IdA stringlengths 6 21 | IdB stringlengths 6 21 | labels float64 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 |
|---|---|---|---|---|---|---|---|
Q13464 | Q2V2M9 | 1 | phosphorylation | up-regulates activity | 0.275 | In addition we were able to throw light on the mechanism of activation of FHOD3 by ROCK1 and could demonstrate the effects of constitutively active FHOD3 on actin filament synthesis in cardiomyocytes.|ROCK1 can directly phosphorylate FHOD3 and FHOD3 seems to be the downstream mediator of the exaggerated actin filament formation phenotype that is induced in cardiomyocytes upon the overexpression of constitutively active ROCK1. | SIGNOR-278903 |
Q13131 | Q9NR19 | 1 | phosphorylation | up-regulates activity | 0.275 | This translocation is mediated by AMP-activated protein kinase (AMPK)-dependent ACSS2 Ser659 phosphorylation and subsequent exposure of the nuclear localization signal of ACSS2 to KPNA1/importin α5 for binding. In the nucleus, ACSS2 forms a complex with TFEB (transcription factor EB) and utilizes the acetate generated from histone deacetylation to locally produce acetyl-CoA for histone acetylation in the promoter regions of TFEB target genes. | SIGNOR-271822 |
O15550 | P31268 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.275 | 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-260024 |
P0DP23 | Q12756 | 1 | 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 |
P18846 | P18146 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.275 | Phosphorylated CREB and ATF1 then bind to the CRE of the egr-1 promoter and cause a stress-dependent transcriptional activation of this gene. | SIGNOR-271686 |
Q9Y6E0 | P61006 | 1 | phosphorylation | up-regulates activity | 0.275 | In a screen for Rab8A kinases we identify TAK1 and MST3 kinases that can efficiently phosphorylate the Switch II residue Threonine72 (Thr72) in a similar manner as LRRK2 in vitro. |Overall our data suggests that the phosphorylation of Rab8A at Ser111 may influence Switch II-binding by regulators, thus disrupting interactions with its cognate GEF and moderately impairs its interaction with GAPs.|The antagonistic interplay between Ser111 phosphorylation and Thr72 phosphorylation is genetically concordant with how respective mutations in PINK1 and LRRK2 cause Parkinson’s disease | SIGNOR-260265 |
P10589 | P22888 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.275 | Functional analysis showed that EAR2 and EAR3/COUP-TFI repressed the hLHR promoter activity, whereas TR4 activated hLHR gene transcription. | SIGNOR-266218 |
P29275 | O95837 | 1 | binding | up-regulates activity | 0.275 | 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-257414 |
Q9NYY3 | O15350 | 1 | phosphorylation | down-regulates activity | 0.275 | PLK2 inhibits TAp73 translocation to the nucleus.|PLK2 phosphorylated TAp73 at residue Ser48 within the TA domain; phosphorylation of TAp73 was abolished by mutating this residue. | SIGNOR-278218 |
Q92585 | P35222 | 1 | binding | up-regulates | 0.275 | Unexpectedly, however, emerging evidence implicate maml proteins as exciting key transcriptional co-activators in other signal transduction pathways including: muscle differentiation and myopathies (mef2c), tumor suppressor pathway (p53) and colon carcinoma survival (beta-catenin). | SIGNOR-157843 |
P05771 | Q01844 | 1 | phosphorylation | down-regulates activity | 0.275 | Here we report thatews, a nuclearrna-bindingprooncoprotein, contains an iq domain, is phosphorylated byproteinkinase c, and interacts with calmodulin. Interestingly, pkc phosphorylation of ews inhibits its binding to rna homopolymers, and conversely,rna binding to ews interferes with pkc phosphorylation./ these data indicate that ews contains an iq domain with ser266 acting as the primary site for pkc phosphorylation. | SIGNOR-52854 |
P27361 | P49418 | 1 | phosphorylation | down-regulates activity | 0.274 | Thus, we propose that mapk phosphorylation of amphiphysin1 controls ngf receptor/trka-mediated endocytosis by terminating the amphiphysin1-ap-2 interaction.Our results indicate that phosphorylation of amphiphysin 1 at ser-285 and/or ser-293 affects the function of amphiphysin1.Mapk phosphorylation of ser-285 and ser-293 could modulate the interaction between prd and ap-2, resulting in the dissociation of amphiphysin1 from ap-2. | SIGNOR-126867 |
P19544 | Q7RTT9 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.274 | ENT4 is transcriptionally activated by both isoforms of EWS/WT1 as evidenced by promoter-reporter and chromatin immunoprecipitation (ChIP) analyses. | SIGNOR-268985 |
O15197 | Q9ULV8 | 1 | binding | up-regulates activity | 0.274 | We suggest that although mammalian EphB6 is kinase-negative, it has retained the allosteric regulatory mechanisms involving the juxtamembrane and the SAM domain linker that are used to regulate the kinase activity of kinase-active Eph receptors. he inability to recruit c-Cbl by EphB6 meant that heightened levels of EphA2 remained active in the cell because they had evaded c-Cbl-mediated degradation. The authors suggest that mutation of residues 901–926 within EphB6 reduces the flexibility of the SAM domain such that c-Cbl cannot be recruited. | SIGNOR-273852 |
Q9UL54 | Q13188 | 1 | phosphorylation | up-regulates | 0.274 | In addition, the thousand-and-one (tao) amino acids kinase or taok13 has been shown to directly phosphorylate and activate hpo or mst1/2. | SIGNOR-201327 |
Q8TDX7 | Q9HC35 | 1 | phosphorylation | up-regulates activity | 0.274 | The mitotic kinases NEK6 and NEK7 phosphorylated the EML4 N-terminal domain at Ser144 and Ser146 in vitro, and depletion of these kinases in cells led to increased EML4 binding to microtubules in mitosis. An S144A-S146A double mutant not only bound inappropriately to mitotic microtubules but also increased their stability and interfered with chromosome congression. In addition, constitutive activation of NEK6 or NEK7 reduced the association of EML4 with interphase microtubules. Together, these data support a model in which NEK6- and NEK7-dependent phosphorylation promotes the dissociation of EML4 from microtubules in mitosis in a manner that is required for efficient chromosome congression. | SIGNOR-273884 |
P35579 | P35222 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.274 | Nuclear MYH9 bound to the CTNNB1 promoter through its DNA-binding domain, and interacted with myosin light chain 9, β-actin and RNA polymerase II to promote CTNNB1 transcription, which conferred resistance to anoikis in GC cells in vitro and in vivo. | SIGNOR-278896 |
P22694 | Q14896 | 1 | phosphorylation | up-regulates | 0.274 | Phosphorylation of cmybp-c by pka speeds actomyosin interactions and contributes to increased cardiac contractility following _-adrenergic stimulation.7, 8 phosphorylation by pka is essential for proper cardiac function /for the human isoform, three pka sites were previously identified (ser275, ser284, and ser304) /our results indicate that pka phosphorylates up to four sites in both the murine and human m-domains including a novel site not previously described for either protein (ser307 for mouse and ser311 for human). | SIGNOR-163772 |
P32239 | P63096 | 1 | binding | up-regulates activity | 0.274 | 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-257037 |
P30989 | P09471 | 1 | binding | up-regulates activity | 0.274 | Altogether, these results reveal for the first time the ability of hNTS1 to directly activate the Gαq-, Gαi1-, GαoA-, and Gα13-mediated signaling pathways | SIGNOR-278061 |
P00441 | Q9NZJ5 | 1 | binding | up-regulates activity | 0.274 | SOD1mut-induced ER stress |we first examined whether SOD1mut induces ER stress in NSC34 motor neurons, as assessed by band-shift analyses of the ER transmembrane kinase receptors IRE1 and PERK. Adenovirus (Ad)-mediated expression of ALS-linked SOD1mut (SOD1G93A) was detectable within 48 h of infection (Supplemental Fig. S1A). SOD1mut (SOD1A4V, SOD1G85R, and SOD1G93A) but not wild-type SOD1 (SOD1wt) activated IRE1 and PERK | SIGNOR-262787 |
P06493 | Q16665 | 1 | phosphorylation | up-regulates activity | 0.274 | In vitro kinase assays reveal that CDK1 directly phosphorylates HIF-1\u03b1 at a previously unidentified regulatory site, Ser668.|Overexpression of CDK1 and/or cyclin B1 is sufficient to stabilize HIF-1alpha under normoxic conditions, whereas inhibition of CDK1 enhances the proteasomal degradation of HIF-1alpha, reducing its half-life and steady-state levels. | SIGNOR-279599 |
Q13976 | P04792 | 1 | phosphorylation | down-regulates | 0.274 | Purified pkg isoforms ia, ib, and ii all caused incorporation of phosphate in recombinant hsp27 at ser-78, ser-82, and thr-143, but not ser-15.These Studies indicate that hsp27 is a genuine substrate for pkg and that pkg may mediate inhibition of platelet aggregation through phosphorylation of hsp27 and subsequent prevent of actin polymerization | SIGNOR-186784 |
P04049 | O14974 | 1 | phosphorylation | down-regulates activity | 0.274 | In hESC, Raf-1 directly phosphorylates and inactivates MYPT1, and this process requires kinase active Raf-1 protein. | SIGNOR-278979 |
P30968 | P38405 | 1 | binding | up-regulates activity | 0.274 | 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-256935 |
P42684 | P17676 | 1 | phosphorylation | up-regulates | 0.274 | The y79 amino acid residue of c/ebpbeta was phosphorylated by c-abl or arg. The phosphorylation of c/ebpbeta resulted in an increased c/ebpbeta stability and a potentiation of c/ebpbeta transcription activation activity in cells | SIGNOR-186427 |
P10244 | P10909 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.274 | Here we show that the human ApoJ/Clusterin gene contains a Myb binding site in its 5' flanking region, which interacts with bacterially synthesized B-MYB protein and mediates B-MYB-dependent transactivation of the ApoJ/Clusterin promoter in transient transfection assays. Endogenous ApoJ/Clusterin expression is induced in mammalian cell lines following transient transfection of a B-MYB cDNA. | SIGNOR-269800 |
P14653 | P32243 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.274 | Transactivation of the mouse OTX2 Luc constructs by the human HOXB1, HOXB2, and HOXB3 proteins. | Likewise, the construct pOTX2LucΔ−710 showed an 8-, 12-, and 6-fold increase in transcriptional activity if co-transfected with pSG-HOXB1, -HOXB2, and -HOXB3, respectively | SIGNOR-261633 |
Q05397 | Q9H9S0 | 1 | phosphorylation | up-regulates activity | 0.274 | In addition, FAK directly phosphorylates Nanog in a dose-dependent manner by in vitro kinase assay and in cancer cells in vivo. The site-directed mutagenesis of Nanog tyrosines, Y35F and Y174F, blocked phosphorylation and binding by FAK. | SIGNOR-276410 |
P35790 | Q00987 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.274 | The data presented here provides evidence for a molecular mechanism by which CKI-dependent phosphorylation of Mdm2 at multiple sites triggers SCF \u03b2-TRCP -mediated Mdm2 destruction ( xref ). | SIGNOR-279606 |
P12931 | O14976 | 1 | phosphorylation | up-regulates activity | 0.274 | GAK is phosphorylated by c-Src and translocated from the centrosome to chromatin at the end of telophase. Cyclin G-associated kinase (GAK) harbors a consensus phosphorylation motif (Y412) for c-Src; however, its physiological significance remains elusive. Here, we show that GAK is phosphorylated by c-Src not only at Y412 but also at Y1149. | SIGNOR-263197 |
Q96RU7 | Q13085 | 1 | 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 |
P49715 | P28845 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.274 | Cotransfection with human CCAAT/enhancer binding protein-alpha (C/EBPalpha) and C/EBPbeta-LAP expression vectors activated the HSD11B1 promoter with the strongest effect within the same region. | SIGNOR-268971 |
Q9BY84 | P42345 | 1 | dephosphorylation | down-regulates activity | 0.274 | MKP7 represses mTOR function.|These results suggest that MKP7 could directly dephosphorylate pmTOR and pPRAS40 and forming complexes with these two proteins ( xref ). | SIGNOR-277067 |
P28702 | P10589 | 1 | binding | up-regulates | 0.274 | Arp-1/rxr, coup-tfi/rxr, and arp-1/coup-tfi heterodimers bound the fp330-3' site | SIGNOR-79449 |
Q8IUH4 | Q01726 | 1 | palmitoylation | up-regulates activity | 0.274 | Collectively these results suggest that ZDHHC13 phosphorylation by ATR following UVB irradiation promotes its interaction with MC1R to stimulate MC1R palmitoylation.Activating MC1R palmitoylation rescues the defect of MC1R RHC variants | SIGNOR-273518 |
P53671 | P60484 | 1 | phosphorylation | down-regulates activity | 0.274 | LIMK2 inhibits PTEN phosphatase activity in vitro and in cells.|PTEN phosphorylation and downregulation by LIMK2 promotes tumorigenesis and EMT in vivo. | SIGNOR-278363 |
Q00535 | P04626 | 1 | phosphorylation | up-regulates activity | 0.274 | Since Tyr-654 is the ERBB2 phosphorylation site on beta-catenin, this result is consistent with our hypothesis that CDK5 activates ERBB2 , which in turn phosphorylates beta-catenin on Tyr-654, leading to a shift of beta-catenin away from the adherens junction and into the nucleus where it can serve as a transcriptional co-activator.|Taken together with the results of our kinase analysis, these observations suggest that CDK5 phosphorylation of both ERBB2 and ERBB3 and AR could drive a feedback loop, in which ERBB2 and ERBB3 promotes beta-catenin transcriptional activity that then contributes to higher expression of ERBB3. | SIGNOR-279155 |
P04626 | P06493 | 1 | phosphorylation | down-regulates | 0.274 | Phosphorylation on tyrosine-15 of p34(cdc2) by erbb2 inhibits p34(cdc2) activation and is involved in resistance to taxol-induced apoptosis | SIGNOR-88671 |
Q92995 | Q9H1Y0 | 1 | deubiquitination | up-regulates quantity by stabilization | 0.274 | Here, we identified USP13 as an essential deubiquitinase that stabilizes ATG5 in a process that depends on the PAK1 serine/threonine-protein kinase and which enhances autophagy and promotes IM resistance in GIST cells. | SIGNOR-275838 |
Q13315 | Q16204 | 1 | phosphorylation | up-regulates | 0.274 | Phosphorylation of ccdc6 at thr434 by atm during dna damage response prevents fbxw7-mediated ccdc6 degradation. | SIGNOR-199276 |
P56178 | P01106 | 1 | transcriptional regulation | up-regulates quantity | 0.274 | Here we demonstrate by luciferase assay that the MYC promoter is specifically activated by overexpression of DLX5 and that two DLX5 binding sites in the MYC promoter are important for transcriptional activation of MYC. We also show that DLX5 binds to the MYC promoter both in vitro and in vivo and that transfection of a DLX5 expression plasmid promotes the expression of MYC in a dose-dependent manner in mammalian cells | SIGNOR-241914 |
P12931 | P11413 | 1 | phosphorylation | up-regulates activity | 0.274 | Here, we show that tyrosine kinase c-Src interacts with and phosphorylates G6PD at Tyr 112. This phosphorylation enhances catalytic activity of G6PD by dramatically decreasing its Km value and increasing its Kcat value for substrate glucose-6-phosphate. | SIGNOR-277550 |
P42345 | Q9HBH9 | 1 | phosphorylation | down-regulates activity | 0.274 | MTOR phosphorylates MNK2a on Ser74. Here, we show that mTORC1, a key regulator of mRNA translation and oncogenesis, directly phosphorylates MNK2 on Ser74. This suppresses MNK2 activity and impairs binding of MNK2 to eIF4G. | SIGNOR-277516 |
Q16539 | P11362 | 1 | phosphorylation | down-regulates | 0.274 | Fgfr1 translocation requires p38 mapk activation which phosphorylates the c-term tail of fgfr1 on ser777 | SIGNOR-166598 |
O43791 | Q49A26 | 1 | binding | down-regulates quantity by destabilization | 0.274 | Here, we analyzed changes in the ubiquitin landscape induced by prostate cancer-associated mutations of SPOP, an E3 ubiquitin ligase substrate-binding protein. SPOP mutants impaired ubiquitylation of a subset of proteins in a dominant-negative fashion. Of these, DEK and TRIM24 emerged as effector substrates consistently up-regulated by SPOP mutants. Up-regulation of DEK, TRIM24 and NCOA3 is a feature of prostate cancer SPOP mutations. | SIGNOR-272824 |
Q16665 | P29375 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.273 | To this end, we confirm that KDM3A, KDM4B, KDM4C, KDM5B, KDM5C, and KDM62 are direct targets of HIF-1a while extent the list of known targets to KDM2A, KDM2B, KDM4D, KDM5A, and KDM6A. The results demonstrated that majority of the KDMs were similarly induced (KDM2A, KDM2B, KDM3A, KDM4B, KDM4C, KDM4D, KDM5A, KDM5B, KDM5C, KDM6B, and KDM7A) or repressed (KDM NO66 and KDM1A) by both HIF-1a and HIF-2a. | SIGNOR-271565 |
Q15831 | Q9H093 | 1 | phosphorylation | up-regulates | 0.273 | A total of 12 human kinases (nuak1, nuak2, brsk1, brsk2, qik, qsk, sik, mark1, mark2, mark3, mark4 and melk) are related to ampk. Here we demonstrate that lkb1 can phosphorylate the t-loop of all the members of this subfamily, apart from melk, increasing their activity >50-fold. | SIGNOR-122717 |
P12931 | P53355 | 1 | phosphorylation | down-regulates activity | 0.273 | Here, we show that the leukocyte common antigen-related (LAR) tyrosine phosphatase dephosphorylates DAPK at pY491/492 to stimulate the catalytic, proapoptotic, and antiadhesion/antimigration activities of DAPK. Conversely, Src phosphorylates DAPK at Y491/492, which induces DAPK intra-/intermolecular interaction and inactivation. | SIGNOR-276074 |
P53355 | Q9UN36 | 1 | phosphorylation | up-regulates activity | 0.273 | DAPK1 phosphorylates and activates N-myc downstream-regulated gene 2 (NDRG2), resulting in increased tau phosphorylation via a reduction in Pin1 expression ( xref ; xref ). | SIGNOR-279983 |
P35790 | Q14693 | 1 | phosphorylation | down-regulates activity | 0.273 | Because CKI is a constitutively active kinase and ubiquitously distributed in many cell types, high mTORC1 activity depending on nutritional status may be a physiological cue for Lipin1 degradation mediated by CKI and beta-TRCP.|Thus, we propose that mTORC1 may function as a priming kinase for CKI to promote the phosphorylation of the degron motif in Lipin1. | SIGNOR-280228 |
P49356 | O14807 | 1 | null | up-regulates activity | 0.273 | Major investments have been made to target Ras through indirect routes. Inhibition of farnesyl transferase to block Ras maturation has failed in large clinical trials. | SIGNOR-242562 |
P28482 | Q86U44 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.273 | Mass spectrometry analysis showed that ERK phosphorylates METTL3 at three highly conserved residues: S43, S50, and S525 (Figures 2D and 2E). Mutational analysis further confirmed these three sites as main ERK phosphorylation sites (Figure 2F). Phosphorylation of METTL3 increases interaction with USP5, decreasing ubiquitination to stabilize the m6 A methyltransferase complex. | SIGNOR-265948 |
P54646 | P28562 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.273 | Taken together, these results imply that nicotine acts via AMPKα2 to phosphorylate MKP1 at Ser334, instigating MKP1 ubiquitination and proteasome-mediated degradation. | SIGNOR-276890 |
P54821 | O60675 | 1 | binding | down-regulates activity | 0.273 | Hoxd12 and MHox, that interact with v-/c-Maf, using the phage display method. The Hox proteins also could associate with the other Maf protein family members, MafB, MafK, MafF, and MafG, but not with Jun and Fos. The Hox proteins negatively regulated the DNA binding, transactivation and cell-transforming abilities of Maf. | SIGNOR-221932 |
Q99705 | P09471 | 1 | binding | up-regulates activity | 0.273 | 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-257235 |
P12931 | O14578 | 1 | phosphorylation | up-regulates activity | 0.273 | CitK is tyrosine phosphorylated by Src in response to EphB2 signaling. | SIGNOR-279484 |
Q04721 | P15923 | 1 | binding | down-regulates | 0.273 | In an effort to identify processes that regulate e47, and potentially b-cell development, we found that activated notch1 and notch2 effectively inhibit e47 activity. | SIGNOR-56222 |
P29320 | P10275 | 1 | phosphorylation | up-regulates activity | 0.273 | These data suggest that Etk may be able to phosphorylate AR at Y534 and Y551/552, and the interaction between the Etk SH2 domain and phosphorylated ARY551/552 may promote their association.|This is supported by our observations that the association between Etk and AR is increased after castration and Etk induces tyrosine phosphorylation of AR, leading an increase in AR stability and transcriptional activity under androgen depleted conditions. | SIGNOR-279371 |
P29274 | P63096 | 1 | binding | up-regulates activity | 0.273 | 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-257038 |
Q13618 | Q8N653 | 1 | binding | up-regulates activity | 0.273 | Leucine zipper-like transcriptional regulator 1 (LZTR1) encodes a member of the BTB-Kelch superfamily, which interacts with the Cullin3 (CUL3)-based E3 ubiquitin ligase complex. | SIGNOR-269070 |
Q13131 | Q8WUI4 | 1 | phosphorylation | down-regulates | 0.273 | Another recently described set of transcriptional regulators targeted by ampk and its related family members across a range of eukaryotes are the class iia family of histone deacetylases (hdacs). | SIGNOR-176491 |
Q9BYT3 | P28482 | 1 | phosphorylation | up-regulates activity | 0.273 | In vitro kinase assay results indicated that STK33 can phosphorylate ERK2.|STK33 phosphorylated ERK2 and increased the activity of ERK2 and promote the tumorigenesis of colorectal cancer HCT15 cells. | SIGNOR-279351 |
P00519 | Q05086 | 1 | phosphorylation | down-regulates activity | 0.273 | Our results suggest that c-Abl protects p53 from HPV-E6-E6AP complex-mediated degradation by phosphorylating E6AP and impairing its E3 ligase activity | SIGNOR-260930 |
Q12834 | Q9UBZ9 | 1 | binding | down-regulates quantity by destabilization | 0.273 | Here, we show that human REV1 undergoes proteosomal degradation mediated by the E3 ubiquitin ligase known as anaphase-promoting complex (APC). REV1 associates with APC. Overexpression of APC coactivator CDH1 or CDC20 promotes polyubiquitination and proteosomal degradation of REV1. | SIGNOR-272892 |
Q9NRW4 | P06239 | 1 | dephosphorylation | down-regulates activity | 0.273 | Because JKAP dephosphorylates and inactivates Lck in T cells [ xref ], we studied whether JKAP downregulation results in Lck activation in SLE T cells. | SIGNOR-277148 |
P12931 | Q15306 | 1 | phosphorylation | up-regulates activity | 0.273 | Further, we show here that c-Src dramatically stimulates IRF4 phosphorylation and activity and that Y61 and Y124 are two key sites responding to c-Src-mediated activation.|We have further shown that inhibition of c-Src activity reduces p-IRF4(Y121/124) and significantly represses transcription of the IRF4 target B cell integration cluster in Epstein-Barr virus-transformed cells. | SIGNOR-279287 |
Q02156 | P61764 | 1 | phosphorylation | down-regulates quantity | 0.273 | These results show that nPKC\u03b5 induces Munc18-1 phosphorylation during synaptic activity and reinforce the idea that nPKC\u03b5 downregulates Munc18-1 levels, induced by the nerve stimulation.|These results show that nPKCepsilon induces Munc18-1 phosphorylation during synaptic activity and reinforce the idea that nPKCepsilon downregulates Munc18-1 levels, induced by the nerve stimulation. | SIGNOR-279479 |
Q9Y566 | P12814 | 1 | relocalization | up-regulates activity | 0.273 | SHANK proteins are ‘master’ scaffolding proteins that tether and organize intermediate scaffolding proteins. They are located at excitatory synapses, where they are crucial for proper synaptic development and function. SAPAP proteins subsequently bind to the PDZ domain of members of the SHANK protein family. SHANK proteins then bind to the actin cytoskeleton and to Homer protein, which in turn interacts with mGluRs. Through these extended links, PSD95, SAPAP, SHANK and Homer proteins form a quaternary complex that brings together mGluR and NMDAR complexes in the PSD (FIG. 3). | SIGNOR-264583 |
P55283 | P63000 | 1 | null | up-regulates activity | 0.273 | Together, these data suggest that R-cadherin expression inhibits myogenesis and induces myoblast transformation through Rac1 activation. Therefore, the properties of R-cadherin make it an attractive target for therapeutic intervention in RMS. | SIGNOR-253103 |
P63167 | P61586 | 1 | gtpase-activating protein | down-regulates activity | 0.273 | 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-260501 |
Q13554 | Q9UQD0 | 1 | phosphorylation | up-regulates activity | 0.272 | CaMKII enhances voltage-gated sodium channel Nav1.6 activity and neuronal excitability|mmobilized peptide arrays and nanoflow LC-electrospray ionization/MS of Nav1.6 reveal potential sites of CaMKII phosphorylation, specifically Ser-561 and Ser-641/Thr-642 within the first intracellular loop of the channel. | SIGNOR-275788 |
Q2Q1W2 | P04637 | 1 | ubiquitination | down-regulates quantity | 0.272 | LIN41 promotes ubiquitination of p53 in response to RA.|Loss of LIN41 elevates p53 steady-state levels and reduces p53 ubiquitination. | SIGNOR-278679 |
Q9Y6E0 | Q05209 | 1 | phosphorylation | down-regulates activity | 0.272 | In addition, MST3 can phosphorylate PTP-PEST and inhibit the tyrosine phosphatase activity of PTP-PEST.|MST3 directly phosphorylates and inactivates protein tyrosine phosphatase PTP-PEST, which enhances cell migration by enhancing the tyrosine phosphorylation of paxillin Y31 and Y118 [ ]. | SIGNOR-279127 |
Q9UQM7 | O95180 | 1 | phosphorylation | down-regulates activity | 0.272 | we also discovered that a novel CaMKII-phosphorylated site, S2137, underwent dephosphorylation by calcineurin. | SIGNOR-277871 |
P00519 | P23759 | 1 | phosphorylation | up-regulates activity | 0.272 | Furthermore, we show that c-Abl interacts with and phosphorylates Pax7 protein.|Indeed, reporter gene assays indicate that c-Abl inhibition decreases Pax7 dependent activation of the 6xPRS9-luc reporter. | SIGNOR-279773 |
Q9Y5X5 | P09471 | 1 | binding | up-regulates activity | 0.272 | 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-256988 |
P51608 | P41145 | 1 | post transcriptional regulation | up-regulates quantity by expression | 0.272 | MeCP2 binds to the promoter region of six target genes. ChIP with anti-MeCP2 antibody shows that MeCP2 binds to the promoter regions of activated targets Sst, Oprk1, Gamt, and Gprin1, and repressed targets Mef2c and A2bp1. | SIGNOR-264677 |
Q13131 | P56524 | 1 | phosphorylation | down-regulates | 0.272 | We show here that in liver, class iia hdacs (hdac4, 5, and 7) are phosphorylated and excluded from the nucleus by ampk family kinases. | SIGNOR-173689 |
O75676 | Q04206 | 1 | phosphorylation | up-regulates | 0.272 | Rela is phosphorylated at: ser276 by the catalytic subunit of protein kinase a (pkac), msk1 and msk2; at ser311 by the atypical pkczeta; at ser468 by ikkbeta, ikkepsilon and glycogen-synthase kinase-3beta (gsk3beta); at ser529 by ck2; and at ser536 by ikkbeta, ikkalfa, ikkepsilon, nf-kb activating kinase (nak, also known as tank-binding kinase-1 tbk1)) and rsk1 (also known as p90 ribosomal protein s6 kinase (p90s6k) msk 1 and 2 can directly phosphorylate and activate transcription factors such as creb, atf1, the nf-kb isoform p65 and stat 1 and 3. | SIGNOR-151436 |
Q00536 | P10644 | 1 | phosphorylation | up-regulates activity | 0.272 | PCTK1 regulates spindle orientation in a kinase-dependent manner. Phosphoproteomic analysis together with an RNA interference screen revealed that PCTK1 regulates spindle orientation through phosphorylation of Ser83 on KAP0, a regulatory subunit of protein kinase A (PKA) | SIGNOR-273018 |
P12931 | P63010 | 1 | phosphorylation | down-regulates | 0.272 | The phosphorylation of beta2-adaptin on tyrosine residue 737 (y737) negatively regulates its interaction with betaarrestin. | SIGNOR-181743 |
P31751 | P15056 | 1 | phosphorylation | down-regulates | 0.272 | We show that phosphorylation of b-raf by akt occurs at multiple residues within its amino terminal regulatory domain, at both the conserved and unique phosphorylation sites. Akt phosphorylated b-raf on s364 and s428 to inactivate its kinase activity b-raf contains three akt consensus sites, table i. One site, ser364 is conserved with c-raf;however, two sites, ser428 and thr439, are unique to b-raf | SIGNOR-78689 |
Q05655 | P19429 | 1 | phosphorylation | up-regulates activity | 0.272 | Src phosphorylates pkcdelta at tyr311 and tyr332 leading to enhanced pkcdelta autophosphorylation at thr505 (its activation loop) and pkcdelta-dependent ctni phosphorylation at both ser23/ser24 and thr144. | SIGNOR-178880 |
P20807 | P49841 | 1 | cleavage | up-regulates activity | 0.272 | Thus, it has been shown that calpain cleaves the inhibitory domain of GSK3 generating two fragments of 40 and 30 kDa. This cleavage enhanced activity of the kinase | SIGNOR-251607 |
Q13464 | P07737 | 1 | phosphorylation | down-regulates | 0.272 | We previously identified pfn1 as a huntingtin aggregation inhibitor, and others have implicated it as a tumor-suppressor. Rho-associated kinase (rock) directly phosphorylates pfn1 at ser-137 to prevent its binding to polyproline sequences. This negatively regulates its anti-aggregation activity. | SIGNOR-196820 |
P08581 | P46940 | 1 | phosphorylation | up-regulates activity | 0.272 | IQGAP1 was phosphorylated exclusively on Tyr-1510 under conditions with enhanced MET or c-Src signaling, including in human lung cancer cell lines. This phosphorylation was significantly reduced by chemical inhibitors of MET or c-Src or by siRNA-mediated knockdown of MET. | SIGNOR-277532 |
P48436 | P49716 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.272 | Sox9 directly binds to the promoter regions of c/ebpbeta and c/ebpdelta to suppress their promoter activity, preventing adipocyte differentiation | SIGNOR-184283 |
O14965 | Q96CX2 | 1 | phosphorylation | up-regulates activity | 0.272 | In addition, Aurora A phosphorylated KCTD12 at serine 243, thereby initiating a positive feedback loop necessary for KCTD12 to exert its cancer-promoting effects. | SIGNOR-273544 |
Q9HAZ1 | P00519 | 1 | phosphorylation | down-regulates | 0.272 | Here, we identify clk1, clk4, mst1, mst2 and ttk (also known as mps1) as novel thr735 kinases in vitro / phosphorylation of thr735 in c-abl is critical for binding to 14-3-3 | SIGNOR-181052 |
Q13237 | P09619 | 1 | phosphorylation | down-regulates activity | 0.272 | Secretory PKG II inhibited PDGF‐BB ‐induced PDGFRβ activation via phosphorylating its Ser254. | SIGNOR-277577 |
P04049 | Q13043 | 1 | 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 |
P00533 | Q7Z699 | 1 | phosphorylation | down-regulates activity | 0.272 | We show that oncogenic EGFR(L858R) signaling leads to the phosphorylation of SPRED1 on serine 105, disrupting the SPRED1-neurofibromin complex. The structural, biochemical, and biological results provide new mechanistic insights about how SPRED1 interacts with neurofibromin and regulates active KRAS levels in normal and pathologic conditions. | SIGNOR-273638 |
P49841 | Q96RR4 | 1 | phosphorylation | down-regulates | 0.272 | Cdk5 and gsk3 phosphorylate ser-129, ser-133, and ser-137. Mutation of ser-129, ser-133, and ser-137 increases autonomous activity with little change in ca2 /cam-dependent activity. | SIGNOR-198134 |
Q9UHD2 | P12830 | 1 | phosphorylation | down-regulates activity | 0.272 | Inhibition of TBK1 increases association of Cdh1 with APC1.|It was found that TBK1 phosphorylates both Cdc20 as well as Cdh1 (Figure 2F). | SIGNOR-278996 |
P41968 | P30679 | 1 | binding | up-regulates activity | 0.272 | 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-257358 |
O75365 | P05787 | 1 | dephosphorylation | down-regulates activity | 0.272 | the cytoskeletal intermediate filament keratin 8 (KRT8) was identified as a physiological PRL-3-interacting protein. Indeed, treatment with the PRL-3 inhibitor effectively suppressed the phosphorylation of KRT8 at S73 and S431 | SIGNOR-248341 |
Q00535 | Q9ULW0 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.272 | CDK5-mediated phosphorylation and stabilization of TPX2 promotes hepatocellular tumorigenesis | SIGNOR-265100 |
O60346 | P04049 | 1 | dephosphorylation | down-regulates activity | 0.272 | PHLPP1 and PHLPP2 dephosphorylate RAF1 to reduce its signaling, increase the invasive and migratory activities of CRC cells, and activate the epithelial-mesenchymal transition. In Apc(Min) mice, loss of PHLPP1 promotes tumor progression. | SIGNOR-237449 |
P51812 | Q9Y4K3 | 1 | phosphorylation | up-regulates activity | 0.272 | These results demonstrate that TRAF6 K63 ubiquitination might be regulated by an RSK2 mediated phosphorylation dependent mechanism and phosphorylation of TRAF6 at Ser46, 47 and 48 enhances its ubiquitin mediated inflammation signaling. | SIGNOR-278302 |
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