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 |
|---|---|---|---|---|---|---|---|
Q15910 | P31260 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.438 | These data support the proposed regulatory impact of particular PRC2-proteins in expression of HOXA9 and HOXA10 in NK/T-cells. In mammalian cells knockdown of PRC2 components EZH2 or PHF1 led to upregulated HOXA gene expression. | SIGNOR-260070 |
P25025 | P19875 | 2 | binding | up-regulates activity | 0.74 | CXCL2/3, also known as macrophage inflammatory protein-2α/2β (MIP-2α/MIP-2β), share the same receptor CXCR2 with CXCL1 and are able to activate neutrophils effectively | SIGNOR-277718 |
P52333 | P31785 | 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 |
Q03135 | P43005 | 2 | binding | down-regulates activity | 0.2 | EAAT3 has previously been shown to form complexes with caveolin-1, a major component of caveolae, which participate in the regulation of transport proteins. The present study explored the impact of caveolin-1 on electrogenic transport by excitatory amino acid transporter isoforms EAAT1-4. caveolin-1 is a powerful negative regulator of the excitatory glutamate transporters EAAT1, EAAT2, EAAT3, and EAAT4. Caveolin-1 has been shown to form complexes with the excitatory amino acid transporter EAAT3 (EAAC1) (Gonzalez et al. 2007) and may thus modify the EAAT isoforms by direct interaction with the carriers. | SIGNOR-264807 |
P17252 | P10415 | 1 | phosphorylation | up-regulates | 0.349 | Purified pkca can efficiently and directly phosphorylate bcl2 at serine 70 | SIGNOR-60120 |
Q9Y6I3 | P00533 | 1 | relocalization | down-regulates | 0.596 | Epsin 1 is involved in recruitment of ubiquitinated egf receptors into clathrin-coated pits this supports the contention that epsin 1 promotes endocytosis of the ubiquitinated egfr. | SIGNOR-182562 |
Q92736 | Q15772 | 0 | phosphorylation | down-regulates activity | 0.248 | Conclusions : Unlike other kinases (PKA, CaMKII) that increase RyR2 activity, SPEG phosphorylation reduces RyR2 mediated SR Ca 2+ -release.|Further, we show that SPEG phosphorylates RyR2 at a previously uncharacterized serine (S2367) located in the central domain of the channel. xref Importantly, in contrast to previously studied phosphorylation sites that activate RyR2 (e.g. S2808, S2814), we show that SPEG mediated RyR2-S2367 phosphorylation suppresses pathogenic diastolic SR Ca 2+ -leak. | SIGNOR-279114 |
Q92769 | Q96KB5 | 0 | phosphorylation | up-regulates activity | 0.2 | The results of in vitro studies further confirmed the effect of TOPK on HDAC activity by showing that TOPK overexpression significantly up-regulated p-HDAC1 and p-HDAC2, resulting in an increase in the acetylation of histones H3 and H4 in BV2 cells.|These results indicated that TOPK overexpression resulted in the phosphorylation of HDAC1 and HDAC2, which might inactivate them and promote the acetylation of Histone 3 and Histone 4. | SIGNOR-279087 |
P15976 | Q5VWQ8 | 2 | binding | up-regulates activity | 0.2 | DAB2IP suppresses transcription of stem cell factor receptor CD117, by interacting with GATA-1 on a silencer element on its gene | SIGNOR-254770 |
O14757 | O00716 | 1 | phosphorylation | up-regulates | 0.328 | These results suggest that e2f3a is directly phosphorylated by chk kinases and that the phosphorylation of serine 124 is required for the posttranslational induction of e2f3a protein by chemotherapy. | SIGNOR-161758 |
Q06330 | Q13642 | 2 | binding | down-regulates | 0.649 | It was demonstrated by emsa that kyot2 can form a complex with dna-bound rbp-j, but the dna-binding affinity of the kyot2rbp-j complex is greatly weakened and it exists mostly dissociated from dna | SIGNOR-54277 |
P31751 | O95989 | 2 | binding | up-regulates | 0.2 | Full-length tcl1 and its isoforms bind to akt / in in vitro kinase assays using gsk-3_ as a substrate, we found that the presence of any of the tcl1 family proteins (tcl1, mtcp1, or tcl1b) as gst fusion proteins significantly enhanced akt-induced gsk-3_ phosphorylation | SIGNOR-81759 |
Q5EBL8 | Q86UF1 | 2 | binding | up-regulates activity | 0.328 | Using cell biological and biochemical methods, we now show that ADAM10 is docked to junctions by its transmembrane partner Tspan33, whose cytoplasmic C terminus binds to the WW domain of PLEKHA7 in the presence of PDZD11. The PLEKHA7-PDZD11 Complex Clusters ADAM10 at Junctions through Tspan33 | SIGNOR-261252 |
P49815 | P28482 | 0 | phosphorylation | down-regulates activity | 0.681 | Here, we show that Erk may play a critical role in TSC progression through posttranslational inactivation of TSC2. Erk-dependent phosphorylation leads to TSC1-TSC2 dissociation and markedly impairs TSC2 ability to inhibit mTOR signaling, cell proliferation, and oncogenic transformation. |Serine to alanine substitution at S664 or double S664A/S540A mutagenesis resulted in a marked reduction in TSC2 phosphorylation to a similar extent. In contrast, S540A substitution only moderately impaired TSC2 phosphorylation (Figure 3D), corroborating the notion that in vivo S664 is the most relevant residue for Erk-mediated phosphorylation. | SIGNOR-249454 |
Q13315 | Q92993 | 0 | acetylation | up-regulates activity | 0.8 | Here, we report that sirtuin 7 (SIRT7)-mediated deacetylation is essential for dephosphorylation and deactivation of ATM. We show that SIRT7, a class III histone deacetylase, interacts with and deacetylates ATM in vitro and in vivo. |Upon DNA damage, ATM is activated via a series of highly organized machineries, including acetylation by the histone acetyltransferase TIP60 at lysine 3016 | SIGNOR-275891 |
P61812 | P36897 | 2 | binding | up-regulates | 0.745 | Tgf-? Signaling mediates a wide range of biological activities in development and disease. Tgf-? Ligands signal through heterodimeric type i and type ii receptors (tgf-? Receptor type i [t?RI, also known as alk5 and tgfbr1] and t?RII) that are members of the serine/threonine kinase family. | SIGNOR-196025 |
Q16832 | P29353 | 2 | binding | up-regulates | 0.393 | Collectively, our findings are consistent with the following mechanism for src-dependent ddr2 activation and signaling: 1) ligand binding promotes phosphorylation of tyr-740 in the ddr2 activation loop by src;2) tyr-740 phosphorylation stimulates intramolecular autophosphorylation of ddr2;3) ddr2 autophosphorylation generates cytosolic domain phosphotyrosines that promote the formation of ddr2 cytosolic domain-shc signaling complexes. | SIGNOR-140724 |
Q9UPT6 | Q13233 | 2 | binding | up-regulates | 0.542 | Overexpression of full-length jsap1 in cos-7 cells led to a considerable enhancement of jnk3 activation, and modest enhancement of jnk1 and jnk2 activation, by the mekk1-sek1 pathwaythe regions of jsap1 that bound jnk, sek1, and mekk1 were distinct from one another. Jnk and mekk1 also bound jsap1 in vitro, suggesting that these interactions are direct. | SIGNOR-71471 |
Q8IYW5 | P0C0S8 | 2 | binding | up-regulates | 0.2 | Rnf168 is recruited to sites of dna damage by binding to ubiquitylated histone h2a. | SIGNOR-183890 |
Q9Y6B2 | Q09472 | 2 | binding | down-regulates activity | 0.421 | Here, we show that EID-1 is a potent inhibitor of differentiation and link this activity to its ability to inhibit p300 (and the highly related molecule, CREB-binding protein, or CBP) histone acetylation activity. | SIGNOR-253379 |
Q9Y5I2 | Q9Y5G6 | 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-265709 |
O75385 | O75592 | 0 | ubiquitination | down-regulates quantity | 0.284 | Cell-based results demonstrate that the human PHR protein PAM restricts ULK1 protein levels (Fig.\u00a05h, i), and is sufficient to ubiquitinate ULK1 in a proteasome-dependent manner (Fig.\u00a05j).|Human PAM ubiquitinates ULK1 and regulates ULK1 levels. | SIGNOR-278765 |
O43318 | Q15653 | 1 | phosphorylation | down-regulates | 0.515 | Overexpression oftak1together with its activator protein,tak1binding protein 1 (tab1), induced thenucleartranslocation of nf-kappa b p50/p65 heterodimer accompanied by the degradation of i kappa b alpha and i kappa b beta, and the expression of kappa b-dependent reporter gene. | SIGNOR-55719 |
Q9UBI6 | Q9P212 | 2 | binding | up-regulates | 0.2 | In the non-canonical wntpathway, frizzled uses galfaq or galfai and gbetagamma dimers to activate phospholipase c (plc), resulting in protein kinase c (pkc) activation and calcium mobilization that regulates the transcription factor nfat, and frizzled also signals through the small gtpases rho and rac to c-jun n-terminal kinase (jnk), which activates the ap1 transcription factor | SIGNOR-152612 |
Q9UBS5 | Q9UQM7 | 0 | phosphorylation | down-regulates | 0.237 | Nmda-dependent internalization of gabab receptors requires activation of ca2+/calmodulin-dependent protein kinase ii (camkii), which associates with gabab receptors in vivo and phosphorylates serine 867 (s867) in the intracellular c terminus of the gabab1 subunit. | SIGNOR-166846 |
Q9Y478 | Q8IYT8 | 0 | phosphorylation | down-regulates | 0.329 | Ulk1/2 in turn phosphorylates all three subunits of ampk and thereby negatively regulates its activity | SIGNOR-173092 |
Q99708 | Q13535 | 0 | phosphorylation | up-regulates | 0.615 | Characterization of this site using phospho-specific antibodies and mutational analysis reveals that it is phosphorylated by atr and is required for binding of ctip to chromatin and subsequent processive resection. | SIGNOR-200245 |
O60674 | P78347 | 1 | phosphorylation | up-regulates activity | 0.328 | Jak2 activates tfii-i and regulates its interaction with extracellular signal-regulated kinase the interaction between tfii-i and erk, which is essential for its activity, can be regulated by jak2 through phosphorylation of tfii-i at tyrosine 248 | SIGNOR-235313 |
Q96CW1 | Q6ZNA4 | 0 | ubiquitination | up-regulates | 0.2 | Arkadia ubiquitylated the _?2 Subunit at lys130. In addition, arkadia interacted with the ap2 complex, and modified endocytosis of epidermal growth factor receptor (egfr) induced by egf. Arkadia thus appears to regulate egf signalling by modulating endocytosis of egfr through interaction with ap2 complex. | SIGNOR-168931 |
P12931 | P31645 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.258 | We found that 1) SERT exists in a tyrosine-phosphorylated form, 2) inhibition of tyrosine kinase(s) reduces SERT expression levels by facilitating SERT protein degradation, 3) Src-kinase activity up-regulates SERT protein expression with a concomitant increase in 5-HT uptake and tyrosine phosphorylation, and 4) mutation of Tyr47 or Tyr142 abolishes src-induced increases in transport function and phosphorylation of SERT. | SIGNOR-276386 |
P28288 | P28328 | 0 | ubiquitination | up-regulates activity | 0.401 | PEX5 and PMP70 are ubiquitinated by PEX2 during amino acid starvation. | SIGNOR-278708 |
P41134 | P31749 | 2 | binding | up-regulates | 0.334 | We have determined that Id1 physically interacts with AKT1, through its C-terminal region, and promotes AKT1 phosphorylation; | SIGNOR-255658 |
Q13627 | O95644 | 1 | phosphorylation | up-regulates activity | 0.429 | DYRK1A phosphorylation of NFATc1 and alphaA at S261, S278, S403 and S409 interfered with NFATc1 ubiquitination and ubiquitin-proteasome degradation.|Here, we demonstrated that DYRK1A increased NFATc1 (NFATc1 and alphaA isoform) protein stability, in contrast to the decrease of NFATc2 protein stability by DYRK1A. | SIGNOR-278278 |
P00519 | P49759 | 0 | phosphorylation | down-regulates | 0.259 | 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-181031 |
P54198 | P31749 | 0 | phosphorylation | up-regulates activity | 0.2 | Consistently, HIRA phosphorylation was effectively decreased by Akt1 knockdown and was completely eliminated by the depletion of both Akt1 and Akt2, suggesting that HIRA is phosphorylated primarily by Akt1 and that Akt2 seemed to contribute to HIRA phosphorylation as a supplementary kinase in myoblasts (XREF_FIG).|In this study, HIRA was more efficiently targeted by Akt1 in myoblasts. | SIGNOR-279584 |
Q96FF9 | P53350 | 0 | phosphorylation | down-regulates activity | 0.705 | Here we show that the mitotic kinases Aurora B and Cyclin-dependent kinase 1 (Cdk1) destabilize interactions between Sororin and the cohesin subunit precocious dissociation of sisters protein 5 (Pds5) by phosphorylating Sororin, leading to release of acetylated cohesin from chromosome arms and loss of cohesion. | SIGNOR-276122 |
Q9Y6C5 | Q15465 | 2 | binding | down-regulates activity | 0.803 | Biochemical analysis of ptch and ptch2 shows that they both bind to all hedgehog family members with similar affinity and that they can form a complex with smo.Current models suggest that binding of Shh to PTCH prevents the normal inhibition of the seven-transmembrane-protein Smoothened (SMO) by PTCH. | SIGNOR-217776 |
Q99683 | P25445 | 2 | binding | up-regulates | 0.694 | Ask1 binds fas | SIGNOR-109676 |
O43921 | P29317 | 2 | binding | up-regulates | 0.816 | Ephrin-a ligands (named ephrin-a1_ephrin-a5) are anchored in the plasma membrane through a gpi-linkage, and each can bind any of the epha subclass of receptors (epha1_epha8) | SIGNOR-65413 |
Q13418 | P49023 | 2 | binding | up-regulates | 0.799 | Co-immunoprecipitation from fibroblasts confirmed that the association between paxillin and ilk occurs in vivo in both adherent cells and cells in suspension. [__] thus, paxillin binding is necessary for efficient focal adhesion targeting of ilk and may therefore impact the role of ilk in integrin-mediated signal transduction events. | SIGNOR-106824 |
P28482 | P62714 | 0 | dephosphorylation | down-regulates activity | 0.479 | Inactivation of p42 MAP kinase by protein phosphatase 2A and a protein tyrosine phosphatase, but not CL100, in various cell lines|Protein phosphatase-2A was the only vanadate-insensitive phosphatase acting on Thr 183 of p42mapk or on MAPKK to be detected in PC12 cell extracts. | SIGNOR-248590 |
P61764 | P05129 | 0 | phosphorylation | down-regulates activity | 0.386 | Munc18a is essential for neurotransmitter release by exocytosis and can be phosphorylated by PKC in vitro on Ser-306 and Ser-313. We demonstrate that it is phosphorylated on Ser-313 in response to phorbol ester treatment in adrenal chromaffin cells. Mutation of both phosphorylation sites to glutamate reduces its affinity for syntaxin and so acts as a phosphomimetic mutation. | SIGNOR-249187 |
Q9Y2G0 | P42356 | 2 | binding | up-regulates quantity | 0.509 | PI4KA is recruited to plasma membrane by the adapter protein EFR3, which has two isoforms, EFR3A and EFR3B | SIGNOR-269093 |
Q63HK5 | P49662 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.27 | Chromatin immunoprecipitation showed a direct interaction of FE65 and Teashirt3 with the promoter region of CASP4. The results were consistent with a model in which reduced expression of Teashirt3, mediated by genetic or other causes, increases caspase-4 expression, leading to progression of AD. | SIGNOR-264815 |
O75771 | Q8WVD3 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.39 | RNF138 dependent ubiquitination of RAD51D and proteasome mediated degradation. | SIGNOR-278775 |
P49674 | P25054 | 1 | phosphorylation | up-regulates activity | 0.614 | Apc can be phosphorylated by ck1epsilon at ser1279 and ser1392. Mutation of conserved serine residues in the beta-catenin regulatory motifs of APC interfered with both axin-dependent phosphorylation and phosphorylation by CKIepsilon and impaired the ability of APC to regulate beta-catenin. | SIGNOR-109664 |
O00311 | Q9HAW4 | 1 | phosphorylation | up-regulates activity | 0.742 | Cdc7 phosphorylates Claspin in a manner dependent on AP and inhibits N\u2013C interaction.|Thus, Cdc7-ASK may activate DNA and PCNA bindings of Claspin through AP-mediated phosphorylation. | SIGNOR-279360 |
P21728 | P63096 | 2 | binding | up-regulates activity | 0.284 | 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-257068 |
P51692 | P17706 | 0 | dephosphorylation | down-regulates activity | 0.733 | In the previous study, we demonstrated that the nuclear isoform of T-cell protein-tyrosine phosphatase (TC-PTP) dephosphorylated and deactivated signal transducer and activator of transcription 5a (STAT5a) and STAT5b, thereby negatively regulating prolactin (PRL)-mediated signaling pathway. | SIGNOR-277126 |
Q14164 | O95644 | 1 | phosphorylation | up-regulates activity | 0.2 | Phosphorylation of NFATC1 at PIM1 target sites is essential for its ability to promote prostate cancer cell migration and invasion. Here we have identified ten PIM1 target sites in NFATC1 and found that prevention of their phosphorylation significantly decreases the transcriptional activity as well as the pro-migratory and pro-invasive effects of NFATC1 in prostate cancer cells. | SIGNOR-276778 |
Q96AV8 | O14757 | 0 | phosphorylation | down-regulates activity | 0.387 | Chk1 inhibits the transcriptional repressor function of E2F7 and E2F8 to promote cell cycle progression and prevent apoptosis.|Here, we demonstrate that Chk1 phosphorylates both E2F7 and E2F8 in response to DNA damage. | SIGNOR-279692 |
P49427 | Q9UBF6 | 0 | polyubiquitination | down-regulates activity | 0.748 | SAG was found to be the second family member of Rbx (RING box protein) or ROC (Regulator of cullins) or Hrt that is a component of SCF E3 ubiquitin ligase. Indeed, like ROC1/Rbx1/Hrt1, SAG binds to Cul1 and SAG-Cul1 complex has ubiquitin ligase activity to promote poly-ubiquitination of E2/Cdc34. | SIGNOR-271443 |
Q13315 | P06748 | 1 | phosphorylation | up-regulates activity | 0.352 | In addition to Serine 125, ATM may also phosphorylate other sites on NPM. | SIGNOR-280182 |
O14807 | P49356 | 0 | 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 |
P27361 | P36956 | 1 | phosphorylation | up-regulates activity | 0.443 | Map kinases erk1/2 phosphorylate sterol regulatory element-binding protein (srebp)-1a at serine 117 in vitro. mutation of serine 117 to alanine abolished erk2-mediated phosphorylation in vitro and the map kinase-related transcriptional activation of srebp-1a by insulin and platelet-derived growth factor in vivo. | SIGNOR-80096 |
P78536 | P46531 | 1 | cleavage | up-regulates activity | 0.739 | ... here we show that an additional processing event occurs in the extracellular part of the receptor, preceding cleavage by the gamma-secretase-like activity. Purification of the activity accounting for this cleavage in vitro shows that it is due to tace (tnfalpha-converting enzyme), a member of the adam (a disintegrin and metalloprotease domain) family of metalloproteases. | SIGNOR-78903 |
P17252 | O60674 | 1 | phosphorylation | up-regulates activity | 0.26 | These results suggest that PKC activates JAK2 and thereby STAT3 by directly phosphorylating T174 and S518. | SIGNOR-277262 |
Q9NR28 | Q96CA5 | 2 | binding | down-regulates | 0.666 | These results suggest that ml-iap might regulate apoptosis by sequestering smac and preventing it from antagonizing xiap-mediated caspases, rather than by direct caspases. | SIGNOR-129869 |
Q9UQD0 | Q9UQM7 | 0 | phosphorylation | up-regulates activity | 0.279 | 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-275785 |
P08754 | Q9Y5X5 | 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-256852 |
Q9Y2X7 | P63000 | 2 | binding | up-regulates activity | 0.656 | Activated RAC1 interacts with GIT1, a GAP protein of ARF6, and causes the inactivation of ARF6 [78]. As ARF6 plays a role in the promotion of the recycling of macropinosomes to the plasma membrane [78], the inactivation of ARF6 by RAC1 reduces the recycling of macropinosomes. | SIGNOR-277783 |
P46531 | Q9H488 | 2 | binding | up-regulates | 0.745 | Notch_ is modified in its epidermal growth factor-like domains by the addition of_ fucose_ to serine or threonine residues. O-fucosylation is mediated by protein o-fucosyltransferase 1 and down-regulation of this enzyme by rna interference or mutation of the ofut1 gene in drosophila or by mutation of the pofut1 gene in mouse prevents notch signaling. | SIGNOR-104627 |
Q03112 | Q01196 | 2 | binding | down-regulates activity | 0.524 | The results that we present here support this model and show that EVI1 interacts with and inhibits RUNX1. As for GATA1, EVI1 seems to repress RUNX1 function by interacting specifically with its DNA-binding domain Runt, leading to destabilization and dissolution of the DNA-RUNX1 complex. | SIGNOR-255716 |
P28482 | P06239 | 1 | phosphorylation | up-regulates activity | 0.583 | Phosphorylation at Ser-59 (or alternatively, its mutation to Glu) reverses the inhibition and allows interaction of the p56lck SH2 domain with p62.|phosphotyrosine-independent binding of p62 to the p56lck SH2 domain appears to provide an alternative pathway for p56lck signaling that is regulated by Ser-59 phosphorylation. | SIGNOR-249412 |
Q13330 | P78368 | 0 | phosphorylation | up-regulates activity | 0.344 | CKI-gamma2 could further potentiate the ER corepressive function of metastasis-associated protein-1 short form.|These findings identified metastasis-associated protein-1 short form as a target of CKI-gamma2, and provided new evidence to suggest that CKI-gamma2 phosphorylates and modulates the functions of metastasis-associated protein-1 short form, and that these extranuclear effects of estrogen might have important implications in regulating the functions of metastasis-associated protein-1 short form in human mammary epithelial and cancer cells. | SIGNOR-280236 |
Q96JK9 | Q06330 | 2 | binding | up-regulates | 0.877 | When bound to the active intracellular domain of notch (nicd), rbpj recruits a coactivator complex, including a mastermind homologue (maml1-3 in mammals), and drives a complex transcriptional program with pervasive phenotypic effects. | SIGNOR-176200 |
P06493 | O94761 | 1 | phosphorylation | up-regulates activity | 0.355 | During S/G2 phases, CDK1 and CDK2 (CDK1/2) phosphorylate RECQL4 on serines 89 and 251, enhancing MRE11/RECQL4 interaction and RECQL4 recruitment to DSBs. | SIGNOR-277375 |
Q00535 | P06241 | 0 | phosphorylation | up-regulates activity | 0.608 | Constitutively active Fyn phosphorylated Tyr15 of Cdk5. Fyn Facilitates Kinase Activity of Cdk5 Via Tyr15 Phosphorylation | SIGNOR-251156 |
Q02548 | O75626 | 2 | transcriptional regulation | down-regulates quantity | 0.502 | Overexpression of BSAP reduced Blimp-1 expression in CH12.LX.A2 clones but not in MPC11 clones. In addition, overexpression of BSAP in CH12.LX.A2 cells suppressed spontaneous appearance of cells with high Syndecan-1 expression and high amounts of intracytosolic as well as secreted Ig synthesi | SIGNOR-269085 |
Q5JVS0 | P17252 | 0 | phosphorylation | down-regulates activity | 0.29 | We found a strong phosphorylation of Ki-1/57 by PKCalphabeta, PKCdelta, PKClambda/zeta, and especially by PKCsigma, however not by PKCmi. These data show that Ki-1/57 can serve in principal as a substrate for a wide variety of different PKC isoforms but also that its phosphorylation is strongest with PKCsigma. | This suggests that the two threonine residues present in this fragment (Thr354 and Thr375) might be the main target residues for phosphorylation by PKC in vitro. | Ki-1/57 Exits the Nucleus upon PMA Activation | SIGNOR-249246 |
P17612 | Q9Y259 | 1 | phosphorylation | up-regulates activity | 0.253 | Choline kinase beta (CKbeta) is one of the CK isozymes involved in the biosynthesis of phosphatidylcholine. | This study provides evidence for CKβ phosphorylation by protein kinase A (PKA).|Phosphorylation sites were located on CKβ residues serine-39 and serine-40 as determined by mass spectrometry and site-directed mutagenesis. Phosphorylation increased the catalytic efficiencies for the substrates choline and ATP about 2-fold, without affecting ethanolamine phosphorylation, and the S39D/S40D CKβ phosphorylation mimic behaved kinetically very similar. | SIGNOR-275629 |
O43295 | Q92558 | 2 | binding | up-regulates | 0.553 | Wrp binds directly to wave-1 through its src homology domain 3 and specifically inhibits rac function in vivo. | SIGNOR-95967 |
O95198 | Q96J92 | 2 | binding | down-regulates quantity by destabilization | 0.519 | We found that KLHL2, as well as KLHL3, was co-immunoprecipitated with all four WNK isoforms. The direct interaction of KLHL2 with WNKs was confirmed on fluorescence correlation spectroscopy. Co-expression of KLHL2 and Cullin3 decreased the abundance of WNK1, WNK3 and WNK4 within HEK293T cells, and a significant increase of WNK4 ubiquitination by KLHL2 and Cullin3 was observed both in HEK293T cells and in an in vitro ubiquitination assay. These results suggest that KLHL2-Cullin3 also functions as an E3-ligase for WNK isoforms within the body. | SIGNOR-272118 |
P08237 | O15294 | 0 | glycosylation | down-regulates activity | 0.346 | Our previous investigation on O-GlcNAcylation of PFK1 has demonstrated that O-GlcNAcylation inhibits PFK1 enzyme activity|In cells, a single set of antagonistic enzymes-O-GlcNAc transferase (OGT) and O-GlcNAc hydrolase are responsible for the addition and removal of GlcNAc moiety, respectively. | SIGNOR-267584 |
Q9Y618 | Q96EB6 | 0 | null | up-regulates | 0.494 | In differentiated adipocyte cell lines, SIRT1 inhibits adipogenesis and enhances fat mobilization through lipolysis by suppressing the activity of PPARγ. SIRT1 achieves this by promoting the assembly of a corepressor complex, involving NCoR1 and SMRT, on the promoters of PPARγ target genes to repress their transcription. | SIGNOR-253506 |
Q9H867 | Q9BZE9 | 2 | binding | up-regulates | 0.342 | In the case of vcp, methylation by mettl21d was stimulated by the addition of the ubx cofactor aspscr1, which we show directly interacts with the methyltransferase. | SIGNOR-200572 |
P10412 | Q96GD4 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.2 | we showed previously that phosphorylation of S27 in human histone H1.4 (H1.4S27-P), prevents binding of heterochromatin protein 1 (HP1) family members (officially known as chromobox protein homologs) to the neighboring dimethylated K26. Here, we present the first functional characterization of H1.4S27-P in vivo and in vitro. We show that H1.4S27 phosphorylation is cell-cycle-regulated and its levels peak on metaphase chromosomes. We identify further Aurora B as the kinase phosphorylating H1.4S27. | SIGNOR-262658 |
P17252 | Q9UEY8 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.334 | Results of in vitro experiments with recombinant alpha adducin demonstrated that PKC-phosphorylated adducin was proteolyzed by calpain more quickly than unphosphorylated adducin. | Phosphorylation of adducin by PKC may be a common mechanism for regulating adducin proteolysis by several proteases. | The antibody used in panel B is specific for the PKC-phosphorylated form of adducin. This antibody was raised against the phosphopeptide CKKFRTP[pS]FLKKNK, corresponding to amino acids 656-668 of human gamma adducin | SIGNOR-249143 |
P63096 | P30550 | 2 | binding | up-regulates activity | 0.268 | 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-257046 |
P49841 | Q15831 | 0 | phosphorylation | down-regulates activity | 0.378 | In this regard, it was shown that LKB1 physically associates with PKC-zeta, which is known to inhibit GSK3beta kinase activity by promoting its phosphorylation.|Thus, inhibitory phosphorylation of GSK3beta by LKB1 and/or AKT may be a cardinal event leading to constitutive activation of Wnt and beta-catenin signaling (XREF_FIG). | SIGNOR-280148 |
P09471 | Q9NQS5 | 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-256983 |
Q13535 | P27707 | 1 | phosphorylation | up-regulates activity | 0.2 | Since activation of dCK by IR was not prevented by KU-60019 at longer times, but could be suppressed if the ATR inhibitor was combined with the ATM inhibitor, we propose that dCK is activated by ATR when ATM is inhibited.|Taken together, these data indicate that ATR, like ATM [15], can directly phosphorylate dCK at Ser 74 in vitro and thereby increase its activity.Most dCK activators share the feature of inducing DNA damage followed by DNA damage response, a complex signaling network aimed to preserve genome integrity. | SIGNOR-279494 |
Q9Y243 | P67775 | 0 | dephosphorylation | down-regulates activity | 0.738 | Protein phosphatase 2A negatively regulates insulin's metabolic signaling pathway by inhibiting Akt (protein kinase B) activity in 3T3-L1 adipocytes | SIGNOR-248654 |
P84022 | P46531 | 2 | binding | up-regulates | 0.543 | Nicd and smad3 were shown to interact directly, both in vitro and in cells, in a ligand-dependent manner, and smad3 could be recruited to csl-binding sites on dna in the presence of csl and nicd | SIGNOR-119374 |
P03372 | Q15466 | 2 | binding | down-regulates | 0.649 | Our results identify shp as an inhibitor of 4-oht agonist activity in rl95-2 human endometrial carcinoma cells that express endogenous er?. We conclude that shp does not decrease er expression, but rather it is the direct interaction of shp with er that inhibits er transcriptional activity. | SIGNOR-115033 |
Q16539 | O43255 | 1 | phosphorylation | up-regulates | 0.2 | We show that siah2 is subject to phosphorylation by p38 mapk, which increases siah2-mediated degradation of phd3. | SIGNOR-149890 |
P48730 | O15534 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.807 | Human casein kinase Idelta phosphorylation of human circadian clock proteins period 1 and 2. We have now extended our previous studies to show that human casein kinase Idelta (hCKIdelta), the closest homologue to hCKIepsilon, associates with and phosphorylates hPER1 and causes protein instability. Furthermore, we observed that both hCKIdelta and hCKIepsilon phosphorylated and caused protein instability of human period 2 protein (hPER2). | SIGNOR-268001 |
Q9UBS5 | Q13554 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.2 | ERK1/2 and CaMKIIβ mediated phosphorylation of GABAB1 at serine 867 (S867) and threonine 872 (T872). We found that, in addition to CaMKIIβ, also ERK1/2 is involved in the degradation pathway of GABAB receptors under physiological and ischemic conditions. In contrast to our previous view, CaMKIIβ does not appear to directly phosphorylate S867. Instead, the data support a mechanism in which CaMKIIβ activates ERK1/2, which then phosphorylates S867 and T872 in GABAB1. | SIGNOR-277851 |
P01106 | P49761 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | C-Myc enhances transcriptional activation of CLK3 promoter in CCA cells. | SIGNOR-274123 |
P08754 | P25090 | 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-256745 |
P49716 | Q9P2J3 | 2 | binding | down-regulates quantity by destabilization | 0.251 | KLHL9 mediates poly-ubiquitylation of C/EBPβ and C/EBPδ isoforms. We confirmed KLHL9 deletions in an independent cohort and showed that this protein is necessary for Cul3-ligase mediated ubiquitylation and proteasomal degradation of established MES-GBM MRs, C/EBPβ and C/EBPδ. | SIGNOR-272459 |
Q02156 | Q8WV44 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | RINCK induces the ubiquitination of PKC both in vitro and in cells. Overexpression of RINCK reduces the levels of PKC in cells, whereas genetic knockdown of endogenous RINCK increases the levels of PKC. The RINCK-mediated ubiquitination is likely to be polyubiquitination, because the ubiquitinated PKCβII was detected as a high molecular weight smear. | SIGNOR-271668 |
P00533 | P98077 | 2 | binding | up-regulates | 0.611 | Shc exists in three different isoforms, p46shc, p52shc and p66shc which are tyrosine phosphorylated upon egf stimulation and bind to the activated egfr and grb2. Interestingly, while the 46 and 52 kda isoforms increase mitogenic signalling after egf stimulation and are able to transform nih3t3 cells (pelicci et al. 1992), p66shc has no transforming potential and negatively influences egf-induced c-fos transcription | SIGNOR-107750 |
Q14194 | P49841 | 0 | phosphorylation | up-regulates | 0.47 | Using in vitro kinase assays and pharmacological inhibition of gsk3 as described above for crmp2 and crmp4, it was found that thr509 (and presumably ser518 and thr514) of human crmp1 is phosphorylated by gsk3, following priming of ser522 by cdk5 | SIGNOR-145999 |
P06239 | P04234 | 1 | phosphorylation | up-regulates activity | 0.571 | Last, we demonstrate directly that members of the CD3 complex, including the gamma, delta, and epsilon chains, as well as a putative zeta subunit, can be phosphorylated at tyrosine residues by the CD4/CD8.p56lck complex. | SIGNOR-259929 |
O95297 | P12931 | 0 | phosphorylation | up-regulates | 0.468 | Indeed, our studies indicated that cross-linking of pzr by cona lead to activation of c-src, which may be responsible for phosphorylation of pzr and possibly other proteins. Phosphorylation of pzr in turn recruits shp-2, which by itself is an essential signal transducertyrosine residues 241 and 263 embedded in the itims are responsible for the tyrosine phosphorylation of pzr | SIGNOR-113410 |
P04049 | P27361 | 0 | phosphorylation | down-regulates activity | 0.637 | Here, we identify six residues of Raf-1 (S29, S43, S289, S296, S301, and S642) that become hyperphosphorylated in a manner coincident with Raf-1 inactivation. | Five of the identified sites are proline-directed targets of activated ERK, and phosphorylation of all six sites requires MEK signaling, indicating a negative feedback mechanism. Hyperphosphorylation of these six sites inhibits the Ras/Raf-1 interaction and desensitizes Raf-1 to additional stimuli.|FLAG-Raf-1 phosphorylated by activated ERK2 | SIGNOR-143688 |
O00468 | Q05901 | 2 | binding | up-regulates activity | 0.2 | Treatment of muscle cells with neural agrin causes tyrosine phosphorylation of the AChR β subunit and induces AChR clustering by promoting anchoring of the receptor protein to postsynaptic cytoskeleton. Regulation of acetylcholine receptor clustering by the tumor suppressor APC. By showing a direct requirement for APC in AChR clustering, our present study suggests that the Wnt/β-catenin pathway may crosstalk with the agrin signaling cascade during the formation of mammalian neuromuscular junction. | SIGNOR-264260 |
Q8WYB5 | Q13950 | 2 | binding | up-regulates | 0.401 | Moz and morf both interact with runx2 / while morf does not acetylate runx2, its sm domain potentiates runx2-dependent transcriptional activation. | SIGNOR-117335 |
P31276 | O15550 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.267 | Evidence for direct involvement of UTX in regulation of HOX gene activity was demonstrated through UTX knockdown experiments in HEK293T cells in which loss of UTX induced transcriptional repression of HOXA and HOXC clusters. | SIGNOR-260027 |
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