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 |
|---|---|---|---|---|---|---|---|
Q9UDY2 | P46937 | 2 | binding | down-regulates | 0.519 | The Crumbs complex component AMOT co-localizes with MST1_ 2, LATS1_ 2 and YAP in a complex at the tight junction to control cell growth. Zona occludens-2 (ZO-2) in the tight junction, and a-catenin, b-catenin, or PTPN14 in the adherence junction, also bind to YAP_TAZ. | SIGNOR-230754 |
O14578 | Q9NQS7 | 1 | phosphorylation | up-regulates activity | 0.426 | Figure 5.CIT-K phosphorylates INCENP. (a) Schematic diagram of INCENP structure illustrating the phosphorylated sites identified by MS. | SIGNOR-280232 |
Q86UR1 | Q8NFA2 | 0 | relocalization | up-regulates activity | 0.777 | Tks4 and Tks5 bind NoxA1 through their SH3 domains in a Rac-independent manner|NoxO1 is required for full Nox1 and Nox3 oxidase activity at least partially because of its role in the plasma membrane recruitment of the NoxA1 activator protein|Tks4 and Tks5 support Nox1- and Nox3-dependent ROS generation | SIGNOR-264709 |
P53355 | P05067 | 1 | phosphorylation | up-regulates quantity | 0.287 | DAPK1, but not its kinase deficient mutant (K42A), significantly increased human Aβ secretion in neuronal cell culture models. Moreover, knockdown of DAPK1 expression or inhibition of DAPK1 catalytic activity significantly decreased Aβ secretion. Furthermore, DAPK1, but not K42A, triggered Thr668 phosphorylation of APP, which may initiate and facilitate amyloidogenic APP processing leading to the generation of Aβ.|Furthermore, DAPK1, but not K42A, triggered Thr668 phosphorylation of APP, which may initiate and facilitate amyloidogenic APP processing leading to the generation of Abeta. | SIGNOR-279518 |
P67775 | P31751 | 1 | dephosphorylation | down-regulates activity | 0.748 | Overexpression of BTBD10 increased phosphorylation levels of Akts at both Thr(308) and Ser(473) while the reduction of the endogenous BTBD10 level resulted in a decrease in the phosphorylation levels of Akts. In vitro analysis indicated that BTBD10 bound to protein phosphatase 2A (PP2A) and inhibited dephosphorylation of Akts by PP2A. | SIGNOR-248632 |
P49674 | Q2M2I3 | 2 | binding | up-regulates quantity | 0.2 | We identified members of the FAM83 family of proteins as partners of CK1 in cells. All eight members of the FAM83 family (FAM83A–H) interacted with the α and α-like isoforms of CK1; FAM83A, -B, -E, and -H also interacted with the δ and ε isoforms of CK1. The intrinsic catalytic activity of CK1 is not affected by or required for the association of CK1 with FAM83 proteins. Our findings imply that the DUF1669 domains of FAM83 proteins anchor CK1 α, α-like, δ, and ε isoforms in specific subcellular compartments and potentially mediate their association with substrates. | SIGNOR-273763 |
P01375 | Q00839 | 0 | post transcriptional regulation | up-regulates quantity by stabilization | 0.2 | In the present study, we show that hnRNP-U specifically enhances the expression of tumor necrosis factor alpha mRNA by increasing its stability, possibly through binding to the 3' untranslated region. We also show that hnRNP-U enhances the expression of several other genes as well, including GADD45A, HEXIM1, HOXA2, IER3, NHLH2, and ZFY, by binding to and stabilizing these mRNAs. | SIGNOR-262281 |
P30550 | P63096 | 2 | binding | up-regulates activity | 0.268 | 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-257046 |
O15119 | Q9Y243 | 0 | phosphorylation | up-regulates activity | 0.354 | We have identified TBX3 as a key substrate of AKT3 in melanomagenesis. we have identified the AKT3 target site at serine residue 720 in the TBX3 protein and show that this site is phosphorylated in vivo. the phosphorylation at S720 promotes TBX3 protein stability, nuclear localization, transcriptional repression of E-cadherin, and its role in cell migration and invasion. | SIGNOR-223534 |
P31749 | Q15633 | 1 | phosphorylation | up-regulates activity | 0.2 | We demonstrate that S6 kinases can phosphorylate the extended C-terminal domain of TRBP and interact with TRBP in situ in primary cells. TRBP serines 283/286 are essential for S6K-mediated TRBP phosphorylation, optimal expression of TRBP, and the S6K-TRBP interaction in human primary cells. | SIGNOR-274067 |
Q9UK17 | P00533 | 0 | phosphorylation | up-regulates activity | 0.2 | Our results demonstrate that human atrial I(to) and cloned hKv4.3 channels are modulated by EGFR kinase via phosphorylation of the Y136 residue and by Src-family kinases via phosphorylation of the Y108 residue|We found that human atrial I(to) was inhibited by the broad-spectrum PTK inhibitor genistein, the selective epidermal growth factor receptor (EGFR) kinase inhibitor AG556, and the Src-family kinases inhibitor PP2. | SIGNOR-275549 |
Q13233 | Q12933 | 2 | binding | up-regulates | 0.718 | Traf2, ubc13, and ikkgamma were required for complex assembly and activation of mekk1 and mapk cascades. | SIGNOR-179476 |
Q15910 | Q8IZL9 | 0 | phosphorylation | up-regulates activity | 0.2 | In addition to the transcriptional feedback loop, we also identified a feed-forward loop in which CCRK induces EZH2 phosphorylation, thereby promoting p-EZH2 Ser21 -AR physical interaction for CCRK promoter co-occupancy and transcriptional activation. | SIGNOR-279017 |
Q06187 | P43405 | 0 | phosphorylation | up-regulates activity | 0.589 | We have demonstrated that BLNK mediates Syk-dependent Btk activation. In a reconstitution cell system, coexpression of BLNK allows Syk to phosphorylate Btk on its tyrosine 551, leading to the enhancement of Btk activity. | SIGNOR-247586 |
Q06413 | Q5JVS0 | 2 | binding | down-regulates activity | 0.338 | MEF2C DNA-binding activity is inhibited through its interaction with the regulatory protein Ki-1/57. | SIGNOR-238283 |
P23458 | P08575 | 0 | dephosphorylation | up-regulates | 0.454 | These negative regulatory effects on ig class switching were concomitant with the ability of cd45 to dephosphorylate the induced phosphorylation of jak1, jak3, | SIGNOR-87154 |
P06239 | P16410 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.749 | Lck and Fyn, but not ZAP70, induce tyrosine phosphorylation of CTLA-4 in the cell line HEK293. Phosphorylation of CTLA-4 occurs on both Y201 and Y218. Phosphorylation of Y201 correlated with accumulation of CTLA-4 on the cell surface. | SIGNOR-251370 |
P53350 | Q13127 | 1 | phosphorylation | down-regulates activity | 0.309 | Mass spectrometry revealed that PLK1 phosphorylates REST on serine-1030 ( xref and xref ).|Notably, PLK1 depletion significantly increased REST protein half-life (XREF_FIG, XREF_SUPPLEMENTARY), indicating PLK1 antagonizes REST abundance by restraining REST protein stability. | SIGNOR-279380 |
O00566 | Q9NQZ2 | 2 | binding | up-regulates activity | 0.934 | Mpp10 is able to bind the ribosome biogenesis factor Utp3/Sas10 through two conserved motifs in its N-terminal region. In addition, Mpp10 interacts with the ribosomal protein S5/uS7 using a short stretch within an acidic loop region. Thus, our findings reveal that Mpp10 provides a platform for the simultaneous interaction with multiple proteins in the 90S pre-ribosome. | SIGNOR-261176 |
P15976 | Q9NQU5 | 0 | phosphorylation | up-regulates activity | 0.2 | In addition, PAK5 knockdown also markedly reduced the association of GATA1 with HDAC3/4.|PAK5 phosphorylates the transcription factor GATA1 mainly at Ser161 and Ser 187, phosphorylated GATA1 recruits more HDAC3/4 to the promoter of E-cadherin and consequently suppresses the transcription of E-cadherin gene and promotes the EMT of breast cancer cells. | SIGNOR-278415 |
Q13642 | O75925 | 0 | sumoylation | down-regulates | 0.256 | Pias1 (the protein inhibitor of activated stat1) interacts with kyot2 directly and attenuates kyot2-mediated transcriptional repression. We demonstrate that kyot2 is modified by sumoylation at two lysine residues, k144 and k171. Sumoylation of the transfected kyot2 is enhanced by pias1 | SIGNOR-154801 |
P13631 | P50613 | 0 | phosphorylation | up-regulates activity | 0.418 | RARg Is Phosphorylated by cdk7 in Its B and F Regions | Mutation into alanine of Ser-77 and Ser-79 located in the A/B region reduced the transcriptional activity of hRARg1 (Fig. 9A), confirming that these phosphorylation sites are required for optimal transcription. | SIGNOR-259853 |
P09619 | O43639 | 2 | binding | up-regulates | 0.615 | The sh2 domains of grb2, nck, and grb4 all precipitated activated pdgf receptor with similar efficiency. | SIGNOR-64740 |
P15923 | Q04721 | 2 | binding | down-regulates | 0.273 | In an effort to identify processes that regulate e47, and potentially b-cell development, we found that activated notch1 and notch2 effectively inhibit e47 activity. | SIGNOR-56222 |
Q8N5S9 | P31749 | 1 | phosphorylation | up-regulates activity | 0.379 | Protein kinase B (PKB) was recently reported to be activated on the phosphorylation of Thr(308) by Ca(2+)/calmodulin-dependent protein kinase kinase alpha (CaM-kinase kinase alpha), suggesting that PKB was regulated through not only the phosphoinositide 3-kinase pathway but also the Ca(2+)/calmodulin protein kinase pathway. | SIGNOR-252609 |
Q96JN8 | O95714 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.456 | NEURL4 is a substrate of HERC2, and together these results indicate that the NEURL4-HERC2 complex participates in the ubiquitin-dependent regulation of centrosome architecture. | SIGNOR-272921 |
P29375 | P84243 | 1 | 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-264301 |
P20807 | P10636 | 1 | cleavage | down-regulates activity | 0.324 | Besides tau phosphorylation, calpain activation might play a role in tau-mediated neurodegeneration by inducing tau cleavage. In vitro studies have shown that both fetal and adult tau isoforms are rapidly proteolyzed by calpains | SIGNOR-251605 |
Q99961 | P12931 | 0 | phosphorylation | down-regulates | 0.639 | Further, we identified an interaction between fak's second pro-rich motif and endophilin a2's sh3 domain. This interaction served as an autophosphorylation-dependent scaffold to allow src phosphorylation of endophilin a2 at tyr315. Tyr315 phosphorylation inhibited endophilin/dynamin interactions, and blockade of tyr315 phosphorylation promoted endocytosis of mt1-mmp. Together, these results suggest a regulatory mechanism of cell invasion whereby fak promotes cell-surface presentation of mt1-mmp by inhibiting endophilin a2-dependent endocytosis. | SIGNOR-139150 |
Q9Y570 | Q14012 | 0 | phosphorylation | up-regulates activity | 0.395 | CaMKI Is the Upstream Kinase for Phosphorylation of PME-1/Ser15 | SIGNOR-277827 |
P42345 | Q9HBH9 | 1 | phosphorylation | down-regulates activity | 0.274 | MTOR phosphorylates MNK2a on Ser74. Here, we show that mTORC1, a key regulator of mRNA translation and oncogenesis, directly phosphorylates MNK2 on Ser74. This suppresses MNK2 activity and impairs binding of MNK2 to eIF4G. | SIGNOR-277516 |
Q9Y243 | P15056 | 1 | phosphorylation | down-regulates | 0.289 | We show that phosphorylation of b-raf by akt occurs at multiple residues within its aminoterminal regulatory domain, at both the conserved and unique phosphorylation sites. Akt phosphorylated b-raf on s364 and s428 to inactivate its kinase activity. | SIGNOR-78693 |
Q96RR4 | Q13131 | 1 | phosphorylation | up-regulates | 0.604 | Ampka1 activators increased phosphorylation level and cytoplasmic localization (reduced nuclear/cytoplasmic ratio). Ampka1 activators reduced rna synthesis in the nucleoli. | SIGNOR-176602 |
P34947 | Q16143 | 1 | phosphorylation | down-regulates activity | 0.321 | GRK5 prefers alpha-synuclein as a substrate. GRK-mediated phosphorylation inhibits synuclein's interaction with both phospholipids and PLD2. Mutation of Ser118 practically abolishes β-synuclein phosphorylation by both GRK2 and GRK5 | SIGNOR-251203 |
Q9Y371 | Q14457 | 2 | binding | up-regulates | 0.543 | Bif-1 forms a complex with beclin1 through uvrag and promotes the activation of the class iii pi3 kinase, vps34, in mammalian cells. | SIGNOR-171899 |
Q86YD1 | Q7Z6Z7 | 0 | ubiquitination | down-regulates quantity | 0.2 | Our data suggest that HUWE1 can ubiquitinate PTOV1 in vitro and depletion of HUWE1 in cells increases the stability of PTOV1 S36A protein in the nucleus.|Our data suggest that depletion of HUWE1 elevates PTOV1 protein levels, which, in turn, promote the expression of cJun, a pro-growth translational target of PTOV1 (18)\n In our model, we propose that HUWE1 mediates the degradation of PTOV1 in the nucleus. | SIGNOR-278755 |
P18031 | Q16539 | 1 | dephosphorylation | down-regulates activity | 0.443 | Here, we show that PTP1B regulates CD40 and BAFF-R signaling and dephosphorylates the mitogen-activated protein kinase p38.|Specifically, PTP1B counteracts p38 mitogen-activated protein kinase activation by directly dephosphorylating Tyr182 of this kinase. | SIGNOR-277167 |
P78344 | P20042 | 2 | binding | up-regulates activity | 0.753 | Unlike eIF4GI/II, DAP5 binds eIF2β, a subunit of the eIF2 complex that delivers methionyl-tRNA to ribosomes. | SIGNOR-266385 |
P38405 | O15552 | 2 | binding | up-regulates activity | 0.2 | 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-256946 |
O95644 | P49841 | 0 | phosphorylation | down-regulates activity | 0.588 | In T-cells, calcineurin de-phosphorylates NFATc1, leading to its nuclear import, while glycogen synthase kinase 3 beta (GSK3beta) phosphorylates NFATc1 and promotes its nuclear export.|We conclude that GSK3beta negatively regulates NFATc1 in vSMCs, and GSK3beta must be inactivated to allow NFAT activation during wound repair.Male Sprague-Dawley rats were obtained from Charles River (Montreal, PQ, Canada). | SIGNOR-279185 |
P11362 | Q96QU1 | 1 | 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 |
Q14493 | Q6DN03 | 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-265382 |
Q96KB5 | Q92769 | 1 | phosphorylation | up-regulates activity | 0.2 | The results of in vitro studies further confirmed the effect of TOPK on HDAC activity by showing that TOPK overexpression significantly up-regulated p-HDAC1 and p-HDAC2, resulting in an increase in the acetylation of histones H3 and H4 in BV2 cells.|These results indicated that TOPK overexpression resulted in the phosphorylation of HDAC1 and HDAC2, which might inactivate them and promote the acetylation of Histone 3 and Histone 4. | SIGNOR-279087 |
P50148 | P43088 | 2 | binding | up-regulates activity | 0.45 | 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-257082 |
Q99626 | Q02817 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | COS-7 cells were transiently transfected with a CDX1 or CDX2 expression construct and then used for the luciferase assay, reverse transcription-polymerase chain reaction, and electrophoretic mobility shift assay (EMSA). The CDX2 expression construct activated the MUC2 promoter and increased the endogenous MUC2 mRNA level, while the CDX1 one did not. | SIGNOR-253966 |
Q14203 | Q9UKA1 | 2 | binding | down-regulates quantity by destabilization | 0.462 | FBXL5 binds to p150(Glued)in vitro and in vivo. FBXL5 and p150(Glued) co-localize primarily in the cytoplasm with peri-nuclear enrichment in HeLa cells. Overexpression of FBXL5 promotes poly-ubiquitination of p150(Glued) and protein turnover of p150(Glued). Our findings provide a potential mechanism by which p150(Glued) protein function is regulated by SCFs. | SIGNOR-271652 |
Q99466 | Q96JK9 | 2 | binding | up-regulates | 0.867 | Moreover, as determined by using coimmunoprecipitation assays, each maml protein was found to be capable of forming a multiprotein complex with the intracellular domain of each notch receptor (icn1 to -4) and csl in vivo | SIGNOR-94109 |
Q8NHL6 | Q86YJ5 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.2 | MARCH9, a member of the RING-CH family of transmembrane E3 ubiquitin ligases, down-regulates CD4, major histocompatibility complex-I (MHC), and ICAM-1 in lymphoid cells. To identify novel MARCH9 substrates, we used high throughput flow cytometry and quantitative mass spectrometry by stable isotope labeling by amino acids in cell culture (SILAC) to determine the differential expression of plasma membrane proteins in a MARCH9-expressing B cell line. This combined approach identified 13 potential new MARCH9 targets. | SIGNOR-271534 |
P08254 | P10915 | 1 | cleavage | down-regulates quantity by destabilization | 0.384 | 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-256330 |
P04626 | P29353 | 2 | binding | up-regulates | 0.807 | Shc interacts with and is an excellent substrate for erbb2 and appears to play an important role in mitogenic signaling through this receptor tyrosine kinase | SIGNOR-65579 |
P50750 | P36873 | 0 | dephosphorylation | up-regulates | 0.2 | Pp1 is an activator of cdk9. Pp1 dephosphorylates cdk9 thr186. | SIGNOR-173454 |
Q99748 | P07949 | 2 | binding | up-regulates | 0.715 | A receptor complex comprised of trnr1 (gdnfr alpha) and ret was recently identified and found to be capable of mediating both gdnf and ntn signaling | SIGNOR-49122 |
P19838 | O00221 | 2 | binding | down-regulates | 0.541 | Nf-kb is normally sequestered in the cell cytoplasm by binding to ikbx, ikbb, ikbe | SIGNOR-102774 |
Q14457 | O75385 | 0 | phosphorylation | up-regulates activity | 0.771 | In the nucleation step of autophagy, The ULK1 complex phosphorylates and activates the Beclin-1-VPS34 complex. | SIGNOR-278503 |
Q6IBW4 | P54274 | 2 | binding | up-regulates activity | 0.2 | Taken together these observations suggest that NCAPH2 promotes telomere stability, possibly through a direct interaction with the TRF1 shelterin component, and prevents telomere dysfunction resulting from impaired DNA replication. | SIGNOR-263914 |
P14416 | O14775 | 2 | binding | up-regulates activity | 0.603 | The D2-class dopamine receptors (D2, D3, and D4) couple to the Gi/o family of G proteins and thus induce inhibition of AC | SIGNOR-264993 |
Q14393 | P30530 | 2 | binding | up-regulates | 0.905 | Receptor tyrosine kinases of the axl family are activated by the vitamin k-dependent protein gas6. We report the identification of ligands for tyro 3 (alternatively called sky, rse, brt, or tif) and axl (alternatively, ark or ufo), members of a previously orphan family of receptor-like tyrosine kinases. These ligands correspond to protein s, a protease regulator that is a potent anticoagulant, and gas6, a protein related to protein s but lacking any known function. | SIGNOR-34339 |
Q8TDV5 | O95837 | 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-257415 |
P35222 | P67775 | 0 | dephosphorylation | up-regulates | 0.462 | In the absence of the wt apc protein, phosphorylated beta-catenin is rapidly dephosphorylated by serine/threonine protein phosphatase 2a (pp2a). phosphorylated beta-catenin associated with the wild-type apc protein is recruited to the scf(beta-trcp) complex, ubiquitin conjugated, and degraded. | SIGNOR-182637 |
P29474 | P17612 | 0 | phosphorylation | up-regulates | 0.399 | Recently many investigators have shown that protein phosphorylation of enos by several serine/threonine kinases is a critical control step for no production by endothelial cells. Phosphorylation by amp kinase, akt (or protein kinase b), or protein kinase aon serine 1179 (bovine) or serine 1177 (human) of enos leads to enhanced activity of the enzyme and, thus, augmented production of no. | SIGNOR-112371 |
P19086 | P17252 | 0 | phosphorylation | up-regulates | 0.442 | Functional role of amino-terminal serine16 and serine27 of g alphaz in receptor and effector coupling. | SIGNOR-48681 |
P0C2W1 | Q96IZ0 | 2 | binding | down-regulates quantity by destabilization | 0.381 | Fbxo45 interacts with Par-4 in the cytoplasm and mediates its ubiquitylation and proteasomal degradation. Fbxo45 silencing results in stabilization of Par-4 with increased apoptosis.Fbxo45 forms an atypical ubiquitin ligase complex that contains Skp1 and the Ring-finger protein PAM (protein-associated with myc) also known as MYCBP2 (myc-binding protein 2). | SIGNOR-272223 |
P53041 | Q14344 | 2 | binding | up-regulates activity | 0.326 | In this study, we show that active forms of G12 and G13 specifically interact with PP5 through its TPR domain and activate its phosphatase activity about 2.5-fold. Active forms of G12 and G13 also enhance the arachidonic acid-stimulated PP5 phosphatase activity about 2.5-fold. | SIGNOR-278081 |
P14921 | P31314 | 2 | binding | down-regulates activity | 0.467 | We show that the cortical thymic maturation arrest in T-lineage ALLs that overexpress TLX1 or TLX3 is due to binding of TLX1/TLX3 to ETS1, leading to repression of T cell receptor (TCR) α enhanceosome activity and blocked TCR-Jα rearrangement. | SIGNOR-259097 |
Q86UL8 | Q8NFZ4 | 2 | binding | up-regulates activity | 0.403 | S-SCAM is a member of the membrane-associated guanylate kinase (MAGUK) family of PDZ-domain-containing proteins that include the synaptic organising molecule PSD-95. The PDZ domain of S-SCAM binds to the C-terminal tail of NL2, forming a ternary complex at the cell membrane (Figure 2b). The DGC is potentially recruited to the postsynaptic membrane though a direct neurexin–dystroglycan interaction and an indirect interaction with NL2 via the synaptic scaffolding protein S-SCAM. | SIGNOR-265444 |
O43257 | Q16539 | 0 | phosphorylation | up-regulates | 0.314 | We show that the srcap subunit named znhit1 or p18(hamlet), which is a substrate of p38 mapk, is recruited to the myogenin promoter at the onset of muscle differentiation, in a p38 mapk-dependent manner. Furthermore, p18hamlet was phosphorylated during myoblast differentiation in a p38 mapk-dependent manner (dal testo pmc) | SIGNOR-165571 |
O00712 | O00712 | 2 | binding | down-regulates activity | 0.2 | Coexpression of NFI-B3 with other isoforms of the NFI-B, -C, and -X family, however, led to a strong reduction of transcriptional activation compared with the expression of these factors alone. NFI-B3 apparently forms heterodimers with other NFI proteins thereby interfering with their function. | SIGNOR-240883 |
P48729 | Q9UGI0 | 1 | phosphorylation | up-regulates activity | 0.2 | Interestingly, ZRANB1 is phosphorylated at Thr35, and Ser209 residues by CSNK1A1, and this phosphorylation activates its deubiquitinating activity. | SIGNOR-273621 |
Q16539 | P06241 | 0 | phosphorylation | up-regulates | 0.489 | T cell src family kinases and zap70 activate p38 by phosphorylating tyr323. | SIGNOR-134293 |
P29317 | P24666 | 0 | dephosphorylation | down-regulates activity | 0.66 | The SAM domain tyrosine Y960 which has been implicated in downstream PI3K signaling is dephosphorylated exclusively by HCPTP-B. The activation loop tyrosine (Y772) which directly controls kinase activity is dephosphorylated about six times faster by HCPTP-A. In contrast, the juxtamembrane tyrosines (Y575, Y588 and Y594) which are implicated in both control of kinase activity and downstream signaling are dephosphorylated by both variants with similar rates | SIGNOR-246023 |
Q13546 | Q13158 | 2 | binding | up-regulates activity | 0.791 | Rip1 is required for the formation of a rip1/fadd/caspase-8 complex that drives caspase-8 activation, cleavage of bid into tbid, mitochondrial outer membrane permeabilization, full activation of caspase-3 and caspase-dependent apoptosis. Tweak induces assembly of a death-signaling complex containing rip1, fadd, and caspase-8 | SIGNOR-191781 |
P06493 | O95239 | 1 | phosphorylation | up-regulates activity | 0.489 | Identification of Cdk phosphorylation of Kif4A at T1161 in early mitosis. We show that Cdk phosphorylation of Kif4A licenses its chromosome localization. | SIGNOR-265994 |
P54278 | P04637 | 0 | 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 |
Q13976 | P31645 | 1 | phosphorylation | up-regulates | 0.382 | These results are consistent with the hypothesis that pkg phosphorylates hsert at thr-276 and increases its activity by modifying the substrate permeation pathway formed, in part, by tm5. | SIGNOR-158186 |
Q8WTR2 | P45983 | 1 | dephosphorylation | down-regulates | 0.421 | Skrp1 was highly specific for c-jun n-terminal kinase (jnk) in vitro and effectively suppressed the jnk activation in response to tumor necrosis factor alpha or thapsigargin skrp1 does not bind directly to its target jnk, but co-precipitation of skrp1 with the mapk kinase mkk7, a jnk activator, was found in vitro and in vivo. | SIGNOR-117260 |
Q13639 | O95837 | 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-257416 |
P09471 | Q9UBY5 | 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-257141 |
P59595 | P16220 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | The transcription factors c-Fos, FosB, CREB-1, and ATF2 were all activated by the addition of SARS-CoV N protein to the sample well | SIGNOR-260729 |
Q92847 | P38405 | 2 | binding | up-regulates activity | 0.267 | 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-256925 |
Q14524 | Q13554 | 0 | phosphorylation | up-regulates activity | 0.408 | Among the sites identified, only six were previously suggested to be the targets for specific kinases using in silico and/or in vitro analyses: S36 and S525 were attributed to the regulation by PKA; S484 and S664 were assigned to the serum- and glucocorticoid-inducible kinase 3 (SGK3); and S516 and S571 were ascribed to CaMKII (reviewed in Marionneau and Abriel, 2015). In marked contrast, several previously described phosphorylation sites were not detected in the present study, including the PKA-dependent S528, the CaMKII-associated T594, the PKC-dependent S1506, the adenosine monophosphate–activated protein kinase (AMPK)–dependent T101 (Liu et al., 2019), and the six Fyn-dependent tyrosines (Ahern et al., 2005; Iqbal et al., 2018).|The simplest interpretation of these findings is that these three phosphorylation clusters, at positions S457-S460, S483-T486, and S664-S671, are likely involved in regulating the basal and/or gating properties of native cardiac NaV1.5 channels. Conversely, the other phosphorylation sites, with lower stoichiometries, may play spatially or temporally distinct roles in the physiological or more pathophysiological regulation of channel expression or gating. | Remarkably, this MS analysis also revealed that the vast majority of identified phosphorylation sites (at least 26) are clustered, suggesting concomitant phosphorylation and roles in regulating channel expression and/or function. Unexpectedly, however, except for S664, S667, and S671, no apparent effects of phosphomimetic or phosphosilent mutations were observed on heterologously expressed (in HEK-293 cells) NaV1.5 | SIGNOR-275773 |
P49639 | O15550 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.403 | Evidence for direct involvement of UTX in regulation of HOX gene activity was demonstrated through UTX knockdown experiments in HEK293T cells in which loss of UTX induced transcriptional repression of HOXA and HOXC clusters. | SIGNOR-260019 |
Q9Y463 | P46734 | 0 | phosphorylation | up-regulates | 0.348 | Mkk3 enhanced mirk kinase activity. Mkk3 possibly activates mirk by phosphorylating it. | SIGNOR-86731 |
Q9Y4K3 | P21580 | 0 | deubiquitination | down-regulates activity | 0.702 | A20 is a deubiquitinating enzyme (dub) for lys63-linked polyubiquitinated signaling mediators such as traf6 | SIGNOR-160223 |
Q9H3R0 | Q16695 | 1 | demethylation | down-regulates activity | 0.2 | As one member of the Jumonji-C histone demethylase family, JMJD2C has the ability to demethylate tri- or di-methylated histone 3 and 2 in either K9 (lysine residue 9) or K36 (lysine residue 36) sites by an oxidative reaction, thereby affecting heterochromatin formation, genomic imprinting, X-chromosome inactivation, and transcriptional regulation of genes.JMJD2C has been proved to be a demethylase for H3K9 methylation, in the manner of catalyzing the demethylation of H3K9me3/me2 (the known repressive markers of gene regulation), a histone mark found in heterochromatin associated with euchromatic transcriptional silencing and heterochromatin formation | SIGNOR-263866 |
Q01538 | P46937 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | Myt1 and Myt1l transcription factors limit proliferation in GBM cells by repressing YAP1 expression. Examination of the gene expression changes in cells expressing Myt1 or Myt1l suggests that both repress expression of the YAP1 transcriptional coactivator, which functions primarily in the Hippo signaling pathway. Expression of YAP1 and its target genes is reduced in Myt-expressing cells, and there is an inverse correlation between YAP1 and MYT1/MYT1L expression in human brain cancer datasets. Together, our data suggest that Myt1 and Myt1l directly repress expression of YAP1, a protein which promotes proliferation and GBM growth. | SIGNOR-266777 |
P01106 | P26599 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.438 | We also demonstrate that the oncogenic transcription factor c-Myc upregulates transcription of PTB, hnRNPA1 and hnRNPA2, | SIGNOR-268689 |
Q9BZI7 | Q92900 | 2 | binding | up-regulates activity | 0.957 | UPF2 and UPF3b increase UPF1 ATPase activity | SIGNOR-265247 |
P41212 | P27361 | 0 | phosphorylation | down-regulates | 0.317 | Tel became phosphorylated by erk on two serine residues, ser213 and ser257, in the internal domain between the hlh and ets domains. Tel lost its abilities to repress transcription through the phosphorylation. | SIGNOR-123656 |
P10415 | Q9BXH1 | 2 | binding | down-regulates activity | 0.663 | Only bimbh3 and bbc3 had comparable strong affinitiesfor all the prosurvival proteins. The members that promote cell survival, including mammalian bcl-2, bcl-xl,bcl-w, mcl-1, and a1. | SIGNOR-133808 |
P27986 | P56945 | 2 | binding | up-regulates activity | 0.563 | One such SH2-domain containing protein is the p85 subunit of PI3K, as its docking with tyrosine-phosphorylated p130cas activates the p110alpha subunit| tyrosine-165 and tyrosine-128 on p130cas both are phosphorylated to a greater extent in parental versus paxillin Y88F mutan | SIGNOR-263980 |
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 |
P29350 | P17252 | 0 | phosphorylation | down-regulates | 0.364 | Protein kinase calpha therefore critically and negatively regulates shp-1 function, forming part of a mechanism to retain shp-1 in a basal active state through interaction with its sh2 domains, and phosphorylating its c-terminal ser591 upon cellular activation | SIGNOR-126876 |
P11441 | O43765 | 2 | binding | up-regulates activity | 0.577 | USP13 and gp78 control ubiquitination of Ubl4A.These data suggest that USP13 and gp78 play antagonizing roles in regulation of Ubl4A ubiquitination: While gp78 assembles ubiquitin chains on Ubl4A, USP13 antagonizes this activity to limit Ubl4A ubiquitination.Ubiquitination of Ubl4A preferentially occurs on Lys48. We identify the Bag6 cofactor Ubl4A as a shared substrate of gp78 and USP13. USP13 depletion is associated with hyper-ubiquitination of Ubl4A and altered interaction between the Bag6 complex and its co-chaperone SGTA. Because the interaction of Ubl4A with SGTA is mediated by positively-charged residues in Ubl4A including Lys48 (Chartron et al., 2012; Xu et al., 2012), which happens to be the major ubiquitination site, the simplest model to explain reduced Bag6-SGTA interaction in USP13 knockdown cells is that ubiquitin conjugates on Ubl4A sterically hinder SGTA binding. | SIGNOR-272858 |
Q8WUW1 | Q6T4R5 | 2 | binding | up-regulates activity | 0.2 | We show that the WHD of NHS interacts with the Abi family of proteins, HSPC300, Nap1 and Sra1, and is important for the localization of NHS to the leading edge. | SIGNOR-253574 |
P42574 | P08590 | 1 | cleavage | down-regulates quantity by destabilization | 0.377 | By sequencing and site-directed mutagenesis, a noncanonical cleavage site for caspase-3 was mapped to the C-terminal DFVE(135)G motif. We demonstrated that vMLC1 cleavage in failing myocardium in vivo is associated with a morphological disruption of the organized vMLC1 staining of sarcomeres, and with a reduction in myocyte contractile performance. | SIGNOR-270593 |
P02647 | O60674 | 0 | null | up-regulates activity | 0.298 | ApoA-I interactions with ABCA1 and lipid efflux to apoA-I were substantially impaired by inhibiting or abolishing JAK2, whereas ABCA1 protein levels were unaffected, and ABCA1 cholesterol translocase activity was only slightly reduced. The most likely explanation for these findings is that JAK2 promotes apolipoprotein interactions with ABCA1 or a closely proximal site, and this facilitates the removal of cellular lipids. the interaction of apolipoproteins with ABCA1-expressing cells activates JAK2, which in turn activates a process that enhances apolipoprotein interactions with ABCA1 and lipid removal from cells | SIGNOR-252107 |
P40337 | P06493 | 0 | phosphorylation | up-regulates activity | 0.2 | Mechanistically, CDK1 directly phosphorylates pVHL at Ser80, which primes the recognition of pVHL by PIN1.|PIN1 and CDK1 cooperatively modulate the protein turnover of pVHL, thereby conferring tumor growth, chemotherapeutic resistance and metastasis both in vitro and in vivo. | SIGNOR-280207 |
Q7Z2W7 | P67775 | 0 | dephosphorylation | down-regulates activity | 0.2 | Using specific pharmacological and molecular tools combined with patch-clamp current recordings, we found that in heterologously expressed HEK-293 (human embryonic kidney) cells, TRPM8 channel is inhibited by the G(i) protein/adenylate cyclase (AC)/cAMP/protein kinase A (PKA) signaling cascade. We further identified the TRPM8 S9 and T17 as two key PKA phosphorylation sites regulating TRPM8 channel activity. the intracellular serine/threonine protein phosphatase 2A (PP2A) dephosphorylates TRPM8 Ser-9 and Thr-17 inhibiting the channel activity. | SIGNOR-273793 |
Q15722 | 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-256691 |
Q13905 | P12931 | 0 | phosphorylation | up-regulates | 0.671 | C3g is activated upon phosphorylation at tyrosine 504 c3g is phosphorylated in vivo on y504 upon coexpression with src or hck, two members of the src family tyrosine kinases. | SIGNOR-128273 |
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