IdA string | IdB string | labels int64 | mechanism string | effect string | score float64 | sentence string | signor_id string |
|---|---|---|---|---|---|---|---|
P40259 | P06241 | 0 | phosphorylation | up-regulates activity | 0.672 | CD79b cytoplasmic tail-containing GST fusion proteins were phosphorylated in vitro by baculovirus-produced Fyn, >80% of phosphorylation occurred on the N-terminal ITAM tyrosine. CD79a and CD79b function as transducers of B cell antigen receptor signals via a cytoplasmic sequence, termed the immunoreceptor tyrosine-based activation motif (ITAM). pY195 and pY206 in CD79b | SIGNOR-251154 |
Q96RD6 | Q15208 | 0 | phosphorylation | up-regulates activity | 0.2 | We identified 5 potential NDR1 substrates in the mouse brain and chose two for functional validation. We show that one NDR1 substrate is another kinase, AP-2 associated kinase-1 (AAK1) which regulates dendritic branching as a result of NDR1 phosphorylation. Another substrate is the Rab8 guanine nucleotide exchange factor (GEF) Rabin8 (a Sec2p homolog) which we find is involved in spine synapse formation. | SIGNOR-263032 |
P35354 | O95644 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.316 | NFAT induces the transcription of the COX2 (cyclo-oxygenase-2) gene incancer cells thereby enhancing invasive migration | SIGNOR-264026 |
P49427 | Q15418 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.335 | RSK1 phosphorylated Thr162 on UBE2R1.RSK1 induced self-ubiquitination and destabilisation of UBE2R1 by phosphorylation. | SIGNOR-277330 |
P31749 | Q92934 | 1 | phosphorylation | down-regulates activity | 0.823 | Experiments in this study reveal that akt phosphorylates bad both in vitro and in vivo and that akt-mediated phosphorylation of bad effectively blocks bad induced cell death.[...] In addition, these findings implicate a particular phosphorylation site on bad, serine 136, in the suppression of bad-mediated death by akt.[...]The Phosphorylation of bad may lead to the prevention of cell death via a mechanism that involves the selective association of the phosphorylated forms of bad with 14-3-3 protein isoforms. Akt phosphorylates bad in vitro and in vivo we show that growth factor activation of the pi3'k/akt signaling pathway culminates in the phosphorylation of the bcl-2 family member bad, thereby suppressing apoptosis and promoting cell survival. Akt phosphorylates bad in vitro and in vivo erbb-mediated phosphorylation of bad by akt promotes survival by blocking the interaction of this pro-apoptotic molecule with bcl-2 and bcl-x proteins | SIGNOR-52863 |
P48729 | P10070 | 1 | phosphorylation | down-regulates | 0.568 | Gli2 can also be phosphorylated directly by ck-1 at the non-optimal sites | SIGNOR-146112 |
Q6UWZ7 | Q13315 | 0 | phosphorylation | up-regulates activity | 0.2 | In this study, we demonstrate that ionizing radiation (IR)-induces ATM-dependent phosphorylation of serine 404 (S404) next to the pSPxF motif. Crystal structures of BRCT/Abraxas show that phosphorylation of S404 is important for extensive interactions through the N-terminal sequence outside the pSPxF motif and leads to formation of a stable dimer. | SIGNOR-255587 |
P51812 | Q13164 | 0 | phosphorylation | up-regulates activity | 0.561 | This suggested that ERK5 may directly activate RSKs.|In vitro active ERK5 also phosphorylated RSK2 that had been immunoprecipitated from transfected cells using an anti-HA antibody ( Fig. 2 B).|Phosphorylation of RSK2 by ERK5 in vitro increased its activity towards GST-S6 as much as 8-fold (Figs. 2 C and E). | SIGNOR-279216 |
O43318 | P52564 | 1 | phosphorylation | up-regulates activity | 0.764 | The activity of tak1 to phosphorylate mkk6, which activates the jnk-p38 kinase pathway, is directly regulated by k63-linked polyubiquitination | SIGNOR-109497 |
P28482 | Q96EP5 | 1 | phosphorylation | down-regulates activity | 0.2 | Further experiments showed that DAZAP1 was phosphorylated stoichiometrically in vitro by ERK2 (extracellular-signal-regulated protein kinase 2) at two Thr-Pro sequences (Thr269 and Thr315), and that both sites became phosphorylated in HEK-293 (human embryonic kidney 293) cells in response to PMA or EGF (epidermal growth factor), or RAW 264.7 macrophages in response to LPS. Phosphorylation of the ARE-binding protein DAZAP1 by ERK2 induces its dissociation from DAZ | SIGNOR-262970 |
P48736 | Q01105 | 1 | phosphorylation | up-regulates activity | 0.336 | We show that PI3Kgamma phosphorylates I2PP2A on serine 9 and 93 residues resulting in enhanced interaction of I2PP2A with PP2A. | SIGNOR-278320 |
P06493 | Q6P1N0 | 1 | phosphorylation | up-regulates activity | 0.2 | We identified the Ser208 residue of Aki1 as a cyclin B1–Cdk1 phosphorylation site. Furthermore, cyclin B1–Cdk1 inhibitor treatment was shown to attenuate the level of Aki1 in complex with Scc1, suggesting that Aki1 phosphorylation by cyclin B1–Cdk1 contributes to Aki1–Scc1 complex formation. | SIGNOR-268297 |
P19838 | O14920 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.853 | Ikkbeta phosphorylates p105 resulting in its degradation, which releases tpl2 resulting in activation of the pro-proliferative map kinase- pathway. | SIGNOR-70473 |
P53778 | P46734 | 0 | phosphorylation | up-regulates | 0.648 | Mkk3, mkk4 and mkk6 all show a strong preference for phosphorylation of the tyrosine residue of the thr-gly-tyr motifs in their known substrates sapk2a/p38, sapk3/p38 gamma and sapk4/p38 delta. we therefore examined the phosphorylation of sapk2a/p38, sapk3/p38? And sapk4/p38? By mkk3, mkk4 and mkk6, which are all known to be capable of activating these enzymes in vitro. | SIGNOR-83718 |
Q05513 | P35236 | 1 | phosphorylation | up-regulates activity | 0.26 | HePTP is phosphorylated by PKC isozymes at Ser-225 in vitro. While all isozymes phosphorylated Ser-225 predominantly and Ser-113 to a lesser extent (Fig. (Fig.5),5), they differed strikingly in how much 32P they incorporated into HePTP during the 30-min assay. PKC θ was the most efficient, while PKC ζ and PKC μ were clearly less potent; PKC δ, ɛ, and η were quite inefficient. | SIGNOR-276047 |
O95071 | P35558 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.308 | Acetylation Regulates Gluconeogenesis by Promoting PEPCK1 Degradation via Recruiting the UBR5 Ubiquitin Ligase |UBR5 ubiquitinates the acetylated PEPCK1 | SIGNOR-267600 |
Q92824 | P01178-PRO_0000020495 | 1 | cleavage | up-regulates quantity | 0.2 | Oxytocin-extended form is further cleaved by enzymatic activity to yield the nine-amino-acid active peptide, OT. The proteolysis may involve several pro-hormone convertases, convertase 2 (PC2) (20p11-1-11.2) and convertase 5 (PC5) (9q21.3) (Gabreels et al 1998). Both enzymes are found in OT neurosecretory vesicles and are a part of a family of subtilisen/kexinlike convertases (Seidah et al 1994). It is a product of the OT gene located at human gene locus 20p13 (Rao et al 1992). The processing cascade results in the production of neurophysin I and OT extended form (OT-X), which is OT with a C-terminal, three-amino-acid extension. | SIGNOR-270334 |
P06241 | P51911 | 1 | phosphorylation | down-regulates activity | 0.333 | We identify, for the first time, tyrosine-phosphorylated calponin h3 within COS 7 cells, before and after their transfection with the pSV vector containing cDNA encoding the cytoplasmic, Src-related, tyrosine kinase, Fyn. we have localized the tyrosines phosphorylated without actin to Tyr261 in calponin h3 and to Tyr261 and Tyr182 in calponin h1. Tyrosine phosphorylation of calponins inhibits their binding to F-actin | SIGNOR-251157 |
Q76N32 | P53350 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.44 | We show that the intercentrosomal linker protein Cep68 is degraded in prometaphase through the SCF(βTrCP) (Skp1-Cul1-F-box protein) ubiquitin ligase complex. Cep68 degradation is initiated by PLK1 phosphorylation of Cep68 on Ser 332, allowing recognition by βTrCP. | SIGNOR-275621 |
O95886 | Q9Y566 | 1 | relocalization | up-regulates activity | 0.8 | SHANK proteins are ‘master’ scaffolding proteins that tether and organize intermediate scaffolding proteins. They are located at excitatory synapses, where they are crucial for proper synaptic development and function. SAPAP proteins subsequently bind to the PDZ domain of members of the SHANK protein family. SHANK proteins then bind to the actin cytoskeleton and to Homer protein, which in turn interacts with mGluRs. Through these extended links, PSD95, SAPAP, SHANK and Homer proteins form a quaternary complex that brings together mGluR and NMDAR complexes in the PSD (FIG. 3). | SIGNOR-264592 |
Q13131 | P06400 | 1 | phosphorylation | down-regulates | 0.2 | Amp-activated protein kinase phosphorylates retinoblastoma protein. Rb phosphorylation sites, ser804 (ser811 in human), resembled the ampk consensus phosphorylation site. | SIGNOR-184052 |
P48730 | P46937 | 1 | phosphorylation | down-regulates | 0.421 | LATS1/2-mediated phosphorylation of a conserved serine in this region (Ser311 in human TAZ; Ser397 in human YAP) primes for further phosphorylation by CK1_/_ kinases (Ser314 on human TAZ; Ser400/403 in human YAP) | SIGNOR-230738 |
O95835 | Q96J02 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.516 | Furthermore, ITCH mediated degradation of LATS1 was associated with enhanced cell growth, induction of epithelial-mesenchymal transition, and increased tumorigenicity.|Ubiquitination of LATS1 catalyzed by ITCH stimulated the proteasomal degradation of LATS1. | SIGNOR-278816 |
O15554 | Q9NRX4 | 0 | dephosphorylation | down-regulates activity | 0.549 | We now show that the mammalian protein histidine phosphatase (PHPT-1) directly binds and inhibits KCa3.1 by dephosphorylating histidine 358 on KCa3.1.|Overexpression of wild-type, but not a phosphatase dead, PHPT-1 inhibited KCa3.1 channel activity. | SIGNOR-277071 |
P84022 | P27361 | 0 | phosphorylation | down-regulates | 0.623 | These results suggest that oncogenic ras, acting through mek1 and erk kinases, induces the phosphorylation of smad2 and smad3. | SIGNOR-66781 |
Q13546 | P23458 | 0 | phosphorylation | up-regulates activity | 0.2 | In addition , our results suggest JAK1 could be recruited to TNF-RSC to modulate RIPK1 activity .|In this study, we show that non-receptor tyrosine kinases JAK1 and SRC could phosphorylate RIPK1 on tyrosine 384 (Y384) in human RIPK1 (Y383 in mouse RIPK1), and serve as essential regulators of RIPK1 in the TNFR1 signaling pathway. | SIGNOR-278948 |
P08253 | P07585 | 1 | cleavage | down-regulates quantity by destabilization | 0.695 | Degradation of decorin by matrix metalloproteinases. These data indicate proteolytic degradation of DCN by MMP-2, MMP-3 and MMP-7, and suggest the possibility that, under pathophysiological conditions, the digestion by the MMPs may induce tissue reactions mediated by TGF-beta1 released from DCN in the connective tissues. | SIGNOR-256350 |
Q15349 | Q92934 | 1 | phosphorylation | down-regulates | 0.373 | The rsks catalyze the phosphorylation of the pro-apoptotic protein bad at serine 112 to promote cell survival. | SIGNOR-184591 |
O43255 | Q16539 | 0 | phosphorylation | up-regulates | 0.2 | We show that siah2 is subject to phosphorylation by p38 mapk, which increases siah2-mediated degradation of phd3. | SIGNOR-149890 |
P17252 | Q99623 | 1 | phosphorylation | down-regulates activity | 0.2 | PKC\u03b1 phosphorylates PHB2-S39. | SIGNOR-279256 |
P36406 | Q9Y4K3 | 1 | ubiquitination | up-regulates activity | 0.313 | We show here that the upregulation of NF-kappaB by UL144 is dependent upon cellular tripartite motif 23 (TRIM23) protein. We propose a mechanism by which UL144 activates NF-kappaB through a direct interaction with the cellular protein TRIM23 in a complex containing TRAF6. we propose that TRIM23 mediates TRAF6 autoubiquitination in the presence of UL144, resulting in the virally controlled activation of NF-κB stimulation at early times of HCMV infection. | SIGNOR-266655 |
Q8NG66 | P51955 | 0 | phosphorylation | up-regulates | 0.393 | Nek2 directly phosphorylated nek11 in the c-terminal non-catalytic region and elevated nek11 kinase activity. | SIGNOR-124944 |
P19784 | P18887 | 1 | phosphorylation | up-regulates activity | 0.46 | XRCC1 is phosphorylated in vivo and in vitro by CK2, and CK2 phosphorylation of XRCC1 on S518, T519, and T523 largely determines aprataxin binding to XRCC1 though its FHA domain | In addition, we present data to show that the acute loss of aprataxin by small interfering RNA (siRNA) renders HeLa cells sensitive to MMS through a mechanism that destabilizes XRCC1. | SIGNOR-251050 |
O15294 | P08237 | 1 | glycosylation | down-regulates activity | 0.346 | Our previous investigation on O-GlcNAcylation of PFK1 has demonstrated that O-GlcNAcylation inhibits PFK1 enzyme activity|In cells, a single set of antagonistic enzymes-O-GlcNAc transferase (OGT) and O-GlcNAc hydrolase are responsible for the addition and removal of GlcNAc moiety, respectively. | SIGNOR-267584 |
P09467 | Q8IYT8 | 0 | phosphorylation | down-regulates activity | 0.2 | Here, we demonstrate that, during deprivation of amino acid and growth factors, ULK1/2 directly phosphorylate key glycolytic enzymes including hexokinase (HK), phosphofructokinase 1 (PFK1), enolase 1 (ENO1), and the gluconeogenic enzyme fructose-1,6-bisphosphatase (FBP1).Phosphorylation of these enzymes leads to enhanced HK activity to sustain glucose uptake but reduced activity of FBP1 to block the gluconeogenic route and reduced activity of PFK1 and ENO1 to moderate drop of glucose-6-phosphate and to repartition more carbon flux to pentose phosphate pathway (PPP), maintaining cellular energy and redox homeostasis at cellular and organismal levels.Similar results were also obtained using ULK2 as the kinase (data not shown). | SIGNOR-274039 |
Q7Z6M1 | P51151 | 0 | null | up-regulates activity | 0.581 | P40 is a very potent transport factor in that the pure, recombinant protein can stimulate, significantly, an in vitro transport assay that measures transport of mannose 6-phosphate receptors from endosomes to the trans-Golgi network. The functional importance of p40 is confirmed by the finding that anti-p40 antibodies inhibit in vitro transport. Finally, p40 shows synergy with Rab9 in terms of its ability to stimulate mannose 6-phosphate receptor transport. These data are consistent with a model in which p40 and Rab9 act together to drive the process of transport vesicle docking. | SIGNOR-253088 |
P16104 | P35226 | 0 | ubiquitination | up-regulates activity | 0.2 | In this process, BMI1 ubiquitinates histone H2A and \u03b3H2AX, thereby facilitating the repair of double-stranded DNA breaks through stimulating homologous recombination and non-homologous end joining. | SIGNOR-278744 |
O60260 | Q03135 | 1 | ubiquitination | down-regulates quantity | 0.2 | Parkin induces the degradation of cav-1 through the proteasome dependent pathway.|We also demonstrated that WT parkin ubiquitinates cav-1 for degradation. | SIGNOR-278710 |
P04637 | O43293 | 0 | phosphorylation | up-regulates | 0.406 | A cell-free ser(20) phosphorylation site assay was used to identify a broad range of calcium calmodulin kinase superfamily members, including chk2, chk1, dapk-1, dapk-3, drak-1, and ampk, as ser(20) kinases.Evaluation of these calcium calmodulin kinase superfamily members as candidate ser(20) kinases in vivo has shown that only chk1 or dapk-1 can stimulate p53 transactivation and induce ser(20) phosphorylation of p53. | SIGNOR-153495 |
P98170 | P04049 | 0 | phosphorylation | up-regulates activity | 0.504 | Interaction and stabilization of X-linked inhibitor of apoptosis by Raf-1 protein kinase.|We also demonstrate that Raf-1 phosphorylates XIAP in vitro and in vivo. | SIGNOR-279105 |
P01106 | P49840 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.406 | Similar to c-myc, similar to c-myc, we report here that phosphorylation of c-jun by gsk3 creates a high-affinity binding site for the e3 ligase fbw7, which targets c-jun for polyubiquitination and proteasomal degradation. | SIGNOR-138596 |
P00519 | Q13315 | 0 | phosphorylation | up-regulates | 0.744 | Ataxia telangiectasia mutant protein activates c-abl tyrosine kinase in response to ionizing radiation. Atm kinase domain corrects this defect, as it phosphorylates the c-abl tyrosine kinase in vitro at ser 465, leading to the activation of c-abl. | SIGNOR-48818 |
P17252 | P11831 | 1 | phosphorylation | up-regulates | 0.245 | Myotonic dystrophy protein kinase (DMPK), a muscle- and neuron-restricted kinase, enhanced SRF-mediated promoter activity of the skeletal and cardiac alpha-actin genes in C2C12 myoblasts as well as in nonmyogenic cells. | Threonine 159 in the MADS box alphaI coil was a specific phosphorylation target in vitro as well as in vivo of both DMPK and protein kinase C-alpha. | SIGNOR-188181 |
Q9UQ80 | Q13153 | 0 | phosphorylation | up-regulates | 0.2 | We found that pak1 phosphorylated ebp1 in vitro and mapped the phosphorylation site to threonine 261. these studies demonstrate for the first time that ebp1 is a substrate of pak1 and the importance of the pak1 phosphorylation site for the functional activity of ebp1 in breast cancer cells. | SIGNOR-160963 |
P58012 | O95835 | 0 | phosphorylation | up-regulates activity | 0.452 | LATS1 phosphorylates forkhead L2 and regulates its transcriptional activity.|Last, we demonstrated that coexpression with LATS1 enhances FOXL2 's activity as a repressor of the StAR promoter, and this results from the kinase activity of LATS1. | SIGNOR-279624 |
Q9H2K2 | P54274 | 1 | ADP-ribosylation | down-regulates activity | 0.549 | Tankyrase 2 poly(ADP-ribosyl)ated itself and TRF1. Overexpression of tankyrase 2 in the nucleus released endogenous TRF1 from telomeres. | SIGNOR-263376 |
Q15797 | Q9UNE7 | 0 | ubiquitination | down-regulates | 0.328 | These results suggest that chip can interact with the smad1/smad4 proteins and block bmp signal transduction through the ubiquitin-mediated degradation of smad proteins. | SIGNOR-120731 |
Q14493 | A0A2R8Y619 | 1 | translation regulation | up-regulates quantity by expression | 0.2 | Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control. | SIGNOR-265380 |
Q9GZQ8 | Q05513 | 0 | phosphorylation | down-regulates activity | 0.2 | LC3B is phosphorylated at Thr-50 within the LDS by serine/threonine kinase (STK) 3 and STK4. Here, we identified LIR motifs in STK3 and atypical protein kinase Cζ (PKCζ) and never in mitosis A (NIMA)-related kinase 9 (NEK9). All three kinases phosphorylated LC3B Thr-50 in vitro A phospho-mimicking substitution of Thr-50 impaired binding of several LIR-containing proteins, such as ATG4B, FYVE, and coiled-coil domain-containing 1 (FYCO1), and autophagy cargo receptors p62/sequestosome 1 (SQSTM1) and neighbor of BRCA1 gene (NBR1). | SIGNOR-273906 |
Q8TDQ0 | Q08881 | 0 | phosphorylation | up-regulates activity | 0.31 | When we tested the effect of ITK on the Y265 mutant, we found a pronounced reduction of ITK-mediated tyrosine phosphorylation, suggesting that Y265 is specifically phosphorylated by ITK (Fig. 3B). Our results demonstrate that specific phosphorylation of Y265 of Tim-3 occurs in the presence of galectin-9, probably through a receptor-ligand interaction. Phosphorylation of Y265, which is situated in a highly conserved SH2 binding domain, could result in the recruitment of SH2 containing adaptor proteins and trigger downstream signalling events regulating the fate of Tim-3 expressing T-cells. | SIGNOR-273644 |
P61586 | Q9P107 | 0 | gtpase-activating protein | down-regulates activity | 0.643 | We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2). | SIGNOR-260505 |
Q9P1Y6 | P09874 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | Furthermore, PHRF1 mediates PARP1 polyubiquitination for proteasomal degradation. | SIGNOR-278774 |
Q09472 | Q04206 | 1 | acetylation | up-regulates activity | 0.822 | Using acetylation assays, p300 was found to effectively acetylate RelA/p65 across the amino-acid region containing 1317 | SIGNOR-238778 |
Q16254 | O15392 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.334 | This TGF-beta response is triggered through a Smad2/3-dependent hypophosphorylation of Rb and the subsequent association of the Rb/E2F4 repressive complex to CDE/CHR elements in the proximal region of the survivin promoter. | SIGNOR-271678 |
O14745 | P06493 | 0 | phosphorylation | down-regulates activity | 0.276 | During the early stages of mitosis in HeLa cells, Cdc2 phosphorylates EBP50 on serine residues 280 and 302.|Phosphorylation by Cdc2 inhibits EBP50's role in forming microvilli in interphase but not mitotic cells. (A) Results from scoring JEG-3 cells for the presence of microvilli; error bars indicate mean \u00b1 SD. (B) Representative images from the microvillar rescue assay. | SIGNOR-278305 |
P48431 | P00533 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.48 | These data indicate that EGFR\u2010induced SOX2 Tyr277 phosphorylation prevents the autophagic degradation of SOX2 and enhances its stability. | SIGNOR-279036 |
Q9BTM1 | Q14493 | 0 | translation regulation | up-regulates quantity by expression | 0.2 | Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control. | SIGNOR-265412 |
P17612 | P20810 | 1 | phosphorylation | up-regulates activity | 0.2 | The results showed that PKA promoted the phosphorylation of calpastatin, and a high phosphorylation level was maintained during incubation. Phosphorylation at serine 133 of calpastatin enhanced its inhibition on calpain activity by maintaining its structural stability, thus inhibiting the tenderization of meat. | SIGNOR-277839 |
O94827 | P61586 | 1 | guanine nucleotide exchange factor | up-regulates activity | 0.771 | We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2). | SIGNOR-260566 |
P17612 | Q9BZE0 | 1 | phosphorylation | down-regulates activity | 0.283 | Protein kinase a (pka) and glycogen synthase kinase 3beta sequentially phosphorylate gli2 at multiple sites, identified by mutagenesis, thus resulting in a reduction of its transcriptional activity | SIGNOR-145131 |
O43541 | Q99717 | 0 | transcriptional regulation | up-regulates quantity | 0.599 | Chromatin immunoprecipitation (ChIP) revealed a subset of the BIG (BMP4 induced genes) signature, including Satb2, Smad6, Hand1, Gadd45γ and Gata3, that was bound by Smad1/5 in the developing mandible, revealing direct Smad-mediated regulation | SIGNOR-268940 |
O00743 | P78527 | 1 | dephosphorylation | up-regulates activity | 0.538 | In addition, siRNA knockdown of either PP6R1 or PP6 significantly decreased IR activation of DNA-PK, suggesting that PP6 activates DNA-PK by association and dephosphorylation.|PP6 may dephosphorylate sites in DNA-PKcs to reduce binding with heterodimer Ku proteins, because DNA-PK activation completely depends on Ku-mediated complex formation with DNA. | SIGNOR-277164 |
Q05397 | P16234 | 0 | phosphorylation | up-regulates activity | 0.429 | Focal adhesion kinase (FAK) has a crucial role in integration of signals from integrins and growth factor receptors. In this study, we demonstrate that growth factor receptors including hepatocyte growth factor receptor Met, epidermal growth factor receptor, and platelet-derived growth factor receptor directly phosphorylate FAK on Tyr194 in the FERM domain (band 4.1 and ezrin/radixin/moesin homology domain). Upon binding to Met or phosphoinositides, FAK may undergo conformational changes, which renders Tyr194 accessible for phosphorylation. Substitution of Tyr194 with Phe significantly suppresses the activation of FAK by Met. | SIGNOR-259400 |
O75901 | O43318 | 0 | phosphorylation | up-regulates activity | 0.2 | As expected, increased expression of TAK1 induced by LV-TAK1 stimulated p-RASSF9, whereas p-MEK and p-ERK were reduced.|We further identified RASSF9 as a downstream target of TAK1 which phosphorylates RASSF9 at S284. | SIGNOR-279534 |
P05114 | P51812 | 0 | phosphorylation | down-regulates activity | 0.364 | We report here that the NBD of the HMGN1 and -N2 protein family is highly and specifically phosphorylated during mitosis and that this phosphorylation has a major functional consequence: it abolishes the interaction of the proteins with its chromatin targets. | SIGNOR-249100 |
Q9H0K1 | P35568 | 1 | phosphorylation | down-regulates quantity | 0.567 | SIK2 is known to attenuate insulin signaling by phosphorylating IRS-1/Ser789 | SIGNOR-265745 |
Q07654 | Q99626 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.391 | The transcription of human TFF3 reporter genes was significantly up-regulated by the transient overexpression of CDX2 in COS-7 cells and AGS gastric cells. | SIGNOR-253967 |
Q9UBE8 | P10242 | 1 | phosphorylation | down-regulates activity | 0.714 | Furthermore, the downregulation of c-Myb by NLK overexpression could be inhibited in cells that had been treated with the 26S proteasome inhibitor MG132 but not in those treated with DMSO ( ).|HIPK2 and NLK directly bind to c-Myb, and NLK phosphorylates c-Myb at multiple sites, resulting in its ubiquitination and proteasome-dependent degradation [32]. | SIGNOR-280049 |
P13762 | Q5T0T0 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | Two E3 ligases, MARCH I and MARCH VIII, have been shown to polyubiquitinate lysine residue 225 in the cytoplasmic tail of I-Abeta and HLA-DRbeta. We show that lysine residue 219 in the cytoplasmic tail of DRalpha is also subject to polyubiquitination. | SIGNOR-271407 |
P98161 | P53355 | 0 | phosphorylation | up-regulates activity | 0.2 | In addition, the tumor suppressor death-associated protein kinase phosphorylates and activates PKD1 in response to oxidative damage ( xref ). | SIGNOR-279985 |
Q14566 | Q13535 | 0 | phosphorylation | up-regulates | 0.562 | Together these data strongly support the conclusion that mec1 directly targets the s/tq sites in mcm4 and mcm6, although it is formally possible that mec1 and mrc1 activate a different s/tq-directed kinase to target mcm4 and mcm6. | SIGNOR-169450 |
O15013 | P63000 | 1 | guanine nucleotide exchange factor | up-regulates activity | 0.442 | We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2). | SIGNOR-260536 |
Q15208 | Q96QF0 | 1 | phosphorylation | up-regulates activity | 0.366 | We identified 5 potential NDR1 substrates in the mouse brain and chose two for functional validation. We show that one NDR1 substrate is another kinase, AP-2 associated kinase-1 (AAK1) which regulates dendritic branching as a result of NDR1 phosphorylation. Another substrate is the Rab8 guanine nucleotide exchange factor (GEF) Rabin8 (a Sec2p homolog) which we find is involved in spine synapse formation. | SIGNOR-263036 |
Q9Y6N7 | P00519 | 0 | phosphorylation | down-regulates | 0.606 | Abl functions to antagonize robo signaling both abl and ena can directly bind to robo's cytoplasmic domain. | SIGNOR-78993 |
Q8NF50 | P17252 | 0 | phosphorylation | down-regulates activity | 0.2 | In response to chemokine stimulation, PKC\u03b1 phosphorylates DOCK8 at its three serine sites, promoting DOCK8 separation from LRCH1 and translocation to the leading edge to guide T cell migration.|Taken our data together, we suggest that PKC\u03b1 phosphorylates DOCK8 at the Ser2077/2082/2087 sites to promote T cell migration. | SIGNOR-279384 |
P28482 | P42229 | 1 | phosphorylation | up-regulates | 0.76 | Gh treatment of chinese hamster ovary cells stably transfected with the gh receptor (choa cells) led to rapid and transient activation of both stat5a and erk1 and erk2. these observations show, for the first time, direct physical interaction between erk and stat5a and also clearly identify serine 780 as a target for erk. | SIGNOR-66239 |
O15355 | P46527 | 1 | dephosphorylation | up-regulates activity | 0.2 | By using genomic phosphatase screening, we identified a PPM family phosphatase, PPM1G, which could reduce p27 phosphorylation at T198.|Functionally, ectopic expression of PPM1G enhanced p27 protein stability and delayed cell cycle progression from G1 to S phase. | SIGNOR-277112 |
Q00535 | Q15833 | 1 | phosphorylation | down-regulates | 0.2 | It was shown that munc18 inhibition of neuronal syntaxin 1 can be overcome by cdk5 phosphorylation, indicating that structural change disrupts the syntaxin-munc18 interaction. | SIGNOR-157528 |
P62136 | P38398 | 1 | dephosphorylation | down-regulates activity | 0.377 | Protein kinases involved in the DNA damage checkpoint control, such as ATM, ATR, and hCds1/Chk2, have been shown to phosphorylate and activate BRCA1 upon DNA damage. |Altogether, these results indicate that PP1α specifically dephosphorylates BRCA1 at multiple serine sites, including S988 [12], S1423, and S1524. | SIGNOR-248560 |
P49840 | P49815 | 1 | phosphorylation | up-regulates | 0.362 | Gsk3 inhibits the mtor pathway by phosphorylating tsc2 in a manner dependent on ampk-priming phosphorylation. | SIGNOR-149377 |
O75928 | Q15759 | 0 | phosphorylation | up-regulates activity | 0.264 | The switch between the coactivating and inhibitory actions of PIASxα is controlled, at least in part, through PIASxα phosphorylation. PIASxα is itself phosphorylated by p38 in vitro and in vivo in response to the activation of stress signaling pathways (Figure 2, Figure 3, Figure 4). We identify Ser113 and Ser 116 as two residues that are phosphorylated by p38 and have important functional roles | SIGNOR-262947 |
Q9P1W9 | Q13541 | 1 | phosphorylation | up-regulates activity | 0.414 | Further, PIM2 triggered phosphorylation of AKT and 4EBP1 (XREF_FIG) clearly demonstrating the activation of PI3K pathway. | SIGNOR-279091 |
Q13464 | O14950 | 1 | phosphorylation | up-regulates | 0.624 | Here we found that rho-kinase has an activity for mrlc diphosphorylation at both threonine 18 and serine 19 in nonmuscle cells using sequential column chromatographies. | SIGNOR-91542 |
Q14164 | Q12933 | 1 | phosphorylation | up-regulates activity | 0.686 | IKKepsilon phosphorylates TRAF2 at Ser11 to activate NF-kappaB and promote malignant transformation. | SIGNOR-279195 |
O94989 | P29323 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.485 | We have identified a RhoA guanine nucleotide exchange factor, Ephexin5, which negatively regulates excitatory synapse development until EphrinB binding to the EphB receptor tyrosine kinase triggers Ephexin5 phosphorylation, ubiquitination, and degradation. EphB2 mediates phosphorylation of Ephexin5 at tyrosine-361 | SIGNOR-262864 |
P28482 | Q9NVD7 | 1 | phosphorylation | up-regulates activity | 0.259 | Actopaxin (alpha-parvin) is a paxillin, integrin-linked kinase, and F-actin binding focal adhesion protein with several serine phosphorylation sites in the amino terminus that contribute to the regulation of cell spreading and migration.|Actopaxin phosphorylation of Ser4/8 enhances cell migration whereas a nonphosphorylatable (Quint) mutant suppresses migration in U2OS osteosarcoma cells (7). | SIGNOR-265759 |
O00330 | Q12778 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.2 | Our genetic analysis indicates that Foxo1 is an effector of Irs2 signaling in pancreatic β cells. Foxo1 inactivation leads to increased Pdx1 expression and β cell proliferation. Since Foxo1 is expressed in a subset of cells embedded within pancreatic ducts, we propose that, in quiescent duct-associated cells that are not committed to a β cell fate, Foxo1 acts as a transcriptional brake on Pdx1. We propose the following mechanism of Foxo1 regulation: small quantities of insulin are released in the pancreatic duct (31), where they activate signaling (32) in the Foxo1-positive duct cell subset, leading to Foxo1 nuclear exclusion and Pdx1 expression. | SIGNOR-278151 |
O95140 | Q9NX47 | 0 | ubiquitination | up-regulates activity | 0.2 | Taken together, these results suggested that MITOL regulates endoplasmic reticulum tethering to mitochondria by activating Mfn2 via K192 ubiquitination.|Therefore, MITOL specifically ubiquitinates mitochondrial Mfn2. | SIGNOR-278553 |
Q9UEE5 | P04637 | 1 | phosphorylation | up-regulates | 0.286 | Genetic and biochemical studies have shown that ser20 phosphorylation in the transactivation domain of p53 mediates p300-catalyzed dna-dependent p53 acetylation and b-cell tumor suppression. a cell-free ser20 phosphorylation site assay was used to identify a broad range of calcium calmodulin kinase superfamily members, including chk2, chk1, dapk-1, dapk-3, drak-1, and ampk, as ser20 kinases. | SIGNOR-153532 |
P17252 | Q96PH1 | 1 | phosphorylation | up-regulates | 0.2 | A constitutively active form of pkc? Robustly increased basal and pma-stimulated nox5 activity and promoted the phosphorylation of nox5 on ser490, thr494, and ser498. | SIGNOR-204550 |
Q15418 | P35568 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.358 | Negative feedback involves s6k, which inactivates irs by phosphorylation at multiple sites, thus inducing its degradation and altered cell localization. | SIGNOR-175687 |
P42768 | P68400 | 0 | phosphorylation | up-regulates | 0.354 | Here we identify two phosphorylation sites in the vca domain of wasp at serines 483 and 484. S483 and s484 are substrates for casein kinase 2 in vitro and in vivo. Phosphorylation of these residues increases the affinity of the vca domain for the arp2/3 complex 7-fold and is required for efficient in vitro actin polymerization by the full-length wasp molecule. | SIGNOR-101268 |
P03952 | P26927 | 1 | cleavage | up-regulates activity | 0.325 | Proteolytic cleavage of pro-MSP at a single site yields active MSP, a disulfide-linked alphabeta-chain heterodimer. human kallikrein cleaved only at Arg483–Val484, the cleavage site for formation of a- and b-chains. | SIGNOR-256511 |
Q05655 | P09874 | 1 | phosphorylation | down-regulates activity | 0.2 | Interestingly, comparable experiments with the Ca 2+ -independent PKC\u03b4 isoform revealed that PKC\u03b4 phosphorylates ARTD1 at the N-terminus (amino acids 1\u2013214) and phosphorylation of ARTD1 by PKC\u03b4 inhibited DNA-induced PAR formation by ARTD1 in vitro (Supplementary Figure S6A and S6B), suggesting that the observed stimulatory effect of the PKCi on PAR formation might be due to inhibition of ARTD1 by PKC\u03b4. | SIGNOR-280085 |
P42681 | P16410 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.498 | We demonstrate that rlk (resting lymphocyte kinase) is capable of phosphorylating ctla-4 at the yvkm motif. Consistent with this finding, rlk is capable of providing conditions for the binding of the sh2 domains of pi 3-kinase to the receptor. Ctla-4 is therefore the first known substrate for rlk suggesting the possibility that this kinase may participate in ctla-4 function | SIGNOR-61624 |
P46734 | Q7L7X3 | 0 | phosphorylation | up-regulates activity | 0.578 | The activation of and binding to MEK3 by TAO1 implicates TAO1 in the regulation of the p38-containing stress-responsive MAP kinase pathway | SIGNOR-60818 |
P48436 | P49841 | 0 | phosphorylation | down-regulates activity | 0.444 | (E) The SOX9 K2 domain is phosphorylated by GSK3\u03b2 at T236.|Based on our findings that inhibition of GSK3\u03b2 prevents DNA damage-induced SOX9 degradation, and that FBW7 targets SOX9 for degradation after DNA damage, we reasoned that phosphorylation of SOX9 by GSK3\u03b2 is required for FBW7-mediated SOX9 degradation. | SIGNOR-279725 |
O15198 | Q9HCE7 | 0 | ubiquitination | down-regulates | 0.669 | Smurf1 and smurf2 are e3 ubiquitin ligases known to suppress tgf-beta signaling through degra-dation of smads and receptors for tgf-beta and bmps | SIGNOR-195669 |
Q05655 | P12830 | 1 | phosphorylation | down-regulates activity | 0.2 | Phosphorylation of E-cadherin at threonine 790 by protein kinase Cδ reduces β-catenin binding and suppresses the function of E-cadherin. | SIGNOR-260893 |
P98170 | P60953 | 1 | ubiquitination | down-regulates quantity | 0.398 | As XIAP can directly ubiquitinate Cdc42, we tested if the RING domain of XIAP is required for modulating the protein levels of Cdc42 in vivo .|We then investigated the molecular mechanisms behind XIAP mediated Cdc42 degradation. | SIGNOR-278799 |
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