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 |
|---|---|---|---|---|---|---|---|
P31751 | P56279 | 2 | binding | up-regulates | 0.547 | Full-length tcl1 and its isoforms bind to akt / in in vitro kinase assays using gsk-3_ as a substrate, we found that the presence of any of the tcl1 family proteins (tcl1, mtcp1, or tcl1b) as gst fusion proteins significantly enhanced akt-induced gsk-3_ phosphorylation | SIGNOR-81683 |
P0DP24 | P06213 | 0 | phosphorylation | down-regulates | 0.352 | 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-266320 |
P28482 | P41162 | 1 | phosphorylation | down-regulates activity | 0.403 | We have optimized a chemical genetic system using analog-sensitive ERK2, a form of ERK2 engineered to use an analog of adenosine 5'-triphosphate (ATP), to tag and isolate ERK2 substrates in vitro. This approach identified 80 proteins phosphorylated by ERK2, 13 of which are known ERK2 substrates. With this improved methodology, we detected 98 sites directly phosphorylated by ERK2 on 80 proteins from NIH 3T3-L1 fibroblasts. Thirteen of these proteins are known substrates and the rest represent previously unknown kinase/substrate interactions. Among the ERK2 substrates, we identified the E-twenty six (ETS) domain-containing protein ETV3. We determined that phosphorylation of this protein by ERK2 was functionally relevant, abrogating the DNA-binding activity of ETV3 at thousands of targets across the genome, thereby providing an additional mechanism for transcriptional regulation downstream of ERK2 activation. | SIGNOR-262758 |
O60503 | P63092 | 2 | binding | up-regulates activity | 0.628 | Adenylyl cyclase 9 (AC9) is a membrane-bound enzyme that converts ATP into cAMP. The enzyme is weakly activated by forskolin, fully activated by the G protein Gαs subunit and is autoinhibited by the AC9 C-terminus. | SIGNOR-278883 |
Q9Y5K5 | P84022 | 1 | deubiquitination | up-regulates activity | 0.397 | Here, we report a novel interaction between smads and ubiquitin c-terminal hydrolase uch37, a deubiquitinating enzyme that could potentially reverse smurf-mediated ubiquitination. In gst pull down experiments, uch37 bound weakly to smad2 and smad3, and bound very strongly to smad7 in a region that is distinct from the -py- motif in smad7 that interacts with smurf ubiquitin ligases | SIGNOR-232101 |
Q8IVT5 | P27448 | 0 | phosphorylation | down-regulates activity | 0.642 | C-TAK1 phosphorylates KSR1 at S392, forming a 14-3-3 binding site.|In mammalian cells, C-TAK1 has been shown to negatively regulate KSR1 by phosphorylation of Ser392. | SIGNOR-279225 |
P24941 | P55273 | 1 | phosphorylation | up-regulates | 0.526 | Cdk2 and pka were found to participate in p19ink4d phosphorylation process and that they would mediate serine 76 and threonine 141 modifications respectively. Nuclear translocation of p19ink4d induced by dna damage was shown to be dependent on serine 76 phosphorylation. | SIGNOR-197270 |
P01133 | O14672 | 0 | cleavage | up-regulates activity | 0.566 | Like ADAM17, ADAM10 has also been implicated in the activation of specific EGFR ligands, especially EGF and betacellulin | SIGNOR-259840 |
P04637 | Q9UEE5 | 0 | phosphorylation | up-regulates | 0.286 | Genetic and biochemical studies have shown that ser20 phosphorylation in the transactivation domain of p53 mediates p300-catalyzed dna-dependent p53 acetylation and b-cell tumor suppression. a cell-free ser20 phosphorylation site assay was used to identify a broad range of calcium calmodulin kinase superfamily members, including chk2, chk1, dapk-1, dapk-3, drak-1, and ampk, as ser20 kinases. | SIGNOR-153532 |
P49841 | Q16584 | 1 | phosphorylation | up-regulates activity | 0.336 | Further, investigation revealed that MLK3 was phosphorylated at two residues Ser789 and Ser793 by GSK3\u03b2 ( xref ).|When, these two sites on MLK3 were mutated to non-phosphorable Ala, the activation of MLK3 by GSK3\u03b2 was blocked, and neuronal cell death upon NGF withdrawal also prevented ( xref ). | SIGNOR-279615 |
P09619 | P22681 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.629 | Overexpression of wild type Cbl in NIH3T3 cells led to an enhancement of the ligand-dependent ubiquitination and subsequent degradation of the PDGFRbeta, as observed with PDGFRalpha. | SIGNOR-272549 |
P06213 | Q12913 | 0 | dephosphorylation | down-regulates | 0.304 | Dephosphorylation of autophosphorylated insulin and epidermal-growth-factor receptors by two major subtypes of protein-tyrosine-phosphatase from human placenta. | SIGNOR-21295 |
P63000 | P63096 | 2 | binding | up-regulates activity | 0.47 | These findings indicate that both G alpha(i) and G beta gamma stimulate Rac and Cdc42 pathways with lysophosphatidic acid-induced cell spreading on fibronectin | SIGNOR-256530 |
P10636 | O15264 | 0 | phosphorylation | down-regulates activity | 0.531 | Phosphorylation of tau by SAPK3 and SAPK4 resulted in a marked reduction in the ability of tau to promote microtubule assembly. | SIGNOR-278313 |
P40424 | P14653 | 2 | binding | up-regulates activity | 0.807 | Pbx1 and exd act as cofactors that enhance the DNA binding specificity of Hox proteins. The structure of the HoxB1Pbx1DNA ternary complex shows that HoxB1 and Pbx1 bind to overlapping binding sites located on opposite faces of the DNA. | SIGNOR-241219 |
P34947 | P04637 | 1 | phosphorylation | down-regulates | 0.37 | Grk5, but not grk2 or grk6, phosphorylates p53 at thr-55, which promotes the degradation of p53, leading to inhibition of p53-dependent apoptotic response to genotoxic damage. | SIGNOR-163707 |
P21728 | P63092 | 2 | binding | up-regulates activity | 0.498 | 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-256796 |
P00519 | Q9NRM7 | 0 | phosphorylation | down-regulates activity | 0.362 | Inhibition of c-Abl by Lats2 was mediated through Lats2 interaction with and phosphorylation of c-Abl. Lats2 phosphorylates c-Abl at Thr197 in vitro. | SIGNOR-276497 |
Q9H1J5 | Q9NPG1 | 2 | binding | up-regulates | 0.621 | Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation. | SIGNOR-131984 |
P50148 | P08912 | 2 | binding | up-regulates activity | 0.452 | 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-257217 |
O15169 | O14640 | 2 | binding | down-regulates activity | 0.819 | We have recently found that Dvl-1 directly binds to Axin and that the binding of Dvl-1 to Axin does not affect the interaction of GSK-3beta with Axin. It is possible that the binding of Dvl to Axin induces the structural change of the Axin complex; therefore GSK-3beta does not effectively phosphorylate Axin. This is the first demostration showing that Dvl inhibits the function of GSK-3beta directly. | SIGNOR-219356 |
P53350 | Q14203 | 1 | phosphorylation | up-regulates | 0.523 | Plk1-mediated phosphorylation of p150(glued) at ser-179 positively regulates its accumulation at the nuclear envelope during prophase. | SIGNOR-167281 |
Q13563 | Q9BZL6 | 0 | phosphorylation | up-regulates activity | 0.2 | Here, we report the identification of a previously unrecognized phosphorylation site within the polycystin-2 C terminus (Ser801), and we demonstrate that it is phosphorylated by protein kinase D. These results suggest that growth factor-stimulated, protein kinase D-mediated phosphorylation of polycystin-2 is essential for its ER channel function and links extracellular stimuli to its effects on cell growth and intracellular calcium regulation. | SIGNOR-276284 |
P15692 | P17948 | 2 | binding | up-regulates | 0.843 | Vegf exerts its action by binding to vegfr-1 and vegfr-2. | SIGNOR-121132 |
P16885 | Q06187 | 0 | phosphorylation | up-regulates | 0.778 | By measuring the ability of human plcgamma2 to restore calcium responses to the b-cell receptor stimulation or oxidative stress in a b-cell line (dt40) deficient in plcgamma2, we have demonstrated that two tyrosine residues, tyr(753) and tyr(759), were important for the plcgamma2 signaling function.Of the two kinases that previously have been proposed to phosphorylate plcgamma2, btk, and syk, purified btk had much greater ability to phosphorylate recombinant plcgamma2 in vitro, whereas syk efficiently phosphorylated adapter protein blnk. | SIGNOR-111069 |
P43405 | P07948 | 0 | phosphorylation | up-regulates activity | 0.61 | Lyn phosphorylates and activates Syk and LAT. | SIGNOR-279415 |
Q13315 | Q14694 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.252 | The translocation and stabilization of USP10 is regulated by ATM -mediated phosphorylation of USP10 at Thr42 and Ser337. | SIGNOR-276276 |
O00327 | P04275 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.324 | We also show that major circadian transcriptional regulators CLOCK and Bmal1 directly regulate the activity of vWF promoter and that lack of Bmal1 results in upregulation of vWF both at mRNA and protein level. Here we report a direct regulation of vWF expression in endothelial cells by biological clock gene Bmal1. This study establishes a mechanistic connection between Bmal1 and cardiovascular phenotype. | SIGNOR-253704 |
Q15021 | P51955 | 0 | phosphorylation | down-regulates activity | 0.269 | Nek2 phosphorylates C-Nap1, rootletin and beta-catenin to regulate centrosome separation. | SIGNOR-279234 |
Q96RK0 | P28482 | 0 | phosphorylation | down-regulates | 0.372 | Specifically, 14-3-3 binds to p90(rsk)-phosphorylated ser?_??_ Of capic?_A thereby modulating dna binding to its hmg (high-mobility group) box, whereas erk phosphorylations prevent binding of a c-terminal nls (nuclear localization sequence) to importin ?4 (kpna3))[...] These results suggest that erk phosphorylation of ser1382 and ser1409 masks the nls and prevents its binding to kpna3 | SIGNOR-169875 |
P35680 | P18846 | 2 | binding | up-regulates activity | 0.307 | The mammalian two-hybrid system showed that the region aa 393 to 476 of LFB3 is involved in the interaction with CREB or ATF1. The importance of this region for mediating cAMP induction was confirmed in transient transfection assays. | SIGNOR-241320 |
Q6ZNA4 | Q96CW1 | 1 | ubiquitination | up-regulates | 0.2 | Arkadia ubiquitylated the _?2 Subunit at lys130. In addition, arkadia interacted with the ap2 complex, and modified endocytosis of epidermal growth factor receptor (egfr) induced by egf. Arkadia thus appears to regulate egf signalling by modulating endocytosis of egfr through interaction with ap2 complex. | SIGNOR-168931 |
P29353 | P04629 | 2 | binding | up-regulates | 0.844 | Autophosphorylated trka binds directly to plc?, Abl, and shc. | SIGNOR-75408 |
Q05655 | P78357 | 1 | phosphorylation | down-regulates activity | 0.2 | Inhibition of PKCdelta increased p190 activity, while PKCdelta overexpression diminished p190 activity.|We further show that PKC\u03b4 was able to phosphorylate and bind distinct domains of p190. | SIGNOR-279260 |
P11388 | P68400 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.595 | This study also reports the novel finding that topoIIα may be a target of GSK3β phosphorylation. Evidence suggests that CK2 serves as a priming kinase, through phosphorylation at Ser1365, for GSK3β-mediated phosphorylation at Ser1361. | SIGNOR-276300 |
Q99608 | O75925 | 2 | binding | down-regulates quantity by destabilization | 0.297 | Necdin bound to PIAS1 central domains that are highly conserved among PIAS family proteins and suppressed PIAS1-dependent sumoylation of the substrates STAT1 and PML (promyelocytic leukemia protein). Remarkably, necdin promoted degradation of PIAS1 via the ubiquitin-proteasome pathway. In transfected HEK293A cells, amino- and carboxyl-terminally truncated mutants of PIAS1 bound to necdin but failed to undergo necdin-dependent ubiquitination. | SIGNOR-253387 |
Q13546 | Q13490 | 0 | polyubiquitination | up-regulates activity | 0.768 | CIAP1/2 are direct E3 ligases conjugating diverse types of ubiquitin chains to receptor interacting proteins kinases 1 to 4 (RIP1-4).Together, our results demonstrate that depleting cIAP1/2 inhibits RIP1-4 mediated NF-kB activation without affecting RIP auto-phosphorylation. | SIGNOR-272710 |
P20827 | Q9UF33 | 2 | binding | up-regulates | 0.811 | Ephrin-a1 binds and activates the tyrosine kinase activity of eph-a2, and has a dissociation constant of 20_30 nm. ephrin-a1 interacts with all the other epha subclass receptors as well, although with different affinity | SIGNOR-56962 |
P30291 | O43660 | 1 | phosphorylation | down-regulates activity | 0.2 | These results indicate that WEE1 promotes PRL1 phosphorylation.|WEE1 promotes PRL1 degradation . | SIGNOR-279579 |
P30291 | Q93096 | 1 | phosphorylation | down-regulates activity | 0.2 | In this study , we found that WEE1 phosphorylates PRL1 and promotes PRL1 degradation .|In this study, we demonstrated that WEE1 phosphorylates and inhibits PRL1 to regulate alternative splicing of CYCD1;1 and CYCD3;1 , which may represent a new cell cycle control mechanism. | SIGNOR-278434 |
P01106 | P09651 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.456 | We also demonstrate that the oncogenic transcription factor c-Myc upregulates transcription of PTB, hnRNPA1 and hnRNPA2, | SIGNOR-268690 |
P29474 | Q04759 | 0 | phosphorylation | down-regulates activity | 0.2 | The phosphorylation of both S617 and S635 have also been shown to promote increased eNOS-derived NO release (Michell et al., 2002). The phosphorylaiton of S617 can be induced by PKA or Akt activity, and may serve to sensitize eNOS to calmodulin binding and modulate the phosphorylation of other eNOS sites | SIGNOR-251636 |
Q14790 | Q5T447 | 0 | polyubiquitination | down-regulates activity | 0.336 | HECTD3, a new E3 ubiquitin ligase, interacts with caspase-8 death effector domains and ubiquitinates caspase-8 with K63-linked polyubiquitin chains that do not target caspase-8 for degradation but decrease the caspase-8 activation. HECTD3 ubiquitinates caspase-8 with K63-linked polyubiquitin chains at K215. | SIGNOR-272077 |
P27361 | Q86U44 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.271 | Mass spectrometry analysis showed that ERK phosphorylates METTL3 at three highly conserved residues: S43, S50, and S525 (Figures 2D and 2E). Mutational analysis further confirmed these three sites as main ERK phosphorylation sites (Figure 2F). Phosphorylation of METTL3 increases interaction with USP5, decreasing ubiquitination to stabilize the m6 A methyltransferase complex. | SIGNOR-265949 |
O15111 | P04637 | 1 | phosphorylation | up-regulates activity | 0.429 | In the nucleus, IKKalpha enhances p53 mediated GADD45 and BAD gene expressions by phosphorylating p53 at Ser20 and stabilizing p53 protein levels , leading to the induction of apoptosis in response to ROS exposure.|PKC-activated nuclear I\u03baB kinase\u03b1 promotes the stability of p53 protein and mediates reactive oxygen species-induced apoptosis [ ]. | SIGNOR-280231 |
P63279 | P35227 | 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 |
P51532 | P15172 | 2 | binding | up-regulates | 0.528 | Myod targets brg1 to the myogenin promoter during the initiation of myogenesis in tissue culture models for skeletal muscle differentiation /initiation of myogenin transcription is dependent upon myod, the pbx homeodomain factor, and swi/snf chromatin-remodeling enzymes | SIGNOR-151685 |
Q9BZI1 | P27361 | 0 | phosphorylation | up-regulates activity | 0.2 | To identify the phosphorylated residue, we introduced a serine-to-alanine substitution at residues 294 and 326 and a threonine-to-alanine substitution at residue 331 in Irx2(291–356). Erk1 phosphorylated S294A and T331A, but not S326A (Fig. 4b), indicating that Ser326 is the bona fide MAP kinase target. | SIGNOR-263061 |
O95136 | P08754 | 2 | binding | up-regulates activity | 0.387 | 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-256871 |
O95863 | Q05513 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.2 | APKC kinases phosphorylate S249 of SNAI1, which leads to protein degradation. | SIGNOR-277437 |
Q16827 | P40763 | 1 | dephosphorylation | down-regulates activity | 0.376 | In addition, this group found that PTPRO dephosphorylated STAT3 at Y705 and S727 then attenuated STAT3 signalling. | SIGNOR-277062 |
P07858 | P02818 | 1 | cleavage | down-regulates quantity by destabilization | 0.33 | This study has been undertaken to compare the degradation of BGP by the cysteine proteinases cathepsins L, B, H, S, and the aspartic proteinase cathepsin D. Cathepsins B, L, H, and S readily cleave BGP at the G7-A8 bond; cathepsin L also cleaves at R43-R44; cathepsin B also cleaves at R44-F45; and cathepsin D cleaves only at A41-Y42. | SIGNOR-256318 |
Q9UKP6 | P09471 | 2 | binding | up-regulates activity | 0.265 | 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-257252 |
O95295 | P17612 | 0 | phosphorylation | up-regulates activity | 0.307 | PKA-phosphorylation of Snapin significantly increases its binding to synaptosomal-associated protein-25 (SNAP-25). Mutation of Snapin serine 50 to aspartic acid (S50D) mimics this effect of PKA phosphorylation | SIGNOR-250053 |
Q96LB1 | 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-256787 |
P15923 | P27361 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.372 | Notch-induced degradation requires phosphorylation of E47 by p42/p44 MAP kinases. |Wild_type E47 but not the Mm mutant reacted to the antibodies, suggesting that E47 is at least phosphorylated at the M2 site (Figure 3A)|anti_phospho_M2 peptide (SSPSpTPVGSPQG) | SIGNOR-249117 |
Q96PD2 | P00519 | 0 | phosphorylation | up-regulates activity | 0.2 | SFKs and Abl differentially phosphorylate DCBLD1 and DCBLD2 at distinct tyrosine phosphorylation sites.|We report that Src family kinases and Abl differentially promote the interaction between the CRKL-SH2 domain and DCBLD1 and DCBLD2, and while Src family kinases and Abl each promote DCBLD1 and DCBLD2 binding to the CRKL-SH2 domain, the effect of Abl is more pronounced for DCBLD1. 45999997={Domain=45999998 LikeProtein=1399} 45999998="sh2 domain" 45999999="sh2 domain"} | SIGNOR-280167 |
O75901 | O43318 | 0 | phosphorylation | up-regulates activity | 0.2 | As expected, increased expression of TAK1 induced by LV-TAK1 stimulated p-RASSF9, whereas p-MEK and p-ERK were reduced.|We further identified RASSF9 as a downstream target of TAK1 which phosphorylates RASSF9 at S284. | SIGNOR-279534 |
P60953 | Q9C0H5 | 0 | gtpase-activating protein | down-regulates activity | 0.577 | 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-260495 |
Q9P212 | P09341 | 2 | binding | up-regulates | 0.2 | In the non-canonical wnt pathway, frizzled uses galfaq or galfai and gbetagamma dimers to activate phospholipase c (plc), resulting in protein kinase c (pkc) activation and calcium mobilization that regulates the transcription factor nfat, and frizzled also signals through the small gtpases rho and rac to c-jun n-terminal kinase (jnk), which activates the ap1 transcription factor. | SIGNOR-152591 |
Q8IVM8 | P20823 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Luciferase reporter gene constructs containing the OAT5 (SLC22A10) and OAT7 (SLC22A9) promoter regions were transactivated by HNF-1 in HepG2 cells. | SIGNOR-268982 |
P31749 | Q8N9L9 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.2 | HSPA1A was found to associate with ACOT4. Furthermore, we found that phosphorylation of ACOT4 at S392 by AKT decreased the binding of ACOT4 to HSPA1A, resulting in ACOT4 accumulation. |AKT phosphorylates ACOT4 at S392 and promotes ACOT4 stability | SIGNOR-271820 |
Q9Y2I6 | P53350 | 0 | phosphorylation | down-regulates activity | 0.7 | Here, we identify a centrosomal plk1 substrate, termed nlp (ninein-like protein), whose properties suggest an important role in microtubule organization. Nlp interacts with two components of the gamma-tubulin ring complex and stimulates microtubule nucleation. Plk1 phosphorylates nlp and disrupts both its centrosome association and its gamma-tubulin interaction | SIGNOR-103356 |
P48436 | P49841 | 0 | phosphorylation | down-regulates activity | 0.444 | (E) The SOX9 K2 domain is phosphorylated by GSK3\u03b2 at T236.|Based on our findings that inhibition of GSK3\u03b2 prevents DNA damage-induced SOX9 degradation, and that FBW7 targets SOX9 for degradation after DNA damage, we reasoned that phosphorylation of SOX9 by GSK3\u03b2 is required for FBW7-mediated SOX9 degradation. | SIGNOR-279725 |
P78527 | P23508 | 1 | phosphorylation | up-regulates activity | 0.2 | MCC is phosphorylated at the ATM/ATR consensus sites Ser118 and Ser120. Finally, mutation of S118/120 to alanine did not affect MCC nuclear shuttling following UV but did impair MCC G2/M checkpoint activity. | SIGNOR-273530 |
P15056 | Q8IVT5 | 2 | binding | up-regulates activity | 0.63 | In mammals, RAF family kinases include three catalytically competent enzymes (ARAF, BRAF and CRAF) and two pseudokinases (KSR1 and KSR2) that have been described as scaffolds owing to their apparent ability to bridge RAF isoforms and their substrate, mitogen-activated protein kinase kinase (MEK).Kinase suppressor of Ras (KSR) pseudokinases were also shown to dimerize with kinase-competent RAFs to stimulate catalysis allosterically. | SIGNOR-273878 |
O14641 | P60484 | 0 | dephosphorylation | down-regulates activity | 0.318 | This showed that while both PTEN WT and the lipid phosphatase-inactive G129E mutant suppressed phosphorylation of DVL2 on serine 143 that accumulated upon PTEN knockdown, the C124S and Y138L mutants did not .|Finally, it is important to point out that while our studies show that PTEN can directly dephosphorylate DVL2 in vitro, it is possible that regulation of serine 143 phosphorylation of DVL2 by PTEN in cells may require additional protein factors, or post-translational modifications. | SIGNOR-277035 |
P05771 | P49768 | 1 | phosphorylation | up-regulates activity | 0.2 | A phosphorylation site at serine residue 346 was identified that is selectively phosphorylated by PKC but not by PKA. This site is localized within a recognition motif for caspases, and phosphorylation strongly inhibits proteolytic processing of PS1 by caspase activity during apoptosis. | SIGNOR-249237 |
O15552 | P09471 | 2 | binding | up-regulates activity | 0.307 | 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-257075 |
P01106 | O75592 | 2 | transcriptional regulation | down-regulates quantity by repression | 0.415 | We identified several E3 ligases as strong candidates responsible for AR and MYC protein loss as HECTD4, MYCBP2, and TRIM49. HECTD4 and MYCBP2 target AR and MYC for degradation while TRIM49 appears to promote AR and MYC stability. We have shown that these E3 ligases in turn are directly regulated by MYC. MYC in turn represses the expression of ubiquitin ligases, HECTD4 and MYCBP2 that promote AR and MYC protein degradation, further suppressing MYC and AR in a feed forward loop. | SIGNOR-267145 |
Q9UMX1 | Q9UMX1 | 2 | binding | up-regulates | 0.2 | Hsu(fu) associated with itself / homo- or heterodimers of hsu(fu) might function to bring together other effector proteins | SIGNOR-72311 |
Q9H5J4 | Q9NP71 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.398 | In this study, we clearly show that mouse and human Elovl6 are direct targets of ChREBP. | SIGNOR-267945 |
P09341 | Q9NPG1 | 2 | binding | up-regulates | 0.2 | In the non-canonical wnt pathway, frizzled uses galfaq or galfai and gbetagamma dimers to activate phospholipase c (plc), resulting in protein kinase c (pkc) activation and calcium mobilization that regulates the transcription factor nfat, and frizzled also signals through the small gtpases rho and rac to c-jun n-terminal kinase (jnk), which activates the ap1 transcription factor gpcrs signal through four relatively small families of galfa proteins (galfas, galfai/o, galfaq, and galfa12/13), and if fzd receptors are classic gpcrs, they should signal through one of these four galfa families. | SIGNOR-152597 |
Q8N653 | Q13618 | 2 | binding | up-regulates activity | 0.273 | Leucine zipper-like transcriptional regulator 1 (LZTR1) encodes a member of the BTB-Kelch superfamily, which interacts with the Cullin3 (CUL3)-based E3 ubiquitin ligase complex. | SIGNOR-269070 |
Q13114 | Q99836 | 2 | binding | up-regulates activity | 0.694 | Using MyD88 as a prototypical adaptor, we identified TNF receptor-associated factor 3 (TRAF3) as a new component of TIR signalling complexes that is recruited along with TRAF6. | SIGNOR-256079 |
P18031 | P53350 | 0 | phosphorylation | up-regulates activity | 0.354 | Cdk1-cyclin B1 directly phosphorylates PTP1B at serine 386 in a kinase assay. Recombinant Plk1 phosphorylates PTP1B on serine 286 and 393 in vitro, however, it requires a priming phosphorylation by Cdk1 at serine 386 highlighting a novel co-operation between Cdk1 and Plk1 in the regulation of PTP1B.|Finally, phosphorylation on serine 286 enhanced PTP1B phosphatase activity. | SIGNOR-272990 |
Q13115 | P45983 | 1 | dephosphorylation | down-regulates | 0.714 | Jnk1 phosphorylation and activation was inhibited by expression of both mkp1 and mkp2 | SIGNOR-27756 |
P52565 | Q9ULL4 | 2 | binding | up-regulates activity | 0.251 | Here, we report the expression of plexin-B3 in glioma cells, which upon stimulation by its ligand Sema5A results in significant inhibition of cell migration and invasion. A search for the underlying mechanism revealed direct interaction of plexin-B3 with RhoGDP dissociation inhibitor α (RhoGDIα), a negative regulator of RhoGTPases that blocks guanine nucleotide exchange and sequesters them away from the plasma membrane. direct interaction of RhoGDIα and the cytoplasmic domain of plexin-B3 (plexin-B3CD) was confirmed by GST pulldown assays. | SIGNOR-268435 |
P30304 | P01106 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.627 | Expression of Cdc25A is transcriptionally regulated by Myc and E2F-1 , both of which are expressed in MCF-7 cells in response to estrogen | SIGNOR-245465 |
P60953 | Q70Z35 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.423 | 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-260572 |
P27361 | Q01094 | 1 | phosphorylation | up-regulates | 0.292 | Erk also undergoes rapid translocation into the nucleus, where it phosphorylates and activates a variety of transcription factor targets, including sp1, e2f, elk-1, and ap1 | SIGNOR-121991 |
Q9Y3R0 | O60282 | 2 | binding | up-regulates activity | 0.324 | HAP1 and GRIP1 are kinesin-1 adaptors that have been implicated individually in the transport of vesicular cargoes in the dendrites of neurons. We find that HAP1a and GRIP1 form a protein complex in the brain, and co-operate to activate the kinesin-1 subunit KIF5C in vitro | SIGNOR-264061 |
Q9NQU5 | Q00987 | 1 | phosphorylation | up-regulates activity | 0.2 | We also showed that PAK6 phosphorylates Mdm2 on Thr-158 and Ser-186, which is critical for AR ubiquitin-mediated degradation. | SIGNOR-276428 |
P05556 | Q9Y5H6 | 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. | SIGNOR-265671 |
P31323 | P31323 | 2 | phosphorylation | up-regulates activity | 0.2 | Ser114 (the autophosphorylation site) of human RII beta. Point mutation of the autophosphorylation site or in the nuclear location signal causes protein kinase A RII beta regulatory subunit to lose its ability to revert transformed fibroblasts. | SIGNOR-250076 |
P27361 | Q9NYV6 | 1 | phosphorylation | up-regulates | 0.2 | Erk-dependent phosphorylation of the transcription initiation factor tif-ia is required for rna polymerase i transcription and cell growth. phosphopeptide mapping and mutational analysis reveals two serine residues (s633 and s649) that are phosphorylated by erk and rsk kinases. Replacement of s649 by alanine inactivates tif-ia, inhibits pre-rrna synthesis, and retards cell growth. | SIGNOR-98984 |
Q96LA5 | 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-271543 |
Q16763 | P12956 | 0 | relocalization | up-regulates activity | 0.347 | As shown in Figure 4, we found that Ku70 (Figure 4b) and Ku80 (Figure 4c) co-immunoprecipitated with UBE2S.>Taken together, these results demonstrate that ETO enhances the UBE2S–Ku70 interaction, and UBE2S can be recruited to the same sites of DSBs with Ku70 upon ETO treatment. | SIGNOR-265079 |
Q9P1A6 | Q9Y566 | 1 | relocalization | up-regulates activity | 0.756 | SHANK proteins are ‘master’ scaffolding proteins that tether and organize intermediate scaffolding proteins. They are located at excitatory synapses, where they are crucial for proper synaptic development and function. SAPAP proteins subsequently bind to the PDZ domain of members of the SHANK protein family. SHANK proteins then bind to the actin cytoskeleton and to Homer protein, which in turn interacts with mGluRs. Through these extended links, PSD95, SAPAP, SHANK and Homer proteins form a quaternary complex that brings together mGluR and NMDAR complexes in the PSD (FIG. 3). | SIGNOR-264589 |
P43004 | Q03135 | 2 | binding | down-regulates activity | 0.248 | EAAT3 has previously been shown to form complexes with caveolin-1, a major component of caveolae, which participate in the regulation of transport proteins. The present study explored the impact of caveolin-1 on electrogenic transport by excitatory amino acid transporter isoforms EAAT1-4. caveolin-1 is a powerful negative regulator of the excitatory glutamate transporters EAAT1, EAAT2, EAAT3, and EAAT4. Caveolin-1 has been shown to form complexes with the excitatory amino acid transporter EAAT3 (EAAC1) (Gonzalez et al. 2007) and may thus modify the EAAT isoforms by direct interaction with the carriers. | SIGNOR-264809 |
Q09472 | O75116 | 0 | phosphorylation | up-regulates activity | 0.297 | Nuclear Rho kinase, ROCK2, targets p300 acetyltransferase.|p300 acetyltransferase activity is dependent on its phosphorylation status in cells, and p300 phosphorylation by ROCK2 results in an increase in its acetyltransferase activity in vitro. | SIGNOR-279482 |
Q9UKV8 | P48729 | 0 | phosphorylation | down-regulates activity | 0.369 | Our experiments demonstrated that target engagement by AGO2 stimulates its hierarchical, multi-site phosphorylation by CSNK1A1 on a series of highly conserved residues (S824-S834).Although this impairs target binding, dephosphorylation by ANKRD52-PPP6C allows AGO2 to engage new targets. Inactivation of this cycle strongly inhibits global miRNA-mediated repression. | SIGNOR-276510 |
Q8NER5 | Q96S42 | 2 | binding | up-regulates activity | 0.636 | Human activin receptor-like kinase 7 (ALK7), a type I receptor for Nodal. activation of the Nodal-ALK7 signaling pathway leads to induction of apoptosis and inhibition of cell proliferation. | SIGNOR-251936 |
O60381 | Q15759 | 0 | phosphorylation | up-regulates | 0.428 | A mutation of the p38 map kinase phosphorylation site at aa 401 [(s-a)401hbp1] also triggered hbp1 protein instability. While protein stability was compromised by mutation, the specific activities of (s-a)401hbp1 and of wild-type hbp1 appeared comparable for transcriptional repression. | SIGNOR-119134 |
Q99705 | P38405 | 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-256905 |
Q96J02 | P08151 | 1 | ubiquitination | down-regulates | 0.578 | The consequent activation of_ itch, together with the recruitment of gli1 through direct binding with_ numb, allows gli1 to enter into the complex, resulting in gli1 ubiquitination and degradation. we demonstrate that the hedgehog transcription factor gli1 is targeted by numb for itch-dependent ubiquitination, which suppresses hedgehog signals, thus arresting growth and promoting cell differentiation | SIGNOR-150847 |
P34925 | P56704 | 2 | binding | up-regulates | 0.763 | Here, we report that ryk directly binds wnt-1 and wnt-3a via its wif domain and is required for the tcf. | SIGNOR-129580 |
P53350 | Q9Y6D9 | 1 | phosphorylation | up-regulates activity | 0.464 | These findings indicate mechanistic roles contributed by protein phosphorylation and Plk1 to the SAC activity of Mad1.Here, we have studied the phosphorylation of Mad1 and mapped using liquid chromatography-tandem mass spectrometry several phosphorylated amino acids in this protein. One phosphorylated residue, Thr680, was characterized to be important for the kinetochore localization of Mad1 and its SAC function. | SIGNOR-276173 |
P55199 | Q96JC9 | 2 | binding | up-regulates | 0.847 | Positive regulation of ell elongation activity depends on stable binding of eaf1 to the ell n terminus | SIGNOR-138516 |
P17252 | P15172 | 1 | phosphorylation | down-regulates activity | 0.363 | FGF inactivates myogenic helix-loop-helix proteins through phosphorylation of a conserved protein kinase C site in their DNA-binding domains. | SIGNOR-248845 |
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