IdA stringlengths 6 21 | IdB stringlengths 6 21 | labels float64 0 2 | mechanism stringclasses 40 values | effect stringclasses 10 values | score float64 0.1 0.99 ⌀ | sentence stringlengths 10 1.63k ⌀ | signor_id stringlengths 12 14 |
|---|---|---|---|---|---|---|---|
Q9GZM8 | Q9NRI5 | 0 | binding | up-regulates activity | 0.58 | Disrupted-In-Schizophrenia 1 (DISC1) is a candidate gene for susceptibility to schizophrenia. DISC1 is reported to interact with NudE-like (NUDEL), which forms a complex with lissencephaly-1 (LIS1) and 14-3-3ε. 14-3-3ε is involved in the proper localization of NUDEL and LIS1 in axons. the association with NUDEL and LIS1 supports the notion that DISC1 contributes to the neuronal development and morphology | SIGNOR-252162 |
Q13761 | P12931 | 0 | phosphorylation | down-regulates activity | 0.58 | In this study, we provide evidence that Src phosphorylates RUNX3 at multiple tyrosine residues.|Our finding that Src inactivates RUNX3 by cytoplasmic sequestration in gastric cancer and breast cancer suggests that the inactivation of RUNX3 may be a key function of oncogenic kinases. | SIGNOR-278199 |
P04637 | P06493 | 0 | phosphorylation | up-regulates activity | 0.579 | The N-terminus of E2F1 can interact directly with a region towards the C-terminus of p53, resulting in increased nuclear retention of p53 and p53-mediated transcription and apoptosis. This is inhibited by competition between p53 and cyclin A at the binding site within E2F19,10. The interaction between p53 and E2F1 is enhanced by phosphorylation of p53 on Ser315, a residue within the E2F1 binding region that is phosphorylated by cell cycle kinases such as cdk1, cdk2, cdk9 and Aurora kinase A | SIGNOR-167779 |
P17480 | P27361 | 0 | phosphorylation | down-regulates | 0.579 | Erk1/2 was found to phosphorylate the architectural transcription factor ubf at amino acids 117 and 201 within hmg boxes 1 and 2, preventing their interaction with dna | SIGNOR-112817 |
Q9HC77 | Q9NYY3 | 0 | phosphorylation | up-regulates | 0.579 | Plk2 phosphorylates the s589 and s595 residues of cpap in vitro and in vivo. This phosphorylation is critical for procentriole formation during the centrosome cycle. | SIGNOR-165999 |
P49815 | O00141 | 0 | phosphorylation | down-regulates activity | 0.579 | SGK1, which is activated by PDK1, contributes to the maintenance of residual mTORC1 activity through direct phosphorylation and inhibition of TSC2. | SIGNOR-277266 |
Q13761 | Q00987 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.579 | RUNX3 protein is ubiquitinated by MDM2 at Lys-94 and Lys-148.|RUNX3 protein is ubiquitinated by MDM2 at Lys 94 and Lys 148.|MDM2 suppresses the transcriptional activity of RUNX3. | SIGNOR-278557 |
Q14524 | P61328 | 0 | binding | down-regulates activity | 0.579 | 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-253416 |
Q13144 | P49841 | 0 | phosphorylation | down-regulates activity | 0.579 | The largest (epsilon) subunit of eIF2B is a substrate for glycogen synthase kinase (GSK)-3 in vitro, and phosphorylation by GSK3 inhibits the activity of eIF2B. The site of phosphorylation has previously been identified as Ser(535). | SIGNOR-251236 |
P15927 | P78527 | 0 | phosphorylation | down-regulates activity | 0.579 | We showed previously that UV irradiation increases phosphorylation of the p34 subunit of human replication protein A (RPA) and that this hyperphosphorylation correlated with loss of activity of the DNA replication complex. | we detected phosphorylation of the RPA complex by DNA-PK on RPA-p34 sites Ser-23, Ser-29, and Ser-11, -12, or -13 | SIGNOR-248981 |
P55017 | Q96J92 | 0 | phosphorylation | up-regulates activity | 0.579 | Threonine 48 was identified as the WNK4 phosphorylation site at mouse NCC|. Thus, WNK4 stimulates NCC in three ways: (1) direct phosphorylation and in turn increasing NCC protein abundance; (2) facilitating the phosphorylation of NCC by SPAK/OSR1 indirectly, and (3) phosphorylating and activating SPAK/OSR1.|Evidences from early studies using Xenopus oocytes and mammalian cells indicate that WNK4 inhibits NCC and PHAII-causing mutations relieve the inhibition | SIGNOR-264631 |
Q2NKX8 | P06493 | 0 | phosphorylation | up-regulates | 0.579 | Following phosphorylation of pich on the cdk1 site t1063, plk1 is recruited to pich and controls its localization. Starting in prometaphase, pich accumulates at kinetochores and inner centromeres. | SIGNOR-152133 |
P49841 | P48729 | 0 | binding | up-regulates activity | 0.579 | In the absence of secreted wnt ligands, cytosolic beta-catenin is phosphorylated at ser45 by the priming kinase casein kinase 1 (ck1). Consequently, glycogen synthase kinase 3 (gsk3), in complex with axin and adenomatous polyposis coli (apc), phosphorylates beta-catenin at thr41, ser37, and ser33 apc cooperates with axin to promote the phosphorylation of b-catenin by gsk3 [which requires priming phosphorylation by casein kinase 1, alpha-isoform (ck1alpha)] | SIGNOR-184696 |
Q8WXE1 | P24941 | 0 | phosphorylation | up-regulates | 0.579 | Atrip is a cdk2 substrate, and cdk2-dependent phosphorylation of s224 regulates the ability of atr-atrip to promote cell cycle arrest in response to dna damage./ One possibility is s224 phosphorylation creates a binding site for another protein involved in the g2-m checkpoint response | SIGNOR-156928 |
P50148 | P20309 | 0 | binding | up-regulates activity | 0.579 | 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-257018 |
P50542 | P28328 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.579 | Here we report on the identification of the protein-ubiquitin ligases that are responsible for the ubiquitination of the peroxisomal protein import receptor Pex5. It is demonstrated that each of the three RING peroxins Pex2, Pex10, and Pex12 exhibits ubiquitin-protein isopeptide ligase activity. Our results show that Pex2 mediates the Ubc4-dependent polyubiquitination whereas Pex12 facilitates the Pex4-dependent monoubiquitination of Pex5.While polyubiquitinated Pex5 is degraded by the proteasome, monoubiquitinated Pex5 is destined for a new round of the receptor cycle. | SIGNOR-253021 |
P63104 | P48729 | 0 | phosphorylation | down-regulates activity | 0.579 | This protein kinase has been identified as casein kinase Ialpha (CKIalpha) by peptide mapping analysis and sequencing. Among mammalian 14-3-3, only 14-3-3 tau possesses a phosphorylatable residue at the same position (Ser-233), and we show that this residue is also phosphorylated by CKI. In addition, we show that 14-3-3 zeta is exclusively phosphorylated on Thr-233 in human embryonic kidney 293 cells. The residue 233 is located within a region shown to be important for the association of 14-3-3 to target proteins. | We have now shown that in vivo phosphorylation of 14-3-3 zeta at the CKIalpha site (Thr-233) negatively regulates its binding to c-Raf, and may be important in Raf-mediated signal transduction. | SIGNOR-250796 |
Q04864 | Q9UHD2 | 0 | phosphorylation | up-regulates | 0.579 | The present results demonstrate that ikkepsilon- and tbk1-mediated phosphorylation of crel in the c-terminal td leads to cytoplasmic dissociation of a crel-ikb_ complex and nuclear accumulation of crel. | SIGNOR-148623 |
P35222 | P55285 | 0 | binding | up-regulates activity | 0.578 | At its C-terminus, cadherin interacts with β-catenin, which dynamically associates with α-catenin, a direct binding partner of filamentous actin | SIGNOR-265868 |
Q9NP31 | P06239 | 0 | phosphorylation | up-regulates activity | 0.578 | Here we mapped Lck phosphorylation and interaction sites on TSAd and evaluated their functional importance. The three C-terminal TSAd tyrosines Tyr(280), Tyr(290), and Tyr(305) were phosphorylated by Lck and functioned as docking sites for the Lck Src homology 2 (SH2) domain. Lck binds to TSAd prolines and phosphorylates and interacts with the three C-terminal TSAd tyrosines. We propose that through multivalent interactions with Lck, TSAd diverts Lck from phosphorylating other substrates, thus modulating its functional activity through substrate competition. | SIGNOR-262888 |
P04637 | P48730 | 0 | phosphorylation | up-regulates | 0.578 | Here we show that the direct association between a p53 n-terminal peptide and mdm2 is disrupted by phosphorylation of the peptide on thr(18) but not by phosphorylation at other n-terminal sites, including ser(15) and ser(37). Thr(18) was phosphorylated in vitro by casein kinase (ck1). | SIGNOR-75889 |
P06400 | P04049 | 0 | phosphorylation | down-regulates activity | 0.578 | Further, Raf-1 was able to phosphorylate Rb in vitro quite efficiently.|Raf-1 can inactivate Rb function and can reverse Rb mediated repression of E2F1 transcription and cell proliferation efficiently. | SIGNOR-279481 |
P16220 | Q6SA08 | 0 | phosphorylation | up-regulates | 0.578 | Tssk5, a novel member of the testis-specific serine/threonine kinase family, phosphorylates creb at ser-133, and stimulates the cre/creb responsive pathway. | SIGNOR-138289 |
P54252 | O95155 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.578 | Mammalian E4B (UFD2a), a ubiquitin chain assembly factor (E4), copurified with the polyubiquitylation activity for ataxin-3. E4B interacted with, and thereby mediated polyubiquitylation of, ataxin-3. Collectively, these data suggest that E4B promotes the degradation of ataxin-3, and that this effect surmounts the stabilization of ataxin-3 conferred by expansion of the polyglutamine tract. | SIGNOR-271502 |
Q15796 | Q92831 | 0 | acetylation | up-regulates | 0.578 | We demonstrate that both smad2 and smad3 are acetylated by the coactivators p300 and cbp in a tgfbeta-dependent manner. Smad2 is also acetylated by p/caf. The acetylation of smad2 was significantly higher than that of smad3. Lys(19) in the mh1 domain was identified as the major acetylated residue in both the long and short isoform of smad2.....acetylation of the short isoform of smad2 improves its dna binding activity in vitro and enhances its association with target promoters in vivo, thereby augmenting its transcriptional activity | SIGNOR-150273 |
P08151 | Q96J02 | 0 | ubiquitination | down-regulates | 0.578 | The consequent activation of_ itch, together with the recruitment of gli1 through direct binding with_ numb, allows gli1 to enter into the complex, resulting in gli1 ubiquitination and degradation. we demonstrate that the hedgehog transcription factor gli1 is targeted by numb for itch-dependent ubiquitination, which suppresses hedgehog signals, thus arresting growth and promoting cell differentiation | SIGNOR-150847 |
P01112 | Q9P212 | 0 | guanine nucleotide exchange factor | up-regulates | 0.578 | The presence of a rasgef motif in the n terminus of plcepsilon suggests that plcepsilon can activate ras by acting as an exchange factor by promoting the exchange of gtp for bound gdp. | SIGNOR-82859 |
Q07869 | P28482 | 0 | phosphorylation | up-regulates activity | 0.578 | We now demonstrate that amino acids 1-92 of hPPARalpha contain an activation function (AF)-1-like domain, which is further activated by insulin through a pathway involving the mitogen-activated protein kinases p42 and p44. Further analysis of the amino-terminal region of PPARalpha revealed that the insulin-induced trans-activation occurs through the phosphorylation of two mitogen-activated protein kinase sites at positions 12 and 21, both of which are conserved across evolution. | SIGNOR-249434 |
Q99665 | P29459 | 0 | binding | up-regulates | 0.578 | Il-12r beta 2 plays an essential role in mediating the biological functions of il-12 in mice. | SIGNOR-84361 |
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 |
O00418 | O15264 | 0 | phosphorylation | down-regulates activity | 0.578 | eEF2 kinase is phosphorylated and inhibited by SAPK4/p38delta. eEF2K[S359A] was phosphorylated (presumably at Ser396) by the high concentrations of SAPK4/p38 used in this experiment. However, the inhibition of eEF2K under these conditions was reduced from 82% in the wild-type enzyme to 19% in eEF2K[S359A] | SIGNOR-250089 |
P46734 | Q7L7X3 | 0 | phosphorylation | up-regulates activity | 0.578 | The activation of and binding to MEK3 by TAO1 implicates TAO1 in the regulation of the p38-containing stress-responsive MAP kinase pathway | SIGNOR-60818 |
P50552 | Q70E73 | 0 | binding | up-regulates activity | 0.578 | Here we show that Lpd is a substrate of Abl kinases and binds to the Abl SH2 domain. Phosphorylation of Lpd positively regulates the interaction between Lpd and Ena/VASP proteins. | SIGNOR-268426 |
Q9H8V3 | P06493 | 0 | phosphorylation | down-regulates | 0.577 | We show that phosphorylation of ect2 at threonine-341 (t341) affects the autoregulatory mechanism of ect2. In g2/m phase, ect2 was phosphorylated at t341 most likely by cyclin b/cyclin-dependent kinase 1 (cdk1) ect2 is biologically active even when it is not phosphorylated at t341 | SIGNOR-140549 |
P06213 | P10586 | 0 | dephosphorylation | down-regulates | 0.577 | Lar ptpase shows strong preference for dephosphorylation first at py5 (at tri-, di-, and monophosphotyrosyl levels). Initially this regioselectivity gives the y5(py9)(py10) diphospho regioisomer, followed by equal dephosphorylation at py9 or py10 to give the corresponding monophosphoryl species on the way to fully dephosphorylated product. | SIGNOR-76005 |
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 |
P18564 | Q9Y490 | 0 | binding | up-regulates activity | 0.577 | Over the past 10 years, the binding of talin to the cytoplasmic tail of integrin-β subunits has been established to have a key role in integrin activation. Binding of the phosphotyrosinebinding (PTB)-domain-like subdomain of the protein 4.1, ezrin, radixin, moesin (FERM) domain of talin to the conserved WxxxNP(I/L)Y motif of the β-integrin tail permits additional weaker interactions between talin and the membrane-proximal region of the tail that trigger integrin activation, probably through the disruption of inhibitory interactions between α- and β-subunit cytoplasmic tails. | SIGNOR-257631 |
O43765 | P11441 | 0 | binding | up-regulates activity | 0.577 | USP13 and gp78 control ubiquitination of Ubl4A.These data suggest that USP13 and gp78 play antagonizing roles in regulation of Ubl4A ubiquitination: While gp78 assembles ubiquitin chains on Ubl4A, USP13 antagonizes this activity to limit Ubl4A ubiquitination.Ubiquitination of Ubl4A preferentially occurs on Lys48. We identify the Bag6 cofactor Ubl4A as a shared substrate of gp78 and USP13. USP13 depletion is associated with hyper-ubiquitination of Ubl4A and altered interaction between the Bag6 complex and its co-chaperone SGTA. Because the interaction of Ubl4A with SGTA is mediated by positively-charged residues in Ubl4A including Lys48 (Chartron et al., 2012; Xu et al., 2012), which happens to be the major ubiquitination site, the simplest model to explain reduced Bag6-SGTA interaction in USP13 knockdown cells is that ubiquitin conjugates on Ubl4A sterically hinder SGTA binding. | SIGNOR-272858 |
P15941 | P00533 | 0 | phosphorylation | up-regulates activity | 0.577 | We also show that the activated egf-r phosphorylates the muc1 cytoplasmic tail on tyrosine at a yekv motif that functions as a binding site for the c-src sh2 domain. The results demonstrate that egf-r-mediated phosphorylation of muc1 induces binding of muc1 to c-src in cells | SIGNOR-109538 |
P16949 | P27361 | 0 | phosphorylation | down-regulates activity | 0.577 | Stress-induced stathmin phosphorylation is not de- pendent on ERK. Stathmin is also known to be phos- phorylated by ERK on Ser-25 and Ser-38 (17). Thus, it is possible that ERK phosphorylates stathmin in 293 cells|In subsequent reports (28, 29) it was shown that phosphorylation of stathmin blocks its ability to destabilize MTs. | SIGNOR-249483 |
P50148 | P24530 | 0 | binding | up-regulates activity | 0.577 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-257379 |
P11021 | Q9H173 | 0 | binding | up-regulates activity | 0.577 | BAP, a Mammalian BiP-associated Protein, Is a Nucleotide Exchange Factor That Regulates the ATPase Activity of BiP. In addition,BAP was associated with BiP in mammalian cells and inter-acted with BiP functionallyin vitro. BAP stimulated the ATPase activity of BiP when added alone or together with the ER DnaJ protein, ERdj4, by promoting the release of ADP from BiP. Together, these data demonstrate that BAP serves as a nucleotide exchange factor for BiP and provide insights into the mechanisms that control protein folding in the mammalian ER. | SIGNOR-261045 |
P60953 | Q9C0H5 | 0 | gtpase-activating protein | down-regulates activity | 0.577 | We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2). | SIGNOR-260495 |
P10071 | Q2M1P5 | 0 | binding | up-regulates quantity by stabilization | 0.577 | These results suggest a role for Kif7 in coordinating Hh signal transduction at the tip of cilia and preventing Gli3 cleavage into a repressor form in the presence of Hh. | SIGNOR-209614 |
Q86TM6 | Q9UBU6 | 0 | binding | up-regulates activity | 0.577 | FAM8A1 enhances binding of Herp to Hrd1, an interaction that is required for ERAD. Our findings support a model of Hrd1 complex formation, where the Hrd1 cytoplasmic domain and FAM8A1 have a central role in the assembly and activity of this ERAD machinery. A conserved Hrd1 cytoplasmic domain interacts with FAM8A1 and Herp | SIGNOR-261348 |
Q05513 | O15530 | 0 | phosphorylation | up-regulates | 0.577 | Our findings suggest that insulin, via pip(3), provokes increases in pkc-zeta enzyme activity through (a) pdk-1-dependent t410 loop phosphorylation, (b) t560 autophosphorylationcytoskeletal reorganization;tnni1(induces);desmin(induces);tpm1(induces);myo1c(induces);tnnt1(induces); | SIGNOR-85501 |
P49815 | P54646 | 0 | phosphorylation | up-regulates | 0.577 | We have observed that ampk directly phosphorylates tsc2, and the ampk-dependent phosphorylation of tsc2 is critical for the coordination between cell growth and cellular energy levels. | SIGNOR-149388 |
Q05655 | O15530 | 0 | phosphorylation | up-regulates activity | 0.577 | PDK1 phosphorylated the activation loop sites of PKCzeta and PKCdelta in vitro and in a phosphoinositide 3-kinase (PI 3-kinase)-dependent manner in vivo in human embryonic kidney (293) cells. PKCδ was also phosphorylated in the activation loop site (T505) | SIGNOR-250269 |
P17947 | P23769 | 0 | binding | down-regulates activity | 0.577 | Here we demonstrate that a region of the PU.1 Ets domain (the winged helix–turn–helix wing) interacts with the conserved carboxyl-terminal zinc finger of GATA-1 and GATA-2 and that GATA proteins inhibit PU.1 transactivation of critical myeloid target genes. | SIGNOR-256071 |
P47712 | Q9BUB5 | 0 | phosphorylation | up-regulates activity | 0.577 | The results suggest that MNK1 or a closely related kinase is responsible for in vivo phosphorylation of cPLA2 on Ser-727. | SIGNOR-226633 |
Q13164 | Q05513 | 0 | phosphorylation | down-regulates activity | 0.577 | Furthermore, PKC\u03b6 phosphorylates ERK5, and mutation analysis showed that the preferred site is S486.|PKCzeta decreases eNOS protein stability via inhibitory phosphorylation of ERK5 | SIGNOR-280090 |
Q92529-2 | P12931 | 0 | phosphorylation | up-regulates activity | 0.576 | We also obtained tryptic phosphopeptide maps of N-Shc protein phosphorylated in vitro by other tyrosine kinases, TrkB, v-Src and EGFR. The overall patterns of the phosphopeptide maps generated by these tyrosine kinases were similar, although there were some differences among these maps (Figure 4a–d).We performed phosphopeptide mapping analysis using GST-fused N-Shc protein, and found that N-Shc phosphorylated by TrkA in vitro was resolved into at least seven phosphopeptides (Y1 through Y7, Figure 4a). Phosphopeptide mapping revealed that N-Shc has novel tyrosine-phosphorylation sites at Y259/Y260 and Y286; in vivo-phosphorylation of these tyrosines was demonstrated by site-specific anti-pTyr antibodies. Phosphorylated Y286 bound to several proteins, of which one was Crk. The pY221/pY222 site, corresponding to one of the Grb2-binding sites of Shc, also preferentially bound to Crk. The phosphorylation-dependent interaction between N-Shc and Crk was demonstrated in vitro and in vivo. | SIGNOR-273921 |
P35222 | Q13634 | 0 | binding | up-regulates activity | 0.576 | At its C-terminus, cadherin interacts with β-catenin, which dynamically associates with α-catenin, a direct binding partner of filamentous actin | SIGNOR-265857 |
P20936 | P29323 | 0 | binding | up-regulates | 0.576 | We have localized an in vitro rasgap-binding site to conserved tyrosine residues y604 and y610 in the juxtamembrane region of ephb2, and demonstrated that substitution of these amino acids abolishes ephrin-b1-induced signalling events in ephb2-expressing ng108-15 cells. | SIGNOR-50100 |
P15498 | P29350 | 0 | dephosphorylation | down-regulates activity | 0.576 | SHP-1 dephosphorylates and inactivates the guanine exchange factor Vav1. | SIGNOR-277171 |
P16333 | P00533 | 0 | binding | up-regulates activity | 0.576 | We show that epidermal growth factor or platelet-derived growth factor stimulation of intact human or murine cells leads to phosphorylation of Nck protein on tyrosine, serine, and threonine residues | SIGNOR-252089 |
P16298 | P0DP25 | 0 | binding | up-regulates | 0.576 | Calcium-bound calmodulin associates with calcineurin (cn), releasing the phosphatase from the repressive effects on an autoinhibitory domain. | SIGNOR-266338 |
O75840 | Q6PIJ6 | 0 | binding | up-regulates activity | 0.576 | Interaction between MoKA and KLF7 was confirmed by the in vitro glutathione S-transferase pull-down assay and by coimmunoprecipitation of the proteins overexpressed in mammalian cells. Functional assays documented that MoKA is a KLF7 coactivator | SIGNOR-224621 |
P61586 | P50148 | 0 | binding | up-regulates | 0.576 | Recently, the dbl-family guanine nucleotide exchange factor (gef) p63rhogef/geft has been described as a novel mediator of galpha(q/11) signaling to rhoa based on its ability to synergize with galpha(q/11) resulting in enhanced rhoa signaling in cells. | SIGNOR-156534 |
Q9BUB5 | P27361 | 0 | phosphorylation | up-regulates | 0.576 | Mnk1 was phosphorylated and activated in vitro by erk1 and p38 map kinasespreliminary results showed that thr344 at least was one of the major sites phosphorylated by erk1 | SIGNOR-48360 |
P14635 | O14965 | 0 | phosphorylation | up-regulates activity | 0.576 | A second wave of Cyclin B1-CDK1 phosphorylation by AurA occurs in late prophase.|Simultaneously, AurA activates and targets the Cyclin B1-CDK1 complex at centrosomes [ xref ]. | SIGNOR-280186 |
Q8TEW6 | P07949 | 0 | binding | up-regulates | 0.576 | We identified two new family members, dok-4 and dok-5, that can directly associate with y1062 of c-ret dok-4 and dok-5 enhance c-ret-dependent activation of mitogen-activated protein kinase | SIGNOR-109513 |
P10721 | P29350 | 0 | binding | down-regulates | 0.576 | Shp-1 binds and negatively modulates the c-kit receptor by interaction with tyrosine 569 in the c-kit juxtamembrane domain. | SIGNOR-56104 |
P35568 | P60484 | 0 | dephosphorylation | down-regulates activity | 0.576 | In contrast, IRS-1 level were significantly decreased and phosphorylation of IRS-1 at Ser 307 was strongly enhanced by PTEN knockdown, suggesting that both reduction in IRS-1 level and increase in IRS-1 phosphorylation at Ser307 upon HCV infection occurred in a PTEN dependent manner.|In contrast, IRS-1 level were significantly decreased and phosphorylation of IRS-1 at Ser-307 was strongly enhanced by PTEN knockdown, suggesting that both reduction in IRS-1 level and increase in IRS-1 phosphorylation at Ser307 upon Hepatitis C virus infection occurred in a PTEN-dependent manner. | SIGNOR-277078 |
Q8WU20 | P22681 | 0 | ubiquitination | down-regulates | 0.576 | The experiments presented in this report illustrate that in response to fgf stimulation, cbl is recruited by grb2 binding to the frs2_ multiprotein complex, resulting in ubiquitination of frs2_ and fgfr. grb2 functions as a link between frs2_ and cbl;grb2 is bound to tyrosine-phosphorylated frs2_ by means of its sh2 domain and to a proline-rich region in the c terminus of cbl by means of its sh3 domains. | SIGNOR-87166 |
P27694 | P54727 | 0 | binding | up-regulates activity | 0.575 | GG-NER is initiated by the GG-NER specific factor XPC-RAD23B, in some cases with the help of UV-DDB (UV-damaged DNA-binding protein). TC-NER is initiated by RNA polymerase stalled at a lesion with the help of TC-NER specific factors CSA, CSB, and XAB2. Both pathways require the core NER factors to complete the excision process|The core NER dual incision reaction has been reconstituted in vitro with purified factors using XPC-RAD23B, TFIIH, XPA, RPA, XPG, and ERCC1-XPF (Aboussekhra et al. 1995; Mu et al. 1995; Araujo et al. 2000).|The core NER dual incision reaction has been reconstituted in vitro with purified factors using XPC-RAD23B, TFIIH, XPA, RPA, XPG, and ERCC1-XPF (Aboussekhra et al. 1995; Mu et al. 1995; Araujo et al. 2000). Functional studies revealed that XPC-RAD23B is the initial damage recognition factor in this system, as the presence of XPC-RAD23B is required for assembly of the other core NER factors and progression through the NER pathway both in vitro and in vivo | SIGNOR-275698 |
P16885 | P06241 | 0 | phosphorylation | up-regulates activity | 0.575 | The phosphorylation of purified phospholipase C-gamma 1 (PLC-gamma 1) and PLC-gamma 2 by src-family-protein tyrosine kinases (PTKs) P56lck, p53/56lyn, p59hck, p59fyn, and p60src was studied in vitro. All five PTKs phosphorylated PLC-gamma 1 and PLC-gamma 2, suggesting that both PLC-gamma isozymes can be phosphorylated in cells by any of the src-family PTKs in response to the activation of cell surface receptors. | SIGNOR-249340 |
Q9UBK2 | Q13131 | 0 | phosphorylation | up-regulates activity | 0.575 | Ampk phosphorylates pgc-1alpha directly both in vitro and in cells. These direct phosphorylations of the pgc-1alpha protein at threonine-177 and serine-538. | SIGNOR-156780 |
Q13882 | P18031 | 0 | dephosphorylation | down-regulates activity | 0.575 | Using a variety of PTEN mutant constructs, we show that protein phosphatase activity of PTEN targets PTK6, with efficiency similar to PTP1B, a phosphatase that directly dephosphorylates PTK6 Y342. | SIGNOR-277082 |
O15393 | P10275 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.575 | The prostate-specific TMPRSS2 gene, while upregulated by AR activity in luminal cells, is also transcribed in basal populations, confirming that AR acts as an expression modulator. | SIGNOR-253687 |
O15350 | P24941 | 0 | phosphorylation | down-regulates activity | 0.575 | Cyclin-dependent kinases phosphorylate p73 at threonine 86 in a cell cycle-dependent manner and negatively regulate p73.Furthermore, cyclin a/cdk1/2, cyclin b/cdk1/2, and cyclin e/cdk2 complexes can phosphorylate multiple p73 isoforms in vitro at threonine 86. | SIGNOR-99746 |
P30307 | P27348 | 0 | relocalization | down-regulates | 0.575 | Cdc25c: nuclear exclusion/cytoplasmic sequestration via binding to 14-3-3 proteins. | SIGNOR-163237 |
P25189 | Q01453 | 0 | binding | up-regulates activity | 0.575 | Our data provide the first direct evidence for the formation of P0–PMP22 complexes at the plasma membrane. These protein interactions probably participate in holding adjacent Schwann cell membranes together and in stabilizing myelin compaction. | SIGNOR-251898 |
Q01860 | P35222 | 0 | binding | up-regulates activity | 0.575 | We provide evidence suggesting that Beta-catenins interaction with the pluripotency regulator Oct-4 at least partially underlies its effects on sustaining pluripotency. | SIGNOR-241981 |
Q92997 | Q9ULV1 | 0 | binding | up-regulates activity | 0.575 | Through study of FZD4 and its associated ligand Norrin, we report that a minimum of three residues distal to the KTXXXW motif in the C-terminal tail of Frizzled-4 are essential for DVL recruitment and robust Lef/Tcf-dependent transcriptional activation in response to Norrin. | SIGNOR-258961 |
Q04721 | Q8NBL1 | 0 | binding | up-regulates | 0.575 | O-glucosylation of epidermal growth factor-like (egf) repeats in the extracellular domain of notch is essential for notch function. O-glucose can be elongated by xylose to the trisaccharide, xylalfa1-3xylalfa1-3glcbeta1-o-ser, whose synthesis is catalyzed by the consecutive action of three glycosyltransferases. A udp-glucose:protein o-glucosyltransferase (poglut/rumi) transfers o-glucose to serine within the o-glucose consensus. | SIGNOR-198716 |
Q15910 | P06493 | 0 | phosphorylation | down-regulates | 0.575 | Cdk1, which phosphorylates ezh2 at threonines 345 and 487.Phosphorylation of thr-345 and thr-487 promotes ezh2 ubiquitination and subsequent degradation by the proteasome | SIGNOR-174058 |
P62136 | P06493 | 0 | phosphorylation | down-regulates activity | 0.575 | Both of these pp1 isoforms contain an arg-pro-ile/val-thr-pro-pro-arg sequence near the c terminus, a known site of phosphorylation by cdc/cdk kinases, and phosphorylation attenuates phosphatase activity. | SIGNOR-151799 |
Q15797 | P46937 | 0 | binding | up-regulates | 0.575 | Yap binds to the phosphorylated smad1 to activate gene transcription. | SIGNOR-201462 |
O95405 | P29590 | 0 | binding | up-regulates | 0.574 | Cytoplasmic pml physically interacts with smad2/3 and sara (smad anchor for receptor activation) and is required for association of smad2/3 with sara and for the accumulation of sara and tgf-beta receptor in the early endosome. | SIGNOR-128744 |
P61586 | Q14344 | 0 | binding | up-regulates | 0.574 | Ga12/13 recruitment of rho-gefs causes rhoa activation and f-actin assembly, which promotes lats1/lat2 inactivation by an unknown, but myosin-independent mechanism. | SIGNOR-192111 |
O75461 | O14757 | 0 | phosphorylation | down-regulates activity | 0.574 | the checkpoint kinase Chk1 phosphorylates E2F6 leading to its dissociation from promoters. | SIGNOR-266371 |
P63000 | Q05397 | 0 | phosphorylation | up-regulates activity | 0.574 | Both Src and FAK phosphorylate Rac1 at tyrosine 64.|Our investigations of direct interactions between Rac1, Src, and FAK were motivated by our previous insights into FAK augmentation of Rac1 activation during cell spreading, and the Cerione lab 's work on the interactions between Src and Cdc42 , . | SIGNOR-279652 |
Q9P2K8 | Q13217 | 0 | binding | down-regulates activity | 0.574 | we show that p58IPK is a general inhibitor of the eIF2 kinases in that it also interacts with GCN2 | SIGNOR-246204 |
P43403 | P06241 | 0 | phosphorylation | up-regulates activity | 0.574 | Subsequently, Lck and Fyn phosphorylate and activate the Syk family kinase ZAP-70 when it is recruited to the phosphorylated ITAM motifs xref . | SIGNOR-279043 |
Q8N5C8 | Q13546 | 0 | binding | up-regulates activity | 0.574 | Tab2 and tab3 activate the jun n-terminal kinase and nuclear factor-kappab pathways through the specific recognition of lys 63-linked polyubiquitin chains by its npl4 zinc-finger (nzf) domain. | SIGNOR-161787 |
Q02750 | P41279 | 0 | phosphorylation | up-regulates | 0.574 | Activation of mek family kinases requires phosphorylation of two conserved ser/thr residues.Phosphopeptide analysis demonstrated that serine residues 218 and 222 of human mek1 are the primary sites for phosphorylation by c-raf | SIGNOR-36453 |
Q14344 | P21731 | 0 | binding | up-regulates activity | 0.574 | 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-257139 |
Q16584 | Q92918 | 0 | phosphorylation | up-regulates | 0.574 | Hpk1 also phosphorylated mlk-3 activation loop in vitro, and ser281 was found to be the major phosphorylation site, indicating that hpk1 also activates mlk-3 via phosphorylation of the kinase activation loop. | SIGNOR-83415 |
P37231 | Q00535 | 0 | phosphorylation | down-regulates activity | 0.574 | CDK5 in turn phosphorylates PPARgamma at Ser273 and prevents the transcription of specific PPARgamma target genes that have anti-diabetic effects . | SIGNOR-278189 |
Q13485 | O43541 | 0 | binding | down-regulates activity | 0.574 | On the other hand, Smad6 competes with R-Smad and forms a non-functional complex with Smad4, which will inhibit BMP signaling in bone formation. Smad6 is involved in a negative feedback loop regulating BMP signaling and is required to limit BMP signaling during endochondral bone formation. | SIGNOR-195648 |
Q15011 | Q86TM6 | 0 | binding | up-regulates activity | 0.574 | FAM8A1 enhances binding of Herp to Hrd1, an interaction that is required for ERAD. Our findings support a model of Hrd1 complex formation, where the Hrd1 cytoplasmic domain and FAM8A1 have a central role in the assembly and activity of this ERAD machinery. A conserved Hrd1 cytoplasmic domain interacts with FAM8A1 and Herp | SIGNOR-261349 |
Q06413 | Q92831 | 0 | binding | up-regulates | 0.573 | The cofactors grip-1, cbp/p300 and pcaf have hat activity and function as co-activators for mef-2c during myogenesis. | SIGNOR-84032 |
Q15154 | O00444 | 0 | phosphorylation | up-regulates activity | 0.573 | Plk4‚Äêmediated phosphorylation of PCM1 at S372 is critical for the proper localisation of centriolar satellites, its dimer formation and interaction with other satellite components|Therefore, Plk4 is responsible for PCM1 phosphorylation at S372. | SIGNOR-279556 |
Q02156 | O15530 | 0 | phosphorylation | up-regulates | 0.573 | In the present study, we analysed the contribution of the phosphoinositide-dependent kinase 1 (pdk-1) and pkcepsilon kinase activity in controlling the phosphorylation of thr(566) and ser(729). pdk-1 phosphorylation of the activation loop triggers autophosphorylation of the hydrophobic motif | SIGNOR-117320 |
Q96EB6 | Q15831 | 0 | phosphorylation | up-regulates activity | 0.573 | Resveratrol promotes the binding between LKB1 and Sirt1, which we first reported, and this binding leads to LKB1-mediated phosphorylation of Sirt1 at three different serine residues in the C terminus of Sirt1. Mechanistically, LKB1-mediated phosphorylation increases intramolecular interactions in Sirt1, such as the binding of the C terminus to the deacetylase core domain, thereby eliminating DBC1 (Deleted in Breast Cancer 1, Sirt1 endogenous inhibitor) inhibition and promoting Sirt1-substrate interaction. | SIGNOR-277323 |
Q86XR7 | Q02156 | 0 | phosphorylation | up-regulates | 0.573 | Here we show that tram is transiently phosphorylated by pkcepsilon on serine-16 our study provides a possible target for these molecules in lps signaling. Dag may activate pkc?, Leading to the phosphorylation and activation of tram. | SIGNOR-146991 |
P50148 | O14842 | 0 | binding | up-regulates activity | 0.573 | 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-257272 |
Q00653 | P20749 | 0 | binding | up-regulates | 0.573 | The cyclin d1 elevation is caused not by increased p65/p50 action but rather by increased nuclear activity of bcl-3-associated nf-kappab p50 and p52. | SIGNOR-146768 |
P01106 | Q13526 | 0 | binding | up-regulates | 0.573 | Pin1 prolyl isomerase enhances recruitment of serine 62-phosphorylated myc and its coactivators to select promoters during gene activation. | SIGNOR-202134 |
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