IdA string | IdB string | labels int64 | mechanism string | effect string | score float64 | sentence string | signor_id string |
|---|---|---|---|---|---|---|---|
P23946 | P14138 | 1 | cleavage | up-regulates activity | 0.374 | Chymase from human mast cells selectively cleaved big endothelins (ETs) at the Tyr31-Gly32 bond and produced novel trachea-constricting 31-amino acid-length endothelins, ETs(1-31), without any further degradation products. | SIGNOR-256355 |
Q9Y6E0 | Q7L7X3 | 1 | phosphorylation | up-regulates activity | 0.2 | Thus, MST3 phosphorylates TAO1 and TAO2, enabling their association with Myosin Va. | SIGNOR-280140 |
Q9BR76 | P17252 | 0 | phosphorylation | down-regulates | 0.324 | We have identified serine 2 (ser-2) on coronin 1b as the major residue phosphorylated by pkc in vivo.In this work, we show that coronin 1b interacts in vivo with the arp2/3 complex and that this interaction is inhibited by pkc phosphorylation. | SIGNOR-138733 |
P17252 | P21399 | 1 | phosphorylation | down-regulates | 0.2 | Irp1 ser-711 is a phosphorylation site, critical for regulation of rna-binding and aconitase activities. | SIGNOR-133188 |
O15350 | P24941 | 0 | phosphorylation | down-regulates activity | 0.575 | Cyclin-dependent kinases phosphorylate p73 at threonine 86 in a cell cycle-dependent manner and negatively regulate p73.Furthermore, cyclin a/cdk1/2, cyclin b/cdk1/2, and cyclin e/cdk2 complexes can phosphorylate multiple p73 isoforms in vitro at threonine 86. | SIGNOR-99746 |
O75044 | P63000 | 1 | gtpase-activating protein | down-regulates activity | 0.588 | 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-260516 |
Q9BXF6 | 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-263035 |
Q14493 | P0C0S8 | 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-265403 |
O95786 | Q96EQ8 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.671 | Here, we found that RIG-I undergoes proteasomal degradation after conjugation to ubiquitin by RNF125. Further, RNF125 conjugates ubiquitin to MDA5, a family protein of RIG-I as well as IPS-1, which is also a downstream protein of RIG-I signaling that results in suppressing the functions of these proteins. Because RNF125 is enhanced by IFN, these functions constitute a negative regulatory loop circuit for IFN production. | SIGNOR-271647 |
O95644 | P48454 | 0 | relocalization | up-regulates | 0.704 | The ca2+ dependent phosphatase calcineurin induces cardiac and skeletal muscle hypertrophy by a process that involves nf-at nuclear translocation, and activation of mef2c. | SIGNOR-179796 |
P49841 | Q14653 | 1 | phosphorylation | up-regulates activity | 0.346 | Invitro, both GSK3alpha and GSK3beta phosphorylate IRF3 at the linker region. | SIGNOR-279182 |
Q14493 | P0C1H6 | 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-265395 |
P23470 | Q14247 | 1 | dephosphorylation | down-regulates activity | 0.2 | PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity. | SIGNOR-254696 |
Q5TG30 | P60953 | 1 | gtpase-activating protein | down-regulates activity | 0.41 | 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-260497 |
O96017 | O15151 | 1 | phosphorylation | down-regulates | 0.723 | Phosphorylation of s342 and s367 in vivo require the chk2 kinase. Chk2 also stimulates mdmx ubiquitination and degradation by mdm2 | SIGNOR-140417 |
Q12879 | P78352 | 0 | relocalization | up-regulates activity | 0.811 | The PDZ domains of PSD-95 and related proteins interact with the COOH-terminal sequences of K+channels and NMDA2 receptors (3). By these interactions, PSD-95 may mediate the clustering of K+ channels and NMDA receptors at synapses. | SIGNOR-264194 |
P04150 | P05026 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | Together these data indicate that the 21-base pair sequence represents a true MRE/GRE and that optimal activation of the human Na/K-ATPase beta1 promoter is controlled by mineralocorticoid and glucocorticoid hormones. It appears that an interaction of MR with GR on the beta1 promoter effectively down-regulates transcription. | SIGNOR-254864 |
P16112 | O60882 | 0 | cleavage | down-regulates quantity by destabilization | 0.477 | Matrix metalloproteinases 19 and 20 cleave aggrecan and cartilage oligomeric matrix protein (COMP)|It has been suggested that MMPs play a role in the hydrolysis of COMP and, therefore, compromise the integrity of the cartilage ECM structure leading to the ultimate loss of joint function | SIGNOR-266981 |
Q14258 | P12931 | 0 | phosphorylation | up-regulates activity | 0.271 | Here, we demonstrated that TRIM25 interacted with c-Src and underwent tyrosine phosphorylation by c-Src kinase upon viral infection and the phosphorylation is required for the complete activation of RIG-I signaling. Analysis using a c-Src inhibitor and TRIM25 mutant, in which tyrosine 278 is substituted by phenylalanine (Y278F), suggested that the phosphorylation positively regulates K63-linked polyubiquitination of RIG-I and subsequent antiviral signaling. | SIGNOR-277405 |
P48431 | O00308 | 0 | ubiquitination | down-regulates quantity | 0.361 | Among the four E3 ligases, only WWP2 knockdown was found to increase SOX2 protein levels in GSCs (Fig.\u00a04A).|We first verified that WWP2 ubiquitinates SOX2 in vitro. | SIGNOR-278798 |
O15297 | Q13950 | 1 | dephosphorylation | up-regulates activity | 0.444 | Activating dephosphorylation of RUNX2 by Wip1 increases its transcriptional activity on the Bax promoter. | SIGNOR-277110 |
P50616 | P45984 | 0 | phosphorylation | down-regulates | 0.34 | Biochemical analyses have then shown that erk mapk (erk2) and jnk/sapk (jnk2) bind to and phosphorylate tob in vitro. | SIGNOR-91067 |
P24941 | P12830 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.429 | Priming phosphorylation of Cdh1 by the Cdk2/cyclin A kinase complex allows Plk1 to bind to Cdh1 and phosphorylate Cdh1 at Ser138 and Ser146. Phosphorylation of Cdh1 at Ser138 and Ser146 then triggers its interaction with, and subsequent ubiquitination by, SCFbeta-TRCP | SIGNOR-274049 |
P04637 | P54278 | 1 | transcriptional regulation | up-regulates quantity | 0.582 | .... numerous potentially novel targets, including the DNA mismatch repair genes MLH1 and PMS2. Both of these genes were determined to be responsive to DNA damage and p53 activation in normal human fibroblasts, and have p53-response elements within their first intron. | SIGNOR-257604 |
O15055 | Q00987 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.356 | We identified PER2 as a previously uncharacterized substrate for the ubiquitin ligase mouse double minute 2 homolog (MDM2) and found that MDM2 targeted PER2 for degradation in a manner independent of PER2 phosphorylation. | SIGNOR-277421 |
Q9UGL1 | Q9H9S0 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.308 | Phosphorylation of KDM5B at Ser1456 attenuated the occupancy of KDM5B on the promoters of pluripotency genes. | SIGNOR-273451 |
P50613 | Q00535 | 1 | phosphorylation | up-regulates activity | 0.517 | In addition, the Cdk7 substrate, CTD of RNAPII, causes a dose-dependent decline in Cdk5 activation by Cdk7.|Likewise, Cdk7 or cyclin H immunoprecipitate from mouse brain specifically phosphorylates wt Cdk5 at Ser159 and enhances Cdk5 and p25 activity. | SIGNOR-278923 |
Q9NVW2 | Q96MM3 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.337 | RNF12 causes ubiquitination and proteasomal degradation of REX1, and Rnf12 knockout embryonic stem cells show an increased level of REX1. | SIGNOR-269002 |
Q96AY2 | P53350 | 0 | phosphorylation | up-regulates activity | 0.447 | In human cells, EME1 is phosphorylated by both cyclin-dependent kinases (CDKs) and PLK1, and this modification is directly correlated with increased MUS81 cleavage activity in\u00a0vitro. | SIGNOR-280068 |
P31749 | P06748 | 1 | phosphorylation | down-regulates activity | 0.534 | We find that AKT phosphorylation of NPM-Ser48 prevents oligomerization that results in nucleoplasmic localization of ARF, constitutive MDM2 inhibition and stabilization of p53. | SIGNOR-276667 |
Q05655 | P40763 | 1 | phosphorylation | up-regulates | 0.596 | Abrogation of pkcdelta activity inhibited insulin-induced stat3 phosphorylation, pkcdelta-stat3 association and nuclear translocation. | SIGNOR-143828 |
P08575 | P06239 | 1 | dephosphorylation | up-regulates activity | 0.797 | CD45 differentially regulates the negatively acting pTyr-505 and positively acting pTyr-394 p56(lck) tyrosine kinase phosphorylation sites. We propose that high wild-type CD45 expression is necessary to dephosphorylate p56(lck) pTyr-394, suppressing CD4 T+ cell lineage commitment and hyperactivity. | SIGNOR-259933 |
Q86XK2 | P04637 | 1 | neddylation | down-regulates | 0.671 | Fbxo11 promotes the neddylation of p53 and inhibits its transcriptional activity / we found that fbxo11 also neddylates p53 on two lysines, lys-320 and lys-321 | SIGNOR-150669 |
Q15672 | Q15759 | 0 | phosphorylation | up-regulates | 0.2 | Phosphorylation of serine 68 of twist1 by mapks stabilizes twist1 protein and promotes breast cancer cell invasiveness. this ser 68 is phosphorylated by p38, c-jun n-terminal kinases (jnk), and extracellular signal-regulated kinases1/2 in vitro | SIGNOR-173405 |
O15151 | P31749 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.509 | We demonstrate that the serine/threonine kinase akt mediates phosphorylation of mdmx at ser367. This phosphorylation leads to stabilization of mdmx and consequent stabilization of mdm2. | SIGNOR-252517 |
Q7Z6Z7 | Q9C0C7 | 0 | relocalization | up-regulates activity | 0.2 | AMBRA1 regulates mitophagy at two critical steps. Upon mitophagy stimulation, AMBRA1 mediates the HUWE1 E3 ubiquitin ligase translocation from cytosol to mitochondria (light blue). AMBRA1 acts as a cofactor for HUWE1 E3 ubiquitin ligase activity, favouring its binding to its substrate MFN2 (and maybe other OMM substrates) and targeting it to the proteasome | SIGNOR-272962 |
O96017 | P00441 | 1 | phosphorylation | up-regulates activity | 0.376 | ROS signaling is mediated by Mec1/ATM and its effector Dun1/Cds1 kinase, through Dun1 interaction with Sod1 and regulation of Sod1 by phosphorylation at S60, 99. In the nucleus, Sod1 binds to the promoters and regulates the expression of oxidative resistance and repair genes. | SIGNOR-262794 |
Q5VTR2 | P36956 | 1 | ubiquitination | down-regulates activity | 0.425 | Here, we reveal that RNF20-induced SREBP1c ubiquitination down-regulates hepatic lipogenic activity upon PKA activation.|Overexpression of RNF20 represses SREBP1c activity, leading to a decrease in the expression of lipogenic genes. | SIGNOR-278643 |
O14965 | P17612 | 0 | phosphorylation | up-regulates activity | 0.512 | Aurora2 is regulated by phosphorylation. phosphorylation occurs on a conserved residue, Threonine 288, within the activation loop of the catalytic domain of the kinase and results in a significant increase in the enzymatic activity. Threonine 288 resides within a consensus motif for the cAMP dependent kinase and can be phosphorylated by PKA in vitro. | SIGNOR-250337 |
P29350 | P35968 | 1 | dephosphorylation | down-regulates activity | 0.668 | Src homology 2 (SH2) domain containing protein tyrosine phosphatase-1 (SHP-1) dephosphorylates VEGF Receptor-2 and attenuates endothelial DNA synthesis, but not migration|Knockdown of SHP-1 by siRNA or inhibition of c-Src by an inhibitor, results in augmented DNA synthesis perhaps due to increased phosphorylation of at least three tyrosine residues of KDR 996, 1059 and 1175 | SIGNOR-248474 |
P10636 | Q00535 | 0 | phosphorylation | down-regulates activity | 0.763 | We found that cdk5 phosphorylated tau(441) at Thr-181, Ser-199, Ser-202, Thr-205, Thr-212, Ser-214, Thr-217, Thr-231, Ser-235, Ser-396, and Ser-404, but not at Ser-262, Ser-400, Thr-403, Ser-409, Ser-413, or Ser-422. GSK-3beta phosphorylated all the cdk5-catalyzed sites above except Ser-235. | SIGNOR-249321 |
P53602 | P63000 | 1 | lipidation | up-regulates activity | 0.2 | Akt modulated the pathway by phosphorylating mevalonate diphosphate decarboxylase (MDD) at Ser96. These data suggest that Akt regulates Rac1 activity by directly phosphorylating MDD at Ser96, which augments Rac1 geranylgeranylation. | SIGNOR-265892 |
Q96BR1 | O15530 | 0 | phosphorylation | up-regulates | 0.461 | Full-length sgk3 contains a complete phox homology (px) domain that targets the protein to endosomes. Both a functional px domain and pi3k activation are necessary for phosphorylation of sgk3 at two regulatory sites (thr-320 and ser-486) and subsequent induction of kinase activity. Pdk1 phosphorylates endosome-associated sgk3 at thr-320 | SIGNOR-147213 |
P61586 | P10911 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.754 | 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-260556 |
P49841 | P18031 | 1 | phosphorylation | down-regulates quantity | 0.469 | GSK-3beta phosphorylates PTP1B at serine residues, and activation of GSK-3beta reduces the mRNA level of PTP1B. | SIGNOR-279724 |
Q02763 | Q14449 | 1 | phosphorylation | up-regulates activity | 0.65 | Together these results suggest a role for the Grb14 SH2 domain in Tie2 mediated Grb14 signaling.|Tyrosine phosphorylation of Grb14 by Tie2. | SIGNOR-279300 |
P31751 | P49840 | 1 | phosphorylation | down-regulates | 0.557 | Activated pi3k/akt pathway results in inhibitory phosphorylation of gsk3 | SIGNOR-138179 |
O60285 | O95835 | 1 | phosphorylation | down-regulates | 0.389 | Moreover, we show that nuak1 phosphorylates lats1 at s464 and this has a role in controlling its stabilitycells that constitutively express nuak1 suffer gross aneuploidies and show diminished expression of the genomic stability regulator lats1 | SIGNOR-161792 |
Q96T49 | P17252 | 0 | phosphorylation | down-regulates activity | 0.2 | PKCα phosphorylated the full length recombinant TIMAP in in vitro kinase assay and Ser331 of TIMAP was shown to be phosphorylated by PKC. Phosphorylation of TIMAP upon PKC activation in endothelial cells results in enrichment of TIMAP in the membrane, but no such change can be observed in PKC depleted cells. Phosphorylation state of TIMAP, through affecting PP1 activity, has a remarkable effect on endothelial barrier function. | SIGNOR-273802 |
P60568 | Q03060 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.481 | In this study we show that CREM is transcriptionally induced in T cells following stimulation through CD3 and CD28, binds to the IL-2 promoter in vivo, and suppresses IL-2 production. | SIGNOR-261576 |
Q96QU1 | P11362 | 0 | phosphorylation | up-regulates activity | 0.2 | FGFR1 mediated protocadherin-15 loading mediates cargo specificity during intraflagellar transport in inner ear hair-cell kinocilia.|We find that on activation, FGFR1 binds and phosphorylates Pcdh15. | SIGNOR-280014 |
Q9NRW4 | P06239 | 1 | dephosphorylation | down-regulates activity | 0.273 | Because JKAP dephosphorylates and inactivates Lck in T cells [ xref ], we studied whether JKAP downregulation results in Lck activation in SLE T cells. | SIGNOR-277148 |
O15379 | P15976 | 0 | relocalization | up-regulates activity | 0.55 | GATA1 is a new substrate of p21-activated kinase 5 (PAK5), which is phosphorylated on serine 161 and 187 (S161 and S187). GATA1 recruits HDAC3/4 to E-cadherin promoter, which is reduced by GATA1 S161A S187A mutant. These data indicate that phosphorylated GATA1 recruits more HDAC3/4 to promote transcriptional repression of E-cadherin, leading to the EMT of breast cancer cells. | SIGNOR-275664 |
Q01970 | Q13237 | 0 | phosphorylation | down-regulates activity | 0.525 | PKG can directly phosphorylate PLC-beta2 and PLC-beta3 in vitro with purified proteins and in vivo with metabolic labeling. Phosphorylation of PLC-beta leads to the inhibition of G-protein-activated PLC-beta3 activity by 50-70% in COS-7 cell transfection assays. By using phosphopeptide mapping and site-directed mutagenesis, we further identified two key phosphorylation sites for the regulation of PLC-beta3 by PKG (Ser(26) and Ser(1105)). Mutation at these two sites (S26A and S1105A) of PLC-beta3 completely blocked the phosphorylation of PLC-beta3 protein catalyzed by PKG. | SIGNOR-249078 |
P17252 | Q8IZQ8 | 1 | phosphorylation | down-regulates activity | 0.2 | PKCalpha directly promoted the basal phosphorylation of endogenous myocardin at serine and threonine residues. | SIGNOR-279099 |
O43903 | P42574 | 0 | cleavage | up-regulates | 0.451 | We now demonstrate that gas2 is a substrate of caspase-3 but not of caspase-6. Proteolytic processing both in vitro and in vivo is dependent on aspartic residue 279. | SIGNOR-72347 |
P18669 | Q8IXJ6 | 0 | deacetylation | up-regulates activity | 0.279 | Here we report that PGAM is acetylated at lysine 100 (K100), an active site residue that is invariably conserved from bacteria, to yeast, plant, and mammals. K100 acetylation is detected in fly, mouse, and human cells and in multiple tissues and decreases PGAM2 activity. The cytosolic protein deacetylase sirtuin 2 (SIRT2) deacetylates and activates PGAM2. | SIGNOR-266517 |
P18433 | P06241 | 1 | dephosphorylation | up-regulates | 0.658 | Ptpalpha is a more widely expressed transmembrane ptp that has been shown to regulate the src family kinases, src and fyn, and is also present in t cells. | SIGNOR-154796 |
Q53ET0 | Q9Y2K2 | 0 | phosphorylation | down-regulates activity | 0.635 | We found that QSK and SIK phosphorylated TORC2 at Ser171 as well as at least two additional residues, namely Ser70 and Ser348|QIK also phosphorylates the CREB co-activator TORC2, in unstimulated cells, to sequester it in the cell cytoplasm, thereby inhibiting CREB-dependent gene-expression | SIGNOR-249170 |
P53350 | Q12778 | 1 | phosphorylation | down-regulates activity | 0.316 | In conclusion, we provide evidence that PLK1-dependent phosphorylation of FOXO1 induces its nuclear exclusion and negatively regulates FOXO1 transcriptional activity in PCa.|We previously demonstrated that PLK1 inhibits the transcriptional activity of FOXO1 by promoting its nuclear exclusion in U2OS cells . | SIGNOR-278269 |
P05023 | Q05513 | 0 | phosphorylation | up-regulates activity | 0.2 | Na,K-ATPase alpha(1) subunit was phosphorylated by PKC in hypoxia-treated AEC. In AEC treated with a PKC-zeta antagonist peptide or with the Na,K-ATPase alpha(1) subunit lacking the PKC phosphorylation site (Ser-18), hypoxia failed to decrease Na,K-ATPase abundance and function. | SIGNOR-263181 |
P37231 | O75688 | 0 | dephosphorylation | up-regulates activity | 0.372 | Furthermore we show that PPM1B can directly dephosphorylate PPARgamma, both in intact cells and in vitro.|In addition PPM1B increases PPARγ-mediated transcription via dephosphorylation of Ser(112).|The serine/threonine phosphatase PPM1B (PP2Cbeta) selectively modulates PPARgamma activity. | SIGNOR-277073 |
P22681 | Q8TBZ2 | 1 | monoubiquitination | up-regulates activity | 0.298 | We moreover found that AMAP1 is monoubiquitinated, rather than polyubiquitinated, by virtue of Cbl and provide evidence that the ability of AMAP1 to be monoubiquitinated is important for its involvement in invasion. | SIGNOR-272627 |
Q14739 | P06493 | 0 | phosphorylation | down-regulates | 0.396 | The binding of the nk fragment to chromatin pretreated with an s-phase extract was suppressed by incubation with an m-phase extract. Enzyme inhibitor experiments revealed that multiple kinases participate in the suppression. One of these kinases was shown to be cdc2 experiments involving a mutant nk fragment showed that the phosphorylation of serine 71 by cdc2 kinase is responsible for the suppression. | SIGNOR-121335 |
Q8N163 | Q13535 | 0 | phosphorylation | up-regulates activity | 0.438 | Here, we report that, in human cell lines, DNA damage triggered the phosphorylation of DBC1 on Thr454 by ATM (ataxia telangiectasia-mutated) and ATR (ataxia telangiectasia and Rad3-related) kinases. Phosphorylated DBC1 bound to and inhibited SIRT1, resulting in the dissociation of the SIRT1-p53 complex and stimulating p53 acetylation and p53-dependent cell death. | SIGNOR-267662 |
P45984 | P40763 | 1 | phosphorylation | up-regulates | 0.482 | Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. | SIGNOR-179275 |
O00308 | P11161 | 1 | ubiquitination | down-regulates quantity | 0.372 | The HECT-type E3 ubiquitin ligase AIP2 inhibits activation-induced T-cell death by catalyzing EGR2 ubiquitination|AIP2 interacts with and promotes ubiquitin-mediated degradation of EGR2, a zinc finger transcription factor that has been found to regulate Fas ligand (FasL) expression during activation-induced T-cell death. | SIGNOR-268849 |
P04637 | Q96M02 | 0 | polyubiquitination | up-regulates quantity by stabilization | 0.459 | The E3 activity of FATS is required for promoting p53 stability and activation in response to DNA damage.FATS is an E2-independent ubiquitin ligase that stabilizes p53 and promotes its activation in response to DNA damage. Here, we show that FATS acts as a p53 activator by inhibiting Mdm2 binding to p53 and stimulating non-proteolytic polyubiquitination of p53. | SIGNOR-272142 |
P17252 | Q99418 | 1 | phosphorylation | down-regulates activity | 0.307 | ARNO is phosphorylated in vivo by PKC on a single serine residue, S392, located within the carboxy-terminal polybasic domain. Mutation of S392 to alanine does not prevent ARNO-mediated actin rearrangements, suggesting that phosphorylation does not lead to ARNO activation [6]. Here, we report that phosphorylation negatively regulates ARNO exchange activity through a 'PH domain electrostatic switch'. | SIGNOR-249023 |
O75925 | P31749 | 1 | sumoylation | up-regulates activity | 0.378 | Although multiple sites on Akt could be SUMOylated, K276 was identified as a major SUMO acceptor site. K276R or E278A mutation reduced SUMOylation of Akt but had little effect on its ubiquitination. Strikingly, these mutations also completely abolished Akt kinase activity. In support of these results, we found that expression of PIAS1 and SUMO1 increased Akt activity, whereas expression of SENP1 reduced Akt1 activity. | SIGNOR-252735 |
P15036 | P02818 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Ets2 is expressed at high levels during the differentiation and matrix mineralization phases of MC3T3-E1 culture. In addition, several extracellular matrix (ECM) associated gene products are targets of Ets2. Some of these matrix associated genes include: bone sialoprotein, osteonectin, osteocalcin and osteopontin | SIGNOR-259875 |
Q86UR1 | P12931 | 0 | phosphorylation | up-regulates | 0.408 | Here, we show that the interaction of noxa1 and tks proteins is dependent on src activity. Interestingly, the abolishment of src-mediated phosphorylation of tyr110 on noxa1 and of tyr508 on tks4 blocks their binding and decreases nox1-dependent ros generation. | SIGNOR-168545 |
Q70Z35 | Q13177 | 0 | phosphorylation | down-regulates activity | 0.359 | P21-activated Kinases (PAKs) Mediate the Phosphorylation of PREX2 Protein to Initiate Feedback Inhibition of Rac1 GTPase. PAK-mediated phosphorylation of PREX2 reduced GEF activity toward Rac1 by inhibiting PREX2 binding to PIP3 and Gβγ. | SIGNOR-277182 |
P00519 | P78527 | 0 | phosphorylation | up-regulates activity | 0.513 | We show that DNA-PK phosphorylates and activates c-Abl in vitro. | SIGNOR-279268 |
P40763 | O75582 | 0 | phosphorylation | up-regulates | 0.385 | Msk (mitogen- and stress-activated kinase) 1 and 2 can directly phosphorylate and activate transcription factors such as creb, atf1, the nf- b isoform p65 and stat (signal transducer and activator of transcription) 1 and 3 | SIGNOR-166664 |
Q8NHM5 | Q16665 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | To this end, we confirm that KDM3A, KDM4B, KDM4C, KDM5B, KDM5C, and KDM62 are direct targets of HIF-1a while extent the list of known targets to KDM2A, KDM2B, KDM4D, KDM5A, and KDM6A. The results demonstrated that majority of the KDMs were similarly induced (KDM2A, KDM2B, KDM3A, KDM4B, KDM4C, KDM4D, KDM5A, KDM5B, KDM5C, KDM6B, and KDM7A) or repressed (KDM NO66 and KDM1A) by both HIF-1a and HIF-2a. | SIGNOR-271567 |
P33076 | P17612 | 0 | phosphorylation | down-regulates activity | 0.309 | Downregulation of ciita function by protein kinase a (pka)-mediated phosphorylation phosphorylation at ciita serines 834 and 1050 accounts for the inhibitory effects of pka on ciita-driven class ii mhc transcription. | SIGNOR-108569 |
P17252 | P10636-2 | 1 | phosphorylation | down-regulates activity | 0.265 | We have studied the relationship between the phosphorylation oftau by several kinases (MARK, PKA, MAPK, GSK3) and its assembly into PHFs. By contrast, MARK and PKA phosphorylate several sites within the repeats (notably theKXGS motifs including Ser262, Ser324, and Ser356, plus Ser320); in addition PKA phosphorylates somesites in the flanking domains, notably Ser214. This type of phosphorylation strongly reduces tau’s affinityfor microtubules, and at the same time inhibits tau’s assembly into PHFs. | SIGNOR-275441 |
Q9Y6W5 | P00519 | 0 | phosphorylation | up-regulates activity | 0.698 | Furthermore, Abl phosphorylates WAVE2 on tyrosine 150, and WAVE2 deficient cells rescued with a Y150F mutant fail to regain their ability to ruffle and form microspikes, unlike cells rescued with wild-type WAVE2.|Together, these data show that c-Abl activates WAVE2 via tyrosine phosphorylation to promote actin remodeling in vivo and that Abi-1 forms the crucial link between these two factors. | SIGNOR-279390 |
Q7KZI7 | Q8IVT5 | 1 | phosphorylation | down-regulates activity | 0.315 | In vivo, MARK2 appears to negatively regulate KSR1 in insulin sensitivity.|These data suggest that MARK2 phosphorylates KSR1 on Ser392, which has been shown previously to function as a negative regulatory site xref . | SIGNOR-279343 |
P14317 | P07948 | 0 | phosphorylation | up-regulates activity | 0.714 | Lyn and Syk synergistically phosphorylate HS1, and that Tyr-378 and Tyr-397 of HS1 are the critical residues for its BCR-induced phosphorylation. tyrosine phosphorylation of HS1 is required for BCR-induced apoptosis and nuclear translocation of HS1 may be a prerequisite for B cell apoptosis. PMID: 9104825 PMCID: PMC2196252 | SIGNOR-251401 |
Q07912 | P10275 | 1 | phosphorylation | up-regulates activity | 0.545 | Ack1 interacted with and phosphorylated AR protein at Tyr 267 and Ack1 was shown to be required for optimal AR target gene expression and AR recruitment.|Two intracellular tyrosine kinases, Ack1 (activated cdc42 associated kinase) and Src, phosphorylate and enhance AR activity and promote prostate xenograft tumor growth in castrated animals. | SIGNOR-278194 |
P46527 | P49336 | 0 | phosphorylation | down-regulates | 0.289 | As a consequence, CDK8 overexpression promoted p27 degradation, whereas CDK8 knockdown reduced it.|We also show that CDK8 promotes phosphorylation of p27 at T187 and then induces p27 ubiquitination and degradation in a Skp2-dependent manner. | SIGNOR-278513 |
P68431 | Q9UGL1 | 0 | demethylation | up-regulates activity | 0.2 | KDM5 subfamily is capable of removing tri‐ and di‐ methyl marks from lysine 4 on histone H3 (H3K4). Depending on the methylation site, its effect on transcription can be either activating or repressing. | SIGNOR-264302 |
P07948 | Q9UN19 | 1 | phosphorylation | up-regulates activity | 0.625 | Src family kinases mediate receptor-stimulated, phosphoinositide 3-kinase-dependent, tyrosine phosphorylation of dual adaptor for phosphotyrosine and 3-phosphoinositides-1 in endothelial and B cell lines|yrosine phosphorylation of DAPP-1 appears important for appropriate intracellular targeting and creates a potential binding site for Src homology 2 domain-containing proteins. | SIGNOR-249378 |
P00533 | P42685 | 0 | phosphorylation | down-regulates activity | 0.409 | Furthermore, Rak/Frk inhibited mutant EGFR phosphorylation at an activating site and dramatically decreased the levels of EGFR\u0394747-749/A750P from the plasma membrane.|Taken together, the results suggest that Rak and Frk inhibits EGFR signaling in cancer cells and has elevated activity against EGFR exon 19 mutants. | SIGNOR-279177 |
Q96GD4 | Q13315 | 1 | phosphorylation | up-regulates | 0.431 | Aurora-b mediated atm serine 1403 phosphorylation is required for mitotic atm activation and the spindle checkpoint | SIGNOR-177280 |
Q96RK0 | P51812 | 0 | phosphorylation | down-regulates | 0.2 | Specifically, 14-3-3 binds to p90(rsk)-phosphorylated ser?_??_ Of capic?_A thereby modulating dna binding to its hmg (high-mobility group) box, whereas erk phosphorylations prevent binding of a c-terminal nls (nuclear localization sequence) to importin ?4 (kpna3) | SIGNOR-169887 |
Q13547 | P37231 | 0 | relocalization | down-regulates | 0.617 | These data suggest that c/ebp beta activates a single unified pathway of adipogenesis involving its stimulation of ppargamma expression, which then activates c/ebp alpha expression by dislodging hdac1 from the promoter for degradation in the proteasome | SIGNOR-143961 |
Q00534 | O43524 | 1 | phosphorylation | up-regulates activity | 0.464 | CDK6 and cyclin D3 complex phosphorylates FOXO3 on S325.|Using cycloheximide (CHX), we observed that CDK6 knockdown decreased FOXO3 stability, particularly in platinum treated cells (Fig XREF_FIG A) and that, following platinum treatment, FOXO3 WT was more stable than the non phosphorylatable mutant FOXO3 S325A (Fig XREF_FIG B). | SIGNOR-279023 |
P18848 | Q9NP81 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress. | SIGNOR-269425 |
Q86V15 | Q9UHF1 | 1 | transcriptional regulation | up-regulates quantity | 0.425 | We have recently demonstrated that a novel transcriptional pathway involving activation of the Epidermal Growth Factor-like Domain 7 (Egfl7) gene by the transcription factor CASTOR (CASZ1) is required for blood vessel assembly and lumen morphogenesis. | SIGNOR-266858 |
Q92985 | P63279 | 0 | sumoylation | down-regulates activity | 0.287 | One mechanism by which LMP1 regulates cellular activation is through the induction of protein posttranslational modifications. We have now identified a specific target of LMP1-induced sumoylation, interferon regulatory factor 7 (IRF7). We hypothesize that during EBV latency, LMP1 induces the sumoylation of IRF7, limiting its transcriptional activity and modulating the activation of innate immune responses. We recently documented that LMP1 induces a third major protein modification by physically interacting with the SUMO-conjugating enzyme Ubc9 through CTAR3 and inducing the sumoylation of cellular proteins in latently infected cells. we identified that IRF7 is sumoylated at lysine 452. | SIGNOR-266837 |
P19544 | P00441 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.265 | The human copper-zinc superoxide dismutase gene (SOD1) proximal promoter is regulated by Sp1, Egr-1, and WT1 via non-canonical binding sites. Egr-1 and two splicing variants of the Egr-related protein WT1 were able to transactivate the SOD1 promoter in co-transfection experiments. | SIGNOR-253898 |
Q9Y6W6 | P45983 | 1 | dephosphorylation | down-regulates | 0.705 | Mkp-5 directly dephosphorylates sapk/jnk and p38 in vitromkp-5 binds to p38 and sapk/jnk, but not to mapk/erk, and inactivates p38 and sapk/jnk | SIGNOR-68986 |
P10912 | P54764 | 0 | phosphorylation | up-regulates activity | 0.2 | EphA4 binds to growth hormone receptor at both its extracellular and intracellular domains and phosphorylates growth hormone receptor when stimulated with a ligand.|These findings suggest that EphA4 activates not only GHR, as shown above, but also JAK2 by direct phosphorylation. | SIGNOR-279461 |
Q14534 | Q12772 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.595 | The processed SREBP2, designated nuclear SREBP2 (nSREBP2), then enters the nucleus as a homodimer, binds to the sterol regulatory element (SRE) sequence in the promoters of target genes, including HMGCR and SQLE (encoding squalene monooxygenase), and upregulates their transcription | SIGNOR-265162 |
O95071 | Q92547 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.462 | Using an in vitro reconstitution, specific E2 (ubiquitin-conjugating) enzymes (human UbcH4, UbcH5B, and UbcH5C) transferred ubiquitin molecules to hHYD, leading to the ubiquitination of TopBP1. TopBP1 was usually ubiquitinated and degraded by the proteosome, whereas X-irradiation diminished the ubiquitination of TopBP1 probably via the phosphorylation, resulting in the stable colocalization of up-regulated TopBP1 with gamma-H2AX nuclear foci in DNA breaks. | SIGNOR-272667 |
Q14653 | P00519 | 0 | phosphorylation | up-regulates activity | 0.2 | The data in this study show that IRF3 is physically associated with c-Abl in vivo and directly binds to c-Abl in vitro. IRF3 is phosphorylated by c-Abl and c-Abl-related kinase, Arg, mainly at Y292. | SIGNOR-277440 |
Q02156 | P46940 | 1 | phosphorylation | up-regulates | 0.2 | Using a mass spectrometry-based assay, we show that egf induces phosphorylation of iqgap1 ser(1443), a residue known to be phosphorylated by pkcthe nonphosphorylatable iqgap1 s1441a/s1443a had no effect. In contrast, the s1441e/s1443d mutation markedly enhanced the ability of iqgap1 to induce neurite outgrowth. | SIGNOR-128718 |
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