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 |
|---|---|---|---|---|---|---|---|
Q03113 | P43657 | 2 | binding | up-regulates activity | 0.359 | 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- signali... | SIGNOR-257286 |
O95071 | Q96BY2 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.345 | We demonstrate that UBR5 interacts physically with MOAP-1, ubiquitylates MOAP-1 in vitro and inhibits MOAP-1 stability in cultured cells. | SIGNOR-278581 |
Q12923 | P98172 | 1 | dephosphorylation | up-regulates activity | 0.708 | Loss of PTPN13 function increases EFNB1 phosphorylation, enhances EFNB1 's interaction with ERBB1 and correlates with potentiated ERK1/2 activation.|Moreover, acquisition of PTPN13 loss-of-function mutations or its decreased expression (due to HPV infection or epigenetic silencing) may further enhance ERBB1 and EFNB1 m... | SIGNOR-277002 |
Q15375 | P31271 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.291 | Analysis of normalized luciferase expression confirmed that wt HOXA13 regulates gene expression through the EphA7 cis-regulatory DNA element | SIGNOR-261631 |
P08575 | P52333 | 1 | dephosphorylation | down-regulates activity | 0.456 | CD45 is a JAK phosphatase and negatively regulates cytokine receptor signalling | SIGNOR-248359 |
Q16612 | Q02156 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Site-directed mutagenesis of S59A retarded P311 degradation and induced glioma cell motility. In contrast, S59D mutation resulted in the rapid degradation of P311 and reduced glioma cell migration.Taken together, our results show that the serine phosphorylation of P311 is dependent on the function of both PKCε and PKCz... | SIGNOR-273830 |
O00506 | O43561 | 1 | phosphorylation | up-regulates activity | 0.2 | In sum, these data reveal that STK25 activates LATS kinases through a mechanism that is distinct from what has been characterized for the MAP4K/MST kinases (Fig.\u00a0 xref ).|Mechanistically, we demonstrate that STK25 promotes LATS phosphorylation at the activation loop in the absence of hydrophobic motif phosphorylat... | SIGNOR-279294 |
Q8TBB1 | P56750 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.294 | We used the Ligand of Numb protein X (LNX) family of E3s, a group of PDZ domain-containing RING-type E3 ubiquitin ligases, to demonstrate the feasibility of this strategy. Many potential substrates of LNX E3s were identified. Eight of the nine selected candidates were ubiquitinated in vitro, and two novel endogenous su... | SIGNOR-272900 |
O00311 | P49736 | 1 | phosphorylation | up-regulates | 0.962 | In this work, by in vitro kinase reactions and mass spectrometry analysis of the products, we have mapped phosphorylation sites in the n terminus of mcm2 by cdc7, cdk2, cdk1, and ck2 | SIGNOR-143984 |
O75807 | P07948 | 0 | phosphorylation | up-regulates | 0.334 | Gadd34 was tyrosine-phosphorylated in vivo in a lyn-dependent manner. | SIGNOR-109934 |
P05412 | Q14774 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | In this study, we have identified cell cycle regulatory genes as downstream targets of the homeobox gene HLX in cultured trophoblast cells, namely RB1, MYC, EGR1, CDKN1C, ELK1, CCNB1, and JUN. RB1 and MYC mRNA expression was increased with HLX inactivation, whereas EGR1, CDKN1C, ELK1, CCNB1, and JUN mRNA expression was... | SIGNOR-261623 |
P29376 | P22681 | 1 | phosphorylation | up-regulates | 0.369 | Although c-cbl is found to be phosphorylated by ltk and therefore is a second candidate linking ltk with the pi3-kinase pathway along with irs-1, we found that the p85 subunit of pi3 kinase directly binds to tyrosine 753 of ltk, which is located within a yxxm motif, a consensus binding amino acid sequence for the sh2 d... | SIGNOR-49528 |
P18146 | P01148 | 2 | binding | up-regulates activity | 0.442 | EGR1 bound to two binding sites on the LHB promoter and this binding was increased by GNRH1. Mutation of either site or knockdown of endogenous EGR1 decreased basal and/or GNRH1-regulated promoter activity. | SIGNOR-254918 |
Q05397 | P07949 | 2 | phosphorylation | up-regulates | 0.639 | Focal adhesion kinase (fak) binds ret kinase via its ferm domain, priming a direct and reciprocal ret-fak transactivation mechanism. following gdnf stimulation, increased phosphorylation of fak at tyr-576/577 as well as phosphorylation of ret at tyr-905 was observed. | SIGNOR-173009 |
Q9BXW4 | Q8IZQ1 | 2 | binding | up-regulates activity | 0.594 | Here, we show that ALFY binds selectively to LC3C and the GABARAPs through a LIR in its WD40 domain. Binding of ALFY to GABARAP is indispensable for its recruitment to LC3B-positive structures and, thus, for the clearance of certain p62 structures by autophagy. | SIGNOR-266795 |
P15923 | P49674 | 0 | phosphorylation | up-regulates | 0.2 | Tcf3 is a substrate for both glycogen synthase kinase (gsk) 3 and casein kinase (ck) 1epsilon, and phosphorylation of tcf3 by ckiepsilon stimulates its binding to beta-catenin, an effect reversed by gsk3. | SIGNOR-110056 |
P52306 | P08134 | 2 | binding | up-regulates | 0.298 | Smggds is a guanine nucleotide exchange factor that specifically activates rhoa and rhoc | SIGNOR-171399 |
Q8IUC6 | Q6SZW1 | 2 | binding | down-regulates | 0.53 | SARM utilizes its TIR domain to negatively regulate TRIF | SIGNOR-252068 |
P56524 | P15976 | 0 | relocalization | up-regulates activity | 0.584 | GATA1 is a new substrate of p21-activated kinase 5 (PAK5), which is phosphorylated on serine 161 and 187 (S161 and S187). GATA1 recruits HDAC3/4 to E-cadherin promoter, which is reduced by GATA1 S161A S187A mutant. These data indicate that phosphorylated GATA1 recruits more HDAC3/4 to promote transcriptional repression... | SIGNOR-275665 |
Q99558 | Q12933 | 2 | binding | down-regulates quantity by destabilization | 0.586 | We report here that one important mechanism of nik regulation is through its dynamic interaction with the tumor necrosis factor receptor-associated factor 3 (traf3). Traf3 physically associates with nik via a specific sequence motif located in the n-terminal region of nik; this molecular interaction appears to target n... | SIGNOR-124233 |
Q15466 | Q07869 | 2 | binding | up-regulates | 0.533 | Surprisingly, shp potentiated transcription by pparalpha/rxralpha heterodimers from the hd-ppre. This is the first demonstration of positive transcriptional activity attributable to shp. Together, these results suggest that shp can modulate pparalpha/rxralpha-mediated transcription in a response element-specific manner... | SIGNOR-108252 |
P01106 | Q02127 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.346 | PPAT, catalyzing the first step of purine synthesis, and DHODH, an enzyme generating uridine in the middle of the pyrimidine synthesis pathway, were validated as direct c-MYC target genes by all criteria. | SIGNOR-267382 |
Q04771 | P18075 | 2 | binding | up-regulates | 0.807 | Bmp-4 and gdf-5 are known to bind to activin receptor-like kinase 3 (alk-3) and/or alk-6 (also termed bmp type ia and type ib receptors, respectively), whereas bmp-6 and bmp-7 preferentially bind to alk-2 | SIGNOR-236913 |
P84243 | P06241 | 0 | phosphorylation | down-regulates activity | 0.2 | Here we provide evidence that fyn kinase, a member of the src kinase family, is involved in the uvb-induced phosphorylation of histone h3 at serine 10 | SIGNOR-130274 |
P47736 | P62834 | 2 | binding | down-regulates activity | 0.837 | Overexpression of Rap1GAP significantly inhibited Rap1 activation, ERK and Akt phosphorylation of HUVECs compared with pcDNA transfection controls | SIGNOR-278054 |
P49841 | P10636 | 1 | phosphorylation | down-regulates activity | 0.739 | We found that cdk5 phosphorylated tau(441) at Thr-181, Ser-199, Ser-202, Thr-205, Thr-212, Ser-214, Thr-217, Thr-231, Ser-235, Ser-396, and Ser-404, but not at Ser-262, Ser-400, Thr-403, Ser-409, Ser-413, or Ser-422. GSK-3beta phosphorylated all the cdk5-catalyzed sites above except Ser-235. | SIGNOR-249346 |
Q13118 | Q96ST3 | 2 | binding | up-regulates activity | 0.447 | detailed biochemical and functional analyses have demonstrated that the TIEG2 _-HRM domain interacts specifically with the PAH2 domain of mSin3A to repress transcription. our data suggest the presence of a conserved _-helical repression motif (_-HRM) in the TIEG and BTEB subfamilies of Sp1-like proteins that mediates t... | SIGNOR-222394 |
Q92985 | P03209 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.2 | EBV Rta selectively down-regulates the expression of IRF3 and IRF7, the main regulators of the Type I IFNs. | SIGNOR-266645 |
P62136 | Q03112 | 1 | dephosphorylation | down-regulates activity | 0.2 | We also identified EVI1 phosphorylation sites by MS analysis and showed that Ser538 and Ser858 can be phosphorylated and dephosphorylated by two EVI1 interactome proteins, casein kinase II and protein phosphatase-1α. Finally, mutations that impair EVI1 phosphorylation at these sites reduced EVI1 DNA binding through its... | SIGNOR-273430 |
Q53ET0 | Q9Y4K3 | 0 | ubiquitination | down-regulates quantity | 0.307 | Consistently, TRAF6 reduced G6pase gene expression or reporter activity induced by wild-type CRTC1 and CRTC2 but not TRAF6-interaction-defective CRTC1 and CRTC2 (XREF_FIG and XREF_SUPPLEMENTARY).|Indeed, TRAF6, the E3 ubiquitin ligase activated by IL-1beta associates with and ubiquitinates CRTC2. | SIGNOR-278725 |
P40426 | P55075 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | 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 heterodi... | SIGNOR-265779 |
Q09472 | P28482 | 0 | phosphorylation | up-regulates | 0.466 | Erk2-mediated c-terminal serine phosphorylation of p300 (ser-2279, ser-2315, and ser-2366) is vital to the regulation of epidermal growth factor-induced keratin 16 gene expression. | SIGNOR-156891 |
P17612 | O95180 | 1 | phosphorylation | down-regulates activity | 0.2 | Here, we identify protein kinase A (PKA) as a molecular switch that allows Gbeta(2)gammax dimers to effect voltage-independent inhibition of Ca(v)3.2 channels. Inhibition requires phosphorylation of Ser(1107), a critical serine residue on the II-III loop of the channel pore protein. S1107A prevents inhibition of unitar... | SIGNOR-263110 |
Q14653 | Q9Y6W6 | 0 | dephosphorylation | down-regulates activity | 0.2 | The inactivation of IRF3 by MKP5 is dependent on MKP5 phosphatase activity or its binding to IRF3.|This is confirmed since MKP5 phosphatasedeficient mutant is unable to dephosphorylate IRF3 and MKP5 mutant lacking IRF3 binding motifs fails to suppress IRF3 nuclear translocation upon virus infection. | SIGNOR-277146 |
P18848 | P68400 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.2 | By using mutants of ATF4 we identified serine 215 as the main CK2 phosphorylation site. The ATF4 S215A mutant turned out to be more stable than the wild-type form. | SIGNOR-276425 |
Q15058 | Q8TDX7 | 0 | phosphorylation | up-regulates activity | 0.371 | Nek7 direct phosphorylation is required for the anaphase localization of Kif14. we generated an EGFP-Kif14-5A construct in which Ser56, Ser607, Ser1217, Ser1219, and Ser1220 were all mutated to Ala. When transfected into HeLa cells, EGFP-Kif14-5A was expressed to similar levels as WT Kif14 (Fig. S3 C), but its localiza... | SIGNOR-266420 |
P17612 | Q07954 | 1 | phosphorylation | up-regulates activity | 0.324 | LRP phosphorylation is mediated by PKA at residue serine 76 of its cytoplasmic tail and that this phosphorylation contributes to receptor-mediated endocytosis. | SIGNOR-250000 |
P31749 | P23588 | 1 | phosphorylation | up-regulates | 0.393 | Using an in vitro kinase assay, we found that pkb can directly phosphorylate eif4b on serine 422 (ser422). This was prevented by pretreatment of cells with the phosphatidylinositol 3-kinase (pi3k) inhibitor ly294002 or pharmacological inhibition of pkb. Phosphorylation regultes the activation of eukaryotic translation ... | SIGNOR-252520 |
Q07817 | O43521 | 2 | binding | down-regulates activity | 0.956 | Bim can induce apoptosis by interacting with anti-apoptotic members of the bcl2 family, including bcl2, bcl-xl and mcl-1.Bim binds bcl-2, bcl2l1, bcl2l2, mcl1 and a1 tightly. | SIGNOR-178679 |
P35226 | P31751 | 0 | phosphorylation | up-regulates activity | 0.292 | the polycomb group silencing protein Bmi1 can be phosphorylated by AKT, which enhances its oncogenic potential in PCa. Overexpression of Bmi1 can act in combination with PTEN haploinsufficiency to induce invasive carcinogenic formation in the prostate | SIGNOR-249582 |
P04839 | P23769 | 0 | transcriptional regulation | down-regulates quantity | 0.25 | These results suggest that GATA-1 is an activator and that GATA-2 is a relative competitive inhibitor of GATA-1 in the expression of the gp91(phox) gene in human eosinophils. | SIGNOR-259948 |
P24941 | Q9Y618 | 1 | phosphorylation | down-regulates activity | 0.429 | Cdk2 and Pin1 negatively regulate the transcriptional corepressor SMRT.|Cdk2 phosphorylates SMRT at consensus Cdk motifs to generate Pin1 binding sites and consequently targets SMRT for degradation, the latter also requiring the PPIase activity of Pin1 (XREF_FIG). | SIGNOR-278306 |
P21127 | O00303 | 1 | phosphorylation | up-regulates activity | 0.515 | EIF3f is phosphorylated by CDK11p46 at Ser46 during apoptosis.|Phosphorylation of eIF3f plays an important role in regulating its function in translation and apoptosis. Phosphorylation of eIF3f enhances the association of eIF3f with the core eIF3 subunits during apoptosis. | SIGNOR-273133 |
P53778 | P05787 | 1 | phosphorylation | up-regulates | 0.2 | Keratin 8 (k8) serine 73 occurs within a relatively conserved type ii keratin motif . Here we show that ser-73 is exclusively phosphorylated in vitro by p38 mitogen-activated protein kinase. The ser-73 --> ala-associated filament reorganization defect is rescued by a ser-73 --> asp mutation. Also, disease-causing kerat... | SIGNOR-114067 |
P53350 | O60566 | 1 | phosphorylation | up-regulates | 0.84 | We identify s676 as a plk1-specific phosphorylation site on bubr1. These findings describe the first in vivo verified phosphorylation site for human bubr1, identify plk1 as the kinase responsible for causing the characteristic mitotic bubr1 upshift, and attribute a kt-specific function to the hyperphosphorylated form o... | SIGNOR-157646 |
Q15303 | Q92529 | 1 | relocalization | up-regulates | 0.497 | Like erbb1, erbb4 recruits grb2, shc and stat5. | SIGNOR-147850 |
P22681 | P17252 | 0 | phosphorylation | down-regulates quantity | 0.322 | However, under normal conditions, PKC activation resulting from CD43 engagement was required to activate the MAPK pathway, suggesting that phosphorylation of Cbl on serine residues by PKC and its association with 14-3-3 molecules may play a role in preventing the Cbl inhibitory effect on the Ras-MAPK pathway. | SIGNOR-249056 |
Q9HC62 | Q15418 | 0 | phosphorylation | down-regulates activity | 0.2 | Here, we determined that d-flow activated the serine/threonine kinase p90RSK, which subsequently phosphorylated threonine 368 (T368) of SENP2. T368 phosphorylation promoted nuclear export of SENP2, leading to downregulation of eNOS expression and upregulation of proinflammatory adhesion molecule expression and apoptos... | SIGNOR-273839 |
Q03164 | Q9H7Z6 | 2 | binding | up-regulates | 0.488 | Mll1 and mof can form a stable complex in vivo / given that an interaction of dmof with msl1 through its zinc finger is essential for correct targeting of mof to the male x chromosome | SIGNOR-138245 |
P04001 | Q92753 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | These observations indicate that RORβ is required for the induction of S opsin and support the conclusion that RORβ regulates Opn1sw transcription in a direct manner through ROREs within its proximal promoter region. In addition, they explain the greatly diminished expression of Opn1sw observed in the retina of RORβ-/-... | SIGNOR-266851 |
P42224 | P42224 | 2 | binding | up-regulates activity | 0.2 | Each STAT1 monomer becomes tyrosine phosphorylated at tyrosine 701 by the JAKs, dissociates from the receptor to form a STAT1-STAT1 homodimer which translocates to the nucleus | SIGNOR-249495 |
Q16777 | Q14493 | 0 | translation regulation | up-regulates quantity by expression | 0.2 | Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cy... | SIGNOR-265398 |
O00267 | P50750 | 0 | phosphorylation | up-regulates | 0.776 | We describe an evolutionarily conserved repetitive heptapeptide motif (consensus = g-s-r/q-t-p) in the c-terminal region (ctr) of hspt5, which, like the c-terminal domain (ctd) of rna pol ii, is highly phosphorylated by p-tefb. Thr-4 residues of the ctr repeats are functionally important phosphorylation sites. In vitro... | SIGNOR-143939 |
P19634 | Q15418 | 0 | phosphorylation | up-regulates | 0.452 | The results indicate that p90rsk phosphorylates serine 703 of nhe-1, and this phosphorylation is required for growth factor stimulation of na+/h+ exchange. | SIGNOR-69171 |
P14921 | O43711 | 2 | binding | down-regulates activity | 0.364 | We show that the cortical thymic maturation arrest in T-lineage ALLs that overexpress TLX1 or TLX3 is due to binding of TLX1/TLX3 to ETS1, leading to repression of T cell receptor (TCR) α enhanceosome activity and blocked TCR-Jα rearrangement. | SIGNOR-259098 |
P51955 | Q5T7B8 | 1 | phosphorylation | up-regulates activity | 0.695 | Nek2 binds and phosphorylates Kif24.|We also provide evidence that Nek2 dependent phosphorylation induces a conformational change in Kif24 that promotes its activity. | SIGNOR-278413 |
Q9Y5H0 | Q9Y5H9 | 2 | binding | up-regulates activity | 0.2 | The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion. They also form oligomers with Pcdh-gamma proteins at the same membrane sites. | SIGNOR-265677 |
P43115 | P08754 | 2 | binding | up-regulates activity | 0.457 | 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- signali... | SIGNOR-256859 |
Q9GZM8 | P62258 | 2 | binding | up-regulates activity | 0.667 | 14-3-3epsilon is involved in the proper localization of NUDEL and LIS1 in axons. 14-3-3ε binds to NUDEL phosphorylated by cyclin-dependent kinase (cdk5) and maintains NUDEL phosphorylation. Deficiency of 14-3-3ε causes mislocalization of the NUDEL/LIS1 complex from axons, suggesting that 14-3-3ε regulates the axonal ta... | SIGNOR-252160 |
P55085 | P08246 | 0 | cleavage | down-regulates activity | 0.395 | PAR1E and PAR2E (10 microM) were incubated in the presence of the different proteases | The enzymes were used at the following concentrations: 0.5 unit/mL thrombin, 2.5 nM trypsin, 20 nM plasmin, 20 nM cathepsin G, 20 nM elastase, 20 nM proteinase 3, and 2 units/mL calpain I and II|Protease-activated receptors (PARs) m... | SIGNOR-263588 |
P30559 | P25098 | 0 | phosphorylation | down-regulates activity | 0.2 | Recent experiments in COS-7 cells transfected with OTR have demonstrated that a rapid GRK2-mediated phosphorylation of the agonist-occupied OTR is a key first step leading to its desensitization, and that it precedes and is required for β-arrestin-dependent internalization | SIGNOR-270329 |
Q9UHI6 | P58012 | 2 | binding | up-regulates | 0.445 | Dp103 further increased the cell killing effect induced by foxl2 probably due to the direct association of dp103 with foxl2 protein. | SIGNOR-140388 |
P51812 | P16220 | 1 | phosphorylation | up-regulates activity | 0.726 | MAPK activates CREB kinase, which in turn phosphorylates and activates CREB. Purification, sequencing, and biochemical characterization of CREB kinase revealed that it is identical to a member of the pp90(RSK) family, RSK2. RSK2 was shown to mediate growth factor induction of CREB serine-133 phosphorylation both in vit... | SIGNOR-248951 |
O96017 | P30304 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.843 | We show that IR-induced destruction of Cdc25A requires both ATM and the Chk2-mediated phosphorylation of Cdc25A on serine 123. | SIGNOR-106808 |
Q01974 | P49674 | 0 | phosphorylation | up-regulates | 0.268 | We also show that ror2 is phosphorylated by ckiepsilon on serine/threonine residues. | SIGNOR-129117 |
Q13547 | Q04206 | 2 | binding | down-regulates | 0.571 | Phosphorylation at thr505 by the chk1 inhibits rela transactivation and results in its increased association with hdac1. | SIGNOR-151425 |
O00257 | O60315 | 1 | sumoylation | down-regulates quantity by destabilization | 0.331 | Pc2 can act directly as an E3 ligase for SIP1 sumoylation.SIP1 sumoylation having a negative effect on its repression of E-cadherin transcription. | SIGNOR-268955 |
P49757 | Q8N448 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.605 | Polyubiquitination of Human Numb by LNX2. The Zn-RING-Zn domain of LNX2 is a dimer and assumes a rigid elongated structure that undergoes autoubiquitination and undergoes N-terminal polyubiquitination. LNX2 can bind numb and induce its ubiquitination and subsequent proteasomal degradation | SIGNOR-272423 |
P07947 | P29317 | 0 | phosphorylation | up-regulates activity | 0.423 | EphA2 interacts with YES1 and phosphorylates YES1 at Tyr426 site. | SIGNOR-277556 |
P05198 | P18848 | 1 | transcriptional regulation | down-regulates quantity | 0.64 | ER stress, viral infection, and other cellular stress signals activate PERK, PKR, HRI, and GCN2 kinases that converge on phosphorylation of eIF2alpha, the core of ISR. This leads to global attenuation of Cap Âdependent translation while concomitantly initiates the preferential translation of ISR Âspecific mRNAs, such... | SIGNOR-260169 |
O15084 | P49840 | 0 | phosphorylation | down-regulates activity | 0.2 | We provide evidence for a dual kinase-mediated regulation of the PITK holoenzyme whereby PITK phosphorylation at S1017 is catalyzed by calcium/calmodulin-dependent kinase II-delta (CaMKIIdelta), promoting the subsequent phosphorylation of S1013 by glycogen synthase kinase-3 (GSK3) in vitro.|the phosphorylation of PITK ... | SIGNOR-264792 |
P46531 | P15923 | 2 | binding | down-regulates | 0.426 | We provide evidence that notch and deltex may act on e47 by inhibiting signaling through ras because (i) full e47 activity was found to be dependent on ras and (ii) both notch and deltex inhibited gal4-jun, a hybrid transcription factor whose activity is dependent on signaling from ras to sapk/jnk. | SIGNOR-56150 |
Q96QT6 | Q96ST3 | 2 | binding | up-regulates activity | 0.796 | Pf1 interacts with mSin3A in vivo. Gal4-Pf1 repressed activity of the reporter gene fivefold relative to Gal4 alone (Fig. (Fig.5A),5A), suggesting that DNA-bound Pf1 was capable of recruiting functional mSin3A complexes. | SIGNOR-266995 |
Q05469 | P17612 | 0 | phosphorylation | up-regulates activity | 0.602 | HSL activity is known to be regulated by phosphorylation (3). PKA increases HSL activity via phosphorylation at Ser563, Ser659, and Ser660 (14,15), although phosphorylation at Ser565 by glycogen synthase kinase, AMP-dependent protein kinase, or Ca2+/calmodulin-dependent protein kinase II has been reported to prevent ac... | SIGNOR-249202 |
Q86UZ6 | P10275 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.2 | Our study confirmed a novel positive association between ZBTB46 activity and LIF levels in prostate cancer tissues and cells. Under androgen regulation, low levels of ZBTB46 are an essential transcriptional factor for maintaining LIF-STAT3 signaling, while the loss of androgen signaling or inhibition of AR signaling ca... | SIGNOR-277989 |
Q96RG2 | Q96RG2 | 2 | phosphorylation | up-regulates activity | 0.2 | We present evidence that the activity of pask is regulated by two mechanisms. Autophosphorylation at two threonine residues located within the activation loop significantly increases catalytic activity. | SIGNOR-109481 |
P37275 | P0C2W1 | 2 | binding | down-regulates quantity by destabilization | 0.285 | One of the hallmarks of EMT is loss of E-cadherin and gain of N-cadherin expression, which are regulated by the core EMT-inducing transcription factors (EMT-TFs), such as Zeb1/2, Snai1/2 and Twist1. Here, we find that EMT-TFs can be dynamically degraded by an atypical ubiquitin E3 ligase complex Skp1-Pam-Fbxo45 (SPFFbx... | SIGNOR-272179 |
P78527 | P16403 | 1 | phosphorylation | down-regulates activity | 0.2 | Similarly, DNA-PK-mediated phosphorylation of H1.2 at T146 enhances p53 transcriptional activity by impeding H1.2 binding to p53 and thereby attenuating its suppressive effects on p53 transactivation. | SIGNOR-273834 |
Q16665 | P27540 | 2 | binding | up-regulates activity | 0.787 | The functional transcription factor exists as a heterodimeric complex consisting of HIF-1alpha and the aryl hydrocarbon receptor nuclear translocator (ARNT). Association of HIF-1 with ARNT is required for its activity; however, no other role has been ascribed to this interaction. | SIGNOR-253720 |
P45983 | Q15672 | 1 | phosphorylation | up-regulates | 0.308 | Phosphorylation of serine 68 of twist1 by mapks stabilizes twist1 protein and promotes breast cancer cell invasiveness. | SIGNOR-173417 |
P27361 | P49815 | 1 | 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 ... | SIGNOR-249457 |
Q9UQD0 | P61328 | 2 | binding | down-regulates activity | 0.317 | 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-253412 |
P28482 | Q01196 | 1 | phosphorylation | up-regulates activity | 0.2 | We have identified four phosphorylation sites on AML1c that are necessary for transcriptional activity of AML1c in K562 and 293T cells (27).4 Mutation of these four sites (serine 276, serine 293, serine 303, and threonine 300) to alanine abolishes transcriptional activation, whereas mutation of these sites to aspartic ... | SIGNOR-138973 |
Q5ST30 | Q2TAL8 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 a... | SIGNOR-269409 |
Q9H410 | Q96GD4 | 0 | phosphorylation | down-regulates | 0.653 | To determine whether the combinatorial regulation of the kmn network by aurora b observed in vitro is critical to controlling kinetochore-microtubule attachments in vivo, we next investigated the effect of the phosphomimetic (to aspartate) and nonphosphorylatable (to alanine) mutants of dsn1, knl1, and ndc80 in vertebr... | SIGNOR-165546 |
Q00987 | P11309 | 0 | phosphorylation | up-regulates | 0.388 | Additionally, the pim kinases phosphorylate mdm2 in vitro and in cultured cells at ser166 and ser186, two previously identified targets of other signaling pathways, including akt. | SIGNOR-178619 |
Q9H9R9 | Q13049 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.2 | TRIM32 is an E3 ubiquitin ligase for dysbindin. TRIM32 targets dysbindin for degradation. | SIGNOR-271422 |
Q15796 | Q9UPN9 | 2 | binding | up-regulates activity | 0.638 | The ubiquitious nuclear protein transcriptional intermediary factor 1gamma (tif1gamma) selectively binds receptor-phosphorylated smad2/3 in competition with smad4. Rapid and robust binding of tif1gamma to smad2/3 occurs in hematopoietic, mesenchymal, and epithelial cell types in response to tgfbeta. Tif1gamma mediates ... | SIGNOR-236064 |
Q06413 | Q9UKX2 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.431 | Myocyte enhancer factor-2 and serum response factor binding elements regulate fast Myosin heavy chain transcription in vivo. We show that the upstream promoter region of the gene most abundantly expressed in mouse skeletal muscles, IIb MyHC, retains binding activity and transcriptional activation for three positive tra... | SIGNOR-238718 |
Q12770 | Q9Y5U4 | 2 | binding | down-regulates activity | 0.717 | insig-2, a second protein of the endoplasmic reticulum that blocks the processing of sterol regulatory element-binding proteins (SREBPs) by binding to SCAP (SREBP cleavage-activating protein) in a sterol-regulated fashion, thus preventing it from escorting SREBPs to the Golgi. | SIGNOR-256209 |
Q07954 | P01009 | 2 | binding | up-regulates | 0.322 | In vitro binding studies revealed that antithrombin iii (atiii)thrombin, heparin cofactor ii (hcii)thrombin, and ?1-antitrypsin (?1AT)trypsin bound to purified lrp | SIGNOR-41180 |
P23470 | P42224 | 1 | dephosphorylation | up-regulates activity | 0.2 | PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and V... | SIGNOR-254727 |
P78563 | P31751 | 0 | phosphorylation | down-regulates activity | 0.2 | AKT-dependent phosphorylation of the adenosine deaminases ADAR-1 and -2 inhibits deaminase activity. Coimmunoprecipitation studies and in vitro kinase assays revealed that AKT-1, -2, and -3 interact with both ADAR1p110 and ADAR2 and phosphorylate these RNA editases. Using site-directed mutagenesis of suspected AKT phos... | SIGNOR-276196 |
P49841 | O95644 | 1 | phosphorylation | down-regulates activity | 0.588 | In T-cells, calcineurin de-phosphorylates NFATc1, leading to its nuclear import, while glycogen synthase kinase 3 beta (GSK3beta) phosphorylates NFATc1 and promotes its nuclear export.|We conclude that GSK3beta negatively regulates NFATc1 in vSMCs, and GSK3beta must be inactivated to allow NFAT activation during wound ... | SIGNOR-279185 |
P01374 | P36941 | 2 | binding | up-regulates | 0.845 | These experiments point toward the lt-alpha 1/beta 2 complex as the predominant membrane form of lt on the lymphocyte surface, and this complex is the primary ligand for the lt-beta receptor. | SIGNOR-35708 |
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 |
P51812 | O60825 | 1 | phosphorylation | up-regulates activity | 0.2 | Heart 6-phosphofructo-2-kinase activation by insulin results from ser-466 and ser-483 phosphorylation and requires 3-phosphoinositide-dependent kinase-1, but not protein kinase b. | SIGNOR-23753 |
P62136 | P29474 | 1 | dephosphorylation | up-regulates activity | 0.2 | The increase in eNOS activity coincided with specific dephosphorylation of eNOS-Thr495, known to enhance eNOS activity. Inhibition of protein phosphatase 1 (PP1) by calyculin A, tautomycetin, or siRNA against PP1 reversed NF-induced eNOS-Thr495 dephosphorylation | SIGNOR-248558 |
P31431 | Q6UXX9 | 2 | binding | up-regulates | 0.265 | We show that rspo3 binds syndecan 4 (sdc4) and that together they activate wnt/pcp signaling. | SIGNOR-172719 |
P49682 | P02778 | 2 | binding | up-regulates activity | 0.787 | The chemokines CXCL9, 10, and 11 exert their action via CXC chemokine receptor-3 (CXCR3), a receptor highly expressed on activated T cells. | SIGNOR-260969 |
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