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 |
|---|---|---|---|---|---|---|---|
P00519 | Q99638 | 1 | phosphorylation | up-regulates activity | 0.477 | The SH3 domain of c-Abl interacts directly with the C-terminal region of Rad9. c-Abl phosphorylates the Rad9 Bcl-2 homology 3 domain (Tyr-28) in vitro and in cells exposed to DNA-damaging agents. | c-Abl-mediated phosphorylation of Rad9 induces binding of Rad9 to Bcl-xL |these findings indicate that Rad9 is regulated by a c-Abl-dependent mechanism in the apoptotic response to genotoxic stress. | SIGNOR-260843 |
P53350 | Q9BTA9 | 2 | binding | up-regulates activity | 0.2 | Here, we report that the activation of Plk1 requires WAC, a WW domain-containing adaptor protein with a coiled-coil region that predominantly localizes to the nucleus in interphase. Cyclin-dependent kinase 1 (Cdk1) phosphorylates WAC, priming its direct interaction with the polo-box domain of Plk1. | SIGNOR-265036 |
Q9UQL6 | Q9BZL6 | 0 | phosphorylation | up-regulates activity | 0.295 | Histone deacetylase (HDAC) 5 and 7, two members of the class II of classical HDAC [62], are in vivo substrates of PKD3 and PKD [63]. In response to a variety of signals, including phorbol esters, T cell receptor engagement, vascular endothelial growth factor and angiotensin stimulation, the activity of HDAC5 and 7 are regulated by a mechanism that involves PKD3 and PKD-mediated phosphorylation of the highly conserved Ser259 and Ser498 residues that are located in N-terminus of class II HDACs [63–67]. | SIGNOR-275929 |
Q15139 | Q8WYL5 | 1 | phosphorylation | down-regulates | 0.479 | Pkd-mediated phosphorylation of serines 937 and 978 regulates ssh1l subcellular localization by binding of 14-3-3 proteins 14-3-3 proteins associate with ssh1l when phosphorylated at serines 937 and 978, thereby sequestering ssh1l in the cytoplasm and preventing translocation of the phosphatase to f-actin_rich membrane protrusions | SIGNOR-186471 |
O75592 | P62826 | 1 | guanine nucleotide exchange factor | up-regulates activity | 0.296 | MYCBP2 Is a Nuclear GEF for Ran in DRG Neurons—Next, we studied whether or not MYCBP2 modulates the interaction between Ran/RanGAP1. MYCBP2 contains an N-terminal RCC1-like domain (Fig. 8C) (13), and RCC1 is a known GEF for Ran, indicating a potential functional interaction between MYCBP2 and Ran. | SIGNOR-261204 |
Q06945 | P35222 | 2 | binding | up-regulates activity | 0.592 | We have demonstrated that Sox17 and Sox4 can directly interact with β-catenin and TCF/LEF proteins.Sox4 enhances β-catenin/TCF activity and the proliferation of SW480 cells.In contrast, Sox4 may function to stabilize β-catenin protein. | SIGNOR-256138 |
P98177 | Q99576 | 0 | relocalization | down-regulates activity | 0.253 | GILZ inhibits FOXO1, FOXO3, and FOXO4 transcriptional activities measured with natural or synthetic FOXO-responsive promoters in HL-60 cells. | SIGNOR-256148 |
Q13315 | Q15797 | 1 | phosphorylation | up-regulates | 0.2 | On genotoxic stress, atm phosphorylates bmps-activated smad1 in the nucleus on s239, which disrupts smad1 interaction with protein phosphatase ppm1a, leading to enhanced activation and upregulation of smad1. | SIGNOR-197533 |
Q06830 | P24941 | 0 | phosphorylation | down-regulates | 0.254 | Peroxiredoxin (prx) i is a member of the peroxiredoxin family of peroxidases and contains a consensus site (thr(90)-pro-lys-lys) for phosphorylation by cyclin-dependent kinases (cdks). This protein has now been shown to be phosphorylated specifically on thr(90) by several cdks, including cdc2, in vitro. Phosphorylation of prx i on thr(90) reduced the peroxidase activity of this protein by 80%.Prx i was also phosphorylated, with an efficiency similar to that observed with cdc2, when incubated in vitro with cdk2, cdk4, or cdk6 that had been immunoprecipitated from hela cell lysates with specific antibodies (data not shown). | SIGNOR-87101 |
P04637 | P68400 | 0 | phosphorylation | up-regulates activity | 0.668 | Furthermore, we demonstrate that anisomycin- and tumor necrosis factor-alpha-induced phosphorylation of p53 at Ser-392, which is important for the transcriptional activity of this growth suppressor protein, requires p38 MAP kinase and CK2 activities. | SIGNOR-250967 |
Q15835 | Q15835 | 2 | phosphorylation | down-regulates activity | 0.2 | The major autophosphorylation site yielded the following sequence: DVGAFS488T489VKGVAFEK, where Ser488 and Thr489 are phosphorylated. Additionally, a minor autophosphorylation site was identified at Ser21. we speculate that autophosphorylation of RK may lower the affinity of the enzyme for Rho* via repulsion between phosphorylated sites on Rho* and the kinase. | SIGNOR-251187 |
P78368 | O14654 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | IRS4 was phosphorylated at Ser859 by CK1γ2 in vitro and in vivo, which promoted the polyubiquitination and degradation of IRS4 through the ubiquitin/lysosome pathway by the carboxyl terminus of Hsc70-interacting protein(CHIP). | SIGNOR-277615 |
P63279 | Q6DJT9 | 1 | sumoylation | down-regulates | 0.277 | Sumoylation decreases the transcriptional activity of plag1 / plag1 is sumoylated at 2 specific lysine residues (lys-244 and lys-263) | SIGNOR-126048 |
Q5S007 | Q99962 | 1 | phosphorylation | down-regulates | 0.472 | We show that lrrk2 affects synaptic endocytosis by phosphorylating endophilin-a1 at s75. | SIGNOR-192072 |
P63092 | P35348 | 2 | binding | up-regulates activity | 0.291 | 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-256812 |
P16591 | P40763 | 1 | phosphorylation | up-regulates activity | 0.402 | Replacing the unique 43-amino acid-long N-terminal tail of p51 (ferT) with a parallel segment from the N-terminal tail of p94 (fer) did not change the subcellular localization of p51 (ferT) but enabled it to activate Stat3.|When combined with immunoprecipitation analysis, this assay showed that p94 (fer) can lead to the tyrosine phosphorylation and activation of Stat3 but not of Stat1 or Stat2. | SIGNOR-279713 |
Q9Y5X5 | 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-256709 |
Q99558 | Q13489 | 0 | ubiquitination | down-regulates | 0.65 | Ciap1/2 (cellular inhibitor of apoptosis 1 and 2) ubiquitinate nik for degradation. | SIGNOR-167298 |
P31260 | O15550 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.267 | 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-260020 |
P06239 | P41240 | 0 | phosphorylation | down-regulates | 0.538 | P50csk tyrosine kinase phosphorylates p56lck at tyr-505 and down regulates its catalytic activity. | SIGNOR-20371 |
Q15831 | Q9UKG1 | 2 | binding | up-regulates | 0.316 | In this study, we identified lkb1 as a new binding partner of appl1 and showed that the bar domain of appl1 is involved in this interaction.Here we show that in muscle cells adiponectin and metformin induce ampk activation by promoting appl1-dependent lkb1 cytosolic translocation. Appl1 mediates adiponectin signaling by directly interacting with adiponectin receptors and enhances lkb1 cytosolic localization by anchoring this kinase in the cytosol. | SIGNOR-186065 |
O00254 | P63096 | 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-257033 |
Q9UHD2 | Q86U44 | 1 | phosphorylation | up-regulates activity | 0.2 | TBK1 also promotes METTL3 activation and m 6 A modification to stabilize IRF3 mRNA .|We here find TBK1, a key kinase of antiviral pathways, phosphorylates the core m 6 A methyltransferase METTL3 at serine 67. | SIGNOR-279299 |
Q13188 | P17252 | 1 | phosphorylation | up-regulates activity | 0.2 | Thus, the phosphorylation of PKCα at Ser226 and Thr228 by Mst1 and Mst2 is required for the optimal activation of PKCα. | SIGNOR-277176 |
Q9UQ26 | O95153 | 2 | binding | down-regulates activity | 0.2 | 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-264368 |
P11309 | P01106 | 1 | phosphorylation | up-regulates activity | 0.697 | FLT3-ITD kinase may regulate c-MYC through STAT5-induced enhancement of PIM kinases (Choudhary et al., 2009), which can modulate c-MYC stability and activity via phosphorylation (van der Lugt et al., 1995s). This is supported by the observation that FLT3-ITD CD34+ cells showed higher PIM activity compared to cells expressing FLT3-WT, indicated by increased expression of the PIM targets including p-BAD (Ser112), p-4EBP1 (Thr37/46), and p-c-MYC (Ser62) (Figure 6C); and by the observation that siRNA-mediated inhibition of PIM1, but not PIM2, expression resulted in significantly decreased p-c-MYC (Ser62), c-MYC, and SIRT1 expression in MV4-11 cells | SIGNOR-261557 |
Q99878 | Q9Y4B6 | 0 | phosphorylation | up-regulates activity | 0.2 | Here we report that VprBP possesses an intrinsic protein kinase activity and is capable of phosphorylating histone H2A on threonine 120 (H2AT120p) in a nucleosomal context. Functional studies reveal that H2AT120p by VprBP is sufficient to repress chromatin transcription. | SIGNOR-279884 |
P48163 | Q8N6T7 | 0 | deacetylation | down-regulates activity | 0.25 | PGAM5-mediated dephosphorylation of malic enzyme 1 (ME1) at S336 allows increased ACAT1-mediated K337 acetylation, leading to ME1 dimerization and activation, both of which are reversed by NEK1 kinase-mediated S336 phosphorylation. SIRT6 deacetylase antagonizes ACAT1 function in a manner that involves mutually exclusive ME1 S336 phosphorylation and K337 acetylation. | SIGNOR-275572 |
Q13464 | Q6WCQ1 | 1 | phosphorylation | down-regulates | 0.296 | Enhanced rho kinase activity induces endothelial barrier dysfunction by a contractile mechanism via inactivation of myosin phosphatase (mp).. | SIGNOR-157593 |
Q9Y5I2 | Q9Y5G9 | 2 | binding | up-regulates activity | 0.2 | The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion. They also form oligomers with Pcdh-gamma proteins at the same membrane sites. | SIGNOR-265697 |
P04637 | Q13535 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.742 | Nhibition of atr kinase activity substantially reduces hypoxia-induced phosphorylation of p53 protein on serine 15 as well as p53 protein accumulation. | SIGNOR-115134 |
Q13315 | Q14683 | 1 | phosphorylation | up-regulates activity | 0.705 | Atm phosphorylates Smc1 on serines 957 and 966 in vitro and in vivo, and expression of an Smc1 protein mutated at these phosphorylation sites abrogates the ionizing irradiation-induced S phase cell cycle checkpoint | SIGNOR-255589 |
Q99638 | Q13315 | 0 | phosphorylation | up-regulates activity | 0.767 | Hyperphosphorylation of hrad9 induced by ir is dependent on atm. Ser(272) of hrad9 is phosphorylated directly by atm in vitro. / our results suggest that the atm-mediated phosphorylation of hrad9 is required for ir-induced checkpoint activation. | SIGNOR-105243 |
P17612 | Q12809 | 1 | phosphorylation | up-regulates | 0.307 | Deletion of protein kinase a phosphorylation sites in the herg potassium channel inhibits activation shift by protein kinase afour consensus pka phosphorylation sites (s283a, s890a, t895a, s1137a) | SIGNOR-70726 |
P17706 | P09619 | 1 | dephosphorylation | down-regulates activity | 0.564 | The PDGF beta receptor is negatively regulated by protein tyrosine phosphatases (PTPs).|In summary, our findings identify TC-PTP as a previously unrecognized negative regulator of PDGF beta receptor signaling and support the general notion that PTPs display site selectivity in their action on tyrosine kinase receptors.The fact that two of the investigated PDGF β receptor sites, Y1021 and Y771, displayed a larger increase in phosphorylation than Y579 and Y751 in TC-PTP ko MEFs indicated that these two sites are preferred substrates for TC-PTP. | SIGNOR-248389 |
Q9C004 | Q15569 | 2 | binding | down-regulates activity | 0.565 | Spry4 negatively regulates the kinase activity of TESK1 by associating with it through the C-terminal cysteine-rich region of Spry4 | SIGNOR-253032 |
Q13043 | P04049 | 2 | binding | down-regulates | 0.272 | Raf1 binding to mst2 sarah domain interdicts mst2 homodimerization and autoactivation, and recruits protein phosphates 2a thereby promoting mst2 inactivation. | SIGNOR-191843 |
Q6PJ69 | Q9NRY4 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | Ubiquitin ligase TRIM65 promotes colorectal cancer metastasis by targeting ARHGAP35 for protein degradation | SIGNOR-272256 |
P05129 | P07900 | 1 | phosphorylation | down-regulates | 0.258 | Threonine residue set, thr(115)/thr(425)/thr(603), of hsp90_ is specifically phosphorylated by pkc_phosphorylation of hsp90_ by pkc_ decreases the binding affinity of hsp90_ towards atp and co-chaperones such as cdc37 (cell-division cycle 37), thereby decreasing its chaperone activity. | SIGNOR-202812 |
P07711 | P59594 | 1 | cleavage | up-regulates activity | 0.2 | A cell-free membrane-fusion system demonstrates that engagement of receptor followed by proteolysis is required for SARS-CoV membrane fusion and indicates that cathepsin L is sufficient to activate membrane fusion by SARS-CoV S. These results suggest that SARS-CoV infection results from a unique, three-step process: receptor binding and induced conformational changes in S glycoprotein followed by cathepsin L proteolysis within endosomes. The requirement for cathepsin L proteolysis identifies a previously uncharacterized class of inhibitor for SARS-CoV infection. | SIGNOR-260218 |
Q13114 | Q99558 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.668 | TRAF2 and TRAF3 mediate NIK ubiquitination by forming a complex with the E3 ligase cIAP (cIAP1 or cIAP2).|We demonstrated further that TRAF3 mediates the degradation of NIK and thereby serves as a pivotal negative regulator of noncanonical NF-kappaB signaling. | SIGNOR-278673 |
Q09472 | Q04206 | 1 | acetylation | up-regulates activity | 0.822 | Using acetylation assays, p300 was found to effectively acetylate RelA/p65 across the amino-acid region containing 1317 | SIGNOR-238778 |
Q96JC1 | Q04771 | 2 | binding | up-regulates activity | 0.2 | TLP interacts with TGF-β and activin receptors in vivo. Endogenous TLP associates with both active and kinase-deficient TGF-beta and activin type II receptors, but interacts with the common-mediator Smad4 only in the presence of TGF-beta/activin signaling. | SIGNOR-261376 |
Q13133 | P68400 | 0 | phosphorylation | down-regulates | 0.2 | Ck2? Also phosphorylated lxr? At s198 in vitro, suggesting that ck2 may be a bona fide s198 kinase. our results show that macrophage lxr? Phosphorylation at s198 affects the transcriptional activity of the receptor in a gene-specific manner (fig. ?(Fig.3a)3a) and restricts the repertoire of genes regulated by lxr? | SIGNOR-160640 |
O43683 | P40763 | 1 | phosphorylation | up-regulates activity | 0.251 | This study showed that the BUB1 kinase drives the progression and proliferation of BCa by regulating the transcriptional activation of STAT3 signaling and may be an attractive candidate for therapeutic targeting in BCa.|We further identified through a series of molecular and cell biological approaches that BUB1 interacted directly with STAT3 and mediated the phosphorylation of STAT3 at Ser727. | SIGNOR-280198 |
P35367 | P17612 | 0 | phosphorylation | down-regulates | 0.2 | Two amino acid residues (ser396, ser398) on hr1 were determined to be pkc phosphorylation sites by in vitro phosphorylation studies.Site-directed mutagenesis studies suggests that the ser398 residue was primarily involved in pkc-mediated desensitization. Possibly, phosphorylation of the residues is required for receptor transport from endosomes to lysosomes. | SIGNOR-128411 |
Q9NY46 | Q96PU5 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.283 | The control of Nav density at the cell membrane is crucial to ensuring normal neuronal excitability. Navs are subject to posttranslational modifications that may influence their cell membrane availability. Ubiquitylation is a key process that orchestrates the internalization and subsequent degradation or recycling of Navs. This is accomplished by ubiquitin protein ligases, such as NEDD4-2 (neuronal precursor cell expressed developmentally downregulated-4 type 2). | SIGNOR-253464 |
Q15418 | Q8IX03 | 1 | phosphorylation | up-regulates | 0.335 | Moreover, we found that rsk1/2 specifically phosphorylates kibra at two highly conserved sites (thr(929) and ser(947)) in vitro and in cells. Rsk-mediated phosphorylation is required for kibra binding to rsk1, but not rsk2. | SIGNOR-203298 |
P08567 | P17252 | 0 | phosphorylation | up-regulates | 0.28 | To determine the role of pkc-dependent phosphorylation in pleckstrin function, we mapped the phosphorylation sites in vivo of wild-type and site-directed mutants of pleckstrin expressed in cos cells. Phosphorylation was found to occur almost exclusively on ser-113 and ser-117. Replacing all these sites with glycine decreased phosphorylation by > 90% and reduced pleckstrin's ability to inhibit phosphoinositide hydrolysis by as much as 80%. | SIGNOR-40048 |
P35637 | P43243 | 1 | relocalization | up-regulates activity | 0.486 | Moreover, FUS interacts with another nuclear matrix-associated protein Matrin3, which is muted in a subset of familial ALS cases and reportedly interacts with TDP-43. Interestingly, ectopic ALS-linked FUS mutant sequestered endogenous Matrin3 and SAFB1 in the cytoplasmic aggregates. | SIGNOR-262822 |
Q99576 | P98177 | 1 | relocalization | down-regulates activity | 0.253 | GILZ inhibits FOXO1, FOXO3, and FOXO4 transcriptional activities measured with natural or synthetic FOXO-responsive promoters in HL-60 cells. | SIGNOR-256148 |
P41743 | P49757 | 1 | phosphorylation | down-regulates | 0.771 | Numb is regulated by phosphorylation since the protein is released from ccss and no longer binds integrins when phosphorylated by atypical protein kinase c (apkc). | SIGNOR-156765 |
Q04759 | Q9BXL7 | 1 | phosphorylation | up-regulates activity | 0.775 | NF-kappaB activation is triggered by PKCteta-dependent phosphorylation of Carma1 after TCR/CD28 co-stimulation. PKCteta-phosphorylated Carma1 was suggested to function as a molecular scaffold that recruits preassembled Bcl10-Malt1 complexes to the membrane|we demonstrate that PP2A removes PKCteta-dependent phosphorylation of Ser645 in Carma1, and show that maintenance of this phosphorylation is correlated with increased T-cell activation. | SIGNOR-249193 |
P29317 | P29317 | 2 | phosphorylation | up-regulates | 0.2 | The binding of ephrin ligands to eph receptors induces the transphosphorylation of the cytoplasmic domains and initiates kinase activity.Taken together, these results suggest that tyr587, tyr593, tyr771, and tyr734 are likely to be autophospho-rylated in vascular endothelial cells. | SIGNOR-178169 |
Q92843 | Q9BXH1 | 2 | binding | down-regulates | 0.552 | 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-133814 |
Q01664 | Q12857 | 2 | binding | up-regulates activity | 0.266 | We also observed moderately increased recruitment of CTCF, HDAC1, and SP1 by the full-length AP-4 onto the WT DNA beads. | SIGNOR-226586 |
P17252 | P17844 | 1 | phosphorylation | down-regulates activity | 0.335 | We report that p68 is phosphorylated by protein kinase C in vitro and binds calmodulin in a Ca(2+)-dependent manner. Both phosphorylation and calmodulin binding inhibited p68 ATPase activity | In addition, a 20-amino acid peptide corresponding to residues 549-568 of p68 was phosphorylated in a Ca- and phospholipid-dependent manner hy PKC | SIGNOR-248896 |
Q9UQL6 | Q05655 | 0 | phosphorylation | down-regulates activity | 0.352 | In this report, we show that VEGF stimulates PKD-dependent phosphorylation of HDAC5 at Ser259/498residues in ECs, which leads to HDAC5 nuclear exclusion and myocyte enhancer factor-2 (MEF2) transcriptional activation. | SIGNOR-260875 |
P31751 | Q13243 | 1 | phosphorylation | up-regulates activity | 0.362 | Here we show that Akt2 kinase phosphorylated SRp40 in vivo and in vitro. Mutation of Ser86 on SRp40 blocked in vitro phosphorylation. | SIGNOR-262633 |
P21554 | P63096 | 2 | binding | up-regulates activity | 0.541 | 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-256724 |
Q99612 | P18847 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.394 | KLF6 binds directly to and activates the ATF3 promoter. | SIGNOR-266051 |
P24941 | P03372 | 1 | phosphorylation | up-regulates | 0.477 | The pi3k/akt pathway is necessary to activate cdk2, which phosphorylates eralphaser294, and mediates the binding between pin1 and eralpha | SIGNOR-200867 |
Q12888 | P16403 | 2 | binding | down-regulates activity | 0.2 | Similarly, DNA-PK-mediated phosphorylation of H1.2 at T146 enhances p53 transcriptional activity by impeding H1.2 binding to p53 and thereby attenuating its suppressive effects on p53 transactivation. | SIGNOR-273833 |
P35408 | 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-256903 |
P63244 | Q9BX84 | 2 | binding | down-regulates activity | 0.2 | We identified RACK1 as the first TRPM6-associated protein and demonstrated that RACK1 inhibits TRPM6 channel activity depending on the phosphorylation state T1851 in the α-kinase domain. | SIGNOR-260921 |
P13807 | P49841 | 0 | phosphorylation | down-regulates activity | 0.686 | Glycogen synthase kinase-3 phosphorylates three serine residues on glycogen synthase (sites 3a, 3b and 3c) which are all located in the same nine-amino-acid segment of the polypeptide chain. The sequence in this region is: Arg-Tyr-Pro-Arg-Pro-Ala-Ser(P)-Val-Pro-Pro-Ser(P)-Pro-Ser-Leu-Ser(P)-Arg-. | SIGNOR-253007 |
P17612 | Q92777 | 1 | phosphorylation | down-regulates activity | 0.326 | Synapsin phosphorylation in the A domain, at the only phosphorylation site shared by all synapsins, dissociates synapsins from synaptic vesicles.This site is located in the N-terminal A domain and is a substrate for both PKA and CaM Kinase I | SIGNOR-250059 |
O96017 | P51530 | 1 | phosphorylation | up-regulates activity | 0.526 | We later observed that Dna2 phosphorylation by Cds1 is necessary for Dna2 association with chromatin in HU treated cells. | SIGNOR-279729 |
Q86UR5 | A6NJZ7 | 2 | binding | down-regulates activity | 0.265 | 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-264362 |
Q16611 | O95831 | 1 | relocalization | up-regulates | 0.297 | First, bax/bak-mediated momp leads to the release of a significant part of the cyt c, smac/diablo and htra2/omi proteins. in a third step, cyt c, smac/diablo and htra2/omi, which were released into the cytosol, trigger caspase activation. This is necessary to alter the physical association of aif and endog with the im to enable their relocation to the cytosol. | SIGNOR-192092 |
P08253 | Q9NPA2 | 0 | cleavage | up-regulates activity | 0.375 | Direct activation of pro-matrix metalloproteinase-2 by leukolysin/membrane-type 6 matrix metalloproteinase/matrix metalloproteinase 25 at the asn(109)-Tyr bond. Leukolysin Cleaves ProMMP-2 at Asn66-Leu and Asn109-Tyr. | SIGNOR-256345 |
P18031 | P06493 | 0 | phosphorylation | up-regulates activity | 0.502 | 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-272970 |
P02458 | P45452 | 0 | cleavage | down-regulates quantity by destabilization | 0.544 | Although it appears that MMP-1 and MMP-13 both cleave type II collagen initially at the same site, MMP-13 affects a secondary cleavage to produce a 1/4-size collagen fragment with an NH2 terminus three amino acids removed from the primary cleavage site.The present work has demonstrated expression of MMP-13 in human osteoarthritic cartilage and shown that MMP-13 has significant type II collagen degrading activity. | SIGNOR-256340 |
Q9P0U3 | Q9NP62 | 1 | desumoylation | up-regulates activity | 0.468 | We show that Epac1 and Rap1, in response to cAMP, activate CaMKI to phosphorylate Ser47 in GCM1. This phosphorylation facilitates the interaction between GCM1 and the desumoylating enzyme SENP1 and thereby leads to GCM1 desumoylation and activation. | SIGNOR-262681 |
P27361 | P05412 | 1 | phosphorylation | up-regulates | 0.781 | Up-regulation of c-jun mrna in cardiac myocytes requires the extracellular signal-regulated kinase cascade, but c-jun n-terminal kinases are required for efficient up-regulation of c-jun protein. | SIGNOR-91379 |
Q9NZQ7 | Q15116 | 2 | binding | up-regulates | 0.936 | Pd-l1, was found to bind pd-1 specifically. The functional significance of this interaction has been demonstrated in t cell assays, in which engagement of pd-1 by pd-l1 leads to the inhibition of tcr-mediated lymphocyte proliferation and cytokine secretion. | SIGNOR-82604 |
Q9UKL0 | O60341 | 2 | binding | up-regulates activity | 0.955 | CoREST protects LSD1 from proteasomal degradation and also plays an indispensable role in LSD1-mediated demethylation of nucleosomal substrates in vitro. in contrast to CoREST, which is a positive regulator of LSD1 activity, the in vitro evidence presented above suggests that BHC80 may function to inhibit LSD1 activity. | SIGNOR-264506 |
P35247 | P53567 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Cotransfection of C/EBPalpha, C/EBPbeta, or C/EBPdelta cDNA in H441 lung adenocarcinoma cells significantly increased the luciferase activity of a wild-type SP-D promoter construct containing 698 bp of upstream sequence (SS698). Transfection of C/EBP also increased the level of endogenous SP-D mRNA in H441 cells| Thus, interactions among C/EBP elements in the near-distal promoter can modulate the promoter activity of SP-D. | SIGNOR-254058 |
P17693 | Q99706 | 2 | binding | up-regulates | 0.764 | Recombinant soluble kir2dl4 binds to cells expressing hla-g but not to cells expressing other hla class i molecules. | SIGNOR-66132 |
Q86TM6 | P05067 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.339 | Thus, HRD1 ubiquitinates and degrades denaturated APP as well as unfolded proteins, suggesting that HRD1 affects APP-A\u03b2 dynamics in the brains of AD patients. | SIGNOR-278616 |
O75838 | Q8TDI7 | 2 | binding | up-regulates activity | 0.352 | Furthermore, we report that calcium and integrin-binding protein 2 binds to the components of the hair cell mechanotransduction complex, TMC1 and TMC2, and these interactions are disrupted by deafness-causing Cib2 mutations. We conclude that calcium and integrin-binding protein 2 is required for normal operation of the mechanotransducer channels and is involved in limiting the growth of transducing stereocilia. | SIGNOR-269665 |
Q9HBW0 | P63092 | 2 | binding | up-regulates activity | 0.388 | 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-256784 |
P49757 | Q14012 | 0 | phosphorylation | down-regulates | 0.334 | Based on experiments using numb mutants, both the initial phosphorylation of ser(264) and the subsequent phosphorylation of ser(283) are sufficient to abolish the binding of numb to ap-2. | SIGNOR-149993 |
O43464 | Q15121 | 2 | binding | down-regulates | 0.485 | Htra2 promotes cell death by binding and degrading the anti-apoptotic protein pea15 | SIGNOR-126966 |
Q92565 | P01112 | 1 | guanine nucleotide exchange factor | up-regulates | 0.508 | Gefs catalyse the transition from gdp-bound, inactive ras to gtp-bound, active ras. | SIGNOR-183732 |
P42336 | P01116 | 2 | binding | up-regulates | 0.91 | Grb2 binds and activates sos, which then activates ras, and this activates p110 independently of p85./it was also described that ras interacts with pi3k in a direct manner./lysine residue 227 is essential for the interaction of ras with pi3k phosphatidylinositol 3-kinase (pi3k) is one of the main effector pathways of ras, regulating cell growth, cell cycle entry, cell survival, cytoskeleton reorganization, and metabolism. | SIGNOR-175204 |
P30679 | P46663 | 2 | binding | up-regulates activity | 0.449 | 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-257411 |
Q13469 | P49841 | 0 | phosphorylation | down-regulates | 0.561 | Gsk3 was previously shown to directly phosphorylate the n-terminal regulatory domain of nfatc1, thus antagonizing the action of calcineurin and inhibiting nuclear shuttling of nfat. | SIGNOR-179784 |
Q00535 | O00429 | 1 | phosphorylation | up-regulates activity | 0.464 | CDK5 activates DRP1 in BTICs.|To determine if CDK5 could directly phosphorylate DRP1, we performed an in vitro kinase assay with CDK5, its regulatory partner p25 and GST-DRP1 (wild type or S616A mutant) and found that CDK5 directly phosphorylates DRP1 on the S616 site (Fig. 7d). | SIGNOR-278275 |
P04637 | Q05086 | 0 | ubiquitination | down-regulates quantity | 0.681 | E6-AP also directly ubiquitylated p53 in an in vitro ubiquitylation assay.|Our result suggests that E6-AP not only enhances the degradation of p53 but also regulates the neuronal cell growth. | SIGNOR-278681 |
P52566 | Q8TEB7 | 0 | polyubiquitination | up-regulates quantity by stabilization | 0.2 | We found that RhoGDIα and RhoGDIβ are ubiquitin E3 substrates of GRAIL. GRAIL uses nonlysine 48-ubiquitin linkage in polyubiquitinating RhoGDI. GRAIL was subsequently demonstrated to bind and ubiquitinate RhoGDI, although GRAIL-mediated ubiquitination of RhoGDI did not result in proteosomal degradation. Our data suggest that ubiquitination of RhoGDI by GRAIL does not result in proteolytic degradation. In fact, GRAIL activity appeared to increase RhoGDI stability. | SIGNOR-271621 |
O75581 | P28482 | 0 | phosphorylation | up-regulates | 0.301 | We show that several proline-directed mitogen-activated protein kinases (mapks), such as p38, erk1/2, and jnk1 are sufficient and required for the phosphorylation of ppps/tp motifs of lrp6. External stimuli, which control the activity of mapks, such as phorbol esters and fibroblast growth factor 2 (fgf2) control the choice of the lrp6-ppps/tp kinase and regulate the amplitude of lrp6 phosphorylation and wnt/beta-catenin-dependent transcription. | SIGNOR-169001 |
Q9UJC3 | Q06124 | 2 | binding | down-regulates activity | 0.353 | The protein-tyrosine phosphatase domain and N-terminal SH2 domain of SHP2 directly interacted with Hook1. Down-regulation of Hook1 increased SHP2 activity. These results suggested that Hook1 was an endogenous negative regulator of SHP2 phosphatase activity. | SIGNOR-260642 |
P0DP23 | Q12756 | 2 | binding | up-regulates activity | 0.275 | To better understand how KIF1A-driven dense core vesicle (DCV) transport is regulated, we identified the KIF1A interactome and focused on three binding partners, the calcium binding protein calmodulin (CaM) and two synaptic scaffolding proteins: liprin-α and TANC2. We showed that calcium, acting via CaM, enhances KIF1A binding to DCVs and increases vesicle motility. We show that Ca2+/CaM-dependent modulation on KIF1A allows for binding to vesicular cargo. Our results indicate that at low calcium concentrations, the tail domain of KIF1A does not bind to vesicular cargo, whereas at high calcium concentrations, CaM binds KIF1A, allowing for subsequent DCV motility. | SIGNOR-266888 |
Q02078 | Q13469 | 2 | binding | up-regulates | 0.409 | Upon dephosphorylation by calcineurin, nfatc2, also referred to as nfatp/nfat1, translocates to the nucleus where it directly associates with mef2a and -d. Nfatc2 stimulates mef2-dependent transcription by facilitating recruitment of the p300 coactivator to mef2-response elements. | SIGNOR-117586 |
Q5JU85 | P62330 | 1 | guanine nucleotide exchange factor | up-regulates activity | 0.457 | Here, we characterized IQ-ArfGEF/BRAG1, a guanine nucleotide exchange factor (GEF) for Arf6, in the mouse brain. In vivo Arf pull down assay demonstrated that IQ-ArfGEF/BRAG1 activated Arf6 more potently than Arf1.IQ-ArfGEF/BRAG1 is a guanine nucleotide exchange factor for Arf6 that interacts with PSD-95 at postsynaptic density of excitatory synapses. Taken together, IQ-ArfGEF/BRAG1 forms a postsynaptic protein complex containing PSD-95 and NMDA receptors at excitatory synapses, where it may function as a GEF for Arf6. | SIGNOR-264906 |
Q9HDB5 | Q8NFZ3 | 2 | binding | up-regulates activity | 0.2 | Pre- and postsynaptic plasma membranes are always precisely aligned, and are separated by a synaptic cleft of ~20 nm. The cleft contains an undefined proteinaceous material in the middle, and is presumably bridged by synaptic cell-adhesion molecules such as Nrxns and Nlgns that align the pre- and postsynaptic elements and mediate trans-synaptic signaling.|Nlgns bind to both alpha- and beta-Nrxns with nanomolar affinities; binding involves the sixth LNS-domain of alpha-Nrxns which corresponds to the only LNS-domain of beta-Nrxns52. The binding affinities differ characteristically between various pairs of Nlgns and Nrxns, and are controlled by alternative splicing of both Nrxns and Nlgns (Figure 1c) | SIGNOR-264168 |
P67775 | Q14653 | 1 | dephosphorylation | down-regulates activity | 0.314 | RACK1 Negatively Regulates the Type I IFN pathway. Here we report that IRF3 is deactivated via dephosphorylation mediated by the serine and threonine phosphatase PP2A and its adaptor protein RACK1. The PP2A-RACK1 complex negatively regulated the IRF3 pathway after LPS or poly(I:C) stimulation or Sendai virus (SeV) infection. | SIGNOR-260944 |
O94901 | Q8NA31 | 2 | binding | up-regulates activity | 0.2 | In this study, we found that SUN1 not only interacted with TERB1 but also interacted with MAJIN, and the interaction of SUN1 with MAJIN is stronger than TERB1. We also found that SUN1 interacted with SPDYA, an activator of CDK2. | It will be of great interest to test this hypothesis to fully understand the mechanisms of stable telomere–NE connection and telomere movement along the NE driven by the LINC complex. | SIGNOR-263299 |
P05771 | P53004 | 0 | phosphorylation | up-regulates | 0.307 | Human biliverdin reductase, a previously unknown activator of protein kinase c ?II the phosphorylation of thr500 was confirmed by immunoblotting of hbvr.pkc betaii immunocomplex. | SIGNOR-152181 |
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