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 |
|---|---|---|---|---|---|---|---|
O14757 | O15297 | 0 | dephosphorylation | down-regulates activity | 0.473 | Here we show that the oncogenic p53-induced serine/threonine phosphatase, PPM1D (or Wip1), dephosphorylates two ATM/ATR targets, Chk1 and p53. PPM1D binds Chk1 and dephosphorylates the ATR-targeted phospho-Ser 345, leading to decreased Chk1 kinase activity. | SIGNOR-248317 |
P59595 | Q05639 | 2 | binding | down-regulates activity | 0.2 | The nucleocapsid protein of severe acute respiratory syndrome coronavirus inhibits cell cytokinesis and proliferation by interacting with translation elongation factor 1alpha | SIGNOR-260260 |
P17612 | Q13002 | 1 | phosphorylation | up-regulates activity | 0.2 | GluR6 glutamate receptor, transiently expressed in mammalian cells, is directly phosphorylated by PKA, and that intracellularly applied PKA increases the amplitude of the glutamate response. Site-specific mutagenesis of the serine residue (Ser 684) representing a PKA consensus site completely eliminates PKA-mediated phosphorylation of this site as well as the potentiation of the glutamate response. | SIGNOR-250315 |
P01344 | P06213 | 2 | binding | up-regulates | 0.707 | Therefore, these results provide genetic evidence that the growth-promoting function of igf-ii during mouse embryogenesis is mediated in part by signaling through the insulin receptor. | SIGNOR-50719 |
O75051 | Q99985 | 2 | binding | up-regulates activity | 0.51 | Genes encoding the neurovascular guiding molecule semaphorin 3C (SEMA3C) and its receptor plexin A2 (PLXNA2) appear to be regulated directly by GATA6, and both GATA6 mutant proteins failed to transactivate these genes. | SIGNOR-253151 |
Q96T58 | Q99708 | 2 | binding | down-regulates | 0.542 | We identify the ctip and ctbp corepressors as novel components of the human rbp-jk/sharp-corepressor complex and show that ctip binds directly to the sharp repression domain. | SIGNOR-141616 |
P26998 | P43320 | 2 | binding | up-regulates activity | 0.453 | At high concentrations or in the lens, βB2-crystallin forms hetero-oligomers with other β-crystallins. These oligomeric β-crystallins further participate in the formation of a supramolecular assembly that is important in lens function-lens transparency. | SIGNOR-252152 |
Q9UJV3 | Q96R06 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.309 | These data indicated that Mid2 was ubiquitinating Astrin at K409 and targeting Astrin for degradation during cytokinesis. | SIGNOR-278549 |
Q9BQN1 | 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-273752 |
O43781 | Q96B36 | 1 | phosphorylation | down-regulates | 0.34 | When dyrk3 is active, it allows stress granule dissolution, releasing mtorc1 for signaling and promoting its activity by directly phosphorylating the mtorc1 inhibitor pras40 | SIGNOR-201002 |
P78423 | P49238 | 2 | binding | up-regulates | 0.785 | Fractalkine/cx3cl1 is a membrane-tethered chemokine that functions as a chemoattractant and adhesion protein by interacting with the receptor cx3cr1. | SIGNOR-109135 |
O75197 | O15169 | 1 | relocalization | down-regulates quantity | 0.83 | Axin is a protein that interacts with the intracellular domain of LRP-5. LRP-5 active form bind Axin and induce LEF-1 activation by destabilizing Axin and stabilizing beta-catenin. | SIGNOR-236997 |
P18146 | P78337 | 2 | binding | up-regulates activity | 0.514 | GNRH1 induces expression of early growth response 1 (EGR1), which interacts with steroidogenic factor 1 (SF1) and paired-like homeodomain transcription factor 1 (PITX1) to regulate Lhb promoter activity. | SIGNOR-254916 |
Q9GZV5 | P43699 | 2 | binding | up-regulates | 0.424 | Taz also binds to the transcription factor ttf-1 that is involved in formation and differentiation of the lungs and respiratory epithelia, and stimulates the production of pulmonary surfactant. | SIGNOR-143472 |
O75093 | O00712 | 0 | transcriptional regulation | up-regulates quantity | 0.249 | For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8) | SIGNOR-268899 |
Q9UM11 | Q9UKT4 | 0 | ubiquitination | down-regulates | 0.756 | Emi1 binds cdh1 and inhibits apc-cdh1 activity. | SIGNOR-113385 |
O00124 | P55072 | 1 | relocalization | down-regulates quantity | 0.521 | The human protein named Rep8 or Ubxd6 as a new cofactor of p97. Rep8 tethers p97 to the ER membrane for efficient ER-associated degradation. | SIGNOR-261002 |
Q9UBK2 | P49841 | 0 | phosphorylation | down-regulates quantity | 0.476 | GSK3\u03b2 is an important serine/threonine kinase to regulate PPAR\u03b3 coactivator-1\u03b1 degradation. , GSK3\u03b2 reduces PPAR\u03b3 coactivator-1\u03b1 levels by phosphorylating PPAR\u03b3 coactivator-1\u03b1 and subsequently stimulating PPAR\u03b3 coactivator-1\u03b1 degradation by the ubiquitin-proteasomal system.|Within them, GSK3beta, which can phosphorylate PGC-1alpha and promote its ubiquitin mediated degradation , , was upregulated significantly in mnd2 mouse brain and spinal cord compared with that in wide-type mice (XREF_FIG). | SIGNOR-279723 |
Q9NYF0 | O14641 | 2 | binding | down-regulates | 0.791 | Dapper 1 antagonizes wnt signaling by promoting dishevelled degradation | SIGNOR-144053 |
Q9P2J9 | P08559 | 1 | dephosphorylation | up-regulates activity | 0.658 | Pyruvate dehydrogenase phosphatase (PDP) is a mitochondrial serine phosphatase that activates phosphorylated pyruvate dehydrogenase complex by dephosphorylation | SIGNOR-251665 |
Q5S007 | Q8N6T3 | 2 | phosphorylation | down-regulates | 0.579 | Arfgap1 is an lrrk2 kinase substrate whose gap activity is inhibited by lrrk2. The phosphorylation of arfgap1 by lrrk2 was subjected to mass spectrometry to determine the sites of phosphorylation. There was 95.3% coverage and serines(s155, s246, s284) and threonine (t189, t216, t292) are phosphorylated by lrrk2. Mutational analysis of these serine and threonine amino acids to alanine reveals that no single amino acid is the predominant phospho-amino acid. | SIGNOR-196732 |
Q8IUH4 | Q13535 | 0 | phosphorylation | up-regulates activity | 0.2 | Collectively these results suggest that ZDHHC13 phosphorylation by ATR following UVB irradiation promotes its interaction with MC1R to stimulate MC1R palmitoylation. | SIGNOR-273517 |
P41161 | Q9H2G2 | 0 | phosphorylation | up-regulates activity | 0.2 | Here, we report that the direct activation of the three mammalian ERMs by the Ste20-like kinase (SLK) is crucial for guiding the mitotic spindle toward the expected orientation in two mammalian models of oriented cell division: micropatterned cells and apical progenitors of the mouse neocortex.|SLK directly phosphorylates mammalian ERMs and controls their cortical activation in mitosis. | SIGNOR-280126 |
P53350 | P30622 | 1 | phosphorylation | up-regulates | 0.703 | Furthermore, we provide evidence that plk1 phosphorylation of clip-170 at s195 enhances its association with ck2 | SIGNOR-167172 |
Q96KB5 | Q96S44 | 1 | phosphorylation | up-regulates activity | 0.418 | In this study, we provide evidence showing that TOPK promotes metastasis of colorectal carcinoma, which is mediated through its phosphorylation of PRPK at Ser250.|Therefore, we conclude that TOPK directly promotes metastasis of colorectal cancer by modulating PRPK. | SIGNOR-278236 |
P63092 | Q9NQ66 | 2 | binding | up-regulates activity | 0.324 | The beta- but not the gamma- and delta-type isozymes of inositol phospholipid-specific phospholipase c (plc) are activated by g protein alpha q and beta gamma subunits. | SIGNOR-265066 |
Q96G91 | 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-257173 |
Q6UXX9 | Q9BXB1 | 2 | binding | up-regulates | 0.766 | Here we demonstrate that lgr4 and lgr5 bind the r-spondins with high affinity and mediate the potentiation of wnt/betBeta-catenin signaling by enhancing wnt-induced lrp6 phosphorylation. | SIGNOR-174486 |
O14770 | P42771 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | 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-267240 |
P62714 | O43815 | 2 | binding | up-regulates activity | 0.595 | The striatin family proteins interact with the structural (A) and catalytic (C) subunits of the protein phosphatase, PP2A, and are also termed the B‴ family of PP2A subunits (4). Within heterotrimeric PP2A complexes, striatins function as one of many regulatory B subunits thought to be responsible for substrate selection and localization of PP2A isoforms | SIGNOR-261700 |
P08590 | P42574 | 0 | cleavage | down-regulates quantity by destabilization | 0.377 | By sequencing and site-directed mutagenesis, a noncanonical cleavage site for caspase-3 was mapped to the C-terminal DFVE(135)G motif. We demonstrated that vMLC1 cleavage in failing myocardium in vivo is associated with a morphological disruption of the organized vMLC1 staining of sarcomeres, and with a reduction in myocyte contractile performance. | SIGNOR-270593 |
P25098 | P17612 | 0 | phosphorylation | up-regulates activity | 0.2 | PKA directly phosphorylates GRK2 on serine 685. This modification increases G subunit binding to GRK2 and thus enhances the ability of the kinase to translocate to the membrane and phosphorylate the receptor. | SIGNOR-250334 |
Q9NRM7 | Q13043 | 0 | phosphorylation | up-regulates | 0.636 | Activation of mst1/2 leads to phosphorylation and activation of their direct substrates, lats1/2. | SIGNOR-175821 |
P23470 | P08581 | 1 | dephosphorylation | down-regulates activity | 0.317 | PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity. | SIGNOR-254712 |
Q9BXW9 | O00255 | 2 | binding | up-regulates | 0.441 | Menin interacts with fancd2 / loss of menin expression in mouse embryonic fibroblasts leads to increased sensitivity to dna damage. Furthermore, menin is localized to chromatin and nuclear matrix, and the association with nuclear matrix is enhanced by gamma-irradiation. Together, these results suggest that menin plays a critical role in repair of dna damage in concert with fancd2. | SIGNOR-103947 |
Q96R06 | P49841 | 0 | phosphorylation | up-regulates | 0.271 | Astrin acts as a substrate for gsk3beta and is phosphorylated at thr-111, thr-937 ((s/t)p motif) and ser-974/thr-978 ((s/t)xxx(s/t)-p motif;p is a phosphorylatable residue). Inhibition of gsk3beta impairs spindle and kinetochore accumulation of astrin and spindle formation at mitosis, suggesting that astrin association with the spindle microtubule and kinetochore may be dependent on phosphorylation by gsk3beta | SIGNOR-159578 |
Q9BXC1 | P38405 | 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-256900 |
P06241 | Q13291 | 1 | phosphorylation | up-regulates activity | 0.658 | All 3 tyrosines of CD150 (Tyr281, Tyr307, Tyr327) are phosphorylated by the src kinase Fyn. CD150 is unique among its homologues in the immunoglobulin superfamily in that it is able to bind SAP, a floating SH2 domain, in the absence of tyrosine phosphorylation. In this study, using a detailed mutagenesis mapping approach we have shown that SAP binding to CD150 is in fact bimodal. Prior to tyrosine phosphorylation, SAP binds the membrane-proximal motif surrounding Tyr281. Following tyrosine phosphorylation by tyrosine kinases such as Fyn, SAP binds additionally to the distal motif surrounding Tyr327. | SIGNOR-251182 |
Q13541 | Q9H0H3 | 2 | binding | down-regulates quantity by destabilization | 0.408 | We identified the KLHL25-CUL3 complex as the E3 ubiquitin ligase, which targets hypophosphorylated 4E-BP1. Thus, the activity of eIF4E is under homeostatic control via the regulation of the levels of its repressor protein 4E-BP1 through ubiquitination. | SIGNOR-272049 |
Q9ULT6 | Q9ULV1 | 1 | ubiquitination | down-regulates quantity | 0.565 | Here we show that the cell-surface transmembrane E3 ubiquitin ligase zinc and ring finger 3 (ZNRF3) and its homologue ring finger 43 (RNF43) are negative feedback regulators of Wnt signalling. ZNRF3 is associated with the Wnt receptor complex, and inhibits Wnt signalling by promoting the turnover of frizzled and LRP6. | SIGNOR-260115 |
Q9BXL7 | Q04759 | 0 | phosphorylation | up-regulates activity | 0.775 | NF-kappaB activation is triggered by PKCteta-dependent phosphorylation of Carma1 after TCR/CD28 co-stimulation. PKCteta-phosphorylated Carma1 was suggested to function as a molecular scaffold that recruits preassembled Bcl10-Malt1 complexes to the membrane|we demonstrate that PP2A removes PKCteta-dependent phosphorylation of Ser645 in Carma1, and show that maintenance of this phosphorylation is correlated with increased T-cell activation. | SIGNOR-249193 |
P11940 | O00571 | 2 | binding | up-regulates activity | 0.57 | In the present study, we indentified the SG marker PABP1 [poly(A)-binding protein 1] as another direct interaction partner of DDX3. Interestingly, down-regulation of DDX3 interfered with SG assembly, led to nuclear accumulation of PABP1 and reduced cell viability following stress. Conversely, supplementation with a shRNA (short hairpin RNA)-resistant DDX3 restored SG formation, the translocation of PABP1 into SGs and cell survival. | SIGNOR-269201 |
P35236 | P17612 | 0 | phosphorylation | down-regulates | 0.361 | B2 adrenergic receptor stimulation induces the pka dependent phosphorylation of heptp and releases bound p38 mapk | SIGNOR-182522 |
Q9UM47 | Q9Y219 | 2 | binding | up-regulates | 0.625 | These results suggest that delta1, jagged1, and jagged2 are ligands for notch1 and notch3 receptors. | SIGNOR-82401 |
Q9H0K1 | P35568 | 1 | phosphorylation | down-regulates quantity | 0.567 | SIK2 is known to attenuate insulin signaling by phosphorylating IRS-1/Ser789 | SIGNOR-265745 |
Q02078 | Q15796 | 2 | binding | up-regulates | 0.39 | Our studies indicate that smad2 and 4 (smad2/4) complexes cooperate with mef2 regulatory proteins in a gal4-based one-hybrid reporter gene assay. | SIGNOR-235846 |
P07900 | Q75N03 | 2 | binding | up-regulates quantity | 0.2 | By immunoprecipitation, we present evidence that Hakai interacts with Hsp90 chaperone complex in several epithelial cells and demonstrate that is a novel Hsp90 client protein. Interestingly, by overexpressing and knocking-down experiments with Hakai, we identified Annexin A2 as a Hakai-regulated protein. Interestingly, geldanamycin-induced Hakai degradation is accompanied by an increased expression of E-cadherin and Annexin A2. Hsp90 participates in the correct folding of its client proteins, allowing them to maintain their stability and activity. | SIGNOR-271474 |
P42229 | P18031 | 0 | dephosphorylation | down-regulates activity | 0.676 | A Cytosolic Protein-tyrosine Phosphatase PTP1B Specifically Dephosphorylates and Deactivates Prolactin-activated STAT5a and STAT5b | SIGNOR-248428 |
P24941 | Q13309 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.799 | The activity of SCF(Skp2) is regulated by the Cyclin-dependent kinase (CDK)2-mediated phosphorylation of Skp2 on Ser64 allows its expression in mid-G1 phase, even in the presence of active APC(Cdh1). Reciprocally, dephosphorylation of Skp2 by the mitotic phosphatase Cdc14B at the M --> G1 transition promotes its degradation by APC(Cdh1). | SIGNOR-249173 |
Q6GPH4 | Q13490 | 2 | binding | down-regulates | 0.415 | Immunoprecipitation studies indicate that xaf1 binds to xiap,birc2,birc3. | SIGNOR-156843 |
P31751 | Q13188 | 1 | phosphorylation | down-regulates | 0.261 | Akt phosphorylates mst2 at thr117 in vitro and in vivo, which leads to mst2 cleavage and kinase activity as well as nuclear translocation. | SIGNOR-164302 |
P00519 | P33981 | 0 | phosphorylation | down-regulates | 0.279 | Ttk phosphorylation of thr735 was associated with partial inhibition of nuclear targeting of c-abl. | SIGNOR-181064 |
Q9H3R0 | Q99814 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | 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-271585 |
Q9H3Y6 | Q02790 | 1 | phosphorylation | down-regulates activity | 0.267 | Together, these data indicate that SRMS inhibits the scaffolding function of its endogenous substrate FKBP51, thus antagonizing FKBP51-dependent inactivation of AKT (S4E Fig).|We demonstrate that SRMS phosphorylates FKBP51 to inhibit its scaffolding activity and promote its degradation through the ubiquitin-proteasome pathway. | SIGNOR-279764 |
Q9Y5H3 | 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-265682 |
Q07955 | P17612 | 0 | phosphorylation | up-regulates | 0.2 | Here, we show that pka phosphorylates srsf1 on serine 119 in vitro. Phosphorylation of srsf1 on this site enhanced the rna binding capacity of srsf1 in vivo | SIGNOR-196397 |
P27815 | P49137 | 0 | phosphorylation | down-regulates activity | 0.347 | Phosphorylation of cAMP-specific PDE4A5 (phosphodiesterase-4A5) by MK2 (MAPKAPK2) attenuates its activation through protein kinase A phosphorylation. In the present study, we show that PDE4A5 is phosphorylated at Ser147, within the regulatory UCR1 (ultraconserved region 1) domain conserved among PDE4 long isoforms, by MK2 (MAPK-activated protein kinase 2, also called MAPKAPK2). Phosphorylation by MK2, although not altering PDE4A5 activity, markedly attenuates PDE4A5 activation through phosphorylation by protein kinase A. This modification confers the amplification of intracellular cAMP accumulation in response to adenylate cyclase activation by attenuating a major desensitization system to cAMP. | SIGNOR-263078 |
P0DPK2 | Q14493 | 0 | 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-265419 |
O75398 | P08908 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.437 | The human 5-HT1A gene (HTR1A) rs6295 risk allele prevents Deaf1 binding to HTR1A, resulting in increased 5-HT1A autoreceptor transcription | SIGNOR-269064 |
P53779 | P04637 | 1 | phosphorylation | up-regulates | 0.628 | The targets of jnk include the transcription factors p53. P75ntr-mediated apoptosis was shown to be dependent of p53 | SIGNOR-120552 |
P15923 | Q9H2X6 | 0 | phosphorylation | down-regulates activity | 0.2 | This result provides a mechanistic explanation for the context-dependent function of HIPK2 in Wnt signaling | SIGNOR-279193 |
P43405 | P46934 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.291 | The latent membrane protein (LMP) 2A of Epstein-Barr virus (EBV) is implicated in the maintenance of viral latency and appears to function in part by inhibiting B-cell receptor (BCR) signaling. LMP2A enhances Lyn and Syk ubiquitination in vivo in a fashion that depends on the activity of Nedd4 family members and correlates with destabilization of the Lyn tyrosine kinase. These results suggest that LMP2A serves as a molecular scaffold to recruit both B-cell tyrosine kinases and C2/WW/Hect domain E3 protein-ubiquitin ligases. | SIGNOR-272581 |
Q13443 | P21802 | 1 | cleavage | down-regulates quantity by destabilization | 0.257 | Truncated FGFR2 was observed in cells transfected with wild-type ADAM9, but not in those with inactive mutant ADAM9 (Figure 5E). In line with this, cells transfected with wild-type ADAM9 showed reduced pErK1/2 in response to FGF2 as compared to controls or cells expressing mutant ADAM9.|Here we show that MT1-MMP forms a complex with FGFR2 and ADAM9 in osteoblasts and proteolytically inactivates ADAM9, hence protecting FGFR2 from ADAM9-mediated ectodomain shedding on the cell surface. | SIGNOR-260300 |
P17612 | Q92917 | 1 | phosphorylation | up-regulates activity | 0.307 | PKA phosphorylates GPKOW at S27 and T316 in vitro. GPKOWs ability to bind RNA is sensitive to mutations of its PKA phosphorylation sites. | SIGNOR-266309 |
Q69YH5 | Q96GD4 | 0 | phosphorylation | down-regulates activity | 0.446 | This result demonstrates that the three sites of Repo-Man (Ser-543, Ser-977, and Ser-981) are phosphorylated by Aurora B in early mitosis. We uncover that PP1γ is recruited to mitotic chromosomes by its regulatory subunit Repo-Man in the absence of Aurora B activity and that Aurora B regulates dissociation of PP1γ by phosphorylating and disrupting PP1γ-Repo-Man interactions on chromatin. | SIGNOR-274001 |
Q9UKN1 | P05412 | 2 | binding | up-regulates activity | 0.256 | MUC12 promoted the recruitment of c-Jun on the promoter of TGF-β1, leading to its transcription. | SIGNOR-265474 |
Q9C0A6 | P84243 | 1 | methylation | up-regulates activity | 0.2 | SETD5 Exhibits Intrinsic Methyltransferase Activity on H3K36. This assay showed that SETD5 has specific histone methyltransferase activity toward K36 but not for other residues such as K4 and K27 (Figure 8B). we revealed that SETD5 is endowed with H3K36 methyltransferase, which is necessary for RNA elongation and processing and, ultimately, correct gene transcription. | SIGNOR-264622 |
O00398 | 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-257005 |
A6ND36 | P36894 | 0 | phosphorylation | up-regulates activity | 0.374 | These results indicate that ALK3 phosphorylates PAWS1 predominantly at Ser610 but can also phosphorylate at Ser614 and Ser616 in vitro. |Here, we report the discovery and characterization of PAWS1/FAM83G as a novel SMAD1 interactor. PAWS1 forms a complex with SMAD1 in a SMAD4-independent manner, and BMP signalling induces the phosphorylation of PAWS1 through BMPR1A. The phosphorylation of PAWS1 in response to BMP is essential for activation of the SMAD4-independent BMP target genes NEDD9 and ASNS. Our findings identify PAWS1 as the first non-SMAD substrate for type I BMP receptor kinases and as a novel player in the BMP pathway. | SIGNOR-264766 |
P55289 | P35222 | 2 | binding | up-regulates activity | 0.509 | At its C-terminus, cadherin interacts with β-catenin, which dynamically associates with α-catenin, a direct binding partner of filamentous actin | SIGNOR-265852 |
P12931 | Q13263 | 1 | phosphorylation | down-regulates activity | 0.2 | Among SFKs, Src strongly induces tyrosine phosphorylation of KAP1.|Immunostaining and chromatin fractionation show that Src and Lyn decrease the association of KAP1 with heterochromatin in a kinase activity-dependent manner. | SIGNOR-280137 |
O14843 | P63096 | 2 | binding | up-regulates activity | 0.2 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-256678 |
Q99638 | P00519 | 0 | phosphorylation | up-regulates activity | 0.477 | The SH3 domain of c-Abl interacts directly with the C-terminal region of Rad9. c-Abl phosphorylates the Rad9 Bcl-2 homology 3 domain (Tyr-28) in vitro and in cells exposed to DNA-damaging agents. | c-Abl-mediated phosphorylation of Rad9 induces binding of Rad9 to Bcl-xL |these findings indicate that Rad9 is regulated by a c-Abl-dependent mechanism in the apoptotic response to genotoxic stress. | SIGNOR-260843 |
P49418 | Q13627 | 0 | phosphorylation | down-regulates | 0.396 | Recent studies show that phosphorylation of amphiphysin1 prd by cdk5 inhibited the association of amphiphysin1 with ap-2 in synaptic vesicle endocytosis (7, 8) similar to that by mapk (present report). Cdk5 appears to phosphorylate amphiphysin1 at serines 261, 272, 276, and 285 and threonine 310, located in the prd | SIGNOR-126843 |
O00141 | Q969H0 | 1 | phosphorylation | up-regulates | 0.291 | Here, we report that the serum- and glucocorticoid-inducible protein kinase sgk1 remarkably reduced the protein stability of the active form of notch1 through fbw7activated sgk1 phosphorylated fbw7 at serine 227 | SIGNOR-170404 |
O94986 | Q96SN8 | 0 | relocalization | up-regulates activity | 0.755 | Primary microcephaly (MCPH) associated proteins CDK5RAP2, CEP152, WDR62 and CEP63 colocalize at the centrosome. We found that they interact to promote centriole duplication and form a hierarchy in which each is required to localize another to the centrosome, with CDK5RAP2 at the apex, and CEP152, WDR62 and CEP63 at sequentially lower positions. MCPH proteins interact with distinct centriolar satellite proteins; CDK5RAP2 interacts with SPAG5 and CEP72, CEP152 with CEP131, WDR62 with MOONRAKER, and CEP63 with CEP90 and CCDC14. These satellite proteins localize their cognate MCPH interactors to centrosomes and also promote centriole duplication. Consistent with a role for satellites in microcephaly, homozygous mutations in one satellite gene, CEP90, may cause MCPH. The satellite proteins, with the exception of CCDC14, and MCPH proteins promote centriole duplication by recruiting CDK2 to the centrosome. | SIGNOR-271721 |
Q16623 | Q9ULU8 | 2 | binding | up-regulates activity | 0.402 | CAPS interacted independently with either syntaxin-1 or SNAP-25 suggesting that CAPS might promote QaQbc-SNARE heterodimer formation. CAPS binding to syntaxin-1 was mediated by the membrane-proximal C-terminal SNARE motif (H3) and membrane linker domain sequences of syntaxin-1 | SIGNOR-264336 |
P01008 | Q07954 | 2 | binding | up-regulates | 0.2 | In vitro binding studies revealed that antithrombin iii (atiii)thrombin, heparin cofactor ii (hcii)thrombin, and ?1-antitrypsin (?1AT)trypsin bound to purified lrp. | SIGNOR-41232 |
Q9BV73 | Q15154 | 0 | relocalization | up-regulates | 0.551 | Recruitment of nek2 and c-nap1 to the centrosome is dependent on pcm-1 | SIGNOR-133334 |
Q14289 | Q14247 | 1 | phosphorylation | up-regulates activity | 0.365 | In conclusion, these data suggest that Pyk2 phosphorylates cortactin on tyrosine residues Y421, Y466, and Y482.|To confirm the direct and indirect effects of Pyk2 on cortactin phosphorylation, we used cells overexpressing Arg YFP and treated with Pyk2 siRNA or a nonsilencing siRNA. | SIGNOR-278344 |
Q96PU5 | Q12809 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.399 | As quantified in Fig. 5 B, only Nedd4-2 significantly increased the basal ubiquitylation of hERG1, while Nedd4-2-C801S and the other ubiquitin ligases had no effect.|The major findings of this study are as follows : 1) hERG1 interacts via its PY motif with the ubiquitin ligase Nedd4-2, 2) this interaction promotes the down-regulation of the functional form of the channel at the plasma membrane through Nedd4-2 ubiquitylation of the channel, and 3) I hERG1 is strongly decreased by Nedd4-2 catalytic dependent activity.The hERG1 PY motif is a highly conserved sequence across animal species lines, highlighting its crucial role in the regulation of the hERG1 channel at the cell surface. | SIGNOR-278771 |
Q13464 | P35241 | 1 | phosphorylation | up-regulates activity | 0.68 | A peak of the phosphopeptide, in which only T573 was phosphorylated, was not detected. Quantitative analyses revealed that _100% of T564, but at most _40% of T573, was phosphorylated when C-rad was incubated with Rho-Kc for 1 h. Then we concluded that the major and primary phosphorylation site of radixin by Rho-kinase was T564 and referred to the Rho-Kcphosphorylated C-rad as T564-phosphorylated C-rad. | In this study, we found that the T564 phosphorylation of radixin markedly suppressed its head-to-tail association. This suggests that the T564-phosphorylation of radixin (and probably also the phosphorylation of ezrin T567 and moesin T558) keeps them open and active. | SIGNOR-248994 |
P51608 | P26358 | 2 | binding | up-regulates activity | 0.528 | Thus, these results indicate that MeCP2-interacting Dnmt1 has significant maintenance DNA methyltransferase activity and that MeCP2 does not vanish Dnmt1 enzymatic activity. | SIGNOR-264541 |
Q9P0J1 | P08559 | 1 | dephosphorylation | up-regulates activity | 0.732 | Sites 1, 2, and 3 were dephosphorylated either individually or in the presence of the other sites by the phospho-E1-phosphatase resulting in complete reactivation of the E1. The rates of dephosphorylation and reactivation were similar for sites 1, 2, and 3, indicating a random dephosphorylation mechanism | SIGNOR-252055 |
P20823 | Q9HAW9 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.281 | Using gel shift and functional assays, HNF1alpha was demonstrated to bind to and activate the UGT1A8, -1A9, and -1A10 promoters. In contrast, Cdx2 bound to and activated the UGT1A8 and -1A10 promoters but could not activate the UGT1A9 promoter. | SIGNOR-253972 |
Q5VTY9 | Q15465 | 1 | palmitoylation | up-regulates | 0.683 | Our molecular analysis of knockout mice deficient in skn, the murine homolog of the drosophila ski gene, which catalyzes hh palmitoylation, and gene-targeted mice producting a non palmitoylated form of shh indicates that hh palmitoylation is essential for its activity as well as the generation of a protein gradient in the developing embryos | SIGNOR-124118 |
Q9ULT6 | Q2MKA7 | 0 | relocalization | down-regulates quantity | 0.803 | Mechanistically, R-spondin interacts with the extracellular domain of ZNRF3 and induces the association between ZNRF3 and LGR4, which results in membrane clearance of ZNRF3. These data suggest that R-spondin enhances Wnt signalling by inhibiting ZNRF3. | SIGNOR-260113 |
P29597 | P52630 | 1 | phosphorylation | up-regulates activity | 0.789 | JAK1 and TYK2 will phosphorylate and activate STAT1 and STAT2 respectively, leading to the formation of the ternary interferon-stimulated gene factor 3 (ISGF3) complex, composed of STAT1, STAT2 and interferon regulatory factor 9 (IRF9). | SIGNOR-279133 |
Q9UQ88 | O75293 | 2 | binding | down-regulates activity | 0.2 | Western blot analysis for SPDEF revealed that overexpression of GADD45α, β and γ prevents SPDEF degradation mediated by CDK11p58 |We identified CDK11p58 as an interaction partner of GADD45α by co-immunoprecipitation analysis. We corroborated these data by co-immunoprecipitation in vitro translation assays, showing that all three members of the GADD45 family interact with CDK11p58. | SIGNOR-273024 |
Q13621 | Q9UEW8 | 0 | phosphorylation | up-regulates activity | 0.577 | We establish that the SPAK and OSR1 kinases activated by WNK interact with an RFQV motif on NKCC2 and directly phosphorylate Thr95, Thr100, Thr105 and, possibly, Ser91.Using these phosphorylation-specific antibodies we establish that hypotonic low-chloride stimulation induces marked phosphorylation of overexpressed NKCC2 in HEK-293 cells at Ser91, Thr100, Thr105 and Ser130 (Fig. 3A). | SIGNOR-276308 |
Q96A54 | Q9UKG1 | 2 | binding | up-regulates | 0.751 | Appl1 interacts with adiponectin receptors in mammalian cells and the interaction is stimulated by adiponectin. | SIGNOR-146212 |
Q9Y5S9 | Q96SB4 | 0 | phosphorylation | down-regulates | 0.261 | We demonstrate that y14 is phosphorylated at its repeated arginine/serine (rs) dipeptides, likely by sr protein-specific kinases. Phosphorylation of y14 abolished its interaction with ejc components as well as factors that function downstream of the ejc. | SIGNOR-139555 |
O00253 | P32245 | 2 | binding | down-regulates | 0.774 | Recombinant agouti-related protein was a potent, selective antagonist of mc3r and mc4r,. | SIGNOR-51104 |
P51692 | P12931 | 0 | phosphorylation | up-regulates | 0.578 | Stat5 is activated by a broad spectrum of cytokines, as well as non-receptor tyrosine kinases, such as src. these conformational differences may in part be due to differential effects of prl and src on stat5b tyrosine phosphorylation, since src induced several additional sites of tyrosine phosphorylation of stat5b at residues other than tyr-699, including tyr-724 and tyr-679. | SIGNOR-99002 |
Q9P2S2 | Q8N2Q7 | 2 | binding | up-regulates activity | 0.829 | Pre- and postsynaptic plasma membranes are always precisely aligned, and are separated by a synaptic cleft of ~20 nm. The cleft contains an undefined proteinaceous material in the middle, and is presumably bridged by synaptic cell-adhesion molecules such as Nrxns and Nlgns that align the pre- and postsynaptic elements and mediate trans-synaptic signaling.|Nlgns bind to both alpha- and beta-Nrxns with nanomolar affinities; binding involves the sixth LNS-domain of alpha-Nrxns which corresponds to the only LNS-domain of beta-Nrxns52. The binding affinities differ characteristically between various pairs of Nlgns and Nrxns, and are controlled by alternative splicing of both Nrxns and Nlgns (Figure 1c) | SIGNOR-264154 |
Q14653 | Q7TFA0 | 2 | binding | down-regulates activity | 0.2 | Accessory proteins 8b and 8ab of severe acute respiratory syndrome coronavirus suppress the interferon signaling pathway by mediating ubiquitin-dependent rapid degradation of interferon regulatory factor 3.We also found that proteins 8b and 8ab could physically interact with IRF3. Overexpression of 8b and 8ab resulted in the reduction of poly (I:C)-induced IRF3 dimerization and inhibition of the IFN-β signaling pathway. | SIGNOR-260239 |
Q9Y4K3 | P52789 | 1 | ubiquitination | down-regulates quantity | 0.2 | The Lys63-linked ubiquitination of HK2 catalyzed by the E3 ligase TRAF6 was critical for the subsequent recognition of HK2 by the autophagy receptor protein SQSTM1/p62 for the process of selective autophagic degradation. | SIGNOR-260003 |
P15941 | Q05655 | 0 | phosphorylation | up-regulates | 0.336 | We show that phosphorylation of muc1 by pkcdelta increases binding of muc1 and beta-catenin in vitro and in vivo. The functional significance of the muc1-pkcdelta interaction is further supported by the demonstration that mutation of the pkcdelta phosphorylation site abrogates muc1-mediated decreases in binding of beta-catenin to e-cadherin | SIGNOR-115501 |
O15360 | Q13315 | 0 | phosphorylation | up-regulates | 0.407 | The s1449a mutant failed to completely correct a variety of fa-associated phenotypes. The dna damage response is coordinated by phosphorylation events initiated by apical kinases atm (ataxia telangectasia mutated) and atr (atm and rad3-related), and atr is essential for proper fa pathway function. Serine 1449 is in a consensus atm/atr site | SIGNOR-182949 |
Q13114 | Q15025 | 2 | binding | down-regulates activity | 0.432 | ABIN1 interacted with the A20 regulatory molecule TAX1BP1 and was essential for the recruitment of TAX1BP1 and A20 to the noncanonical IkappaB kinases TBK1 and IKKi in response to poly(I:C) transfection. ABIN1 and TAX1BP1 together disrupted the interactions between the E3 ubiquitin ligase TRAF3 and TBK1/IKKi to attenuate lysine 63-linked polyubiquitination of TBK1/IKKi. | SIGNOR-275736 |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.