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 |
|---|---|---|---|---|---|---|---|
Q99550 | Q6IQ55 | 0 | phosphorylation | down-regulates quantity | 0.2 | Additionally, in vivo ubiquitin assays showed that expression of either the kinase-dead TTBK2 or the MPP9-S629 and S636-2A mutant significantly decreased the ubiquitination level of MPP9.|Also, the S629A mutant almost abolished the phosphorylation of MPP9 by TTBK2 in the kinase assay in vitro, suggesting that S629 is the main site for MPP9 phosphorylation by TTBK2. | SIGNOR-278998 |
Q00987 | Q13315 | 0 | phosphorylation | down-regulates activity | 0.756 | Dephosphorylation stabilizes mdm2 and increases its affinity for p53, inducing p53 degredation. ;phosphorylated s260 and s395 ands260d and s395d mutant peptides inhibited binding of binding of a specific monoclonal antibody raised to mdm2. Phosphorylation of mdm2 regulates p53 degradation. | SIGNOR-94268 |
O00303 | Q7Z6M2 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | Mediation of eIF3-f polyubiquitination by the SCFMAFbx. The association of MAFbx with the essential Skp1, Roc 1 and Cul1 proteins, specific components of an E3 ubiquitin–protein ligase (SCFMAFbx), was previously described. Here, we present evidence that during muscle atrophy MAFbx targets the eukaryotic initiation factor 3 subunit 5 (eIF3-f) for ubiquitination and degradation by the proteasome. | SIGNOR-271768 |
P08581 | P17706 | 0 | dephosphorylation | down-regulates | 0.501 | We have identified ptp1b and tcptp as negative regulators of the hepatocyte growth factor receptor, the met receptor-tyrosine kinase. In vivo, loss of ptp1b or tcptp enhances hepatocyte growth factor-mediated phosphorylation of met. | SIGNOR-181331 |
P48546 | P63092 | 2 | binding | up-regulates activity | 0.444 | The GPCRs are allocated in five families where the GLP-1R and GIPR are found within the secretin family, also classified as class B [31,32]. Upon stimulation by an extracellular stimuli (ligand), GPCRs undergo conformational changes, and triggers downstream intracellular signals by coupling with G proteins (or other intracellular proteins such as arrestins), causing a wide range of both physiological and pathological processes.To stimulate insulin secretion, and in the presence of elevated blood glucose concentrations, GLP-1R activation in pancreatic beta cells promote recruitment and activation of Gαs protein leading to adenylate cyclase-mediated cAMP production, elevation of Ca2+, and ERK1/2 phosphorylation (Fig. 3) | SIGNOR-278138 |
P07196 | P61981 | 2 | binding | down-regulates activity | 0.294 | These results suggest the important role of 14-3-3 in the dynamic regulation of NF-L assembly, and in the capacity to prevent the formation of NF-L aggregates. all seven isoforms specifically interacted with NF-L, but not NF-M or NF-H. specific interaction of 14-3-3 proteins with phosphorylated NF-L subunits also indicated the role of 14-3-3 and NF-L phosphorylation in the disassembly of neurofilaments. What is more, binding of 14-3-3 to phosphorylated NF-L subunits may prevent the dephosphorylation of these subunits by phosphatases, maintaining the hyperphosphorylation state of the subunits, which facilitates the disassembly of neurofilaments. | SIGNOR-252400 |
Q16513 | Q15118 | 0 | phosphorylation | up-regulates activity | 0.338 | PDK1 phosphorylates the PRKs at their conserved activation loop threonines (Thr-774 and Thr-816 for PRK1 and PRK2, respectively) both in vitro and in vivo. | SIGNOR-250265 |
P31749 | O15519 | 1 | phosphorylation | down-regulates quantity | 0.466 | TNFalpha enhanced FLIP(L) serine phosphorylation, which was increased by activated Akt-1. Serine 273, a putative Akt-1 phosphorylation site in FLIP(L), was critical for the activation-induced reduction of FLIP(L). Thus, these observations document a novel mechanism where by TNFalpha facilitates the reduction of FLIP(L) protein, which is dependent on the phosphatidylinositol 3-kinase/Akt signaling. | SIGNOR-252548 |
P35222 | P12931 | 0 | phosphorylation | down-regulates activity | 0.761 | beta-catenin is a good substrate of pp60c- srctyrosine kinase in vitro;this kinase modifies specifically tyr-86 and tyr-654although consistently detected, this negative effect of tyr-86 phosphorylation on tbp binding was clearly less important than the positive effect observed after tyr-654 phosphorylation. | SIGNOR-106458 |
Q96FF9 | Q7Z5K2 | 2 | binding | down-regulates activity | 0.2 | We show that DNA replication and cohesin acetylation promote binding of Sororin to cohesin, and that Sororin displaces Wapl from its binding partner Pds5. | SIGNOR-265266 |
P29353 | P43405 | 0 | phosphorylation | up-regulates | 0.762 | The syk-family kinases (syk and zap-70) were able to phosphorylate the y239 and y240 sites, and less efficiently the y317 site on sch1 (iso2). | SIGNOR-59635 |
P63096 | P30542 | 2 | binding | up-regulates activity | 0.458 | 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-256697 |
P40189 | P07947 | 1 | phosphorylation | up-regulates activity | 0.2 | Binding of LIF to the LIFR-gp130 receptor complex has been previously shown to activate YES and YAP/TAZ-TEAD -dependent transcription, which is required to maintain self-renewal in embryonic stem cells | SIGNOR-278033 |
P06730 | Q9BUB5 | 0 | phosphorylation | up-regulates | 0.779 | Mnk1 and mnk2 regulate protein synthesis by phosphorylating the initiation factor eif4e. | SIGNOR-166646 |
P40763 | P17677 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.3 | In this study, we demonstrated for the first time that growth-associated protein 43 (GAP43), a well known growth cone protein that promotes axonal regeneration, can be induced in rat brain astrocytes by the proinflammatory endotoxin lipopolysaccharide via both nuclear factor-κB and signal transducer and activator of transcription 3-mediated transcriptional activation. | SIGNOR-266772 |
P12830 | Q00535 | 0 | phosphorylation | down-regulates activity | 0.298 | Using both the Cdk inhibitor roscovitine and an RNA interference strategy, it was also demonstrated that Cdh1 was phosphorylated by Cdk5, an enzyme that can be persistently activated when bound to p25 [ xref ], the proteolytic product of p35 that has previously been shown to accumulate in the neurons of patients with Alzheimer\u2019s disease [ xref ]. | SIGNOR-279679 |
P04637 | P25445 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.605 | In an attempt to understand how CD95 expression is regulated by p53, we identified a p53-responsive element within the first intron of the CD95 gene, as well as three putative elements within the promoter. The intronic element conferred transcriptional activation by p53 and cooperated with p53-responsive elements in the promoter of the CD95 gene. wt p53 bound to and transactivated the CD95 gene, | SIGNOR-62376 |
O14775 | P14416 | 2 | binding | up-regulates activity | 0.603 | The D2-class dopamine receptors (D2, D3, and D4) couple to the Gi/o family of G proteins and thus induce inhibition of AC | SIGNOR-264993 |
O95631 | Q92859 | 2 | binding | up-regulates activity | 0.825 | Experiments have demonstrated that Neogenin also mediates Netrin-1 attractive functions. Both DCC and Neogenin are type I transmembrane receptors that belong to the immunoglobulin superfamily proteins. | SIGNOR-268169 |
Q8N8S7 | Q13976 | 0 | phosphorylation | down-regulates activity | 0.302 | Vertebrate Ena/VASP proteins are phosphorylated by PKA, as well as PKG, and the phosphorylation is required for full function in a number of cellular contexts. PKG may preferentially phosphorylate sites of Ena/VASP proteins that reduce or inactivate these proteins. Inactivated Ena/VASP proteins dissociate from actin filaments, allowing capping proteins to bind and block monomer addition to plus ends, resulting in filament retraction. | SIGNOR-268288 |
P53350 | Q53GT1 | 2 | binding | down-regulates activity | 0.446 | Here, we identify PLK1 as a target of the cullin 3 (CUL3)-based E3 ubiquitin ligase, containing the BTB adaptor KLHL22, which regulates chromosome alignment and PLK1 kinetochore localization but not PLK1 stability. In the absence of KLHL22, PLK1 accumulates on kinetochores, resulting in activation of the spindle assembly checkpoint (SAC). CUL3-KLHL22 ubiquitylates Lys 492, located within the PBD, leading to PLK1 dissociation from kinetochore phosphoreceptors. | SIGNOR-272108 |
Q14457 | Q9Y2M5 | 2 | binding | down-regulates quantity by destabilization | 0.277 | Cul3-KLHL20 Ubiquitin Ligase Governs the Turnover of ULK1 and VPS34 Complexes to Control Autophagy Termination. KLHL20 promotes ubiquitination of phagophore-residing VPS34 and Beclin-1 | SIGNOR-272415 |
Q9H0A0 | P04637 | 1 | acetylation | up-regulates quantity by stabilization | 0.337 | NAT10 acetylates p53 at K120 and stabilizes p53 by counteracting Mdm2 action. In addition, NAT10 promotes Mdm2 degradation with its intrinsic E3 ligase activity. | SIGNOR-272406 |
P18031 | P49841 | 0 | phosphorylation | down-regulates quantity | 0.469 | GSK-3beta phosphorylates PTP1B at serine residues, and activation of GSK-3beta reduces the mRNA level of PTP1B. | SIGNOR-279724 |
Q9UKV0 | Q06413 | 2 | binding | down-regulates | 0.633 | Mirk activated mef2 not through direct phosphorylation of mef2 but by phosphorylation of its inhibitors, the class ii histone deacetylases (hdacs). Mef2 is sequestered by class ii hdacs such as hdac5 and mef2-interacting transcriptional repressor (mitr). Mirk antagonized the inhibition of mef2c by mitr, whereas kinase-inactive mirk was ineffective. Mirk phosphorylates class ii hdacs at a conserved site within the nuclear localization region, reducing their nuclear accumulation in a dose-dependent and kinase-dependent manner | SIGNOR-235642 |
Q2M2I3 | 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-273750 |
O15111 | Q9C0C7 | 1 | phosphorylation | up-regulates activity | 0.2 | Furthermore, we show that mitophagy function of AMBRA1 is post-translationally controlled, upon HUWE1 activity, by a positive phosphorylation on its serine 1014. This modification is mediated by the IKKα kinase and induces structural changes in AMBRA1, thus promoting its interaction with LC3/GABARAP (mATG8) proteins and its mitophagic activity. | SIGNOR-272974 |
O75581 | Q9H1J7 | 2 | binding | up-regulates | 0.625 | Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation. | SIGNOR-131888 |
Q05469 | P28482 | 0 | phosphorylation | up-regulates activity | 0.368 | Thus, activation of the ERK pathway appears to be able to regulate adipocyte lipolysis by phosphorylating HSL on Ser(600) and increasing the activity of HSL. | SIGNOR-249413 |
P40425 | P55075 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.251 | Our results in ES cells suggest that Engrailed inhibits Fgf8 expression in the absence of Pbx1. We identified single Engrailed- and Pbx-binding sites in the Fgf8 intron that inhibit expression of Fgf8 in mouse ES cells, but that together can allow full Fgf8 expression. Our data support the model that Engrailed heterodimerized with Pbx might activate transcription, while Engrailed or Pbx proteins alone might repress transcription | SIGNOR-265778 |
Q9HC98 | P23443 | 1 | phosphorylation | up-regulates activity | 0.367 | Here we demonstrate that in addition to phosphorylating S6K1 and SGK1 at their hydrophobic motif, NEK6 also phosphorylates S6K1 at two other sites and phosphorylates SGK1 at one other site in vitro. Analysis of the peptides phosphorylated by NEK6 (Fig 2), performed in the present study has confirmed this, and identified two novel sites on S6K1 (Ser53 and Ser403) as major sites of NEK6 phosphorylation. | SIGNOR-262953 |
P49815 | P27361 | 0 | phosphorylation | down-regulates activity | 0.694 | 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-249457 |
P05141 | Q9NQU5 | 0 | phosphorylation | up-regulates quantity | 0.2 | In the present study, it was demonstrated that ANT2 was phosphorylated by PAK6 at T107.|Moreover, PAK6 overexpression upregulated the protein expression of ANT2, while PAK6 knockdown led to opposing effects. | SIGNOR-279473 |
P53990 | Q6PHR2 | 0 | phosphorylation | down-regulates activity | 0.624 | ULK3 phosphorylation of IST1 is required to sustain the abscission checkpoint and inhibits IST1 function in abscission. | SIGNOR-278205 |
Q16539 | Q12948 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.2 | P38 interacts with and phosphorylates the Ser241 and ser272 sites of FOXC1 to maintain its stability by inhibiting ubiquitination and degradation. | SIGNOR-275913 |
P17252 | Q15311 | 1 | phosphorylation | up-regulates activity | 0.389 | In deletion mutant analyses of potential phosphorylation sites in RLIP76, we identified T297 and S509 as targets for phosphorylation by PKCalpha. Phosphorylation at T297 increased doxorubicin (DOX)-transport activity approximately 2-fold for RLIP76 purified from recombinant source | SIGNOR-263164 |
Q96EB6 | O15105 | 1 | deacetylation | down-regulates | 0.441 | Sirt1 reversed acetyl-transferase (p300)-mediated acetylation of two lysine residues (lys-64 and -70) on smad7. sirt1-mediated deacetylation of smad7 enhanced smad ubiquitination regulatory factor 1 (smurf1)-mediated ubiquitin proteasome degradation, which contributed to the low expression of smad7 in sirt1-overexpressing mesangial cells. | SIGNOR-150595 |
P01111 | Q06124 | 0 | dephosphorylation | up-regulates activity | 0.673 | Here we identify SHP2 as the ubiquitously expressed tyrosine phosphatase that preferentially binds to and dephosphorylates Ras to increase its association with Raf and activate downstream proliferative Ras/ERK/MAPK signalling. | SIGNOR-255754 |
Q06124 | Q6P1J9 | 1 | dephosphorylation | up-regulates activity | 0.494 | We found in this work that SHP2 dephosphorylates parafibromin and Cdc73, a component of the nuclear RNA polymerase II associated factor (PAF) complex, which can function as a tumor suppressor or oncoprotein in a context dependent manner. | SIGNOR-277036 |
P31946 | Q05513 | 0 | phosphorylation | down-regulates activity | 0.368 | Our results with the 14-3-3 mutants indirectly imply a new phosphorylation site, 130Ser (and to a lesser extent 141Thr), in 14-3-3b that regulates the association}dissociation of 14-3-3b and PKC-f. | SIGNOR-249035 |
P06213 | P01308 | 2 | binding | up-regulates activity | 0.934 | Our previous studies indicated that amino acid residues 240-250 in the cysteine-rich region of the human insulin receptor alpha-subunit constitute a site in which insulin binds. | SIGNOR-23001 |
P04637 | Q92481 | 2 | binding | up-regulates quantity by stabilization | 0.335 | These data suggest that AP-2β enhances transactivation of p53 and regulates CRYAB transcription via p53. Further study demonstrated that AP-2β interacts with p53 and augments its protein stability. Taken together, our results indicate that AP-2β up-regulates the transcription of the CRYAB gene through stabilizing p53. | SIGNOR-255422 |
P98177 | P31749 | 0 | phosphorylation | down-regulates | 0.763 | Foxo4 transcription factor, also referred to afx, contains three putative phosphorylation motif sites for protein kinase b (pkb), thr32, ser197, and ser262, and it is proposed that phosphorylated foxo4 stays in the cytosol and is imported to the nucleus through dephosphorylation to induce target gene expression | SIGNOR-252486 |
Q13639 | P63092 | 2 | binding | up-regulates activity | 0.497 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ‚â• -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ‚â• -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ‚â• -1.0. | SIGNOR-256769 |
Q9H1K0 | Q16539 | 0 | phosphorylation | up-regulates | 0.2 | We found that p38alpha can phosphorylate the rab5 effectors eea1 and rabenosyn-5 on thr-1392 and ser-215, respectively, and these phosphorylation events regulate the recruitment of eea1 and rabenosyn-5 to membranes | SIGNOR-140143 |
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 |
P17252 | Q92888 | 1 | phosphorylation | up-regulates activity | 0.439 | We showed that the first and second phase of RhoA activity are dependent on p63 and Ca2+/PKC, respectively, and further identified phosphorylation of serine 240 on p115 RhoGEF by PKC to be the mechanistic link between PKC and RhoA. | SIGNOR-277530 |
P17252 | P23677 | 1 | null | down-regulates activity | 0.37 | In contrast, phosphorylation of the A isoform with PKC caused a significant decrease in activity whether assayed in the presence or absence of calcium/calmodulin (to _25% of the unphosphorylated enzyme activity). | SIGNOR-248991 |
P12931 | P23528 | 1 | phosphorylation | down-regulates | 0.553 | Tyrosine phosphorylation of cofilin at y68 by v-src leads to its degradation through ubiquitin-proteasome pathway | SIGNOR-188352 |
P16949 | O14965 | 0 | phosphorylation | down-regulates activity | 0.388 | Inhibition of AURKA activity activates stathmin function via reduced phosphorylation and facilitates microtubule destabilization in RB1 -/- cells, heavily impacting the bipolar spindle formation and inducing mitotic cell death selectively in RB1 -/- cells.|Two serine phosphorylation sites, Ser16 and Ser63, in stathmin contain a consensus sequence for AURKA phosphorylation and the mutations in these two serine sites abolished stathmin phosphorylation by AURKA, suggesting that stathmin is a substrate of AURKA for phosphorylation xref , xref . | SIGNOR-278913 |
P18583 | Q96T37 | 2 | binding | up-regulates | 0.239 | Here we report that the human nxf1-binding protein rbm15 binds specifically to human dbp5 and facilitates its direct contact with mrna in vivo. | SIGNOR-188264 |
P14416 | P63096 | 2 | binding | up-regulates activity | 0.483 | 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-256701 |
Q9NX47 | Q9NX47 | 2 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | Rapid degradation of MITOL by autoubiquitination activity. Taken together, these results suggested that MITOL strictly controls its protein expression level by rapid degradation of MITOL through the PHD-dependent autoubiquitination activity. | SIGNOR-271895 |
Q03113 | P33032 | 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-257441 |
O95405 | P36897 | 2 | binding | up-regulates activity | 0.631 | Sara functions to recruit smad2 to the tgfbeta receptor by controlling the subcellular localization of smad2 and by interacting with the tgfbeta receptor complex | SIGNOR-62868 |
Q99062 | P09603 | 2 | binding | up-regulates | 0.321 | A crystal structure of the signaling complex between human granulocyte colony-stimulating factor (gcsf) and a ligand binding region of gcsf receptor (gcsf-r), has been determined to 2.8 a resolution | SIGNOR-144737 |
Q9Y4C0 | Q8NFZ4 | 2 | binding | up-regulates activity | 0.825 | The neurexin–NL2 interaction is sufficient to induce GABAergic differentiation and clustering of GABAARs at postsynaptic sites | SIGNOR-265457 |
P16519 | P10997 | 1 | cleavage | up-regulates activity | 0.465 | The processing of proinsulin to insulin occurs in the secretory granules at the C-terminal end of pairs of basic amino acids, Arg31-Arg32 and Lys64-Arg65 [9,10]. Following cleavage, by the prohormone convertases, PC3 (also known as PC1) and PC2, the pair of basic amino acids are removed rapidly by carboxypeptidase E (CPE) to produce the mature insulin molecule | SIGNOR-261791 |
Q9NT99 | P10586 | 2 | binding | up-regulates activity | 0.617 | The NGL (netrin-G ligand; LRRC4) family of synaptic cell adhesion molecules belongs to the superfamily of leucine-rich repeat (LRR) proteins. The three known members of the NGL family, NGL-1, NGL-2, and NGL-3, are mainly localized to the postsynaptic side of excitatory synapses, and interact with the presynaptic ligands, netrin-G1, netrin-G2, and LAR, respectively. | SIGNOR-264049 |
P16220 | P49137 | 0 | phosphorylation | up-regulates activity | 0.691 | Neverthless, some transcription factors, such as e47, er81, srf and creb are also phosphorylated by mk2. | SIGNOR-166619 |
P49841 | Q6PGQ7 | 1 | phosphorylation | up-regulates | 0.258 | It suggests that gsk3_ activity is required for hbora-mediated mitotic entry through ser274 and ser278 phosphorylation | SIGNOR-201519 |
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 |
P49841 | P15260 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.2 | Our data suggest that glycogen synthase kinase 3 beta (GSK3beta) phosphorylates IFNGR1 thereby enhancing receptor protein stability by limiting ubiquitin proteasomal degradation. | SIGNOR-279720 |
P30968 | P38405 | 2 | 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 |
P50148 | P32238 | 2 | binding | up-regulates activity | 0.465 | 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-257303 |
P24385 | Q5XUX0 | 2 | binding | down-regulates quantity by destabilization | 0.413 | FBXO31 serves as the substrate-recognition component of the SKP/Cullin/F-box protein class of E3 ubiquitin ligases and has been shown to direct degradation of pivotal cell-cycle regulatory proteins including cyclin D1 and the p53 antagonist MDM2. | SIGNOR-277379 |
P49674 | P12830 | 1 | phosphorylation | down-regulates activity | 0.259 | Casein kinase 1 is a novel negative regulator of E-cadherin-based cell-cell contacts|CK1 colocalizes with E-cadherin and phosphorylates the cytoplasmic domain of E-cadherin in vitro and in a cell culture system. We show that the major CK1 phosphorylation site of E-cadherin is serine 846 | SIGNOR-274047 |
P27361 | O43521 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.731 | In vitro, bimel was phosphorylated by extracellular signal-regulated kinase on ser(69), which resides in the bimel-specific insert region. Using phosphospecific antibody against this site, we show that this residue is actually phosphorylated in cells. We also show that phosphorylation of ser(69) promotes ubiquitination of bimel. We conclude that mek inhibitors sensitize mda-mb231 and hbc4 cells to anoikis by blocking phosphorylation and hence degradation of bimel | SIGNOR-129878 |
P16066 | P02763 | 1 | phosphorylation | up-regulates activity | 0.2 | On TORC1 inhibition by rapamycin treatment or nutrient limitation, Npr1 phosphorylates and activates Orm1 and Orm2, which in turn promotes synthesis of complex sphingolipids downstream of SPT.|Thus Npr1 directly phosphorylates Orm1 and Orm2 downstream of TORC1. | SIGNOR-278966 |
Q92915 | Q99250 | 2 | binding | down-regulates activity | 0.375 | Sodium channel fast inactivation is modulated by alpha subunit interaction with a family of cytoplasmic proteins termed fibroblast growth factor homologous factors (FHFs). In this paper, we report that all A-type FHFs exert rapid onset long-term inactivation on Nav1.6 and other sodium channels. | SIGNOR-253429 |
Q96KR7 | Q00535 | 0 | phosphorylation | down-regulates quantity | 0.2 | We show that scapinin is phosphorylated at a highly conserved site in the central region of the protein (Ser-277) by Cdk5 in vitro. Expression of a scapinin phospho-mimetic mutant (S277D) restored normal axon elongation without affecting actin binding. Instead, phosphorylated scapinin was sequestered in the cytoplasm of neurons and away from the axon. | SIGNOR-273607 |
O43524 | Q8IW41 | 0 | phosphorylation | up-regulates activity | 0.475 | Analysis of mutant alleles of FoxO3a showed that MK5 phosphorylated FoxO3a predominantly at S215, but that mutation of four of the identified sites was required to essentially abolish phosphorylation of FoxO3a by MK5 (\u201c4A\u201d) ( Figure\u00a04 C and data not shown).|MK5 phosphorylates and activates the transcription factor FoxO3a and potentially other FoxO factors. | SIGNOR-279469 |
Q9HC97 | 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-256860 |
P24666 | P31751 | 1 | dephosphorylation | down-regulates activity | 0.2 | Reduction in the levels of both LMW-PTP isoforms in vitro and in vivo increased tyrosine phosphorylation of IR and AktSer473 and increased IRS-1- and IRS-2-associated PI3-K activities in both liver and fat.|Activated PI3-K stimulates Akt (or protein kinase B) that in turn phosphorylates and inactivates glycogen synthase kinase-3 | SIGNOR-248456 |
P53778 | Q6JBY9 | 1 | phosphorylation | down-regulates activity | 0.504 | Peptide T2 was sequenced and shown to comprise residues 79–112 of CapZIP, phosphorylated at Ser-108 (Figure 2B). The identity of peptide T1 is unknown. These experiments established that the SAPK3/p38γ substrate was CapZIP. Using this antibody, we showed by immunoblotting that bacterially expressed CapZIP was phosphorylated at Ser-108 by SAPK4/p38δ, JNK1α1 and ERK2 in vitro, as well as by SAPK3/p38γ (results not shown). An important clue to the function of CapZIP and its phosphorylation came from the finding that it binds to the actin-capping protein CapZ (Figure 7A), and that cellular stresses trigger the dissociation of these two proteins (Figure 7B).Such an effect is presumably lost when CapZIP is phosphorylated and dissociates from CapZ. | SIGNOR-263083 |
P10275 | P07288 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.822 | TH1 also associates with AR at the active androgen-responsive prostate-specific antigen (PSA) promoter in the nucleus of LNCaP cells. Decrease of endogenous AR protein by TH1 interferes with androgen-induced luciferase reporter expression and reduces endogenous PSA expression. | SIGNOR-253657 |
Q8N0W4 | Q9HDB5 | 2 | binding | up-regulates activity | 0.767 | 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-264170 |
P05230 | P11362 | 2 | binding | up-regulates activity | 0.914 | Together these data highlight the unique nature of the role of FGF-1 during the earliest stages of adipogenesis and establish a role for FGFR1 in human adipogenesis, identifying FGFR1 as a potential therapeutic target to reduce obesity. | SIGNOR-236936 |
Q96P20 | P45983 | 0 | phosphorylation | up-regulates activity | 0.369 | Ethanol induced JNK1 phosphorylation activated the NLRP3 inflammasome that induced caspase-1 dependent mitophagy inhibition, thereby exacerbating ROS accumulation and causing cell death.|However, recent studies suggested that Ser 194 phosphorylation of NLRP3 was essential for the control of inflammasome activation and that JNK1 directly phosphorylates NLRP3, which stimulates the self-association and oligomerization of NLRP3 [ xref , xref ]. | SIGNOR-280034 |
Q9C004 | P04049 | 2 | binding | down-regulates activity | 0.433 | Here we show that mammalian Sprouty4 suppresses vascular epithelial growth factor (VEGF)-induced, Ras-independent activation of Raf1 but does not affect epidermal growth factor (EGF)-induced, Ras-dependent activation of Raf1. Sprouty4 binds to Raf1 through its carboxy-terminal cysteine-rich domain, and this binding is necessary for the inhibitory activity of Sprouty4. | SIGNOR-253033 |
P26951 | P08700 | 2 | binding | up-regulates | 0.888 | The results demonstrate that both the association and dissociation rates for the binding of il-3 to the il-3ralpha are altered by truncation and by amino acid substitution at individual sites. Intracellular signaling studies using k116w and e43n demonstrate that differences in the il-3alpha binding characteristics are reflected in magnitude and kinetics of stat5 phosphorylation. | SIGNOR-111404 |
Q8IUC6 | Q12933 | 0 | polyubiquitination | up-regulates | 0.433 | Here, we show that the TRAF family proteins directly bind TICAM-1 and demonstrate that TRAF2 and TRAF6 bind different sites of the N-terminal TICAM-1 and accelerate its polyubiquitination. we speculate that polyubiquitination of TICAM-1 by TRAF2 and TRAF6 is required for TICAM-1 to induce IRF-3 and NF-κB activation. This is supported by the observation that polyubiquitination of TICAM-1 was required for TRAF3-binding to TICAM-1 | SIGNOR-271427 |
P04049 | Q13043 | 2 | 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 |
Q01196 | Q92785 | 2 | binding | down-regulates activity | 0.2 | The interaction between RUNX1 and DPF2 is dependent on the RUNX1 methylation status | SIGNOR-261966 |
Q16539 | Q9Y6W6 | 0 | dephosphorylation | down-regulates | 0.695 | Mkp-5 binds to p38 and sapk/jnk, but not to mapk/erk, and inactivates p38 and sapk/jnk, but not mapk/erk. p38 is a preferred substrate | SIGNOR-68983 |
P16234 | P16234 | 2 | phosphorylation | up-regulates activity | 0.2 | We have identified two autophosphorylation sites, Tyr-988 and Tyr-1018, in the platelet-derived growth factor (PDGF) alpha-receptor carboxyl-terminal tail, which are involved in binding of phospholipase C-gamma (PLC-gamma). We conclude that phosphorylated Tyr-988 and Tyr-1018 in the PDGF α-receptor carboxyl-terminal tail bind PLC-γ, but this association leads to only a relatively low level of tyrosine phosphorylation and activation of PLC-γ. | SIGNOR-250252 |
P98170 | P42574 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.939 | Xiap promotes the degradation of active-form caspase-3, but not procaspase-3, in living cells. Both the association of XIAP with caspase-3 and the RING finger domain of XIAP were essential for ubiquitination. XIAP promotes the degradation of caspase-3, which enhances its anti-apoptotic effect. | SIGNOR-109243 |
Q9BY44 | Q9P2K8 | 0 | phosphorylation | down-regulates activity | 0.484 | Activated GCN2 phosphorylates and inhibits eukaryotic translation initiation factor 2A (eIF2\u03b1), leading to a transient reduction in protein synthesis, while enhancing the translation of ATF4 ( xref ), a transcription factor that activates stress-induced gene expression ( xref \u2013 xref ). | SIGNOR-280005 |
P30622 | P68400 | 0 | phosphorylation | up-regulates | 0.293 | Herein, we have identified polo-like kinase 1 (plk1) and casein kinase 2 (ck2) as two kinases of clip-170 and mapped s195 and s1318 as their respective phosphorylation sites.Plk1- and ck2-associated phosphorylations of clip-170 are involved in the timely formation of kinetochore-microtubule attachments in mitosis | SIGNOR-167168 |
P19784 | Q13541 | 1 | phosphorylation | down-regulates activity | 0.333 | The kinase is quite distinct from casein kinase 2, which also phosphorylates Ser-111 of 4E-BP1. The possible importance of these kinases in the phosphorylation of 4E-BP1 in fat cells is discussed. It is suggested that the phosphorylation of Ser-111 might be a priming event that facilitates the subsequent phosphorylation of Thr-36, Thr-45, Ser-64 and Thr69 by a rapamycin-sensitive process that initiates the dissociation of 4E-BP1 from eIF4E and hence the formation of the eIF4F complex. | SIGNOR-249334 |
Q9Y6Q9 | O14920 | 0 | phosphorylation | up-regulates activity | 0.378 | We demonstrated the in vitro phosphorylation of SRC-3 by the two catalytic subunits of the IKK complex, IKKα and IKKβ. IKK kinase activity is required for synergistic activation with SRC-3 | SIGNOR-251298 |
Q13547 | Q00987 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.468 | MDM2 induces ubiquitination of HDAC1 in VSMCs.|Under calcification inducing conditions, proteasomal degradation of HDAC1 precedes VC and it is mediated by MDM2 E3 ubiquitin ligase that initiates HDAC1 K74 ubiquitination. | SIGNOR-278761 |
Q8IZL9 | P24941 | 1 | phosphorylation | up-regulates | 0.387 | P42 is essential for the phosphorylation of thr-160 and activation of cdk2. | SIGNOR-118986 |
P16520 | P43115 | 2 | binding | up-regulates | 0.498 | Ep3 receptor signals are primarily involved in adenylyl cyclase via g(i) activation, and in ca(2+)-mobilization through g(beta)(gamma) from g(i) | SIGNOR-88192 |
Q63HR2 | P30530 | 0 | phosphorylation | up-regulates quantity | 0.2 | In this study, however, we demonstrate for the first time that Axl directly binds to and phosphorylates TNS2 at Y483.|Overall these results suggest that Axl positively regulates TNS2 expression. | SIGNOR-278471 |
O00501 | P11308 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.224 | ETS-related gene (ERG) controls endothelial cell permeability via transcriptional regulation of the claudin 5 (CLDN5) gene. | SIGNOR-261596 |
P53350 | Q96GD4 | 0 | phosphorylation | up-regulates activity | 0.599 | Aurora B phosphorylates PLK1 on Thr210 to activate its kinase activity at the kinetochores during mitosis.|Thus, we conclude that Aurora B indirectly promotes the phosphorylation of MCAK on Ser715 at the kinetochores through phosphorylation of PLK1 at Thr210 and its ensuing activation. | SIGNOR-279358 |
P53350 | Q6IBW4 | 1 | phosphorylation | up-regulates activity | 0.444 | Plk1 phosphorylation of CAP-H2 at Ser288 is required for the accumulation of CAP-H2 and accurate chromosomal condensation during prophase. | SIGNOR-278419 |
Q06330 | Q92585 | 2 | binding | up-regulates | 0.875 | Maml1 binds to the ankyrin repeat domain of all four mammalian notch receptors, forms a dna-binding complex with icn and rbp-jkappa, and amplifies notch-induced transcription of hes0 | SIGNOR-84919 |
Q9UMX1 | O00422 | 2 | binding | up-regulates | 0.673 | Here we report that the mouse homolog of su(fu) [msu(fu)] specifically interacts with sap18, a component of the msin3 and histone deacetylase complex. In addition, we demonstrate that msu(fu) functionally cooperates with sap18 to repress transcription by recruiting the sap18-msin3 complex to promoters containing the gli-binding element. | SIGNOR-117311 |
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