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 |
|---|---|---|---|---|---|---|---|
Q02156 | Q02156 | 2 | phosphorylation | down-regulates | 0.2 | Protein kinase-inactive mutants of pkcepsilon were not phosphorylated at ser(729) in cells, and phosphorylation of this site leads to dephosphorylation of the activation-loop thr(566) | SIGNOR-117324 |
Q8TEB7 | P52565 | 1 | polyubiquitination | up-regulates quantity by stabilization | 0.266 | 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-271622 |
Q14653 | P00519 | 0 | phosphorylation | up-regulates activity | 0.2 | The data in this study show that IRF3 is physically associated with c-Abl in vivo and directly binds to c-Abl in vitro. IRF3 is phosphorylated by c-Abl and c-Abl-related kinase, Arg, mainly at Y292. | SIGNOR-277440 |
Q9Y5H2 | Q9Y5H9 | 2 | binding | up-regulates activity | 0.2 | The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion. They also form oligomers with Pcdh-gamma proteins at the same membrane sites. | SIGNOR-265690 |
Q96RI0 | P08754 | 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-257157 |
P16333 | Q07889 | 2 | binding | up-regulates | 0.615 | We also found that nck binds directly to the guanine nucleotide exchange factor sos. / by binding to sos, nckmay bring sos to cell membrane where the ras protein is located. | SIGNOR-236321 |
P47901 | P08754 | 2 | binding | up-regulates activity | 0.267 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-257176 |
P68431 | Q15652 | 0 | demethylation | down-regulates activity | 0.2 | We now determine that JMJD1C is recruited by USF-1 to various lipogenic genes for H3K9 demethylation to enhance chromatin accessibility in the fed state. | SIGNOR-265171 |
P37173 | Q96JC1 | 2 | binding | up-regulates activity | 0.325 | 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-261374 |
P14921 | P01100 | 1 | transcriptional regulation | up-regulates quantity | 0.718 | Furthermore, the possible involvement of an Ets protein in the control of c-fos has interesting implications for proto-oncogene cooperation in cellular growth control. | SIGNOR-256495 |
P06493 | Q12888 | 1 | phosphorylation | down-regulates activity | 0.599 | Nuclear import of 53BP1 is required for proper localization of 53BP1 and maintenance of genome integrity. 53BP1 has a classical bipartite nuclear localization signal (NLS) of sequence 1666-GKRKLITSEEERSPAKRGRKS-1686. Ser1678 within the 53BP1 NLS can be phosphorylated by CDK1/cyclin B, and a phosphomimetic substitution of Ser1678 with aspartate has been shown to negatively regulate nuclear import of 53BP1. | SIGNOR-264412 |
P25021 | P50148 | 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-257375 |
Q16566 | P53667 | 1 | phosphorylation | up-regulates activity | 0.256 | An active form of CaMKIV but not CaMKI enhanced Thr 508 phosphorylation of LIMK1 and increased the kinase activity of LIMK1.|Taken together, our results suggest that LIMK1 mediated cofilin phosphorylation is critical for ionomycin induced neurite outgrowth and that CaMKIV mediates ionomycin induced LIMK1 activation. | SIGNOR-280201 |
P06493 | O94992 | 1 | phosphorylation | down-regulates activity | 0.257 | Given that Cdk1 phosphorylation promotes Clp1 nucleoplasmic accumulation upon genotoxic stress and Cdk1 phosphorylation inhibits Clp1 activity, Clp1 may be only primed by its nucleolar release but not actually active under these circumstances.|In addition, Cdk1 directly phosphorylates Clp1 on TP sites primarily in early mitosis and inhibits Clp1 catalytic activity. | SIGNOR-279508 |
Q02078 | P15172 | 2 | binding | up-regulates activity | 0.742 | Myod-e protein heterodimers interact with mef2 proteins to synergistically activate myogenesis. | SIGNOR-54086 |
O43318 | O75688 | 0 | dephosphorylation | down-regulates activity | 0.551 | In vitro, PP2Cbeta-1 dephosphorylated and inactivated TAK1. | SIGNOR-277154 |
Q8WYL5 | O14654 | 2 | binding | up-regulates activity | 0.311 | Insulin Receptor Substrate-4 Binds to Slingshot-1 Phosphatase and Promotes Cofilin Dephosphorylation. In addition, IRS4 co-localized with SSH1 in F-actin-rich membrane protrusions in insulin-stimulated cells, which suggests that the association of IRS4 with SSH1 contributes to localized activation of cofilin in membrane protrusions. | SIGNOR-277617 |
P25963 | O15111 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.896 | We described the purification of a 900 kda protein kinase complex, the ikb kinase (ikk), that phosphorylates ikbalfa and ikbbeta at the sites that mediate their ubiquitination and degradation | SIGNOR-52875 |
Q15910 | P10275 | 2 | binding | up-regulates activity | 0.54 | This study demonstrates that phosphorylation of EZH2 at Ser21, mediated directly or indirectly by the PI3K-Akt pathway, can switch its function from a Polycomb repressor to a transcriptional coactivator of AR (and potentially other factors). | SIGNOR-251542 |
P53801 | P12931 | 0 | phosphorylation | up-regulates activity | 0.2 | Src induction leads to phosphorylation at PBF residue Y174. Abrogation of this residue results in PM retention and a markedly reduced ability to bind NIS. | SIGNOR-273810 |
P62166 | P14416 | 2 | binding | down-regulates activity | 0.68 | Here we show that the neuronal calcium sensor-1 (NCS-1) can mediate desensitization of D2 dopamine receptors. Analysis of D2 receptors expressed in human embryonic kidney 293 cells indicates that NCS-1 attenuates agonist-induced receptor internalization via a mechanism that involves a reduction in D2 receptor phosphorylation. Coimmunoprecipitation experiments from striatal neurons reveal that NCS-1 is found in association with both the D2 receptor and G-protein-coupled receptor kinase 2, a regulator of D2 receptor desensitization. | SIGNOR-263964 |
P0DTC2 | Q9BYF1 | 2 | binding | down-regulates activity | 0.2 | SARS-CoV and likely SARS-CoV-2 lead to downregulation of the ACE2 receptor, but not ACE, through binding of the spike protein with ACE2. This leads to viral entry and replication, as well as severe lung injury. | SIGNOR-260742 |
P17676 | P84022 | 2 | binding | down-regulates activity | 0.597 | Thus, repression of the activity of C/EBPs by Smad3/4 at C/EBP binding sites inhibited transcription from the PPAR2 and leptin promoters | SIGNOR-250567 |
O15552 | P50148 | 2 | binding | up-regulates activity | 0.492 | 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-257188 |
Q13153 | Q13363 | 1 | phosphorylation | down-regulates activity | 0.403 | Pak1 phosphorylates ctbp selectively on ser158 within a putative regulatory loop, triggering ctbp cellular redistribution and blocking ctbp ak1 superphosphorylates ctbp and inhibits ctbp dehydrogenase activitycorepressor functions. | SIGNOR-103943 |
Q8IVM0 | P00533 | 0 | phosphorylation | down-regulates activity | 0.415 | We also detected tyrosine phosphorylation of Ymer by EGF stimulation as previously reported (Fig. 1A). Furthermore, we verified that EGF receptor-mediated tyrosine phosphorylation of Ymer is inhibited by AG1478, which is known as an EGF receptor tyrosine kinase inhibitor (Fig. 1B). A luciferase reporter assay showed that mutation of tyrosines on Ymer (YmerY217/279/304F) results in loss of the inhibitory activity for NF-kappaB signaling. | SIGNOR-262851 |
P35269 | P13984 | 2 | binding | up-regulates activity | 0.962 | Direct Interaction Between the Subunit RAP30 of Transcription Factor IIF (TFIIF) and RNA Polymerase Subunit 5, Which Contributes to the Association Between TFIIF and RNA Polymerase II. we showed that RPB5 binds RAP30 but not RAP74 and associates to TFIIF through the binding to RAP30. | SIGNOR-261180 |
Q4V328 | Q9Y3R0 | 2 | binding | up-regulates activity | 0.508 | We have identified several GRIP-associated proteins (GRASPs) that bind to distinct PDZ domains within GRIP. GRASP-1 is a neuronal rasGEF associated with GRIP and AMPA receptors in vivo. GRIP1 has seven PDZ domains, which mediate protein–protein interactions, allowing the recruitment of GRASP-1 to a large signal-transducing complex | SIGNOR-260638 |
P29317 | P20827 | 2 | binding | up-regulates | 0.937 | Ephrin-a1 binds and activates the tyrosine kinase activity of eph-a2, and has a dissociation constant of 20_30 nm | SIGNOR-56901 |
P35367 | P17252 | 0 | phosphorylation | down-regulates | 0.2 | In this study, we demonstrated that ser396 and ser398 are phosphorylated by pkc and, that phosphorylation of ser398 is particularly involved in pmainduced desensitization of the h1r. | SIGNOR-66015 |
Q96RU7 | Q13085 | 2 | binding | down-regulates quantity by destabilization | 0.274 | TRB3 appears to inhibit ACC activity by functioning as an adaptor for COP1. Taken together, these results suggest that TRB3 may promote loss of fat by mediating the COP1-dependent ubiquitination and inactivation of ACC. Taking these results together, we propose that TRB3 may protect against diet-induced obesity by stimulating fatty acid oxidation in adipose during fasting through the COP1-mediated ubiquitination and degradation of ACC (Fig. 4D). | SIGNOR-271600 |
P61586 | Q07960 | 0 | gtpase-activating protein | down-regulates activity | 0.864 | 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-260458 |
P29350 | Q14790 | 1 | dephosphorylation | up-regulates activity | 0.354 | Caspase-8 is tyrosine-phosphorylated in freshly isolated neutrophils but spontaneously dephosphorylates in culture, in association with the progression of constitutive apoptosis. Phosphorylation of caspase-8 on Tyr-310 facilitates its interaction with the Src-homology domain 2 containing tyrosine phosphatase-1 (SHP-1) and enables SHP-1 to dephosphorylate caspase-8, permitting apoptosis to proceed. The non-receptor tyrosine kinase, Lyn, can phosphorylate caspase-8 on Tyr-397 and Tyr-465, rendering it resistant to activational cleavage and inhibiting apoptosis. Exposure to lipopolysaccharide reduces SHP-1 activity and binding to caspase-8, caspase-8 activity, and rates of spontaneous apoptosis. | SIGNOR-248478 |
Q16539 | P05787 | 1 | phosphorylation | up-regulates | 0.592 | Keratin 8 (k8) serine 73 occurs within a relatively conserved type ii keratin motif ((68)nqsllspl) and becomes phosphorylated in cultured cells and organs during mitosis, cell stress, and apoptosis. Here we show that ser-73 is exclusively phosphorylated in vitro by p38 mitogen-activated protein kinase.The ser-73 --> ala-associated filament reorganization defect is rescued by a ser-73 --> asp mutation. Also, disease-causing keratin mutations can modulate keratin phosphorylation and organization, which may affect disease pathogenesis. | SIGNOR-114079 |
O15297 | Q16539 | 1 | dephosphorylation | down-regulates activity | 0.444 | Wip1 selectively inactivates p38 by specific dephosphorylation of its conserved threonine residue | SIGNOR-84793 |
P62330 | Q9NRD0 | 2 | binding | down-regulates quantity by destabilization | 0.71 | Fbx8 Is a Component of the SCF Complex and Mediates Ubiquitination of Arf6. We first examined whether Fbx8 makes a complex with Cul1, through its binding to Skp1. We expressed GST-tagged Fbx8 together with FLAG-tagged Skp1 and Myc-tagged Cul1 in Cos-7 cells and found that Myc-Cul1 is coprecipitated with GST-Fbx8 in the presence of FLAG-Skp1 (Figure 1A). | SIGNOR-271764 |
P04150 | Q14469 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.2 | HES1 binding to the promoter of the NC3C1 gene inhibits its expression and results in insufficient production of the encoded glucocorticoid receptor- rendering these cells resistant to treatment with dexamethasone | SIGNOR-251674 |
O75688 | P37231 | 1 | dephosphorylation | up-regulates activity | 0.372 | Furthermore we show that PPM1B can directly dephosphorylate PPARgamma, both in intact cells and in vitro.|In addition PPM1B increases PPARγ-mediated transcription via dephosphorylation of Ser(112).|The serine/threonine phosphatase PPM1B (PP2Cbeta) selectively modulates PPARgamma activity. | SIGNOR-277073 |
Q9UKB1 | P35222 | 2 | binding | down-regulates | 0.746 | We conclude that beta-trcp is a component of an e3 ubiquitin ligase that is responsible for the targeted degradation of phosphorylated beta-catenin. we found that the binding of beta-trcp to beta-catenin was direct. | SIGNOR-65429 |
P04626 | P00533 | 2 | binding | up-regulates | 0.613 | Although erbb-2 binds neither ligand, even in a heterodimeric receptor complex, it is the preferred heterodimer partner of the three other members, and it favors interaction with erbb-3. | SIGNOR-147838 |
Q96AP0 | O14746 | 2 | binding | up-regulates | 0.557 | We find that tpp1 and pot1 form a complex with telomeric dna that increases the activity and processivity of the human telomerase core enzyme. | SIGNOR-152321 |
O14727 | Q07817 | 2 | binding | down-regulates activity | 0.842 | These experiments demonstrate that bcl-xl associates with caspase-9 and apaf-1, and show that bcl-xl inhibits the maturation of caspase-9 mediated by apaf-1. | SIGNOR-56399 |
Q9HB96 | O14757 | 0 | phosphorylation | up-regulates | 0.716 | Chk1 directly phosphorylates the fance subunit of the fa core complex on two conserved sites (threonine 346 and serine 374). chk1-mediated phosphorylation of fance is required for the fanconi anemia/brca pathway. | SIGNOR-153023 |
O75197 | Q9ULV1 | 2 | binding | up-regulates activity | 0.704 | Here we report that Wnt receptor Frizzled (Frz) and theco-receptors LRP5 and LRP6 (LRP5/6) directly interact with each other and this interaction is regulated by the LRP6 ectodomain. | SIGNOR-258967 |
P46937 | P51955 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.2 | NEK2 promotes the migration and proliferation of ESCC via stabilization of YAP1 by phosphorylation at Thr-143 | SIGNOR-276586 |
O95071 | Q8IYW5 | 1 | ubiquitination | down-regulates quantity | 0.442 | Here, we show that TRIP12 and UBR5, two HECT domain ubiquitin E3 ligases, control accumulation of RNF168, a rate-limiting component of a pathway that ubiquitylates histones after DNA breakage. We find that RNF168 can be saturated by increasing amounts of DSBs. Depletion of TRIP12 and UBR5 allows accumulation of RNF168 to supraphysiological levels, followed by massive spreading of ubiquitin conjugates and hyperaccumulation of ubiquitin-regulated genome caretakers such as 53BP1 and BRCA1. | SIGNOR-266782 |
P40424 | O43474 | 2 | binding | up-regulates activity | 0.479 | We show that the Pbx1 and Meis2 homeodomain proteins interact with Klf4 and can be recruited to DNA elements comprising a Klf4 site or G C box, with adjacent Meis and Pbx sites. Meis2d and Pbx1a activate expression of p15(Ink4a) and E-cadherin, dependent on the Meis2d transcriptional activation domain. We suggest a model in which genes with Klf4 sites can be cooperatively activated by Meis2/Pbx1 and Klf4, dependent primarily on recruitment by Klf4. | SIGNOR-267237 |
Q92859 | O00634 | 2 | binding | up-regulates activity | 0.72 | Experiments have demonstrated that Neogenin also mediates Netrin-1 attractive functions. Both DCC and Neogenin are type I transmembrane receptors that belong to the immunoglobulin superfamily proteins. | SIGNOR-268171 |
Q9H0M0 | P36897 | 1 | ubiquitination | down-regulates | 0.533 | Similar to smurfs, wwp1 associated with smad7 and induced its nuclear export, and enhanced binding of smad7 to tgf-beta type i receptor to cause ubiquitination and degradation of the receptor. Consistent with these results, wwp1 inhibited phosphorylation of smad2 induced by tgf-beta. Wwp1 thus negatively regulates tgf-beta signaling in cooperation with smad7 | SIGNOR-126581 |
Q8TDX7 | P54274 | 1 | phosphorylation | up-regulates activity | 0.342 | Using KR-TRF2 to induce telomeric DNA damage, we found that TRF1 degradation was also exacerbated when ATM was inhibited after damage induction (55.2% of mock treated cells) (XREF_FIG), indicating that the ATM signal pathway is required for Nek7 mediated TRF1 stabilization.|We show that Nek7 phosphorylates TRF1 at Ser114 and in turn maintains stability of the shelterin complex at telomeres. | SIGNOR-278447 |
Q13315 | P54646 | 1 | phosphorylation | up-regulates activity | 0.264 | ATM phosphorylates AMPKalpha2 to induce inhibitory phosphorylation of HIPK2| | SIGNOR-275488 |
Q9HC98 | P52732 | 1 | phosphorylation | up-regulates activity | 0.444 | Nek6 phosphorylated Eg5 at several sites in vitro and one of these sites, Ser1033, is phosphorylated in vivo during mitosis. Whereas CDK1 phosphorylates nearly all Eg5 at Thr926 during mitosis, Nek6 phosphorylates approximately 3% of Eg5, primarily at the spindle poles. | SIGNOR-273886 |
P11717 | P01344 | 2 | binding | up-regulates | 0.727 | Insulin-like growth factor ii receptor (igf2r) is a multifunctional cell surface receptor implicated in tumour suppression. Its growth inhibitory activity has been associated with an ability to bind igf-ii. | SIGNOR-115250 |
Q16512 | P18669 | 1 | phosphorylation | down-regulates | 0.254 | Activated pak1 inhibits glycolysis by association of its catalytic domain with pgam-b and subsequent phosphorylation of the enzyme on serine residues 23 and 118, thereby abolishing pgam activity. | SIGNOR-91602 |
Q02750 | P32121 | 1 | phosphorylation | up-regulates activity | 0.587 | Here, we show that activation of serotonin 5-HT2C receptors, which engage Erk1/2 pathway via a _-arrestin-dependent mechanism, promotes MEK-dependent _-arrestin2 phosphorylation at Thr383 | SIGNOR-252027 |
P17544 | Q16514 | 2 | binding | up-regulates activity | 0.515 | We show that overexpression of hsTAF12 potentiates ATF7-induced transcriptional activation through direct interaction with ATF7, suggesting that TAF12 is a functional partner of ATF7. | SIGNOR-225249 |
P10415 | Q92570 | 2 | binding | down-regulates activity | 0.2 | NR4A3 physically interacted with an anti-apoptotic Bcl-2 protein hence sequestering it from blunting apoptosis. | SIGNOR-259399 |
P09471 | P21554 | 2 | binding | up-regulates activity | 0.464 | 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-257003 |
Q8IW41 | Q16659 | 0 | phosphorylation | up-regulates activity | 0.69 | ERK3, ERK4 and p38 MAPK can all phosphorylate MK5 at Thr 182 , , , - ], but it is not known whether these enzymes also can phosphorylate Ser 115 and whether this modification contributes to ERK3-, ERK4-, or p38 MAPK -regulated subcellular localization of MK5. | SIGNOR-279073 |
Q8NEG4 | P48729 | 2 | binding | up-regulates quantity | 0.2 | We identified members of the FAM83 family of proteins as partners of CK1 in cells. All eight members of the FAM83 family (FAM83A–H) interacted with the α and α-like isoforms of CK1; FAM83A, -B, -E, and -H also interacted with the δ and ε isoforms of CK1. The intrinsic catalytic activity of CK1 is not affected by or required for the association of CK1 with FAM83 proteins. Our findings imply that the DUF1669 domains of FAM83 proteins anchor CK1 α, α-like, δ, and ε isoforms in specific subcellular compartments and potentially mediate their association with substrates. | SIGNOR-273751 |
Q00341 | P38398 | 2 | binding | up-regulates activity | 0.2 | We show that vigilin interacts with the DNA damage response (DDR) proteins RAD51 and BRCA1, and vigilin depletion impairs their recruitment to DSB sites. | SIGNOR-266698 |
Q99873 | Q92804 | 1 | methylation | up-regulates | 0.431 | The methylation of taf15 by prmt1 is required for the ability of taf15 to positively regulate the expression of the studied endogenous taf15-target genes. | SIGNOR-183137 |
P24723 | P49841 | 1 | phosphorylation | down-regulates | 0.2 | Gsk3 is different from most kinases in that it is constitutively partially active and the most common regulatory mechanism is inhibition by phosphorylation of ser21 in gsk3_ or ser9 in gsk3_. This inhibitory phosphorylation can be mediated by several kinases, such as akt/protein kinase b (pkb), protein kinase c (pkc) and protein kinase a (pka). | SIGNOR-188585 |
P22674 | P24941 | 2 | binding | up-regulates activity | 0.453 | Phosphorylation of cyclin O, a novel cyclin family protein containing a cyclin-like domain, is involved in the activation of cyclin-dependent kinase 2|This activity was reduced in cells overexpressing cyclin O, in which the 81st serine had been replaced with alanine (S81A). These results suggest that cyclin O is a novel cyclin family protein that regulates CDK2 kinase activity, which is mediated by the phosphorylation of the 81st serine residue of cyclin O | SIGNOR-275616 |
Q9UM73 | P23246 | 1 | phosphorylation | down-regulates | 0.2 | Furthermore, psf was shown to be a direct substrate of purified alk kinase domain in vitro, and psf tyr293 was identified as the site of phosphorylation. Psf phosphorylation also increased its binding to rna and decreased the psf-mediated suppression of gage6 expression. | SIGNOR-155298 |
P29275 | P63092 | 2 | binding | up-regulates activity | 0.516 | 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-256767 |
Q9P227 | P63000 | 1 | gtpase-activating protein | down-regulates activity | 0.43 | 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-260480 |
Q9UQM7 | Q9P0L9 | 1 | phosphorylation | down-regulates activity | 0.2 | CaM inhibits the function of TRPP3 through promoting CaMK2's phosphorylation towards T591 on TRPP3. | SIGNOR-277812 |
Q08881 | Q8TDQ0 | 1 | phosphorylation | up-regulates activity | 0.31 | When we tested the effect of ITK on the Y265 mutant, we found a pronounced reduction of ITK-mediated tyrosine phosphorylation, suggesting that Y265 is specifically phosphorylated by ITK (Fig. 3B). Our results demonstrate that specific phosphorylation of Y265 of Tim-3 occurs in the presence of galectin-9, probably through a receptor-ligand interaction. Phosphorylation of Y265, which is situated in a highly conserved SH2 binding domain, could result in the recruitment of SH2 containing adaptor proteins and trigger downstream signalling events regulating the fate of Tim-3 expressing T-cells. | SIGNOR-273644 |
P51812 | Q14790 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.369 | The ribosomal S6 kinase 2 (RSK2) is a member of the p90 ribosomal S6 kinase (p90RSK) family of proteins and plays a critical role in proliferation, cell cycle, and cell transformation. Here, we report that RSK2 phosphorylates caspase-8, and Thr-263 was identified as a novel caspase-8 phosphorylation site. In addition, we showed that EGF induces caspase-8 ubiquitination and degradation through the proteasome pathway, and phosphorylation of Thr-263 is associated with caspase-8 stability. | SIGNOR-272997 |
Q9BUB5 | Q16539 | 0 | phosphorylation | up-regulates | 0.672 | Mnk1, but not mnk2, also binds strongly to the stress-activated kinase, p38. | SIGNOR-48346 |
Q13467 | O75581 | 2 | binding | up-regulates activity | 0.738 | Here we show that both Fz and Dvl functions are critical for Wnt-induced Lrp6 phosphorylation through Fz-Lrp6 interaction. | SIGNOR-258966 |
P57078 | P98170 | 0 | polyubiquitination | up-regulates activity | 0.333 | In this study, we report that in addition to RIP1 and RIP2, also RIP3 and RIP4 directly interact with XIAP, cIAP1 and cIAP2. When comparing the ability of these IAPs to directly conjugate RIP1–RIP4 with ubiquitin chains, we found that cIAP1 was the most effective E3 and was capable of ubiquitinating all four RIPs in the presence of the E2 component UbcH5a. On the contrary, XIAP was only capable of inducing weak ubiquitination of RIP4. | SIGNOR-272716 |
P21554 | Q03113 | 2 | binding | up-regulates activity | 0.358 | 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-257285 |
Q02156 | P61586 | 1 | phosphorylation | up-regulates activity | 0.439 | Our laboratory reported that PKCepsilon modulates RhoA activity in HNSCC presumably through posttranslation phosphorylation .|Phosphopeptide mapping revealed that PKCepsilon phosphorylates RhoA at T127 and S188. | SIGNOR-279478 |
Q14493 | Q9BTM1 | 1 | translation regulation | up-regulates quantity by expression | 0.2 | Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control. | SIGNOR-265412 |
O60469 | O00410 | 0 | relocalization | up-regulates activity | 0.2 | DSCAM and DSCAML1 specifically interacted with the importin beta IPO5, whereas deletion of the identified NLSs abolished this specific interaction and suppressed nuclear translocation of the DSCAM/L1 ICDs in cell lines and cultured neurons. This suggests a direct role of IPO5 in the nuclear import of the DSCAM/L1 ICDs. | SIGNOR-264273 |
P04150 | P35575 | 1 | transcriptional regulation | up-regulates quantity | 0.2 | Further, CRTC2 is required for the glucocorticoid-associated cooperative mRNA expression of the glucose-6-phosphatase, a rate-limiting enzyme for hepatic gluconeogenesis, by facilitating the attraction of GR and itself to its promoter region already occupied by CREB | SIGNOR-256104 |
Q13618 | Q03933 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.326 | Here we show that the PEST sequences of a short-lived protein called HSF2 interact with Cullin3, a subunit of a Cullin-RING E3 ubiquitin ligase, and that this interaction mediates the Cul3-dependent ubiquitination and degradation of HSF2 | SIGNOR-239129 |
O15111 | Q13568 | 1 | phosphorylation | down-regulates activity | 0.474 | These data indicate that in context of MyD88 signaling pathway IKKalpha suppresses IRF-5 activation.|These data showed that the IKK\u03b1 phosphorylates IRF-5 and that IKK\u03b1 mediated phosphorylation stimulates formation of IRF-5 dimers. | SIGNOR-278293 |
O75688 | Q13627 | 1 | dephosphorylation | down-regulates activity | 0.236 | In conclusion, our study demonstrates that DYRK1A autophosphorylates Ser258, the dephosphorylation target of PPM1B, and PPM1B negatively regulates DYRK1A activity.|We found that PPM1B dephosphorylates DYRK1A at Ser258, contributing to the inhibition of DYRK1A activity. | SIGNOR-277108 |
P06396 | P42574 | 0 | cleavage | down-regulates | 0.639 | Caspase-3 mediates cleavage of gelsolin, generating a fragment that severs actin filaments in an unregulated fashion. The cleavage of gelsolin causes cells to round up, detach and undergo nuclear fragmentation. | SIGNOR-51652 |
Q13541 | Q13315 | 0 | phosphorylation | down-regulates | 0.512 | Here we report that atm... phosphorylates 4e-bp1 at ser 111cells lacking atm kinase activity exhibit a significant decrease in the insulin-induced dissociation of 4e-bp1 from eif-4e. | SIGNOR-85619 |
P16112 | O75173 | 0 | cleavage | down-regulates quantity by destabilization | 0.767 | Aggrecan Degradation in Human Cartilage Evidence for both Matrix Metalloproteinase and Aggrecanase Activity in Normal, Osteoarthritic, and Rheumatoid Joints|Stromelysin-1 (MMP-3), as well as other MMPs, cleave aggrecan in the interglobular domain between Asn341 and Phe342 to generate a G1 fragment with the COOH terminus VDIPEN341 (11–13). This fragment has been isolated and identified by NH2-terminal sequence analysis from human OA cartilage (11). A second proteolytic activity identified as “aggrecanase” also cleaves aggrecan in the interglobular domain, but between Glu373 and Ala374 (19–24), generating a G1 fragment with a COOH terminus of NITEGE373 | SIGNOR-266984 |
P53779 | P45985 | 0 | phosphorylation | up-regulates | 0.744 | Two mapkks, sek1 and mkk7, synergistically activate jnk. Sek1 prefers the tyr-185 residue, and mkk7 prefers the thr-183 residue (17, 19). | SIGNOR-137605 |
O95235 | Q15173 | 0 | dephosphorylation | up-regulates activity | 0.2 | We identify MKlp2 as an essential protein for promoting abscission, which may regulate tethering and stabilizing of the PM to the microtubule cytoskeleton. Aurora B phosphorylation of MKlp2 S878 in the LAM is a key inhibitory signal for abscission. Conversely, B56-PP2A promotes abscission by opposing Aurora B phosphorylation of MKlp2 S878. | SIGNOR-262660 |
Q15746 | P31260 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Results from these experiments demonstrated that in 10T1/2 cells Hoxa10-1 increased the activity of the telokin promoter 3-fold without affecting the activity of the other promoters analyzed (Fig. 2A). Similar results were also observed in A10 SMC (data not shown). In contrast, Hoxb8 significantly repressed the activity of the telokin, smooth muscle α-actin, and SM22α promoters by 70, 50, and 70%, respectively | SIGNOR-261643 |
Q92831 | P84243 | 1 | acetylation | down-regulates activity | 0.2 | The HAT module within the SAGA and ADA complexes acetylates histone H3, mainly on residues K9 and K14. | SIGNOR-269620 |
Q9H9S0 | Q9UJQ4 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.792 | We conclude that the Nanog enhancer activity is regulated by both Sall4 and Nanog. | SIGNOR-266079 |
P43250 | O14745 | 1 | phosphorylation | down-regulates activity | 0.405 | GRK6A phosphorylates NHERF on Ser289, the primary site of constitutive phosphorylation of NHERF in HEK-293 cells. The interaction of NHERF and NHE3 is mediated by the region of NHERF encompassing the second PDZ domain and the tail (25), and it is therefore reasonable that phosphorylation of the serine-rich stretch in the center of this region (including Ser289) might affect the physical interaction of NHERF with NHE3. | SIGNOR-251214 |
P35568 | P49841 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.454 | HG activates GSK3beta, which phosphorylates IRS1 at serine 332, leading to the ubiquitination and proteasome mediated degradation of IRS1. | SIGNOR-279183 |
Q5VWQ8 | P01112 | 1 | gtpase-activating protein | down-regulates activity | 0.6 | The GAP domain of DAB2IP is homologous to other Ras-GAPs, such as GAP120 and neurofibromin (NF1), and can stimulate the GTPase activity of RAS proteins both in vitro and in cancer cell lines. DAB2IP is able to stimulate in vitro and in vivo the GTPase activity of RAS proteins (H-Ras, K-Ras, and N-Ras) facilitating GTP hydrolysis to GDP. | SIGNOR-254745 |
P43657 | 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-257004 |
P19634 | Q13464 | 0 | phosphorylation | up-regulates activity | 0.685 | We then engineered the T653A NHE1 mutant (ROCKA mutant), which can not be phosphorylated by p160ROCK.|p160ROCK has also been shown to activate NHE1 at threonine 653 , in close vicinity to the Akt phosphorylation site at serine 648. | SIGNOR-279566 |
Q00535 | P17600 | 1 | phosphorylation | up-regulates | 0.563 | Synapsin i (syni), a major sv phosphoprotein involved in the regulation of sv trafficking and neurotransmitter release, is one of the presynaptic substrates of cdk5, which phosphorylates it in its c-terminal region at ser(549) (site 6) and ser(551) (site 7). Phosphorylation of syni by cdk5 is physiologically regulated and enhances its binding to f-actin. | SIGNOR-78883 |
P10636 | P06241 | 0 | phosphorylation | down-regulates | 0.535 | In this study we determined that human tau tyr18 was phosphorylated by the src family tyrosine kinase fyn. | SIGNOR-123099 |
P61764 | Q16623 | 2 | binding | up-regulates activity | 0.922 | Munc18-1 is a neuronal protein that interacts with syntaxin 1 and is required for synaptic vesicle exocytosis. We have now identified two Munc18-1-interacting proteins called Mint1 and Mint2 that may mediate the function of Munc18-1. | SIGNOR-264042 |
Q9UBN6 | P50591 | 2 | binding | down-regulates | 0.728 | One function of trail-r4 may be inhibition of trail cytotoxicy. Dcr2 functions as an inhibitory apo2l receptor. | SIGNOR-53447 |
Q14790 | Q16539 | 0 | phosphorylation | down-regulates | 0.55 | P38-mapk can directly phosphorylate and inhibit the activities of caspase-8 | SIGNOR-122103 |
P19525 | Q9H3R0 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | In the absence of Wnt3a, protein kinase R phosphorylated KDM4C at Ser918, inducing KDM4C ubiquitination and degradation. | SIGNOR-277497 |
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