24500695). Many other compounds with diverse scaffolds were found to act as either covalent (e.g. nitroquinoxalines, nitroimidazoles) or non-covalent (e.g. the benzothiazole derivative TCA1, the 2-carboxyquinoxaline Ty38C, 8-pyrrole-benzothiazinones, 1,4-azaindoles, pyrazolopyridones, 4-aminoquinolone piperidine amides) DprE1 inhibitors (PubMed:23776209, PubMed:25427196, PubMed:25987616, PubMed:24215368, PubMed:24818517, PubMed:27666194)
When the two monomeric subunits are covalently linked by a S-S bond, the enzyme is essentially inactive. When the disulfide bond is reduced, its component sulfhydryls can associate with K-keto acids through formation of a thiohemiacetal, resulting in enzyme activation. Pyruvate increases Vmax, but not the substrate affinity
The regulatory activity of LicR is modulated by phosphorylation and dephosphorylation of the various LicR domains. It becomes activated via phosphoryl group transfer from PEP, EI and HPr on the two conserved histidine residues in the PRD 2 domain, whereas phosphorylation of the EIIA-like domain on His-559 by the PTS EIIB component LicB inactivates LicR (By similarity)
Binds cyclosporin A (CsA). CsA mediates some of its effects via an inhibitory action on PPIase (Probable)
Produced as a latent enzyme which is activated by dsRNA generated during the course of viral infection (Probable). Strongly activated by long dsRNAs at least 50 nucleotides in length (PubMed:25775560). ssRNA does not activate the enzyme (PubMed:25775560)
GAP activity is stimulated by phosphatidylinositol 4,5-bisphosphate (PIP2) and, to a lesser extent, by phosphatidylinositol 3,4,5-trisphosphate (PIP3). Phosphatidic acid potentiates PIP2 stimulation (By similarity)
The full-length protein before cleavage is inactive: intramolecular interactions between the N-terminal domain and the C-terminal region mediate autoinhibition. The pyroptosis-like-inducing activity is carried by the released N-terminal domain (Gasdermin bGSDM, N-terminus)
Inhibited by strychnine. Inhibited by picrotoxin (PubMed:16672662). Channel activity is enhanced by 5 uM Zn(2+) and inhibited by 100 uM Zn(2+) (PubMed:17114051)
Reversibly inhibited by micromolar concentrations of Hg(2+) or Ag(+), but irreversibly inhibited by alkylation in presence of urea. Competitive inhibition by p-nitrophenyl beta-D-thioglucoside (pNPTGlc), glucotetrazole, and para-hydroxy-S-mandelonitrile beta-glucoside (dhurrin)
Activated by phosphatidate (PA) and phosphatidylglycerol (PG) (PubMed:20023301). Inhibited by galvestine-1 (PubMed:21946275)
Redox regulation; active in reducing conditions, inactive in oxidizing conditions
(Microbial infection) In monocytes, human coronavirus SARS-CoV-2 increases HIF1A levels and activity which promotes a pro-inflammatory state
Under complex allosteric control mediated by deoxynucleoside triphosphates and ATP binding. The type of nucleotide bound at the specificity site determines substrate preference. It seems probable that ATP makes the enzyme reduce CDP and UDP, dGTP favors ADP reduction and dTTP favors GDP reduction. Lacks the N-terminal activity site
Channel activity is controlled by multiple regulatory mechanisms in different subcellular compartments (By similarity). Channel function is transiently modulated by changes in Ca(2+), and inhibited by a reduction of pH; pH changes modify the aggregation state of unitary channels; a negative cooperativity between extracellular/lumenal Ca(2+) and H(+) is suggested (PubMed:29019981). Regulated by phosphoinositides in a compartment-specific manner: in lysosomes activated by PtdIns(3,5)P2 (Phosphatidylinositol 3,5-bisphosphate) and at the plasma membrane inhibited by PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) (PubMed:29019981)
Channel activity is regulated by the ancillary beta subunit SCN1B. SCN1B strongly enhances the presence of the pore-forming alpha subunit at the cell surface (By similarity). Interaction with SCN1B is required for rapid channel inactivation and rapid recovery after inactivation, and prevents decrease of channel activity in response to repetitive, high-frequency depolarizations (By similarity). The channel is inhibited by tetrodotoxin (PubMed:11834499)
Regulated by pH. Activity inhibited by all inhibitors of several anion channels and transporters, including 4,4'-Di-isothiocyanatostilbene-2,2'-disulfonic acid (DIDS), diphenylamine-2-carboxylic acid and glybenclamide
Inhibited competitively by both alpha-difluoromethyllysine and alpha-difluoromethylornithine
Inhibited by castanospermine, Ag(+) and Cu(2+). 34% inhibition by Zn(2+) and not affected by EDTA
Activated by calcium and magnesium. Inhibited by copper
Inhibited by EDTA, laminarin sulfate and, to a lower extent, by heparin and sulfamin and activated by calcium and magnesium
3-fold increase in activity by addition of 10 mM 2-mercaptoethanol. Addition of CoCl(2) and to a lesser extent MnCl(2) increase the activity but not MgCl(2). Inhibited by phosphate buffers but not by 5,5'-dithio-2-nitrobenzoic acid
Stimulated by Fe(2+)
Glutamate uptake is inhibited by beta-hydroxyaspartate and cysteic acid
Probably regulates its own activity by autocleavage, which removes the PDZ domain (PubMed:18479146). Inhibited by the serine protease inhibitor diisopropylfluorophosphate (DFP) (PubMed:20061478). Inhibited by fluoroquinolone such as ciprofloxacin, moxifloxacin and ofloxacin and their analogs (PubMed:23440996)
Regulated by a negative feedback mechanism through sterols and non-sterol metabolites derived from mevalonate (PubMed:6995544). Phosphorylation at Ser-872 down-regulates the catalytic activity (By similarity). Inhibited by statins, a class of hypolipidemic agents used as pharmaceuticals to lower cholesterol levels in individuals at risk from cardiovascular disease due to hypercholesterolemia (PubMed:11349148, PubMed:18540668). Inhibition of HMGCR in the liver stimulates the LDL-receptors, which results in an increased clearance of LDL from the bloodstream and a decrease in blood cholesterol levels (PubMed:11349148, PubMed:18540668). The first results can be seen after one week of statin use and the effect is maximal after four to six weeks (PubMed:11349148, PubMed:18540668)
Is activated by autophosphorylation of activation loop threonine residues, which results in conformational change and allows substrate binding. It seems that following ATP binding, phosphate is first transferred to Thr-180 via a cis mechanism to activate the kinase activity; phosphorylation of Thr-180 triggers PknA to phosphorylate Thr-172/Thr-174 via a trans mechanism. Phosphorylation of all of the activation loop threonines is necessary for efficient catalytic activity
Inhibited by substrate concentrations above 0.5 mM
Inhibited by S-adenosyl-L-homocysteine
Iron oxidation is inhibited by Zn(2+), which binds at the ferroxidase center with a higher affinity that Fe(2+). The occupation of the ferroxidase center by Zn(2+) also severely restricts the ability of BFR to form an iron core
The regulatory activity of MtlR is modulated by phosphorylation and dephosphorylation of the various MtlR domains. It becomes activated via phosphoryl group transfer from PEP, EI and HPr on the two conserved histidine residues in the PRD 2 domain, whereas phosphorylation of the EIIA-like domain on His-599 by the PTS EIIB-Mtl domain of MtlA inactivates MtlR (By similarity)
ATPase activity is decreased by cholesterol and ceramide. ATPase activity is stimulated by phosphatidylserine, phosphatidylcholine and sphingomyelin, but phosphatidylserine is more effective
Inhibition by uncomplexed, free UTP
L,L-2,6-diaminopimelate and D,D-2,6-diaminopimelate competitively inhibit the oxidative deamination of meso-2,6-diaminopimelate. The enzyme is also inhibited by L-cysteine, and by p-chloromercuribenzoate, iodoacetic acid and HgCl(2) in vitro
Not inactivated by cyanide
Weakly inhibited by n-undecyl phosphonate (C11Y4) (PubMed:25219509). Activity unaffected by paraoxon (PubMed:25219509)
Moderately stimulated in the presence of potassium cations. Inhibited by increasing concentrations of pantoate. Activity is not affected by CoA/acetyl-CoA
Protease activity is induced in response to various mitochondrial stress, such as changes in membrane potential, oxidative stress or chronic hyperpolarization, and depends on its C-terminal region
Inhibited by dicoumarol
Transferase and hydrolase activities are inhibited by L-Ala and L-Gln, and also by GGT affinity labeling reagents such as azaserine and 6-diazo-5-oxo-nor-leucine
Exposure to indole-3-acetic acid (IAA) probably relieves the repressor activity
Transport is abolished by the proton uncoupler 2,4-dinitrophenol
Strongly inhibited by Ag(+). The cations Ca(2+), Mg(2+), Co(2+) and Cu(2+) do not significantly reduce the lipolytic activity of SCO1725. Is also inhibited by DTT in vitro, but not by EDTA or by the reagent masking SH-groups, p-hydroxymercuribenzoate (pHMB). Is resistant to PMSF inhibition, except in the presence of Ca(2+). Is also strongly inhibited by 3,4-dichloroisocoumarin (DCI), another inhibitor of serine hydrolases. Addition of tetrahydrofuran and 1,4-dioxane significantly increases (2- and 4- fold, respectively) hydrolytic activity of lipase towards p-nitrophenyl caprylate
Inhibited by 1 mM Cu(2+) and by the class II alpha-mannosidase inhibitor swainsonine
ATPase activity is stimulated by potassium and other monovalent cations. Stimulation is maximal in the presence of K(+), followed by NH(4)(+), Rb(+), Na(+) and Cs(+)
Present in an inactive conformation in the absence of bound ligand. FLT3LG binding leads to dimerization and activation by autophosphorylation
Activated by pyruvate, unaffected by NADH, ATP and PEP, unlike Pta
Inactivation of this channel is specifically inhibited by the spider toxins Hm1a and Hm1b (H.maculata, AC P60992 and AC P0DOC5) in somatosensory neurons to elicit acute pain and mechanical allodynia (PubMed:27281198)
Inactivated in the presence of the effectors sulfoquinovose and sulfoquinovosyl glycerol, leading to the de-repression of the target genes
Metal coordination and the nucleotide-bound state of HypB directly influence each other (PubMed:24338018). Binding of nickel in the G-domain decreases GTPase activity and modulates the oligomeric state of the protein (PubMed:21239585, PubMed:24338018). Binding of zinc inhibits the GTPase activity (PubMed:21239585, PubMed:24338018). GTP and GDP modulate coordination, stoichiometry, and affinity of nickel, but not zinc (PubMed:24338018). Potassium increases the GTPase activity but has no effect on the other biochemical properties of the protein (PubMed:24338018)
The matrix-open state (m-state) is inhibited by the membrane-permeable bongkrekic acid (BKA) (By similarity). The cytoplasmic-open state (c-state) is inhibited by the membrane-impermeable toxic inhibitor carboxyatractyloside (CATR) (By similarity). Proton transporter activity is inhibited by ADP:ATP antiporter activity (PubMed:31341297)
Mycophenolic acid (MPA) is a non-competitive inhibitor that prevents formation of the closed enzyme conformation by binding to the same site as the amobile flap. In contrast, mizoribine monophosphate (MZP) is a competitive inhibitor that induces the closed conformation. MPA is a potent inhibitor of mammalian IMPDHs but a poor inhibitor of the bacterial enzymes. MZP is a more potent inhibitor of bacterial IMPDH. Also inhibited by ADP
Active toward L-galactopyranoside and D-arabinopyranoside but no D-fucopyranoside activity detected
Binds free ubiquitin non-covalently via its RING-type zinc finger. Ubiquitin-binding leads to enhance the E3 ubiquitin-protein ligase activity by stabilizing the ubiquitin-conjugating enzyme E2 (donor ubiquitin) in the 'closed' conformation and activating ubiquitin transfer (PubMed:26656854)
In contrast to other acyl-coenzyme A oxidases which bind to and are activated by ATP, does not bind ATP
The E3 ubiquitin-protein ligase activity is inhibited by phosphorylation by AURKA. Activity is increased by phosphatase treatment
Transport is inhibited by ammonium. The C-terminal domain of NrtC is involved in the ammonium-promoted inhibition of the nitrate/nitrite transporter
Inhibited by capped and uncapped RNA (PubMed:16199859). Not inhibited by dinucleotide cap or methylated nucleotide analogs (PubMed:16199859)
Inhibited by lauroyl-CoA
Strongly inhibited by acifluorfen
Inhibited by O-sulfated heparin, which is produced by a downstream step in the heparin biosynthesis pathway
Partially inhibited by Li(2+)
Inhibited by divalent cation chelators such as BPS and EDTA
Partially inhibited by MSH when MSmB is used as substrate. Competitively inhibited by the GlcNAc-cyclohexyl derivative 5-(4-chlorophenyl)-N-((2R,3R,4R,5S,6R)-2-(cyclohexylthio)-tetrahydro-4,5-dihydroxy-6-(hydroxymethyl)-2H-pyran-3-yl)furan-2-carboxamide, which also inhibits MshB
Partially inhibited by MSH when MSmB (a bimane derivative of MSH) is used as substrate
Strongly inhibited by Cu(2+) and Zn(2+) and to less than 30% by Co(2+) and Fe(2+)
Requires micromolar levels of Zn(2+) for activity. Inhibited by millimolar levels of Zn(2+)
Inhibited by TorC apocytochrome
Activated in response to cold and salt stresses through serine and threonine phosphorylation by MEKK1
Inhibited by CCCP, but is apparently not affected by the concentration of sodium
Activated by Ca(2+)/calmodulin. Binding of calmodulin results in conformational change that relieves intrasteric autoinhibition and allows phosphorylation of Thr-200 within the activation loop by CaMKK1 or CaMKK2. Phosphorylation of Thr-200 results in a 10-20-fold increase in total activity to generate Ca(2+)/calmodulin-independent activity. Autophosphorylation of the N-terminus Ser-12 and Ser-13 is required for full activation. Inactivated by protein phosphatase 2A (PPP2CA/PPP2CB) which dephosphorylates Thr-200, thereby terminating autonomous activity and helping to maintain the enzyme in its autoinhibited state
Activated by chitin-mediated homodimerization
The activity of this enzyme is controlled by adenylation under conditions of abundant glutamine. The fully adenylated enzyme complex is inactive (By similarity)
Gating is voltage-dependent and repressed by decavanadate. Calmodulin-binding confers the Ca(2+) sensitivity. ATP is able to restore Ca(2+) sensitivity after desensitization. Phosphatidylinositol 4,5-bisphosphate (PIP2)-binding strongly enhances activity, by increasing the channel's Ca(2+) sensitivity and shifting its voltage dependence of activation towards negative potentials. Activity is also enhanced by 3,5-bis(trifluoromethyl)pyrazole derivative (BTP2) (By similarity). Inhibited by flufenamic acid and glibenclamide (PubMed:17188667)
Transporter activity is regulated by CA2/carbonic anhydrase 2, cAMP and PKA. Insensitive to stilbene derivatives. Inhibited by 5-(N-ethyl-N-isopropyl)-amiloride (EIPA)
Alternates between an inactive GDP-bound form and an active GTP-bound form (PubMed:32144363). Intrinsic GTPase activity is almost undetectable in vitro (By similarity). Activated by a guanine nucleotide-exchange factor (GEF) and inactivated by GTPase-activating protein ARFGAP1 (PubMed:32144363)
Protease activity is inhibited by serine protease inhibitors but not by cysteine protease inhibitors
Inhibited at high G1P concentrations
Inhibited by 1,2,3-triazole urea covalent inhibitors KT172, DH376 and DO34 (PubMed:26668358). Inhibited by p-hydroxy-mercuri-benzoate and HgCl(2), but not to PMSF. Also inhibited by RHC80267 (PubMed:14610053). Diacylglycerol lipase activity is inhibited by the phosphorylation of Ser-782 and Ser-808 by CAMK2A (PubMed:23502535)
Up-regulated in the presence of cardiolipin
Inhibited by NaCl, KCl, ATP, ADP, GTP and aspartate. Unlike E.coli, not regulated by acetyl-CoA
Potassium uptake increases at lower external pH and is abolished by the proton ionophore carbonyl cyanide m-chlorophenylhydrazone (CCCP) (PubMed:32005818). Binds cyclic di-AMP (c-di-AMP), which inhibits the potassium transport activity (PubMed:31061098)
Down-regulated by KIN10 through its protein phosphorylation
Under conditions of nitrogen excess, the DNA-binding activity is inhibited by the formation of a stable complex with feedback-inhibited GlnA (PubMed:11719184, PubMed:25691471). The presence of glutamine and AMP increases the inhibitory activity of glutamine synthetase by more than 1000-fold (PubMed:11719184)
Regulated by CLPS and bile salts levels ranging 1-5 mM in neonates and 2-30 mM in healthy adults. CLPS stimulates milk fat digestion in the presence of 4 mM bile salts (PubMed:23732775). Triacylglycerol lipase activity toward short- and medium-chain triglycerides is inhibited by increasing concentrations of bile salts and weakly reactivated by CLPS (PubMed:15287741, PubMed:17401110, PubMed:21652702, PubMed:26494624). Optimal triacylglycerol lipase activity is reached at bile salts concentrations ranging from 0.1 to 0.5 mM and then decreases at concentrations higher than 1 mM (PubMed:21652702, PubMed:15287741, PubMed:17401110). Lipase activity toward long-chain glycerolipids is stimulated by CLPS in the presence of 4 mM bile salts (PubMed:21652702). Galactolipase activity is inhibited at high concentrations of bile salts (PubMed:20083229). Triacylglycerol lipase activity is inhibited by anti-obesity drug tetrahydrolipstatin (PubMed:17401110)
Inhibited by mixanpril, an orally-active drug used for the treatment of hypertension
Transport is inhibited by the protonophore CCCP
Allosterically inhibited by SAM and methionine
2-ketogluconate acts as a molecular effector and causes dissociation of PtxS from its target promoter
Inhibited by arabinose-5-phosphate, D-erythrose-4-phosphate and D-erythronic acid
Inhibited by iodoacetamide and irreversibly by its product, dihydrosanguinarine
Inhibited by chloride with an IC(50) of 60 mM
Negatively regulated by hyperphosphorylation during mitosis. The hyperphosphorylated form does not associate with CCNB1-CDC2 complexes. The PLK1 protein kinase may be required for mitotic phosphorylation (By similarity)
Activated by dithioerythritol (5 mM) and inhibited by the thiol-blocking agent iodoacetamide (0.1 mM)
Activated by the cyclic di-AMP (c-di-AMP) receptor DarB in the absence of c-di-AMP
Inhibited by serum
GTPase-activating activity is inhibited in the folliculin complex (LFC), which stabilizes the GDP-bound state of RRAGA/RagA (or RRAGB/RagB), because Arg-164 is located far from the RRAGC/RagC or RRAGD/RagD nucleotide pocket (By similarity). Disassembly of the LFC complex upon amino acid restimulation liberates the GTPase-activating activity (By similarity)
Inhibited by quinine, quinidine, barium, and internal acidification
Strongly inhibited by 1-deoxymannojirimycin, an inhibitor of class I alpha-mannosidases, and by EDTA. EDTA inhibition is reversed by the addition of calcium, but not of magnesium
Inhibited by adenosine 5'-phosphosulfate (APS), but not by 3'phosphoadenosine 5'-phosphosulfate (PAPS). Inhibited by AMP, ADP, CTP, GTP, ITP, UTP and anions other than those in group IV
Activated by ATP, other nucleotide triphosphates and small peptides. Inhibited by bacitracin
Activated by an increase in cytosolic calcium levels that induce a conformational change of the N-terminal regulatory domain, uncapping the channel and allowing transport (By similarity). Inhibited by bathophenanthroline, mersalyl, p-hydroxymercuribenzoate, bromcresol purple, tannic acid, pyridoxal 5'-phosphate and p-hydroxymercuribenzoate (PubMed:15123600)
Independent from inorganic phosphate availability, and apparently submitted to catabolite repression, it is positively controlled by cAMP and the cAMP receptor protein
Inhibited by soybean trypsin inhibitor, benzamidine, the synthetic peptide R13K, Z-Gly-Leu-Phe-CH2Cl, phenylmethylsulfonyl fluoride, 3,4-dichloroisocoumarin, DFP, SBTI and alpha-1-antitrypsin. Inhibited by LPS from P.aeruginosa but not by LPS from S.minnesota. Not inhibited by elastinal, CMK, TLCK, ETDA or leupeptin
(Microbial infection) Inhibited reversibly by S.aureus EapH1
(Microbial infection) Activity is induced by the Td92 surface protein of the periodontal pathogen T.denticola
Inactivated by thiol-reactive agents. Inhibited by free UDP
Phosphatidylcholine flippase activity is inhibited by glucosylsphingosine, lactosylsphingosine, lysophosphatidylcholine and to a lesser degree sphingosine-1-phosphate and lysosphingomyelin (PubMed:33060204). Glucosylceramide flippase activity is inhibited by lysophosphatidylcholine, glucosylsphingosine and to a lesser degree lactosylsphingosine whereas lysosphingomyelin has a stimulatory effect at low concentrations (PubMed:33060204)
Inhibited by N-methyl-D-glucamine (PubMed:10747860). Inhibited by choline (PubMed:10811809, PubMed:10859363, PubMed:11716780). Allosteric regulation of sodium ions binding by pH (PubMed:16629640, PubMed:11756489)
Inhibited by 20 mM Fe(3+) and Mn(2+). Partially inhibited by Zn(2+) and Ni(2+). Activity is slightly enhanced by 2 mM Fe (3+), Mn (2+), Ca(2+) or Li(+) and by 20 mM Mg(2+), Ca(2+) or Li(+)
Activated by both the alpha and the beta-gamma G proteins following stimulation of G protein-coupled receptors (GPCRs). Activation by GPCRs is assisted by the regulatory subunits (PIK3R5 or PIK3R6) leading to the translocation from the cytosol to the plasma membrane and to kinase activation. Inhibited by AS-604850 and AS-605240
Strongly Inhibited by F-amidine and N-alpha-benzoyl-N5-(2-chloro-1-iminoethyl)-L-ornithine amide (Cl-amidine). These inhibitors are however not specific to PADI4 and also inhibit other members of the family (PubMed:17002273). Incorporation of a carboxylate ortho to the backbone amide of Cl-amidine results in inhibitors with increased specificity for PADI4: N-alpha-(2-carboxyl)benzoyl-N(5)-(2-fluoro-1-iminoethyl)-L-ornithine amide (o-F-amidine) and N-alpha-(2-carboxyl)benzoyl-N(5)-(2-chloro-1-iminoethyl)-L-ornithine amide (o-Cl-amidine) (PubMed:21882827). Strongly and specifically inhibited by Thr-Asp-F-amidine (TDFA); other members of the family are not inhibited (PubMed:22004374)
Catalytic activity is inhibited by the antibiotic polymixin B and by Re endotoxin
Ubiquitination of histone H2B by the RAD6/UBC2-BRE1 complex to form H2BK123ub1 is required for efficient DOT1 methyltransferase activity on histone H3. Interaction with DNA is required for optimal histone methyltransferase activity
Stimulated by GTP
Is potently inhibited by sulfonamides, with Ki values between 25 nM and 850 nM
Fully inhibited by 1,10-phenanthroline or EDTA
Inhibited by 8 mM 1,10-phenanthroline, but not by EDTA or PMSF
Inhibited by rhodanine compounds. Some of them almost exclusively kill non-replicating mycobacteria in synergy with products of host immunity, such as nitric oxide and hypoxia, and are effective on bacteria within macrophages
Phosphorylation inactivates the enzyme; while. Thr-145 phosphorylation is required for the catalytic activity of the enzyme (By similarity)
Amino acid transport activity is increased by sodium and is most active at acidic pH (PubMed:25561175, PubMed:31295473). Transport of L-glutamine, leucine and tyrosine is increased by arginine binding (PubMed:29053970, PubMed:31295473)
Phosphorylation at Thr-17 or Tyr-18 inactivates the enzyme, while phosphorylation at Ser-230 activates it
Inhibited by beta-mercaptoethanol and organophosphorothioates such as parathion or terbufos
Inactivated by 1 mM Ag(+) and by 5 mM Cu(2+). Partially inhibited by 5 mM Zn(2+), Mn(2+), Co(2+), Fe(2+) and Ni(2+). Unaffected by 10 mM Na(+), K(+) and Li(+) and by 0.5 mM Mg(2+), Mn(2+), Fe(2+), Ca(2+), Co(2+) and Zn(2+). Inhibited by the sulfhydryl blocking agent 5,5'-dithio-bis-(2-nitrobenzoate), SDS and N-bromosuccinimide. Unaffected by sodium azide and EDTA. Inactivated following treatment with diethyl pyrocarbonate; this inactivation is reversible by treatment with hydroxylamine
The zymogen is inhibited from undergoing autoactivation by BofC. The protease is inactivated by proteolytic cleavage
Activated upon binding to PBP1 or PBP2
Inhibited by nicotinamide. Inhibited by surfactin, which is a competitive inhibitor of NAD and an uncompetitive inhibitor of acetylated peptide
Activity is up-regulated by histamine
Negatively regulated by PtxS, which interacts with PtxR and prevents its activity
Inhibited by poly(L-proline)
Subject to allosteric regulation, exists in two distinct conformational states, a catalytically incompetent (or open) conformation stabilized by the binding of acetyl(acyl)-CoA, and a catalytically competent (or closed) conformation stabilized by ATP-binding. Inhibited by acetyl-CoA and its thioesters which act as allosteric inhibitors and compete with the ATP-binding site
Non-competitively inhibited by 2-hydroxy-4H-isoquinoline-1,3-dione. Activity is down-regulated during cold shock by direct interaction with YmdB. Also down-regulated during entry into stationary phase by an YmdB-independent mechanism
Allosterically regulated and controlled by phosphorylation. 5-phosphoribose 1-diphosphate (PRPP) is an activator while UMP and UTP are inhibitors of the CPSase reaction (By similarity)
Under complex allosteric control mediated by deoxynucleoside triphosphates and ATP binding to separate specificity and activation sites on the large subunit. The type of nucleotide bound at the specificity site determines substrate preference. It seems probable that ATP makes the enzyme reduce CDP and UDP, dGTP favors ADP reduction and dTTP favors GDP reduction. Stimulated by ATP and inhibited by dATP binding to the activity site
The activity is thought to be regulated mainly by the availability of decarboxylated S-adenosylmethionine
Inhibited by 1.1 mM 4-aminopyridine (4-AP) and by 20 mM tetraethylammonium (TEA), but not by charybdotoxin (CTX)(PubMed:19912772). Inhibited by dendrotoxin (DTX) (PubMed:19307729)
Partially inhibited by hydroxylamine
Inhibited by Cyclosporin A
Has no constitutive proton transporter activity and has to be activated by long-chain fatty acids/LCFAs. Inhibited by purine nucleotides. Both purine nucleotides and LCFAs bind the cytosolic side of the transporter and directly compete to activate or inhibit it. Activated by noradrenaline and reactive oxygen species. Despite lacking canonical translational encoding for selenocysteine, a small pool of the protein has been observed to selectively incorporate selenocysteine at 'Cys-255'. Selenocysteine-modified protein is highly sensitive to redox modification and may constitute a pool of protein highly sensitive to activation by elevated levels of reactive oxygen species (ROS)
Irreversibly inhibited by DTT and iodoacetamide at pH 5.7 or pH 5.2, but not at pH 7.2 (Ref.5, Ref.3). Regulated through Ca(2+) gating of H(+) flux at the CFoH(+) channel (PubMed:16228481). Requires the presence of lipids forming reverse hexagonal structures such as monogalactosyldiacylglyceride (MGDG) or phosphatidylethanolamine (PubMed:15078086). A negative curvature elastic stress in the thylakoid lipid bilayer is required for VDE1 activity (PubMed:17618598)
Activated by Ca(2+)/calmodulin. Binding of calmodulin results in conformational change that relieves intrasteric autoinhibition and allows phosphorylation of Thr-177 within the activation loop by CaMKK1 or CaMKK2. Phosphorylation of Thr-177 results in several fold increase in total activity. Unlike CaMK4, is unable to exhibit autonomous activity after Ca(2+)/calmodulin activation (By similarity)
Activated by phosphatidic acid binding (By similarity). Activated by hydrogen peroxide (in vitro). Activated by reactive oxygen species (ROS)
Activated by cAMP, and at 10-100 times higher concentrations, also by cGMP. cAMP binding promotes tetramerization and formation of an active channel. Compared to other family members, cAMP has less stimulatory effect on HCN1 because part of the molecules already contain bound cAMP and form homotetramers when cAMP levels are low
Cap-specific adenosine methyltransferase activity is inhibited by zinc
Is irreversibly inactivated by the beta-lactams carbapenems via the formation of a covalent adduct resulting from enzyme acylation; imipenem is the most efficient drug for in vitro LdtMt4 inactivation
Inhibited by reserpine and verapamil
Activity is inhibited by EDTA, o-phenanthroline, bestatin and amastatin
Activated by the MAPK kinase wisl, and negatively regulated by pypl and pyp2 tyrosine phosphatases
Inhibited by AEBSF (4-(2-aminoethyl)benzenesulfonyl fluoride, Pefabloc SC)
The triglyceride lipase activity is inhibited by BEL ((E)-6-(bromomethylene)-3-(1-naphthalenyl)-2H-tetrahydropyran-2-one), a suicide substrate inhibitor (PubMed:17032652). No differences in the acylglycerol transacylase was detected in the presence or absence of ATP (PubMed:15364929)
Activity is regulated by phosphorylation at Ser-49 and Ser-52, which stabilizes the eIF2/GDP/eIF-2B complex and prevents the eIF-2B-mediated exchange of GDP for GTP, thereby preventing the formation of the 43S pre-initiation complex (43S PIC) (PubMed:11106749, PubMed:12176355, PubMed:15277680, PubMed:19131336, PubMed:21285359). This results in the global attenuation of 5' cap-dependent protein synthesis and concomitant translation of ISR-specific mRNAs that contain a short upstream open reading frame (uORF) in their 5' UTR, such as ATF4, ATF5, DDIT3/CHOP and PPP1R15A/GADD34 (PubMed:15277680, PubMed:19131336, PubMed:21285359)
MJ33 or lithium;[(2R)-1-hexadecoxy-3-(2,2,2-trifluoroethoxy)propan-2-yl] methyl phosphate inhibits its phospholipase A2 activity (PubMed:26830860). CI-976 or 2,2-Dimethyl-N-(2,4,6-trimethoxyphenyl)dodecanamide inhibits its lysophosphatidylcholine acyltransferase activity (PubMed:26830860)
Activated by ascorbate (PubMed:17991826). Inhibited by N-oxalylglycine, fumarate and succinate (PubMed:17991826)
Inhibited by the propeptide produced by autocleavage (PubMed:9468501). Long isoform of CD74/Ii chain stabilizes the conformation of mature CTSL by binding to its active site and serving as a chaperone to help maintain a pool of mature enzyme in endocytic compartments and extracellular space of APCs. IFNG enhances the conversion into the CTSL mature and active form (By similarity). Inhibited by CST6. Inhibited by the glycopeptide antibiotic teicoplanin (PubMed:26953343). Inhibited by amantadine (PubMed:32361028)
Insensitive to all selective PDE inhibitors
Inactivated by phosphorylation. Repressed by roscovitine (seliciclib, CYC202), R547 (Ro-4584820) and SNS-032 (BMS-387032). The association of p53/TP53 to the CAK complex in response to DNA damage reduces kinase activity toward CDK2 and RNA polymerase II repetitive C-terminal domain (CTD), thus stopping cell cycle progression. The inactivation by roscovitine promotes caspase-mediated apoptosis in leukemic cells
Initially produced in an inactive form and is activated by binding to viral dsRNA, which causes dimerization and autophosphorylation in the activation loop and stimulation of function. ISGylation can activate it in the absence of viral infection. Can also be activated by heparin, pro-inflammatory stimuli, growth factors, cytokines, oxidative stress and the cellular protein PRKRA. Activity is markedly stimulated by manganese ions. Activation is blocked by the viral components HIV-1 Tat protein and large amounts of HIV-1 trans-activation response (TAR) RNA element as well as by the cellular proteins TARBP2, DUS2L, NPM1, NCK1 and ADAR. Down-regulated by Toscana virus (TOS) and Rift valley fever virus (RVFV) NSS which promote its proteasomal degradation. Inhibited by vaccinia virus protein E3, probably via dsRNA sequestering
Inhibited by trichostatin A (TSA), a well-known histone deacetylase inhibitor
Negatively regulated by the anti-sigma-I factor RsgI8
The proteolytic activity is dependent on ATP, both the ATPase and protease activities are inhibited by ADP
Activity is increased under anaerobic growth conditions
Inhibited by cysteine protease inhibitor iodoacetic acid (CH3COOI) but not by N-[N-(L-3-transcarboxirane-2-carbonyl)-leucyl]-agmatine (E-64) or benzyloxycarbonyl-DEVD-fluoro-methyl ketone (Z-DEVD-FMK)
Inhibited by methionine sulfoximine, ADP and pyrophosphate, but not by various nitrogen-containing metabolites that inhibit other GS enzymes
Mammalian nucleoside transport inhibitors dipyridamole and NBMPR inhibit adenosine transport by NUP
Zinc acts as a corepressor and is required for DNA-binding activity. Binds up to two zinc ligands per monomer. Inactive under zinc deprivation
FMN is a competitive inhibitor of NADH, and therefore leads to the preferential utilization of NADPH
Inhibited 16-fold better by the beta-lactamase inhibitor tazobactam than by clavulanic acid
Activity is increased sixfold following autotrophic growth on methanol compared with that of heterotrophically grown cells
Activity is inhibited by about 80% in the presence of 18% sodium chloride
Can alternate between a fully active homooctamer and a low-activity homohexamer. A bound magnesium ion may promote the assembly of the fully active homooctamer. The magnesium-binding site is absent in the low-activity homohexamer. Inhibited by compounds that favor the hexameric state. Inhibited by divalent lead ions. The lead ions partially displace the zinc cofactor
Regulated at the post-translational level in response to alterations of sphingolipid and sterol biosynthetic pathways. Negatively regulated by a PP2A-dependent dephosphorylation occurring at a site different than Ser-577. Completely inhibited by mevinolin (IC(50) = 12.5 nM). Reversibly inactivated by phosphorylation at Ser-577 by spinach or Brassica oleracea HMGR kinases in a cell-free system (PubMed:7588795, PubMed:10318703). Down-regulated by KIN10 through its phosphorylation at Ser-577 (PubMed:28263378)
The formation of the proteasomal ATPase PAN-20S proteasome complex, via the docking of the C-termini of PAN into the intersubunit pockets in the alpha-rings, triggers opening of the gate for substrate entry. Interconversion between the open-gate and close-gate conformations leads to a dynamic regulation of the 20S proteasome proteolysis activity (By similarity). In vitro, the chymotrypsin-like activity of the alpha1-beta proteasome is potently inhibited by carbobenzoxyl-leucinyl-leucinyl-leucinal-H (MG132) and significantly by N-acetyl-leucinyl-leucinyl-norleucinal-H (calpain inhibitor I)
The amylase activity is stimulated by addition of Ca(2+), but this cation and other divalent cations inhibit the trehalose synthase activity. In addition, trehalose synthase activity, but not amylase activity, is strongly inhibited, and in a competitive manner, by validoxylamine. On the other hand, amylase, but not trehalose synthase activity, is inhibited by the known transition-state amylase inhibitor, acarbose, suggesting the possibility of two different active sites. Other metal ions such as Mg(2+), Mn(2+), and Co(2+) are also somewhat effective in the stimulation of amylase activity, but Hg(2+), Cu(2+), Ni(2+) and Zn(2+) are inhibitory
Inhibited by p-(chloromercuri)benzenesulfonic acid and cobalt
The uptake of taurocholate is inhibited by taurolithocholate sulfate with an IC(50) of 9 uM. Pravastatin competitively inhibits the transport of taurocholic acid. Cyclosporin A, glibenclamide, rifampicin and troglitazonestrongly competitively inhibit the transport activity of taurocholate. The canalicular transport activity of taurocholate is strongly dependent on canalicular membrane cholesterol content. The uptake of taurocholate is increased by short- and medium-chain fatty acids. Cholesterol increases transport capacity of taurocholate without affecting the affinity for the substrate
Inhibited by sulfhydryl-modifying agents such as N-ethylmaleimide, monoiodoacetic acid and p-hydroxymercuribenzoic acid. No inhibition by riboflavin and lycorine
Inhibited by the specific aspartic proteinase inhibitors diazoacetyl-noleucine methyl ester and pepstatin
Inhibited by cholesterol and thiol reagents
When exposed to oxidative stress, Gsp amidase activity is transiently inhibited in vivo by oxidation of the catalytic Cys-59 thiol to sulfenic acid; this modification does not affect Gsp synthetase activity
Type I PDE are activated by the binding of calmodulin in the presence of Ca(2+) (PubMed:8810348). Different splice variants may have different sensitivities to Ca(2+) (PubMed:8810348)
Exhibits a higher sensitivity to Ca(2+) stimulation than isoforms 1 and 2 (PubMed:8810348)
Inhibited by malonate and by inorganic phosphate
Inhibited by 1,4-disubstituted imidazoles, 1,4-benzodiazepine, naphthyridinone derivatives, triclosan and its diphenyl ether analgues
Inhibited by FK506, ascomycin and rapamycin
Activated by dithiothreitol and inhibited by EDTA
Cysteine desulfurase activity is increased 2-fold in the presence of CsdE
Activity is inhibited by Zn(2+) and Co(2+). No activity in the presence of Fe(2+)
Inhibited by phenylmethanesulfonyl fluoride (PMSF) and chymostatin (CST), but not by Bowman-Birk type trypsin-chymotrypsin inhibitor (BBI)
Oxydation of Cys-21 leads to partial activation of RclR, followed by the formation of an intramolecular disulfide bond between Cys-21 and Cys-89, which stabilizes the active form of RclR
Activated by non-covalent binding of the propeptide to the catalytic domain (PubMed:15494009, PubMed:17302431, PubMed:29239122). The concentration of the propeptide is regulated in the endoplasmic reticulum and the propeptide thus regulates the amount of the active enzyme at various stages of the growth cycle (PubMed:17302431). The dimeric enzyme has about half of the maximal activity in the presence of one bound propeptide, but is fully active with two bound O-glycosylated propeptides (PubMed:15494009, PubMed:17302431). Inhibited by N-acetylglucosamine (NAG)-thiazoline (PubMed:17302431)
Three specific sites, one in the kinase domain (Thr-308) and the two other ones in the C-terminal regulatory region (Ser-473 and Tyr-474), need to be phosphorylated for its full activation (PubMed:20481595, PubMed:21392984, PubMed:9512493, PubMed:9736715). Inhibited by pyrrolopyrimidine inhibitors like aniline triazole and spiroindoline (PubMed:18456494, PubMed:20810279)
Homodimerization regulates its activity by maintaining the kinase in an autoinhibitory conformation. NPRL2 down-regulates its activity by interfering with tyrosine phosphorylation at the Tyr-9, Tyr-373 and Tyr-376 residues. The 14-3-3 protein YWHAQ acts as a negative regulator by association with the residues surrounding the Ser-241 residue. STRAP positively regulates its activity by enhancing its autophosphorylation and by stimulating its dissociation from YWHAQ. SMAD2, SMAD3, SMAD4 and SMAD7 also positively regulate its activity by stimulating its dissociation from YWHAQ. Activated by phosphorylation on Tyr-9, Tyr-373 and Tyr-376 by INSR in response to insulin
Activated by automethylation
Inhibited by wide spectrum metalloproteinase inhibitor batimastat (BB-94). Also inhibited by EDTA (By similarity)
Phosphorylation on Thr-45 decreases activity (PubMed:19074144). Sensitive to thiolactomycin and resistant to cerulenin in vitro (PubMed:10840036). Inhibited by decylSSCoA, which modify both of the active site cysteines through disulfide linkage to the decylthio-group (PubMed:18096200)
Enzymatic activity and neurotoxicity are inhibited by Triton X-100 (By similarity). Triton X-100 has been determined to be located in the center of the hydrophobic channel of the enzyme (PubMed:19500614)
Inhibited by N-ethylmaleimide and p-chloromercuribenzoic acid
Inhibited competitively by amidines and guanidines, and irreversibly inhibited by diisopropylfluorophosphate
Inhibited by 4-O-MeGlcA
Protease activity can be inhibited in vitro by either a zinc specific chelator, 1,10-phenanthroline, or a metal chelator, EDTA. The enzyme is resistant to phenylmethylsulfonyl fluoride and iodoacetic acid
Activity is independent of metal ions
CCCP treatment reduces SAM intracellular uptake by 50%
Activated by phosphorylation on Thr-172 (PubMed:15980064). Binding of AMP to non-catalytic gamma subunit (PRKAG1, PRKAG2 or PRKAG3) results in allosteric activation, inducing phosphorylation on Thr-172 (PubMed:15980064). AMP-binding to gamma subunit also sustains activity by preventing dephosphorylation of Thr-172 (PubMed:15980064). ADP also stimulates Thr-172 phosphorylation, without stimulating already phosphorylated AMPK (PubMed:15980064). ATP promotes dephosphorylation of Thr-172, rendering the enzyme inactive (PubMed:15980064). Under physiological conditions AMPK mainly exists in its inactive form in complex with ATP, which is much more abundant than AMP. AMPK is activated by antihyperglycemic drug metformin, a drug prescribed to patients with type 2 diabetes: in vivo, metformin seems to mainly inhibit liver gluconeogenesis. However, metformin can be used to activate AMPK in muscle and other cells in culture or ex vivo (PubMed:11602624). Selectively inhibited by compound C (6-[4-(2-Piperidin-1-yl-ethoxy)-phenyl)]-3-pyridin-4-yl-pyyrazolo[1,5-a] pyrimidine. Activated by resveratrol, a natural polyphenol present in red wine, and S17834, a synthetic polyphenol. Salicylate/aspirin directly activates kinase activity, primarily by inhibiting Thr-172 dephosphorylation
Inhibited by the kinase inhibitors staurosporine and H-7
Strongly inhibited by wheat xylanase inhibiting protein I (XIP-I), and by proteinaceous endoxylanase Triticum aestivum xylanase inhibitors I and II (TAXI-I and TAXI-II)
The adenylation activity is stimulated by glutamine and PII (GlnB), and inhibited by 2-oxoglutarate (PubMed:4867671, PubMed:4920894, PubMed:33597, PubMed:9312015). Deadenylation activity is stimulated by PII-UMP (GlnB-UMP) and 2-oxoglutarate, and inhibited by glutamine (PubMed:4893578, PubMed:4934180, PubMed:33597, PubMed:9312015, PubMed:14766310)
Activated by millimolar concentrations of calcium
Inhibited by cyanide ions
Uptake of D-serine is inhibited by D-alanine, D-cycloserine, glycine and at high concentrations of D-threonine
Kynurenine transamination is competitively inhibited by cysteine, glutamine, histidine, methionine, leucine, or phenylalanine
2,3-iminosqualene and N,N-dimethyldodecylamine~N-oxlde are effective inhibitors with IC(50) values of 50 and 30 nM, respectively
Inhibited by pyridoxal phosphate and chloride ions
Inhibited by L-penicillamine (PubMed:31442408). Beta-lactamase activity is inhibited by cilastatin (PubMed:6334084, PubMed:31442408)
Inhibited by cyclopiazonic acid (CPA)
Inhibition of aspartate kinase activity by threonine and leucine and 3-fold activation by cysteine, isoleucine, valine, serine and alanine at 2.5 mM. Partial inhibition of homoserine dehydrogenase activity by threonine and cysteine (14% of activity remaining at saturation with either amino acid). No synergy between the effectors for both activation or inhibition
Activated by K(+) and Mg(2+). Inhibited by Ca(2+), N,N'-dicyclohexylcarbodiimide (DCCD), N-ethylmaleimide (NEM) and aminomethylenediphosphonate (AMDP), and, to a lower extent, by fluoride (KF)
Inhibited by ALK inhibitor TAE684
Inhibited by 5-phosphoarabinonate (PAB) and 6-phosphogluconate
Activated by external aluminum
Present in an inactive conformation in the absence of bound ligand. KITLG/SCF binding leads to dimerization and activation by autophosphorylation
Repressed by 4-(3-hydroxyanilino)-quinolines derivatives, indolin-2-one-derivatives, 2-(alkylsulfanyl)-4-(3-thienyl) nicotinonitrile analogs, 3- and 4-substituted beta-carbolin-1-ones, vandetanib, motesanib, sorafenib (BAY 43-9006), cabozantinib (XL184), sunitinib, and withaferin A (WA). Inactivation by sorafenib both reduces kinase activity and promotes lysosomal degradation
Activity is regulated by the nitrogen regulatory protein GlnK1 via direct interaction (PubMed:17203075). Formation of the GlnK1/Amt1 complex is decreased in the presence of Mg-ATP or 2-oxoglutarate. The presence of both effectors abolishes the formation of the complex (PubMed:17203075)
Very weakly inhibited by biuret. Significant inhibition only at biuret concentrations greater than 50 mM
Phosphorylated by MAP2K1/MEK1 and MAP2K2/MEK2 on Thr-202 and Tyr-204 in response to external stimuli like insulin or NGF. Both phosphorylations are required for activity. This phosphorylation causes dramatic conformational changes, which enable full activation and interaction of MAPK1/ERK2 with its substrates. Dephosphorylated and inactivated by DUSP3, DUSP6 and DUSP9
DNA binding is strongly activated by Mn(2+) and Cd(2+), but it is poorly activated by non-cognate metal cations, including Co(2+), Fe(2+), Ni(2+), Ca(2+) and Zn(2+). In the strict absence of divalent transition metal ions, MntR has a low affinity for DNA
Inhibited by p-hydroxymercuribenzoate and EDTA
Carboxylase activity of the AccA3/AccD5 complex is stimulated by interaction with AccE5
Inhibited by EDTA, and 1,10-phenanthroline
ATPase activity is inhibited by bicyclomycin and dihydrobicyclomycin
Slightly inhibited by sn-glycerol 3-phosphate
RNA triphosphatase activity is inhibited by magnesium
Completely inhibited by 100 nM sodium azide and by the proton ionophore carbonyl cyanide m-chlorophenylhydrazone (CCCP) (PubMed:17307853). Is also strongly inhibited by 100 mM potassium fluoride (PubMed:17307853)
Greatly decreased inhibitory activity against papain protease by metal ions including ZnSO(4), CuSO(4), HgCl(2) and CoCl(2). Decreased inhibitory activity against papain protease by detergents including Tween 20, SDS and Brij 35
The enzyme activity is specifically activated by double-stranded RNA (dsRNA) (PubMed:34261127, PubMed:34261128). Recognizes long dsRNA (>30 bp) with no preference for 5' RNA phosphorylation (PubMed:34261127)
Inhibited by EDTA, and 1,10-phenanthroline, but not by PMSF
Interaction with long chain acyl-CoA derivatives (oleoyl-CoA and, to lesser extent, stearoyl-CoA) prevents binding to DNA, leading to the expression of the target genes. Long chain acyl-CoA derivatives may serve as biological indicators of the bacterial metabolic state
Inhibition by zinc ions (Potential). Inactivated by EDTA
Activity provided by the Kae1 region seems to be regulated via phosphorylation by the protein kinase Bud32, which is itself activated by Cgi121
Inhibited by hydroxylamine, sodium borohydride, D-cycloserine, hydrazine, semicarbazine and succinic dehydrazine (PubMed:6767707). D-serine is a competitive inhibitor (PubMed:6767707). Cleavage and catalytic activity are regulated by PanZ in a coenzyme A (CoA)-dependent fashion (PubMed:23170229, PubMed:25910242)
Heparin inhibits the myotoxic activity (PubMed:7961981). Suramin inhibits the myotoxic activity (PubMed:15961104). High level of membrane cholesterol content reduces cytolytic activity, whereas low level of membrane cholesterol content increases cytolytic activity (PubMed:21506137)
Activity is regulated by phosphorylation at Ser-49 and Ser-52, which stabilizes the eIF-2/GDP/eIF-2B complex and prevents the eIF-2B-mediated exchange of GDP for GTP, thereby preventing the formation of the 43S pre-initiation complex (PIC). This results in the global attenuation of 5' cap-dependent protein synthesis and concomitant translation of ISR-specific mRNAs that contain a short upstream open reading frame (uORF) in their 5' UTR
Cu(2+), Hg and p-chloromercuribenzoate are strong inhibitors of enzyme activity and Ca(2+), Mg(2+), Zn(2+), Mn(2+), Cd(2+) and Sn(2+) have no effect on activity indicating a cysteine residue in the protein is essential for enzyme activity or to maintain the proper structure of the enzyme. Nitrite and nitrate inhibit some enzyme activity, however cyanide, azide, thiocyanate and cyanate are strong inhibitors of the enzymatic reaction. The inhibition of cyanide is competitive with formate and reversible
Competitively inhibited by 5'-thioacetyladenosine (TAA) and di-(5'-thioadenosine) (DTA)
Activated by phosphate. Inhibited by cardiolipin and phosphatidate
Activated by magnesium and PDK1. Inhibited by staurosporine. Repressed by calcium
Inhibited by N-ethylmaleimide, p-chloromercuribenzoic acid and diethylpyrocarbonate (DEPC)
Activated by phosphorylation by MPK3 and MPK6 (PubMed:18273012). Down-regulated by KIN10 that controls its protein stability under a phosphorylation-dependent manner (PubMed:28600557). Satnilitzed during hypoxia (e.g. submergences) via a ceramides-triggered and CTR1-dependent manner (PubMed:25822663)
Activity is increased by Mn(2+) ions. Inhibited by Zn(2+), Ni(2+), Co(2+), Cu(2+) and Al(3+). No significant activity change by Na(+), K(+), Ca(2+), Mg(2+) and Ba(2+) ions. Both isoform are completely inhibited by L-Cys and reduced glutathione. O-phenanthroline, beta-mercaptoethanol and PMSF completely inhibit the enzymatic activity of LAAOII, but have no activity on LAAOI. Iodoacetic acid inhibits the enzymatic activity of LAAOII by 46% but has no effect on the LAAOI activity
Expression is dependent on and stimulated by NADPH, calcium, BH4 and calmodulin. The activity is not dependent on FAD and is not stimulated by its presence
Pyruvate dehydrogenase activity is inhibited by phosphorylation of PDHA2; it is reactivated by dephosphorylation
Serine/threonine protein kinase activity is increased upon interaction with FAM20A
Is potently inhibited by the reaction product N(5)-(L-1-carboxyethyl)-L-ornithine
Redox-insensitive
Activated by chloride and fluoride, but not bromide. Inhibited by MLN-4760, cFP_Leu, and EDTA, but not by the ACE inhibitors linosipril, captopril, enalaprilat
Allosterically regulated and controlled by phosphorylation. 5-phosphoribose 1-diphosphate (PRPP) is an activator while UMP and UTP are inhibitors of the CPSase reaction
Subject to competitive inhibition by coenzyme A (CoA)
Inhibited by pepstatin, diazoacetyl-DL-norleucine methyl ester (DAN) and nelfinavir (PubMed:22933181). Inhibited by the proteinase inhibitors lopinavir and ritonavir (PubMed:21266539)
The uptake of leucine, tyrosine and tryptophan is inhibited by the different iodothyronines, in particular T3 (PubMed:11564694). The uptake of T3 is almost completely blocked by coincubation with leucine, tryptophan, tyrosine, and phenylalanine, or 2-amino-bicyclo-(2,2,1)-heptane-2-carboxylate (BCH) (PubMed:11564694). Methionine uptake was inhibited by the L-system substrates L-leucine, BCH, L-cysteine and by the MeHg-L-cysteine complex and structurally related S-ethyl-L-cysteine (PubMed:12117417). MeHg-L-cysteine uptake is inhibited by L-methionine, L-leucine, BCH and S-ethyl-L-cysteine (PubMed:12117417). L-leucine transport is inhibited by phenylalanine, tyrosine, L-dopa, 3-O-methyldopa, a-methyltyrosine, a-methyldopa, gabapentin, triiodothyronine, thyroxine, melphalan and BCH (PubMed:12225859). L-leucine uptake was inhibited by L-CNSO (PubMed:15769744). Tyrosine uptake in fibroblasts was inhibited by D-methionine, and methyl-aminoisobutyric acid (MeAIB) (PubMed:18262359)
Inhibited by 2-hydroxydodecanoic acid, a typical inhibitor of medium-chain acyl-CoA synthetases
Strongly inhibited by reserpine and tetrabenazine (PubMed:8643547, PubMed:8860238). Also inhibited to a lesser extent by ketanserin and fenfluramine. Inhibited by tetrabenazine
Inhibited by flavin concentrations greater than 15 uM. Also inhibited by excess p-hydroxyphenylacetate (HPA)
Phosphorylated by MAP2K1/MEK1 and MAP2K2/MEK2 on Thr-183 and Tyr-185 in response to external stimuli like insulin or NGF. Both phosphorylations are required for activity. This phosphorylation causes dramatic conformational changes, which enable full activation and interaction of MAPK1/ERK2 with its substrates. Phosphorylation on Ser-27 by SGK1 results in its activation by enhancing its interaction with MAP2K1/MEK1 and MAP2K2/MEK2. Dephosphorylated and inactivated by DUSP1, DUSP3, DUSP6 and DUSP9. Inactivated by pyrimidylpyrrole inhibitors
Is activated by the HinT protein. Is inhibited by D-cycloserine
Inhibited by high concentration of cysteine and by 3-phosphonooxypyruvate. Not inhibited by serine, threonine, valine, glycine, tryptophan and O-acetyl-L-serine
Inhibited by diprotin A
Inhibited by (E)-2-fluoro-p-hydroxycinnamate
Inhibited by Li(+) (IC(50)=0.20 millimolar) and Na(+) (IC(50)=200 millimolar)
Phosphorylation at Ser-460 and Ser-480 by PRK2 releases ROPGEF1 auto-inhibition, thereby activating ROPGEF1, which in turn activates ARAC11/ROP1
Seems to require potassium ions for its activity and stability. Slightly inhibited by N-ethylmaleimide
AMP causes 20-40% inhibition and diphosphate causes 20-50% inhibition. ADP, citrate, PEP and FBP have no effect
Inhibited by zinc Zn(2+), copper Cu(2+) and silver Ag(+) ions
In contrast to most ribotoxins, activity is completely inhibited by EDTA
Inhibited by free nucleotide diphosphates (NDPs)
Is inhibited by EDTA, o-phenanthroline and tetraethylenepentamine
ATPase activity is stimulated by binding to either DNA or nucleosomes
Lipoxygenase activity is stimulated by calcium, sodium, lithium and potassium ions. Calcium binding promotes interaction with membranes and thus facilitates access to substrates
EsxB binding to the third FtsK domain causes multimerization; a subsequent unknown step relieves the allosteric inhibition of linker 2 on FtsK domain 1, activating the ATPase activity (By similarity)
Activated by forskolin (PubMed:15385642). Is not activated by calmodulin. Inhibited by calcium ions, already at micromolar concentration. Activated by the G protein alpha subunit GNAS. Activated by the G protein beta and gamma subunit complex (By similarity). Phosphorylation by RAF1 results in its activation (PubMed:15385642). Phosphorylation by PKC activates the enzyme (By similarity)
Is not choline-responsive
Phosphorylation at Thr-15 or Tyr-16 inactivates the enzyme, while phosphorylation at Thr-160 activates it
Allosterically inhibited by the product c-di-GMP
Inhibited by azalanstat (PubMed:7665087). Inhibited by azole antifungal agents ketoconazole, itraconazole and fluconazole (PubMed:10544287)
Activated by binding small G proteins. Binding of GTP-bound CDC42 or RAC1 to the autoregulatory region releases monomers from the autoinhibited dimer, and enables activation by phosphorylation of Thr-423 (PubMed:10995762, PubMed:11804587, PubMed:15893667, PubMed:9032240). Phosphorylation of Thr-84 by OXSR1 inhibits activation (By similarity)
Is inhibited by L-proline and L-lysine. Is not activated by small concentrations of L-arginine, and is even inhibited by about 50% at 0.5 mM L-arginine
Transport activity is significantly increased in response to dietary phosphate deprivation
Negatively regulated by the anti-sigma-I factor RsgI5 (By similarity). Binding of the polysaccharide substrate to RsgI5 may lead to the release and activation of SigI5 (By similarity)
Zinc acts as a coregulator and is required for DNA-binding activity (PubMed:20804771, PubMed:21603707)
Subject to product inhibition by ADP-ribose
Inhibited by hexestrol with an IC(50) of 2.8 uM, 1,10-phenanthroline with an IC(50) of 2100 uM, 1,7-phenanthroline with an IC(50) of 1500 uM, flufenamic acid with an IC(50) of 0.9 uM, indomethacin with an IC(50) of 75 uM, ibuprofen with an IC(50) of 6.9 uM, lithocholic acid with an IC(50) of 0.07 uM, ursodeoxycholic acid with an IC(50) of 0.08 uM and chenodeoxycholic acid with an IC(50) of 0.13 uM (PubMed:8573067). The oxidation reaction is inhibited by low micromolar concentrations of NADPH (PubMed:14672942)
The dipeptidyl carboxypeptidase activity is specifically inhibited by lisinopril, captopril and enalaprilat (PubMed:15665832, PubMed:35201898). The N-terminal catalytic domain, but not the C-terminal catalytic domain, is specifically inhibited by the phosphinic peptide RXP 407 (PubMed:11303049)
The putative GPIase activity is nearly insensitive to captopril
Inhibited by chymostatin, phenylmethanesulfonyl fluoride and diisopropyl fluorophosphate
Esterase activity is down-regulated by salicylic acid (SA). Down-regulated by agrochemicals Paraoxon, 3,4-DCl and Profenofos
Not inhibited by sulfate
Activated by Co(2+) at 1 mM. Completely inhibited by Hg(2+) but not affected by other divalent cations. Intensely inhibited by NaCl and KCl at 150 mM, in particular by the Na(+) and K(+) ions but not the Cl(-) ions. Partially inhibited by iodoacetamide and N-ethylmaleimide at 1 mM but not by dithiothreitol, reduced glutathione or 2-mercaptoethanol
Inhibited by N-(12-imidazolyl-dodecanoyl)-L-leucine
Activated by phosphorylation on Thr-182. Also activated by phosphorylation on Thr-322 in response to increases in intracellular sodium in parallel with elevations in intracellular calcium through the reversible sodium/calcium exchanger
Inhibited by dithiothreitol (DTT) and 2-mercaptoethanol (PubMed:16229686). Activity is mildly stimulated by Ca(2+) and Mg(2+), but is not inhibited by EDTA (PubMed:10781606, PubMed:16229686). Activity is inhibited by millimolar levels of Fe(2+), Zn(2+) and Cu(2+) (PubMed:16229686, PubMed:17475390). Inhibited by cholesterol (PubMed:17475390)
Inhibited by chloro-3-hydroxyacetone and D,L-glyceraldehyde
Phosphorylation at Thr-14 or Tyr-15 inactivates the enzyme, while phosphorylation at Thr-158 activates it (By similarity). Activated by cyclin cyc-1 in vitro (PubMed:10722743, PubMed:12869562). Activated by cyclin cyc-3 in vitro (PubMed:12869562)
Inhibited by the competence and sporulation stimulating factor (CSF), encoded by phrC, which prevents RapC-ComA interaction
Glutathione increases enzyme activity
The activity is calcium-dependent (By similarity). Requires phosphatidylserine for maximal activity (PubMed:8034597)
Strongly inhibited by iodoacetate, potassium cyanide (KCN), 2-mercaptoethanol, dithiothreitol (DTT), p-chloromercuribenzoate, menadione and estradiol. Weakly inhibited by 4'-(9-acridinylamino)methanesulfon-m-anisidine (mAMSA) and tritonX-100. Not affected by allopurinol
Activity is not dependent on divalent cations, but it is enhanced by Mg(2+)
Does not require divalent metal ions
Inhibited by methionine and cystathionine
May be activated by autophosphorylation (PubMed:19210548, PubMed:20226672). May be inhibited by csk-1-mediated phosphorylation (PubMed:12527374)
Antiviral activity is neutralized by the simian immunodeficiency virus rhesus (SIV-mac) virion infectivity factor (VIF)
Catalytic activity is inhibited by the morphilines tridemorph, fenpropimorph, and fenpropidin
The activity is completely inhibited by miconazole and reduced by voriconazole (6% substrate conversion), posaconazole (10%), itraconazole (16%), (R)-N-(1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethyl)-4-(5-phenyl-1,3,4-oxadiazol-2-yl)benzamide (VNI) (20%), and (R)-N-(1-(3,4'-difluorobiphenyl-4-yl)-2-(1H-imidazol-1-yl)ethyl)-4-(5-phenyl-1,3,4-oxadiazol-2-yl)benzamide (VFV) (31%). The weakest inhibitory effect is observed with fluconazole (PubMed:26459890, PubMed:26269599, PubMed:28461309). Activity is also inhibited by ketoconazole, as well as by the azole-based drug candidates VT-1161 and VT-1598 (PubMed:28461309). Activity is inhibited by the novel and long-acting fungicidal azole PC1244 (PubMed:29439966)
Specifically inhibited by BAY-73-6691 (1-(2-chlorophenyl)-6-((2R)-3,3,3- trifluoro-2-methylpropyl)-1,5-dihydro-4H-pyrazolo(3,4-d)pyrimidine-4-one) (PubMed:18674549). Specifically inhibited by PF-04447943 (6-[(3S,4S)-4-methyl-1-(pyrimidin-2-ylmethyl)pyrrolidin-3-yl]-1-(tetrahydro-2H-pyran-4-yl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one) (PubMed:22070409)
Binds cyclic di-AMP (c-di-AMP), which may regulate the activity
Transcription of the aapA3 gene generates a full-length transcript whose folding impedes translation. Processing of the 3' end of the aapA3 message generates a shorter transcript that becomes translatable after a structural rearrangement
Inhibited by acetylation at Lys-642 and activated by deacetylation mediated by the deacetylase SIRT3
Inhibited by hydroxylamine and O-methylhydroxylamine
Dependent on high salt concentrations for activity and stability. Strongly inhibited by the serine protease inhibitors diisopropyl fluorophosphate (DFP), phenylmethyl sulfonylfluoride (PMSF) and chymostatin. Also inhibited by denaturing agents such as SDS, urea, and HCl guanidinium. Activated by thiol-containing reducing agents such as dithiotreitol (DTT) and 2-mercaptoethanol
Inhibited by L-leucine, the pathway end product
msDNA synthesis is inhibited by rifampicin and chloramphenicol
Completely inhibited by most divalent metal cations, however magnesium and molybdene have no effect
Activated by millimolar concentrations of calcium, and by phosphatidylinositol 4,5-diphosphate, phosphatidylinositol 4-monophosphate, phosphatidylinositol and phosphatidic acid
Dephosphorylated by daf-18
Activated by NADH and inhibited by phosphoenolpyruvate
The cyclooxygenase activity is inhibited by nonsteroidal anti-inflammatory drugs (NSAIDs) including aspirin, ibuprofen, flurbiprofen, celecoxib, flufenamic, mefenamic and tolfenamic acids as well as by hydroperoxide scavenger erythrocyte glutathione peroxidase GPX1 (PubMed:26859324, PubMed:27226593, PubMed:7592599, PubMed:9048568). Aspirin triggers enzyme acetylation turning off its ability to generate pro-inflammatory prostaglandins, but switches on its capacity to produce anti-inflammatory lipid mediators involved in inflammation resolution (PubMed:11034610, PubMed:12391014). Aspirin enhances lipoxygenase-type activity toward production of epimers with R stereochemistry such as 15R-HETE, 18R-HEPE, 15R-HEPE and 17R-HDHA (PubMed:11034610, PubMed:11192938, PubMed:22068350, PubMed:12391014, PubMed:9048568, PubMed:21206090). Atorvastatin, a cholesterol-lowering drug, triggers enzyme S-nitrosylation increasing production of 13-series resolvins (RvTs) (PubMed:26236990)
Strongly activated by monovalent cations, such as K(+), Na(+), and NH4(+)
The ATPase activity is inhibited by the ADP product
Activated by Triton X-100, insensitive to inhibition by adenosine and inhibited by wortmannin (PubMed:8662589). The PI4K complex acts as a regulator of phosphatidylinositol 4-phosphate (PtdIns(4)P) synthesis (By similarity). Interaction with TMEM150A regulates PtdIns(4)P synthesis (By similarity)
Mn(2+), Co(2+), Zn(2+), Fe(2+), Mg(2+), and Ca(2+) inhibit the hydrolysis activity of the enzyme whereas EGTA and EDTA do not affect the activity
Binding to ERDJ3A activates the ATPase activity of BIP1
Inhibited by L- and D-pipecolic acid, nipecotic acid, isonipecotic acid, L- and D-cycloserine, and L-2-azetidine-carboxylate
Inhibited by hexestrol with an IC(50) of 9.5 uM, 1,10-phenanthroline with an IC(50) of 55 uM, 1,7-phenanthroline with an IC(50) of 72 uM, flufenamic acid with an IC(50) of 6.0 uM, indomethacin with an IC(50) of 140 uM, ibuprofen with an IC(50) of 950 uM, lithocholic acid with an IC(50) of 25 uM, ursodeoxycholic acid with an IC(50) of 340 uM and chenodeoxycholic acid with an IC(50) of 570 uM (PubMed:8573067). The oxidation reaction is inhibited by low micromolar concentrations of NADPH (PubMed:14672942)
Inhibited by fosmidomycin and 3-(N-acetyl-N-hydroxyamino)-propylphosphonic acid (FR-900098)
Inhibits by captopril, thiorphan, dimercaprol and tiopronin (PubMed:25815530). This enzyme is not susceptible to inactivation by the beta-lactamase-blocking agents clavulanic acid (PubMed:19770275)
Activity dramatically decreases in the presence of the general protein phosphatase inhibitor sodium phosphate. Slightly inhibited by sodium fluoride. Activity decreases in the presence of the metal chelator EDTA
Synthesis of cA6 is inhibited by EDTA
Competitively inhibited by UDP-N-acetylglucosamine 3'-phosphate, with a Ki of 7 uM (PubMed:21445328). In vitro inhibited by covalent binding of fosfomycin and the fungal product terreic acid in the presence of substrate UDP-N-acetylglucosamine, with an inactivation rate constant of 102 M(-1)sec(-1) for terreic acid (PubMed:20392080)
Active when the heme iron is in the ferrous state (PubMed:16233624, PubMed:19740758). The activity is enhanced by reducing agents, such as Na(2)S, Na(2)S(2)(O4), 2-mercaptoethanol, and L-cysteine and supplementary additions of electron acceptors such as flavins, sulfite ion, and vitamin K3 (PubMed:16233624). The effect of various chemicals on the enzyme activity is different in the presence and absence of the reducing reagent, Na(2)S, which acts not only as a reductant but also changes the substrate specificity of the enzyme (PubMed:16233624)
Ethylene-responsive transcription factor RAP2-12, N-terminally processed: The N-terminal cysteine residue of can be oxidized by PCO1 or PCO2, thus preparing the protein for N-end rule pathway-mediated proteasomal degradation
Most potently inhibited by zaprinast and dipyridamole
GTPase activity is stimulated by the presence of 50S ribosomal subunits. Hydrolysis is probably regulated by the HflX N-terminal domain
Phosphorylation at Thr-448 or Tyr-449 inactivates the enzyme, while phosphorylation at Thr-595 activates it
Activated by Ca(2+) (PubMed:18005666, PubMed:23506317, PubMed:28089596, PubMed:22529389). In response to calcium binding, the 280-loop, a disordered loop consisting of residues 269-275, undergoes a conformational change which stabilizes substrates in the active site (PubMed:22529389). The binding to the substrate triggers the release of the N-terminal region resulting in the activation of the enzyme (PubMed:22529389). Proteolytic cleavage is required for catalytic activity towards large protein substrates (PubMed:28089596)
Strongly inhibited by reserpine, ketanserin and methamphetamine. Also inhibited weakly by tetrabenazine
Strongly inhibited by TIMP-2, TIMP-3 and TIMP-4, while TIMP-1 is less efficient
Inhibited by CCCP but unaffected by sodium depletion
Inhibited by excess of xanthin, uric acid and ascorbic acid, and by 100 um N,N-dicyclohexylcarbodiimide and 30 um carbonyl cyanide m-chlorophenyl-hydrazone
May be inhibited by csk-1-mediated phosphorylation at Tyr-500
Channel activation is inhibited by binding to phosphatidylinositol-4,5-bisphosphate, and to a much lesser degree by phosphatidylinositol-3,4,5-trisphosphate. Not inhibited by phosphatidylinositol-3,4-bisphosphate and phosphatidylinositol-3,5-bisphosphate
BIRC2/c-IAP1 stimulates its transcriptional activity
Inhibited by the proton gradient disruptor carbonyl cyanide m-chlorophenylhydrazone (CCCP), but not by the sodium gradient disruptor ouabain. Hypoxanthine, xanthine, cytosine and uric acid act as competitive inhibitors
Maintained in an autoinhibited state via homodimerization in which the CARD domain forms an extensive interaction with the adjacent linker and coiled-coil regions (By similarity). Activation downstream of C-type lectin receptors, by phosphorylation by PRKCD and/or ubiquitination by TRIM62, triggers disruption of the CARD domain-coiled coil interface, CARD9 homooligomerization and BCL10 recruitment, followed by activation of NF-kappa-B and MAP kinase p38 pathways (PubMed:22265677). Zinc-binding inhibits activation by stabilizing the CARD ground-state conformation and restricting its capacity to form BCL10-nucleating filaments (By similarity)
Interaction with PEX3 inhibits the translocase activity by preventing unfolding of target proteins
Acetyltransferase activity increases in presence of the kinase substrate, sphingosine (By similarity). In Purkinje cells, kinase activity on sphingosine increases in presence of VEGFA (PubMed:25417698). In neurons, kinase activity increases during the first 24h in presence of Amyloid-beta protein 42 to decrease after 96h (By similarity)
Strongly inhibited by orthovanadate and EDTA. Also inhibited by inorganic phosphate
Okadaic acid, an inhibitor of protein phosphatase 1 (PP1), protein phosphatase 2A (PP2A) and protein phosphatase 5 (PP5), increases AURKC activity. AURKC is also stabilized through its interaction with INCENP, which acts also as an activator (By similarity)
Inhibited by n-undecyl phosphonate (C11Y4) (PubMed:25219509). Inhibited by paraoxon (PubMed:8286366, PubMed:25219509)
Activated by autocatalytic cleavage (PubMed:23682772). Inhibited by serine-borate (PubMed:21447318)
Is competitively inhibited by anthranilate when using benzoate as substrate
AMP and XMP inhibit AICAR formyltransferase activity (By similarity). AICAR formyltransferase activity is inhibited by N-(6-fluoro-1-oxo-1,2-dihydroisoquinolin-7-yl)-5- [(3R)-3-hydroxypyrrolidin-1-yl]thiophene-2-sulfonamide (LSN 3213128), which acts as a tumor suppression in cancer cell lines (PubMed:29072452)
Inhibited by Mn(2+) and Zn(2+)
Activated upon caspase cleavage to generate the XK-related protein 8, processed form (By similarity). Does not act prior the onset of apoptosis (By similarity)
Lipase activity is inhibited by phenylmethylsulfonyl fluoride (PMSF), but not neostigmine bromide (NB)
Phosphatidylinositol 4,5-bisphosphate (PIP2) is able to partially restore sensitivity to Ca(2+) after desensitization. Inhibited by flufenamic acid with an IC(50) of 24.5 uM and spermine with an IC(50) of 37 uM
Is not feedback inhibited by lysine
Classical (or conventional) PKCs (PRKCA, PRKCB and PRKCG) are activated by calcium and diacylglycerol (DAG) in the presence of phosphatidylserine. Three specific sites; Thr-499 (activation loop of the kinase domain), Thr-640 (turn motif) and Thr-659 (hydrophobic region), need to be phosphorylated for its full activation
Phosphorylation at Thr-14 or Tyr-15 inactivates the enzyme
The inhibitor activity of SEC14 is controlled by whether PI or PC is bound to SEC14. The pPC-bound form of SEC14 is an inhibitor, while the PI-bound form is not. The phospholipid binding/exchange activity of SEC14 represents a mechanism by which the regulatory activity of SEC14 is itself controlled
Activated by anticancer drug 5,6-dimethylxanthenone 4-acetic acid (DMXAA) (PubMed:23910378, PubMed:26669264). Specifically inhibited by nitrofuran derivatives C-178 and C-176, which covalently bind Cys-91 and prevent palmitoylation and subsequent activation od STING1 (PubMed:29973723)
Activated by threonine and tyrosine phosphorylation. Inhibited by dual specificity phosphatases, such as DUSP1 (By similarity). Phosphorylation and activation in response to DNA damaging agents, serum stimulation. Constitutively activated when phosphorylated on Tyr-178. Activity depends on the relative rates of MAPK15 autophosphorylation and dephosphorylation by PTPN1 (By similarity)
Activated by DAG and phorbol esters. Phorbol-ester/DAG-type domain 1 binds phorbol ester with high affinity and mediates accumulation at the cell periphery. Phorbol-ester/DAG-type domain 2 binds phorbol ester with low affinity but may mediate initial contact, resulting in a conformational change allowing previously occluded domain 1 to anchor the kinase. Phosphorylation on Thr-588 is then also required for activation and may also result in a further conformational change
Phosphatase activity is inhibited by the phosphatase regulator PhrA (PubMed:8643670, PubMed:9238025, PubMed:11923303, PubMed:22267516). Interaction with PhrA dissociates the RapA-Spo0F complex (PubMed:11923303). Activity is abolished in the presence of EDTA (PubMed:11923303)
Activated by cytokinins to initiate phosphorelay signaling
Is inhibited by Tenovin-6 in vitro, but not by nicotinamide
Activated by DAG and phorbol esters (PubMed:12058027, PubMed:17962809, PubMed:28428613). Phorbol-ester/DAG-type domains bind DAG, mediating translocation to membranes (PubMed:17962809). Autophosphorylation of Ser-710 and phosphorylation of Ser-706 by PKC relieves auto-inhibition by the PH domain (PubMed:17962809). Catalytic activity is further increased by phosphorylation at Tyr-717 in response to oxidative stress (PubMed:28428613)
4,4'-diisothiocyanatodihydrostilbene-2,2'- disulfonic acid (H2DIDS) potently inhibits chloride/hydrogencarbonate antiporter activity with 50% inhibition at about 5 uM (PubMed:12225984). Completely inhibits chloride/hydrogencarbonate antiporter activity at 200 uM of 4,4'-diisothiocyano-trans-stilbene-2,2'-disulfonic acid (DIDS) (PubMed:12225984)
DBT degradation completely inhibited by Cu(2+), Mn(2+), p-chloromercuribenzoic acid, 2,2-bipyridyl, 1,10-phenanthroline, and strongly inhibited by Zn(2+), 5,5'- Dithiobis(2-nitrobenzoic acid) and 8-quinolinol
Rubredoxin (Rd) increases the NADH consumption rate by serving as an intermediary electron-transfer shuttle between NROR and Rbr2
Competitively inhibited by tartronate
Uptake of cadaverine at neutral pH is greatly inhibited by carbonyl cyanide m-chlorophenylhydrazone (CCCP), which dissipates the proton motive force, valinomycin, which dissipates the membrane potential, and nigericin, which dissipates the transmembrane pH gradient (PubMed:14982633). Cadaverine uptake at neutral pH is also inhibited by putrescine and lysine (PubMed:14982633). Cadaverine-lysine antiporter activity is not inhibited by CCCP (PubMed:14982633)
Inhibited by sulfite and nitrate
Activity is inhibited by binding to OTUB1, which prevents 'Lys-63'-linked polyubiquitination (By similarity). Activity is inhibited by GPS2, leading to prevent 'Lys-63'-linked polyubiquitination (PubMed:22424771, PubMed:28039360, PubMed:28123943, PubMed:29499132)
Activated by Triton X-100, insensitive to inhibition by adenosine and inhibited by wortmannin. The PI4K complex acts as a regulator of phosphatidylinositol 4-phosphate (PtdIns(4)P) synthesis (By similarity). Interaction with TMEM150A regulates PtdIns(4)P synthesis (By similarity)
Inhibited by the protoberberine derivative HWY-289 in a non-competitive manner. Inhibited by miconazole. Not inhibited by CI-976, polyoxin D, amphotericin B or nikkomycin Z
Channel activity is regulated by phosphorylation (PubMed:16551655, PubMed:20881056, PubMed:26269590). Channel activity is regulated by intracellular Ca(2+) (PubMed:11854751)
Inhibited by ionic detergents such as Barlox-12, an amine oxide, and sodium dodecyl sulfate
Inhibited by benzamidine and partially inhibited by EDTA
RING domain dimerization is required for catalysis, TRIM25-mediated RIG-I ubiquitination, interferon induction, and antiviral activity
Phospholipid scramblase activity is activated upon caspase cleavage to generate the XK-related protein 4, processed form. Does not act prior the onset of apoptosis
Homodimerizes upon caspase cleavage. Phospholipid scramblase activity is activated following interaction with the processed C-terminus of XRCC4 (protein XRCC4, C-terminus)
Binding to the target genes is abolished by GlcN6P, a central molecule in N-acetylglucosamine metabolism
Undergoes a sequential loss of the oxygenase and pseudoperoxidase activities which is dependent on the structural characteristics of the substrate for the reaction, on oxygen concentration and on exposure to phospholipids and calcium (PubMed:8631361). 15-HETE and other 15-mono-hydroxyeicosanoids exhibit the highest inhibitory potencies in their capability of suppressing 5-lipoxygenation of arachidonic acid, whereas the other HETEs, (5S,15S)-dihydroxy-(6E,8Z,11Z,13E)-eicosatetraenoic acid (5,15-diHETE) as well as octadecanoids, are modest or poor inhibitors (PubMed:8615788). The formation of (5S)-hydroperoxy-(15S)-hydroxy-(6E,8Z,11Z,13E)-eicosatetraenoate is strongly stimulated by either hydroperoxypolyenoic fatty acids or arachidonic acid (PubMed:8615788). Arachidonate 5-lipoxygenase and leukotriene A4 synthase activities are allosterically increased by ATP (PubMed:24893149)
Requires calcium ions (PubMed:19014349). Inhibited by exogenous phosphatidylserine (PubMed:19014349)
Active in presence of diverse metals including Fe(2+), Zn(2+) and Mn(2+). Binds two metal cations in two adjacent alpha and beta metal-binding pockets
60% inhibition by 5 mM Ca(+), Mg(+) or Cu(+)
Specifically inhibited by camptothecin (CPT), a plant alkaloid with antitumor activity
Inhibited by copper, zinc and iron, p-Chloromercuri-benzoic acid (PCMBA) and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), but not by N-ethylmaleimide (NEM), dithioerythritol (DTE), calcium or magnesium
Strongly inhibited by Fe(2+), Fe(3+), K(3)[Fe(CN)(6)], Ag(+) and Cu(2+)
Activity is inhibited both by interaction with VMA13 and by V-ATPase acidification of the lumen. The activity of VMA13 is not required for YND1 inhibition
Activated through localization to mitochondria in specific growth phases
Substrate specificity and tendency to aggregate are influenced by archease
Inhibited by AUDA, a known epoxide hydrolase inhibitor
ATPase activity is stimulated by phosphatidylserine (PS) and minimally by phosphatidylethanolamine (PE) (PubMed:16618126, PubMed:20224745). ATPase activity is inhibited by the vanadate and by the presence of calcium (PubMed:20224745)
Strongly inhibited by methionine
Does not require any metal cations for activity
Activation of mTORC1 by growth factors such as insulin involves AKT1-mediated phosphorylation of TSC1-TSC2, which leads to the activation of the RHEB GTPase a potent activator of the protein kinase activity of mTORC1. Insulin-stimulated and amino acid-dependent phosphorylation at Ser-1261 promotes autophosphorylation and the activation of mTORC1. Activation by amino acids requires relocalization of the mTORC1 complex to lysosomes that is mediated by the Ragulator complex, SLC38A9, and the Rag GTPases RRAGA, RRAGB, RRAGC and RRAGD (PubMed:18497260, PubMed:20381137, PubMed:25561175, PubMed:25567906). On the other hand, low cellular energy levels can inhibit mTORC1 through activation of PRKAA1 while hypoxia inhibits mTORC1 through a REDD1-dependent mechanism which may also require PRKAA1. The kinase activity of MTOR within the mTORC1 complex is positively regulated by MLST8 and negatively regulated by DEPTOR and AKT1S1. MTOR phosphorylates RPTOR which in turn inhibits mTORC1. MTOR is the target of the immunosuppressive and anti-cancer drug rapamycin which acts in complex with FKBP1A/FKBP12, and specifically inhibits its kinase activity. mTORC2 is also activated by growth factors, but seems to be nutrient-insensitive. It may be regulated by RHEB but in an indirect manner through the PI3K signaling pathway
Inhibited by cellobiose and lactose, but not by glucose
Activated by magnesium or manganese. Inhibited by vanadate
Autophosphorylation activity enhanced by calcium/calmodulin
Inhibited by bee venom neurotoxin apamin (PubMed:8781233). Inhibited by d-tubocurarine and tetraethylammonium (TEA) (By similarity)
Inhibited by high substrate concentration and by products glucosamine 6-phosphate and acetate. Completely inactivated by the treatment with 5,5'-dithio-bis(2-nitrobenzoate) or 2,2'-dithio-pyridine (2-DPDS). Inhibited by 1,10-phenanthroline and EDTA
PMSF, soybean trypsin inhibitor (SBTI) and chymostatin strongly inhibit the proteinase
MI transport activity inhibited by D-chiro-inositol (DCI), phlorizin (Pz) and sodium (Na(+)) (By similarity). Insulin increases D-chiro-inositol uptake (PubMed:19032932)
Dephosphorylation by SIT4 activates NPR1 kinase activity
Inhibited by the cdc6-2 protein. The ATPase activity is not stimulated in the presence of DNA molecules
The cation channel is gated following an off-response property by acid: gated open after the removal of acid stimulus, but not during acid application (PubMed:23212381). Channel activity is inhibited by phosphatidylinositol-4,5-bisphosphate (PIP2) (PubMed:29425510)
Inhibited by thioisatinate
Bacterial uptake is inhibited by EDTA and by anti-E-cadherin antibodies
Estradiol 17-beta-dehydrogenase and dihydrotestosterone oxidoreductase activities are selectively inhibited by 4-methyl-4-aza-5alpha-androstane derivatives, such as 17beta-[(N-Heptyl)methylamino]-4-aza-5r-androstan-3-one and 17beta-(N-Decylformamido)-4-aza-5r-androstan-3-one
Its activity is synergistically stimulated by magnesium and dithiothreitol (DTT) in vitro
Activated by potassium and other monovalent cations at 0.25 M, but partially inhibited at greater concentrations (PubMed:3131312). Inhibited by validoxylamine A 6'-O-phosphate (PubMed:20077550)
Channel activity is regulated by the ancillary beta subunit SCN1B. SCN1B strongly enhances the presence of the pore-forming alpha subunit at the cell surface (By similarity). Interaction with SCN1B is required for rapid channel inactivation and rapid recovery after inactivation, and prevents decrease of channel activity in response to repetitive, high-frequency depolarizations. The channel is inhibited by tetrodotoxin (By similarity)
Slightly inhibited by N-acetyldopamine but not by N-acetylserotonin or melatonin
Transport activity is limited by threshold levels of luminal peptide (PubMed:25646430). ATP hydrolysis is reduced in the presence of the spatial challenging 18-mer peptide by 50% and the branched 16-mer peptide by 75% (PubMed:31417173). Transport rate of the longer peptides is strongly reduced (PubMed:31417173)
Inhibited by O-aryl carbamates and alpha-keto heterocytes
Has no constitutive proton transporter activity and has to be activated by long-chain fatty acids/LCFAs. Inhibited by purine nucleotides. Both purine nucleotides and LCFAs bind the cytosolic side of the transporter and directly compete to activate or inhibit it. Activated by noradrenaline and reactive oxygen species. Despite lacking canonical translational encoding for selenocysteine, a small pool of the protein has been observed to selectively incorporate selenocysteine at 'Cys-256'. Selenocysteine-modified protein is highly sensitive to redox modification and may constitute a pool of protein highly sensitive to activation by elevated levels of reactive oxygen species (ROS)
Inhibited by clorgyline (PubMed:22203607). Inhibited by RC21v3, a 4-methoxy-2,3,6-trimethylbenzenesulphonyl derivative of the D-octapeptide D-FFKWQRRR, via the interaction with the ectodomain (PubMed:22788839). FK506, enniatin, milbemycin alpha-11, and milbemycin beta-9 also inhibit CDR1 activity (PubMed:22788839). Inhibited by milbemycin A3/A4 oxim derivatives (PubMed:23208712, PubMed:24838041)
Negatively regulated by LabA, mainly during the dark
Is salt-dependent and is active over a wide range of NaCl concentrations. Activity is slightly promoted by Ni(2+), and inhibited by most of the tested metal ions, including Li(+), K(+), Ba(2+), Mg(2+), Zn(2+), Ca(2+), Mn(2+) and Al(3+)
Activated by Ca(2+)/calmodulin (PubMed:8898358). Binding of calmodulin may relieve intrasteric autoinhibition (Probable)
Contrary to HPrK/P of B.subtilis and other bacteria, that of M.pneumoniae is active as a kinase at very low ATP concentrations in the absence of fructose 1,6-bisphosphate (FBP). Kinase activity is slightly activated by FBP, and inhibited by inorganic phosphate (Pi), but FBP prevents kinase inhibition by Pi. Dephosphorylation of P-Ser-HPr by M.pneumoniae HPrK/P is strictly dependent on the presence of Pi, and is inhibited by FBP. This unique mode of control of HPrK/P activity is proposed to reflect the parasitic lifestyle of M.pneumoniae, that is strictly adapted to its ecological niche on nutrient-rich human mucous membranes
Inhibited by coumarins, sulfonamide derivatives such as acetazolamide (AZA), saccharin and Foscarnet (phosphonoformate trisodium salt)
Activated by calcium/calmodulin binding after calcium-induced autophosphorylation. Autophosphorylation is associated with a time-dependent loss of kinase activity sensitive to reaction pH and ATP concentration. In vitro inactivation leads to the formation of network-like structures
Strongly inhibited by diethyl paranitrophenyl phosphate, which is a specific inhibitor of serine hydrolases
Inhibited by abamine and abamineSG
Activity is greatly increased when AURKB is within the CPC complex (PubMed:12925766, PubMed:14722118, PubMed:15249581). In particular, AURKB-phosphorylated INCENP acts as an activator of AURKB (PubMed:14722118, PubMed:15249581). Positive feedback between HASPIN and AURKB contributes to CPC localization (PubMed:14722118, PubMed:15249581)
Activated by autophosphorylation at Tyr-1162, Tyr-1166 and Tyr-1167 on the kinase activation loop; phosphorylation at all three tyrosine residues is required for optimal kinase activity. Inhibited by MSC1609119A-1, BMS-754807, PQIP, benzimidazole pyridinone, isoquinolinedione, bis-azaindole, 3-cyanoquinoline, 2,4-bis-arylamino-1,3-pyrimidine, pyrrolopyrimidine, pyrrole-5-carboxaldehyde, picropodophyllin (PPP), tyrphostin derivatives. While most inhibitors bind to the ATP binding pocket, MSC1609119A-1 functions as allosteric inhibitor and binds close to the DFG motif and the activation loop (By similarity). Dephosphorylated by PTPN1 (By similarity)
Inhibited by arginine. Inhibition is relieved by binding to GLB1
Inhibited by INKA1; which inhibits the serine/threonine-protein kinase activity by binding PAK4 in a substrate-like manner
Inhibited by ammonium sulfate. Inhibited by pentaglutamate derivative of DDATHF, but isoform 2 is inhibited to a greater extent at lower concentrations of the compound that is isoform 5. Isoform 5 is virtually unaffected by H(4)PteGlu(5) and 5,10-CH(2)-H(4)PteGlu(5) at concentrations that substantially inhibits the activity of isoform 2. Isoform 2 and 5 are equally sensitive to polyglutamates of 10-CHO-H(4)-PteGlu
Inhibited by 2,4-dinitrophenyl-2-fluoro-2-deoxy-beta-D-glucopyranoside (PubMed:11784319). Inhibited by sodium taurocholate (PubMed:11389701). Inhibited by alpha-1-C-nonyl-DIX/AnDIX (PubMed:20728381). The glucosylceramidase activity is slightly inhibited by conduritol B epoxide/CBE while the galactosylceramidase activity is not (PubMed:17595169)
TAFI/CPB2 is unique among carboxypeptidases in that it spontaneously inactivates with a short half-life, a property that is crucial for its role in controlling blood clot lysis. The zymogen is stabilized by interactions with the activation peptide. Release of the activation peptide increases a dynamic flap mobility and in time this leads to conformational changes that disrupt the catalytic site and expose a cryptic thrombin-cleavage site present at Arg-324 (By similarity)
The cytoplasmic tail of TRAP and probably other adhesins acts as a competitive inhibitor as the binding sites of the glycolytic substrate fructose 1,6-bisphosphate and TRAP partially overlap (By similarity). Inhibited by suramin, an antiparasitic drug used to treat Trypanosome-mediated infection (PubMed:2204832)
The PCL7-PHO85 cyclin-CDK is inhibited by PHO81 in low-phosphate conditions
Activated by UDP-GlcNAc and inhibited by 2-acetamidoglucal and UDP. Activity is strongly decreased in the presence of Co(2+) and abolished in the presence of Mn(2+) or Zn(2+)
Enzymatic activity is dependent on membrane association and requires the presence of lipids
Inhibited by emetine, quinidine and verapamil. The IC(50) of emetine is 4.2 uM. Not inhibited by valproic acid (PubMed:10966938). Transport of (R)-carnitine is stimulated by cholesterol in the plasma membrane (PubMed:33334877)
The homodimer exhibits allosteric regulation by isocitrate
Transport is inhibited by the proton ionophore carbonyl cyanide m-chlorophenylhydrazone (CCCP)
Endonuclease activity inhibited by all NTPs, dNTPs, NDPs (at 0.5 mM, UDP not tested) and AMP-PNP; not inhibited by any tested NMP, dNMP or nucleoside. Inhibited by 100 mM NaCl, 100 mM KCl, 0.5 mM Co(2+) and 0.5 mM Ni(2+)
Mycophenolic acid (MPA) is a non-competitive inhibitor that prevents formation of the closed enzyme conformation by binding to the same site as the amobile flap. In contrast, mizoribine monophosphate (MZP) is a competitive inhibitor that induces the closed conformation. MPA is a potent inhibitor of mammalian IMPDHs but a poor inhibitor of the bacterial enzymes. MZP is a more potent inhibitor of bacterial IMPDH. Potently inhibited by MPA
Allosterically inhibited by tyrosine and phenylalanine. Activated by tryptophan
Inhibited by ATP via mitoK(ATP) channel
Inhibited by Zn(2+). Not inhibited by pyrrole-2-carboxylate nor its derivative 2-thiophenecarboxylate
Inhibited by sodium fluoride (NaF) in vitro, similarly to other class A type inorganic pyrophosphatases
Activated by inorganic phosphate (PubMed:4306285, PubMed:4324215). In addition to form a complex with ATP, Mg(2+) also acts as a cofactor (PubMed:4306285, PubMed:4324215). Strongly inhibited by ADP (or Mg-ADP) through competitive binding at the activation site and at a specific allosteric site (PubMed:4324215, PubMed:4346344, PubMed:6277896). Competitively inhibited by Ca(2+) (PubMed:4324215, PubMed:4346344)
Inhibited by high concentrations of substrate
Is inhibited by L- and D-cystine, and by other cystine derivatives, via the formation of a covalently bound cysteine at the active site Cys-135
Upon Mg(2+) depletion, MgtA is stabilized by interaction with MgtS
Inhibited by clotrimazole, econazole, ketoconazole, and miconazole
Exhibits substrate-dependent heparin activation. Drug-mediated inhibition leads to a delay of the oscillations with the magnitude of this effect dependent upon the timing of drug administration. Inhibited by phosphorylation (By similarity)
The redox state of the cysteines plays a crucial role in the regulation of NemR activity (PubMed:23506073, PubMed:23536188). Inactivated by reversible oxidation of cysteine residues in the presence of inducers such as quinones, glyoxals and reactive chlorine species (PubMed:23506073, PubMed:23536188). Also irreversibly inactivated by alkylation in the presence of N-ethylmaleimide (NEM) and other Cys modification reagents (PubMed:18567656). Inactivation by inducers decreases DNA-binding affinity and leads to the derepression of the nemRA-gloA operon (PubMed:18567656, PubMed:23506073, PubMed:23536188)
Regulation occurs at the protein level, via degradation of LpxC by the FtsH protease (PubMed:10048027, PubMed:16420369, PubMed:21193611, PubMed:23417489). Degradation is growth rate-dependent. LpxC is degraded rapidly during slow growth, probably to avoid toxic overproduction of lipopolysaccharides, but is highly stable under optimal growth conditions (PubMed:23417489). Increased amounts of LpxC are made under conditions that reduce the lipid A content of cells (PubMed:8824222). Inhibited by metal chelators such as EDTA and dipicolinic acid (DPA) and by high concentrations of Zn(2+) (PubMed:10026271)
Catalytically inactive when the propeptide is intact and associated with the mature enzyme (PubMed:11481247). The disintegrin and cysteine-rich regions modulate access of substrates to exerts an inhibitory effect on the cleavage of ADAM10 substrates (By similarity)
Activated more than 1.5 fold by Ca(2+), Mg(2+), Mn(2+), Ni(2+), Fe(2+), DDT and 1,10-phenanthroline. Strongly inhibited by Ag(+) and Hg(+). Inhibited by addition of 20% (v/v) glycerol. No effect by addition of NADH or NADPH
Esterase activity is down-regulated by salicylic acid (SA) or by tetraFA, a synthetic SA analog
Usually inhibited by pterin-based metabolites such as 6-formylpterin (6-FP, a product of folic acid photodegradation). 6-FP competitively inhibits MAIT cell activation by 5-OP-RU (PubMed:28166217). Modulated by commonly prescribed anti-inflammatory drug metabolites. Inhibited by salicilates such as 3-formylsalicylic and 5-formylsalicylic acids. Activated by diclofenac and/or its hydroxy metabolites (PubMed:28166217)
Activated by the thiol-reducing agents cysteine, 2-mercaptoethanol and dithiothreitol. Inhibited by iodacetamide, iodoacetic acid, leupeptin, tosyl-L-lysine and tosyl-L-phenylalanine. Not inhibited by elastatinal, chymostatin, cystatins, alpha1-antichymotrypsin or the serine protease inhibitors phenylmethylsulfonyl fluoride and diisopropylfluorophosphate. Not inhibited by metal ion chelators. Inhibited by the heavy metal ions Fe(3+), Zn(2+), Cu(2+) and Mn(2+)
Inhibited by D-erythro-MAPP
Assembly into ribonucleoprotein complexes of high-molecular-mass (HMM) inhibits its enzymatic activity. Antiviral activity is neutralized by the HIV-1 virion infectivity factor (Vif), that prevents its incorporation into progeny HIV-1 virions by both inhibiting its translation and/or by inducing its ubiquitination and subsequent degradation by the 26S proteasome. Can also be neutralized by simian immunodeficiency virus sooty mangabey monkey virus (SIV-sm) and chimpanzee immunodeficiency virus (SIV-cpz) Vif
Positively regulated by the regulatory subunit PAN3. Negatively regulated by PAB1-binding protein PBP1. Inhibited under stress conditions. Inhibition of deadenylation under stress increases mRNA stability, which may be a mechanism to retain the majority of the cytoplasmic pool of mRNAs for later reuse and recovery from stress
Potassium binding stabilizes the enzyme and increases its specific activity (PubMed:12682056, PubMed:16797027). Activity is also stimulated by sulfate (PubMed:16797027). Inhibited by arsenite (mixed inhibitor) (PubMed:11862551)
Oligomerization is required for catalytic activity and is metal-dependent (PubMed:33303633, PubMed:35691342). The type of metal that binds the 2 metal binding sites influences catalytic activity and substrate specificity (PubMed:17107951, PubMed:19408962, PubMed:33303633). In vitro, activated by Co(2+), Mn(2+), Ni(2+), Mg(2+) and Zn(2+) with decreasing strength (PubMed:17107951, PubMed:19408962, PubMed:33303633). Occupancy of the site 2 is essential and sufficient for activating the enzyme but occupation of the 2 sites is necessary for full catalytic activity (PubMed:19408962). Inhibited by fungal metabolite bestatin (PubMed:17107951, PubMed:19408962, PubMed:34133730). Inhibited by Phe-Naphthyl (PNAP) (PubMed:21844374)
Both 3,4-dihydroxy-2-heptylquinoline (PQS) and its precursor 4-hydroxy-2-heptylquinoline (HHQ) function as ligands and promote MvfR DNA-binding activity leading to transcriptional activation
Inhibited by the proteinaceous endoxylanase inhibitor I from T.aestivum (TAXI-I)
The repressive effect at the glaH promoter site is specifically relieved upon glutarate binding
Binds cyclosporin A (CsA). CsA mediates some of its effects via an inhibitory action on PPIase. PPIase activity is optimal in reduced form and minimal in oxidized form. Reduction of the oxidized form is mediated by thioredoxin (TRX-M)
Potently inhibited by benzbromarone, 3',3'',5',5''-tetrabromophenolphthalein (TBPP) and o-cresolphthalein
Inhibited by PMSF and Pefabloc
Glucose-1,6-bisphosphate enhances phosphorylation of the active site Ser-117, and thereby increases enzyme activity
Kinase activity is rapidly and transiently increased in response to chemoattractant stimulation
Inhibited by pyrrole-2-carboxylic acid (PYC)
Is inhibited by diphenylamine (DPA). Is also slightly inhibited by NAD, NADP or ATP in the presence of FAD
Inhibited by AMP and ATP
Inhibited by KCN and H(2)O(2)
In resting state, adopts an open conformation, anion-binding promoting the inactive configuration (PubMed:27434672). Upon aromatic amino acid-binding, the groove in the extracellular venus flytrap module is closed, thereby inducing the formation of a novel homodimer interface between subunits (PubMed:27434672, PubMed:27386547). Calcium ions stabilize the active state by enhancing homodimer interactions between membrane-proximal domains to fully activate the receptor (PubMed:27434672, PubMed:27386547). Activated by AMG 416, a D-amino acid-containing peptide agonist that is being evaluated for the treatment of secondary hyperparathyroidism in chronic kidney disease patients receiving hemodialysis (PubMed:26290606). AMG 416 agonist acts by forming a disulfide bond with Cys-482 (PubMed:26290606)
Glutamate uptake is inhibited by L-cysteate and beta-hydroxyaspartate. Inhibited by the uncoupler carbonylcyanide m-chlorophenylhydrazone (CCCP)
Agmatine acts as a competitive inhibitor of the condensation reaction where the L-arginine and agmatine substrates compete for the same site
Inhibited by phenylglyoxal and 2,3-butanedione. NADP provides a partial protection against inhibition by phenylglyoxal. Increasing the methanol concentration in the assay causes inhibition of the enzyme
Activated by both the alpha and the beta-gamma G proteins following stimulation of G protein-coupled receptors (GPCRs). Activation by GPCRs is assisted by the regulatory subunits (PIK3R5 or PIK3R6) leading to the translocation from the cytosol to the plasma membrane and to kinase activation. When bound to PIK3R5 the PI3K activity of PIK3CG could be activated greater than 100-fold by the beta-gamma G proteins
Expression and activity are regulated by acid media by increasing the rate of trafficking to the apical membrane (PubMed:22088432). Inhibited by HOE694 and S3226 (PubMed:18209477)
Activated by the G protein alpha subunit. Activated by the G protein beta and gamma subunit complex. Activated by GNA13 and GNA12. Ethanol and phorbol 12,13-dibutanoate significantly potentiate adenylate cyclase activity generated in response to the activation of the prostanoid receptor by the agonist prostaglandin E1(1-) in a PKC-dependent manner (By similarity). Inhibited by lithium (By similarity)
Autophosphorylates on Ser residues
Inactivated by exposure to air within less than 15 minutes
Rubredoxin (Rd) increases the NADH consumption rate by serving as an intermediary electron-transfer shuttle between NROR and RubY
Severely inhibited by copper, and competitively inhibited by dithiothreitol (DTT). Zinc concentrations above 2.5 mM and cobalt or nickel concentrations above 1 mM are inhibitors
Acetyltransferase activity increases in presence of the kinase substrate, sphingosine (By similarity). In Purkinje cells, kinase activity on sphingosine increases in presence of VEGFA (By similarity). In neurons, kinase activity increases during the first 24h in presence of Amyloid-beta protein 42 to decrease after 96h (PubMed:26334640)
The ATP-dependent phosphatidylcholine transport is competitively inhibited by miltefosine
Activated by extracellular calcium and inhibited by extracellular protons
Inhibited by crotapotin
Exopolyphosphatase activity is inhibited by (p)ppGpp alarmones produced during the bacterial stringent response
Activated by ATP. Activated by sulfate ions (in vitro). Inhibited by phosphate ions
Inhibited by beryllium trifluoride
Completely inhibited by EDTA and partially inhibited by Zn(2+), Mg(2+) and Cu(2+)
Channel activity is inhibited by interaction with Ca(2+)-bound calmodulin. Interaction of a single pore-forming alpha subunit with a calmodulin chain is sufficient to promote channel closure (By similarity). Extracellular magnesium ion concentrations up to 4 mM modulate channel activity by slowing down current activation in a reversible fashion. Channel activity is not regulated by cyclic nucleotides (PubMed:9524140). Channel activity is inhibited by binding intracellular phosphatidylinositol-3,5-bisphosphate and phosphatidylinositol-4,5-bisphosphate (PIP2), but is not inhibited by phosphatidylinositol 4-phosphate (By similarity)
Both activities are inhibited by L-phenylalanine
Inhibited by L-cystine and L-cysteine, and to a lesser extent by D-cystine
Octameric ced-4 activates zymogen autoprocessing and enhances activity of processed ced-3 (PubMed:18776901, PubMed:19575016, PubMed:27723735, PubMed:24065769, PubMed:20434985). Zymogen autoactivation is inhibited by csp-3 (PubMed:18776901). csp-3 has no effect on active ced-3 (PubMed:18776901). Zymogen autoactivation is inhibited by csp-2 (PubMed:19575016). Inhibited by cysteine protease inhibitor iodoacetic acid (CH3COOI) (PubMed:8654923, PubMed:9857046, PubMed:18776901, PubMed:19575016, PubMed:27723735). Inhibited by benzyloxycarbonyl-DEVD-fluoro-methyl ketone (zDEVD-fmk) (PubMed:8654923, PubMed:9857046, PubMed:25432023). Inhibited by benzyloxycarbonyl-VAD-fluoro-methyl ketone (zVAD-fmk) (PubMed:17371877, PubMed:21909434). Not inhibited by N-[N-(L-3-transcarboxirane-2-carbonyl)-leucyl]-agmatine (E-64) or by the serine and cysteine protease inhibitor L-1-chloro-3-[4-to-osylamido]-7-amino-2-heptanone (TLCK) (PubMed:8654923, PubMed:9857046)
Activation of PanD processing occurs even at low CoA concentrations. In contrast, full inhibition of PanD catalytic activity only occurs at sufficiently high CoA concentrations
(Microbial infection) Antiviral activity is neutralized by the HIV-1 virion infectivity factor (Vif), that prevents its incorporation into progeny HIV-1 virions by both inhibiting its translation and/or by inducing its ubiquitination and subsequent degradation by the 26S proteasome
Selectively inhibited by AZD3965, that acts as a competitive inhibitor binding to the central channel in the outward open conformation
Methyltransferase activity is regulated by miRNAs via a sequence pairing mechanism (PubMed:25683224). Methyltransferase activity is inhibited by sumoylation (By similarity)
Inhibited by purine nucleotides and inorganic phosphate (in vitro)
Inactivated by deimination on Arg-132
Is insensitive to lysine-feedback inhibition. Shows ASA substrate inhibition
Repressor activity is regulated by binding of sugars to TrmB. Binding of maltose and trehalose results in derepression of the malE operon. Maltose is much more effective (50-100 uM) than trehalose (2.5 mM)
Alternates between an inactive form bound to GDP and an active form bound to GTP. Inactivated by TSC1-TSC2 via the GTPase activating protein (GAP) domain of TSC2 (By similarity)
Stabilized by calcium (PubMed:4197814). Inhibited by di-isopropyl phosphorofluoridate (DFP), phenylmethanesulfonylfluoride (PMSF), p-nitrophenyl-p'-guanidinobenzonate (p-NPGB), p-chloromercuribenzoate (PCMB), ethylenediaminetetraacetic acid (EDTA), urea and CI-13c (PubMed:4197814, PubMed:4197815, PubMed:7981662)
Uptake is stimulated by ammonium sulfate and abolished by 2,4-dinitrophenol (PubMed:8297211). Is affected both topologically and kinetically by phospholipid composition of the membrane (PubMed:15890647). In cells lacking phosphatidylethanolamine (PE), the N-terminal hairpin is inverted relative to the membrane and the rate of GABA transport is reduced by more than 99% (PubMed:15890647)
Ubiquitination catalyzed by SdeA is insensitive to the cysteine alkylation agent maleimide, suggesting that a cysteine conjugation of ubiquitin does not form during the reaction
Competitively Inhibited by GMP. Allosterically inhibited by AMP
Inhibited by ppGpp, also known as the alarmone
Inhibited by diisopropylfluorophosphate (DFP) and PMSF
Requires cobalamin (vitamin B12) for repressor activity. In the dark, binding of cobalamin to CarH induces its oligomerization, which enhances binding to the DNA and repressor activity. Light causes cobalamin photolysis and disruption of the cobalamin-CarH complex, which decreases interaction with DNA and allows transcription of the target genes
Inhibited by EDTA, excess zinc, and also significantly by batimastat in vitro. Is not inhibited by other metalloprotease inhibitors like phosphoramidon, captopril and galardine or those targeting other classes of proteases
DNA supercoiling inhibited by (fluoro)quinoline antibiotics such as sparfloxacin and levofloxacin, which usually act on GyrA (PubMed:15047530, PubMed:17015625). DNA supercoiling inhibited by the coumarin antibiotic novobiocin which acts on GyrB (PubMed:16876125). Quinolones lead to gyrase-mediated dsDNA cleavage while preventing reclosure (PubMed:15047530, PubMed:16876125, PubMed:23869946). DNA supercoiling activity inhibited by aminopyrazinamide and pyrrolamide derivatives, probably via effects on the GyrB subunit (PubMed:23268609, PubMed:24126580). DNA relaxation inhibited by ATP and its analogs (PubMed:16876125). DNA supercoiling, relaxation, decatenation and quinolone-promoted DNA cleavage are inhibited by MfpA (50% inhibition occurs at 2 uM), inhibition of gyrase activities is enhanced in a concentration-dependent manner by MfpA (PubMed:19060136)
Activated by manganese or magnesium ions (PubMed:9874775). In the presence of magnesium ions, the enzyme is activated by bicarbonate (PubMed:12609998). Calcium mildly increases the enzyme activity, also in the presence of magnesium ions
Allosterically activated by magnesium, and possibly also other divalent metal cations. Allosterically activated by ATP, ADP or GTP (By similarity). Competitively inhibited by malonate
Inhibited by phosphate ions and squalestatin
Activated by phosphorylation on Thr-221
Uptake of Hg(2+) is decreased by iodoacetamide and iodoacetate, and is completely inhibited by the thiol-modifying reagent N-ethylmaleimide (NEM)
Rab activation is generally mediated by a guanine exchange factor (GEF), while inactivation through hydrolysis of bound GTP is catalyzed by a GTPase activating protein (GAP). YPT1 is activated by the GEFs DSS4 and TRAPP complex, and inactivated by GAPs GYP1, GYP5 and GYP8
Inhibited by verapamil but not by carbonyl cyanide m-chlorophenylhydrazone (CCCP)
Inhibited by pepstatin and by diazoacetyl-D,L-norleucine methyl ester (DAN) in the presence of Cu(2+) ions
Inhibited by coumarins, saccharin, sulfonamide derivatives such as acetazolamide (AZA), benzenesulfonamide and derivatives (4-carboxyethylbenzene-sulfonamide, 4-carboxyethylbenzene-sulfonamide ethyl ester, 4-(acetyl-2-aminoethyl)benzene-sulfonamide, 4-aminoethylbenzene-sulfonamide) and Foscarnet (phosphonoformate trisodium salt)
Synthesized as an inactive zymogen to protect the intracellular components of the bacteria from proteolytic activity during protein production (By similarity). Once secreted into the extracellular milieu, cleaved into the active protease: maturation can be mediated in cis by autocatalytic cleavage, or in trans by mature SpeB or host proteases (PubMed:12621045). Protease activity is strongly inhibited by zinc and copper, which prevent its maturation into an active protease: inhibition by metal ions may be required to prevent proteolysis of streptococcal proteins (PubMed:24799625)
Addition of 1 mM MnCl(2), NiCl(2), CoCl(2), ZnCl(2), CuCl(2), or 0.1 mM HgCl(2) inhibits the enzyme activity to 0-6%. Activity is increased in vitro upon addition of CaCl(2), DTT (relative activity 147%), KCl (180%), or EDTA (180%), as well as after heating of the enzyme. Is not inhibited by acarbose, a potent alpha-amylase and alpha-glucosidase inhibitor; on the contrary, acarbose is degraded quantitatively by AglB, yielding glucose
Activity is increased by phosphorylation
Inactivated by oxidation of Cys-107 to a sulfenic acid
Inhibited by PMSF. The amidolytic activity is also inhibited by benzamidine derivatives
2-ketogluconate acts as a molecular effector and causes dissociation of the PtxS/PtxR complex
Activated upon binding to the hydrolysis-resistant 2'3'-cG(s)A(s)MP, an analog of cGAMP, in which phosphodiester linkages are replaced by phosphothioate linkages (PubMed:25344812). Specifically inhibited by small-molecule H-151 (N-(4-ethylphenyl)-N'-1H-indol-3-yl-urea), which covalently binds Cys-91 and prevents palmitoylation and subsequent activation of STING1 (PubMed:29973723, PubMed:35045565). In contrast to mouse protein, not activated by anticancer molecule 5,6-dimethylxanthenone 4-acetic acid (DMXAA) (PubMed:26669264, PubMed:23910378, PubMed:25199835). Inhibited by compound 18 ([(3S,4S)-2-(4-tert-butyl-3-chlorophenyl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-7-fluoro-1-oxo-1,2,3,4-tetrahydroisoquinolin-4-yl]acetate), a competitive inhibitor with slow dissociation kinetics and good oral bioavailability (PubMed:30655953)
Activity is regulated by pH (PubMed:7896730). Active at alkaline pH (PubMed:7896730). Amiloride strongly reduces affinity for Na(+), but does not change the Vmax (PubMed:7896730)
Activated by manganese or magnesium ions (PubMed:12609998, PubMed:24616449). In the presence of magnesium ions, the enzyme is activated by bicarbonate (PubMed:12609998, PubMed:15659711, PubMed:24567411). In the presence of manganese ions, the enzyme is inhibited by bicarbonate (PubMed:15659711). In the absence of magnesium and bicarbonate, the enzyme is weakly activated by calcium (PubMed:15659711). Calcium mildly increases the enzyme activity, also in the presence of magnesium ions (PubMed:15659711, PubMed:25040695)
Regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP, GTPase activating proteins (GAPs) which increase the GTP hydrolysis activity, and GDP dissociation inhibitors which inhibit the dissociation of the nucleotide from the GTPase (Probable). Inhibited by GAPs such as ARHGAP44 (PubMed:25498153)
Higher divalent cation concentrations lead to decrease in the turnover of riboflavin and the 5'-phosphotransferase activity, while the adenylyltransferase activity increases
During activation, the N-terminal prodomain is removed by cleavage (By similarity). Concomitantly, double cleavage gives rise to a large 18-kDa and a small 11-kDa subunit (By similarity). The two large and two small subunits then assemble to form the active CASP6 complex (By similarity). Intramolecular cleavage at Asp-191 is a prerequisite for CASP6 self-activation (By similarity)
Inhibited by fusidic acid and sordarin, which prevent the release of eEF2 from the ribosome after the translocation step (PubMed:9452424, PubMed:12692531, PubMed:14976550, PubMed:17082187). While fusidic acid acts on all eukaryotic eEF2, sordarin specifically binds and inhibits only selected fungal eEF2 (PubMed:9452424, PubMed:17082187)
Synergistically stimulated by magnesium and dithiothreitol (DTT) in vitro
Activated by 5 mM Ca(2+) and inhibited by 5 mM Zn(2+)
Efficiently inhibited by Cu(2+) ion, Zn(2+) ion and N-ethylmaleimide, while the addition of Mg(2+), Ca(2+) or Fe(3+) ions has minimal effect. Inhibited in a competitive manner by vanadate
Mature protein inhibited by dithiothreitol and Zn(2+) chelators such as 1,10-phenanthroline, EDTA and EGTA. Not inhibited by serine-protease inhibitors, N-ethylmaleimide or phosphoramidon (which inhibits elastase)
Activity is stimulated by zinc ions, potassium ions and DTT (PubMed:33892036). Activity is inhibited by manganese and chloride ions (PubMed:33892036)
Stimulated by the presence of a monovalent cation (PubMed:11948193). Highly unstable in exponential growth phase. This instability is due to the binding of SsrA/tmRNA and its associated protein SmpB to the C-terminal region of RNase R (PubMed:20688916). In contrast, RNase R becomes stabilized upon entry into stationary phase. The difference in stability between exponential and stationary phase is due to the acetylation of a single lysine residue (PubMed:21981926)
Autoinhibited by the N-terminal domain, containing the KxGQ motif, that completely occludes the typical substrate binding pocket. Nucleotide-binding relieves inhibition (PubMed:27499294)
Catalytic activity is inactivated under iron-limiting conditions
E3 ligase activity is robustly activated by 5-hydroxy-methylcytosine
Inhibited by copper
Regulated by autophosphorylation, can both activate or decrease activity (By similarity). Heme regulates its activity by enhancing the phosphorylation on Tyr-1007 and Tyr-1008 (PubMed:21036157)
Can function in vivo with either divalent iron or manganese occupying di- and trimetal sites. Dimetal is necessary and sufficient to catalyze conversion of c-di-GMP to pGpG, but conversion of pGpG to GMP requires an occupied trimetal site
Present in an inactive conformation in the absence of bound ligand. Binding of PDGFB and/or PDGFD leads to dimerization and activation by autophosphorylation on tyrosine residues. Inhibited by imatinib
The first ATP-binding region has low ATPase activity (PubMed:21454554). The second ATP-binding region is responsible for ATPase activity (PubMed:21454554). ATP binding to the first ATP-binding region induces intrinsic activity of the second ATP-binding region (PubMed:21454554). While ATP binding to the first ATP-binding region appears to prevent ATP hydrolysis by the second ATP-binding region, ADP-binding to first region promotes the coordinate and cooperative ATPase cycle of the second ATP-binding region (PubMed:21454554). ATP binding to the first ATP-binding region induces a conformational change, promoting the rotation of the first ATP-binding region relative to the second ATP-binding region in the hexamer (PubMed:24055316). Inhibited by N-ethylmaleimide (NEM) (PubMed:18782221)
Inhibited by iodoacetate, p-hydroxymercuric benzoate and copper ions
The antibiotic bicyclomycin inhibits ATPase activity but does not affect termination function
Inhibited by NADH and ATP. Pyruvate and PEP act as activators of the acetyl phosphate forming reaction while inhibiting the formation of acetyl-CoA
The side chain of Glu-255 determines which of the two opposing activities (AMPylase or de-AMPylase) will take place. In response to endoplasmic reticulum stress, mediates de-AMPylase activity (By similarity). Adenylyltransferase activity is inhibited by the inhibitory helix present at the N-terminus: Glu-255 binds ATP and competes with ATP-binding at Arg-394, thereby preventing adenylyltransferase activity (By similarity). In unstressed cells, disengagement of Glu-255 promotes adenylyltransferase activity (By similarity). Activation dissociates ATP-binding from Glu-255, allowing ordered binding of the entire ATP moiety with the alpha-phosphate in an orientation that is productive for accepting an incoming target hydroxyl side chain (By similarity)
Under certain stress conditions, activity is inhibited by the anti-adapter proteins IraP, IraD and IraM. IraP is involved in response to phosphate stavation, IraD in response to DNA damage and IraM in response to magnesium starvation. IraD and IraM interact with inactive RssB, blocking its ability to interact with RpoS. IraP may mimic RpoS in its interaction with RssB and directly competing with RpoS for binding to RssB
Inhibited at more than 90% by SL-11144, SL-11150 and SL-11158, at concentrations less than 1 uM
Lysophospholipase D activity is increased by magnesium and manganese and inhibited by calcium in a concentration dependent manner (PubMed:27637550). Loss of lysophospholipase D activity by addition of EDTA (By similarity)
Allosterically inhibited by NADPH and NADH. NADPH is the primary inhibitor during aerobic growth and NADH during anaerobic growth
During activation, the N-terminal disordered prodomain is removed by cleavage (PubMed:18667412). Concomitantly, double cleavage gives rise to a large Caspase-7 subunit p20 and a small Caspase-7 subunit p11 (PubMed:18667412). The two large and two small subunits then assemble to form the active CASP7 complex (PubMed:18667412). Can be cleaved and activated by different caspases, depending on the context (PubMed:18667412, PubMed:35705808). Cleaved and activated by initiator caspases (CASP8 and/or CASP9), leading to execution phase of apoptosis (By similarity). Cleavage and maturation by GZMB regulates granzyme-mediated programmed cell death (PubMed:35705808). Cleavage and maturation by CASP1 regulates pyroptosis (PubMed:18667412, PubMed:35705808). Inhibited by XIAP, which directly binds to the active site pocket and obstructs substrate entry (By similarity). Phosphorylation at Ser-30 and Ser-239 by PAK2 inhibits its activity (By similarity)
Mn(2+)-activated peptidase is inhibited by Mn(2+) at concentration above 1 mM and by increasing concnentrations of Co(2+). There is a competitive inhibitor effect between the substrates. Hydrolysis of Asp-Leu by Mn(2+)-activated DapE is inhibited by SDAP, and hydrolysis of SDAP by Co(2+)-activated DapE is inhibited by Asp-Ser
Inactivated by nitrosylation of the iron center in the dark and activated by photo-induced nitric oxide (NO) release. Inactivated by oxidation of Cys-115 to a sulfenic acid
Activated by autophosphorylation on the second tyrosine residue in the Tyr-X-Tyr motif in the activation loop
The presence of lignin presents a significant source of antioxidants, which probably increase the activity by trapping liberated oxidized fragments
Kinase activity is stimulated by UhpC
Channel opening is promoted by binding phosphatidylinositol-4,5-bisphosphate (PIP2)
The NADPH oxidase activity is calcium-dependent. Peroxidase activity is inhibited by aminobenzohydrazide
Inhibited by halofuginone
Inhibited by asymmetric aryl disulfides, triazolopyrimidine sulfonanilide compounds, isatin derivatives, and sulfonylurea and imidazolinone herbicides. Insensitive to feed-back inhibition by branched-chain amino acids
Inhibited by FK866. FK866 competes for the same binding site as nicotinamide, but due to its very low dissociation rate, it is essentially an irreversible inhibitor
Inhibited by tetrahydrobiopterin. Unlike its mammalian orthologs, pah-1 does not exhibit allosteric binding behavior for phenylalanine
Activity is pH-dependent. A proximal hydrogen bond between Asp-132 and the heme axial ligant His-170 is essential for heme degradation activity (PubMed:28481076). Heme-degradation reaction is inhibited by iron chelators (PubMed:28352909)
Inhibited by inhibitor protein (IP) which may be a form of sucrose synthase
Allosterically activated by ADP and other diphosphonucleosides (By similarity). Allosterically inhibited by phosphoenolpyruvate which induces the dissociation of the active tetramer into an inactive two-subunit forms
Enzyme activity is tightly regulated to prevent the accumulation of reactive oxygen species in the endoplasmic reticulum. Reversibly down-regulated by the formation of disulfide bonds between the active site Cys-99 and Cys-138, and between Cys-104 and Cys-109. Glutathione may be required to regulate its activity in the endoplasmic reticulum (By similarity)
No enhancing of inhibitory effects are observed with divalent metal ions. Slightly inhibited by hypoxanthine
Inhibited by flavonoids, including myricetin, quercetin, luteolin, isorhamnetin, rhamnetin, kaempferol, diosmetin and apigenin
Calcium-independent phospholipase (PubMed:10833412, PubMed:10744668). Inhibited by (E)-6-bromomethylene-3-1-naphthalenyl-2H-tetrahydropyran-2-one (BEL) (PubMed:10744668, PubMed:15908428, PubMed:18171998). The activity toward 1-hexadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine is stimulated by cardiolipin (PubMed:28442572)
Magnesium-independent phospholipid phosphatase (PubMed:17590538). Inhibited by N-ethylmaleimide (PubMed:17590538)
Regulated by chloride and fluoride, but not bromide (PubMed:11815627). Chloride increases angiotensin I and decreases angiotensin II cleavage (PubMed:19021774). Inhibited by MLN-4760, cFP_Leu, and EDTA (PubMed:15231706, PubMed:10924499), but not by the ACE inhibitors lisinopril, captopril and enalaprilat (PubMed:10969042, PubMed:10924499). Highly potent and selective in vitro ACE2 inhibitors were identified (PubMed:12358520)
The racemization activity of Lyr is completely inhibited by hydroxylamine
Inhibited by divalent copper and zinc ions, but not by nickel or cobalt (PubMed:10644685). Inhibited by its prosegment, but not smaller fragments (PubMed:10644685). Inhibited by 4-(2-aminoethyl)benzenesulfonyl fluoride (AEBSF), a serine protease inhibitor (PubMed:12782636)
The first ATP-binding region has low ATPase activity (By similarity). The second ATP-binding region is responsible for ATPase activity (By similarity). ATP binding to the first ATP-binding region induces intrinsic activity of the second ATP-binding region (PubMed:21454554). While ATP binding to the first ATP-binding region appears to prevent ATP hydrolysis by the second ATP-binding region, ADP-binding to first region promotes the coordinate and cooperative ATPase cycle of the second ATP-binding region (By similarity). ATP binding to the first ATP-binding region induces a conformational change, promoting the rotation of the first ATP-binding region relative to the second ATP-binding region in the hexamer (By similarity)
Stimulated by the activator protein Act wich requires the presence of magnesium ions. Inhibited by 1,10-phenanthroline
Phosphate inhibits both the depolymerization and severing activities
3'-5' exonuclease activity is activated by sodium and manganese (PubMed:16687656). 3'-5' exonuclease and 3'-phosphodiesterase activities are stimulated in presence of PCNA (PubMed:19443450)
Inhibited by EDTA and bestatin in vitro. Is insensitive to papain, antipain, chymostatin, leupeptin, pepstatin and aprotinin
Activated by magnesium ions and inhibited by manganese ions. Inhibited by dipyridamole, moderately sensitive to IBMX and inhibited by vinpocetine
Inhibited by S-adenosylhomocysteine and sinefungin
Inhibited by warfarin (coumadin) (PubMed:15879509). Warfarin locks VKORC1 in both redox states into the closed conformation (By similarity)
Inhibited by 1,4-benzodiazepine and naphthyridinone derivatives
Not inhibited by antipain, 4-amidinophenylmethanesulfonyl fluoride, aprotinin, chymostatin, 3,4-dichloroisocoumarin, diisopropyl fluorophosphate, E64, EDTA, EGTA, iodoacetamide, leupeptin, pepstatin, o-phenanthroline, N-ethylmaleimide, phosphoramidon or phenylmethylsulfonyl fluoride
Activated by autophosphorylation on the second tyrosine residue in the Tyr-X-Tyr motif in the activation loop. Inhibited by acridine analogs, purvalanol, and barely by harmine. Inhibited by leucettine and leucettine derivatives
Activated by binding to the regulatory factor DNMT3L
Inhibited by DTT
Activated by binding to the regulatory factor DNMT3L. Auto-methylation at Cys-710 in absence of DNA inactivates the DNA methyltransferase activity
Activated by the negatively charged lipids phosphatidylglycerol (PG), cardiolipin (CL), nonbilayer-prone 1,3-DAG, 1,2-dioleoylphosphatidylglycerol (DOPG) and 1,2-dioleoylphosphatidylserine (DOPS). Inhibited by 1,2-diacyl-3-O-(alpha-D-galactopyranosyl)-sn-glycerol, 1,2-diacyl-3-O-[6-O-acyl(alpha-D-glucopyranosyl)]-sn-glycerol and 1,2-diacyl-3-O-[alpha-D-glucopyranosyl-(1->2)-O-(6-O-acyl-alpha-D-glucopyranosyl)]-sn-glycerol
Enzyme activity is enhanced by dsDNA (double-stranded DNA) and ssDNA (single-stranded DNA)
The matrix-open state (m-state) is inhibited by the membrane-permeable bongkrekic acid (BKA) (By similarity). The cytoplasmic-open state (c-state) is inhibited by the membrane-impermeable toxic inhibitor carboxyatractyloside (CATR) (By similarity). Proton transporter activity is inhibited by ADP:ATP antiporter activity (By similarity)
Inhibited by mercury ions (PubMed:9405233). Fully active at pH 6.5 to 7.5. Activity decreases with decreasing pH. Inactive at pH 5.5 (PubMed:30423801, PubMed:30420639)
Activated by anionic phospholipids, specially cardiolipin and phosphatidylserine
Activated by the presence of DNA (PubMed:11948185). Stimulated by XRCC1 (PubMed:23316050)
Inhibited by ubiquitin aldehyde
Inhibited by protease inhibitors diisopropylfluorophosphate, leupeptin, antipain, benzamidine, phenylmethylsulfonyl fluoride and soybean trypsin inhibitor
Protease activity is inhibited by EDTA
Inhibited by the quinazolinone-based compound febrifugine from the Chinese plant Dichroa febrifuga which is used to treat malaria-associated fever (PubMed:25817387, PubMed:27798837). Also inhibited by febrifugine derivatives such as halofuginone (PubMed:25817387, PubMed:27798837)
Kinase activity is regulated by the GTPase activity of the ROC domain (Probable). GTP-bound LLRK2 kinase activity is stimulated by RAB29 (Probable). Inhibited by small molecule inhibitors MLi-2 and LRRK2-IN-1 (PubMed:26824392, PubMed:28720718)
Strong substrate inhibition (PubMed:19648114). Was thought to be due to mutually exclusive productive and non-productive modes of substrate binding in the active site (PubMed:19648114). Alternatively, SALR may undergo significant conformational changes during catalytic turnover (PubMed:21169353)
Regulated by feedback inhibition by CoA and its thioesters
Regulated predominantly by intracellular cAMP levels
Activated by oxaloacetate (OAA), 2-ketoglutarate, succinate and fumarate as homodimer and by OAA, 2-ketoglutarate, succinate, fumarate and coenzyme A (acetyl-CoA and CoA) as heterodimer NAD-MEH
The uptake of glucose is inhibited by cytochalasin B and Phe-amide core-scaffold inhibitors GLUT-i1 and GLUT-i2 (PubMed:27078104). These inhibitors bind in the central cavity of the inward-open state and overlap the glucose-binding site (PubMed:27078104). Glucose uptake is increased in response to phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment: TPA-induced glucose uptake requires phosphorylation at Ser-226 (PubMed:25982116)
Activity is inhibited by 1,2-epoxyhexane
Allosterically activated by fructose 1,6-bisphosphate (FBP). It binds two fructose 1,6-bisphosphate (FBP) molecules per tetramer
Atypical PKCs (PRKCI and PRKCZ) exhibit an elevated basal enzymatic activity (that may be due to the interaction with SMG1 or SQSTM1) and are not regulated by diacylglycerol, phosphatidylserine, phorbol esters or calcium ions. Two specific sites, Thr-409 (activation loop of the kinase domain) and Thr-559 (turn motif), need to be phosphorylated for its full activation. Phosphatidylinositol 3,4,5-trisphosphate might be a physiological activator (By similarity)
Inhibited by sulfide and to a lesser extent by nitrite
Activity of the AccA3/AccD6 complex is inhibited by interaction with the epsilon subunit AccE5 (PubMed:17114269). Inhibited by dimethyl itaconate, C75, the herbicide haloxyfop, cerulenin, and 1,2-cyclohexanedione (PubMed:17114269, PubMed:25092705)
Activated by forskolin (PubMed:2255909, PubMed:1633161, PubMed:24363043). After forskolin treatment, activity is further increased by calcium/calmodulin (PubMed:1633161). In the absence of forskolin, calcium/calmodulin has little effect on enzyme activity (PubMed:1633161)
Inhibited by EDTA. Slightly activated in the presence of Ca(2+)
The side chain of Glu-255 determines which of the two opposing activities (AMPylase or de-AMPylase) will take place. In response to endoplasmic reticulum stress, mediates de-AMPylase activity (By similarity). Adenylyltransferase activity is inhibited by the inhibitory helix present at the N-terminus: Glu-255 binds ATP and competes with ATP-binding at Arg-395, thereby preventing adenylyltransferase activity (By similarity). In unstressed cells, disengagement of Glu-255 promotes adenylyltransferase activity (By similarity). Activation dissociates ATP-binding from Glu-255, allowing ordered binding of the entire ATP moiety with the alpha-phosphate in an orientation that is productive for accepting an incoming target hydroxyl side chain (By similarity)
Inhibited by K3 herbicides such as alachlor, allidochlor, anilofos, cafenstrole, fentrazamide and flufenacet (PubMed:15277688). Strongly inhibited by metazachlor and mefluidide (PubMed:22284369)
Feedback inhibition by lysine and threonine, but he enzyme is moderately inhibited by lysine alone, and threonine alone has no effect
The phosphatase activity is completely inhibited by trisodium orthovanadate, a tyrosine phosphatase specific inhibitor
Strongly inhibited by potato carboxypeptidase inhibitor, and the chelating agents EDTA and 1,10-phenanthroline. Also inhibited by compounds with multiple carboxylic acid groups such as citrate and succinate, and to a lesser exent the amino acids aspartate and glutamate. Not significantly inhibited by benzylsuccinic acid
Inhibited by tetrodotoxin (PubMed:23077250). Weakly inhibited by saxitoxin (PubMed:23077250)
Inhibited by sodium oxalate
The ModE dimer binds two molecules of molybdate (MoO4(2-)) with a Kd of 0.8 uM, which results in major changes in the conformation of the DNA-binding domain and confers high-affinity DNA-binding to the transcription factor (PubMed:9210473, PubMed:9044285, PubMed:11259434, PubMed:12581638). Additionally molybdate binding moves the 2 Mop domains closer together, trapping the ligand between them (PubMed:12581638). Can also bind tungstate (PubMed:9210473, PubMed:11259434). Molybdate is bound at the dimer interface using residues from each monomer (PubMed:11259434, PubMed:12581638)
Is strongly and competitively inhibited by NO and hydroxylamine
Inhibited by EDTA and 1,10-phenanthroline (PubMed:8193588). Is also inhibited by endogenous tripeptide inhibitors pyroGlu-Asn-Trp, pyroGlu-Gln-Trp, and pyroGlu-Lys-Trp (PubMed:9703966, PubMed:12071970)
Requires a lipid activator for activity. Activation is observed with cardiolipin and a large number of phospholipids, sulfolipids, neutral lipids, fatty acids, alkylglycosides or detergents (PubMed:6277376, PubMed:6303781, PubMed:2984194, PubMed:3009449, PubMed:3021764, PubMed:2828054). A lipid cofactor-induced conformational change may occur as part of the activation process (PubMed:3021764). Requires a second divalent cation in addition to Mg(2+)-ATP (PubMed:3009449). Inhibited by the tetraphosphate-linked ATP-DAG bisubstrate analog (PubMed:9305868)
Activated by calcium. Upon calcium binding to the EF-hand domains, the C-terminus of the junction domain (J domain) undergoes a conformational change which results in the dissociation of the pseudo-substrate inhibitory motif from the catalytic domain. This, in turn, may facilitate the autophosphorylation of the activation loop at Thr-234, which leads to the kinase activation. Intracellular calcium increase is triggered by xanthurenic acid (XA), a small mosquito molecule that induces the differentiation of specialized transmission stages, the gametocytes, into male and female gametes. Activated by a decrease in temperature (20 degrees Celsius) and an increase in pH (7.6) occurring when the parasite is ingested by in the mosquito
Inhibited by N2-(p-n-butylphenyl) deoxyguanosine 5'-triphosphate and N2-(p-n-butylphenyl) deoxyadenosine 5'-triphosphate (PubMed:3129427). DNA synthesis is not inhibited by fungal toxin alpha-amaitin (PubMed:6806812). The 3'-5' exonuclease activity is inhibited by 10mM dGMP (PubMed:3129427)
Inhibited by 1,10-phenanthroline (OP)
Inhibited by ZPCK
Inhibited by L-kynurenine
Inhibited by rolipram and diazepam
Competitively inhibited by (2S,4S)-4-fluoroglutamate, 2-methyleneglutarate, (2R,3RS)-3-fluoroglutamate and (S)-3-methylitaconate
ATPase activity is inhibited by intracellular L-methionine (PubMed:18621668, PubMed:22095702, PubMed:25678706, PubMed:30352853). Binding of methionine to the dimerized C-terminal regulatory domain stabilizes an inward-facing, ATPase-inactive conformation of the transporter, and as a consequence, the rate of ATP hydrolysis decreases (PubMed:18621668, PubMed:22095702, PubMed:30352853). ADP is a competitive inhibitor (PubMed:25678706)
Highly active without 3'phosphoglycerate, and is only slightly affected by the activator 3'phosphoglycerate and inhibitor orthophosphate
Produced as a latent enzyme which is activated by double stranded RNA (dsRNA) generated during the course of viral infection (PubMed:29117179). The dsRNA activator must be at least 15 nucleotides long, and no modification of the 2'-hydroxyl group is tolerated (By similarity). ssRNA or dsDNA do not act as activators (By similarity). Strongly inhibited by copper, iron and zinc ions (By similarity). Partially inhibited by cobalt and nickel ions (By similarity)
Repressed by 20-hydroxyecdysone
Inhibited by 2-hydroxy-3-butynoic acid, but not by p-chloromercuribenzoate, n-ethylmaleimide, or 5,5'-dithiobis(2-nitrobenzoic acid)
Inhibited by thiazide-type diuretics including polythiazide, metolazone, cyclothiazide, hydrochlorothiazide and chlorthalidone
Binds a Ca(2+) ion, which has little effect on either the binding affinity or the secondary structure, but plays an important role in maintaining the stability of TmoX (PubMed:26283766). It may modulate the protein stability in response to biological needs and environmental changes (PubMed:26283766). Thermostability is dramatically decreased when Ca(2+) is removed by EDTA (PubMed:26283766)
Strongly inhibited by iodoacetic acid and CuCl(2). Completely inhibited by N-ethylmaleimide and HgCl(2)
In response to starvation, RelA is activated resulting in the accumulation of (p)ppGpp, which causes the degradation of PopD in an FtsH(D)-dependent manner, thereby releasing pre-formed PopC for secretion
Activated by catalase. Inhibited by chelating reagents such as EDTA and Tiron (4,5-dihydroxy-1,3-benzene disulphonic acid), and by DTNB (5,5'-dithio-bis-2-nitrobenzoate) and hydrogen peroxide
Binding to DNA induces dimerization, which is required for DNA helicase activity
Phosphorylated by MAP2K1/MEK1 and MAP2K2/MEK2 on Thr-203 and Tyr-205 in response to external stimuli like insulin or NGF. Both phosphorylations are required for activity. This phosphorylation causes dramatic conformational changes, which enable full activation and interaction of MAPK1/ERK2 with its substrates. Dephosphorylated and inactivated by DUSP3, DUSP6 and DUSP9
Enhanced activity by NaCl. Inhibited by UDP
Inhibited by 3-bromo substituents and Leu, the pathway end product
Deoxyglucose transport is inhibit by D-glucose, D-galactose and maltose (PubMed:8457197). Galactose transport is inhibited by D-glucose and maltose (PubMed:8457197)
The enzyme activity is strongly inhibited by Ag(+), Ni(+), Hg(+), and p-chloromercuribenzoate, and partially inhibited by Li(+), Ca(2+), Mn(2+), Co(2+), Cu(2+), and Zn(2+)
Strongly inhibited by Ag(+). The cations Ca(2+) and Mg(2+) do not significantly reduce the lipolytic activity of SCO7513, whereas high concentrations of Co(2+) and Cu(2+) partially inhibit it. Is not inhibited by DTT in vitro. Is resistant to PMSF inhibition, except in the presence of Ca(2+)
Completely inhibited by p-chloromercuribenzoate (PCMB) and heavy metal salts. Partially inhibited by proline and proline derivatives with proline as the amino terminus. Enzyme inactivated by PCMB is reactivated by incubation with 2-mercaptoethanol
Activity is stimulated by phosphatidylethanolamine and phosphatidylglycerol, but not by phosphatidylcholine and cardiolipin (PubMed:3512540). Proline uptake is inhibited by the sulfhydryl reagent N-ethylmaleimide (NEM) (PubMed:3053687, PubMed:1567896). Proline, in the presence of Na(+) or Li(+), protects the carrier functions from NEM-inactivation (PubMed:1567896)
Inhibited by thiol-reactive reagents
Lysophospholipase D activity is increased by magnesium and manganese and inhibited by calcium in a concentration dependent manner (By similarity). Loss of lysophospholipase D activity by addition of EDTA (By similarity)
Activity is enhanced by dithioerythritol, and is slightly inhibited by fructose 2,6-bisphosphate. AMP does not inhibit the enzyme activity
EsxB binding to the second FtsK domain of EccCb1 causes multimerization; a subsequent unknown step relieves the allosteric inhibition of linker 2 on FtsK domain 1 (in EccCa1 subunit), activating the ATPase activity (PubMed:25865481)
Activated through phosphorylation at Thr-68 by ATM in response to DNA double-strand breaks. Activation is modulated by several mediators including MDC1 and TP53BP1. Induces homodimerization with exchange of the T-loop/activation segment between protomers and transphosphorylation of the protomers. The autophosphorylated kinase dimer is fully active. Negatively regulated by PPM1D through dephosphorylation of Thr-68 (By similarity)
Requires Mg(2+) and a monovalent cation, with NH(4) preferred over K(+) (PubMed:6130093). KCl, NaCl and NaF salts inhibit the exopolyphosphatase activity (PubMed:8394006)
Inhibited by pyridoxal 5-phosphate but not mersalyl
Inhibited by L-leucine hydroxamate and phosphoramidon. Not inhibited by phenylmethanesulfonyl fluoride. Reversibly inactivated by straight-chain aliphatic alcohols
Inhibited by cystatin-C
Is inhibited by AP3 (DL-2-amino-3-phosphonopropionate) and, to a lesser extent, by L-aspartate or AP4 (DL-2-amino-4-phosphonobutyrate). Is also inhibited by EDTA in vitro
Strongly inhibited by 1 mM Zn(2+), Cu(2+), Mn(2+) and Co(2+) ions. Also inhibited by 5,5'-dithiobis(2-nitrobenzoic acid) (Ellman reagent) in vitro
Phosphoenolpyruvate carboxykinase activity is regulated by acetylation and glucose levels (PubMed:20167786, PubMed:30193097). The anaplerotic conversion of phosphoenolpyruvate to oxaloacetate is improved by PCK1 acetylation on Lys-91 (K91ac), Lys-473 (K473ac) and Lys-521 (K521ac) (By similarity). High glucose concentrations favor PCK1 anaplerotic activity by triggering acetylation on Lys-91 (K91ac). At low glucose levels, SIRT1-mediated deacetylation of Lys-91 promotes the cataplerotic conversion of oxaloacetate to phosphoenolpyruvate (PubMed:30193097). Phosphorylation at Ser-90 reduces the binding affinity to oxaloacetate and converts the enzyme into an atypical protein kinase using GTP as donor (PubMed:32322062)
Activated by cleavage by B.anthracis lethal toxin (LT) endopeptidase (PubMed:16429160, PubMed:24935976). Cleavage by LT promotes ubiquitination and degradation of the N-terminal part, releasing the cleaved C-terminal part of the protein (NACHT, LRR and PYD domains-containing protein 1b, C-terminus), which polymerizes and forms the Nlrp1b inflammasome (By similarity). Nlrp1b inflammasome is inhibited by DPP8 and DPP9, which sequester the C-terminal fragment of Nlrp1b (NACHT, LRR and PYD domains-containing protein 1b, C-terminus) in a ternary complex, thereby preventing Nlrp1b oligomerization and activation (By similarity). Nlrp1b inflammasome is activated by Val-boroPro (Talabostat, PT-100), an inhibitor of dipeptidyl peptidases DPP8 and DPP9 (PubMed:31383852). Val-boroPro relieves inhibition of DPP8 and/or DPP9 by promoting disruption of the ternary complex, releasing its C-terminal part from autoinhibition (By similarity). Activated by metabolic inhibitors, such as 2-deoxy-D-glucose and sodium azide (PubMed:24935976). Not activated by muramyl dipeptide, nor by full-length bacterial peptidoglycan (PubMed:24935976)
Its catalytic activity is inhibited by the inhibitor CCT241950. In the presence of this inhibitor, displays an autoinhibited conformation: Tyr-70 side chain points into the active site, interacts with the activation loop, and blocks the alphaC helix
Activated through serine and threonine phosphorylation by MEKK1 and MAPKKK20 in response to abscisic acid (ABA). Inhibited through phosphorylation by GSK3/Shaggy-like kinase ASKs. Inhibited through ADP-Ribosylation by P.syringae HopF2. Activated after high light stress
The disulfide bridge formed between Cys-39 in the propeptide and the active site residue Cys-96 may prevent activation of the zymogen through formation of a reversible covalent bond with the active site residue
Calcium plays an important structural role, providing stability to this protein in the cytoplasm. Outside the cell, the decrease of the calcium concentration triggers the autoproteolysis
Strongly inhibited by diisopropyl fluorophosphate, leupeptin, antipain, aprotinin, and soybean trypsin inhibitor, but hardly inhibited by secretory leukocyte protease inhibitor at 10 microM
Activity is increased by oligomerization of the protein into filaments that correspond to the most active form of the carboxylase. The oligomerization and the activity of the enzyme are inhibited by phosphorylation at Ser-212 (PubMed:24913514). Inhibited by its own product malonyl-CoA. Activation by MID1IP1 is citrate dependent
Subject to autoinhibition, mediated by interactions between the FERM domain and the kinase domain. Activated by autophosphorylation at Tyr-397. This promotes interaction with SRC and phosphorylation at Tyr-576 and Tyr-577 in the kinase activation loop by SRC. Phosphorylation at Tyr-397, Tyr-576 and Tyr-577 is required for maximal kinase activity
Present in an inactive conformation in the absence of bound ligand. Ligand binding leads to dimerization and activation by sequential autophosphorylation on tyrosine residues. Inhibited by ARQ 069; this compound maintains the kinase in an inactive conformation and inhibits autophosphorylation. Inhibited by PD173074
Inhibited by hydroxamates, mimicking the putative enediol reaction intermediate. Most potent inhibition, with an IC(50) of 0.7 uM, is obtained with the 4 carbon-based hydroxamate containing acetyl moieties
Regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP, GTPase activating proteins (GAPs) which increase the GTP hydrolysis activity and GDP dissociation inhibitors which inhibit the dissociation of the nucleotide from the GTPase. Activated by GEFs such as ARHGEF2, ARHGEF3, ARHGEF28 and BCR (PubMed:23940119, PubMed:12221096). Inhibited by GAPs such as ARHGAP30 (PubMed:21565175). Inhibited by GDP dissociation inhibitors such as ARHGDIA (PubMed:20400958)
Rab activation is generally mediated by a guanine exchange factor (GEF), while inactivation through hydrolysis of bound GTP is catalyzed by a GTPase activating protein (GAP) (Probable). That Rab is activated by the DENND4C and RABIF guanine exchange factors (GEF) (PubMed:20937701, PubMed:31540829)
Inhibited by the not secondly cleaved propeptide (PubMed:9130696, PubMed:11799113). Inhibited by m-guanidinomethyl-phenylacetyl-Arg-Val-Arg-(amidomethyl)-benzamidine (m-guanidinomethyl-Phac-RVR-Amb) and 4-guanidinomethyl-phenylacetyl-Arg-Tle-Arg-4-amidinobenzylamide (MI-1148) (PubMed:24666235, PubMed:25974265). Inhibited by Decanoyl-Arg-Val-Lys-Arg-chloromethylketone (decanoyl-RVKR-CMK) (PubMed:32362314). Inhibited by heparin/heparan sulfate-binding (PubMed:2408021)
Not stimulated by calcium/calmodulin. Aspirin inhibits expression and function of this enzyme and effects may be exerted at the level of translational/post-translational modification and directly on the catalytic activity
Inhibited by NaCl
Enzymatic activity and neurotoxicity are inhibited by Triton X-100, which has been determined to be located in the center of the hydrophobic channel of the enzyme
Thymine cleavage is completely inhibited by Ni(2+), Co(2+), Zn(2+), Cu(2+) and Mn(2+). Activity is not affected by Mg(2+) and Ca(2+)
Inhibited by sulfonamides and sulfamates
Inhibited by Zn(2+), (2,3,4)-trihydroxybenzoate and (3,4,5)-trihydroxybenzoate (PubMed:7744052). Ammonium and rubidium ions decrease the activity of the carboxylation of 3,4-dihydroxybenzoate by about 20% (PubMed:7744052)
Negatively regulated by acyl-ACP, possibly by binding to either the free enzyme or the acyl-enzyme intermediate (PubMed:8631920). Inhibited by the SB418011 antibiotic (PubMed:11375394). Not inhibited by cerulenin, and weakly inhibited by thiolactomycin (PubMed:11375394)
Activated by cobalt and manganese. Strongly inhibited by the presence of a 3'-CCA sequence or a 3'-phosphoryl group
Specifically inhibited by XAV939, a small molecule, leading to inhibit the Wnt signaling pathway by stabilizing AXIN1 and AXIN2 (PubMed:19759537). Inhibited by talazoparib (PubMed:33361107)
Inhibited by L-1-tosylamido-2-phenylethyl chloromethyl ketone (TPCK) and N-ethylmaleimide, but not by EDTA
The phosphatase and kinase activities are regulated by the nitrogen regulatory proteins P-II 1 (GlnB) and P-II 2 (GlnK) (PubMed:2874557, PubMed:2574599, PubMed:10074086, PubMed:10231487). GlnB acts by binding to NtrB, leading to activation of the phosphatase activity and inhibition of the kinase activity. Binding of GlnB to NtrB is allosterically controlled by the small-molecule effector 2-ketoglutarate. At low 2-ketoglutarate concentrations, GlnB interacts with NtrB, but not at high 2-ketoglutarate concentrations (PubMed:10074086). Uridylylation of GlnB also prevents interaction with NtrB (PubMed:7961766)
Inhibited by the microbial peptide pepstatin A
Allosterically regulated by polyamines (PubMed:25623305, PubMed:26410587). Polyamines trigger conformational changes and induce the symmetric closed dodecameric state of the protein when they bind to their allosteric sites (PubMed:26410587)
ATPase activity is stimulated by phosphatidylserine (PS) and minimally by phosphatidylethanolamine (PE). ATPase activity is inhibited by N-ethylmaleimide (NEM) and vanadate. Flippase activity is inhibited by NEM and 1,2-dioleoyl-sn-glycero-3-phospho-L-serine (DOPS)
Activated by phosphorylation on Thr-211. Inhibited by phosphorylation on Thr-564
The ATPase activity of RuvB is enhanced by RuvA
Inhibited by Mn(2+), Cd(2+), Zn(2+), Cu(2+) and Be(2+)
Enzymatic activity is inhibited by EDTA in vitro
The carbonate dehydratase activity is not substantially changed by the addition of Zn(2+)
The 2:2 CdnC:Cap7 (Cap7 is also called HORMA) complex is activated for cAAA synthesis by long dsDNA, but not 40 bp dsDNA or ssDNA; the 1:1 complex is inactive in vitro. The 2:2:DNA complex is catalytically disassembled and inactivated by Cap6 (also called Trip13)
In contrast to bacterial and eukaryotic HMG-CoA synthases, is insensitive to feedback substrate inhibition by acetoacetyl-CoA. Enzymatic activity is inhibited by hymeglusin, which also blocks the propagation of H.volcanii cells in vivo, indicating the critical role that the mevalonate pathway plays in isoprenoid biosynthesis by these archaea
Is insensitive to feedback inhibition by (S)-lysine
Subject to allosteric regulation. Activated by ADP (PubMed:11903050). Inhibited by GTP and ATP (PubMed:11254391, PubMed:11032875, PubMed:9571255, PubMed:11903050, PubMed:11297618). ADP can occupy the NADH binding site and activate the enzyme (PubMed:16023112). Inhibited by SIRT4 (PubMed:16959573). Inhibited by HADH (By similarity)
Potently inhibited by L-vesamicol
Activation may be calcium-dependent (PubMed:16322767). Inhibited by the non-covalent interaction with the cleaved propeptide (PubMed:16322767)
Inactivated by reductive stress
Inhibited by phosphate and molybdate
Formation of the FtsZ ring is inhibited by SulA, MinCD, DicB and toxins CbtA and CptA. Inhibition by toxin CbtA, SulA or DicB overexpression is neutralized by cytoskeleton bundling-enhancing protein CbeA, while inhibition by toxin CptA is neutralized by antitoxin CptB (PubMed:21166897, PubMed:22239607, PubMed:22515815, PubMed:8752322). Either FtsA or ZipA is required for Z ring formation and stabilization (PubMed:11847116)
EDTA and DTT reversibly abolish carboxypeptidase activity
Mycophenolic acid (MPA) is a non-competitive inhibitor that prevents formation of the closed enzyme conformation by binding to the same site as the amobile flap. In contrast, mizoribine monophosphate (MZP) is a competitive inhibitor that induces the closed conformation. MPA is a potent inhibitor of mammalian IMPDHs but a poor inhibitor of the bacterial enzymes. MZP is a more potent inhibitor of bacterial IMPDH. Resistant to mycophenolic acid (MPA) inhibition (PubMed:15269207)
Gamma-aminobutyric acid (GABA) transport is inhibited by beta-alanine, taurine, hypotaurine, beta-guanidinopropionic acid, 2,3-diaminopropionic acid, guvacine and nipecotic acid (PubMed:8420981, PubMed:22896705). Beta-alanine transport is inhibited by GABA (PubMed:8420981). Taurine transport is inhibited by GABA, beta-alanine, SNAP-5114, nigericin, nipecotic acid and ouabain (PubMed:22896705)
Competitively inhibited by oxalate. Also inhibited by high concentrations of Cd(2+) (1 mM) in vitro. Appears to be allosterically activated by aldehyde turnover occurring in BphJ, partly via NADH
Activity enhanced by Mg(2+) ion but inhibited by Ca(2+), Zn(2+) and Be(2+) ions. Inorganic phosphate and ATP are competitive inhibitors, whereas pyrophosphate and AMP have no effect
Activity may be controlled by xylonate
Active in presence of Mn(2+), Mg(2+) and Zn(2+), but is not functional with Ca(2+) or Cu(2+) (PubMed:11883897). Has a higher affinity for Mn(2+) than for Mg(2+) (PubMed:11883897). RAN inhibits its autophosphorylation and its ability to phosphorylate histone H3 (PubMed:18617507)
Inhibited by the thiol inhibitors p-chloromercuribenzoate, N-ethylmaleimide and iodoacetamide. Also inhibited by various divalent cations
Inhibited by the product iminoaspartate (PubMed:8706749). Competitively inhibited by mesotartrate (PubMed:2187483). NAD acts as a competitive inhibitor to FAD (PubMed:7033218, PubMed:2187483). Inhibited by iodoacetic acid, diethylpyrocarbonate and tetranitromethane (PubMed:2187483)
Inhibited by 1 mM NaN(3), 10 mM thiourea, 10 mM 1,10-phenanthroline, 0.1 mM DL-dithiothreitol (DTT) and 1 mM L-cysteine. The inhibition by DTT and L-cysteine is likely caused by reduction of the oxidized substrate and not by inhibition of the enzyme
Inhibited by Zn(2+) chelator 1,10-phenanthroline
Zinc, and cobalt and nickel at a lesser extent, are able to increase the catalytic activity (2.2-, 1.3- and 1.1-fold respectively) at concentrations of 1 mM. Higher concentrations have an inhibitory effect. Magnesium, manganese and calcium have no effect on activity at concentrations between 0 and 10 mM. At 100 mM, the catalytic activity is increased between 1.2- and 2.1-fold. Hydroxamates like TSA and SAHA inhibit the enzyme (PubMed:15060035). Is also inhibited by azobenzenes, stilbenes and arylazopyrazoles (PubMed:27756124)
Less sensitive to zinc ions as compared to the mammalian homologs
Competitively inhibited by phosphomycin and inorganic orthophosphate
Subject to competitive inhibition by the reaction product proline. Subject to competitive inhibition by stearoyl coenzyme A
Inhibited by K3 herbicides such as allidochlor, cafenstrole and flufenacet (PubMed:15277688). Strongly inhibited by metazachlor and only slightly by mefluidide (PubMed:22284369)
Inhibited by the action of reducing agents such as dithiothreitol and 2-mercaptoethanol
Allosterically regulated by its own products; pppGpp simulates synthesis 10-fold more than ppGpp. 2 pppGpp molecules bind in a regulatory cleft in the middle of the tetramer in an asymmetric manner. There is a specific contact of Lys-25 to the gamma-phosphate of pppGpp, explaining why pppGpp stimulates activity but ppGpp does not (PubMed:26460002)
The enzyme is active only in the presence of branched-chain amino acids. Valine results in much higher activation than leucine or isoleucine
Activated by threonine and tyrosine phosphorylation, potentially by the dual-specificity kinase, MKK7. Indirectly activated by Wnt5a
Competitively inhibited by the bisubstrate analog Ap5A, by 7-deazaadenosine 5'-monophosphate (TuMP) and 8-bromo-AMP
The presence of K(+) or NH4(+) is essential for activity
Autoinhibited by the ariadne domain, which masks the second RING-type zinc finger that contains the active site and inhibits the E3 activity
Ubiquitin ligase activity of the BCR(KEAP1) complex is inhibited by oxidative stress and electrophile metabolites such as sulforaphane (PubMed:15983046, PubMed:17046835, PubMed:29590092, PubMed:30323285). Electrophile metabolites react with reactive cysteine residues in KEAP1 and trigger non-enzymatic covalent modifications of these cysteine residues, leading to inactivate the ubiquitin ligase activity of the BCR(KEAP1) complex (PubMed:19489739, PubMed:17127771, PubMed:18251510, PubMed:29590092, PubMed:30323285). Selective autophagy also inactivates the BCR(KEAP1) complex via interaction between KEAP1 and SQSTM1/p62, which sequesters the complex in inclusion bodies and promotes its degradation (PubMed:20495340, PubMed:20452972)
Completely inhibited by 5 mM N-ethylmaleimide or 0.1 mM Cu(2+). Partially inhibited by 0.1 mM Fe(2+) or 0.1 mM Hg(2+)
Inhibited by O(2)
Allosterically inhibited by ATP. Allosteric ATP-binding requires the presence of the substrate ATP. Inhibited by monovalent cations with ionic radii larger than Na(+) (e.g. K(+), Cs(+)). The monovalent cations increase the affinity of the allosteric site for ATP. PFK-2 is sensitive to inhibition by fructose 1,6-diphosphate
Histone acetyltransferase activity is inhibited by GMNN in the context of a complex with CDT1, inhibiting histone H4 acetylation and DNA replication licensing
Phosphatase activity is inhibited by NaF but not by okadaic acid
Ap4A synthesis is inhibited by tRNA, via the disruption of the second ATP-binding site by direct blocking and/or by tRNA-induced conformational change
Regulated via serine phosphorylation of its input domain. Phosphotransfer from DegS to DegU is stimulated by phosphorylation on Ser-76 and by DegQ
Activated by mek-1 mediated phosphorylation. No differences in basal activation between larvae and adults (PubMed:22554143). Inhibited by phosphatase vhp-1 (PubMed:15116070)
Signaling in response to agonists such as dopamine, epinephrine and norepinephrine is modulated by Na(+); lower Na(+) levels result in higher receptor activity (in vitro)
Inhibited by pyrimidines
Inhibited by metalloporphyrins in the following order of decreasing potency: tin mesoporphyrin > tin protoporphyrin > zinc protoporphyrin > manganese protoporphyrin > cobalt protoporphyrin
Competitively inhibited by the carboxylic acids butyric acid, valeric acid and hexanoic acid (PubMed:15968570). Competitively inhibited by the dicarboxylic acid succinic acid (PubMed:15968570). Competitively inhibited by the alcohols propan-1-ol, butan-1-ol, hexan-1-ol, octan-1-ol, and butane-1,4-diol (PubMed:15968570)
Non-allosteric. Competitively inhibited by fructose 2,6-bisphosphate
Inhibited by glycyrrhetinic acid (By similarity). Induced by progesterone, through the Ihh signaling pathway (By similarity)
Activity is inhibited by unphosphorylated GarA
Pyrrole-2-carboxylate is a competitive inhibitor. N-(cyclopropyl)glycine (CPG) is a mechanism-based inhibitor and inactivates the enzyme by covalently modifying the flavin
High level of membrane cholesterol content reduces cytolytic activity, whereas low level of membrane cholesterol content increases cytolytic activity (PubMed:21506137)
Not inhibited by RNase inhibitor RNasin
Alcohol dehydrogenase activity show inverse correlation with the decreasing availability of oxygen
Possesses an autoinhibitory domain. Autophosphorylation appears to increase the enzymatic activity. Activation is gbdC-dependent. Does not have a calmodulin-binding domain
Phosphorylation at Thr-176 is required for enzymatic activity
By peroxide and bfr-bound iron
Translocation activity is inhibited by the ATPase inhibitor vanadate and the calcium channel blocker verapamil (PubMed:17523162, PubMed:23468132). Translocation activity is enhanced by the addition of the bile salt taurocholate (PubMed:17523162, PubMed:23468132)
Inhibited by argininamide
The neuronal activity and the influx of calcium positively regulate the kinase activity and the internalization of the receptor which are both important for active signaling. Regulated by NGFR that may control the internalization of the receptor. NGFR may also stimulate the activation by BDNF compared to NTF3 and NTF4. SH2D1A inhibits the autophosphorylation of the receptor, and alters the recruitment and activation of downstream effectors and signaling cascades. The formation of active receptors dimers able to fully transduce the ligand-mediated signal, may be negatively regulated by the formation of inactive heterodimers with the non-catalytic isoforms (By similarity)
Inhibited by dipyridamole, IBMX and SCH 51866 (PubMed:10814504, PubMed:10872825). Insensitive to zaprinast, rolipram, and milrinone (PubMed:10814504, PubMed:10872825)
Homodimers are probably inactive, their assembly into a homodecamer at low pH requires neutralization of negatively charged residues. This uses cytoplasmic protons, contributing pH regulation and stabilizes the homodecamer
Inhibited by brefeldin A (BFA) (PubMed:15616190). Inhibited by golgicide A (GCA) (By similarity)
Nuclease function requires interaction with the PCNA heterotrimer. Inhibited by SSB, even in the presence of PCNA
Activity is inhibited by chloride
Activated by Ca(2+). In response to calcium binding, the 280-loop, the 280-loop, a disordered loop consisting of residues 269-275, undergoes a conformational change which stabilizes substrates in the active site. The binding to the substrate triggers the release of the N-terminal region resulting in the activation of the enzyme. Proteolytic cleavage is required for catalytic activity towards large protein substrates
Retinol oxidation is inhibited by the detergent Tween 80 (PubMed:15369820). Ethanol inhibits both all-trans-retinol and 9-cis-retinol oxidation (PubMed:9600267). 13-cis-retinol is an effective competitive inhibitor of the 9-cis-retinol oxidation (PubMed:9600267). All-trans-retinoic acid is a powerful inhibitor of all-trans-retinol oxidation (PubMed:9600267). 13-cis-retinoic acid is a powerful inhibitor of all-trans-retinol oxidation (PubMed:9600267). Cimetidine competitively inhibited ethanol oxidation (PubMed:9600267)
By arsenate for both the forward and reverse reactions
Activated by Ca(2+)-bound calmodulin following an increase in intracellular Ca(2+) (PubMed:11352578, PubMed:10608845, PubMed:9765812, PubMed:8681950). At low Ca(2+) concentrations, the catalytic subunit (also known as calcineurin A) is inactive and is bound to the regulatory subunit (also known as calcineurin B) in which only two high-affinity binding sites are occupied by Ca(2+) (PubMed:11352578). In response to elevated calcium levels, the occupancy of the low-affinity sites on calcineurin B by Ca(2+) causes a conformational change of the C-terminal regulatory domain of calcineurin A, resulting in the exposure of the calmodulin-binding domain and in the partial activation of calcineurin A (PubMed:11352578). The subsequent binding of Ca(2+)-bound calmodulin leads to the displacement of the autoinhibitory domain from the active site and possibly of the autoinhibitory segment from the substrate binding site which fully activates calcineurin A (PubMed:11352578, PubMed:10608845, PubMed:9765812, PubMed:8681950). Activated by arachidonic acid, linoleic acid and oleic acid to the same extent as calmodulin (PubMed:10608845)
Activated by Pka-C1-mediated phosphorylation of Ser-334
Inhibited by ethylenediaminetetraacetic acid (EDTA) and 1,10-phenanthroline. Not inhibited by tosyl-L-lysine chloromethyl ketone (TCLK) and phenylmethanesulfonylfluoride (PMSF)
Phosphorylation at Thr-11 or Tyr-12 inactivates the enzyme, while phosphorylation at Thr-158 activates it
Non-specific ssRNase activity is allosterically activated about 1000-fold by cyclic hexaadenylate (cA6), a second messenger produced by Cas10 of the ternary Csm effector complex in the presence of a cognate target RNA. ssRNase activity is inhibited by physiological concentrations of ATP (1 mM), activity is restored by cOA
Activated by threonine and tyrosine phosphorylation (By similarity). Activated in response to sphingolipid elicitor (SE)
Activity is altered by insulin and estrogen
Activated by glutathione
Inhibited by excess phosphatidylserine, but not by phosphatidylcholine nor phosphatidylethanolamine
Activity is inhibited by the presence of dithiothreitol (DTT)
Activated by Ca(2+) which induces self-processing and is required for the activity of the mature enzyme
Slightly activated by Ba(2+), Ca(2+), Mn(2+), Mg(2+), and Co(2+), while Hg(2+) and Cu(2+) cause marked inhibition of the activity. Ni(2+), Zn(2+) and Cd(2+) have no effect on the catalytic activity. Is also slightly inhibited by lactate, pyruvate, succinate, acetate and formate
Inhibited by O-(2-acetamido-2-deoxy-D-glucopyransylidene)-amino-N-phenylcarbamate (PUGNAc) (PubMed:21692744). Inhibited by thiabendazole (TMG)-chitotriomycin (PubMed:21692744, PubMed:21106526, PubMed:23300622). Inhibited by 6-(dimethylamino)-2-(2-(((5-methyl-1,3,4-thiadiazol-2-yl)methyl)amino)ethyl)- 1H-benzo[de]isoquinoline-1,3(2H)-dione (Q2), a synthesized non-carbohydrate unsymmetrical dyad of naphthalimide and thiadiazole having a dimethylamino group at C4 of the naphthalimide (PubMed:25155420). Inhibited poorly by N-acetyl-glucosamine (NAG)-thiazoline (NGT), but when the thiazoline ring of NGT is replaced by a bulky substituent such as in compound 1,2-dideoxy-2'-methylamino-alpha-D-glucopyranoso-[2,1-d]-Delta2'-thiazoline (NMAGT), the inhibition constant Ki is lowered 600-fold compared to that of NGT (PubMed:25436416). Inhibited by berberine, berberine analogs thalifendine and palmatine, and berberine derivative SYSU-1, but not by berberine analog tetrahydroberberine (PubMed:30135205)
Coactivator activity on nuclear receptors and NF-kappa-B pathways is enhanced by various hormones, and the TNF cytokine, respectively. TNF stimulation probably enhances phosphorylation, which in turn activates coactivator function. In contrast, acetylation by CREBBP apparently suppresses coactivation of target genes by disrupting its association with nuclear receptors. Binds to CSNK1D
Active under aerobic and anaerobic conditions
Inhibited by EDTA and by Zn(2+)
P-chloromercuribenzoate inhibits the accumulation of both N-acetyl-D-glucosamine and antibiotic streptozotocin (2-deoxy-2-(3-methyl-3-nitrosoureido)-D-glucopyranose). N-acetyl-D-glucosamine is a competitive inhibitor for the uptake of streptozotocin
Active in presence of diverse metals including Fe(2+), Zn(2+) and Mn(2+) (PubMed:25123664, PubMed:27930312, PubMed:28504306). Binds two metal cations in two adjacent alpha and beta metal-binding pockets (PubMed:25123664, PubMed:27930312, PubMed:28504306). The activity is the highest with Fe(2+) bound to the 2 metal-binding sites (PubMed:27930312). The activity is slightly lower with Fe(2+) bound to the beta site and Zn(2+) to the alpha site and decreases further when only Zn(2+) is bound (PubMed:27930312). No activity with Mn(2+) (PubMed:27930312). However, another study showed activity with Mn(2+) bound to the beta site and Zn(2+) to the alpha site (PubMed:28504306). Mn(2+) appears unable to bind to the alpha site (PubMed:25123664)
Activity is lost when the metal is removed through urea denaturation or chelation, and can be regained by addition of metal
ATPase activity is stimulated by phosphatidylserine (PS) and minimally by phosphatidylethanolamine (PE). ATPase activity is inhibited by beryllium fluoride and aluminum trifluoride (PubMed:31416931)
Two specific sites, Thr-707 (activation loop of the kinase domain) and Thr-849 (turn motif), need to be phosphorylated for its full activation
Activity is enhanced by Zn(2+) and strongly enhanced by Ca(2+). Inhibited by chalcone, a precursor of several flavonoids, which blocks the SrtA active site
Inhibited by the drug efflux pump inhibitors verapamil, resperine, piperine, chlorpromazine and carbonyl cyanide m-chlorophenylhydrazone (CCCP)
ATPase activity is stimulated upon the addition of RNA
Is potently inhibited by metal ions Fe(3+), Cu(2+) and Zn(2+). Is enhanced by Mn(2+). Ca(2+) and Mg(2+) have no effect
Activated by nsy-1-mediated phosphorylation
Inhibition of this enzyme by phosphorylation regulates the branch point between the Krebs cycle and the glyoxylate bypass, which is an alternate route that accumulates carbon for biosynthesis when acetate is the sole carbon source for growth. The phosphorylation state of this enzyme is controlled by isocitrate dehydrogenase kinase/phosphatase (AceK)
Angiopoietin binding leads to receptor dimerization and activation by autophosphorylation at Tyr-990 on the kinase activation loop
Activity enhanced by Fe(2+) and Mg(2+) ions
The condensation reaction is inhibited by free CoA. The cleavage reaction is characterized by substrate inhibition by acetoacetyl-CoA, which is partially relieved by free CoA
Weakly inihibited by inorganic phosphate (Pi) (PubMed:26095028). Competitive inhibition by 2-hydroxy-3-(1,2,4-triazol-1-yl) (e.g. C348), a potential herbicide (PubMed:27717128)
Significantly inhibited by the wheat xylanase inhibiting protein I (XIP-I) and the proteinaceous endoxylanase Triticum aestivum xylanase inhibitors I (TAXI-I), whereas no inhibition is detected with TAXI-II
Inhibited by Ca(2+), Co(2+), Fe(2+), Fe(3+), Cu(2+) or Zn(2+). No effect of Mg(2+)
Almost complete inhibition by ethanolamine in both the mitochondria-associated membrane (MAM) and endoplasmic reticulum (ER) per se
Activated through phosphorylation at Thr-68 by ATM in response to DNA double-strand breaks. Activation is modulated by several mediators including MDC1 and TP53BP1. Induces homodimerization with exchange of the T-loop/activation segment between protomers and transphosphorylation of the protomers. The autophosphorylated kinase dimer is fully active. Negatively regulated by PPM1D through dephosphorylation of Thr-68
Inhibited by glucono-1,5-lactone, but not by bromoconduritol or conduritol B epoxide
Exists in an autoinhibited state in the absence of substrate protein, due to interactions of the leucine-rich repeat domain with the catalytic domain. Is activated upon binding to a substrate protein
Activated by iron. Other divalent metal ions have no effect
Activated in response to stimuli that lead to increased intracellular Ca(2+) levels; this activation is indirect and may be mediated by calcium-mediated production of reactive oxygen species (ROS). Activated by autophosphorylation at Tyr-402; this creates a binding site for SRC family kinases and leads to phosphorylation at additional tyrosine residues. Phosphorylation at Tyr-402, Tyr-579 and Tyr-580 is required for optimal kinase activity. Inhibited by PF-562,271, BIRB796, PF-4618433 and by PF-431396, PF-2318841 and their derivatives. Inhibited by sulfoximine-substituted trifluoromethylpyrimidines. Inhibited by 4-amino and 5-aryl substituted pyridinone compounds
Subject to competitive inhibition by methyl-gerfelin
Inhibited by PMSF. Not inhibited by benzamidine, aprotinin, SBTI, EDTA, EGTA, 2-mercaptoethanol, iodoacetic acid or pepstatin A
Inhibited by heparin and EDTA
ADP-ribosyltransferase activity is inhibited by PJ34; inhibition is however not specific to TIPARP and other PARP-domain containing proteins are also inhibited by PJ34 (PubMed:30373764). Partially inhibited by KU0058948 (PubMed:30373764)
L-leucine uptake by TR-iBRB2 cells was inhibited by L-leucine, L-phenylalanine, L-methionine, L-isoleucine, L-valine, L-tyrosine, L-tryptophan, D-leucine, D-phenylalanine, D-methionine and by 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH) (a specific inhibitor of system L transport)
Inhibited by coenzyme A (CoA) and CoA thioesthers (PubMed:33420031). Two related chemical scaffolds that potently inhibit the activity of the CoaB moiety of CoaBC through a cryptic allosteric site that sits in the dimer interface region of the CoaB enzyme were identified (PubMed:33420031)
Inhibited by p-chloromercuribenaoate
Non-specific ssRNase activity is allosterically activated about 1000-fold by cyclic tetraadenylate (cA4), which probably binds to its CARF domain
Strongly inhibited by aprotinin, moderately inhibited by secretory leukoprotease inhibitor, the Kunitz-type soybean trypsin inhibitor, and leupeptin, and not inhibited by urinary trypsin inhibitor or alpha-1 protease inhibitor
Transferase activity is inhibited by NH(4)Cl
Inhibited by the natural product emetine produced by the ipecac root
Strongly inhibited by EDTA, zinc and Cu(2+)
Activation of the apo-enzyme requires the three accessory proteins LarB, LarE and LarC, that are involved in the biosynthesis of the nickel-pincer cofactor of LarA (PubMed:24710389, PubMed:27114550). Inhibited by sulfite that behaves as a mixed inhibitor (PubMed:26138974)
Inhibited by flavonoids (kaempferol, quercetin, quercitrin, genistein), myristic acid, pyrazole, barbital, phenobarbital and CuSO4
By diethyl pyrocarbonate (DEPC)
Activity increases about 2-fold over 72 h of hypoxia compared with normoxia (PubMed:16234850). Activity increases in the presence of phenobarbital, chenodeoxycholic and NR1H4/FXR-specific agonist GW4064 (PubMed:17975826)
Inhibited by spinorphin, an opioid peptide derived from hemoglobin
Autoinhibits at very high concentrations, possibly because of extreme junction distortion. Inhibition (and activity at low concentrations of enzyme) is stimulated by dsDNA and Sso7d (PubMed:11709558). Activity stimulated by PCNA subunit PCNA1 (PubMed:17011573)
In the autoinhibited state the side chain of Phe-481 inserts into a hydrophobic groove in RING-0, occluding the ubiquitin acceptor site Cys-449, whereas the REP repressor element binds RING-1 and blocks its E2-binding site (By similarity). Activation of park requires 2 steps: (1) phosphorylation at Ser-94 by Pink1 and (2) binding to phosphorylated ubiquitin, leading to unlock repression of the catalytic Cys-449 by the RING-0 region via an allosteric mechanism and converting park to its fully-active form (PubMed:25474007, PubMed:18957282, PubMed:20194754, PubMed:24901221, PubMed:27906179). According to another report, phosphorylation at Ser-94 by Pink1 is not essential for activation and only binding to phosphorylated ubiquitin is essential to unlock repression (By similarity)
Protease activity is activated upon binding to 1D-myo-inositol hexakisphosphate (InsP6), which induces conformational reorganization (PubMed:17334356). Inhibited by bezlotoxumab, also named Zinplava, a monoclonal antibody approved by the Food and Drug Administration (FDA), which specifically targets TcdB (PubMed:24821719)
Inhibited by flavonoids that occupy the ATP-binding pocket. Inhibited by myricetin, quercetin, luteolin, kaempferol, isorhamnetin and diosmetin, and to a lesser degree by rhamnetin and apigenin
More active at positive than at negative voltages (PubMed:27216227). Repressed by the general anion channel inhibitors dithiocyanatostilbene-2,20-disulphonic acid (DIDS) and niflumic acid (PubMed:27216227)
cGMP transport is highly sensitive to inhibitors of cGMP phosphodiesterase, such as zaprinast, trequinsin and sildenafil
Two specific sites, one in the kinase domain (Thr-305) and the other in the C-terminal regulatory region (Ser-472), need to be phosphorylated for its full activation (By similarity). IGF-1 leads to the activation of AKT3, which may play a role in regulating cell survival
Is not inhibited by EDTA in vitro
Inhibited by oxidized glutathione, p-chloromercuriphenylsulfonic acid and iodoacetic acid. Not inhibited by the chelating agent alpha,alpha-dipyridyl. Activity is slightly increased by EDTA. Not activated by Fe(2+), Mg(2+), Mn(2+) or Ca(2+). Unaffected by K(+), Na(+), NH4(+), Rb(+) or Li(+)
Activated by the ototoxic drug cisplatin. Activated by NOXO1. Cooperatively activated by NCF1 and NCF2 or NOXA1 in a phorbol 12-myristate 13-acetate (PMA)-dependent manner. Inhibited by diphenyleneiodonium chloride
Inhibited in cells after FCER1A triggering
Inhibited by glycyrrhetinic acid (By similarity). Induced by progesterone, through the Ihh signaling pathway (PubMed:31600723)
Stabilized in the inactive form by an association between the SH3 domain and the SH2-TK linker region, interactions of the N-terminal cap, and contributions from an N-terminal myristoyl group and phospholipids. Activated by autophosphorylation as well as by SRC-family kinase-mediated phosphorylation. Activated by RIN1 binding to the SH2 and SH3 domains. Also stimulated by cell death inducers and DNA-damage. Phosphatidylinositol 4,5-bisphosphate (PIP2), a highly abundant phosphoinositide known to regulate cytoskeletal and membrane proteins, inhibits also the tyrosine kinase activity (By similarity). Activated by 5-(1,3-diaryl-1H-pyrazol-4-yl)hydantoin, 5-[3-(4-fluorophenyl)-1-phenyl-1H-pyrazol-4-yl]-2,4-imidazolidinedione (DPH) (PubMed:28428613). Inhibited by ABI1, whose activity is controlled by ABL1 itself through tyrosine phosphorylation. Also inhibited by imatinib mesylate (Gleevec) which is used for the treatment of chronic myeloid leukemia (CML), and by VX-680, an inhibitor that acts also on imatinib-resistant mutants (PubMed:28428613)
Inhibited by zinc, cobalt and copper ions
Calcium-dependent
May function more efficiently in K(+) concentrations higher than 10 mM
Arginine transport is strongly inhibited by lysine, glutamate, leucine, glutamine, methionine and histidine, in the presence of Na(+) (PubMed:10903140). Also inhibited by protein kinase C (PKC) and treatment with phorbol-12-myristate-13-acetate (PMA) (PubMed:17329401)
ATPase activity is decreased by cholesterol and ceramide. ATPase activity is stimulated by phosphatidylcholine and to a lesser degree by phosphatidylserine and sphingomyelin. Phospholipid translocase activity is highly reduced by berylium fluoride and aluminum flouride and reduced by N-ethylmaleimide
Inhibited by Myc
Is reversibly and partially inactivated by betaine aldehyde in the absence of NAD(+) in a time- and concentration-dependent mode
Inhibited by 2-hydrazinopyridine
Inhibited by GMP. Inhibited by chloride. Inhibited in a highly specific manner by the binding of a 44-base DNA oligonucleotide carrying the ARS core consensus sequence
Subject to strong product inhibition. N-glycosyl hydrolysis proceeds 100-fold faster than product release
Inhibited by EDTA, beta-mercaptoethanol, but not by PMSF, p-tosyl-L-phenylalanine chloromethyl ketone, p-tosyl-L-lysine chloromethyl ketone, soybean trypsin inhibitor and aprotinin
Activated in cardiovascular cells and Hela cells following exposure to hypoxia. Inhibited by polynitrogen compounds probably by chelation to Fe(2+) ions
Activated by histamine, L-adrenaline, L- and D-histidine, and L- and D-phenylalanine. Inhibited by coumarins, sulfonamide derivatives such as acetazolamide (AZA), by saccharin and Foscarnet (phosphonoformate trisodium salt)
Is inhibited by azobenzenes, stilbenes and arylazopyrazoles
Inhibited by 1,8-naphthalimide (NAP) as well as a number of poly(ADP-ribose) polymerase inhibitors and other compounds
Activity is controlled at multiple levels (PubMed:22812682). Regulation includes a positive autoregulatory loop on mgsR transcription and a post-translational redox-sensitive activation step by an intramolecular disulfide bond formation in response to ethanol stress (PubMed:22812682). In addition, protein stability is strictly controlled by rapid proteolytic degradation by the ClpXP and ClpCP proteases (PubMed:22812682, PubMed:32477307). The McsB protein-arginine kinase might serve as a proteolytic adapter for the ClpX ATPase in the degradation mechanism of MgsR (PubMed:32477307)
Activated by manganese and, to a lesser extent, by other divalent metals such as cobalt and calcium. Inhibited by copper, ferric and zinc ions
NAD-dependent protein-lysine deacetylase and deacylase activities are activated by nucleic acids (PubMed:26907567, PubMed:27997115). Histone deacetylase activity is activated by DNA and nucleosomes (PubMed:27997115, PubMed:35939806). Protein-lysine deacylase activity is activated by RNA (PubMed:26907567). H3K18Ac histone deacetylase activity is inhibited by methylation at Arg-388 (PubMed:30420520). H3K18Ac histone deacetylase activity is inhibited by deubiquitination by USP7 (PubMed:28655758)
Binding to DNA is inhibited by L-arabinose
Under complex allosteric control mediated by deoxynucleoside triphosphates and ATP binding to separate specificity and activation sites on the alpha subunit. The type of nucleotide bound at the specificity site determines substrate preference. It seems probable that ATP makes the enzyme reduce CDP and UDP, dGTP favors ADP reduction and dTTP favors GDP reduction. Stimulated by ATP and inhibited by dATP binding to the activity site. In vitro, its activity is increased by dithiothreitol (DTT) or thioredoxins (non-specific). Inhibited by hydroxyurea, leads to dNTP depletion, replication fork arrest and genomic instability (PubMed:20005847)
Inhibited by EDTA and calcium. Diumycin and moenomycin stimulate activity at concentrations of up to 100 ug/ml, and then inhibit at higher concentrations
Inhibited by tert-butyl 4-(3-thiophen-2-yl-1,2,4-oxadiazol-5-yl) piperidine-1-carboxylate (RF1) and 1-(thiophen-2-ylacetyl)-4-(3-thiophen-2-yl-1,2,4-oxadiazol-5-yl)piperidine (RF3)
PAP phosphatase and IMPase activities are inhibited by Li(+). To a lesser extent, PAP hydrolysis is also inhibited by Na(+) and K(+), with IC50 values of 150 and 250 mM, respectively, so much higher than IC50 with Li(+) (0.5 mM). Exhibits about 50% residual IMPase activity at 5 mM Li(+) and about 10% at 30 mM Li(+). Na(+) and K(+) have no significant effect on IMPase activity between 0 and 200 mM
Activated by Mg(2+). Retains 73.3%, 61.2%, 36%, 22.6% and 4.1% of the maximal activity with Mn(2+), Co(2+), Ni(2+), Zn(2+) and MoO4(2-), respectively. Nearly loss of activity with Cu(2+), Ca(2+), Fe(2+) and WO4(2-)
Present in an inactive conformation in the absence of bound ligand. Ligand binding leads to dimerization and activation by autophosphorylation on tyrosine residues. Inhibited by ARQ 523 and ARQ 069; these compounds maintain the kinase in an inactive conformation and inhibit autophosphorylation
Inhibited by the benzophenone containing OSC inhibitor Ro48-8071 and to a lesser extent by other benzophene containing inhibitors
Inhibited by brefeldin A (BFA)
Methylesterase activity is activated via phosphorylation in response to negative chemotactic stimuli and is inhibited in the presence of attractants (PubMed:392505, PubMed:2188960). Activation requires both CheA and CheW (PubMed:2188960)
Shows cooperative activation. Allosterically activated by asparagine
Product-inhibited by apurinic/apyrimidinic sites
Activity not stimulated by acetyl-CoA in the absence of any allosteric inhibitor, while the corresponding protein from E.coli is strongly stimulated
Divalent cations are not required for activity, but the presence of Mn(2+), Mg(2+) or Ca(2+) stimulates activity
Inhibited by KCN and diethyldithiocarbamate
Inhibited by diethylpyrocarbonate (DEPC)
By ethanol. Thioesterase and esterase reactions are highly repressed in the presence of high ethanol concentrations
The ion channel is gated following an off-response property by acid: gated open after the removal of acid stimulus, but not during acid application (PubMed:18535624, PubMed:19464260, PubMed:20406802, PubMed:22420714, PubMed:28904867, PubMed:29567962). Responses to acid stimulus are inhibited by capsaicin (PubMed:22420714)
Inhibited by carbonlycyanide m-chlorophenylhydrazone (CCCP) and DEPC
Complete loss of activity in the presence of Ni(2+), Co(2+), Cd(2+), Zn(2+) and hydrogen peroxide, however activity with hydrogen peroxide partially restored upon addition of excess ascorbate. Partially inhibited by Fe(2+), Mg(2+), Ca(2+), Mn(2+), Cu(2+) and also by EDTA, at 2 mM concentration. Total activity inhibited in the presence of catechol or 4-nitrocatechol but completely restored after removal of catechol and addition of 2 mM Fe(2+) and 5 mM ascorbate
KSH activity is completely inhibited by zinc ions. KshB is specifically inhibited by Cu(2+) ions
Activity increased by up to 80-fold under blue light
Competitively and allosterically inhibited by NADH and NADPH at physiological concentrations, whereas inhibition by NADP is only slight. Inhibited by p-chloromercuribenzoate and HgCl(2)
The formation of active receptors dimers able to fully transduce the ligand-mediated signal, may be negatively regulated by the formation of inactive heterodimers with the non-catalytic isoforms (By similarity). The neuronal activity and the influx of calcium positively regulate the kinase activity and the internalization of the receptor which are both important for active signaling. Regulated by NGFR that may control the internalization of the receptor. NGFR may also stimulate the activation by BDNF compared to NTF3 and NTF4. SH2D1A inhibits the autophosphorylation of the receptor, and alters the recruitment and activation of downstream effectors and signaling cascades
The DD-carboxypeptidase activity is not inhibited by beta-lactam antibiotics
GTPase activity is enhanced by ARC3
Activity somewhat enhanced by calcium ions, inhibited by zinc and Fe(3+) ions and by p-chloromercuribenzoic acid and EDTA. Activity is enhanced by salivary peptide cystatin and reduced by salivary peptide histatin
Completely inhibited by vanadate(3-). Also inhibited by lanthanoid atom and phosphate. Not inhibited by N-ethylmaleimide, 1,3-dicyclohexylcarbodiimide, oligomycin, ouabain, valinomycin, nigericin, thapsigargin, cyclopiazonic acid or fluorescein isothiocyanate
Stimulated by cytosolic Ca(2+). Stimulated by anionic phospholipids such as phosphatidylserines, phosphatidates and phosphatidylinositols
Requires glucose 1,6-bisphosphate (G1,6P) as an activator (PubMed:8050998, PubMed:11716469). Reaction making glucose 6-phosphate is subject to substrate inhibition, reactions making mannose 1-phosphate or glucose 1-phosphate are not. 1-deoxyglucose 6-phosphate competitively inhibits glucose 1-phosphate (PubMed:11716469). Inhibited by xylose 1-phosphate (PubMed:16880541)
Activated by autophosphorylation on Thr-1400 and Thr-1412 following oligomerization
The regulatory activity of ManR is modulated by phosphorylation and dephosphorylation of the various ManR domains. It becomes activated via phosphoryl group transfer from PEP, EI and HPr on the two conserved histidine residues in the PRD 2 domain, whereas phosphorylation of the EIIA-like domain on His-570 by the PTS EIIB-Man domain of ManP inactivates ManR (PubMed:23551403)
Activated by PRDX1 by reduction of an intramolecular disulfide bond
Inhibited by Li(+) with IC50 value of 0.9 mM but not by Na(+) or K(+). Also inhibited by Zn(2+) (IC50 value of 0.5 uM) and by concentrations of Mg(2+) higher than 100 mM
Negatively regulated by ABI2
Inhibited by mono-unsaturated fatty acids, palmitoleic acid and oleic acid and nonionic detergents, triton X-100 and polyethylene glycol hexadecyl ether (Brij 58)
The activity is independent of the presence of oxygen
Copurifies with a tightly bound zinc ion. Activated by release of zinc. His and other agents that promote the release of bound zinc ions activate the enzyme (in vitro). Inhibited by S-nitrosylation. Zinc protects the protein against S-nitrosylation
Inhibited by the 4-azasteroids 4-MA
Activated by iron
By phosphorylation. Activated by N-methylethanolamine (PubMed:8185307). Activated by oleic acid-containing phosphatidylcholine vesicles (PubMed:8381041)
GTPase-activating activity is inhibited in the folliculin complex (LFC), which stabilizes the GDP-bound state of RRAGA/RagA (or RRAGB/RagB), because Arg-164 is located far from the RRAGC/RagC or RRAGD/RagD nucleotide pocket (PubMed:31672913). Disassembly of the LFC complex upon amino acid restimulation liberates the GTPase-activating activity (PubMed:31672913)
Allosterically activated by GTP, when glutamine is the substrate; GTP has no effect on the reaction when ammonia is the substrate. The allosteric effector GTP functions by stabilizing the protein conformation that binds the tetrahedral intermediate(s) formed during glutamine hydrolysis. Inhibited by the product CTP, via allosteric rather than competitive inhibition (By similarity). Is inhibited by the EthA-activated metabolites of compounds 7947882 (5-methyl-N-(4-nitrophenyl)thiophene-2-carboxamide) and 7904688 (3-phenyl-N-[(4-piperidin-1-ylphenyl)carbamothioyl]propanamide), that have been shown to have anti-tubercular activity against M.tuberculosis in its replicating, non-replicating, and intracellular states; active metabolites of 7947882 correspond to the S-dioxide and S-monoxide derivatives (PubMed:26097035). One active metabolite was shown to behave as a competitive inhibitor toward the ATP-binding site of PyrG (PubMed:26097035). Direct inhibition of PyrG decreases CTP levels, leading to disruption of the nucleotide metabolic network, characterized by increased levels of several intermediates in the biosynthesis of pyrimidines and purines (PubMed:26097035)
Inhibited by coformycin but not by methylthiocoformycin (MT-coformycin)
Is inhibited by riboflavin. Product inhibition may be the major mechanism by which RS regulates its enzymatic activity in vivo
Activation may be calcium-dependent (PubMed:16879884). Inhibited by the non-covalent interaction with the cleaved propeptide (PubMed:16879884, PubMed:19214190)
Inhibited by methylglyoxal bis(cyclopentylamidinohydrazone)(MGBCP)
The elicitor proteolytic activity is completely inhibited by PMSF. The activity is also significantly reduced by aprotinin (leading to 37% residual activity), by leupeptin (leading to 54% residual activity), by the ovomucoid trypsin inhibitor (leading to 65% residual activity), and by p-aminobenzamidine (leading to 26% residual activity)
Rapidly inactivated by p-chloromercuriphenylsulfonic acid (p-CMB). Dithiothreitol incubation restores the activity
During activation, the N-terminal disordered prodomain is removed by cleavage (PubMed:8900201, PubMed:8663580, PubMed:19133298, PubMed:28864531). Concomitantly, double cleavage gives rise to a large 18-kDa and a small 11-kDa subunit (PubMed:8663580, PubMed:19133298). The two large and two small subunits then assemble to form the active CASP6 complex (PubMed:8663580). Can be cleaved and activated by different caspases, depending on the context (PubMed:9463409, PubMed:19133298). Cleaved and activated by caspase-8 (CASP8) and subsequently by caspase-3 (CASP3) (PubMed:9463409). Can also undergo autoactivation by mediating autocleavage at Asp-179 and Asp-193, while it is not able to cleave its N-terminal disordered prodomain (PubMed:19133298, PubMed:28864531). Intramolecular cleavage at Asp-193 is a prerequisite for CASP6 self-activation (PubMed:20890311, PubMed:28864531). Cleaved and activated by CASP1 in neurons, possibly in the context of inflammation (PubMed:16123779). Phosphorylation at Ser-257 inhibits autocleavage, preventing caspase activation (PubMed:15273717, PubMed:32029622, PubMed:22433863, PubMed:22483120). Specifically inhibited by compound 3 (benzyloxycarbonyl (Z)-VEID-tetrafluorophenoxymethyl ketone) (PubMed:23227217)
Kinase activity is suppressed by interaction with CML9
Resistant to aphidicolin, but sensitive to dideoxythymindine triphosphate (ddTTP) and N-ethyl malemide (NEM)
No inhibition by ethanolamine, choline or their phosphoesters
Inactive in absence of double-stranded DNA (dsDNA) (PubMed:26197926, PubMed:22483801). Homooligomerizes upon binding to dsDNA, dsDNA serving as an oligomerization platform (PubMed:26197926, PubMed:33980849). AIM2 requires large dsDNA to generate a structural template that couples dsDNA ligand-binding and homooligomerization (PubMed:26197926). Homooligomerization is followed by recruitment of PYCARD/ASC to initiate speck formation (nucleation) (PubMed:26197926, PubMed:29440442, PubMed:22483801, PubMed:33980849). AIM2 and PYCARD/ASC homooligomer filaments assemble bidirectionally and the recognition between AIM2 and PYCARD/ASC oligomers occurs in a head-to-tail manner (PubMed:33980849). Clustered PYCARD/ASC nucleates the formation of CASP1 filaments through the interaction of their respective CARD domains, acting as a platform for CASP1 polymerization and activation (PubMed:19158675, PubMed:19158676). Active CASP1 then specifically processes protein precursors, such as gasdermin-D (GSDMD), IL1B and IL18, leading to the release of mature cytokines in the extracellular milieu or pyroptosis, depending on cell type (PubMed:16432157, PubMed:19158676, PubMed:19158675). AIM2 can be activated in response to events that cause genomic DNA (HIV protease inhibitor nelfinavir) or mitochondrial DNA release in the cytoplasm (such as Perfluoroalkyl substance pollutants or cholesterol overload) (By similarity). Activation of the AIM2 inflammasome is inhibited by isoform IFI16-beta of IFI16, which prevents the interaction between AIM2 and PYCARD/ASC (PubMed:30104205). Activation of the AIM2 inflammasome is inhibited by TRIM11, which promotes autophagy-dependent degradation of AIM2 (PubMed:27498865)
Inhibited by phenylmethylsulfonyl fluoride (PMSF)
Suramin inhibits the myotoxic activity (PubMed:18586854)
Inhibited by cysteine protease inhibitors ICP1 and ICP2
Carbon monoxide dehydrogenase activity is inhibited by KCN and is rapidly inactivated by O(2)
Inhibited by GlcNAc, 2-acetamido-1-N-(4-L-aspartyl)-2-deoxy-beta-D-glucopyranosylamine (GlcNAc-Asn) and O-(2-acetamido-2-deoxy-D-glucopyranosylidene)-amino-N-phenylcarbamate (PUGNAc)
Oxidized glutathione (GSSG) stimulates ATP hydrolysis without affecting ATP binding, whereas reduced glutathione (GSH) inhibits ATP binding and hydrolysis
Inhibited by sulfatide (PubMed:19168031). Inhibited by sphinganine, sphingenine, and N,N-Dimethylsphingosine (DMS) (PubMed:16269826). Cardiolipin at 0.1 uM significantly increases activity, whereas at concentrations >1 uM has an inhibitory effect (PubMed:27725450)
Non-specific ssRNase activity is allosterically activated by cyclic oligoadenylates (cOA), a second messenger produced by Cas10 of the ternary Csm effector complex in the presence of a cognate target RNA
Kinase activity is activated by fructose 1,6-bisphosphate (FBP) only at low concentrations of enzyme or at high ATP concentrations
ATPase activity is stimulated by high magnesium salt levels (up to a 0.1 M), and potassium salts (glutamate, chloride or acetate) are more effective than the corresponding sodium salts (PubMed:10648783, PubMed:18499658). ATPase activity is enhanced by the long non-coding RNA (lncRNA) cohesion regulator noncoding RNA (CONCR) (PubMed:27477908). Double-stranded DNA helicase activity is maximal with magnesium ions at low concentrations (0.5-1 mM) whereas is markedly inhibited at higher levels (5 mM and above) (PubMed:10648783, PubMed:18499658). Double-stranded DNA helicase activity is stimulated by 25-50 mM potassium acetate, stimulated to a lesser extent by 25 mM of ammonium acetate, and markedly inhibited by sodium acetate (PubMed:18499658)
Inhibited (at 40%) by the coenzyme M analog 2-bromoethanesulfonate (BES). BES is a time-dependent inactivator of dithiothreitol-reduced 2-KPCC, where the redox active cysteines are in the free thiol forms. BES does not inactivate air-oxidized 2-KPCC, where the redox active cysteine pair is in the disulfide form. BES specifically alkylates the interchange thiol that facilitates thioether bond cleavage and enolacetone formation during catalysis
Inhibited by ZPR3
Autoinhibited. Intramolecular binding of the interdomains A and B (also called linker region) to parts of the catalytic domain keep the catalytic center in an inactive conformation. The phosphorylation of the interdomains or the binding of the SH2 domains with dually phosphorylated ITAM domains on transmembrane proteins disrupt those intramolecular interactions allowing the kinase domain to adopt an active conformation. The phosphorylation of SYK and of the ITAM domains which is responsible for SYK activation is essentially mediated by SRC subfamily kinases, like LYN, upon transmembrane receptors engagement. May also be negatively regulated by PTPN6 through dephosphorylation. Downstream signaling adapters and intermediates like BLNK or RHOH may mediate positive and/or negative feedback regulation. Negatively regulated by CBL and CBLB through ubiquitination and probable degradation (By similarity). Phosphorylates SH3BP2 which in turn may regulate SYK through LYN (By similarity)
E1S, DHEA-S and PregS transports are regulated by steroid hormones. In the case of testosterone, transport of E1S and DHEA-S was inhibited, whereas progesterone stimulated E1S, DHEA-S and PregS uptake (PubMed:16908597). Progesterone stimulates high-affinity uptake of E1S whereas it inhibits low-affinity uptake of E1S (Ref.24). Progesterone doesn't affect the uptake of PGE2 (Ref.24)
Dithiothreitol greatly stimulates activity, maximum stimulation being at 5-20 mM dithiothreitol concentration. Fe(3+), Fe(2+) and Mn(2+) severely inhibit activity (88%, 82% and 50%, respectively), whereas Zn(2+) has a slightly inhibitory effect (23%) and Mg(2+), Ca(2+), Cu(2+) and Cu(+) have no effect
Inhibited by carbenoloxone
Novel PKCs (PRKCD, PRKCE, PRKCH and PRKCQ) are calcium-insensitive, but activated by diacylglycerol (DAG) and phosphatidylserine. Three specific sites; Thr-565 (activation loop of the kinase domain), Thr-709 (turn motif) and Ser-728 (hydrophobic region), need to be phosphorylated for its full activation
Inhibited by NaF and orthovanadate, as well as by divalent cations such as Ni(2+) and Zn(2+). Inhibited by polylysine with myelin basic protein as substrate, but activated by polylysine with pNPP as substrate. Reversibly regulated by redox agents. Inhibited by submillimolar Pi concentrations. Slightly repressed by calmodulin (CaM)
Phosphoenolpyruvate carboxykinase activity is regulated by acetylation and glucose levels (PubMed:30193097). The anaplerotic conversion of phosphoenolpyruvate to oxaloacetate is improved by PCK1 acetylation on Lys-91 (K91ac), Lys-473 (K473ac) and Lys-521 (K521ac) (By similarity). High glucose concentrations favor PCK1 anaplerotic activity by triggering acetylation on Lys-91 (K91ac). At low glucose levels, SIRT1-mediated deacetylation of Lys-91 promotes the cataplerotic conversion of oxaloacetate to phosphoenolpyruvate (By similarity). Phosphorylation at Ser-90 reduces the binding affinity to oxaloacetate and converts the enzyme into an atypical protein kinase using GTP as donor (By similarity)
Activated by magnesium and mangenese ions, and inhibited by calcium, zinc and copper ions
Inhibited in vitro by metal chelators such as EDTA and 1,10-phenanthroline
Inhibited by orthovanadate, berylium fluoride and aluminum flouride
The enzyme is completely inhibited by dithiothreitol (DTT) and diisopropylfluorophosphate (DFP), and partially inhibited by HgCl(2) and by enzyme3-(p-nitrophenoxy)propane (EPNP) (PubMed:1929416, Ref.2). Activity is not affected by N-ethylmaleimide (NEM) or phenylmethylsulfonyl fluoride (PMSF) (PubMed:1929416, Ref.2)
Inhibited by sodium orthovanadate. Weakly inhibited by sodium fluoride and okadaic acid
Inhibited by L-histidine (46%), L-arginine (38%) and L-methionine-DL-sulphoximine. The activity of this enzyme is not controlled by adenylation
Inhibited by diisopropylfluorophosphate
Internal adenine may inhibit transport
Extremely resistant to denaturating agents, such as SDS and organic solvents
Inhibited by manganese
Inhibited by AMP-DMN/N -((5-adamantane-1-yl-methoxy)pentyl)-deoxynojirimycin (PubMed:11489889, PubMed:30308956). Activated by Mn(2+), Co(2+) and Mg(2+) and inhibited by Zn(2+) (PubMed:11489889). Enzymatic activity is dependent on membrane association and requires the presence of lipids (PubMed:11489889). The membrane-associated enzyme is not inhibited by condutiriol B epoxide and bromocondutiriol B epoxide (PubMed:11489889)
Novel PKCs (PRKCD, PRKCE, PRKCH and PRKCQ) are calcium-insensitive, but activated by diacylglycerol (DAG) and phosphatidylserine. Three specific sites; Thr-538 (activation loop of the kinase domain), Ser-676 (turn motif) and Ser-695 (hydrophobic region), need to be phosphorylated for its full activation. Inhibited by PRKCH upstream open reading frame 2 (PubMed:34593629)
Crotonylated lysine binding is strongly inhibited by the peptide XL-07i, carrying a 2-furancarbonyl side chain and capped with a hydrophobic carboxybenzyl group (PubMed:30374167). XL-07i targets the unique pi-pi-pi stacking interaction at the crotonylation recognition site (PubMed:30374167)
Inhibited by very high concentrations of cyclopiazonic acid (CPA)
APOA1 is the most potent activator in plasma (PubMed:19065001, PubMed:8016111). Also activated by APOE, APOC1 and APOA4 (PubMed:19065001, PubMed:8016111). Inhibited by haptoglobin and 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB) (PubMed:8016111, PubMed:24620755)
Activated by the presence of mitochondrial RNA
Inhibited by the tyrosine phosphatase inhibitor orthovanadate, but resistant to the serine/threonine phosphatase inhibitors okadaic acid and microcystin. Inhibited by phosphate analogs NaF and Na(3)VO(4), and the adenylates ATP and ADP. Inactivated by zinc ions
Activity of the GroEL-GroES chaperonin complex requires Mg-ATP
Inhibited by D-4-phosphoerythronic acid
The formation of the complex with AroG activates the chorismate mutase activity by more than two orders of magnitude to a catalytic efficiency (kcat/Km) typical for chorismate mutase. This activation is primarily caused by a more than 30-fold-decreased Km value, but also by a four-fold increase in kcat. The activity of the complex is inhibited by phenylalanine and tyrosine by about 70 and 40%, respectively
Appears to be allosterically activated by NADH
Maximal reductase activity is achieved only upon trigonelline (TG) binding to the reductase component before interaction with NADH. It seems that TgnA undergoes an allosteric transition upon trigonelline (TG) binding accounting for the positive cooperativity toward NADH oxidation
Inhibited by cytochrome C, miconazole, aminobenzotriazole, metyrapone and clotrimazole
RNase activity on target is decreased by EDTA (PubMed:27256883). Target RNA acts as an activator for non-specific ssRNA degradation (PubMed:27256883)
Inhibited by methyl-p-nitrophenyl-octylphosphonate
Activated by divalent cations (PubMed:17655883). Activated by bile acids (By similarity). Activated by membrane phospholipids such as phosphatidylethanolamines. Inhibited by cardiolipins (PubMed:17655883)
Inhibited by swainsonine
12-fold increase in the presence of 2-oxoglutarate. Up to 18-fold increase in the presence of 2-oxoglutarate and GlnK1 or GlnK2. Inhibited by AMP and glutamine
Inhibited by (p-amidinophenyl) methanesulfonyl fluoride, p-nitrophenyl-p'-guanidinobenzoate, D-phenylalanyl-L-prolyl-L-arginyl chloromethane, leupeptin, antipain and to a lesser extent by antithrombin III
Slightly inhibited by N-acetylcastanospermine
Specifically activated by lumenal, but not cytosolic Ca(2+). Inhibited by Zn(2+) or Cu(2+). Mg(2+) or Mn(2+) have no effect on ceramidase activity (PubMed:20089856). Inhibited by De-MAPP (PubMed:20207939)
Active at low pH (under pH 4.6): proton channel activity is activated by luminal side protons (PubMed:35750034). Polyunsaturated fatty acids, such as arachidonic acid, also activate the channel activity (PubMed:35750034). Channel activity is activated following interaction with AKT (AKT1, AKT2 or AKT3): interaction promotes activation from closed to an open state (PubMed:33505021). Activation by AKT is independent of AKT serine/threonine-protein kinase activity (PubMed:33505021)
Phosphorylation at Ser-510 by PRK2 may release ROPGEF12 auto-inhibition, thereby activating ROPGEF12 and downstream Rop signaling
Activated by the substrate 5-phospho-alpha-D-ribosyl-1-pyrophosphate and inhibited by the purine ribonucleotides, the end products of purine biosynthesis
The antiport activity is markedly inhibited by both valinomycin and CCCP, and modestly by nigericin
Isoform 1 and isoform 2 are activated by phosphate, due to increased affinity for glutamine (PubMed:22228304, PubMed:23935106, PubMed:27542409). At phosphate concentrations above 10 mM, isoform 2 is more efficient than isoform 1
Nitric oxide synthase activity is increased by trpS2
Inhibited by high level of NaCl or urea
PDPK1 activates its transcriptional activity independently of its kinase activity. Interacts with HELZ2 and THRAP3; the interaction enhances the transcriptional activity of PPARG (By similarity)
Inhibited by DEPC, protonophores (e.g. dinitrophenol and carbonyl cyanide m-chlorophenyl-hydrazone (CCCP)), and SH group inhibitors (e.g. N-ethylmaleimide (NEM) and p-chloromercuriphenyl sulphonic acid (PCMPS))
Not inhibited by fluoride
D-galactonate binds DgoR and induces a conformational change in the protein, which decreases its affinity for DNA and consequently derepresses transcription of the dgoRKADT operon
Inhibited by ornithine
Inhibited by PMEI
The disulfide bridge formed between Cys-38 in the propeptide and the active site residue Cys-95 may prevent activation of the zymogen through formation of a reversible covalent bond with the active site residue
Inhibited by 6-diazo-5-oxo-L-norleucine (DON). The inhibition is competitive with glutamine but uncompetitive with chorismate. Also inhibited by 2-fluorochorismate
Activity is modulated by phosphorylation and interaction with other transcriptional regulators. Probably up-regulated by YmgA/AriR, and possibly down-regulated by YcgZ, all 3 are connector proteins providing additional signal input into the signaling system
Activated under anaerobic conditions by NrdG, a tightly associated activase. Activation involves the formation of a glycyl radical at Gly-681
Autophosphorylation is stimulated by Mn(2+)
Transport is inhibited by thiosulfate, phosphate, molybdate, selenate and tungstate. Not inhibited by oxalate, citrate, succinate, phenol red or 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS)
Gas or ligand binding and heme iron redox state regulate the histidine kinase activity: heme-free AfGcHK and the heme Fe(II) complex are less active forms, whereas the heme Fe(III)-OH(-), Fe(III)-CN(-), Fe(III)-imidazole, Fe(II)-CO, and Fe(II)-O(2) complexes are active forms. The activation of the functional domain seems to be dependent on the formation of a six-coordinate low-spin heme iron complex. Mg(2+) ions, and to a lesser extent, Mn(2+) ions, enhance the autophosphorylation reaction, although the presence of a divalent metal ion does not appear to be essential for the reaction. Co(2+), Ni(2+), Zn(2+), and Cd(2+) totally inhibit autophosphorylation activity
Unable to bypass a single 1,N(6)-ethenoadenine (epsilon-dA) or an abasic site lesions in DNA templates
Inhibited by PMSF, SSI, the peptide Phe-Val and by Phe, but not by EDTA
Under complex allosteric control mediated by deoxynucleoside triphosphates and ATP binding to separate specificity and activation sites on the M1 subunit. The type of nucleotide bound at the specificity site determines substrate preference. It seems probable that ATP makes the enzyme reduce CDP and UDP, dGTP favors ADP reduction and dTTP favors GDP reduction. Stimulated by ATP and inhibited by dATP binding to the activity site, the dATP inhibition is mediated by AHCYL1 which stabilizes dATP in the site
Adenylyltransferase activity is inhibited by the inhibitory helix present at the N-terminus: Glu-73 binds ATP and competes with ATP-binding at Arg-209, thereby preventing adenylyltransferase activity. Activation dissociates ATP-binding from Glu-73, allowing ordered binding of the entire ATP moiety with the alpha-phosphate in an orientation that is productive for accepting an incoming target hydroxyl side chain
Stimulated by various salts
The channel is sensitized by ATP binding. Repeated stimulation with capsaicin gives rise to progressively smaller responses, due to desensitization. This desensitization is triggered by the influx of calcium ions and is inhibited by elevated ATP levels. Ca(2+) and CALM displace ATP from its binding site and trigger a conformation change that leads to a closed, desensitized channel. The double-knot toxin (DkTx) from the Chinese earth tiger tarantula activates the channel and traps it in an open conformation (By similarity). The Scolopendra mutilans RhTx toxin potentiates the heat activation pathway mediated by this channel by binding to the charge-rich outer pore region (in an activated state) (PubMed:26420335). Channel activity is activated via the interaction with PIRT and phosphatidylinositol 4,5-bisphosphate (PIP2). Both PIRT and PIP2 are required to activate channel activity. Intracellular PIP2 inhibits desensitization (By similarity)
Irreversibly inhibited by Cd(2+) concentrations above 50 uM
Inactivated by oxidized glutathione (GSSG) at pH 8.0
Inhibited by divalent cations (zinc, copper, mercury) and by the sulfhydryl reagents 5,5-dithiobis(2-nitrobenzoic acid), N-ethylmaleimide and p-chloromercuribenzoate
Activated by monothiol glutaredoxin GRXS14 and CXIP4. Inhibited by excess of Ca(2+) and Cd(2+), Na(+) and K(+), but not Mn(2+)
Repressed in minimal medium by the presence of glucose and NH4(+), glycerol and NH4(+), or glycerol and asparagine
Requires 4 M NaCl for maximal activity. Loss of activity if DTT or beta-mercaptoethanol is omitted from buffers. Addition of 5-20 mM EDTA, 1 mM Cu(2+) or 1 mM Zn(2+) results in loss of activity
The full-length protein before cleavage is inactive: intramolecular interactions between N- and C-terminal domains mediate autoinhibition in the absence of activation signal. The intrinsic pyroptosis-inducing activity is carried by the released N-terminal moiety (Gasdermin-C4, N-terminal)
Inhibited by EDTA. Not inhibited by the serine proteinase inhibitors aprotinin and benzamidine
L-lactate acts as a positive effector on the binding and multimerization of LarR on DNA, while D-lactate antagonizes the positive effect of L-lactate
Inhibited by cis-2-hydroxy-3-cyclohexen-1-carboxylate, cis-2-hydroxycyclohexane-1-carboxylate and trans-2-hydroxycyclohexane-1-carboxylate
Channel activity is activated via the interaction with PIRT and phosphatidylinositol 4,5-bisphosphate (PIP2). Both PIRT and PIP2 are required to activate channel activity (By similarity). The channel is sensitized by ATP binding. Repeated stimulation with capsaicin gives rise to progressively smaller responses, due to desensitization. This desensitization is triggered by the influx of calcium ions and is inhibited by elevated ATP levels. Ca(2+) and CALM displace ATP from its binding site and trigger a conformation change that leads to a closed, desensitized channel. Intracellular PIP2 inhibits desensitization. The double-knot toxin (DkTx) from the Chinese earth tiger tarantula activates the channel and traps it in an open conformation. The Scolopendra mutilans RhTx toxin potentiates the heat activation pathway mediated by this channel by binding to the charge-rich outer pore region (in an activated state) (By similarity)
Subject to allosteric regulation. Activated by AMP and ADP
Autophosphorylates on Ser residues (PubMed:8625415). Inhibited by retinoblastoma tumor suppressor protein, RB1 (PubMed:9858607). Binding to TAF7 or CIITA inhibits the histone acetyltransferase activity (PubMed:11592977, PubMed:22711989)
Phosphorylation results in activation of its activity (PubMed:10653665). Glucose 6-phosphate, fructose 6-phosphate, fructose 2,6-bisphosphate, ribulose 5-phosphate, and fructose 1,6-bisphosphate also act as activators (PubMed:10653665)
Formation of the GlnK-AmtB complex is influenced by intracellular pools of the effector molecules ATP, ADP, Mg(2+) and 2-oxoglutarate (PubMed:16864585, PubMed:20639578). The rapid drop in the 2-oxoglutarate pool upon ammonium influx and a simultaneous, but transient, change in the ATP/ADP ratio promotes AmtB-GlnK complex formation (PubMed:20639578). ADP orients the surface of GlnK for AmtB blockade (PubMed:17190799). The GlnK-AmtB interaction is also controlled by the level of intracellular glutamine and the uridylylation status of GlnK (PubMed:11847102, PubMed:14668330, PubMed:16864585). The uridylylation state of GlnK influences the dynamics of its interaction with AmtB, but association and dissociation of the complex in response to cellular nitrogen status can occur in the absence of GlnK post-translational modification (PubMed:25566239)
Unlike other bacteria, is not activated by GTP. UTP is a competitive inhibitor against UMP and a non-competitive inhibitor toward ATP
Apurinic/apyrimidinic (AP) endonuclease activity is enhanced with increasing concentrations of Mn(2+), while Zn(2+) initially enhances activity but subsequently inhibits activity in a concentration-dependent manner (PubMed:31386260). Co(2+) inhibits apurinic/apyrimidinic (AP) endonuclease activity at concentrations greater than 2.5 mM (PubMed:31386260)
Inactive when associated with isoform c. Dissociation from isoform c, which is dependent on the phosphorylation of the C-terminal hexapeptide, results in self-association and activation. Transient increase in Ca(2+) levels caused by axonal injury or synaptic activity triggers the dissociation of isoform a from isoform c; the dissociation may be influenced by the phosphorylation status of the C-terminal hexapeptide
Regulated by autophosphorylation, can both activate or decrease activity. Heme regulates its activity by enhancing the phosphorylation on Tyr-1004 and Tyr-1005
Strongly inhibited by non-esterified CoA (CoASH), acetyl-CoA and malonyl-CoA (PubMed:12095677). Also inhibited by palmitoyl CoA (PubMed:12095677). Inhibited by calcium hopantenate (PubMed:17379144)
Strongly inhibited by acetyl-CoA and modestly by malonyl-CoA (PubMed:16040613, PubMed:10625688, PubMed:12095677). Refractory to inhibition by both CoA and palmitoyl-CoA (PubMed:16040613). Inhibited by calcium hopantenate (PubMed:17379144)
Inhibited by the reaction product NADH. Inhibited by oxalate; this is a non-competitive inhibitor
An internal loop (autoregulatory loop) inhibits the catalytic activity of the enzyme by blocking the histone H3K9 substrate-binding pocket. Autocatalytic methylation of specific lysine residues in this loop promote a conformational switch that enhances the H3K9me activity of clr4
Regulated by reversible dimerization. Dimerization reduces its catalytic activity
Inhibited by Li(+), ADP, ATP and glucose-6-phosphate
Significantly inhibited by palmitoyl-CoA concentrations greater than 100 uM
Inhibited by the not secondly cleaved propeptide. Inhibited by m-guanidinomethyl-phenylacetyl-Arg-Val-Arg-(amidomethyl)-benzamidine (m-guanidinomethyl-Phac-RVR-Amb) and 4-guanidinomethyl-phenylacetyl-Arg-Tle-Arg-4-amidinobenzylamide (MI-1148). Inhibited by Decanoyl-Arg-Val-Lys-Arg-chloromethylketone (decanoyl-RVKR-CMK). Inhibited by heparin/heparan sulfate-binding
Is inhibited by Cu(2+), Zn(2+) and Fe(3+)
Inhibited by N,N,-dimethylsphingosine
Slightly inhibited by GlcNAc and N-acetylmuramic acid and strongly inhibited by N-acetylglucosaminolactone
Inhibited by diethyl pyrocarbonate, slightly by EDTA. Not inhibited by PMSF, diisopropyl fluorophosphate, 2-mercaptoethanol or N-ethylmaleimide
Strongly inhibited by diisopropylfluorophosphate (DFP) and to a lesser extent by PMSF, benzamidine and 4,6-diamidino-2-phenylindole. Low inhibition by hirudin
Does not show substrate inhibition at uroporphyrinogen III concentrations of up to 20 uM, in contrast to SUMT from Sinorhizobium (previously believed to be P.denitrificans)
Repressed by alpha-difluoromethylornithine (DFMO), 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB) and salicylaldehyde
Inactivated by piperonylic acid
Autoprocessing and proteolytic activity are completely inhibited by EDTA and 1,10-phenanthroline in vitro. Proteolytic activity is 3-fold enhanced by Ca(2+) due to stabilization of the protein structure but inhibited by an excess of Zn(2+) (PubMed:19919176). Inhibitory studies of karilysin identified several phage display-selected peptides with apparent inhibition constants (Ki) in the micromolar range, among which is the tetrapeptide SWFP (Ki=10.7 uM) (PubMed:23119051)
Stimulated by low concentrations of hydrogen peroxide (5 uM), ascorbate (0.1-0.3 mM), and sodium hydrosulfite (0.1 mM). Inhibited by high concentrations of hydrogen peroxide (0.1 mM), ascorbate (10 mM), and sodium hydrosulfite (1 mM)
Peroxidase activity is inhibited by aminobenzohydrazide (By similarity). The NADPH oxidase activity is calcium-dependent
Inhibited by CBL3 in a calcium-dependent manner (PubMed:18945934). Inhibited by 5'-methylthiotubercidin (MTT) and by formycin A (FMA) (PubMed:18342331)
Inhibited by isoleucine
Activity is stimulated by Mg(2+). Activated by K(+) in the presence of triethanolamine (pH 7.3)
Cytolysis of host cells is inhibited by cholesterol
Subject to autoinhibition, mediated by intramolecular interactions involving the SH2 and SH3 domains. Kinase activity is also regulated by phosphorylation at regulatory tyrosine residues. Phosphorylation at Tyr-409 is required for optimal activity. Phosphorylation at Tyr-520 inhibits kinase activity. Inhibited by PP1
Transferase activity occurs when RelA binds to a complex containing uncharged tRNA, ribosomes, and mRNA (RelA activating complex or RAC). The addition of charged tRNA to this complex has the opposite effect, inhibiting transferase activity and activating hydrolysis activity
Fibrinogenolytic activity is completely inhibited by EDTA, but not by PMSF
Strongly inhibited by 50 mM Zn(2+). Not inhibited by EDTA. Competitively inhibited by beta-alanine, 5-aminolevulinic acid (ALA), beta-aminoisobutyrate and 4-ureidobutyrate
Inhibited by PtdIns (product inhibition), phosphatidylinositol phosphate, and nucleoside di- and tri-phosphates
Activity is enhanced by 10 mM Co(2+), Cu 2(2+) and Mn(2+) to levels as high as 44% (PubMed:31110561). Partial inhibition of activity from 5 to 15% is observed in the presence of the following compouinds at a centration of 10 mM (from higher inhibition to lower): EDTA > Mg(2+) > urea, Zn(2+) > Fe(3+) (PubMed:31110561)
Activated by phosphorylation on Thr-806. Catalytically active only when complexed with MAP3K5, with MAP3K5 supporting the stability and the active configuration of MAP3K6 and MAP3K6 activating MAP3K5 by direct phosphorylation
Inhibited by mercuric ions
Amines and amino acids act as activators of catalytic activity, whereas natural product-based phenols, dithiocarbamates, aliphatic and aromatic carboxylates, boronic acids, and sulfonamides act as inhibitors of enzymatic activity. Also inhibited by anions such as cyanide and carbonate, and to a lesser extent by sulfate, phenylboronic, and phenyl arsonic acid
Inhibited by 49c, a hydroxyethylamine scaffold-based compound
(N-phenoxypropyl)-carboxamides such as carpropamid and derivatives of norephedrine act as inhibitors of scytalone dehydratase activity
Ras proteins such as HRAS mediate the activation of RAF proteins such as RAF1 or BRAF which in turn activate extracellular signal-regulated kinases (ERK) through MAPK (mitogen-activated protein kinases) and ERK kinases MAP2K1/MEK1 and MAP2K2/MEK2. Activation occurs through phosphorylation of Ser-218 and Ser-222. MAP2K1/MEK1 binds KSR1 or KSR2 releasing the inhibitory intramolecular interaction between KSR1 or KSR2 protein kinase and N-terminal domains (By similarity). This allows KSR1 or KSR2 dimerization with BRAF leading to BRAF activation and phosphorylation of MAP2K1 (By similarity). MAP2K1/MEK1 is also the target of negative feed-back regulation by its substrate kinases, such as MAPK1/ERK2. These phosphorylate MAP2K1/MEK1 on Thr-292, thereby facilitating dephosphorylation of the activating residues Ser-218 and Ser-222. Inhibited by serine/threonine phosphatase 2A
Formation of the GlnK1/Amt1 complex is decreased in the presence of Mg-ATP or 2-oxoglutarate. The presence of both effectors abolishes the formation of the complex
Strongly inhibited by Pb(2+) and weakly inhibited by Cu(2+), Hg(2+) and Fe(2+). Stable in presence of Ag(+)
Inhibited by UDP-Xylose
Uptake activity, but not antiporter activity, is inhibited by CCCP and N-ethylmaleimide (NEM). Uptake of putrescine is inhibited by high concentrations of ornithine
Enzyme activity is increased by liposomes containing anionic phospholipids, phosphatidic acid and cardiolipin. Inhibited by naringenin with an IC(50) of 5 uM (PubMed:22888116, PubMed:22935222). Enzyme activity is increased by cytochrome b5
Weakly inhibited by ATP (apparent Ki = 10 mm)
Inhibited by N-ethylmaleimide treatment
Inhibited by FR171456, a natural product with broad antifungal activity
Allosterically activated by GTP. Inhibited by UTP, 5-bromo-UTP and 5-iodo-UTP
Activated by the two-component regulatory system MalK/MalR in response to malate. The regulator MalR binds to the promoter region of maeN
Irreversibly inactivated by DL-propargylglycine
ATP and calmodulin are essential for its activation. Channel activity is inhibited by CFTR protein and by chloride inhibitors such as niflumic acid (NFA) and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) (By similarity). Activated by heat with activation seen at temperatures above 44 degrees Celsius (PubMed:22634729). Activated by BDNF in radial glial cells (PubMed:31147466)
The nuclease activity is inhibited by ATP or ADP
Inhibited by the lipoate analog 8-bromo-octanoate (BrO) (PubMed:17244193). Catalytic activity is increased in the presence of Mg(2+) (PubMed:17244193)
Symport activity is inhibited in the presence of the uncoupling agents carbonyl cyanide m-chlorophenylhydrazone (CCCP) and tetrachlorosalicylanilide and 2,4-dinitrophenol (PubMed:6282256). Activity is partially inhibited by N-ethylmaleimide (PubMed:7030324)
Inhibited by N-ethylmaleimide (PubMed:15314065). Strongly and specifically inhibited by ubiquitin variants UbV(SP.2) and UbV(SP.3) (PubMed:34425109). Also inhibited by UbV(SP.1); an ubiquitin variant that also inhibits STAMBPL1 (PubMed:34425109)
Inhibited by cinnamic acid derivatives
Zn(2+) inhibits the RNase activity while Mg(2+), Ca(2+), Mn(2+), K(+), Na(+), EDTA and EGTA show little effect on the exoribonuclease activity (PubMed:28322335)
Inhibited by EDTA, mercuric salts and by leucine. Inhibition by leucine is non-competitive with respect to 3-methyl-2-oxobutanoate and competitive with respect to acetyl-CoA, and is more sensitive at pH 6.5 than pH 8.5
Competitively inhibited by 9-cis-retinoic acid and 13-cis-retinoic acid
Inhibited by EDTA and O-phenanthroline. Not inhibited by PMSF, benzamidine, irreversible serine-proteinase inhibitors and cysteine proteinase inhibitor E-64 (By similarity)
Activity is enhanced by Mg(2+), being optimal with a concentration of 1-10 mM Mg(2+)
Shows competitive inhibition of GHBDH activity by the product succinic semialdehyde, and non-competitive inhibitions by the three other substrate-product combinations. The conversion of GHB to SSA is activated by two different saturating purified nudix hydrolases, B.methanolicus activator ACT and E.coli NudF. The nudix hydrolases do not activate the reverse reaction
The alpha-fibrinogenase activity is inhibited by EDTA, but not by pefabloc
Activated by phosphate ions and by potassium ions
Activated by tyrosine and threonine phosphorylation (By similarity). Hypoviruses like CHV1-EP713 induce inactivation by lowering the degree of phosphorylation in response to various environmental stresses
Two specific sites, one in the kinase domain (Thr-314) and the other in the C-terminal regulatory region (Ser-479), need to be phosphorylated for its full activation
Inhibited by threonine
Dependent on PFL-activase
Two specific sites, Thr-718 (activation loop of the kinase domain) and Thr-860 (turn motif), need to be phosphorylated for its full activation
Allosterically activated by ATP, by magnesium, and possibly also by other divalent metal cations
The switch between the enzymatic activity and the repressor activity is regulated by cellular demand for biotin. The switch occurs by swapping of protein interaction partners by holoBirA. In conditions of high biotin demand, holoBirA associates with apoBCCP to transfer biotin. In conditions of low biotin demand, holoBirA dimerizes, binds DNA and represses transcription of the biotin operon
Activity is unaffected by metalloprotease inhibitors 5 mM EDTA and 5 mM Zn(2+). Activity partially inhibited by 1,10-phenanthroline and 1,7-phenanthroline
Activated by magnesium and calcium, and inhibited by zinc, nickel and cobalt
Anions including Cl(-) and CH3COO(-), and SO4(2-) salts stimulate activity 20-40% at 100 mM
Inhibited by HgCl(2). Activity is recovered by the addition of 2-mercaptoethanol
May be regulated by calcium or a calmodulin-like protein
Inhibited by phosphoramidon (PubMed:18992253). Activated by K49-P1-20, a twenty-residue synthetic peptide shortened from the snake B.asper myotoxin II (PubMed:26931059)
Not inhibited by the DNA gyrase inhibitor novobiocin, instead inhibited by eukaryotic topoisomerase inhibitors such as m- and o-amsacrine, ellipticine, and the quinolone CP-115,953 (PubMed:7961685). Radicicol inhibits the ATPase activity (PubMed:16920739)
Not inhibited at high fructose concentration
Ribosome-associated GTPase is not affected by low levels of ppGpp, >40 uM ppGpp and >50 uM GDP inhibit GTPase (PubMed:18621905). The C-terminus (residues 387-607 or 481-607) inhibits GTPase activity, in its absence kcat increases, but GTPase is no longer stimulated by 70S ribosome or 30S or 50S subunits (PubMed:19803466)
Inhibited by quercetin
Inhibited by swainsonine but not by 1-desoxymannojirimycin
Inhibited by deoxyguanosine (dG), deoxythymidine (dT) and azidothymidine (AZT)
Activity is inhibited by phenylmethylsulfonyl fluoride (PMSF), but not by EDTA
Up-regulated by Ca(2+)/CaM
Inhibited by bisphosphonates
Inhibited by diphenyleneiodonium (DPI)
Inhibited by cobalt, copper and EDTA
Inhibited by reserpine
Inhibited by phosphonic acids and very slightly inhibited by aminophosphonic acids
Oxidoreductase activity is reduced by 50% in the presence of 2 mM UDP, 2 mM UDP-Glc or 3 mM UDP-GalNAc. Activity is unaffected by metal ions
Inhibited by pyridoxal 5'-phosphate and bathophenanthroline
Uridylyltransferase (UTase) activity is inhibited by glutamine, while glutamine activates uridylyl-removing (UR) activity. Uridylylation process is dependent on ATP and 2-oxoglutarate, which are effector molecules that likely bind to PII proteins and control their activity
Totally inhibited by EDTA in vitro
Inhibited by citrate
Kinase activity is inhibited by ASC24
The rate of FAD reduction is independent of the presence of HPA, demonstrating that, in contrast to HPAH from A.baumannii, the activity of the HPAH reductase is not allosterically regulated by the substrate
Inhibited by valine, sulfometuron methyl (SM), sulfonylureas (SU) and imidazolinones (IM). Pyrazosulfuron ethyl (PSE), promisulfuron methyl (PSM), sulfometuron methyl (SMM), metsulfuron methyl (MSM), and chlorimuron ethyl (CE) inhibited more than 80% of the activity
The glyoxalase activity is inhibited by copper and zinc cations, activated by ferrous cations, and inactivated by thiol-blocking reagents (PubMed:21696459, PubMed:7848303). The aminopeptidase activity is inhibited by iodoacetamide, dithiothreitol, EDTA and 1, 10-phenanthroline (PubMed:15550391). Binding of ATP at high temperatures induces a conformational change that reduces HchA surface hydrophobicity, interferes with its ability to capture substrate proteins and inhibits chaperone activity (PubMed:12235139)
(Microbial infection) Specifically inhibited by the cowpox virus Crma protein
Competitively inhibited by the antibiotic fosmidomycin
Inhibited by the serine protease inhibitors, antipain, aprotinin, DFP, leupeptin, STI and TLCK, and by the cysteine proteinase inhibitors DTNB and to a lesser extent E-64. Not inhibited by the metalloproteinase inhibitor EDTA
Is inhibited by the substrate analog pyrrole-2-carboxylate, and by 2-picolinate
Inhibited by p-hydroxybenzaldehyde (pHBA) and p-nitrophenol (pNP)
Inhibited by Cs(1+) and ivabradine. Is apparently not activated by cAMP or cGMP
Subject to feedback inhibition by dTTP
Activity is increased by oligomerization of the protein into filaments (PubMed:19900410). The oligomerization and the activity of the enzyme are inhibited by phosphorylation at Ser-222 (PubMed:12488245). Inhibited by its product, malonyl-CoA (PubMed:16854592). Activated by citrate (PubMed:16854592). Activation by MID1IP1 is citrate-dependent (PubMed:20457939). Soraphen A, inhibits the enzyme by preventing the formation of active filamentous oligomers (Probable)
Heparin and wedelolactone inhibit the myotoxic activity (PubMed:9920492). The PLA2 inhibitor, para-bromophenacyl bromide (BPB), inhibits the myotoxic activity (PubMed:9920492)
Inhibited during sporulation by acidification of the forespore, thus allowing accumulation of the spore's large depot of 3-phosphoglyceric acid
The first ATP-binding region has low ATPase activity. The second ATP-binding region is responsible for ATPase activity. ATP binding to the first ATP-binding region induces intrinsic activity of the second ATP-binding region. While ATP binding to the first ATP-binding region appears to prevent ATP hydrolysis by the second ATP-binding region, ADP-binding to first region promotes the coordinate and cooperative ATPase cycle of the second ATP-binding region. ATP binding to the first ATP-binding region induces a conformational change, promoting the rotation of the first ATP-binding region relative to the second ATP-binding region in the hexamer
Protein N-terminal methyltransferase activity is inhibited by GTP and GDP
Leucine uptake was inhibited by ileum, valine histidine and phenylalanine as well as by 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH) (a specific inhibitor of system L transport)
Inhibited by malate and nitrotyrosine by approximately 20% at the higher concentration. At 100 uM, canaline and carboxymethoxylamine inhibit aminotransferase activity by 35 and 70%, respectively. Addition of 1.0 mM carboxymethoxylamine lead to a complete inhibition of the aminotransferase activity
Adenylyltransferase activity is inhibited by the inhibitory helix present at the N-terminus: Glu-224 binds ATP and competes with ATP-binding at Arg-364, thereby preventing adenylyltransferase activity. Activation dissociates ATP-binding from Glu-224, allowing ordered binding of the entire ATP moiety with the alpha-phosphate in an orientation that is productive for accepting an incoming target hydroxyl side chain (By similarity)
Activity is inhibited by metalloprotease inhibitors and activated by Mg(2+) and Ca(2+)
Inhibited by serum and NaCl
Strongly and specifically activated by Cl(-) and Br(-), which act as positive allosteric effectors. Inactivated by metal-chelating agents
Cdc2 activity is required for activation
ATPase activity is stimulated by interaction with RNase E
Subject to allosteric regulation (By similarity). Low glucose and high fructose-6-phosphate triggers association with the inhibitor GCKR followed by sequestration in the nucleus (PubMed:10456334)
Inhibited by the 1,2,3-triazole urea covalent inhibitors KT109 and KT172 (By similarity). Inhibited by p-hydroxy-mercuri-benzoate and HgCl(2), but not by PMSF. Also inhibited by RHC80267, a drug that blocks 2-AG formation
Digests 23S rRNA in the absence of Mg(2+), increasing Mg(2+) concentrations decrease its efficiency
Inhibited by PMSF at 2 mM concentration but not by EDTA
Highly resistant to inhibition by potato carboxypeptidase inhibitor (PCI). Moderately inhibited by leech carboxypeptidase inhibitor (LCI) and tick carboxypeptidase inhibitor (TCI)
Bacterial binding activity is inhibited by D-galactose (PubMed:23886951). Hemagglutinating activity is independent of divalent cations Ca2(+) or Mg2(+). It is strongly inhibited by N-acetyl-D-galactosamine (GalNAc), D-galactose and D-talose, and to a lesser extent by melibiose and raffinose. Also inhibited by glycoprotein asialo-bovine submaxillary mucin (BSM). Not inhibited by D-glucose, D-fucose, D-galactitol, N-acetyl-D-glucosamine or lactose (PubMed:9568372, PubMed:26439416). Fungal binding activity is inhibited by D-galactose (PubMed:25482060). Cytotoxic activity against Raji cell line is completely inhibited by galactose, melibiose and raffinose, but not by glucose or lactose (PubMed:28636877). Galactose inhibits binding to laminin and BSM, but not to collagen, gelatin or fibronectin (Ref.3)
L-glutamine efflux and L-glutamine uptake are regulated by CO2/HCO3(-) through SLC4A4 leading to modulation of cytosolic pH and Na(+)concentration
Acyltransferase activity is regulated by the binding of GTP and Ca(2+): inactivated by GTP, which stabilizes its closed structure, thereby obstructing the accessibility of substrates to the active sites (PubMed:17179049). In contrast, Ca(2+) acts as a cofactor by inducing conformational change to the active open form. In absence of Ca(2+), Mg(2+) may bind Ca(2+)-binding sites, promoting GTP-binding and subsequent inhibition of the acyltransferase activity (By similarity)
Partially inhibited by 1,8-naphthalimide (NAP)
Inhibited by glutaconyl-CoA
The allosteric modulators NNC0640, PF-06372222 and MK-0893 inhibit the increase of intracellular cAMP levels in response to GLP-1
Inhibited by FK506 and its derivates, such as ascomycin, and rapamycin (PubMed:15664653, PubMed:15850699). FK506 and rapamycin inhibit peptidylprolyl isomerase activity but not chaperone activity (PubMed:15664653). Inhibited by N-(2-ethyl-phenyl)-2-(3H-imidazao [4, 5-b] pyridin-2-yl-sulfanyl)-acetamide (D44) (PubMed:23974147). Not inhibited by cyclosporin A (PubMed:15664653, PubMed:15850699). Inhibition of calcineurin phosphatase activity is enhanced by FK506 (PubMed:15850699)
The enzyme activity is strongly increased by double-stranded DNA (dsDNA), but not by single-stranded DNA or RNA (By similarity). DNA-binding induces the formation of liquid-like droplets in which CGAS is activated (By similarity). Liquid-like droplets also create a selective environment that restricts entry of negative regulators, such as TREX1 or BANF1/BAF, allowing sensing of DNA (By similarity). A number of mechanisms exist to restrict its activity toward self-DNA (PubMed:32911481, PubMed:32911480, PubMed:32913000). The nucleotidyltransferase activity is inhibited in the nucleus via its association with nucleosomes: interacts with the acidic patch of histones H2A and H2B, thereby blocking DNA-binding and subsequent activation (PubMed:32156810, PubMed:32911481, PubMed:32911480, PubMed:32913000). CGAS is also inactive when associated with mitotic chromatin (By similarity). Chromatin-bound CGAS cannot be activated by exogenous DNA in mitotic cells: phosphorylation of the N-terminal disordered part by AURKB during the G2-M transition blocks CGAS liquid phase separation and activation (By similarity). Activity toward self-DNA is inhibited by BANF1/BAF upon acute loss of nuclear membrane integrity: BANF1/BAF acts by outcompeting CGAS for DNA-binding, thereby preventing CGAS activation (PubMed:32156810). DNA-induced activation at micronuclei is also limited by TREX1, which degrades micronuclear DNA upon nuclear envelope rupture, thereby preventing CGAS activation (By similarity). Acetylation at Lys-372, Lys-382 and Lys-402 inhibits the cyclic GMP-AMP synthase activity (By similarity). Acetylation by KAT5 increases the cyclic GMP-AMP synthase activity by promoting DNA-binding and subsequent activation (By similarity). Phosphorylation at Ser-291 suppresses the nucleotidyltransferase activity (PubMed:26440888). Phosphorylation at Ser-420 promotes the cyclic GMP-AMP synthase activity (PubMed:32474700). Phosphorylation at Thr-52 and Ser-199 inhibits its cyclic GMP-AMP synthase activity (By similarity). Ubiquitination at Lys-372 via 'Lys-27'-linked polyubiquitination enhances the cyclic GMP-AMP synthase activity (By similarity). Monoubiquitination at Lys-335 promotes oligomerization and subsequent activation (PubMed:29426904). Sumoylation at Lys-335, Lys-372 and Lys-382 prevents DNA-binding, oligomerization and nucleotidyltransferase activity (PubMed:28095500). The enzyme activity is impaired by the cleavage by CASP1 (PubMed:28314590). In addition to DNA, also activated by collided ribosomes upon translation stress: specifically binds collided ribosomes, promoting its activation and triggering type-I interferon production (By similarity). In hematopoietic stem cells, binding to circular RNA cia-cGAS inhibits the cyclic GMP-AMP synthase activity (PubMed:29625897). Strongly inhibited by compound RU.521, which is specific for mouse protein (PubMed:28963528, PubMed:30007416)
Slightly activated by Ca(2+). Inhibited by divalent cations such as Zn(2+), Cu(2+), Fe(2+), Mg(2+), Mn(2+), but only slightly inhibited by EDTA
Negatively regulated by the anti-sigma-I factor RsgI3 (By similarity). Binding of the polysaccharide substrate to RsgI3 may lead to the release and activation of SigI3 (By similarity)
Contrary to other SAPs, SAP7 is insensitive to pepstatin A inhibition, which is due restriction of the accessibility of pepstatin A to the active site by Met-242 and Thr-467
Inhibited by rapamycin
Inhibited by high concentrations of prolinamide
Is inhibited by the chelating agent o-phenanthroline in vitro
The ATPase activity is regulated by monovalent cations and pH. Up-regulated by K(+) ions in a dose-dependent way. Down-regulated by Na(+) ions (PubMed:11341842). Inhibited by Na(+)/K(+)-ATPase inhibitor ouabain and H(+)/K(+)-ATPase inhibitor SCH-28080 with an intermediate sensitivity to completely resistant Na(+)/K(+)-ATPases and highly sensitive H(+)/K(+)-ATPases (PubMed:7485470, PubMed:8853415, PubMed:11341842)
Cerulenin, a potent non-competitive pharmacological inhibitor of FAS, binds covalently to the active site of the condensing enzyme region, inactivating a key enzyme step in fatty acid synthesis
Inhibited by 2-(1-ethyl-2-hydroxyethylamino)-6-benzylamino-9-isopropylpurine (roscovitine), 1-isopropyl-4-aminobenzyl-6-ether-linked benzimidazoles, resveratrol, AT-7519 and olomoucine. Activated by CDK5R1 (p35) and CDK5R2 (p39) during the development of the nervous system; degradation of CDK5R1 (p35) and CDK5R2 (p39) by proteasome result in down regulation of kinase activity, during this process, CDK5 phosphorylates p35 and induces its ubiquitination and subsequent degradation. Kinase activity is mainly determined by the amount of p35 available and subcellular location; reversible association to plasma membrane inhibits activity. Long-term inactivation as well as CDK5R1 (p25)-mediated hyperactivation of CDK5 triggers cell death. The pro-death activity of hyperactivated CDK5 is suppressed by membrane association of CDK5, via myristoylation of p35. Brain-derived neurotrophic factor, glial-derived neurotrophic factor, nerve growth factor (NGF), retinoic acid, laminin and neuregulin promote activity. Neurotoxicity enhances nuclear activity, thus leading to MEF2 phosphorylation and inhibition prior to apoptosis of cortical neurons. Repression by GSTP1 via p25/p35 translocation prevents neurodegeneration
Inhibited by p-chloromercuribenzoate and HgCl(2) and by Cu(2+) and Pb(2+) salts, unaffected by amino acids such as D-alanine and beta-alanine or by nucleotides or nucleosides
Severely inhibited by reagents which covalently modify Cys groups in proteins
During activation, the N-terminal disordered prodomain is removed by cleavage. Concomitantly, double cleavage gives rise to a large 18-kDa and a small 11-kDa subunit. The two large and two small subunits then assemble to form the active CASP6 complex. Can be cleaved and activated by different caspases, depending on the context. Cleaved and activated by caspase-8 (CASP8) and subsequently by caspase-3 (CASP3). Can also undergo autoactivation by mediating autocleavage at Asp-162 and Asp-176, while it is not able to cleave its N-terminal disordered prodomain. Intramolecular cleavage at Asp-176 is a prerequisite for CASP6 self-activation. Cleaved and activated by CASP1 in neurons, possibly in the context of inflammation. Phosphorylation at Ser-240 inhibits autocleavage, preventing caspase activation
Assembly into ribonucleoprotein complexes of high-molecular-mass (HMM) inhibits its enzymatic activity. Antiviral activity is neutralized by the HIV-1 virion infectivity factor (VIF) and simian immunodeficiency virus (SIV-cpz) VIF, that prevents its incorporation into progeny virions by both inhibiting its translation and/or by inducing its ubiquitination and subsequent degradation by the 26S proteasome (By similarity)
The tyrosine phosphatase activity is inhibited by sodium vanadate
Inhibited by the small molecule aphidicolin (PubMed:15135399). Activity is markedly inhibited by manganese ions (PubMed:15135399)
Activated particularly by Ca(2+) and Zn(2+), and to a lesser extent by Na(+), K(+), Mg(2+) and Cu(2+). Activation effect of the divalent metal ions Ca(2+), Zn(2+), Mg(2+) and Cu(2+) is reduced significantly by the addition of EDTA. Strongly inhibited by Mn(2+), Hg(2+) and Ag(+)
Inhibited by pyridochromanone
Activated by free Cu(II) ions and pH values above 8
Inhibited by normal intracellular concentrations of ATP
Strongly inhibited by 15-aza-dihydrogeranylgeraniol and 5-isopropyl-N,N,N,2-tetramethyl-4-(piperidine-1-carbonyloxy)benzenaminium chloride (Amo-1618). Inhibited by GGPP concentrations higher than 50 uM
In vitro, activated by tetrachlorohydroquinone (TCHQ) at low concentrations and inhibited at high concentrations (above 200 uM). However, PcpD would only be stimulated by tetrachlorohydroquinone (TCHQ) under in vivo conditions due to the toxicity of tetrachlorohydroquinone (TCHQ). Competitively inhibited by pentachlorophenol (PCP) in a concentration-dependent manner. PcpD is regulated by tetrachlorohydroquinone (TCHQ) and pentachlorophenol (PCP) using a mechanism, which maintains tetrachlorobenzoquinone at a level that would neither significantly decrease the biodegradation of pentachlorophenol (PCP) nor cause cytotoxicity in cells
Inhibited by phosphorylation (PubMed:16326698, PubMed:29899443). Citrate promotes oligomerization of the protein into filaments that correspond to the most active form of the carboxylase (PubMed:29899443). Inhibited by palmitoyl-CoA (PubMed:29899443)
Phosphatase activity is slightly inhibited by ADP, NADH and ATP, and moderately inhibited by NAD and 5'-AMP (PubMed:16192277). Kinase activity is slightly inhibited by ADP and NADP (PubMed:16192277)
Seems to be inhibited by acidic phospholipids
Inhibited by hydrolysis end products D-galactose and D-glucose. The hydrolysis of o-nitrophenyl-beta-D-galactopyranoside (ONPG) is slightly activated by monovalent ions, Na(+) and K(+). Concentrations of these ions in the range of 1-100 mM exert the stimulating effects. The presence of 1 mM Mn(2+) together with the presence of 10 mM Na(+) slightly stimulates the activity, while presence of 10 mM Mn(2+) inhibits the activity by about 40%
Significantly inhibited by the wheat xylanase inhibiting protein I (XIP-I) and the proteinaceous endoxylanase Triticum aestivum xylanase inhibitors I (TAXI-I), but not TAXI-II
Inhibited by lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P). Inhibited by EDTA and EGTA (Probable)
Inhibited by leupeptin and the cysteine protease inhibitor E64 (L-trans-epoxysuccinyl-leucylamide-(4-guanido)-butane)
Inhibited by gamma-tocopherol
Inhibited by ethylenediaminetetraacetic acid (EDTA) but not by serine, aspartic or cysteine protease inhibitors. Inhibited by high concentration of Zn(2+) (> 0.1 mM)
Activated by mkh1
Inhibited by Zn(2+) at 10 mM and by metal chelating agents EDTA and 1,10-phenanthroline
Activated by a Pi-dependent pyrophosphorylation and inactivated by an ADP-dependent phosphorylation on a regulatory threonine. Both reactions are mediated by the bifunctional serine/threonine kinase and phosphorylase PpsR
Degraded by Lon protease; degradation is inhibited in a HipA-HipB complex and when bound to the operator consensus sequence dsDNA
Activity is strongly inhibited by SRGAP2C, which heterodimerize with SRGAP2/SRGAP2A, thereby reducing SRGAP2/SRGAP2A levels through proteasome-dependent degradation
Is selectively inhibited by the gamma-phospholipase A2 inhibitor (PLI) CgMIP-I (AC P0DQP7) but not by the alpha-PLI CgMIP-II (AC P0DQP8)
In contrast to human ortholog, not inhibited by myricetin
Inhibited by excess of riboflavin or FMN. Also inhibited by protonophores such as CCCP and FCCP or in the absence of glucose
There is conflicting data about the effect of NAD cofactors on activity. PubMed:11441146 suggests that the redox state of the cell can modulate the transcriptional activity of the CLOCK-BMAL1 heterodimer; NADH and NADPH enhance the DNA-binding activity of the heterodimer. PubMed:23229515 reports that NADH and NADPH have no significant effect on DNA-binding activity of the CLOCK-BMAL1 heterodimer
10-fold more active in the presence of saturating ATP
Stimulated 3-fold by galactose and inhibited by vanadate, N-ethylmaleimide, and 5-methoxyindole-2-carboxylic acid
Inhibited by N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC)
Activity is increased at acidic pH (6.5) (PubMed:29791142). Inhibited in the presence of high extracellular K(+) (PubMed:29791142, PubMed:30914478)
Is inhibited by the antituberculous drug D-cycloserine (DCS), which is a structural analog of D-alanine (PubMed:20956591, PubMed:23286234). Is activated by K(+) (PubMed:23286234)
Calcium plays an important structural role, providing stability to this protein in the cytoplasm. Outside the cell, the decrease of the calcium concentration triggers the autoproteolysis. PrtV activity is increased by 25 mM of Sr(2+) or Mg(2+) and to some extent by Ba(2+); however, Ba(2+) inhibits PrtV at higher concentrations. Completely inhibited by EDTA and 1,10-phenanthroline
Two-fold decrease in activity in the presence of PPi, iodoacetate or para-chloromercuribenzoate
Channel activity is reduced by low extracellular/lumenal pH level (PubMed:19940139)
Inhibited by sodium borohydride
Inhibited by metal-chelating reagents. Strongly inhibited by 1 mM Zn(2+), slightly inhibited by 0.1 mM Zn(2+), not inhibited by 0.01 mM Zn(2+). Not inhibited by cobalt ions
Inhibited by divalent calcium or cadmium ions
Synthesis and activity are sensitive to the allosteric inhibitor lysine, one of the end metabolites of the aspartic acid family branched pathway
Inhibited by the mycotoxin fumonisin B(1), a sphingosine analog mycotoxins produced by pathogenic fungi (PubMed:26276842, PubMed:26635357). Activated by divalent cation such as magnesium Mg(2+), zinc Zn(2+), manganese Mn(2+) and calcium Ca(2+) (PubMed:26635357)
Activated by Ca(2+)/calmodulin. Binding of calmodulin results in conformational change that relieves intrasteric autoinhibition and allows phosphorylation of Thr-179 within the activation loop by cmkC
Dofequidar (MS-209) and ochratoxin A inhibited the 17beta-estradiol 17-O-(beta-D-glucuronate) influx
Produced as a latent enzyme which is activated by double stranded RNA (dsRNA) generated during the course of viral infection(PubMed:9880569). The dsRNA activator must be at least 15 nucleotides long, and no modification of the 2'-hydroxyl group is tolerated (PubMed:9880569). ssRNA or dsDNA do not act as activators (PubMed:9880569). Strongly inhibited by copper, iron and zinc ions (PubMed:11682059). Partially inhibited by cobalt and nickel ions (PubMed:11682059)
Activated by trypsin, chymotrypsin and subtilisin (PubMed:6798971, PubMed:6814426). Activated by alpha-chymotrypsin, thermolysin and Pronase. Inhibited by its product L-DOPA and tyrosine (PubMed:6814426)
Partially inhibited by Co(2+) or Zn(2+) and significantly inhibited by Ag(+), Cu(2+) and Hg(2+)
Esterase activity is significantly inhibited by the serine modifier phenylmethylsulfonyl fluoride (PMSF)
Inhibited by metalloporphyrins such as Sn-, Co-, Mn- and Zn-protoporphyrins
Angiopoietin binding leads to receptor dimerization and activation by autophosphorylation at Tyr-984 on the kinase activation loop
Activated by calmodulin in the presence of calcium ions
Inhibited by N-acetylglucosamine and not N-acetylgalactosamine
Inhibited by phenylmethanesulfonyl fluoride (PMSF). Not inhibited by EDTA, EGTA, beta-mercaptoethanol, indoacetamide, benzamidine, aprotinin, pepstatin A and trypsin inhibitor
Inhibited by the ATP analog flavopiridol, purvalanol A, purvalanol B, staurosporine and CR8
Competitively inhibited by SC-58272, a peptidomimetic derived from the N-terminal sequence of a natural substrate
Binding to MAS2 is required for catalytic activity (PubMed:9654444, PubMed:9299349). Inhibited by high levels (> 1uM) of zinc (PubMed:9654444). Inhibited by metal chelators ethylenediaminetetraacetic acid (EDTA) and O-phenanthroline (PubMed:9654444)
Inactivated by N,N-dialkylcarbamoyl-CoA substrate-product analogs
Activity is promoted by magnesium, Fe(2+), nickel, zinc and cadmium ions (PubMed:34467865). Completely inhibited by IAA (cysteine protease inhibitor), PMSF (serine protease inhibitor) and DEP (histidine protease inhibitor) (PubMed:34467865). Inhibited by CTAB, SDS and EDTA (PubMed:34467865). Inhibited by lithium, sodium, aluminum, potassium, calcium, manganese, Fe(3+), barium and mercury ions (PubMed:34467865)
Inhibited by malate, citrate, glutamate, NAD(+) and azaserine, but not by 2-2' dipyridil and N-ethylmaleimide
The covalent binding to the substrate at Lys-342 causes inactivation of the enzyme, and possibly serves as a signal for the export of the protein. Inhibited by fluoride ion
Inhibited by fructose 6-P, activated by glycerol 3-P
Transport activity is induced by farnesoid X receptor (FXR) agonists such as chenodeoxycholate
Inhibited by manganese, copper, mercury, and iron ions
Reducing the electrochemical proton gradient across the plasma membrane by the addition of the protonophore carbonyl cyanide m-chlorophenylhydrazone (CCCP) leads to a drastic reduction in the rate of inosine excretion
Activated in response to stimuli that lead to increased intracellular Ca(2+) levels; this activation is indirect and may be mediated by calcium-mediated production of reactive oxygen species (ROS). Activated by autophosphorylation at Tyr-402; this creates a binding site for SRC family kinases and leads to phosphorylation at additional tyrosine residues. Phosphorylation at Tyr-402, Tyr-579 and Tyr-580 is required for optimal kinase activity
Regulated by at least two independent mechanisms. First, it is inactivated via its interaction with securin/PTTG1, which probably covers its active site. The association with PTTG1 is not only inhibitory, since PTTG1 is also required for activating it, the enzyme being inactive in cells in which PTTG1 is absent. PTTG1 degradation at anaphase, liberates it and triggers RAD21 cleavage. Second, phosphorylation at Ser-1121 inactivates it. The complete phosphorylation during mitosis, is removed when cells undergo anaphase. Activation of the enzyme at the metaphase-anaphase transition probably requires the removal of both securin and inhibitory phosphate (By similarity)
Activated by RNAs having enough uridines
Channel activity is inhibited by interaction with Ca(2+)-bound calmodulin (PubMed:10880439, PubMed:27325704, PubMed:27005320, PubMed:27618660). Interaction of a single pore-forming alpha subunit with a calmodulin chain is sufficient to promote channel closure (PubMed:10880439). Channel activity is not regulated by cyclic nucleotides (By similarity). Channel activity is inhibited by binding intracellular phosphatidylinositol-3,5-bisphosphate and phosphatidylinositol-4,5-bisphosphate (PIP2), but is not inhibited by phosphatidylinositol 4-phosphate (PubMed:27005320). Inhibited by the spider kappa-theraphotoxin-Aa1a and mu/kappa-theraphotoxin-Ap1a (PubMed:30149017)
Activated by phosphorylation by CDKF-1. Down-regulated by phosphorylation by WEE1
Inhibited by p-chloromercuribenzoate but not by cloxacillin
May be activated by phosphorylation
Regulated by Mg(2+) ions, cytosolic Mg(2+) selectively inhibits outward current while lysosomal Mg(2+) modestly inhibits both the outward and inward currents. In the absence of Mg(2+), NAADP readily activates TPCN2, with properties similar to PI(3,5)P2 (PubMed:24502975). Na(+) current is inhibited by ATP in a MTORC-dependent manner. ATP sensitivity is independent of PI(3,5)P2 (PubMed:23394946). Both current elicited by PI(3,5)P2 as well as NAADP are inhibited by tetrandrine
Counter-exchange transport activity is saturable and inhibited by pyridoxal-5'-phosphate, EDTA and EGTA (PubMed:26140942, PubMed:26444389). Activated by calcium Ca(2+) and manganese Mn(2+) ions, and slightly by iron Fe(2+) and zinc Zn(2+) ions (PubMed:26140942, PubMed:28695448, PubMed:26444389). Repressed by copper ions Cu(2+) and slightly by magnesium Mg(2+) ions (PubMed:28695448). Magnesium Mg(2+) ions promotes slightly ATP uptake, ATP-Mg(2+) being exchanged with ATP(4-) (PubMed:26444389)
Inhibited by UDP-phenol and NaBH3CN
Inhibited by antipain and leupeptin
Inhibited by 5',5'-dithio-bis(2-nitrobenzoic acid) (DTNB) and 4-(hydroxymercuri)benzoic acid (p-HMB)
In colonic crypts activated by low pHi, hyperosmolarity, and an increase in intracellular cAMP levels
Inhibited by 5'-deaza-1'-aza-2c-deoxy-1'-(9-methylene) immucillin-H (DADMe-ImmH)
(Microbial infection) Kinase activity is enhanced by alphavirus genomic RNA sequences (PubMed:16601681). Kinase activity is stimulated upon binding to uncharged tRNAs (PubMed:16601681). Activated by serum starvation (in vitro) (PubMed:10504407)
Not inhibited by Tyr, Phe or Trp
Constitutively active and not activated by phosphorylation
Activated by light-induced dephosphorylation. Inhibited by dark-induced phosphorylation. Both reactions are catalyzed by PDRP1 (By similarity). Very cold-tolerant
Activated by phosphorylation on Thr-211. Activated by phosphorylation at Ser-600 AKT1 during glucose starvation; the relevance of such activation in normal cells is however unsure
The redox state of the cell can modulate the transcriptional activity of the CLOCK-BMAL1 and NPAS2-BMAL1 heterodimers; NADH and NADPH enhance the DNA-binding activity of the heterodimers
Tris(hydroxymethyl)aminomethane (Tris) is a competitive inhibitor of the reaction
Inhibited by clavulanic acid and sulbactam
Inhibited by high substrate concentrations (100 mg/ml). No effect on activity with various EDTA concentrations (0-1 mM). 20-fold higher activity when cells grown on TOS than when cells grown on galactose, glucose and lactose
Inhibited by 100 uM quinine. Slightly inhibited by Ba(+) (PubMed:17452494). Activity is first increased and then decreased when the extracellular pH is lowered to 6.0 (PubMed:17452494, PubMed:22948150)
Interaction with KaiA stimulates autophosphorylation, KaiC interaction with KaiB sequesters KaiA, preventing it stimulating the KaiC kinase, leading to autodephosphorylation. A KaiA dimer is sufficient to enhance KaiC phosphorylation (PubMed:15347812, PubMed:12391300, PubMed:12727878, PubMed:12727879). Interaction of KaiA with the A-loop stimulates autokinase activity (PubMed:18728181)
SUMT exhibits a substrate inhibition phenomenon at uroporphyrinogen III concentrations above 0.5 uM; this property might play a regulatory role in cobalamin biosynthesis
Activated by NDFIP1- and NDFIP2-binding (PubMed:25632008). Activated by PI4K2A-binding (By similarity). Inhibited by DTX3L-binding (By similarity). Inhibited by N4BP1 binding (PubMed:17592138)
Allosteric activation by glucose-6-phosphate. Phosphorylation reduces the activity towards UDP-glucose. When in the non-phosphorylated state, glycogen synthase does not require glucose-6-phosphate as an allosteric activator; when phosphorylated it does
Enzymatic activity is induced by 25-hydroxycholesterol, cholestyramine and lovastatin
Binding of glucose is strongly inhibited by galactose and mannose
Inhibited by metal ion chelators EDTA and 1,10-phenanthroline, bradykinin analogs, cysteine, CONA65, and several hydroxamate compounds, particularly tyrosine hydroxamate. Not inhibited by 3,4-dichloroisocourmarin, soybean trypsin inhibitor, or the cysteine proteinase inhibitors iodoacetic acid and E-64
Flipping activity is inhibited by increasing concentrations of gentiobiose, a disaccharide with the same chemical composition and conformation as the anchor-LLD headgroup. Not inhibited by other disaccharides such as lactose, sucrose and trehalose at a similar concentration
Activation requires a combination of a divalent cation, magnesium or manganese, and a monovalent cation, potassium or ammonium. Above the optimum concentration for activation, magnesium and manganese are rather inhibitory. Also activated by 2-mercaptoethanol, dithiothreitol, cysteine and glutathione. Inhibited by divalent cations (mercury, cobalt, zinc, copper, silver), chelating agents (EDTA, EGTA and o-phenanthroline), and analogs of beta-alanine (taurine, gamma-aminobutyrate, gamma-amino-beta-hydroxybutyrate)
Riboflavin transport is Na(+)-independent but moderately pH-sensitive (PubMed:20463145). Activity is strongly inhibited by riboflavin analogs, such as lumiflavin (PubMed:20463145). Weakly inhibited by flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) (PubMed:20463145)
Inhibited by D-saccharic acid 1,4-lactone and taurocholic acid
Target ssRNase is inhibited by EDTA
Inhibited by 4,5 dithiohydroxyphthalic acid (DTHPA) analogs, which bind to the catalytic iron site of the [4Fe-4S] cluster
Competitive inhibition of adenine transport by isopentenyladenine, kinetin, benzylaminopurine, trans- and cis-zeatin and trans-zeatin riboside
Inhibited by quisqualate
Directly inhibited by juglone anti-parasite drug. Not inhibited by buparvaquone anti-parasite drug
Inhibited by nipecotic acid, cis-3-aminocyclohexane carboxylic acid and 2,4-diaminobutyric acid
Autoinhibited. Intramolecular binding of the interdomains A and B (also called linker region) to parts of the catalytic domain keep the catalytic center in an inactive conformation. The phosphorylation of the interdomains or the binding of the SH2 domains with dually phosphorylated ITAM domains on transmembrane proteins disrupt those intramolecular interactions allowing the kinase domain to adopt an active conformation. The phosphorylation of SYK and of the ITAM domains which is responsible for SYK activation is essentially mediated by SRC subfamily kinases, like LYN, upon transmembrane receptors engagement. May also be negatively regulated by PTPN6 through dephosphorylation. Downstream signaling adapters and intermediates like BLNK or RHOH may mediate positive and/or negative feedback regulation. Negatively regulated by CBL and CBLB through ubiquitination and probable degradation. Phosphorylates SH3BP2 which in turn may regulate SYK through LYN (By similarity)
Inhibited by 1,10-phenanthroline and EDTA
Inhibited by validoxylamine A, a non-reactive trehalose analog
Activated by calcium (PubMed:9247932). Upon calcium binding to the EF-hand domains, the C-terminus of the junction domain (J domain) undergoes a conformational change which results in the dissociation of the pseudo-substrate inhibitory motif from the catalytic domain. This, in turn, may facilitate the autophosphorylation of the activation loop at Thr-232, which leads to the kinase activation (By similarity)
Insensitive to okadaic acid (PubMed:15808505). Deubiquitination by WDR48-USP12 complex positively regulates PHLPP1 stability (PubMed:24145035)
Activated by 3'phosphoglycerate, inhibited by orthophosphate. Allosteric regulation (By similarity)
Under physiological conditions, G3BP1 adopts a compact state that is stabilized by intramolecular interactions between the RG-rich and the acidic regions that inhibit phase separation (PubMed:32302570, PubMed:32302571, PubMed:32302572). Upon stress, polysomes disassemble and mRNAs are released in an unfolded protein-free state (PubMed:32302570, PubMed:32302571, PubMed:32302572). Binding of unfolded mRNA to G3BP1 outcompetes the intramolecular interactions and RNA-bound G3BP1 adopts an expanded conformation in which the RG-rich region becomes exposed to engage in protein-protein and protein-RNA interactions, allowing physical cross-linking of RNA molecules to form protein-RNA condensates, leading to liquid-liquid phase separation (LLPS) (PubMed:32302570, PubMed:32302571, PubMed:32302572)
Protease activity is inhibited by PMSF, suggesting this is a serine protease
Sortase activity is regulated by monomer-homodimer equilibrium. Mutant cells with monomeric SrtA display more adhesive proteins on the cell surface and are more invasive than wild-type cells, which have majority of SrtA in dimeric form. Dimerization may suppress the enzymatic activity on cell membranes (PubMed:26129884). Stimulated by calcium ions, which promote substrate binding (PubMed:11371637, PubMed:16269411). Calcium ions bind to SrtA and modulate both the structure and dynamics of a large active site loop (PubMed:16269411). Can also be stimulated, to a lesser extent, by Mg(2+) and Mn(2+) (PubMed:11371637). Inhibited by sulfhydryl-modifying reagents (PubMed:10535938, PubMed:10446208)
Activated by calcium (PubMed:15137943). Upon calcium binding to the EF-hand domains, the C-terminus of the junction domain (J domain) undergoes a conformational change which results in the dissociation of the pseudo-substrate inhibitory motif from the catalytic domain (By similarity). This, in turn, may facilitate the autophosphorylation of the activation loop at Thr-234, which leads to the kinase activation (By similarity). Intracellular calcium increase is triggered by xanthurenic acid (XA), a small mosquito molecule that induces the differentiation of specialized transmission stages, the gametocytes, into male and female gametes (Probable). Activated by a decrease in temperature (20 degrees Celsius) and an increase in pH (7.6) occurring when the parasite is ingested by in the mosquito (By similarity)
Inhibited by diethyldithiocarbamate and kojic acid
Inhibited by both FK506 and rapamycin. Binds FK506 with 15-fold lower affinity than FKB1
Exhibits synergistic gating by Ca(2+) and voltage (By similarity). Inhibited by some non-specific cation channel blockers such as: ruthenium red, 2-aminoethyl diphenylborinate (2APB), gadolinium and cadmium ions (By similarity)
(Microbial infection) Activated by SARS coronavirus-2/SARS-CoV-2 spike protein
Sequentially activated from an inactive dimer (Zur(2):Zn(2)) to a partially active asymmetric dimer (Zur(2):Zn(3)), and finally to the fully zinc-loaded active form (Zur(2):Zn(4)). Binds a maximum of 4 Zn(2+) ions per dimer
Inhibited by acetyl-CoA
Transport of glycerol is blocked by mercuric ions (Hg(2+)) but not N-ethylmaleimide
Inhibited by the bisphosphonate inhibitor BPH-629
By hypertonicity (By similarity). Activation requires autophosphorylation of Ser-380, that may be regulated by calcium. Phosphorylation of Ser-376 also promotes increased activity (By similarity)
Repressed by leupeptin, a peptidic cysteine, serine and threonine protease inhibitor (PubMed:16793521). Resistant to proteolysis mediated by pepsin and chymotrypsin but degraded by trypsin (PubMed:16793521)
Down-regulated by K(+)-competitive acid blockers (P-CABs) such as vonoprazan
Inhibited by sodium fluoride (NaF)
Activation of CDK1, appears to be an upstream event of AURKA activation (By similarity). Phosphatase inhibitor-2 (PPP1R2) and TPX2 act also as activators (By similarity). Inactivated by the G2 checkpoint (By similarity). Inhibited by GADD45A and p53/TP53, and through dephosphorylation by protein phosphatase type 1 (PP1) (By similarity). MLN8054 is also a potent and selective inhibitor (By similarity). Activated during the early phase of cilia disassembly in the presence of FBXL7 and PIFO (By similarity). Inhibited by the small molecule inhibitor VX-680 (By similarity)
1 mM DTT required for activity. Activated by ATP and inhibited by iodoacetamide
Inhibited by phenylethyl thio-beta-D-galactoside (PETG), isopropyl thio-beta-D-galactoside (IPTG), L-ribose, D-galactonolactone, lactose and 2-amino-D-galactose
Present in an inactive conformation in the absence of bound ligand. KITLG/SCF binding leads to dimerization and activation by autophosphorylation on tyrosine residues. Activity is down-regulated by PRKCA-mediated phosphorylation on serine residues. Inhibited by imatinib/STI-571 (Gleevec) and sunitinib; these compounds maintain the kinase in an inactive conformation
Treatment with the His-directed reagents diethyl pyrocarbonate (DEPC) and dichloro-(2,2*:6*,2(-terpyridine))-platinum(II) dihydrate inhibits kinase activity, including autophosphorylation
The uptake activity is inhibited by divalent metal ions such as Ca(2+), Mg(2+) and Ni(2+)
Activated by salicylate
Is active at both alkaline and acidic pH. Activity is inhibited by 4,4'-Di-isothiocyanatostilbene-2,2'-disulfonic acid (DIDS - an inhibitor of several anion channels and transporters)
Activated by Thr-177 phosphorylation and Tyr-24 dephosphorylation (By similarity). Rapidly down-regulated prior to cell differentiation (e.g. erythroid and osteoblast) (By similarity)
ATPase activity is stimulated in the presence of linear dsDNA (PubMed:22135300). Helicase activity requires the presence of NurA (PubMed:22135300)
Activated by phosphorylation at Tyr-216. In response to insulin, inhibited by phosphorylation at Ser-9 by PKB/AKT1; phosphorylation at this site causes a conformational change, preventing access of substrates to the active site. Inhibited by lithium
Addition of ZnSO(4) decreases the activity to 70%
Requires N-acetyl-L-glutamate (NAG) as an allosteric activator. Activated by glycerol in the absence of NAG, whereas in the presence of NAG it is inhibited by increasing concentrations of glycerol
Regulated at the post-transcriptional level
Inhibited by N-acetylserotonin and to a lesser extent by melatonin
Not inhibited by ARL 67156
Competitively inhibited by ATP, GTP and TTP
The apoenzyme can be activated in vitro in the presence of nickel ions and carbon dioxide, which promotes carboxylation of 'Lys-217' of the UreC (alpha) subunit
Requires chloride ions for optimal activity
Carbonic anhydrase (CA) activity is probably under redox control to remain inactive in the cytoplasm. Carbonic anhydrase (CA) activity of full-length protein and N-terminal fragment is inhibited by ethoxyzolamide. N-terminal fragment CA activity is activated under oxidizing conditions and inhibited under reducing conditions
Inhibited by glycyrrhetinic acid (derived from liquorice)
Feed-back regulated by NAD. At high levels of NAD the RN kinase activity is inhibited
Feedback inhibited by glycine and alanine, and inhibited by low concentrations of methionine sulfoximine
Oxydation of 20-HETE is inhibited by low concentrations of N-heptylformamide (PubMed:16081420). Oxydation of 20-HETE is a decreased by 55-65% by either all-trans-retinol or all-trans-retinoic acid. Strongly inhibited by omega-hydroxy fatty acids (By similarity)
Inhibited by sulfatide (PubMed:19168031). Kinase activity is increased by phosphorylation by MAPK2 upon PMA or EGF treatments (PubMed:17311928)
Glutamate to glutamine ratio influences catalytic activity (PubMed:19895308). At glutamate to glutamine ratios greater than 4, decarboxylase activity ceases (PubMed:19895308). In the presence of manganese, synthetase activity is limited to concentrations between 10 mM and 20 mM, whereas decarboxylase activity is not affected (PubMed:19895308). Both catalytic activities are inhibited by avidin (PubMed:19895308)
Activated by manganese ions, inhibited by iodoacetic acid
The catalytic activity is increased by manganese cathions, but strongly inhibited by other metal ions such as cupper, aluminum, silver, iron, nickel, zinc and magnesium cathions
Activated by hypophosphorylated form of ATG13 (present in nitrogen starvation conditions). Also activated by autophopsphorylation of Thr-226 and inhibited by phosphorylation of Ser-34
Inhibited by phosphoadenosine 5'-phosphate (PAP)
K(+), Ca(2+), Mg(2+) and Mn(2+) increase enzyme activity while Cu(2+) and Zn(2+) inactivate the enzyme
Activated by Mn(2+) ions
Activated by Mg(2+) ions. Inhibited by metal-chelating agents such as EDTA, EGTA, 1,10-phenanthroline, 2,2'-dipyridyl, and by PtCl4 and KPdCl4 as well as Ni(2+) and Co(2+). Also inhibited by iodoacetamide, N-tosyl-L-phenylalanine chloromethyl ketone, and 5,5'-dithiobis(2-nitrobenzoic acid), as well as glutamycin
Activity is modulated by MzrA (PubMed:19432797, PubMed:20889743). In the presence of 0.2 M NaCl, 2.0 mM sodium cholate (bile salts) decreases expression from the ompC promoter; how this is mediated is unknown (PubMed:28423182). Autophosphorylation is inhibited by the angucycline antibiotic waldiomycin in a non-competitive manner; waldiomycin prevents dimerization of the cytoplasmic domain and autophosphorylation (PubMed:27999439)
Cyclic di-AMP is a negative regulator of the Kdp system
Na(+) increases lipase activity (PubMed:1748875). Inhibited by diethyl p-nitrophenyl phosphate and 3,4-dichloroisocoumarin (DCI) (PubMed:1576157, PubMed:1748875)
The matrix-open state (m-state) is inhibited by the membrane-permeable bongkrekic acid (BKA) (PubMed:30611538). The cytoplasmic-open state (c-state) is inhibited by the membrane-impermeable toxic inhibitor carboxyatractyloside (CATR) (PubMed:30611538)
Homodimerization via the leucine zipper domains is required for autophosphorylation of multiple sites in the activation loop and subsequent activation. Autophosphorylation at Thr-312 is the key step in activation of MAP3K9/MLK1 and is required for full phosphorylation. Autophosphorylation at Thr-304 and Ser-308 have been shown to be of secondary importance in the activation of MAP3K9/MLK1. CEP-1347 and many indolocarbazole analogs have been shown to act as inhibitors of MAP3K9/MLK1 activity
Both CHA aldolase and oxaloacetate decarboxylase activity are activated in the presence of phosphate ion, and inhibited by N-ethylmaleimide. CHA aldolase activity is also inhibited by oxaloacetate with a Ki value of 23 uM; thus, the amount of oxaloacetate in the cells might control the production of oxaloacetate from CHA
In the resting state, through the dimerization of its C-terminal domain, HSP90 forms a homodimer which is defined as the open conformation (PubMed:18400751). Upon ATP-binding, the N-terminal domain undergoes significant conformational changes and comes in contact to form an active closed conformation (PubMed:18400751). After HSP90 finishes its chaperoning tasks of assisting the proper folding, stabilization and activation of client proteins under the active state, ATP molecule is hydrolyzed to ADP which then dissociates from HSP90 and directs the protein back to the resting state (PubMed:18400751). Co-chaperone TSC1 promotes ATP binding and inhibits HSP90AA1 ATPase activity (PubMed:29127155). Binding to phosphorylated AHSA1 promotes HSP90AA1 ATPase activity (PubMed:29127155). Inhibited by geldanamycin, Ganetespib (STA-9090) and SNX-2112 (PubMed:29127155, PubMed:12526792)
Each monomer can bind on GSH molecule but only one subunit is catalytically active
Inhibited strongly by Cu(2+), Zn(2+), Cd(2+) and Ni(2+) ions. No effect on activity with Na(+), Li(+), K(+), Ca(2+), Mg(2+) or Mn(2+) ions
Strongly inhibited by aryl-substituted MTA analogs, alkyl-substituted MTA analogs, 5'-methylthioformycin, 5'-chloroformycin, S-formycinylhomocysteine, 5'-methylthiotubercidin, S-tubercidinylhomocysteine and S-8-aza-adenosylhomocysteine. Poorly inhibited by 5'-isobutylthioinosine, 5'-n-butylthioinosine, 5'-methylthio-3-deaza-adenosine, 5'-isobutylthio-3-deaza-adenosine, S-n-6-methyl-3-deaza-adenosylhomocysteine, S-adenosylhomocysteine sulphoxide and Sinefungin
Accumulates in an inactive autophosphorylated state. The presence of spermine results in a dose-dependent reduction in autophosphorylation
In contrast to allele 1, does not undergo autocatalytic cleavage within the FIIND domain and its mode of activation remains unclear (PubMed:32558991). In contrast to alleles 1 and 2, allele 3 is not activated by Val-boroPro (Talabostat, PT-100) (PubMed:31383852). Not activated by cleavage by B.anthracis lethal toxin (LT) endopeptidase (PubMed:16429160, PubMed:23230290, PubMed:31383852). Not activated by metabolic inhibitors, such as 2-deoxy-D-glucose and sodium azide (PubMed:23230290)
Allosterically feedback inhibited by L-lysine and L-threonine individually and also subject to a concerted feedback inhibition by these amino acids
Activated by RHOA binding (By similarity). Inhibited by Y-27632
KSH activity is completely inhibited by zinc ions. KshA is specifically inhibited by Fe(3+), Co(2+), Zn(2+) and Ni(2+) ions
Activated by ATP (PubMed:27551084). ATP binding leads to a conformational change that promotes FAD cofactor binding and enzyme activity (PubMed:27551084). ATP binding likely occurs during acox-1.2 folding and/or dimer formation (PubMed:27551084). The preference for processing substrates with shorter fatty acid chains is likely due to the closed conformation of the active site (PubMed:27551084)
Inhibited by diethylpyrocarbonate, p-chloromercuribenzoate, Hg(2+) and Cu(2+). Not inhibited by the chelating reagents EDTA, 2,2'-dipyridyl, 1,10-phenanthroline, 8-hydroxyquinoline and tiron
Kinase activity is activated upon binding to Rho proteins (RHOA, RHOB and RAC1). Activated by lipids, particularly cardiolipin and to a lesser extent by other acidic phospholipids. Activated by caspase-3 (CASP3) cleavage during apoptosis. Two specific sites, Thr-778 (activation loop of the kinase domain) and Ser-920 (turn motif), need to be phosphorylated for its full activation
Contains three consecutive and one non-consecutive disulfide bonds and shows a strong dependence on DsbC for its full activity (PubMed:15642731). Competitively inhibited by tartaric acid and by sodium fluorid (PubMed:6282821, PubMed:8387749)
Displays feedback inhibition by L-serine
Completely inhibited by thiol-reducing agents, such as DTT and 2-mercaptoethanol. Activity was also inhibited by sodium orthovanadate, sodium molybdate, N-ethylmaleimide, EDTA and zinc ion, but was not inhibited by okadaic acid
Activated by Ca(2+)/calmodulin. Binding of calmodulin results in conformational change that relieves intrasteric autoinhibition and allows phosphorylation of Thr-196 within the activation loop by CaMKK1 or CaMKK2. Phosphorylation of Thr-196 results in a 10-20-fold increase in total activity to generate Ca(2+)/calmodulin-independent activity. Autophosphorylation of the N-terminus Ser-11 and Ser-12 is required for full activation. Inactivated by protein phosphatase 2A (PPP2CA/PPP2CB) which dephosphorylates Thr-196, thereby terminating autonomous activity and helping to maintain the enzyme in its autoinhibited state (By similarity)
The flippase activity is inactivated by caspase-mediated cleavage in apoptotic cells, allowing for PS exposure on the cell surface and engulfment of apoptotic cells by macrophages. The ATPase activity is up-regulated by aminophospholipids PS and PE and down-regulated by Increasing intracellular Ca2+ levels
Inhibited by ADP. Active in the presence of ATP (PubMed:16951743). Cold labile, it dissociates into inactive monomers at low temperature (By similarity)
GSH transferase activity is inhibited by S-hexyl glutathione
Activated by peptide binding to the PDZ domain
66% inhibition by 5 mM Zn(2+)
Inhibited by L-N-acetylproline and by D-N-acetylproline
The quaternary structure is constitutionally similar to the active conformation of allosteric LDHs, and the regulation is independent of the fructose 1,6-bisphosphate-binding site
Activated by 10 mM sodium bicarbonate
Phosphorylation of the transporter leads to changes in its substrate affinity, resulting in a regulation of the transport activity (PubMed:15389554). In contrast with rat ortholog, ASP uptake is inhibited by protein kinase A (PKA) and C (PKC) activation (PubMed:15389554). ASP uptake is also endogenously activated by calmodulin, the calmodulin-dependent kinase II and LCK tyrosine kinase (PubMed:15389554). Inhibited by cGMP, most likely through a cGMP-binding protein that interacts with OCT1 (By similarity)
Inhibited by p-chloromercuribenzoic acid, monoiodoacetic acid, mercury and nickel ions
Activity is strongly promoted by Co(2+), Ni(2+), Mg(2+), Mn(2+), Ca(2+), Zn(2+) and Cu(2+) (PubMed:27322068). Activity is inhibited by EDTA (PubMed:27322068)
Hyaluronidase activity is inhibited by Mn(2+), Cu(2+) and Fe(3+)
ATPase activity is stimulated by Cu(+) ions
The CARD domain inhibits the activation of E3 ubiquitin ligase activity by preventing RING domain dimerization and E2 ubiquitin donor binding and activation. The CARD domain-mediated autoinhibition of the E3 ubiquitin-protein ligase activity suppresses cell proliferation and migration. USP19 regulates the stability of BIRC2/c-IAP1 by preventing its ubiquitination
Diadenylate cyclase activity is inhibited by the interaction with RadA (By similarity). Diadenylate cyclase activity is not affected by ssDNA or dsDNA, but three- and four-way junctions strongly inhibit the activity of DisA, suggesting the enzyme is regulated by branched nucleic acids
Sugar binding is accompanied by a dramatic hinge-bending movement that enhances interactions with Mg-ATP
Inhibited by peptidomimetic inhibitor WEHI-842 (PubMed:26214367). Inhibited by Cu(2+) and Hg(2+) (PubMed:25447707)
Activation of CadC requires two stimuli, lysine and low pH (PubMed:18086202, PubMed:21216950, PubMed:21486484, PubMed:24056175). CadC shows an extremely low affinity for lysine, and it senses the extracellular lysine not directly but indirectly via interaction with the lysine permease LysP (PubMed:18086202). At a low external lysine concentration, CadC is inactivated by an interaction with LysP. When lysine is abundantly available, the interaction between LysP and CadC is released, and CadC becomes susceptible to activation by low pH (PubMed:18086202, PubMed:24056175). Acidification of the external milieu is sensed by protonation of a patch of acidic amino acids within the periplasmic domain and associated to conformational and/or oligomerization effects (PubMed:21216950). The pH-dependent regulation may be due to the presence/absence of a disulfide bond within the periplasmic domain (PubMed:21486484). At pH 7.6, a disulfide bond is found in the inactive state of CadC. At pH 5.8, disulfide bond formation is prevented, which transforms CadC into a semi-active state with respect to both the pH and the lysine stimuli (PubMed:21486484). Activity is also feedback inhibited by cadaverine (PubMed:22999955). Cadaverine binds first to the central cavity, which putatively triggers intramolecular rearrangements to expose the binding sites for cadaverine at the dimer interface, which inactivates CadC and consequently shuts off transcription of the cadBA operon (PubMed:22999955)
Inhibitory effects on GlnA1 are abolished in the presence of the effector 2-oxoglutarate
Activated by cleavage by B.anthracis lethal toxin (LT) endopeptidase (PubMed:20502689). Cleavage by LT promotes ubiquitination and degradation of the N-terminal part, releasing the cleaved C-terminal part of the protein (NACHT, LRR and PYD domains-containing protein 1a, C-terminus), which polymerizes and forms the Nlrp1a inflammasome (By similarity). Nlrp1a inflammasome is inhibited by DPP8 and DPP9, which sequester the C-terminal fragment of Nlrp1a (NACHT, LRR and PYD domains-containing protein 1a, C-terminus) in a ternary complex, thereby preventing Nlrp1a oligomerization and activation (PubMed:33731929). Nlrp1a inflammasome is weakly activated by Val-boroPro (Talabostat, PT-100), an inhibitor of dipeptidyl peptidases DPP8 and DPP9 (PubMed:31383852). Val-boroPro relieves inhibition of DPP8 and/or DPP9 by promoting disruption of the ternary complex, releasing its C-terminal part from autoinhibition (By similarity). Weakly activated by Toxoplasma gondii (PubMed:31383852)
APE1 displaces NTHL1 from the N-glycosylase-generated AP site in DNA, thereby increasing the turnover of the DNA N-glycosylase activity (PubMed:11287425, PubMed:12519758). AP lyase activity is stimulated by YBX1 (PubMed:11287425). ERCC5/XPG stimulates NTHL1 activity and NTHL1 binding to its DNA substrate (PubMed:9927729)
Weakly inhibited by L-methionine-S,R-sulphoximine (MSO) and strongly inhibited by D,L-buthionine-S,R-sulphoximine (BSO) in vitro
The phosphatase activity is inhibited by the product IMP
Inhibited by UGI, a B.subtilis bacteriophage PBS2 peptide inhibitor
Abscisic acid (ABA) causes weak inhibition of RuBisCO catalytic activity, but more potent inhibition of RuBisCO activation
Tyrosine phosphorylation of the transporter leads to activation of the transport activity (PubMed:26979622). TEA uptake is activated by tyrosine phosphorylation (PubMed:26979622). Inhibited by cGMP, most likely through a cGMP-binding protein that interacts with OCT2 (By similarity)
Inhibited by the dinucleoside pentaphosphate compound P1,P5-di(adenosine-5') pentaphosphate (AP5A)
Activity is regulated by pH (PubMed:1645730, PubMed:23836890, PubMed:10455127, PubMed:14604993). Active at alkaline pH (PubMed:1645730, PubMed:23836890, PubMed:10455127, PubMed:14604993). Activity is strongly down-regulated below pH 6.5 and a dramatic increase in activity is observed upon increase of the pH from 6.5 to 8.5 (PubMed:1645730)
Autokinase activity is stimulated by DNA damage. Stimulated by PQQ and DNA ends in vitro
Activated by adducts between glutathione and electrophiles
Activated by Ca(2+)-bound calmodulin following an increase in intracellular Ca(2+) (PubMed:19154138, PubMed:26794871, PubMed:25720963). At low Ca(2+) concentrations, the catalytic subunit (also known as calcineurin A) is inactive and is bound to the regulatory subunit (also known as calcineurin B) in which only two high-affinity binding sites are occupied by Ca(2+) (PubMed:19154138, PubMed:26794871). In response to elevated calcium levels, the occupancy of the low-affinity sites on calcineurin B by Ca(2+) causes a conformational change of the C-terminal regulatory domain of calcineurin A, resulting in the exposure of the calmodulin-binding domain and in the partial activation of calcineurin A (PubMed:19154138, PubMed:26794871). The subsequent binding of Ca(2+)-bound calmodulin leads to the displacement of the autoinhibitory domain from the active site and possibly of the autoinhibitory segment from the substrate binding site which fully activates calcineurin A (PubMed:19154138, PubMed:26794871)
Converted into plasmin by plasminogen activators, both plasminogen and its activator being bound to fibrin. Activated with catalytic amounts of streptokinase. Plasmin activity inhibited by SERPINE2
Inhibited by diethylp-nitrophenyl phosphate but not inhibited by thiol reagents 5,5'-dithiobis(2-nitrobenzoic acid) or 4,4'-dithiopyridine
Activity is completely abolished in the presence of hydroxylamine, a known specific pyridoxal-phosphate inhibitor
Assembly into ribonucleoprotein complexes of high-molecular-mass (HMM) inhibits its enzymatic activity. Antiviral activity is neutralized by the simian immunodeficiency virus (SIV-agm) virion infectivity factor (VIF), that prevents its incorporation into progeny virions by both inhibiting its translation and/or by inducing its ubiquitination and subsequent degradation by the 26S proteasome (By similarity)
Inhibited by Cibacron blue 3 GA
Partially inhibited by EDTA. Activity is restored by Co(2+), and to a lesser extent by Ni(2+) and Mg(2+). Unaffected by Cs(2+) and Ca(2+). Activity is reduced by Mn(2+) and Cu(2+)
Inhibited by UbV(SP.1), an ubiquitin variant that also inhibits STAMBP
Inhibited by 3-isobutyl-1-methylxanthine (IBMX), zaprinast and dipyridamole. cGMP acts as an allosteric activator
Inhibited by zaprinast; inhibitor is however not specific to PDE9A (PubMed:9624146). Specifically inhibited by BAY-73-6691 (1-(2-chlorophenyl)-6-((2R)-3,3,3- trifluoro-2-methylpropyl)-1,5-dihydro-4H-pyrazolo(3,4-d)pyrimidine-4-one) (PubMed:16150925). BAY-73-9961 has two enantiomers, (R) and (S), due to the presence of a chiral center, and both forms vary in their pattern of interaction (PubMed:20121115, PubMed:21483814). Specifically inhibited by PF-4181366 (4H-Pyrazolo[3,4-d]pyrimidin-4-one, 1- cyclopentyl-1,5-dihydro-6-[(3S,4S)-4-methyl- 1-(6-quinoxalinylmethyl)-3-pyrrolidinyl]-one) (PubMed:19919087). Specifically inhibited by PF-4449613 ((R)-6-(1-(3-phenoxyazetidin-1-yl)ethyl)-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-d]pyrimidin- 4(5H)-one) (PubMed:25799991). Specifically inhibited by inhibitor 28 (2-((1-(2-Chlorophenyl)-4-hydroxy-1Hpyrazolo[ 3,4-d]pyrimidin-6-yl)amino)-N-(4- methoxyphenyl)propanamide): inhibitor forms a hydrogen bond with Tyr-484 and Gln-513 (PubMed:22985069). Specifically inhibited by 1-Cyclopentyl-6-[(1r)-1-(3-phenoxyazetidin- 1-Yl)ethyl]-1,5-dihydro-4h-pyrazolo[3,4-D] pyrimidin-4-one: inhibitor forms a hydrogen bond with Tyr-484 and Gln-513 (PubMed:23025719)
Activated by DAG and phorbol esters. Phorbol-ester/DAG-type domain 1 binds phorbol ester with low affinity. Phorbol-ester/DAG-type domain 2 binds phorbol ester with high affinity and targets the kinase to the cell periphery, enabling phosphorylation and activation by colocalized tpa-1. Both domains 1 and 2 appear to bind DAG with equal affinity so may contribute equally to translocation and activation (By similarity)
Leucine uptake was inhibited by ileum, valine histidine and phenylalanine as well as by 2-amino-bicyclo-(2,2,1)-heptane-2-carboxylate (BCH) (a specific inhibitor of system L transport)
Enzymatic activity is inhibited in the presence of acetone, methanol and metal ions such as Ag(2+) and Hg(2+). Is also inhibited by various thiol reagents such as DTNB, p-chloromercuribenzoate, p-hydroxymercuribenzoate, iodacetamide and iodacetate. EDTA has no influence on activity
Activated by LIP5 and PROS
Activated by cold
Glycohydrolase activity is completely inhibited by interaction with the immunity factor for TNT (IFT). This inhibition protects M.tuberculosis from self-poisoning
Activity is strongly inhibited by metalchelating agents, such as EDTA and dipicolinic acid
Inhibited by mazindol, GBR 12783 dihydrochloride, GBR 12909 dihydrochloride, nomifensine, diclofensine, amfonelic acid, Lu 19005, Win-35428, amphetamine, bupropion, cocaine and ritalin
Phosphorylation is necessary for activity
Ubiquitin ligase activity of the BCR(KEAP1) complex is inhibited by oxidative stress and electrophile metabolites such as sulforaphane. Electrophile metabolites react with reactive cysteine residues in keap1 and trigger non-enzymatic covalent modifications of these cysteine residues, leading to inactivate the ubiquitin ligase activity of the BCR(KEAP1) complex
Inhibited by arginine, norvaline
Regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP, GTPase activating proteins (GAPs) which increase the GTP hydrolysis activity, and GDP dissociation inhibitors which inhibit the dissociation of the nucleotide from the GTPase (Probable). Activated in response to insulin (By similarity)
Insensitive to vanadate
Sildenafil (Viagra) is a highly selective and potent inhibitor of PDE5A and is effective in the treatment of penile erectile dysfunction. Also inhibited by zaprinast
Chorionic gonadotropin stimulates expression in the ovaries
Calcium increases vitamin B12 binding affinity by a factor of 50-100
The 3',5'-cyclic-AMP phosphodiesterase activity is stimulated by 3',5'-cyclic GMP (By similarity). Specifically inhibited by Bay 60-7550 (PubMed:28463107)
Alpha-amylase expression underlies catabolite repression by glucose
Channel activity is activated by PtdIns(3,5)P2 (phosphatidylinositol 3,5-bisphosphate) (PubMed:29019979). Inhibited by lumenal H(+) and Na(+). The channel pore shows dynamic behavior and undergoes spontaneous, Ca(2+)-dependent modulation when conducting Ca(2+)
Strongly inhibited by acetyl-CoA and its thioesters (PubMed:15659606, PubMed:17825826, PubMed:17242360, PubMed:16272150). Activated by palmitoylcarnitine (PubMed:17825826, PubMed:17242360)
Activity is increased by the procollagen C-endopeptidase enhancer protein
Activity is enhanced by 1mM Mn(2+), but is not affected by 1mM Ca(2+), Mg(2+), Zn(2+), K(+), Na(+) or Li(+). Activity is not inhibited by EDTA (in vitro)
Inhibited by dicumarol, p-hydroxymercuribenzoate and salicyl hydroxamate
Inhibited by beta-mercaptoethanol and the organophosphorothioate terbufos
Inhibited by zinc and cadmium
Ethidium export is inhibited by N-ethylmaleimide (NEM)
Inhibited by chelating agents such as EDTA and 1,10-phenanthroline
Activated by calcium. Autophosphorylation may play an important role in the regulation of the kinase activity (By similarity). Repressed by THI1 through a negative regulation of the autophosphorylation activity in the presence of Ca(2+) (PubMed:26662273)
Inhibited by GDP over 10 mM and by over 2 mM MgCl(2)
Oxalate transport activity is inhibited by 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS)
Chloride, bicarbonate and sulfate transport activities are inhibited by 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS)
Autorepressed by intramolecular binding of the C-terminus which dissociates following phosphorylation by NEK2 isoform 1 in G1/S-arrested cells. NEK2 isoform 2 is largely not present in the nucleolus, and does not appear to phosphorylate NEK11. Activated in response to DNA damage. Inhibited by zinc
The NAD(+)-dependent dehydrogenase is activated by inorganic phosphate
Inhibited by the immunosuppressant drug cyclosporin A and by SDZ NIM811, a PPIase inhibitor
Inhibited by benzyloxycarbonyl leucyltyrosine chloromethylketone (Z-LY-CMK)
Inhibited by Zn(2+) and Hg(2+), while it is unaffected by Ca(2+)
Activity is inhibited by 4,4'-Di-isothiocyanatostilbene-2,2'-disulfonic acid (DIDS - an inhibitor of several anion channels and transporters)
Activity is inhibited by 4,4'-Di-isothiocyanatostilbene-2,2'-disulfonic acid (DIDS - an inhibitor of several anion channels and transporters) (PubMed:18577713). Zinc-binding negatively regulates its activity (Probable)
Kinase activity is slightly activated by fructose 1,6-bisphosphate (FBP), and inhibited by inorganic phosphate (Pi), but FBP prevents kinase inhibition by Pi. Dephosphorylation of P-Ser-HPr is slightly inhibited by FBP
Activated by cAAA and to a lesser extent cAA; both cyclic nucleotides are products of its cognate CD-NTase. Cyclic nucleotide binding causes hexamerization
Activated by magnesium and inorganic phosphate. Competitively or non-competitively inhibited by ADP, 2,3-bisphosphoglyceride or GDP
Allosterically regulated (Probable); feedback inhibited by cytidine monophosphate-N-acetylneuraminic acid (CMP-Neu5Ac), the end product of neuraminic acid biosynthesis. Activity is dependent on oligomerization. The monomer is inactive, whereas the dimer catalyzes only the phosphorylation of N-acetylmannosamine; the hexamer is fully active for both enzyme activities (By similarity). Up-regulated after PKC-dependent phosphorylation
Inhibited by the dinucleoside pentaphosphate compound P1,P5-di(guanosine-5') pentaphosphate (GP5A)
Cleavage of 4-carboxy-4-hydroxy-2-oxoadipate, and to a lesser extent 4-hydroxy-4-methyl-2-oxoglutarate, is inhibited by lysine modification caused by diethyl pyrocarbonate. Decarboxylation of oxaloacetate is unaffected by diethyl pyrocarbonate. Inhibited by BeCl(2), CaCl(2), NiCl(2), BaCl(2), HgCl(2), SrSO(4), CrCl(3) and FeCl(3). Partially inhibited by p-chloromercuribenzoate and N-ethylmaleimide. Activated by inorganic phosphate, arsenate, phosphorous acid, acetyl phosphate, thiamine diphosphate, ADP, ATP and diphosphate
Inhibited by sodium lauryl sulfonate
Activity is probably potentiated by the DAT/PAT transporter MmpL10. Inhibited by the lipase inhibitor tetrahydrolipstatin (THL)
L-cysteine inhibits cystathionine beta-lyase activity competitively (PubMed:7049234). Inhibited by aminoethoxyvinylglycine (AVG) (PubMed:9376370)
Activated by a signal molecule generated by ThsB
Feedback inhibited by CoA, which is competitive with ATP, 4'-phosphopantetheine and 3'-dephospho-CoA (PubMed:17873050, PubMed:10480925). Binds 0.5 CoA tightly per monomer in the same position as 3'-dephospho-CoA but in a different fashion (PubMed:12837781, PubMed:17873050). Is inhibited by the very potent and specific inhibitor PTX042695 dipeptide, with an IC(50) of 6 nM, a compound which has no activity against porcine PPAT (PubMed:12750020). A series of pyrazoloquinolones were also characterized as ATP-competitive inhibitors of PPAT (PubMed:20486930)
Inhibited by protonophores (e.g. carbonyl cyanide m-chlorophenyl-hydrazone (CCCP)), but not by SH group inhibitors (e.g. p-chloromercuribenzene sulphonic acid (PCMBS))
Activated by cAMP, and at 10-100 times higher concentrations, also by cGMP. cAMP binding promotes tetramerization and formation of an active channel. Compared to other family members, cAMP has less stimulatory effect on HCN1 because part of the molecules already contain bound cAMP and form homotetramers when cAMP levels are low (By similarity)
Directly stimulated by the effector molecule 2-oxoglutarate. Inhibited by GlnK1. 2-oxoglutarate antagonizes the inhibitory effects of GlnK1, but does not prevent GlnK1/GlnA1 complex formation
Inhibited by erastin and sulfasalazine (PubMed:35352032). Inhibited by (S)-lactate (PubMed:11417227). Inactivated by p-chloromercuribenzoic acid and p-chloromercuribenzenesulfonic acid (PubMed:14722095)
Strongly inhibited by MCPA-CoA, a metabolite of hypoglycin which is present in unripened fruit of the ackee tree
Inhibited by K3 herbicides such as alachlor, allidochlor, anilofos, cafenstrole, fentrazamide and flufenacet (PubMed:15277688). Strongly inhibited by metazachlor and only slightly by mefluidide (PubMed:22284369)
Unlike HsaF, HsaG is active both in the presence and absence of its partner enzyme
Inhibited by the dianisidine derivative redoxal and by brequinar
Inhibited by the sulfhydryl reagents N-ethylmaleimide and p-chloromercuribenzoate, and by chloride. Competitively inhibited by acetyl-CoA
The first ATP-binding region has low ATPase activity (By similarity). The second ATP-binding region is responsible for ATPase activity (By similarity). ATP binding to the first ATP-binding region induces intrinsic activity of the second ATP-binding region (By similarity). While ATP binding to the first ATP-binding region appears to prevent ATP hydrolysis by the second ATP-binding region, ADP-binding to first region promotes the coordinate and cooperative ATPase cycle of the second ATP-binding region (By similarity). ATP binding to the first ATP-binding region induces a conformational change, promoting the rotation of the first ATP-binding region relative to the second ATP-binding region in the hexamer (By similarity). Inhibited by N-ethylmaleimide (NEM) (PubMed:18782221)
Inhibited by aurintricalboxylic acid but not by Zn(2+), Mn(2+), Hg(2+), 2-mercaptoethanol and sodium citrate. Neither inhibited nor activated by ATP
Inhibited by tetcyclasis but not by 1-aminobenzotriazole (ABT)
Upon extracellular signal or mitogen stimulation, phosphorylated at Thr-577 in the C-terminal kinase domain (CTKD) by MAPK1/ERK2 and MAPK3/ERK1. The activated CTKD then autophosphorylates Ser-386, allowing binding of PDPK1, which in turn phosphorylates Ser-227 in the N-terminal kinase domain (NTDK) leading to the full activation of the protein and subsequent phosphorylation of the substrates by the NTKD
Completely inhibited by CuCl(2), FeCl(3), HgCl(2) and N-bromosuccinimide. Moderately inhibited by AgCl, AlCl(3), Pb(CH(3)COO)(2) and dithiothreitol. BaCl(2), CaCl(2), KCl, MgCl(2), MnCl(2), NaCl, ZnCl(2), ethylenediaminetetraacetic acid, N-ethylmaleimide, iodoacetic acid and p-chloromercuribenzoic acid have little or no effect on activity
Kynurenine transaminase activity is competitively inhibited by aminoadipate, asparagine, glutamate, histidine, cysteine, lysine, 3-hydroxy-kynurenine and phenylalanine
Allosterically activated by fructose 1,6-bisphosphate (FBP) alone under acidic conditions, while it requires additional activation factors such as divalent cations (Mn(2+)) under neutral conditions (PubMed:14601, PubMed:7766183). Under acidic conditions, Mn(2+) is an inhibitor in the absence of fructose 1,6-bisphosphate (FBP) (PubMed:14601, PubMed:7766183). In case of L.casei, L-LDH binds four fructose 1,6-bisphosphate (FBP) molecules per tetramer, while usual allosteric L-LDH binds only two fructose 1,6-bisphosphate (FBP) molecules per tetramer (PubMed:14601, PubMed:7766183)
Phosphate transport activity is competitively inhibited by arsenate
Kinase activity is specifically inhibited by 2 classes of compounds: biphenyl compounds (1,1'-(biphenyl-4,4'-diyl)bis(2,2-dihydroxyethanone)) and 1,2,7-trialky-1H-imidazo[4,5-g]quinoxalin-6-one. Activated by phosphorylation on Thr-174 and potentially by autophosphorylation
Transport is chloride sensitive and transtimulated by glutaric acid (PubMed:31553721). Transport is inhibited by anionic compounds from different chemical classes (PubMed:31553721)
Inhibited by trans-2-hexadecanoyl-CoA
Kinase activity is inhibited by inorganic phosphate (Pi). In contrast to many other bacteria, neither kinase activity nor phosphorylase activity is affected by fructose 1,6-bisphosphate (FBP)
Activated when autophosphorylated at Thr-153 and inactivated when phosphorylated at Ser-260 by SnRK1.1/KIN10
Ferroxidase and phenoloxidase activities are enhanced considerably in the presence of excess copper ions (PubMed:11466290, PubMed:11527384, PubMed:11867755, PubMed:15516598, PubMed:17804014). A labile regulatory copper ion near the T1 copper site is important for the copper associated activation of enzyme activity (PubMed:12794077). Ag(+) acts as a potent inhibitor of oxidase activity by binding at Cu(+) binding sites, blocking Cu(+) substrate binding and oxidation (PubMed:21903583). pPD oxidase activity is strongly inhibited by sodium azide, an inhibitor of the electron transfer (PubMed:11527384)
The enzyme is subject to substrate inhibition by adenosine and is competitively inhibited by the adenosine analog iodotubercidin. Unlike other adenosine kinases it is not stimulated by inorganic phosphate. Activity is stimulated in the presence of potassium (PubMed:14594827). Is inhibited by a series of 7-(het)aryl-7-deazaadenine ribonucleosides bearing small and bulky substituents in position 7; some of them display micromolar antimycobacterial activity and low cytotoxicity (PubMed:25259627)
Activated by histamine, L-adrenaline, D-phenylalanine, L- and D-histidine. Inhibited by coumarins, saccharin, sulfonamide derivatives such as acetazolamide and Foscarnet (phosphonoformate trisodium salt)
Activated by calcium. Allosterically activated by phosphatidic acid in the presence of calcium. Proteolytically cleaved PLD is more active than the full-length enzyme, but is no longer activated by phosphatidic acid
Neither activated nor inhibited by coenzyme A
Inhibited by the chymotrypsin inhibitor LTCI
Stimulated by Mg(2+) (PubMed:12761666). Inhibited by Cd(2+) (PubMed:12761666). Inhibited by N-methylmesoporphyrin (N-MeMP) and 2,4-disulfonic acid deuteroporphyrin IX (dSDP) (PubMed:10704318, PubMed:16140324, PubMed:18423489)
Activated by 2C-methyl-D-erythritol 4-phosphate (MEP)
DNA polymerase II activity is regulated by the lexA gene during the SOS response
Allosterically activated by NADP(+)
Inhibited by clavulanic acid, sulbactam and tazobactam
Inhibited by 5-hydroxy-1,4-naphthoquinone (juglone), but not by FK506 or cyclosporin A
Activated by homooligomerization induced by direct binding to cytosolic LPS, in a TLR4-independent manner. In addition to LPS, CASP4/CASP11 may also be activated by oxidized phospholipid 1-palmitoyl-2-arachidonoyl- sn-glycero-3-phosphorylcholine, an oxidized phospholipid (oxPAPC), in dendritic cells, promoting adaptive immunity. The role of oxPAPC is however unclear and another report suggests that oxPAPC competes with LPS-binding and inhibits the non-canonical inflammasome in macrophages
Inhibited by quinolones, such as levofloxacin (PubMed:20596531)
Autoinhibited (By similarity). Activated by diacylglycerol and calcium binding, which induces a conformational change releasing the autoinhibitory state (PubMed:9582122). Regulated by DGKA. Regulated by DGKZ. Regulated by PLC gamma and F-actin polymerization (By similarity)
Inhibited by divalent cations and N-ethylmaleimide. Activity is reduced under anaerobic growth conditions
Activated by threonine and tyrosine phosphorylation (By similarity). Activated by two independent mechanisms, the binding of CAMs in a calcium-dependent manner and the phosphorylation by MAP kinase kinase MKK3. Activated in response to mechanical wounding, hydrogen peroxide and jasmonic acid (JA)
Inhibited by hydrogen peroxide, sulfhydryl reagents and quinine, but not by EDTA
By phosphorylation (By similarity). Activated by N-methylethanolamine (PubMed:8185307)
Strongly inhibited by vanadate
Is inhibited by scorpion cyclotide trypsin inhibitor TopI1
Inactivated by exposure to extracellular pH between 4.0 and 6.5; irreversibly inactivated when open channels are exposed to extracellular pH between 4.0 and 6.5, while pre-exposure of closed channels to extracellular pH 5.5 gives rise to currents that rapidly inactivate, but protects against irreversible inactivation (PubMed:20660597). Inactivated by intracellular ATP (PubMed:11509734). Activated by arachidonic acid (PubMed:11804595). Inhibited by 2-aminoethyl diphenylborinate (2-APB) (PubMed:28775320)
Inhibited by quinine at micromolar levels (By similarity). Modestly sensitive to millimolar levels of tetraethylammonium (TEA) (PubMed:1550672). Modestly sensitive to millimolar levels of 4-aminopyridine (4-AP)
Requires the presence of relatively high concentrations of either sulfate or phosphate for maximal activity
Inhibited by ruthenium red, a potent blocker of TRPV channels (PubMed:14712238). Selectively inhibited by A-967079 (PubMed:21402443)
Inhibited by penicillin G
Inhibited by the tryptophan-modifying reagent, N-bromosuccinimide (NBS), by the lysine-modifying reagent, N-acetylsuccinimide and by the arginine-modifying reagent, phenylglyoxal. Complex formation with ferredoxin prevents these inhibitions
L-tyrosine uptake is stimulated in trans by aromatic and large neutral amino acids, but not smaller or charged amino acids
The uptake of leucine, tyrosine and tryptophan is inhibited by the different iodothyronines, in particular T3 (PubMed:11564694). The uptake of T3 is almost completely blocked by coincubation with leucine, tryptophan, tyrosine, and phenylalanine, or 2-amino-bicyclo-(2,2,1)-heptane-2-carboxylate (BCH) (PubMed:11564694). Methionine uptake was inhibited by the L-system substrates L-leucine, BCH, L-cysteine and by the MeHg-L-cysteine complex and structurally related S-ethyl-L-cysteine (PubMed:12117417). MeHg-L-cysteine uptake is inhibited by L-methionine, L-leucine, BCH and S-ethyl-L-cysteine (PubMed:12117417). L-leucine transport is inhibited by phenylalanine, tyrosine, L-dopa, 3-O-methyldopa, a-methyltyrosine, a-methyldopa, gabapentin, triiodothyronine, thyroxine, melphalan and BCH (PubMed:12225859). L-leucine uptake was inhibited by L-CNSO (PubMed:15769744)
Inhibited by BasR. This regulation does not occur at the level of transcription, but rather following the assembly of LpxT into the inner membrane
Autoinhibited by the ariadne domain, which masks the second RING-type zinc finger that contains the active site and inhibits the E3 activity (By similarity). Inhibition is relieved upon binding to neddylated cullin-RING ubiquitin ligase complexes, which activate the E3 ligase activity of ARIH1 (PubMed:24076655)
Dimerization causes loss of catalytic activity (PubMed:20435072). Inhibited by pepstatin A (PubMed:16624575). Inhibited by Zn(2+) (PubMed:20435072)
Channel activity is strongly inhibited by mibefradil (PubMed:9670923, PubMed:9930755). Channel activity is strongly inhibited by Ni(2+) ions (PubMed:9930755)
The metalloproteinase is inhibited by EDTA, o-phenanthroline, and cysteine. Glutathione does not inhibit the enzymatic activity
Activated by glutamine
Autoinhibited. In the autoinhibited state, the TPR domain interacts with the catalytic region and prevents substrate access to the catalytic pocket (By similarity). daf-21/Hsp90 probably releases the autoinhibition by the TPR repeat (PubMed:26593036, PubMed:23569206)
Activated by arachidonic acid and other unsaturated fatty acids (PubMed:9628867). Not affected by volatile general anesthetics such as chloroform, diethyl ether, halothane and isoflurane (PubMed:10321245)
Subject to autoinhibition, mediated by intramolecular interactions between the SH2 domain and the C-terminal phosphotyrosine. Phosphorylation at Tyr-397 is required for optimal activity. Phosphorylated by CSK at Tyr-508; phosphorylation at Tyr-508 inhibits kinase activity. Kinase activity is modulated by dephosphorylation by PTPRC/CD45. Inhibited by dasatinib, PP2, and SU6656
Inhibition by oxidized glutathione (GSSG), S-nitrosoglutathione (GSNO), hydrogen peroxide and sodium nitroprusside (SNP)
Inhibited by the carbonyl reagents hydroxylamine, phenylhydrazine and semicarbazide. Inhibited by the chelating agent EDTA. Inhibited by the sulfhydryl reagent p-chloromercuribenzoic acid, and by sodium cyanide. Inhibited by iodoacetate, Ag(2)SO(4), HgCl(2) and CdCl(2). Competitively inhibited by beta-hydroxyaspartate and O-phospho-DL-threonine
Insensitive to feedback inhibition by L-tyrosine
Activated by 2-ketoglutarate, phosphoenolpyruvate (PEP), fructose 1,6-biphosphate (FBP) and coenzyme A (acetyl-CoA and CoA) as homodimer and by oxaloacetate (OAA), 2-ketoglutarate, succinate, fumarate and CoA as heterodimer NAD-MEH. Repressed by succinate and fumarate as homodimer, in the presence of NAD(+) and competitively toward the substrate L-malate
Inactivated by metal-chelating agents phenanthroline and EDTA. Inhibited by bestatin, an aminopeptidase inhibitor. Not inhibited by pepstatin A and PMSF, inhibitors of aspartic and the serine proteases, respectively. Not inhibited by carboxypeptidase inhibitor
Might be regulated by a phosphorylation/dephosphorylation mechanism
E3 ligase activity is robustly activated by 5-hydroxymethylcytosine
Autophosphorylates on tyrosine residues
Activated by threonine and tyrosine phosphorylation. Activated by oxidative stress
Inhibited by aprotinin, leupeptin, benzamidine and soybean trypsin inhibitor. Partially inhibited by PMSF and DFP (By similarity)
FAEE-synthesizing and PNPB-hydrolyzing activities are both inhibited by DFP
Allosterically activated by GTP, when glutamine is the substrate (PubMed:15296735). GTP has no effect on the reaction when ammonia is the substrate. The allosteric effector GTP functions by stabilizing the protein conformation that binds the tetrahedral intermediate(s) formed during glutamine hydrolysis. Inhibited by the product CTP, via allosteric rather than competitive inhibition (By similarity)
ATP/GTP hydrolysis is stimulated by the addition of acetyl-CoA and tRNA(Met). Binding of acetyl-CoA to TmcA activates both ATPase and tRNA-binding activities (PubMed:18668122, PubMed:19322199). ATP promotes the 2-hydroxyisobutyryltransferase activity (PubMed:34903851)
Inhibited by small molecule 49c (PubMed:29074775). Inhibited by small molecules WM382, WM4, and WM5 (PubMed:32109369)
During elevated serum iron levels, liver-derived hepcidin/HAMP negatively regulates cell surface ferroportin/SLC40A1 by inducing its ubiquitination, internalization, and degradation. Indeed, hepcidin/HAMP affinity towards ferroportin/SLC40A1 increases by 80-fold in the presence of iron
Inhibited by 7-keto-8-aminopelargonic acid at concentrations above 80 uM
Synthesized as an inactive zymogen to protect the intracellular components of the bacteria from proteolytic activity during protein production (PubMed:8675287). Once secreted into the extracellular milieu, cleaved into the active protease: maturation can be mediated in cis by autocatalytic cleavage, or in trans by mature SpeB, host trypsin (PRSS1) or host subtilisin (PubMed:10429198). Protease activity is strongly inhibited by zinc and copper, which prevent its maturation into an active protease: inhibition by metal ions may be required to prevent proteolysis of streptococcal proteins (By similarity). Specifically inhibited by 2S-alkyne, a nitrile-based specific covalent inhibitor (PubMed:32662975)
Inactivated by thiol reagents 5,5'- dithiobis(2-nitrobenzoic acid) and 4,4'-dithiopyridine
Transport activity is inhibited by the grapefruit juice component naringin
Strongly inhibited by Hg(2+) and Zn(2+). Activated by Na(+), NH(4)(+), Ca(2+), Cu(2+) and Mg(2+)
Activity is strongly inhibited by Cu(2+) and Fe(3+)
Inhibited by sinefungin, A9145C and S-adenosyl-L-homocysteine
Acetylation by KAT5/TIP60 stimulates the protein kinase activity (PubMed:22539723). The protein kinase activity is activated by unanchored 'Lys-63'-linked polyubiquitin chains: unanchored 'Lys-63'-linked polyubiquitin chains are catalyzed by TRIM32 in an AMBRA1-dependent manner (By similarity)
Activated by tyrosine and threonine phosphorylation after pheromone treatment or carbon/nitrogen limitation
Kinase activation is repressed by the phosphatase PP2C38
Activated by threonine and tyrosine phosphorylation by the upstreamm MAPKK mkk2
May be activated by phosphorylation at Ser-221 and Ser-225
Activity is blocked by the allylamine class antifungal terbinafine
Inhibited by NaF
Stimulated in vitro in a concentration-dependent fashion by extracellular death factor (EDF, a quorum sensing pentapeptide sequence NNWNN, probably produced from the zwf gene product glucose-6-phosphate 1-dehydrogenase), which is able to overcome inhibition by cognate antitoxin ChpS
Enhanced by Mg(2+) and Ca(2+) ions, ethylenediaminetetraacetic acid, ethylene glycol tetraacetic acid and citrate. Inhibited by Al(3+), Fe(3+), Co(2+), Cu(2+), Zn(2+), Pb(2+) and Ag(+) ions, iodoacetate, 4-chloromercuribenzoate and N-bromosuccinimide
P-hydroxymercuribenzoate irreversibly abolishes ureolytic activity, but does not inhibit the ability to activate platelets (PubMed:11696010). Also inhibited by acetohydroxamic acid (AHA), a chelator of Ni2+ and Zn2+ ions (PubMed:11696010)
Significantly inhibited by EDTA (PubMed:33820885). Activity is enhanced by Fe(2+), but is strongly inhibited by Mn(2+), Cu(2+), Zn(2+), Ni(2+) and Co(2+) (PubMed:33820885)
Subject to negative translational control in pollen
Inhibited by ribitol, L-arabitol and dulcitol (PubMed:4632320). Isomerization of L-xylulose to L-xylose is inhibited by xylitol (PubMed:22133443)
Activated by autophosphorylation of the T-loop at Thr-167 and Ser-171: in contrast to other members of the SNF1 subfamily, phosphorylation at Thr-167 is not mediated by STK11/LKB1 but via autophosphorylation instead. Inhibited by calcium-binding. Kinase activity is also regulated by reducing agents: dithiothreitol (DTT) or reduced glutathione are required for kinase activity in vitro; such dependence is however not due to the presence of disulfide bonds (By similarity)
Inhibited by bacterioopsin
Inhibited by sulfonamides and sulfamates. The best inhibitors are 3-bromosulfanilamide and indisulam
Inhibited by tetracyclic diterpene antibiotic aphidicolin
Synthesized as an inactive form which is proteolytically cleaved to generate an active enzyme. Processing at the upstream site is particularly important for activation of the proenzyme, whereas processing at the boundary between the pro-domain and the catalytic domain does not appear to be essential. Inhibited by hydroxamic acid-based inhibitors
Activated by WNK3. Inhibited by thiazide-type diuretic metolazone
Inhibited by itaconate, itaconic anhydride, bromopyruvate and 3-nitropropionate (3-NP), when M.tuberculosis grows on fatty acids, but not on glucose. At 5 mM, oxalate and malate also inhibit the activity to approximately 50%
Both lipid anchor in the outer membrane and peptidoglycan binding are required for full activity (PubMed:22719254). Once activated by certain cell stress, the dimeric YfiB transforms from a compact conformation to a stretched conformation, allowing the periplasmic domain of the membrane-anchored YfiB to penetrate the cell wall and sequester the YfiR dimer (PubMed:27113583). GMP enhances the binding affinity between YfiB and YfiR (PubMed:28870806)
Retinol oxidation is inhibited by the detergent Tween 80. Ethanol inhibits both all-trans-retinol and 9-cis-retinol oxidation. 13-cis-retinol is an effective competitive inhibitor of the 9-cis-retinol oxidation. All-trans-retinoic acid is a powerful inhibitor of all-trans-retinol oxidation. 13-cis-retinoic acid is a powerful inhibitor of all-trans-retinol oxidation (By similarity). Cimetidine and ranitidine inhibited ethanol oxidation (PubMed:9600267)
Activated by nucleoside triphosphates. Inhibited by phosphoenolpyruvate. EDTA and biphosphonates play the role of inhibitors of kinase activity
Inhibited by phosphorylation of Ser-34
CLPS stimulates triacylglycerol lipase activity. Triacylglycerol lipase activity is not inhibited by increasing bile salt concentration
Specifically inhibited by XAV939, a small molecule, leading to inhibit the Wnt signaling pathway by stabilizing AXIN1 and AXIN2 (PubMed:19759537). Inhibited by talazoparib (PubMed:33361107). Not inhibited by olaparib, niraparib and veliparib (PubMed:33361107)
Substrate inhibition by genkwanin (GENK) at concentrations above 2.5 mM
Activated by N-acetylglucosamine-1-P or K(+) at low UDP-ManNAc concentrations
Inhibited by 4,4'-dithiodipyridine
Coactivator activity on nuclear receptors and NF-kappa-B pathways is enhanced by various hormones, and the TNF cytokine, respectively. TNF stimulation probably enhances phosphorylation, which in turn activates coactivator function. In contrast, acetylation by CREBBP apparently suppresses coactivation of target genes by disrupting its association with nuclear receptors (By similarity)
Sulbactam is an effective progressive inhibitor but a poor competitive inhibitor
The dipeptidyl carboxypeptidase activity is strongly activated by chloride (By similarity). Specifically inhibited by lisinopril (PubMed:7902354). Inhibited by mixanpril, an orally-active drug used for the treatment of hypertension (PubMed:8171037)
In the autoinhibited state the side chain of Phe-460 inserts into a hydrophobic groove in RING-0, occluding the ubiquitin acceptor site Cys-428, whereas the REP repressor element binds RING-1 and blocks its E2-binding site (PubMed:26161729). Activation of park requires 2 steps: (1) phosphorylation at Ser-92 by Pink1 and (2) binding to phosphorylated ubiquitin, leading to unlock repression of the catalytic Cys-428 by the RING-0 region via an allosteric mechanism and converting park to its fully-active form (PubMed:26161729). According to another report, phosphorylation at Ser-92 by Pink1 is not essential for activation and only binding to phosphorylated ubiquitin is essential to unlock repression (By similarity)
Inhibited by a synthetic peptide corresponding to the inhibitory cysteine switch motif (PubMed:1988438). Inhibited by ethylenediaminetetraacetic acid (EDTA), 1,10-pheanthroline, 2-mecaptoethanol, dithiothreitol and metalloproteinase inhibitor protein TIMP (PubMed:1963430, PubMed:2841336)
Up-regulated by DARS and EEF1A1, but not by AIMP2
Inhibited by 1 mM 4-(2-aminoethyl)-benzenesulfonyl fluoride (AEBSF), a general inhibitor of serine proteinases, but not by the more selective serine protease inhibitors N-alpha-tosyl-L-lysinyl-chloromethylketone (TLCK), N-tosyl-L-phenylalaninyl-chloromethylketone (TPCK), leupeptin, aprotinin or benzamidine (PubMed:19332543). Its proteolytic activity is autoinhibited by the non-covalent binding of the propeptide to the catalytic domain (PubMed:27451395). No effect on activity by the addition of CaCl(2) or calcium chelators (PubMed:19805099)
Not inhibited by mercury ions
Inhibited by DEPC. Completely inhibited by ZnSO(4), strongly inhibited by CuSO(4), partially inhibited by MnCl(2). Unaffected by MgCl(2) or CaCl(2)
Activity is dependent of phosphatidylinositol 4,5-bisphosphate and the regulator SRF1. Inhibited by magnesium
Kinase activity is regulated by the GTPase activity of the ROC domain (PubMed:29212815, PubMed:18230735). GTP-bound LLRK2 kinase activity is stimulated by RAB29 (PubMed:29212815). Inhibited by small molecule inhibitor MLi-2 (PubMed:26824392, PubMed:29127255)
Inhibited weakly by Mn(2+), Mg(2+) and Ca(2+), but not affected by Zn(2+), Co(2+), Cu(2+), EDTA or EGTA
Activated by tyrosine and threonine phosphorylation after pheromone treatment
Regulated by PknD under osmotic stress
Inhibited by ethylene glycol-bis(2-aminoethylether)-N,N,N,N-tetraacetic acid (EGTA), ethylenediaminetetraacetic acid (EDTA) and o-phenanthroline
Inhibited by bestatin (By similarity). Inhibited by captopril (PubMed:1544505). The epoxide hydrolase activity is restrained by suicide inactivation that involves binding of LTA4 to Tyr-379. 4-(4-benzylphenyl)thiazol-2-amine (ARM1) selectively inhibits the epoxide hydrolase activity (By similarity)
Inhibited by the reaction end product PPi. Inhibited by dCDP. Inhibited by triptolide
Activated during oocyte maturation by phosphorylation on Ser-361 by cdk-1. The pseudotyrosine phosphatases egg-4 and egg-5 sequester activated mbk-2 until the meiotic divisions and inhibit mbk-2 kinase activity directly, using a mixed-inhibition mechanism that does not involve tyrosine dephosphorylation (By similarity)
Requires hairpin 92 of 23S rRNA for optimal activity. ATPase activity is stimulated by interaction of the N-terminal domain with RNA
Inhibited by 50 mM NaF (sodium fluoride)
Is inhibited by diphenylamine
Inhibited by 4-aminopyridine (4-AP) (PubMed:11717161). Inhibited by dendrotoxin (DTX) and charybdotoxin (CTX), but not by tetraethylammonium (TEA) (By similarity). Inhibited by tityustoxin-K alpha (TsTX-Kalpha), a toxin that is highly specific for KCNA2 (By similarity). Inhibited by maurotoxin (By similarity). Inhibited by kappaM conotoxins kappaM-RIIIJ and kappaM-RIIIK (By similarity)
The formation of an intramolecular disulfide bond negatively regulates both the N-terminal endonuclease and the C-terminal glutaredoxin activities
Strongly inhibited by Ag(+) and Hg(+), and comnpletely inhibited by p-chloromercuribenzoic acid
VAMP2 cleavage inhibited by EDTA
Activity is not influenced by the addition of S-adenosylmethionine, the allosteric activator of TS from Arabidopsis thaliana
N-terminal autoinhibitory domain interacts with the C-terminal kinase domain, inhibiting kinase activity, and preventing interaction with its substrate, MAP2K6. The GADD45 proteins activate the kinase by binding to the N-terminal domain. Activated by phosphorylation on Thr-1505
Serine-threonine kinase activity is inhibited by linear polyubiquitination ('Met-1'-linked) by the LUBAC complex
In contrast with PFK1 this enzyme is not affected by phosphoenolpyruvate
Subject to allosteric regulation, exists in two distinct conformational states, a catalytically incompetent (or open) conformation stabilized by the binding of acetyl(acyl)-CoA, and a catalytically competent (or closed) conformation stabilized by ATP-binding (By similarity). Acetyl-CoA and its thioesters act as allosteric inhibitors and compete with the ATP-binding site (By similarity). Strongly inhibited by acetyl-CoA, malonyl-CoA and palmitoyl CoA and modestly inhibited by CoA (PubMed:16040613). Inhibited by calcium hopantenate (PubMed:17379144)
Translocase activity is inhibited by verapamil and is sensitive to energy depletion (PubMed:8898203). C1orf115 regulates drug efflux through modulation of ABCB1 localization and activity (PubMed:35970996)
Fatty acyl-AMP ligase activity and transferase activity onto Pks13 are both inhibited by phosphorylation (PubMed:27590338). The acyl-AMP ligase activity is inhibited by the alkylphosphate ester of AMP, adenosine 50-dodecylphosphate (AMPC12) (PubMed:19477415, PubMed:26900152). Also inhibited by eicosyl-AMP (AMPC20) (PubMed:26900152). Loading of the acyl-AMP onto Pks13 is inhibited by 5'-O-[N-(11-phenoxyundecanoyl)sulfamoyl]adenosine (PhU-AMS) (PubMed:27547819)
Activation requires multiple phosphorylation events on serine/threonine residues. Activation appears to be first mediated by phosphorylation of multiple sites in the autoinhibitory domain, which facilitates phosphorylation at Thr-412, disrupting the autoinhibitory mechanism and allowing phosphorylation of Thr-252 by PDPK1. The active conformation of the kinase is believed to be stabilized by a mechanism involving three conserved phosphorylation sites located in the kinase domain activation loop (Thr-252) and in the AGC-kinase C-terminal domain (Ser-394 in the middle of the tail/linker region and Thr-412 within a hydrophobic motif at its end). Activated by mTORC1; isoform Alpha I and isoform Alpha II are sensitive to rapamycin, which inhibits activating phosphorylation at Thr-412. Activated by PDPK1
Repressed by PtdIns4P, adenosine and wortmannin, but stimulated by other negatively charged lipids such as PtdIns3P, PtdOH, and phosphatidyl-serine (PtdSer)
Negatively regulated by FLU and heme
Inhibited by tranylcypromine, but not by pargyline, deprenyl or rasagiline (PubMed:19407342). Histone H3K4me1 and H3K4me2 demethylase activity is inhibited by DNA, this inhibition is released in complex with GLYR1 (By similarity)
Activated upon caspase cleavage to generate the XK-related protein 9, processed form (PubMed:25231987). Does not act prior the onset of apoptosis (PubMed:25231987)
In rod outer segments, activated by light. Inhibited by I-OMe tyrphostin AG-538 (I-OMe-AG-538), acting as an ATP-competitive inhibitor (PubMed:23326584)
Despite being transcribed during bacterial growth in culture the protein is only detected in infected mice
LY294002, an inhibitor of the catalytic subunit of PI3-kinase, blocks NHE1-dependent (but not NHE1-independent) increase in intracellular pH in response to cAMP
Inhibited by dihydropyridines (DHP), such as isradipine (PubMed:8392192, PubMed:7737988, PubMed:9607315, PubMed:8099908). Inhibited by nifedipine (By similarity). Channel activity is regulated by Ca(2+) and calmodulin (PubMed:29742403) (Probable). Binding of STAC1, STAC2 or STAC3 to a region that overlaps with the calmodulin binding site inhibits channel inactivation by Ca(2+) and calmodulin (PubMed:29078335). Binding of calmodulin or CABP1 at the same regulatory sites results in opposite effects on the channel function (PubMed:15140941, PubMed:15980432). Shear stress and pressure increases calcium channel activity (PubMed:12176756)
Activity requires salt; 100 mM sodium or potassium salts of chloride, phosphate or sulfate are equally effective. Not inactivated by O(2). Inhibited by hydrogen-producing 5,10-methenyltetrahydromethanopterin hydrogenase which has a higher affinity for their shared substrate (PubMed:1765081). Enzyme is O(2)-stable and strictly dependent on coenzyme F420 (PubMed:7852356)
The reaction is stimulated by 0.01% CHAPS, but strongly inhibited by sodiumdeoxycholate, Tween 80 and Triton X-100
Inhibited by the antibiotics globomycin and myxovirescin. They act by blocking the catalytic dyad
Inhibited by (R)-6-hydroxynicotine (PubMed:5849820, PubMed:4965794). Inhibited by high concentrations of phenanthroline (PubMed:5646150). Activity is strongly affected by Hg(2+) and p-chloromercuriphenylsulfonate, but not by N-ethylmaleimide and 5,5'-dithiobis-(2-nitrobenzoate) (PubMed:5646150)
Metal ions, copper, iron and N-bromosuccinimide decrease enzyme activity. Manganese, calcium, L-tryptophan, beta-mercaptoethanol, L-cysteine and dithiodipyridine stimulate the enzyme activity
Regulated by Coenzyme A (CoA) through feedback inhibition
Redox regulation; active in reducing conditions, inactive in oxidizing conditions. The reduction of the cysteine pairs allows the access binding of the tetrahydrofolate substrate to its binding site. This mechanism appears to be unique to Plasmodium species
Activated by ATP (By similarity). pH-dependent and inhibited by acidic pH (By similarity)
AMP and XMP inhibit AICAR formyltransferase activity (PubMed:10985775). AICAR formyltransferase activity is inhibited by N-(6-fluoro-1-oxo-1,2-dihydroisoquinolin-7-yl)-5- [(3R)-3-hydroxypyrrolidin-1-yl]thiophene-2-sulfonamide (LSN 3213128), which acts as a tumor suppression in cancer cell lines (PubMed:29072452)
Two related chemical scaffolds that potently inhibit the activity of the CoaB moiety of CoaBC through a cryptic allosteric site that sits in the dimer interface region of the CoaB enzyme were identified
Melamine catalysis is highly inhibited in the presence of aminoatrazine
Inhibited by AMP-PNP. Partially inhibited by N-ethylmaleimide, orthovanadate and NaN(3)
Inhibited by Fe(3+), Ni(2+) and Cu(2+)
Inhibited by divalent lead ions
Weakly inhibited by D-2-aminopimelate
Inhibited by divalent cations different from calcium ions (cadmium, magnesium, manganese, zinc), since they act as competitive antagonists of this cofactor (PubMed:23509754). Crotapotin F3 from C.durissus cascavella rattlesnake venom and antihemorrhagic factor DA2-II from D.albiventris opossum sera inhibit its enzymatic activity (PubMed:23509754)
Strongly inhibited by Cu(2+) and Zn(2+). Slightly stimulated by of Mn(2+) or Co(2+), but also by metal-chelating agents such as EDTA or EGTA
Activated by K(+) and Na(+) ions, whereas NH(4)(+) ions appear to inhibit endonuclease activity
Binding to the promoter region of BhsA/ComC is released in the presence of copper
Is inhibited by the transition state analog BuT-DADMe-ImmA. This compound is also able to inhibit H.pylori growth and is more efficient than antibiotics commonly used in ulcer therapy
Inhibited by GDP and GDP-D-glucose
Inhibited by Ni(2+) ions. Fe(2+) ions do not inhibit zinc uptake
Inhibited by hydralazine and menadione. Not inhibited by BOF-4272 or allopurinol, xanthine dehydrogenase potent inhibitors. In contrast to guinea pig, human and rat, isovanillin is not an inhibitor but a substrate for AOX1 in rabbit
Inhibited by protonophores (e.g. dinitrophenol and carbonyl cyanide m-chlorophenyl-hydrazone (CCCP)) and SH group inhibitors (e.g. p-chloromercuribenzene sulphonic acid (PCMBS))
The dimers display cooperative channel gating. The channel activity is inhibited by zinc ions
Inhibited by gabaculine
Ca(2+) is required for hemolytic activity and the activity increases with increasing calcium concentration. Hemolytic activity is inhibited by N-acetylgalactosamine (GalNAc), lactose, lactulose, galactosamine, dextran with molecular masses greater than 4 kDa, to a lesser extent by inulin and only slightly by sucrose and melezitose, but not by glucose or mannose. The activity is abolished in the presence of 10 mM EDTA (PubMed:11471734, PubMed:19420692, PubMed:7798179, PubMed:9058193, PubMed:7876091). Lactose-binding increases with increasing calcium concentration, but calcium has no effect on hemagglutinating activity (PubMed:9058193, PubMed:11471734). Cytotoxic effect on Madin-Darby canine kidney (MDCK) cell line is strongly inhibited by galactose, lactose and N-acetylgalactosamine (GalNAc), but not by raffinose, N-acetylglucosamine (GlcNAc), glucose, mannose, ribose or sucrose (PubMed:9133626). Pore formation in artificial lactosyl ceramide (LacCer) or globotetraosylceramide (Gb4Cer) containing liposomes is strongly inhibited by lactose (PubMed:10478454)
Inhibited by beryllium trifluoride (BeF(3-)) and tetrafluoroaluminate (AlF(4-)) but not by sodium fluoride (NaF) or sodium orthovanadate (Na3VO4)
3-alpha,7-alpha,12-alpha-trihydroxy-5-beta-cholestanate (THCA) inhibits the activation of cholate
Channel activity is regulated by phosphorylation (By similarity). The channel is activated by increased cytoplasmic Ca(2+) (in the uM range) and by membrane depolarization (PubMed:27760766)
Insensitive to guanine nucleotides
Inhibited by ortho-phenanthroline and UDP (competitive inhibitor relatively to UDP-Gal only) and inactivated by citraconic anhydride, tert-butoxycarbonyl-L-methionine hydrosuccinimidyl ester (SLR) and N-ethylmaleimide (NEM)
Inhibited by thiol-inactivating reagents such as iodoacetamide and Hg(2+) ions
Na(+) current is inhibited by ATP in a MTORC-dependent manner. ATP sensitivity is independent of PI(3,5)P2 (PubMed:23394946). Probably regulated by Mg(2+) ions, cytosolic Mg(2+) selectively inhibits outward current while lysosomal Mg(2+) modestly inhibits both the outward and inward currents. In the absence of Mg(2+), NAADP readily activates TPCN2, with properties similar to PI(3,5)P2 (By similarity). Both current elicited by PI(3,5)P2 as well as NAADP are inhibited by tetrandrine
Unlike mammalian IP3K, may not be regulated by calmodulin
Activated by threonine and tyrosine phosphorylation by two dual specificity kinases, MAP2K4 and MAP2K7. MAP2K7 phosphorylates MAPK10 on Thr-221 causing a conformational change and a large increase in Vmax. MAP2K4 then phosphorylates Tyr-223 resulting in a further increase in Vmax. Inhibited by dual specificity phosphatases, such as DUSP1. Inhibited by HDAC9
Phosphorylation by CSK at Tyr-529 inhibits kinase activity. Inhibitory phosphorylation at Tyr-529 is enhanced by heme. Further phosphorylation by CDK1 partially reactivates CSK-inactivated SRC and facilitates complete reactivation by protein tyrosine phosphatase PTPRC. Integrin engagement stimulates kinase activity. Phosphorylation by PTK2/FAK1 enhances kinase activity. Butein and pseudosubstrate-based peptide inhibitors like CIYKYYF act as inhibitors. Phosphorylation at Tyr-418 increases kinase activity
Inhibited by ATP, citrate and S-2,3-dicarboxyaziridine
A cytosolic factor (probably pyrophosphate, polytriphosphate, polyP4, polyP25, polyP45, and/or polyP65) is necessary for TRPA1 activation by irritants (PubMed:17567811). Such factor acts by keeping TRPA1 in a agonist-sensitive state (PubMed:17567811). Inhibited by the potent blocker of TRPV channels ruthenium red, A-967079 (PubMed:15843607, PubMed:29703838, PubMed:31447178). Activated by icilin, sulfhydryl reactive agent MTSEA, N-methyl maleimide (NMM), and PF-4840154 (PubMed:17237762, PubMed:29703838)
Inhibited by zinc and copper ions (PubMed:16782809). Repressed by 4-bromo-cinnamyl acetate (PubMed:16782809). Desactivated by the competitive inhibitor EMDF ((7S,8S)-ethyl(7,8-methylene)-dihydroferulate) (PubMed:17912370)
Slightly stimulated in the presence of 1 mM Mg(2+)
P-bromophenacyl bromide (BPB) completely inhibit the catalytic activity whereas it only partially reduces the toxic activities. EDTA and magnesium ions partially inhibit the catalytic activity and partially reduce the toxic activities
PA phosphatase activity inhibited by N-ethylmaleimide with an IC(50) value of 10 mM
GABA transport is inhibited by SNAP-5114
Inhibited by N-ethylmaleimide (PubMed:12473658, PubMed:21177865). Redox-regulated during autophagy since reducing conditions activate ATG4A whereas an oxidizing environment such as the presence of H(2)O(2) inhibits its activity (PubMed:17347651)
Inhibited by long N-sulfated sequences (more than 6 sugar residues) accumulating in its substrates heparan sulfate, and heparin
Four natural products, alpha-lapachone, 9-hydroxy-alpha-lapachone, Paulownin, and Yangambin, show strong inhibitory activities against CGS. All these four inhibitors prevent the binding of OSHS to CGS in a non-competitive fashion. These compounds are specific inhibitors against CGS from H.pylori relative to E.coli since they exhibit very low inhibition activities against CGS from E.coli
Completely inhibited by metalloprotease inhibitors EDTA, 1,10-phenanthroline, and phosphoramidon, but not by inhibitors specific for serine, cysteine, and aspartate proteases, such as PMSF, antipain, leupeptin, chymostatin, and pepstatin. Zn(2+) and, to a lesser extent, Co(2+) reversed the inhibition of 1,10-phenanthroline
Not inhibited by relatively high concentrations of palmitoyl-CoA (PubMed:11279212). Inhibited by both D-cycloserine (DCS) and L-cycloserine (LCS), which inactivate SPT by transamination to form a free pyridoxamine 5'-phosphate (PMP) and beta-aminooxyacetaldehyde that remain bound at the active site (PubMed:20445930). Inhibition is reversed by incubation with excess pyridoxal phosphate (PubMed:20445930). Inhibited by the fungal natural product myriocin, which acts as a competitive inhibitor for both L-serine and palmitoyl-CoA substrates (PubMed:23957439)
Stimulated by arachidonic acid and other unsaturated fatty acids, and by arachidoyl coenzyme A
D-glucose and maltose competitively inhibit fructose transport (PubMed:8457197). D-glucose, D-fructose and maltose inhibit deoxyglucose transport (PubMed:8457197). Glucose and fructose transport are inhibited by flavonoids such as epigallocatechin gallate, apigenin and quercetin (PubMed:29548810)
Inhibited by o-methoxybenzoylalanine (OMBA)
Formation of theanine is repressed by a high concentration of glutamic acid
Allosterically regulated by all of the three aromatic amino acids (phenylalanine, tyrosine and tryptophan). Inhibited by low concentrations of aromatic amino acids and highly activated at higher concentrations. Ionic interactions are required for optimal activity
In vitro, is completely inhibited by l,l0-phenanthroline, and by isocaproic acid and Bz-Arg
Alpha-beta methylenyl ATP, an ATP-analog inhibitor of the synthase activity also reduces the hydrolase activity about 4-fold
Inhibited by calcium
Stimulated by dithiothreitol and inhibited by 2-mercaptoethanol, p-chloromercuribenzoate and hydroxylamine
Displays a strong preference for selenocysteine as a substrate in vitro and is only very slightly active using cysteine. The interactions with SufE and the SufBCD complex act synergistically to enhance, up to 50-fold, its cysteine desulfurase activity
Activated by cysteine desulfurase, Fe(2+) ions and cysteine and inhibited by oxygen and ADP
Inhibited by the serine protease inhibitors NPGB, PMSF, p-aminobenzamidine and aprotinin. Not inhibited by soybean trypsin inhibitor or EDTA
Is markedly inactivated in vitro by heavy metal ions, N-bromosuccinimide, ethoxyformic anhydride, and dye-sensitized photooxidation
Uptake is inhibited by the protonophore uncouplers carbonyl cyanide m-chlorophenylhydrazone (CCCP) and 2,4-dinitrophenol, and by NaN(3)
Irreversibly inhibited the sulfhydryl reagent N-ethylmaleimide (NEM)
Each dimer has two allosteric binding sites that can bind the regulatory effectors tryptophan or tyrosine (PubMed:10894726). Can bind either one tryptophan or one tyrosine, two tryptophan or two tyrosine or one tryptophan and one tyrosine, which differentially affect the catalytic activity (By similarity). Activated by tryptophan and subject to feedback inhibition by tyrosine (PubMed:10894726). In the presence of both tryptophan and tyrosine, the enzyme is in the activated state (By similarity)
Pyrrolopyrimidines inhibit both GyrB and its paralog in topoisomerase IV (parE) (PubMed:23294697, PubMed:23352267, PubMed:24386374)
Is displaced from DNA by low concentrations of fructose-1-phosphate
Present in an inactive conformation in the absence of bound ligand. Binding of VEGFC or VEGFD leads to dimerization and activation by autophosphorylation on tyrosine residues. Inhibited by MAZ51
Each dimer has two allosteric binding sites that can bind the regulatory effectors tryptophan or tyrosine (PubMed:31498992, PubMed:2187528, PubMed:10428795, PubMed:9642265). Can bind either one tryptophan or one tyrosine, two tryptophan or two tyrosine or one tryptophan and one tyrosine, which differentially affect the catalytic activity (PubMed:31498992). Activated by tryptophan and subject to feedback inhibition by tyrosine (PubMed:10428795, PubMed:31498992, PubMed:2646272, PubMed:2187528). In the presence of both tryptophan and tyrosine, the enzyme is in the activated state (PubMed:2646272, PubMed:31498992)
Sulfoluciferin formation is inhibited by the product adenosine 3',5'-bisphosphate