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 |
|---|---|---|---|---|---|---|---|
P51955 | Q15021 | 1 | phosphorylation | down-regulates activity | 0.269 | Nek2 phosphorylates C-Nap1, rootletin and beta-catenin to regulate centrosome separation. | SIGNOR-279234 |
Q13144 | Q92837 | 2 | binding | up-regulates activity | 0.288 | In contrast to the GS‐1 peptide, glycogen synthase and the eIF2B peptide, the GSK3‐catalysed phosphorylation of Tau was completely inhibited by FRATtide|This prevents GSK3 from phosphorylating and inhibiting glycogen synthase [2, 3] and protein synthesis initiation factor eIF2B | SIGNOR-262835 |
Q15077 | P09471 | 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-257076 |
Q9H0F5 | P04637 | 1 | ubiquitination | down-regulates activity | 0.363 | Here we demonstrate that RNF38 is a functional ubiquitin protein ligase (E3). We show that RNF38 isoform 1 is localized to the nucleus by a bipartite nuclear localization sequence (NLS). We confirm that RNF38 is a binding partner of p53 and demonstrate that RNF38 can ubiquitinate p53 in vitro and in vivo. Finally, we show that overexpression of RNF38 in HEK293T cells results in relocalization of p53 to discrete foci associated with PML nuclear bodies. | SIGNOR-272130 |
Q00005 | O15530 | 2 | binding | down-regulates activity | 0.331 | Here, we show that PPP2R2B, encoding the B55² regulatory subunit of the PP2A complex, is epigenetically inactivated by DNA hypermethylation in colorectal cancer. B55²-associated PP2A interacts with PDK1 and modulates its activity toward Myc phosphorylation. | SIGNOR-243511 |
P21453 | P08754 | 2 | binding | up-regulates activity | 0.504 | 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-256856 |
P46527 | Q8TAS1 | 0 | phosphorylation | up-regulates | 0.367 | Hkis is a nuclear protein that binds the c-terminal domain of p27(kip1) and phosphorylates it on s10 in vitro and in vivo, promoting its nuclear export to the cytoplasm.Phosphorylation at serine 10, a major phosphorylation site of p27(kip1), increases its protein stability | SIGNOR-90274 |
O43791 | P35659 | 2 | binding | down-regulates quantity by destabilization | 0.438 | Here, we analyzed changes in the ubiquitin landscape induced by prostate cancer-associated mutations of SPOP, an E3 ubiquitin ligase substrate-binding protein. SPOP mutants impaired ubiquitylation of a subset of proteins in a dominant-negative fashion. Of these, DEK and TRIM24 emerged as effector substrates consistently up-regulated by SPOP mutants. Up-regulation of DEK, TRIM24 and NCOA3 is a feature of prostate cancer SPOP mutations. This result aligns well with the observation that multiple ubiquitylated DEK lysine residues were detected in the initial proteome analysis (fig. S2E). | SIGNOR-272826 |
P12270 | Q13257 | 2 | binding | up-regulates | 0.309 | Tpr directly binds to mad1 and mad2. / depletion of tpr decreases the levels of mad1 at kinetochores during prometaphase, correlating with the inability of mad1 to activate mad2, which is required for inhibiting apc(cdc20). | SIGNOR-181975 |
P48730 | P35968 | 1 | phosphorylation | down-regulates activity | 0.328 | CKIdelta phosphorylates VEGFR2 at both DSG and DDTD phosphodegrons to promote its interaction with beta-TRCP1.|In a reciprocal set of experiments, we found that overexpression of CKIdelta markedly decreased the half-life of VEGFR2 (XREF_FIG). | SIGNOR-280235 |
O15105 | Q96EB6 | 0 | deacetylation | down-regulates | 0.441 | Sirt1 reversed acetyl-transferase (p300)-mediated acetylation of two lysine residues (lys-64 and -70) on smad7. sirt1-mediated deacetylation of smad7 enhanced smad ubiquitination regulatory factor 1 (smurf1)-mediated ubiquitin proteasome degradation, which contributed to the low expression of smad7 in sirt1-overexpressing mesangial cells. | SIGNOR-150595 |
Q96GD4 | P04637 | 1 | phosphorylation | down-regulates | 0.719 | We show that aurora b phosphorylates p53 at s183, t211, and s215 to accelerate the degradation of p53 through the polyubiquitination-proteasome pathway, thus functionally suppressing the expression of p53 target genes involved in cell cycle inhibition and apoptosis (e.g., p21 and puma). | SIGNOR-197598 |
P06493 | P63279 | 1 | phosphorylation | up-regulates activity | 0.512 | Overall, these results suggest that Cdk1 and cyclin B mediates the phosphorylation of Ubc9 at serine 71. | SIGNOR-278174 |
Q16512 | O15553 | 1 | phosphorylation | down-regulates activity | 0.384 | PKNs bind to human pyrin and phosphorylate S208 and S242. Pyrin forms an inflammasome when mutant or in response to bacterial modification of the GTPase RhoA. We found that RhoA activated the serine-threonine kinases PKN1 and PKN2 that bind and phosphorylate pyrin. Phosphorylated pyrin bound to 14-3-3 proteins, regulatory proteins that in turn blocked the pyrin inflammasome. | SIGNOR-275461 |
Q13501 | Q14680 | 0 | phosphorylation | up-regulates activity | 0.2 | Consistent with our SILAC experiments, MELK directly phosphorylated SQSTM1 (XREF_FIG).|Furthermore, we show that MELK promotes melanoma growth by activating NF-kappaB pathway activity via Sequestosome 1 (SQSTM1 and p62). | SIGNOR-279544 |
P17677 | O95372 | 0 | deacetylation | down-regulates quantity by destabilization | 0.477 | Acyl-protein thioesterase 2 catalyzes the deacylation of peripheral membrane-associated GAP-43. In this work, we investigated the deacylation of growth-associated protein-43 (GAP-43), a dually acylated protein at cysteine residues 3 and 4. Thus, the results demonstrate that APT-2 is the protein thioesterase involved in the acylation/deacylation cycle operating in GAP-43 subcellular distribution.we demonstrated that the reduction in the protein level was abrogated when cells were also treated with proteasome inhibitors (chloroquine, MG132 and lactacystin) which strongly suggest that GAP-43 deacylation is an early and necessary step for its later ubiquitination and degradation by the proteasome. In addition, it also suggests that acyl-protein thioesterase levels not only regulate palmitate turnover but also global protein turnover of GAP-43. | SIGNOR-266768 |
P36897 | P62942 | 2 | binding | down-regulates activity | 0.853 | Blocking fkbp12/type i receptor interaction with fk506 nonfunctional derivatives enhances the ligand activity, indicating that fkbp12 binding is inhibitory to the signaling pathways of the tgf beta family ligands | SIGNOR-236142 |
O00254 | P63092 | 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 ‚â• -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 ‚â• -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ‚â• -1.0. | SIGNOR-256761 |
Q99942 | Q9Y4P1 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.405 | These results substantiate the notion that RNF5 negatively regulates ATG4B availability with concomitant effect on LC3 processing and autophagy under normal growth conditions.|These results suggest that RNF5 directly induces ATG4B ubiquitination. | SIGNOR-278664 |
P27361 | P35228 | 1 | phosphorylation | up-regulates | 0.354 | Erk phosphorylated inos on ser745. Mutation of ser745 to ala did not affect basal inos activity but eliminated inos phosphorylation and activation in response to b1r agonist. | SIGNOR-157711 |
Q02750 | P17542 | 1 | phosphorylation | down-regulates | 0.2 | We found that hypoxia greatly accelerated tal1 turnover in these cells through mitogen-activated protein kinase (mapk)2-mediated phosphorylation, ubiquitination, and proteasomal degradation. | SIGNOR-116149 |
P31751 | Q13418 | 0 | phosphorylation | up-regulates activity | 0.615 | ILK mediated activation of Akt2 is required for Tbeta4 inducible expression of MMP-2 and EC motility.|Our experiments suggest that ILK phosphorylates Akt2 at Ser474, that Akt2 is a better substrate than Akt1, and that a post-translational modification to ILK is required for its activity. | SIGNOR-279055 |
P17252 | P19174 | 2 | phosphorylation | down-regulates | 0.556 | The observation that pka also phosphorylates plc-yl on serine 1248 suggests that phosphorylation of this residue may be a common mechanism by which pkc and pka inhibit plc-yl. | SIGNOR-17905 |
P00748 | P50281 | 0 | cleavage | down-regulates quantity by destabilization | 0.331 | The data presented in this study show for the first time the degradation of Factor XII of the blood clotting system by matrix metalloproteinases. MMP-12, MMP-13, and MMP-14 cleave at Gly376Leu377|However, no activity of Factor XII can be observed after MMPinduced cleavage. | SIGNOR-263610 |
P30838 | Q9NXK8 | 2 | binding | down-regulates quantity by destabilization | 0.32 | We now show that SCFFBXL12 is an authentic E3 for the ALDH3 family of enzymes. We now show that the ubiquitin-dependent degradation of ALDH3 mediated by FBXL12 (F box and leucine-rich repeat protein 12) is essential for execution of the differentiation program of trophoblast stem cells (TSCs). FBXL12 is present only in eutherian mammals, and its expression is largely restricted to the placenta during mouse embryogenesis. FBXL12 was found to interact specifically with members of the ALDH3 family and to mediate their polyubiquitylation. Finally, coimmunoprecipitation analysis revealed that FBXL12 interacted efficiently only with members of the ALDH3 family (ALDH3A1, ALDH3A2, and ALDH3B1), showing little if any association with those of the ALDH1 family (ALDH1A1, ALDH1A2, and ALDH1A3) (Fig. 2H). Collectively, these results suggested that SCFFBXL12 is an authentic E3 specific for ALDH3 family members. | SIGNOR-272813 |
P00519 | P04040 | 1 | phosphorylation | up-regulates activity | 0.403 | C-abl and arg phosphorylated catalase at tyr231 and tyr386 in vitrocatalase is a major effector in the defense of aerobic cells against oxidative stress. Recent studies have shown that catalase activity is stimulated by the c-abl and arg tyrosine kinases | SIGNOR-101302 |
P51812 | Q9H6Z4 | 1 | phosphorylation | up-regulates quantity | 0.328 | RSK phosphorylates RanBP3 at Serine 58 residue in vitro and in vivo.RanBP3 phosphorylation increases its affinity towards Ran | SIGNOR-276148 |
P35227 | P63279 | 2 | binding | down-regulates activity | 0.608 | Based on this finding of interaction between MEL-18 and UBC9, we envisioned a mechanism in which MEL-18 bound to HSF2 inhibits its sumoylation by binding to and inhibiting the activity of UBC9 enzymes that approach HSF2. | SIGNOR-226248 |
P27635 | P05412 | 2 | binding | down-regulates | 0.387 | The qm gene encodes a 24.5 kda ribosomal protein l10 known to be highly homologous to a jun-binding protein (jif-1), which inhibits the formation of jun-jun dimers. | SIGNOR-90750 |
O95837 | P46663 | 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-257362 |
P40763 | Q99558 | 0 | phosphorylation | up-regulates activity | 0.26 | Activation of Stat3 by NIK requires NIK kinase activity as showed by kinase assays.|When we transfected NIK into LNCaP cells, NIK was able to phosphorylate Stat3 at both tyrosine 705 and serine 727 residues ( Fig. 3 A). | SIGNOR-279341 |
Q6PIJ6 | O75840 | 2 | binding | up-regulates activity | 0.576 | Interaction between MoKA and KLF7 was confirmed by the in vitro glutathione S-transferase pull-down assay and by coimmunoprecipitation of the proteins overexpressed in mammalian cells. Functional assays documented that MoKA is a KLF7 coactivator | SIGNOR-224621 |
Q9ULW0 | Q00535 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.272 | CDK5-mediated phosphorylation and stabilization of TPX2 promotes hepatocellular tumorigenesis | SIGNOR-265100 |
Q96JP5 | P52597 | 1 | ubiquitination | down-regulates quantity | 0.2 | Collectively, our results indicate that ZFP91 polyubiquitinated hnRNP F at Lys 185.|We found that silencing ZFP91 increased hnRNP F protein levels, but not hnRNP F mRNA levels, while ectopically expressing ZFP91 decreased hnRNP F protein levels, but not hnRNP F mRNA levels. | SIGNOR-278802 |
P17676 | P24941 | 0 | phosphorylation | up-regulates | 0.395 | Mass spectrometric analysis revealed that cdk2/cyclina phosphorylates c/ebpbeta on thr(188) and is required for phosphorylation (on ser(184) or thr(179)) of c/ebpbeta by gsk3beta and maintenance of dna binding activity. | SIGNOR-196372 |
Q99608 | Q01094 | 2 | binding | down-regulates activity | 0.601 | Necdin interacts with E2F transcription factors and suppresses E2F1-dependent transcriptional activation of the cyclin-dependent kinase Cdk1 gene. Here we show that necdin serves as a suppressor of NPC proliferation in the embryonic neocortex. | SIGNOR-253382 |
O15534 | Q16649 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.346 | E4BP4, a basic leucine zipper transcription factor, contains a DNA-binding domain closely related to DBP, HLF, and TEF, which are PAR proteins. Here, we show that the phase of e4bp4 mRNA rhythm is opposite to that of the dbp, hlf, and tef rhythms in the suprachiasmatic nucleus (SCN), the mammalian circadian center, and the liver. The protein levels of E4BP4 and DBP also fluctuate in almost the opposite phase. All PAR proteins activate, whereas E4BP4 suppresses the mPer1 promoter through the same sequence | SIGNOR-268056 |
Q15466 | P49715 | 2 | binding | down-regulates activity | 0.269 | SHP repressed C/EBPalpha (CCAAT/enhancer-binding protein alpha)-driven transcription of PEPCK through direct interaction with C/EBPalpha protein both in vitro and in vivo. The formation of an active transcriptional complex of C/EBPalpha and its binding to DNA was inhibited by SHP, resulting in the inhibition of PEPCK gene transcription. | SIGNOR-254831 |
Q6IQ22 | A2RUS2 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.624 | ULK-mediated phosphorylation of the guanine nucleotide exchange factor DENND3 at serines 554 and 572 upregulates its GEF activity toward the small GTPase Rab12.|active Rab12 facilitates autophagosome trafficking, thus establishing a crucial role for the ULK/DENND3/Rab12 axis in starvation-induced autophagy. | SIGNOR-264734 |
P06241 | P51812 | 1 | phosphorylation | up-regulates | 0.326 | Epidermal growth factor stimulates rsk2 activation through activation of the mek/erk pathway and src-dependent tyrosine phosphorylation of rsk2 at tyr-529. By mass spectroscopy-based studies, we identified src tyrosine kinase family members src and fyn as upstream kinases of rsk2 tyr-529. | SIGNOR-160048 |
P42575 | P78527 | 0 | phosphorylation | up-regulates | 0.297 | Here we show that dna damage induced by gamma-radiation triggers the phosphorylation of nuclear caspase-2 at the s122 site within its prodomain, leading to its cleavage and activation. This phosphorylation is carried out by the nuclear serine/threonine protein kinase dna-pkcs | SIGNOR-183895 |
Q8NDV7 | Q6PJ69 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.445 | Ubiquitination assays demonstrate that TRIM65 is an ubiquitin E3 ligase for TNRC6 proteins. The combination of overexpression and knockdown studies establishes that TRIM65 relieves miRNA-driven suppression of mRNA expression through ubiquitination and subsequent degradation of TNRC6. | SIGNOR-272174 |
P05129 | P04004 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.285 | Phosphorylation of vitronectin on Ser362 by protein kinase C attenuates its cleavage by plasmin. | SIGNOR-248964 |
P07949 | Q9P104 | 2 | binding | up-regulates | 0.624 | Dok-4 and dok-5 enhance c-ret-dependent activation of mitogen-activated protein kinase | SIGNOR-109516 |
O14529 | Q8TE12 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.285 | Lmx1a drives Cux2 expression in the cortical hem through activation of a conserved intronic enhancer. Lmx1a knockdown abolishes activation of the Cux2 enhancer in the cortical hem | SIGNOR-263961 |
Q96KK5 | Q14493 | 0 | translation regulation | up-regulates quantity by expression | 0.2 | Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control. | SIGNOR-265402 |
P42566 | O60260 | 0 | ubiquitination | up-regulates | 0.2 | Treatment of cells with egf stimulates parkin binding to both eps15 and the egfr and promotes parkin-mediated ubiquitination of eps15 | SIGNOR-148218 |
Q15910 | P49841 | 0 | phosphorylation | down-regulates activity | 0.33 | GSK3beta phosphorylates EZH2 at Ser363 and Thr367 in vitro, and activating GSK3beta upregulates Thr367 phosphorylationin vivo. | SIGNOR-278176 |
O15379 | P49841 | 0 | phosphorylation | up-regulates activity | 0.285 | Given that pharmacological inhibition of GSK3beta inhibits HDAC3 neurotoxicity, we explored the possibility that HDAC3 was directly phosphorylated by GSK3beta.|HDAC3 is directly phosphorylated by GSK3\u03b2, suggesting that the neuronal death-promoting action of GSK3\u03b2 could be mediated through HDAC3 phosphorylation. | SIGNOR-278400 |
P38405 | O14842 | 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-256942 |
Q13501 | Q8IZQ1 | 2 | binding | up-regulates quantity | 0.562 | We show here that p62 is required to recruit the large phosphoinositide-binding protein ALFY to cytoplasmic p62 bodies generated upon amino acid starvation or puromycin-treatment. ALFY, as well as p62, is required for formation and autophagic degradation of cytoplasmic ubiquitin-positive inclusions. | SIGNOR-266792 |
K9N643 | Q9UHD2 | 2 | binding | down-regulates activity | 0.2 | Previous studies have shown that MERS-CoV ORF4b antagonizes the early antiviral alpha/beta interferon (IFN-α/β) response, which may significantly contribute to MERS-CoV pathogenesis; however, the underlying mechanism is poorly understood. Here, we found that ORF4b in the cytoplasm could specifically bind to TANK binding kinase 1 (TBK1) and IκB kinase epsilon (IKKε), suppress the molecular interaction between mitochondrial antiviral signaling protein (MAVS) and IKKε, and inhibit IFN regulatory factor 3 (IRF3) phosphorylation and subsequent IFN-β production. these results indicate that MERS-CoV ORF4b inhibits the induction of type I IFN through a direct interaction with IKKε/TBK1 in the cytoplasm | SIGNOR-260593 |
Q8N2W9 | O15033 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.403 | In this study, we discovered a new protein isoform encoded by KIAA0317, termed fibrosis-inducing E3 ligase 1 (FIEL1), which potently stimulates the TGFβ signaling pathway through the site-specific ubiquitination of PIAS4.FIEL1 targets PIAS4 using a double locking mechanism that is facilitated by the kinases PKCζ and GSK3β. Specifically, PKCζ phosphorylation of PIAS4 and GSK3β phosphorylation of FIEL1 are both essential for the degradation of PIAS4. | SIGNOR-275575 |
P36956 | P28482 | 0 | phosphorylation | up-regulates | 0.406 | Map kinases erk1/2 phosphorylate sterol regulatory element-binding protein (srebp)-1a at serine 117 in vitro. mutation of serine 117 to alanine abolished erk2-mediated phosphorylation in vitro and the map kinase-related transcriptional activation of srebp-1a by insulin and platelet-derived growth factor in vivo. | SIGNOR-80092 |
P10275 | Q14192 | 2 | binding | up-regulates | 0.522 | Fhl2 contains a strong, autonomous transactivation function and binds specifically to the ar in vitro and in vivo. | SIGNOR-74703 |
P42768 | P19784 | 0 | phosphorylation | up-regulates activity | 0.347 | We identify two phosphorylation sites in the VCA domain of WASP at serines 483 and 484. S483 and S484 are substrates for casein kinase 2 in vitro and in vivo. Phosphorylation of these residues increases the affinity of the VCA domain for the Arp2/3 complex 7-fold and is required for efficient in vitro actin polymerization by the full-length WASP molecule. | SIGNOR-251048 |
P56178 | P10451 | 1 | transcriptional regulation | up-regulates quantity | 0.373 | Dlx5 initiates a complete osteogenic differentiation in these early primary cells, by triggering Runx2, osteopontin, alkaline phosphatase, and other gene expression according to the sequential temporal sequence observed during skull osteogenesis in vivo. | SIGNOR-245340 |
O14974 | Q13418 | 0 | phosphorylation | down-regulates activity | 0.584 | MYPT1 was phosphorylated by ILK and phosphorylation sites in the N- and C-terminal fragments of MYPT1 were detected. From sequence analyses, three sites were identified: a primary site at Thr(709), and two other sites at Thr(695) and Thr(495). ILK produced an intermediate level of inhibition | SIGNOR-262884 |
B0YJ81 | P49327 | 1 | chemical activation | up-regulates activity | 0.2 | Very long-chain fatty acids are produced through a four-step cycle. However, the 3-hydroxyacyl-CoA dehydratase catalyzing the third step in mammals has remained unidentified. Mammals have four candidates, HACD1-4, based on sequence similarities to the recently identified yeast Phs1, although HACD3 and HACD4 share relatively weak similarity. We demonstrate that all four of these human proteins are indeed 3-hydroxyacyl-CoA dehydratases, | SIGNOR-267760 |
O14757 | Q7Z2Z1 | 1 | phosphorylation | down-regulates activity | 0.432 | In principle, phosphorylation of Treslin by Chk1 may alter its conformation or directly affect its interactions with other proteins to preclude helicase activation.|The fact that the TRCT domain blocks the binding of Chk1 to Treslin suggests that Chk1 suppresses the initiating function of Treslin. | SIGNOR-278924 |
Q01094 | O15379 | 2 | binding | up-regulates | 0.496 | Furthermore, smad7 caused hdac-1 bind to e2f-1 to form a ternary complex on chromosomal dna containing an e2f-binding motif and leading to repression in the activity of the e2f target genes. | SIGNOR-199961 |
Q13285 | P51843 | 2 | binding | down-regulates activity | 0.702 | The in vivo existence of an SF-1 corepressor complex consisting of DAX-1, RNF31, and SMRT at the steroidogenic promoters of the human StAR and CYP19 genes. We demonstrate that RNF31 is necessary for the stable association of the DAX-1 corepressor complex with chromatin-bound SF-1, thereby inhibiting the recruitment of coactivators and Pol II and controlling basal transcription levels of SF-1 target genes. | SIGNOR-271784 |
O14744 | P12931 | 0 | phosphorylation | down-regulates activity | 0.261 | Here, we demonstrate that PRMT5 is phosphorylated at residue Y324 by Src kinase, a negative regulator of its activity. | SIGNOR-277523 |
P11309 | Q13200 | 1 | phosphorylation | up-regulates activity | 0.2 | Seven of these kinases (PIM1/2/3, MAP4K1/2, PKA, and NEK6) directly and robustly phosphorylated recombinant GST-Rpn1 at S361 in vitro (Fig. 3D and SI Appendix, Fig. S3 A and B). | SIGNOR-273895 |
Q13526 | P35568 | 1 | isomerization | up-regulates activity | 0.2 | In this study, the association of Par14 with insulin receptor substrate 1 (IRS-1) was demonstrated in HepG2 cells|Therefore, although Pin1 and Par14 associate with different portions of IRS-1, the prolyl cis/trans isomerization in multiple sites of IRS-1 by these isomerases appears to be critical for efficient insulin receptor-induced IRS-1 phosphorylation|Par14 overexpression in HepG2 markedly enhanced insulin-induced IRS-1 phosphorylation and its downstream events | SIGNOR-265757 |
Q15818 | Q92934 | 1 | relocalization | up-regulates activity | 0.2 | Immunofluorescence staining and subcellular fractionation analyses revealed increased mitochondrial translocation of Bad and Bax proteins from cytoplasm following OGD (4 h) and simultaneously increased release of Cyt C from mitochondria followed by activation of caspase-3. NP1 protein was immunoprecipitated with Bad and Bax proteins; OGD caused increased interactions of NP1 with Bad and Bax, thereby, facilitating their mitochondrial translocation and dissipation of mitochondrial membrane potential | SIGNOR-261483 |
Q13144 | P20042 | 1 | guanine nucleotide exchange factor | up-regulates activity | 0.877 | EIF2B converts the protein synthesis initiation factor 2 (eIF2) from an inactive GDP-bound form to an active eIF2-GTP complex owing to its guanine nucleotide exchange factor (GEF) activity. | SIGNOR-269128 |
Q86VP1 | P21580 | 2 | binding | up-regulates activity | 0.683 | Tx1bp1 appears to be a novel a20-binding protein which mediate the anti-apoptotic activity of a20; tax1bp1 phosphorylation was pivotal for cytokine-dependent interactions among tax1bp1, a20, itch and rnf11 and downregulation of signaling by the transcription factor nf-Kb. | SIGNOR-69921 |
Q9UQ26 | O15034 | 2 | binding | down-regulates activity | 0.531 | SH3 domains of RBPs interact with RIMs. The enhancement of depolarization-induced secretion in PC12 cells by fusion proteins that suppress the associations of RBPs with RIMs and α1 suggests that RBPs may repress RIMs, either directly or through associated proteins. | SIGNOR-264366 |
Q6ZMG9 | P68400 | 0 | phosphorylation | up-regulates activity | 0.2 | Most of the phosphorylated residues conformed to a consensus motif for phosphorylation by casein kinase 2 (CK2), and treatment of cells with the CK2-specific inhibitor CX-4945 lowered the phosphorylation levels of CERS2, -4, -5, and -6. Phosphorylation of CERS2 was especially important for its catalytic activity, acting mainly by increasing itsVmaxvalue. | SIGNOR-273992 |
Q15303 | Q6UW88 | 2 | binding | up-regulates | 0.394 | Areg (amphiregulin), btc (beta-cellulin), egf, epgn (epigen), ereg (epiregulin), hbegf, nrg1, nrg2, nrg3, nrg4 and tgfa (tgfalpha) constitute egf family ligands for erbb family receptors. | SIGNOR-147835 |
O14920 | Q02156 | 0 | phosphorylation | up-regulates activity | 0.547 | Monoubiquitylated PKC\u03b5 interacts with a ubiquitin-binding domain in NEMO zinc finger and recruits the cytosolic IKK complex to the plasma membrane, where PKC\u03b5 phosphorylates IKK\u03b2 at Ser177 and activates IKK\u03b2.|These results indicate that PKCepsilon phosphorylates IKKbeta at S177 and activates IKKbeta, which in turn induces PKM2 upregulation. | SIGNOR-278323 |
Q9NYQ6 | P53350 | 0 | phosphorylation | down-regulates activity | 0.2 | In contrast to the non autonomous polarity defects caused by transgenic expression of Celsr1 LLtoAA, Plk1 inhibition did not cause a significant alteration in Celsr1 interphase polarity (XREF_FIG).|Plk1 phosphorylates the Celsr1 cytoplasmic domain in\nvitro . | SIGNOR-279094 |
P41743 | Q6P1M3 | 1 | phosphorylation | up-regulates activity | 0.687 | This finding indicates that both mLgl-2 and mLgl-1 are phosphorylated in vivo in an aPKC lambda activity-dependent manner. | SIGNOR-263180 |
O14827 | P60953 | 1 | guanine nucleotide exchange factor | up-regulates activity | 0.554 | 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-260575 |
Q9BR39 | Q15772 | 0 | phosphorylation | up-regulates activity | 0.36 | Studies in HEK293 cells confirmed that SPEG overexpression increases JPH2 phosphorylation . | SIGNOR-279759 |
O14939 | Q00535 | 0 | phosphorylation | up-regulates activity | 0.368 | In this study, we suggest that the phosphorylation and activation of PLD2 by cyclin-dependent kinase 5 (Cdk5) is critical for EGF-dependent insulin secretion.|We determined that Cdk5 phosphorylates PLD2 at Ser 134 of PLD2 and that this phosphorylation was suggested to be important for EGF-dependent insulin secretion. | SIGNOR-278395 |
Q9UQB8 | Q92558 | 2 | binding | up-regulates | 0.629 | Here we demonstrate that irsp53, a substrate forinsulinreceptor with unknown function, is the 'missing link' between rac and wave. Activated rac binds to the amino terminus of irsp53, and carboxy-terminal src-homology-3 domain of irsp53 binds to wave to form a trimolecular complex. | SIGNOR-85299 |
P17181 | P29597 | 0 | phosphorylation | up-regulates activity | 0.91 | We demonstrate that, in vitro, p135tyk2 phosphorylates two tyrosines on IFNaR1. A phosphopeptide corresponding to the major phosphorylation site (Tyr466) binds STAT2, but not STAT1, in an SH-2-dependent manner. Furthermore, only latent, non-phosphorylated STAT2 interacts with this phosphopeptide. When this phosphopeptide is introduced into permeabilized cells, the IFN alpha-dependent tyrosine phosphorylation of both STATs is blocked. Finally, mutant versions of IFNaR1, in which Tyr466 is changed to phenylalanine, can act in a dominant negative manner to inhibit phosphorylation of STAT2. | SIGNOR-246934 |
P05771 | P54792 | 2 | binding | up-regulates | 0.2 | Taken together, these results suggest that site-specific dvl2 phosphorylation is required for dvl2 association with pkc_. This interaction is likely to be one of the mechanisms essential for wnt3a-dependent neurite outgrowth. | SIGNOR-199457 |
O94889 | O14965 | 2 | binding | up-regulates activity | 0.368 | We identify Aurora-A as a KLHL18-interacting partner. Overexpression of KLHL18 and CUL3 promotes Aurora-A ubiquitylation in vivo, and the CUL3-KLHL18-ROC1 ligase ubiquitylates Aurora-A in vitro. Our study reveals that the CUL3-KLHL18 ligase is required for timely entry into mitosis, as well as for the activation of Aurora-A at centrosomes.We also noticed that overexpression of both CUL3 and KLHL18 stimulated mono-ubiquitylation of Aurora-A as well (Fig. 8A,B). | SIGNOR-272021 |
P30304 | O96017 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.843 | We show that IR-induced destruction of Cdc25A requires both ATM and the Chk2-mediated phosphorylation of Cdc25A on serine 123. | SIGNOR-106808 |
P37088 | Q96PU5 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.775 | The serum and glucocorticoid inducible kinase 1 (SGK1) is induced in the aldosterone sensitive distal nephron (ASDN) where it may stimulate Na reabsorption, partly by inhibiting ubiquitin ligase Nedd4-2-mediated retrieval of epithelial Na+ channel ENaC from the luminal membrane. | SIGNOR-251948 |
Q92502 | P61586 | 1 | gtpase-activating protein | down-regulates activity | 0.557 | 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-260519 |
Q8IXL6 | P10451 | 1 | phosphorylation | down-regulates quantity | 0.683 | OPN phosphorylation by Fam20C decreased OPN secretion, and OPN neutralization reduced Fam20C-deficiency-induced osteoclast differentiation and bone metastasis. | SIGNOR-278936 |
Q12772 | P27361 | 0 | phosphorylation | up-regulates | 0.392 | Insulin-activated erk-mitogen-activated protein kinases phosphorylate sterol regulatory element-binding protein-2 at serine residues 432 and 455 in vivo.Further characterization by electrophoretic mobility shift assay and promoter reporter gene analyses revealed that phosphorylation does not influence protein/dna interaction, but enhances trans-activity. | SIGNOR-123053 |
O00141 | Q9BUB5 | 1 | phosphorylation | down-regulates activity | 0.2 | We show that SGK1 phosphorylates MNK1 at a conserved site, which represses its activity. | SIGNOR-277357 |
Q12933 | O95819 | 0 | phosphorylation | down-regulates quantity | 0.521 | A key finding of our study is that HGK induces lysosomal degradation of TRAF2 by directly phosphorylating TRAF2 Ser35.|Conversely, TRAF2 levels were decreased by ectopically expressed HGK in an overexpression system (XREF_FIG). | SIGNOR-279536 |
Q8NG68 | P68363 | 1 | tyrosination | down-regulates | 0.46 | Tubulin tyrosine ligase (ttl) adds a c-terminal tyr to __tubulin as part of a tyrosination/detyrosination cycle present in most eukaryotic cells. / ttl inhibits spontaneous tubulin polymerization | SIGNOR-176915 |
P31749 | P05106 | 1 | phosphorylation | down-regulates activity | 0.613 | A survey of several protein kinases revealed that Thr-753 was avidly phosphorylated by PDK1 and Akt/PKB in vitro. These observations suggest that activation of PDK1 and/or Akt/PKB in platelets may modulate the binding activity and/or specificity of beta(3) for signaling molecules. | SIGNOR-252552 |
P09038 | P22607 | 2 | binding | up-regulates | 0.82 | Fgf-2 and fgf-9 increased expression of other osteogenic factors bmp-2 and tgf-beta1, and endogenous fgf/fgfr signaling is a positive upstream regulator of the bmp-2 gene in calvarial osteoblasts. | SIGNOR-134788 |
Q00978 | P52630 | 2 | binding | up-regulates activity | 0.921 | Coimmunoprecipitation assays demonstrate p48 association with STAT2 but not STAT1.The studies demonstrate the in vivo existence of a STAT2.p48 complex and a distinct STAT2.STAT1 complex after IFN-alpha stimulation. Data suggest that distinct bipartite complexes STAT2.p48 and STAT2.STAT1 translocate to the nucleus and associate on the DNA target site as ISGF3. | SIGNOR-217806 |
P68400 | Q9BRS2 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.332 | Casein kinase 2 (CK2) phosphorylates RIOK1 at T410, which stabilizes RIOK1 by antagonizing K411 methylation and impeding the recruitment of FBXO6 to RIOK1. | SIGNOR-273630 |
Q00535 | P06400 | 1 | phosphorylation | down-regulates | 0.336 | Phosphorylation was observed 6 hours after p25 induction and was abolished in the presence of a cdk5 inhibitor, roscovitine, which does not inhibit the usual rb cyclin-d kinases cdk4 and cdk6. Furthermore, analyses of levels and subcellular localization of cdk-related cyclins did not reveal any change following cdk5 activation, arguing for a direct effect of cdk5 activity on rb protein. Rb phosphorylation was visualized using phosphorylation-dependent antibodies (p-rbser795 and p-rbser807/811). | SIGNOR-134468 |
P12931 | Q9UN19 | 1 | phosphorylation | up-regulates activity | 0.586 | 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 linesyrosine phosphorylation of DAPP-1 appears important for appropriate intracellular targeting and creates a potential binding site for Src homology 2 domain-containing proteins. | SIGNOR-247119 |
Q7L099 | Q13153 | 0 | phosphorylation | up-regulates quantity | 0.277 | (a) PAK1 phosphorylates RUFY3 in vitro.|Taken together, these results indicate that PAK1 can upregulate RUFY3 protein expression. | SIGNOR-279243 |
P28482 | P19525 | 1 | phosphorylation | up-regulates | 0.2 | Our results provide strong evidence that dsrna binding is required for dimerization of full-length pkr molecules in vivo, leading to autophosphorylation in the activation loop and stimulation of the eif2alpha kinase function of pkr. | SIGNOR-56337 |
P23458 | P42224 | 1 | phosphorylation | up-regulates activity | 0.79 | The central event in cytokine_dependent transcriptional regulation is phosphorylation of STATs on a single tyrosine residue at their C_terminus (Darnell, 1997b). The reaction is catalyzed by cytokine receptor_associated tyrosine kinases of the Janus type (Jak) at the cell membrane and triggers the homo_ and heterodimerization of STAT molecules via reciprocal phosphotyrosineSH2 domain interactions | SIGNOR-236373 |
P06493 | P52948 | 1 | phosphorylation | down-regulates activity | 0.397 | We show that npc disassembly is a phosphorylation-driven process, dependent on cdk1 activity and supported by members of the nima-related kinase (nek) family. mitotic hyperphosphorylation of nup98 is accomplished by multiple kinases, including cdk1 and neks. | SIGNOR-172217 |
Q99708 | Q96M94 | 2 | binding | down-regulates quantity by destabilization | 0.474 | Here, we identify the Cullin3 E3 ligase substrate adaptor Kelch-like protein 15 (KLHL15) as a new interaction partner of CtIP and show that KLHL15 promotes CtIP protein turnover via the ubiquitin-proteasome pathway. | SIGNOR-272410 |
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