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 |
|---|---|---|---|---|---|---|---|
Q08050 | P35222 | 2 | binding | up-regulates activity | 0.519 | Nuclear FoxM1 then directly interacted with nuclear β‐catenin, which released β‐catenin from ICAT and enhanced recruitment of β‐catenin to the promoter of Wnt target gene, hence increasing the expression of Wnt target gene. | SIGNOR-277211 |
Q6NXT2 | Q92830 | 0 | 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-269608 |
P06493 | P60891 | 1 | phosphorylation | up-regulates activity | 0.254 | CDK1 contributes to upregulation of PRPS1 activity by phosphorylating PRPS1 at S103|In conclusion, compared with upregulation of PRPS1 expression levels, increased PRPS1 activity, which is marked by S103 phosphorylation | SIGNOR-265728 |
Q9H2X6 | Q8IUQ4 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.514 | Here we demonstrate that HIPK2 is an unstable protein that colocalizes and interacts with the E3 ubiquitin ligase Siah-1 in unstressed cells. Siah-1 knockdown increases HIPK2 stability and steady-state levels, whereas Siah-1 expression facilitates HIPK2 polyubiquitination, degradation and thereby inactivation. | SIGNOR-276166 |
P04150 | P49841 | 0 | phosphorylation | down-regulates activity | 0.54 | We found hormone-dependent GR phosphorylation on serine 404 by GSK-3beta [ ]Cells expressing a GR that is incapable of GSK-3beta phosphorylation had a redirection of the global transcriptional response to hormone, including the activation of additional signaling pathways, in part due to the altered ability of unphosphorylatable GR to recruit transcriptional cofactors CBP/p300 and the p65 (RelA) subunit of NF-kappaB | SIGNOR-181541 |
P45983 | Q12904 | 1 | phosphorylation | down-regulates | 0.473 | We further demonstrated that serine-140 residue of aimp1 was phosphorylated by jnk and alanine mutation of serine-140 suppressed lps-induced cell surface altogether, these results suggest that aimp1 is phosphorylated by jnk through tlr-myd88 pathway and lose the regulatory activity for er retention of gp96expression of gp96. | SIGNOR-165763 |
Q9BZL6 | Q9UBF8 | 1 | phosphorylation | up-regulates | 0.2 | Binding of 14-3-3 proteins to pi4kiiibeta involved the pkd phosphorylation site ser294, evident from reduced 14-3-3 binding to a s294a pi4kiiibeta mutant. Phospho-specific binding of 14-3-3 proteins to phosphatidylinositol 4-kinase iii beta protects from dephosphorylation and stabilizes lipid kinase activity. | SIGNOR-148880 |
Q8IW41 | P31152 | 2 | phosphorylation | up-regulates | 0.63 | This is due to mk5-dependent phosphorylation and only this retarded erk4 species is both phosphorylated on ser(186) and co-immunoprecipitates with wild-type mk5. We conclude that binding between erk4 and mk5 facilitates phosphorylation of ser(186) and stabilization of the erk4-mk5 complex. | SIGNOR-17069 |
P63162 | Q86YT6 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.2 | These data indicate that Mib1 reduces SMN protein stability by targeting it for degradation by the proteasome and represents a new modifier of the SMA phenotype.|Through this study, we provide evidence that the E3 ligase Mib1 ubiquitinates and catalyzes SMN protein degradation. | SIGNOR-278632 |
P10636 | Q9BXM7 | 0 | phosphorylation | down-regulates activity | 0.384 | Simultaneously overexpressing PINK1 significantly reduced the levels of exogenous total and phosphorylated tau proteins (Figures 4A,B,E).|Taken together, our data revealed that PINK1 overexpression promoted degradation of abnormal accumulated tau via the autophagy-lysosome pathway, indicating that PINK1 may be a potential target for AD treatment. | SIGNOR-279250 |
Q9UKX5 | Q02447 | 0 | null | up-regulates quantity by expression | 0.2 | We speculate that the "mesenchymal signature" of alpha11 integrin gene expression is controlled by the activity of Sp1/Sp3, fibroblast-specific combinations of Ets family members and yet unidentified enhancer-binding transcription factors. | SIGNOR-253351 |
P55210 | P09874 | 1 | cleavage | down-regulates | 0.719 | Caspase-7 cleaves parp;redundancy exists between the caspase-3 and -7 at the level of parp proteolysis. | SIGNOR-83703 |
P08833 | P17483 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | These data showed that Hox genes selectively activate the transcription of theIGFBP-1 | SIGNOR-261636 |
Q5JU85 | P42263 | 1 | relocalization | up-regulates quantity | 0.2 | BRAG1 increases the synaptic recycling pool of AMPARs.these data suggest that the BRAG1 enhancement of AMPAR transmission is mediated by the increased expression of the recycling pool of synaptic GluA2/3 receptors. | SIGNOR-264914 |
P47712 | P17252 | 0 | phosphorylation | up-regulates | 0.564 | Pkcalfa, but not pkcbeta, is the predominant cpkc isoenzyme required for cpla2 protein phosphorylation and maximal induction of cpla2 enzymatic activity. | SIGNOR-149406 |
O60674 | P24394 | 0 | phosphorylation | up-regulates activity | 0.624 | Downstream intracellular signaling from the IL-4IL-4Rc complex involves activation of the Jak1 and Jak3 kinases, phosphorylation of the Stat6 transcription factor, and activation of the insulin receptor substrate (IRS)-2 and Dok2-signaling intermediates. IL-13 initially binds to IL-13R1 with intermediate affinity, and then heterodimerizes with IL-4R. The IL-13IL-13R1IL-4R complex activates the Tyk2, Jak2, and Jak1 kinases and Stat6. | SIGNOR-249530 |
P50222 | Q8N5U6 | 2 | binding | up-regulates activity | 0.375 | RFN10 co-immunoprecipitates with MEOX2. RNF10 potentiates MEOX2 transcriptional activation | SIGNOR-236968 |
Q16512 | Q12778 | 1 | phosphorylation | down-regulates | 0.2 | Furthermore, estrogen induced phosphorylation and perinuclear localization of the cell survival forkhead transcription factor fkhr in the cytoplasm in a pak1-dependent manner. In addition, pak1 directly interacted with fkhr and phosphorylated it. The noticed phosphorylation-dependent exclusion of fkhr from the nucleus impaired the ability of fkhr to activate its target fas ligand promoter containing the fkhr binding motif (fre) in cells treated with estrogen or expressing catalytically active pak1. | SIGNOR-97882 |
Q5JTC6 | P35222 | 2 | binding | down-regulates activity | 0.776 | We show that Amer1 binds directly to beta-catenin via a novel interaction motif, the REA repeats. This amino acid motif, including the core sequence arginine, glutamic acid and alanine, and this REA repeats mediate binding of Amer1 to the armadillo repeats of beta-catenin. The data suggest that Amer1 exerts its negative regulatory role in Wnt signaling by acting as a scaffold protein for the beta-catenin destruction complex and promoting stabilization of Axin at the plasma membrane. | SIGNOR-217950 |
P63096 | P50406 | 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-257073 |
O75151 | Q16695 | 1 | demethylation | down-regulates activity | 0.2 | PHF2, a jmjC demethylase, is enzymatically inactive by itself, but becomes an active H3K9Me2 demethylase through PKA-mediated phosphorylation. This modification leads to targeting of the PHF2–ARID5B complex to its target promoters, where it removes the repressive H3K9Me2 mark. | SIGNOR-264520 |
P27694 | Q9BX63 | 2 | binding | up-regulates activity | 0.696 | Our data are consistent with a model in which FANCJ associates with RPA in a DNA damage-inducible manner and through the protein interaction RPA stimulates FANCJ helicase to better unwind duplex DNA substrates. These findings identify RPA as the first regulatory partner of FANCJ. | SIGNOR-259187 |
P98177 | Q13043 | 0 | phosphorylation | up-regulates | 0.427 | The other major signaling modules that directly regulate the activity of the foxo factors include the stress-activated jun-n-terminal kinase (jnk), the mammalian ortholog of the ste20-like protein kinase (mst1), and the deacetylase sirt1 | SIGNOR-178193 |
P15173 | O43257 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.259 | We show that the srcap subunit named znhit1 or p18hamlet, which is a substrate of p38 mapk, is recruited to the myogenin promoter at the onset of muscle differentiation, in a p38 mapk-dependent manner. We also show that p18hamlet is required for h2a.z accumulation into this genomic region and for subsequent muscle gene transcriptional activation. | SIGNOR-165613 |
Q15139 | O94768 | 1 | phosphorylation | up-regulates activity | 0.252 | Coexpression of DRAK2 and a constitutively active PKD mutant (CA-PKD1; PKD1-S738/742E) were sufficient to greatly enhance DRAK2 autophosphorylation, supporting the hypothesis that PKD catalytic activity promotes DRAK2 function.|We note that PKD was able to phosphorylate DRAK2 outside of its C terminus, suggesting that PKD mediated phosphorylation occurs on a site in the 1-290 fragment of DRAK2. | SIGNOR-279753 |
O15379 | Q01094 | 2 | binding | up-regulates | 0.496 | Furthermore, smad7 caused hdac-1 bind to e2f-1 to form a ternary complex on chromosomal dna containing an e2f-binding motif and leading to repression in the activity of the e2f target genes. | SIGNOR-199961 |
P62714 | Q9Y243 | 1 | dephosphorylation | down-regulates activity | 0.494 | Overexpression of BTBD10 increased phosphorylation levels of Akts at both Thr(308) and Ser(473) while the reduction of the endogenous BTBD10 level resulted in a decrease in the phosphorylation levels of Akts. In vitro analysis indicated that BTBD10 bound to protein phosphatase 2A (PP2A) and inhibited dephosphorylation of Akts by PP2A. | SIGNOR-248611 |
O95837 | P41595 | 2 | binding | up-regulates activity | 0.435 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-257228 |
P49841 | Q969R2 | 1 | phosphorylation | up-regulates activity | 0.2 | CK1a1, JNK1 and CDK1 had the highest site-specific activity for ORP4L, while CDK1, GSK3a, CK1a1 and GSK3b showed the highest specificity for the site when corrected for background activity with ORP4L-S4A. Because of the complexity of the serine/proline-rich site, we did not determine which serine(s) in ORP4L were phosphorylated by candidate kinases.|We conclude that phosphorylation of a unique serine/proline motif in the ORD induces a conformation change in ORP4L that enhances interaction with vimentin and cholesterol extraction from membranes. | SIGNOR-264874 |
O14965 | P49841 | 2 | phosphorylation | down-regulates activity | 0.559 | The recombinant human AURKA protein phosphorylated the GSK-3beta protein at Ser 9 in a concentration-dependent manner, in vitro. | SIGNOR-279357 |
P55286 | Q14653 | 1 | transcriptional regulation | up-regulates quantity | 0.2 | CHD8 binds to histone H3 di- and trimethylated on lysine 4. It resides on the human U6 promoter as well as the mRNA IRF3 promoter in vivo and contributes to efficient transcription from both these promoters | SIGNOR-266898 |
P10915 | P09237 | 0 | cleavage | down-regulates quantity by destabilization | 0.322 | Matrix metalloproteinases cleave at two distinct sites on human cartilage link protein. Sequencing studies of modified link protein components revealed that stromelysins-1 and -2, gelatinases A and B and collagenase cleaved specifically between His16 and Ile17, and matrilysin, stromelysin-2 and gelatinase A cleaved between Leu25 and Leu26. Based on previously determined in situ cleavage sites it is evident that matrix metalloproteinases are not solely responsible for the accumulation of link protein degradation products in adult human cartilage, indicating that additional proteolytic agents are involved in the normal catabolism of human cartilage matrix. | SIGNOR-256329 |
Q16665 | P28482 | 0 | phosphorylation | up-regulates | 0.586 | We show that at least two different nuclear protein kinases, one of them identified as p42/p44 mapk, can modify hif-1_. Analysis of in vitro phosphorylated hif-1_ by mass spectroscopy revealed residues ser-641 and ser-643 as possible mapk phosphorylation sites these data suggest that phosphorylation of ser-641/643 by mapk promotes the nuclear accumulation and transcriptional activity of hif-1_ | SIGNOR-178723 |
Q16539 | P40763 | 1 | phosphorylation | up-regulates | 0.621 | All stats are phosphorylated on at least one serine residue in their tad specifically, ser727 in stats 1 and 3 and ser721 in stat4. Stat serine kinases have been identified through the use of inhibitors, dominant-negative alleles, and in vitro kinase assays. They include mapk (p38mapk: stats 1, 3, 4;erk: stat3, 5;jnk: stat3), pkc_ (stat1, stat3), mtor (stat3), nlk (stat3 (42)), and camkii and ikk_ (stat1 (39, 40, 43)).STAT Serine phosphorylation regulates transcriptional activity (see below). | SIGNOR-154783 |
O95398 | P25098 | 0 | phosphorylation | down-regulates activity | 0.2 | The observation that GRK2 co-immunoprecipitates with Epac1 suggests a direct association between GRK2 and Epac1 in DRGs. xref A detailed study of the influence of GRK2 on the Epac1 level found that phosphorylation of ser108 in Epac1 by GRK2 can lead to a reduction of Epac1 activation. xref Downstream consequence of a reduction of GRK2 was explored. xref Low GRK2 expression in GRK2(\u00b1) DRGs was found to facilitate CPT-induced Rap1 activation and increase the phosphorylated ERK1/2 level. | SIGNOR-280001 |
Q92542 | P49810 | 2 | binding | up-regulates | 0.941 | Nicastrin, a transmembrane glycoprotein, forms high molecular weight complexes with presenilin 1 and presenilin 2. | SIGNOR-81936 |
O00311 | P33991 | 1 | phosphorylation | up-regulates | 0.958 | Activation of the eukaryotic replicative dna helicase, the mcm2-7 complex, requires phosphorylation by cdc7/dbf4 (dbf4-dependent kinase or ddk), which, in turn, depends on prior phosphorylation of mcm2-7 by an unknown kinase (or kinases).we propose that the resulting mec1 modification of mcm4 and mcm6 further activates ddk phosphorylation of mcm2-7 ( fig. 7aii ). | SIGNOR-169453 |
P62745 | P52306 | 2 | binding | up-regulates | 0.279 | Smggds has been previously shown to activate a wide variety of small gtpases, including the ras family members rap1a, rap1b, and k-ras, as well as the rho family members cdc42, rac1, rac2, rhoa, and rhob | SIGNOR-171615 |
Q8N2C7 | Q9P2D8 | 2 | binding | up-regulates activity | 0.803 | The NALCN complex in the brain consists of NALCN, UNC80 and UNC79. UNC80 directly associates with NALCN and UNC79 forms part of the complex by its interaction with UNC80. | SIGNOR-265183 |
P53675 | Q13492 | 2 | binding | up-regulates | 0.729 | Calm interacts with the clathrin heavy chain through its c-terminal third and with phophoinositides through its ap180 n-terminal homology (anth) domain, promoting assembly of clathrin triskelia into clathrin cagesin vitro | SIGNOR-144733 |
P38936 | O60260 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.2 | Next, we defined whether pJNK is involved in parkin mediated p21 degradation.|Parkin ubiquitinates p21 in vivo and in vitro in an E3 ligase-substrate dependent manner. | SIGNOR-278640 |
P29597 | P29597 | 2 | phosphorylation | up-regulates activity | 0.2 | These results indicate that tyk2 is activated by phosphorylation on tyr-1054 and/or tyr-1055The K930R mutant, bearing a mutation in the ATP binding site, is catalytically inactive (Fig. 3B, lanes 5 and 6). This protein is not basally phosphorylated, while the wt and the Y1054F/Y1055F proteins are (Fig. 3A), suggesting that autophosphorylation is responsible for the basal level of phosphorylation. | SIGNOR-43092 |
Q13283 | O95786 | 2 | binding | down-regulates activity | 0.338 | G3BP1 binds RIG-I and that this interaction involves the C-terminal RGG domain of G3BP1, G3BP1 significantly enhances RIG-I-induced ifn-b mRNA synthesis. | SIGNOR-260980 |
P17948 | Q12913 | 0 | dephosphorylation | down-regulates | 0.362 | Vegf acts by binding to two high affinity receptor tyrosine kinases: vegf receptor (vegfr)* 1 also called flt-1, and vegfr-2, also called flk-1/kdr a dominant-negative mutant of high cell densityenhanced ptp 1 (dep-1)//cd148 as well as reduction of its expression by rna interference partially restore vegfr-2 phosphorylation and map kinase activation. | SIGNOR-101272 |
P29323 | P20936 | 2 | binding | up-regulates | 0.576 | We have localized an in vitro rasgap-binding site to conserved tyrosine residues y604 and y610 in the juxtamembrane region of ephb2, and demonstrated that substitution of these amino acids abolishes ephrin-b1-induced signalling events in ephb2-expressing ng108-15 cells. | SIGNOR-50100 |
Q9P2N7 | Q96GD4 | 2 | binding | up-regulates activity | 0.742 | Aurora B Interacts with the Cul3 Complex during Mitosis and Is Ubiquitylated in a Cul3-Dependent Manner In Vivo and In Vitro. our results suggest that Cul3/KLHL9/KLHL13 activity is required to remove the chromosomal passenger protein Aurora B from mitotic chromosomes, and that Aurora B is ubiquitylated in vivo and in vitro in a KLHL9/13-dependent manner. We conclude that the Cul3/KLHL9/KLHL13 E3 ligase is an important cell-cycle regulator which, in addition to the anaphase-promoting complex (APC), coordinates mitotic progression and completion of cytokinesis. | SIGNOR-271657 |
Q13316 | Q8IXL6 | 0 | phosphorylation | up-regulates quantity | 0.659 | Fam20c knockdown decreased Dmp1 mRNA and increased Fgf23 mRNA in UMR-106 cells.|Relative migration distances of OPN and DMP1, which were the ratio of the migration distances of OPN or DMP1 co-expressed with mutant FAM20C to that with WT FAM20C, showed that only WT FAM20C could fully phosphorylate OPN and DMP1. | SIGNOR-280011 |
P49448 | Q9Y6E7 | 0 | glycosylation | down-regulates activity | 0.508 | We show that SIRT4 is a mitochondrial enzyme that uses NAD to ADP-ribosylate and downregulate glutamate dehydrogenase (GDH) activity. | SIGNOR-268559 |
P54132 | P49841 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.259 | We now provide evidence that BLM undergoes K48-linked ubiquitylation and subsequent degradation during mitosis due to the E3 ligase, Fbw7α. Fbw7α carries out its function after GSK3β- and CDK2/cyclin A2-dependent phosphorylation events on Thr171 and Ser175 of BLM which lies within a well-defined phosphodegron, a sequence which is conserved in all primates. | SIGNOR-276906 |
P31947 | P45984 | 0 | phosphorylation | down-regulates | 0.2 | Jnk phosphorylates 14-3-3zeta_ at ser-184 and 14-3-3sigma_ at ser-189 | SIGNOR-124027 |
Q8IZP0 | Q96EV8 | 2 | binding | up-regulates activity | 0.353 | Dysbindin-1, WAVE2 and Abi-1 form a complex that regulates dendritic spine formation. Although dysbindin-1, WAVE2 and Abi-1 form a ternary complex, dysbindin-1 promoted the binding of WAVE2 to Abi-1. | SIGNOR-265660 |
P20248 | P24941 | 0 | phosphorylation | up-regulates | 0.977 | Here we present evidence from in vitro and in vivo assay systems that the degradation of human cyclin a can be inhibited by kinase-inactive mutants of cdk2 and cdc2cdk2 can phosphorylate cyclin a on ser-154 | SIGNOR-74466 |
Q96PU5 | P51795 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.292 | The presence of albumin triggers the formation of an endocytic complex that includes ClC-5. (iii) Nedd4-2 is recruited to this complex and ubiquitinates ClC-5. This ubiquitination by Nedd4-2 shunts ClC-5 into the albumin uptake/degradative pathway. | SIGNOR-272665 |
P63000 | Q8IVF5 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.589 | 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-260578 |
Q53GL7 | P53350 | 0 | phosphorylation | up-regulates activity | 0.2 | PLK1, an important regulator for cell mitosis, directly interacts with and phosphorylates PARP10 at T601. PARP10 phosphorylation at T601 significantly decreases its binding to NEMO and disrupts its inhibition to NEMO ubiquitination, thereby enhancing the transcription activity of NF-κB toward multiple target genes and promoting HCC development. | SIGNOR-273728 |
Q96LB1 | P50148 | 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-257385 |
P21579 | Q7L0J3 | 2 | binding | up-regulates quantity | 0.535 | Recent studies have revealed that sybII and synaptotagmin-1 interact with other SV cargoes to ensure a high fidelity of retrieval. These cargoes are synaptophysin (for sybII) and SV2A (for synaptotagmin-1). SV2A Acts as an iTRAP to Direct Synaptotagmin-1 Retrieval to SVs. | SIGNOR-264116 |
Q8WW43 | Q9NZ42 | 2 | binding | up-regulates | 0.942 | Furthermore, overexpression of aph-1 facilitates pen-2-mediated ps1 proteolysis, resulting in a significant increase in ps1 fragments. Our data reveal a direct role of pen-2 in proteolytic cleavage of ps1 and a regulatory function of aph-1, in coordination with pen-2, in the biogenesis of the ps1 complex. | SIGNOR-97110 |
Q14CB8 | P61586 | 1 | gtpase-activating protein | down-regulates activity | 0.568 | 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-260471 |
Q7Z628 | P61586 | 1 | guanine nucleotide exchange factor | up-regulates activity | 0.832 | 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-260561 |
P11387 | P68400 | 0 | phosphorylation | up-regulates activity | 0.383 | In vitro kinase assays demonstrated that Ser(10) can be phosphorylated by casein kinase II, Ser(21) can be phosphorylated by protein kinase Calpha, and Ser(112) and Ser(394) can be phosphorylated by Cdk1.Collectively these results indicate that topo I is phosphorylated during mitosis at multiple sites, one of which enhances DNA relaxation activity in vitro and interaction with DNA in cells. | SIGNOR-276155 |
P54646 | P05549 | 1 | phosphorylation | up-regulates activity | 0.307 | Inhibition of AMPKalpha2 with either siRNA or compound C significantly suppressed the AngII- or nicotine enhanced AP-2alpha activity and the binding of AP-2alpha to DNA.|We report that nicotine, a major component of cigarette smoke, activates AMPK in VSMCs and that AMPKalpha2 phosphorylates AP-2alpha at serine 219 resulting in aberrant expression of MMP2 and consequent AAA formation. | SIGNOR-279648 |
Q9Y5H9 | Q9Y5G1 | 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-265685 |
P51812 | Q14934 | 1 | phosphorylation | up-regulates | 0.385 | The results indicated that rsk2 phosphorylated two additional sites at ser289 (peptide 2) and ser344 (peptide 3)rsk2 induced nuclear localization of nfat3. Rsk2 phosphorylated nfat3 in vitro (km=3.559 microm), and activation of nfat3 by rsk2 enhanced the promoter activity of nfat3 downstream target genes in vivo. | SIGNOR-234473 |
Q13370 | P31749 | 0 | phosphorylation | up-regulates | 0.687 | Pde3b is a physiological substrate of akt and that akt-mediated phosphorylation of pde3b on serine-273 is important for insulin-induced activation of pde3b. | SIGNOR-252583 |
Q96IZ0 | P0C2W1 | 2 | binding | down-regulates quantity by destabilization | 0.381 | Fbxo45 interacts with Par-4 in the cytoplasm and mediates its ubiquitylation and proteasomal degradation. Fbxo45 silencing results in stabilization of Par-4 with increased apoptosis.Fbxo45 forms an atypical ubiquitin ligase complex that contains Skp1 and the Ring-finger protein PAM (protein-associated with myc) also known as MYCBP2 (myc-binding protein 2). | SIGNOR-272223 |
O15409 | O15409 | 2 | binding | up-regulates activity | 0.2 | Our studies also reveal that the FOXP2 forkhead domain can form a domain-swapped dimer. The most surprising finding from these studies is that the FOXP2 forkhead domain can form a domain-swapped dimer. Disease-related mutations, sequence comparison, and biochemical analyses argue strongly that this domain swapping is a physiologically relevant function evolved in the P branch of FOX proteins. | SIGNOR-225738 |
Q01995 | Q05655 | 0 | phosphorylation | down-regulates activity | 0.327 | Of the three consensus protein kinase C or casein kinase II phosphorylation sites in SM22, only Ser-181 was readily phosphorylated by protein kinase C in vitro, and such phosphorylation greatly decreased actin binding. | SIGNOR-249061 |
Q8N5B7 | P68400 | 0 | phosphorylation | up-regulates activity | 0.2 | Most of the phosphorylated residues conformed to a consensus motif for phosphorylation by casein kinase 2 (CK2), and treatment of cells with the CK2-specific inhibitor CX-4945 lowered the phosphorylation levels of CERS2, -4, -5, and -6. Phosphorylation of CERS2 was especially important for its catalytic activity, acting mainly by increasing itsVmaxvalue. | SIGNOR-273987 |
P25490 | P46531 | 2 | binding | down-regulates activity | 0.623 | Taken together, these results indicate that transcription factor YY1 may modulate Notch signaling via association with the high molecular weight Notch complex [..] both YY1 and N1IC were present in a large complex of the nucleus to suppress the luciferase reporter activity transactivated by Notch signaling. | SIGNOR-251654 |
Q9UQQ2 | P06239 | 0 | phosphorylation | up-regulates | 0.569 | In vitro tyrosine phosphorylation of lnk by lck and zap-70. Tyrosine 297 would appear to be an attractive target for phosphorylation within the c-terminal domain. Our studies suggest that although lnk may participate in tcr signaling, its functions are in no way limiting during t cell development or activation. | SIGNOR-48850 |
P19793 | P10826 | 2 | binding | up-regulates | 0.682 | Here we report that the transcriptional activity of rar and rxr can be reciprocally modulated by direct interactions between the two proteins | SIGNOR-16668 |
Q9UBK2 | Q969K3 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.319 | Mechanistically, PGC1α was phosphorylated at serine (S) 636 by DNA-dependent protein kinase in response to irradiation. Phosphorylation at S636 promoted the degradation of PGC1α by facilitating its binding to the E3 ligase RNF34. | SIGNOR-277912 |
Q14247 | Q15139 | 0 | phosphorylation | down-regulates | 0.421 | Pkd phosphorylates cortactin in vitro and in vivo at serine 298 thereby generating a 14-3-3 binding motif. In vitro, a phosphorylation-deficient cortactin-s298a protein accelerated vca-arp-cortactin-mediated synergistic actin polymerization and showed reduced f-actin binding | SIGNOR-164756 |
O96014 | Q9NPG1 | 2 | binding | up-regulates activity | 0.656 | Human wnt5a, wnt5b and wnt11 are non-canonical wnt ligands transducing pcp signals through fzd3 or fzd6 receptors. | SIGNOR-141428 |
Q00987 | P31751 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.56 | Mitogen-induced activation of phosphatidylinositol 3-kinase (pi3-kinase) and its downstream target, the akt/pkb serine-threonine kinase, results in phosphorylation of mdm2 on serine 166 and serine 186. Phosphorylation on these sites is necessary for translocation of mdm2 from the cytoplasm into the nucleus.. Both akt expression and serum treatment induced phosphorylation of mdm2 at ser186. | SIGNOR-109732 |
P49841 | P17676 | 1 | phosphorylation | up-regulates activity | 0.457 | We found that expression of srebf1a depended on GSK3β activity and that GSK3β activity was necessary for C/EBPβ phosphorylation at Thr188 | SIGNOR-251644 |
Q96A98 | P49190 | 2 | binding | up-regulates | 0.763 | Subsequent efforts led to the isolation and definition of the primary structure of a novel peptide, referred to as tip39, from bovine hypothalamus and the synthetic peptide was shown to efficiently activate human, rat, and zebrafish pth2 receptors | SIGNOR-115124 |
Q14164 | Q12933 | 1 | phosphorylation | up-regulates activity | 0.686 | IKKepsilon phosphorylates TRAF2 at Ser11 to activate NF-kappaB and promote malignant transformation. | SIGNOR-279195 |
P34925 | Q9NZ42 | 0 | cleavage | up-regulates | 0.2 | Ryk activity is modulated through cleavage of its icd by gamma-secretase | SIGNOR-182145 |
P16220 | 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-256105 |
Q15645 | Q15013 | 2 | binding | up-regulates activity | 0.47 | We have indeed showed that TRIP13 action to disassemble the Cdc20–Mad2 complex requires the presence of p31comet (Fig. 3A). We furthermore found that the joint action of TRIP13 and p31comet is also required for the release of Mad2 from MCC, for the complete disassembly of MCC and for relieving APC/C from checkpoint inhibition (Figs. 3 and and4).4). | SIGNOR-265971 |
Q15831 | P17612 | 0 | phosphorylation | up-regulates activity | 0.502 | Phosphorylation of the protein kinase mutated in Peutz-Jeghers cancer syndrome, LKB1/STK11, at Ser431 by p90(RSK) and cAMP-dependent protein kinase, but not its farnesylation at Cys(433), is essential for LKB1 to suppress cell growth. | SIGNOR-250055 |
Q4V328 | P45983 | 2 | binding | up-regulates activity | 0.311 | To examine whether GRASP‐1 interacts with MEKK1 and JNK1 in neurons, co‐immunoprecipitation experiments were performed with detergent‐solubilized extracts from cultured cortical neurons. Both antiJNK1 and anti‐MEKK1 antibodies immunoprecipitated GRASP‐1 from neuronal lysates. These results suggest that GRASP‐1 interacts with MEKK1 and JNK1 in neurons. GRASP-1 potently activates JNK pathway signaling, with no effect on ERK signaling. Such JNK pathway activating activity requires binding of GRASP-1 to both JNK and the upstream JNK pathway activator MEKK-1. | SIGNOR-260639 |
Q15418 | P46527 | 1 | phosphorylation | up-regulates activity | 0.393 | As for other PI3K effectors, RSK1 phosphorylates p27 at T198.|RSK1 overexpression increases p27pT198, p27-cyclin D1-Cdk4 complexes, and p27 stability. | SIGNOR-279653 |
P24530 | P50148 | 2 | binding | up-regulates activity | 0.577 | 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-257379 |
P31785 | P52333 | 2 | binding | up-regulates | 0.746 | Jak3 is associated with the ?c20,21. Cytokine binding mediates the trans-phosphorylation of receptor associated jak kinases, which in turn phosphorylate tyrosine residues on the receptors themselves. The receptor phosphotyrosines serve as docking sites for sh2 domain proteins including the stat family of transcription factors which are activated by jak-mediated phosphorylation. | SIGNOR-178491 |
P55211 | Q05513 | 0 | phosphorylation | down-regulates | 0.348 | Inhibitor sensitivity and interactions with caspase 9 indicate that the predominant kinase that targets ser144 is the atypical protein kinase c isoform zeta (pkczeta). | SIGNOR-141629 |
P08069 | P42345 | 0 | phosphorylation | up-regulates activity | 0.494 | Both recombinant mTOR and immunoprecipitated mTORC2 phosphorylate IGF-IR and InsR on Tyr1131/1136 and Tyr1146/1151, respectively.|Here we show that mTOR possesses unexpected tyrosine kinase activity and activates IGF-IR/InsR. | SIGNOR-280044 |
P29474 | Q05513 | 0 | phosphorylation | down-regulates activity | 0.371 | 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-251637 |
P55316 | Q9UGL1 | 2 | binding | up-regulates activity | 0.403 | Human PLU-1 Has transcriptional repression properties and interacts with the developmental transcription factors BF-1 and PAX9. In a reporter assay system, PLU-1 has potent transcriptional repression activity. BF-1 and PAX9 also represses transcription in the same assay, but co-expression of PLU-1 with BF-1 or PAX9 significantly enhances this repression | SIGNOR-223878 |
Q9HDB5 | Q14118 | 2 | binding | up-regulates activity | 0.2 | The DGC is potentially recruited to the postsynaptic membrane though a direct neurexin–dystroglycan interaction and an indirect interaction with NL2 via the synaptic scaffolding protein S-SCAM. | SIGNOR-265462 |
Q9Y251 | P18146 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.37 | Promoter CpG hypomethylation and transcription factor EGR1 hyperactivate heparanase expression in bladder cancer. | SIGNOR-254267 |
P17612 | Q9NP97 | 1 | phosphorylation | up-regulates | 0.2 | Our results show that km23-1 is required for camp-responsive element (cre) transcriptional activation by tgf_, with s73-km23-1 being required for the cre-dependent tgf_ stimulation of fibronectin (fn) transcription. | SIGNOR-200456 |
P17612 | Q9NS28 | 1 | phosphorylation | up-regulates activity | 0.2 | Cyclic AMP- and cyclic GMP-dependent kinases (PKA, PKG) inhibit the interaction of RGS18 and 14-3-3 by phosphorylating S216. | SIGNOR-273786 |
P53350 | Q15013 | 1 | phosphorylation | down-regulates activity | 0.41 | Purified Plk1 bound to p31comet and phosphorylated it, resulting in the suppression of its activity (with TRIP13) to disassemble checkpoint complexes. We conclude that Plk1 phosphorylates p31 on S102 and on five additional sites. The phosphorylation of the additional sites was possibly not detectable in HeLa cell extracts due to the opposing action of protein phosphatases. | SIGNOR-265970 |
Q86UR1 | P04637 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.26 | As a transcription factor, p53 induces several pro-apoptotic Bcl-2 members including Bax, Puma, Noxa and Bid, and represses the transcription of certain anti-apoptotic genes, including those encoding Bcl-2, Bcl-xL and survivin 3_and_5. | SIGNOR-209687 |
P09471 | P43657 | 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 |
P24530 | P05305 | 2 | binding | up-regulates | 0.946 | Endothelin-1 (et-1) and angiotensin ii (angii), two potent vasoactive peptides involved in the regulation of cardiovascular homeostasis, also induce mitogenic and pro-angiogenic responses in vitro and in vivo. Both peptides are produced by cleavage of inactive precursors by metalloproteases (endothelin-converting enzyme and angiotensin-converting enzyme, respectively) and activate two subtypes of membrane receptors (eta-r and etb-r for et-1, at1r and at2r for angii) that all belong to the superfamily of g-protein coupled receptors. | SIGNOR-145762 |
Q8IY67 | P26599 | 2 | binding | up-regulates activity | 0.493 | Raver1 was identified in two-hybrid screens by its interactions with the cytoskeletal proteins actinin and vinculin, and was also found to interact with PTB || Here we show that raver1 is able to promote the smooth muscle-specific alternative splicing of TM by enhancing PTB-mediated repression of exon 3. This suggests a novel mechanism for PTB-mediated splicing repression involving recruitment of raver1 as a potent splicing co-repressor. | SIGNOR-272475 |
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