IdA stringlengths 6 21 | IdB stringlengths 6 21 | labels int64 0 2 | mechanism stringclasses 40
values | effect stringclasses 10
values | score float64 0.1 0.99 ⌀ | sentence stringlengths 10 1.63k ⌀ | signor_id stringlengths 12 14 |
|---|---|---|---|---|---|---|---|
Q99558 | Q00653 | 1 | phosphorylation | up-regulates activity | 0.677 | NIK-induced p100 processing requires phosphorylation of p100 at serines 866 and 870 | SIGNOR-105553 |
P30559 | O15530 | 0 | phosphorylation | up-regulates activity | 0.2 | We found that Ser261 in OXTR was phosphorylated by protein kinase D1 (PKD1).|In HEK293A cells, the PKD1-mediated phosphorylation of OXTR promoted its binding to Gq protein and, in turn, OXTR-mediated phosphorylation of PKD1, indicating a positive feedback loop. | SIGNOR-268577 |
Q14493 | Q16695 | 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-265417 |
P26378 | O14672 | 1 | post transcriptional regulation | up-regulates quantity | 0.2 | Neuronal ELAV (nELAV) proteins are RNA-binding proteins which play a physiological role in controlling gene expression in memory formation, and their alteration may contribute to cognitive impairment associated with neurodegenerative pathologies such as Alzheimer's disease (AD). The experiments show for the first time that ADAM10mRNA represents a nELAV target and that these RNA-binding proteins can play a role in the post-transcriptional regulation of ADAM10 expression. nELAV proteins specifically bind the ADAM10 mRNA and this binding is disrupted following Aβ exposure | SIGNOR-266865 |
P49959 | Q13315 | 2 | binding | up-regulates | 0.2 | One of the earliest events is recruitment and activation of the atm at the damaged dna sites through the mre11rad50nbs1 (mrn) sensor complex. the mre11/rad50/nbs1 (mrn) complex maintains genomic stability by bridging dna ends and initiating dna damage signaling through activation of the atm kinase. | SIGNOR-175006 |
P25054 | O60566 | 0 | phosphorylation | up-regulates activity | 0.428 | These findings support a model in which BubR1 kinase may directly regulate APC function involved in stable kinetochore microtubule attachment.|Using purified components, BubR1 directly phosphorylates APC and forms a ternary complex with APC and microtubules. | SIGNOR-279393 |
Q92934 | Q13153 | 0 | phosphorylation | down-regulates | 0.335 | Pak phosphorylates bad in vitro and in vivo on ser112 and ser136, resulting in a markedly reduced interaction between bad and bcl-2 or bcl-x(l) and the increased association of bad with 14-3-3tau. | SIGNOR-73533 |
P10747 | Q08881 | 0 | phosphorylation | up-regulates | 0.69 | We demonstrate that emt can phosphorylate all four tyrosines of the cd28 tail, in contrast to lck, which phosphorylates only tyrosine 173. Together with evidence that in vivo, tyrosines other than tyrosine 173 become phosphorylated following cd28 stimulation, this finding suggests that, like lck, one function of emt during cd28 signaling is phosphorylation of the receptor | SIGNOR-198747 |
O15297 | P53778 | 1 | dephosphorylation | down-regulates | 0.297 | Ppm1d selectively inhibits p38 activation by dephosphorylating thr 180. | SIGNOR-135976 |
P04637 | P35232 | 2 | binding | up-regulates activity | 0.443 | Our previous studies have shown that prohibitin physically interacts with the marked-box domain of E2F family members and represses their transcriptional activity; in contrast, prohibitin could bind to and enhance the transcriptional activity of p53. | SIGNOR-268978 |
P42575 | P62136 | 0 | dephosphorylation | up-regulates activity | 0.2 | nutrient-replete oocytes inhibit C2 via S135 phosphorylation catalyzed by calcium/calmodulin-dependent protein kinase II. We now show that C2 phosphorylated at S135 binds 14-3-3zeta, thus preventing C2 dephosphorylation. Moreover, we determined that S135 dephosphorylation is catalyzed by protein phosphatase-1 (PP1), which directly binds C2. | SIGNOR-248564 |
P10147 | Q01196 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | We show that RUNX1 can specifically bind to both RUNX sites but that only the proximal RUNX site is essential for PMA/ PHA stimulation of the MIP-1a promoter in Jurkat T-cells. We also show that the endogenous MIP-1a promoter is constitutively bound by RUNX1. | SIGNOR-251738 |
Q8N9I0 | Q9H4A3 | 0 | phosphorylation | up-regulates activity | 0.603 | Endogenous WNK1 and Syt2 coimmunoprecipitate and colocalize on a subset of secretory granules in INS-1 cells. Phosphorylation by WNK1 increases the amount of Ca2+ required for Syt2 binding to phospholipid vesicles; mutation of threonine 202, a WNK1 phosphorylation site, partially prevents this change. These findings suggest that phosphorylation of Syts by WNK1 can regulate Ca2+ sensing and the subsequent Ca2+-dependent interactions mediated by Syt C2 domains. . In contrast, WNK1 phosphorylated Syt2 on T202 and T386 within the C2 domains (Figure 6B). | SIGNOR-263049 |
P40425 | Q96AQ6 | 2 | binding | down-regulates activity | 0.267 | This protein that we have termed hematopoietic PBX-interacting protein (HPIP) is mainly localized in the cytosol and in small amounts in the nucleus. The region of PBX that interacts with HPIP includes both the homeodomain and immediate N-terminal flanking sequences. Strikingly, electrophoretic mobility shift assays revealed that HPIP inhibits the ability of PBX-HOX heterodimers to bind to target sequences. | SIGNOR-273667 |
Q14563 | O14786 | 2 | binding | up-regulates activity | 0.913 | Further examination of the composition of the functional Sema3B receptor revealed that, unlike Sema3A, which signals exclusively using the NP1 receptor, Sema3B utilizes both NP1 and NP2 for signal transduction. | SIGNOR-261815 |
P31749 | Q96J02 | 1 | phosphorylation | up-regulates quantity | 0.319 | AKT1-mediated phosphorylation of ITCH at Ser257 drives its nuclear translocation | SIGNOR-272922 |
P49841 | Q14653 | 1 | phosphorylation | up-regulates activity | 0.346 | Invitro, both GSK3alpha and GSK3beta phosphorylate IRF3 at the linker region. | SIGNOR-279182 |
Q9UK53 | P12931 | 0 | phosphorylation | down-regulates activity | 0.367 | Src Decreases the Stability and Level of ING1.|This study, as well as a previous report identifying Ser-126 of ING1 as a kinase target, confirm that ING1 stability is also regulated by phosphorylation. However, the mechanism may be complex since phosphorylation of Ser-126 stabilizes the protein while phosphorylation by Src reduces ING1 stability and causes a relocalization of ING1 from the nucleus to the cytoplasm. | SIGNOR-279760 |
P37231 | P28482 | 0 | relocalization | down-regulates | 0.457 | The genomic activity of ppargamma is modulated, in addition to ligand binding, by phosphorylation of a serine residue by mapks, such as extracellular signal-regulated protein kinases-1/2 (erk-1/2), or by nucleocytoplasmic compartmentalization through the erk activators mapk kinases-1/2 (mek-1/2). These mapks phosphorylate (in humans) ser 84 in the ppargamma1 and ser 114 in ppargamma2 isoform | SIGNOR-179400 |
P54132 | Q13535 | 0 | phosphorylation | up-regulates activity | 0.852 | It is noteworthy that an active BLM seems to be unnecessary to the activation of BRCA1, either after gamma-rays or HU, even though BRCA1 and BLM helicase are activated by ATR in response to stalled replication, and despite the fact that they colocalize after replication arrest.|These results show that BLM phosphorylation by ATR after replication fork arrest is not important for its relocalization. | SIGNOR-278978 |
P11802 | Q14106 | 1 | phosphorylation | up-regulates activity | 0.2 | Taken together, these observations strongly support the notion that several different CDK-cyclin complexes are involved in the phosphorylation of Tob2 at S254.A more detailed regulatory context of Tob2 phosphorylation at S254 is provided by our findings from mass-spec and in vitro kinase analyses that suggest connections to PP2B and PP2C phosphatases and CDK-cyclin complexes, particularly CDK1, CDK2, and CDK4 (Table 1; Supplemental Table S2).One possibility is that the phosphorylation of S254 helps stabilize the interaction of Tob2 with the Ccr4–Not complex, which could contribute to Tob2's ability to recruit the entire Ccr4–Not complex and thus further enhances deadenylation. | SIGNOR-273602 |
Q13191 | Q6EIG7 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | Furthermore, we found that Cbl-b, an E3 ubiquitin ligase, mediates the ubiquitination and degradation of the activated Dectin-2 and Dectin-3 to negatively regulate CLR mediated innate immune responses against fungal infections. | SIGNOR-278625 |
P21802 | Q13443 | 0 | cleavage | down-regulates quantity by destabilization | 0.257 | Truncated FGFR2 was observed in cells transfected with wild-type ADAM9, but not in those with inactive mutant ADAM9 (Figure 5E). In line with this, cells transfected with wild-type ADAM9 showed reduced pErK1/2 in response to FGF2 as compared to controls or cells expressing mutant ADAM9.|Here we show that MT1-MMP forms a complex with FGFR2 and ADAM9 in osteoblasts and proteolytically inactivates ADAM9, hence protecting FGFR2 from ADAM9-mediated ectodomain shedding on the cell surface. | SIGNOR-260300 |
Q6DJT9 | P63279 | 0 | sumoylation | down-regulates | 0.277 | Sumoylation decreases the transcriptional activity of plag1 / plag1 is sumoylated at 2 specific lysine residues (lys-244 and lys-263) | SIGNOR-126048 |
P49715 | P49841 | 0 | phosphorylation | up-regulates activity | 0.379 | Glycogen synthase kinase 3 (GSK3) phosphorylates T222 and T226, causing a conformational change in C/EBPα. GSK3-mediated phosphorylation does not, in itself, dramatically alter the activity of C/EBPα in our assays. phosphorylation of C/EBPalpha and other substrates by GSK3 may be required for adipogenesis, since treatment of differentiating preadipocytes with lithium inhibits their conversion to adipocytes. | SIGNOR-251231 |
P06213 | P27986 | 1 | phosphorylation | up-regulates activity | 0.67 | The alpha-type 85-kDa subunit of phosphatidylinositol 3-kinase is phosphorylated at tyrosines 368, 580, and 607 by the insulin receptor. | SIGNOR-251321 |
P0DP25 | P06213 | 0 | phosphorylation | down-regulates | 0.375 | The in vitro phosphorylation of calmodulin by the insulin receptor tyrosine kinase. Phosphorylated calmodulin does not exhibit the characteristic ca2+ shift normally observed with calmodulin in electrophoretic gels, an observation that is consistent with this modification affecting the biological activity of the molecule. | SIGNOR-266336 |
P10721 | P23470 | 0 | 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-254710 |
P05771 | Q13131 | 1 | phosphorylation | down-regulates activity | 0.2 | Purified PKC and Akt both phosphorylated AMPKα1 Ser487 in vitro with similar efficiency. PKC activation was associated with reduced AMPK activity, as inhibition of PKC increased AMPK activity and phorbol esters inhibited AMPK, an effect lost in cells expressing mutant AMPKα1 Ser487Ala. Consistent with a pathophysiological role for this modification, AMPKα1 Ser487 phosphorylation was inversely correlated with insulin sensitivity in human muscle. | SIGNOR-276460 |
O60346 | P48729 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.309 | We show that the beta-TrCP-mediated degradation requires phosphorylation of PHLPP1 by casein kinase I and glycogen synthase kinase 3beta (GSK-3beta), and activation of the phosphatidylinositol 3-kinase/Akt pathway suppresses the degradation of PHLPP1 by inhibiting the GSK-3beta activity. | SIGNOR-276262 |
P04626 | Q00535 | 0 | phosphorylation | up-regulates activity | 0.274 | Since Tyr-654 is the ERBB2 phosphorylation site on beta-catenin, this result is consistent with our hypothesis that CDK5 activates ERBB2 , which in turn phosphorylates beta-catenin on Tyr-654, leading to a shift of beta-catenin away from the adherens junction and into the nucleus where it can serve as a transcriptional co-activator.|Taken together with the results of our kinase analysis, these observations suggest that CDK5 phosphorylation of both ERBB2 and ERBB3 and AR could drive a feedback loop, in which ERBB2 and ERBB3 promotes beta-catenin transcriptional activity that then contributes to higher expression of ERBB3. | SIGNOR-279155 |
Q15788 | P03372 | 2 | binding | up-regulates | 0.845 | Steroid receptor co-activator (src1) is one of a number of transcriptional co-activators that are capable of potentiating the activity of nuclear receptors including the oestrogen receptor (er). | SIGNOR-54442 |
Q15746 | Q13177 | 0 | phosphorylation | down-regulates activity | 0.533 | PAK2 can directly phosphorylate MLCK, inhibiting its activity and limiting the development of isometric tension. PAK2 catalyzes MLCK phosphorylation on serine residues 439 and 991. | SIGNOR-250223 |
P36873 | O15084 | 2 | binding | up-regulates activity | 0.443 | Phosphatase Interactor Targeting K protein (PITK) was previously identified as a novel PP1 targeting subunit implicated in modulating the phosphorylation of the transcriptional regulator heterogeneous nuclear ribonucleoprotein K (hnRNP K) | SIGNOR-264794 |
Q13404 | Q9Y4K3 | 2 | binding | up-regulates activity | 0.699 | We find that traf6, a ring domain protein, functions together with ubc13/uev1a to catalyze the synthesis of unique polyubiquitin chains linked through lysine-63 (k63) of ubiquitin | SIGNOR-83603 |
Q13131 | Q92538 | 1 | phosphorylation | down-regulates | 0.2 | These results indicate that gbf1 is a novel ampk substrate and that the ampk-mediated phosphorylation of gbf1 at thr(1337) has a critical role, presumably by attenuating the function of gbf1, in the disassembly of the golgi apparatus induced under stress conditions that lower the intracellular atp concentration. | SIGNOR-159639 |
O00712 | P23352 | 1 | transcriptional regulation | down-regulates quantity | 0.2 | By integrating transcriptomic profiling (RNA-seq) of Nfia- and Nfix-deficient GNPs with epigenomic profiling (ChIP-seq against NFIA, NFIB and NFIX, and DNase I hypersensitivity assays), we reveal that these transcription factors share a large set of potential transcriptional targets, suggestive of complementary roles for these NFI family members in promoting neural development | SIGNOR-268878 |
Q06413 | Q16539 | 0 | phosphorylation | up-regulates activity | 0.696 | We found that in monocytic cells, lps increases the transactivation activity of mef2c through p38-catalysed phosphorylation. | SIGNOR-47136 |
P17612 | P07101 | 1 | phosphorylation | up-regulates activity | 0.368 | HTH1 was phosphorylated at Ser40 by PKA. Tyrosine hydroxylase (TH) has been reported to require binding of 14-3-3 proteins for optimal activation by phosphorylation. phosphorylationof hTH1‚4 at Ser40, to a stoichiometry of up to 1.0 molphosphate per mol TH subunit, dramatically increases their binding to 14-3-3 proteins. | SIGNOR-250061 |
O15379 | Q9UHD2 | 0 | phosphorylation | up-regulates activity | 0.2 | The feedback of activation of HDAC3 by TBK1 was able to further enhance IFN production and IFN-STAT activation.|We found that HDAC3 could be phosphorylated by TBK1. | SIGNOR-279662 |
Q12866 | Q8NB16 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.2 | TAM kinases phosphorylate MLKL to promote necroptosis. MLKL is then recruited to the plasma membrane, where TAM kinases phosphorylate MLKL at Tyr376 (Figure 5G, step 5), promoting its oligomerization and formation of membrane-rupturing pores that result in necrotic cell death (Figure 5G, step 6). | SIGNOR-274118 |
Q8IWV1 | P06239 | 0 | phosphorylation | up-regulates activity | 0.399 | Upon stimulation via the B or T cell receptors, LAX is rapidly phosphorylated by Src and Syk family tyrosine kinases and interacts with Grb2, Gads, and p85. | SIGNOR-273528 |
Q15672 | P27361 | 0 | phosphorylation | up-regulates | 0.328 | 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-173413 |
P84022 | Q9NYA4 | 0 | dephosphorylation | down-regulates | 0.517 | Here we demonstrate that myotubularin-related protein 4 | SIGNOR-163034 |
P41221 | Q9NPG1 | 2 | binding | up-regulates activity | 0.707 | Human wnt5a, wnt5b and wnt11 are non-canonical wnt ligands transducing pcp signals through fzd3 or fzd6 receptors. | SIGNOR-141434 |
P27361 | P30304 | 0 | dephosphorylation | down-regulates | 0.395 | We found that cdc25a physically interacted with and de-phosphorylated phospho-erk both in vitro and in cell culture. | SIGNOR-133392 |
Q8NFZ5 | Q96J02 | 0 | ubiquitination | down-regulates | 0.268 | Here we show that tnfa-mediated jnk activation accelerates turnover of the NF-kappaBinduced antiapoptotic protein c-flip, an inhibitor of caspase-8. This is not due to direct c-flip phosphorylation but depends on jnk-mediated phosphorylation and activationof the e3ubiquitin ligaseitch, which speci?cally Ubiquitinates c-flip and induces its proteasomal degradation. | SIGNOR-144453 |
Q05397 | Q12965 | 2 | binding | up-regulates activity | 0.2 | Myosin-1E (MYO1E), an actin-dependent molecular motor protein, directly interacts with FAK to induce Y397 autophosphorylation, which, in turn, causes changes in gene expression commonly observed in aggressive cancer. | SIGNOR-265427 |
Q9UM73 | Q92529 | 1 | phosphorylation | up-regulates | 0.44 | Anaplastic lymphoma kinase (alk), which turned out to be one of these phosphoproteins, was constitutively activated and associated with the ptb domain of shcc in three neuroblastoma cells. In vitro kinase assay revealed that shcc is a potent substrate of the activated alk kinase. The alk gene locus was significantly amplified in both of these cell lines, suggesting that gene amplification leads to constitutive activation of the alk kinase, which results in hyperphosphorylation of shcc. | SIGNOR-91537 |
Q13131 | Q9Y478 | 1 | phosphorylation | up-regulates | 0.925 | Mutation of serine 108 to alanine, an autophosphorylation site within the glycogen binding domain of the beta1 subunit, almost completely abolishes activation of ampk by a-769662 in cells and in vitro, while only partially reducing activation by amp | SIGNOR-157553 |
P20749 | P31751 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.27 | Here we show that Akt, Erk2, and IKK1/2 phosphorylate Bcl3. Phosphorylation of Ser33 by Akt induces switching of K48 ubiquitination to K63 ubiquitination and thus promotes nuclear localization and stabilization of Bcl3. Phosphorylation by Erk2 and IKK1/2 of Ser114 and Ser446 converts Bcl3 into a transcriptional coregulator by facilitating its recruitment to DNA. | SIGNOR-277359 |
Q14012 | Q14012 | 2 | phosphorylation | up-regulates activity | 0.2 | CaM kinase I was autophosphorylated in a Ca2+/CaM-dependent manner at a threonyl residue (Thr-177) which is located at a position equivalent to that of the threonyl residue (Thr-197) autophosphorylated in cAMP-dependent protein kinase. | SIGNOR-250612 |
P05771 | O15530 | 0 | phosphorylation | up-regulates | 0.522 | One of the most studied events controlled by ptdins(3,4,5)p3, comprises the activation of a of agc family protein kinases, including isoforms of protein kinase b (pkb)/akt, p70 ribosomal s6 kinase (s6k), serum and glucocorticoid-induced protein kinase (sgk) and protein kinase c (pkc), which play crucial roles in regulating physiological processes relevant to metabolism, growth, proliferation and survival. Here, we review recent biochemical, genetic and structural studies on the 3-phosphoinositide-dependent protein kinase-1 (pdk1), which phosphorylates and activates the agc kinase members regulated by pi 3-kinase. We also discuss whether inhibitors of pdk1 might have chemotherapeutic potential in the treatment of cancers in which the pdk1-regulated agc kinases are constitutively activated. | SIGNOR-126069 |
P42574 | Q15173 | 0 | dephosphorylation | up-regulates | 0.2 | Dephosphorylation of caspase-3 at ser150 site by pp2a increased caspase-3 activity,which was essential to trigger apoptosis in neutrophils. | SIGNOR-131435 |
Q13546 | Q9Y572 | 2 | phosphorylation | up-regulates activity | 0.754 | In the current scenario, RIPK1 phosphorylates and activates RIPK3, and activated RIPK3 then phosphorylates MLKL. | SIGNOR-278429 |
Q9Y5H4 | Q9Y5H9 | 2 | binding | up-regulates activity | 0.2 | The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion. They also form oligomers with Pcdh-gamma proteins at the same membrane sites. | SIGNOR-265686 |
Q71U36 | Q5SQI0 | 0 | acetylation | up-regulates quantity by stabilization | 0.268 | Alpha-Tubulin acetyltransferase (alphaTAT1) is the major α-tubulin lysine-40 (K40) acetyltransferase in mammals, nematodes, and protozoa, and its activity plays a conserved role in several microtubule-based processes.|The tubulin subunits of microtubules are acetylated, and lysine-40 (K40) of the alpha-tubulin subunit has been identified as an important conserved site of microtubule acetylation (6–8). This modification is considered a hallmark of stable, long-lived microtubules | SIGNOR-272251 |
Q9UJM3 | P04626 | 2 | binding | down-regulates activity | 0.707 | The cytoplasmic protein MIG6 (mitogen-induced gene 6; also known as ERRFI1) interacts with and inhibits the kinase domains of EGFR and ERBB2 | SIGNOR-252077 |
Q9UQD0 | Q92914 | 2 | binding | down-regulates activity | 0.253 | Sodium channel fast inactivation is modulated by alpha subunit interaction with a family of cytoplasmic proteins termed fibroblast growth factor homologous factors (FHFs). In this paper, we report that all A-type FHFs exert rapid onset long-term inactivation on Nav1.6 and other sodium channels. | SIGNOR-253414 |
P12931 | P51813 | 1 | phosphorylation | up-regulates | 0.535 | Coexpression of v-src and etk led to a transphosphorylation on tyrosine 566 of etk and subsequent autophosphorylation. These events correlated with a substantial increase in the kinase activity of etk. | SIGNOR-75330 |
P38405 | P34969 | 2 | binding | up-regulates activity | 0.444 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-256926 |
Q9BPZ3 | O95071 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.445 | We demonstrate a mechanism for this co-regulation that involves an E3 ubiquitin ligase, EDD, which targets Paip2 for degradation. PABP depletion by RNA interference (RNAi) causes co-depletion of Paip2 protein without affecting Paip2 mRNA levels. Upon PABP knockdown, Paip2 interacts with EDD, which leads to Paip2 ubiquitination. | SIGNOR-272648 |
Q13291 | P06241 | 0 | phosphorylation | up-regulates activity | 0.658 | All 3 tyrosines of CD150 (Tyr281, Tyr307, Tyr327) are phosphorylated by the src kinase Fyn. CD150 is unique among its homologues in the immunoglobulin superfamily in that it is able to bind SAP, a floating SH2 domain, in the absence of tyrosine phosphorylation. In this study, using a detailed mutagenesis mapping approach we have shown that SAP binding to CD150 is in fact bimodal. Prior to tyrosine phosphorylation, SAP binds the membrane-proximal motif surrounding Tyr281. Following tyrosine phosphorylation by tyrosine kinases such as Fyn, SAP binds additionally to the distal motif surrounding Tyr327. | SIGNOR-251182 |
P00738 | P69905 | 2 | binding | down-regulates quantity | 0.738 | Haptoglobin forms a complex of extremely high affinity with Hb via a well-characterized globin site. Our results show that upon Hb-haptoglobin binding, the globin radical, loses its ability to be terminated by forming globin dimers. | SIGNOR-251816 |
P33981 | Q9Y6D9 | 1 | phosphorylation | up-regulates activity | 0.819 | Furthermore, although catalytically inactive Mps1 can restore kinetochore localization of Mad1, only the active kinase restores Mad2 localization.|Indeed, Mps1 can phosphorylate Mad1 in vitro. | SIGNOR-279000 |
P15036 | P10451 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.251 | We demonstrated that Ets2 is capable of binding to and transactivating the OPN promoter using gel shift and transient transfection assays | SIGNOR-259872 |
P51608 | O00548 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | As the first step to reveal how MeCP2 phosphorylation may regulate Notch signaling, we conducted chromatin immunoprecipitation (ChIP) experiment to determine whether the phosphor-mutant MeCP2 protein has altered promoter occupancy at the promoters of Dll1 and Notch1. We found increased binding of the phosphor-mutant protein at the promoters of both Dll1 and Notch1 | SIGNOR-264674 |
Q96ST3 | Q96QT6 | 2 | binding | up-regulates activity | 0.796 | Pf1 interacts with mSin3A in vivo. Gal4-Pf1 repressed activity of the reporter gene fivefold relative to Gal4 alone (Fig. (Fig.5A),5A), suggesting that DNA-bound Pf1 was capable of recruiting functional mSin3A complexes. | SIGNOR-266995 |
P49841 | Q13148 | 0 | post transcriptional regulation | down-regulates quantity by repression | 0.267 | Importantly, we found that TDP-43 protein could interact with GSK3β mRNA and regulate the level of GSK3β protein translation. Taken together, our findings suggest that TDP-43 may activate the Wnt/β-catenin pathway by targeting the inhibition of GSK3β protein translation|TDP-43 activates Wnt/β-catenin pathway probably by inhibiting the GSK3β protein translation. A. Interaction between TDP-43 protein and GSK3β mRNA was analyzed using RIP assay. | SIGNOR-262113 |
P21731 | P63096 | 2 | binding | up-regulates activity | 0.25 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-256744 |
P51654 | P27487 | 2 | binding | down-regulates | 0.352 | The interaction occurred with both the glycosylated and unglycosylated forms of gpc3 and led to the inhibition of cd26 peptidase activity. | SIGNOR-155527 |
P53779 | P14778 | 0 | phosphorylation | up-regulates activity | 0.2 | Il-1 binding to its receptor triggers a cascade of signaling events, including activation of the stress-activated mitogen-activated protein (map) kinases, c-jun nh2-terminal kinase (jnk) and p38 map kinase, as well as transcription factor nuclear factor kappab (nf-kappab | SIGNOR-249515 |
Q9NP62 | Q9BVJ7 | 0 | dephosphorylation | up-regulates quantity by stabilization | 0.464 | DUSP23 prevents GCM1 from ubiquitination and prolongs the half-life of GCM1.|Second, DUSP23 is able to dephosphorylate Ser322 in GCM1 in vitro and in a stable cell line expressing HA-GCM1. | SIGNOR-276982 |
O14641 | Q9NPB6 | 2 | binding | up-regulates | 0.643 | In pcp , dvl binds to proteins such as pkc, atypical pkc (apkc), dvl-associated activator of morphogenesis 1 (daam1), dvl-associating protein with a high frequency of leu residues (daple) and partitioning defective 6 (par6), which are important for the regulation of small gtpases such as rho and rac and, consequently, the cytoskeleton and cell polarity58. | SIGNOR-199500 |
Q92736 | P17612 | 0 | phosphorylation | up-regulates activity | 0.478 | PKA-mediated hyperphosphorylation of a conserved serine, Ser-2843 in skeletal RyR and Ser-2809 in cardiac RyR, results in an aberrant SR function during heart failure. hyperphosphorylated RyRs are leaky and therefore lead to a reduced SR Ca2+ load and impaired contractile function in heart failure | SIGNOR-250079 |
P17612 | P42261 | 1 | phosphorylation | up-regulates activity | 0.494 | Phosphorylation of Ser-845 on GluR1 by PKA potentiates its response to glutamate. | SIGNOR-249987 |
Q86UR5 | P20336 | 1 | relocalization | up-regulates activity | 0.805 | N-terminal interactions of RIMs with RAB3 and MUNC13 regulate DCV fusion. Through N-terminal interactions, RIMs position MUNC13 and recruit DCVs via RAB3, which is located on the vesicle | SIGNOR-264381 |
P12931 | P18433 | 2 | phosphorylation | up-regulates activity | 0.743 | Transient overexpression of c-src together with rptp alpha in human embryonic kidney 293 cells increased phosphorylation of tyr789, suggesting that c-src may phosphorylate rptp alpha in vivo. | SIGNOR-111306 |
Q8NG68 | P16949 | 2 | binding | down-regulates | 0.389 | Stathmin depresses ttl tubulin tyrosination activityin vitro. | SIGNOR-193465 |
Q9Y6B2 | Q00987 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.424 | Degradation of EID-1 occurs via ubiquitin-dependent proteolysis and correlates with MDM2 binding. These results are consistent with a model wherein destruction of EID-1 is linked to its ability to interact with MDM2 via either p300 or pRB. | SIGNOR-272582 |
P09237 | P10915 | 1 | cleavage | down-regulates quantity by destabilization | 0.322 | Matrix metalloproteinases cleave at two distinct sites on human cartilage link protein. Sequencing studies of modified link protein components revealed that stromelysins-1 and -2, gelatinases A and B and collagenase cleaved specifically between His16 and Ile17, and matrilysin, stromelysin-2 and gelatinase A cleaved between Leu25 and Leu26. Based on previously determined in situ cleavage sites it is evident that matrix metalloproteinases are not solely responsible for the accumulation of link protein degradation products in adult human cartilage, indicating that additional proteolytic agents are involved in the normal catabolism of human cartilage matrix. | SIGNOR-256329 |
Q15569 | Q9Y281 | 1 | phosphorylation | down-regulates activity | 0.321 | Like TESK1, TESK2 phosphorylated cofilin specifically at Ser-3 and induced formation of actin stress fibers and focal adhesionsExpression of cofilin or S3A-cofilin into HeLa cells induced marked decreases in rhodamine-phalloidin staining due to the actin binding and -depolymerizing activity of cofilin | SIGNOR-246719 |
Q92974 | Q16512 | 0 | phosphorylation | down-regulates | 0.291 | Here we identify a region in the carboxyl terminus of gef-h1 that is important for suppression of its guanine nucleotide exchange activity by microtubules. This portion of the protein includes a coiled-coil motif, a proline-rich motif that may interact with src homology 3 domain-containing proteins, and a potential binding site for 14-3-3 proteins. We show that phosphorylation of gef-h1 at ser(885) by pak1 induces 14-3-3 binding to the exchange factor and relocation of 14-3-3 to microtubules. | SIGNOR-122191 |
Q86YT6 | P63162 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | These data indicate that Mib1 reduces SMN protein stability by targeting it for degradation by the proteasome and represents a new modifier of the SMA phenotype.|Through this study, we provide evidence that the E3 ligase Mib1 ubiquitinates and catalyzes SMN protein degradation. | SIGNOR-278632 |
O60260 | Q99497 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | Together, these results demonstrate that parkin selectively recognizes and ubiquitinates misfolded DJ-1 in vivo. | SIGNOR-278526 |
P28482 | P68400 | 1 | phosphorylation | up-regulates | 0.369 | Erk2, which is activated by egfr signaling, directly binds to ck2alpha via the erk2 docking groove and phosphorylates ck2alpha primarily at t360/s362, subsequently enhancing ck2alpha activity | SIGNOR-161855 |
P28482 | Q13322 | 1 | phosphorylation | up-regulates | 0.373 | We show that grb10 is a direct substrate of the p42/44 mitogen-activated protein kinase (mapk)we identified ser(150), ser(418), and ser(476) of human grb10zeta as mapk-mediated in vitro phosphorylation sites. Replacing ser(150) and ser(476) with alanines reduced the inhibitory effect of human grb10zeta on insulin-stimulated irs1 tyrosine phosphorylation. Taken together, our findings suggest that phosphorylation of the adaptor protein may provide a feedback inhibitory mechanism by which grb10 regulates insulin signaling. | SIGNOR-138163 |
P49137 | P63104 | 1 | phosphorylation | down-regulates activity | 0.625 | We confirmed that MAPKAPK2 interacted with and phosphorylated 14-3-3zeta in vitro and in HEK293 cells. Mutation analysis showed that MAPKAPK2 phosphorylated 14-3-3zeta at Ser-58. S58D mutation significantly impaired both 14-3-3zeta dimerization and binding to Raf-1. | SIGNOR-250151 |
P06493 | Q9UKT4 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.753 | We find that both Emi1 phosphorylation by cyclin and Cdc2 and phosphorylation on a consensus site (DSGxxS) direct recruitment of betaTrCP and subsequent Emi1 ubiquitination and destruction. | SIGNOR-279143 |
O15111 | P20749 | 1 | phosphorylation | up-regulates activity | 0.429 | Here we show that Akt, Erk2, and IKK1/2 phosphorylate Bcl3. Phosphorylation of Ser33 by Akt induces switching of K48 ubiquitination to K63 ubiquitination and thus promotes nuclear localization and stabilization of Bcl3. Phosphorylation by Erk2 and IKK1/2 of Ser114 and Ser446 converts Bcl3 into a transcriptional coregulator by facilitating its recruitment to DNA. | SIGNOR-277362 |
O15294 | P17858 | 1 | glycosylation | down-regulates activity | 0.277 | O-GlcNAcylation was induced at serine 529 of phosphofructokinase 1 (PFK1) in response to hypoxia. Glycosylation inhibited PFK1 activity and redirected glucose flux through the pentose phosphate pathway| O-GlcNAc transferase (OGT) catalyzes the transfer of N-acetylglucosamine from uridine diphospho-N-acetylglucosamine (UDP-GlcNAc) to serine or threonine residues | SIGNOR-267585 |
Q07817 | P21796 | 2 | binding | down-regulates activity | 0.566 | The anti-apoptotic protein Bcl-x(L) closes VDAC by binding to it directly | SIGNOR-249614 |
Q8TCJ0 | O00165 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.331 | FBXO25 encodes an orphan F-box protein that determines the substrate specificity of the SCF (SKP1-CUL1-F-box)(FBXO25) ubiquitin ligase complex. An unbiased screen uncovered the prosurvival protein HCLS1-associated protein X-1 (HAX-1) as the bona fide substrate of FBXO25 that is targeted after apoptotic stresses. Protein kinase Cdelta (PRKCD) initiates this process by phosphorylating FBXO25 and HAX-1, thereby spatially directing nuclear FBXO25 to mitochondrial HAX-1. | SIGNOR-275563 |
Q8TD19 | P53350 | 0 | phosphorylation | up-regulates activity | 0.611 | We now identify Plk1 as Nek9 direct activator and propose a two-step activation mechanism that involves Nek9 sequential phosphorylation by CDK1 and Plk1. while CDK1 activity is necessary for Nek9 phosphorylation in mitosis and the resulting change in electrophoretical mobility, Nek9 Thr210 phosphorylation and mitotic activation requires both CDK1 and Plk1. | SIGNOR-273888 |
P00533 | P12004 | 1 | phosphorylation | up-regulates | 0.341 | Here, we show that the chromatin-bound pcna protein is phosphorylated on tyr 211, which is required for maintaining its function on chromatin and is dependent on the tyrosine kinase activity of egf receptor (egfr) in the nucleus. Phosphorylation on tyr 211 by egfr stabilizes chromatin-bound pcna protein and associated functions. | SIGNOR-150852 |
Q13153 | Q14247 | 1 | phosphorylation | up-regulates | 0.707 | Strikingly, we find that pak1 phosphorylation of cortactin on serine residues 405 and 418 increases its association with n-wasp. Thus, pak1, by controlling the interaction between cortactin and n-wasp, could regulate the polymerization of actin during clathrin-independent endocytosis. | SIGNOR-169690 |
O95243 | P04626 | 0 | phosphorylation | up-regulates activity | 0.2 | Importantly, we found that overexpression of HER2 alone is sufficient to induce MED1 phosphorylation at Thr (1032), a key site that is known to be critical for its functions, whereas blockage of HER2 or its downstream MAP kinase diminishes its phosphor ylation levels in these cells. | SIGNOR-279408 |
O75122 | Q9UDT6 | 2 | binding | up-regulates activity | 0.589 | CLIP-associating protein (CLASP) 1 and CLASP2 are mammalian microtubule (MT) plus-end binding proteins, which associate with CLIP-170 and CLIP-115.|We demonstrate that the middle part of CLASPs binds directly to EB1 and to MTs. | Both EB1- and cortex-binding domains of CLASP are required to promote MT stability. | SIGNOR-265093 |
Q9UKP6 | O95837 | 2 | binding | up-regulates activity | 0.435 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-257426 |
Q16665 | O94953 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.261 | 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-271569 |
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