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 |
|---|---|---|---|---|---|---|---|
Q9HCD6 | P78352 | 2 | binding | up-regulates activity | 0.312 | In the present study, we provide evidence that TANC1 and its close relative TANC2 regulate dendritic spines and excitatory synapses. our results indicate that TANC-dependent spine/synapse maintenance requires TANC binding to PSD-95, which promotes synaptic localization of TANC proteins. Thus, it is likely that interaction with PSD-95 concentrates TANC proteins at synapses, where they play a role in mediating PSD-95-dependent maintenance of spines and synapses. | SIGNOR-266895 |
P54845 | Q96SL8 | 2 | binding | up-regulates activity | 0.55 | Interaction of Fiz1 and NRL-leucine zipper was validated by GST pulldown assays and co-immunoprecipitation from bovine retinal nuclear extracts. Fiz1 suppressed NRL- but not CRX-mediated transactivation of rhodopsin promoter activity in transiently transfected CV1 cells. | SIGNOR-223796 |
Q13043 | P42574 | 0 | cleavage | up-regulates activity | 0.617 | In response to apoptotic stimuli, caspase cleavage of mst1 occurs at asp-326 and asp-349, resulting in the separation of its n-terminal kinase domain from the nes-containing c-terminal domain. Thus, caspase cleavage of mst1 serves two purposes: one is activation of mst1 kinase activity and the other is translocation of mst1 into the nucleus. | SIGNOR-109878 |
Q9UQC2 | P43403 | 0 | phosphorylation | up-regulates activity | 0.46 | In the present study, we found that gab2 is phosphorylated by zap-70, associates with the tcr signaling complex, and acts as an inhibitory adaptor molecule via recruitment of shp-2 following tcr ligation. | SIGNOR-110731 |
P41145 | P01189 | 0 | chemical activation | up-regulates activity | 0.652 | Accordingly, for the OTDP, the binding affinity and activity of a large number of opiate compounds have been tested at μ-, δ-, and κ-opiate receptors. Binding studies were originally conducted in guinea pig brain membranes, and subsequent studies have been carried out in CHO cells transfected with human receptors. Table 7 shows a biochemical method for determining activity and potency of opioid compounds, stimulation of [35S]GTPγS binding in membranes from cells transfected with human μ, δ, or κ receptors. | SIGNOR-258410 |
Q12913 | P68400 | 0 | phosphorylation | up-regulates activity | 0.2 | CK2-dependent phosphorylation of DEP-1 T1318 promotes Y1320 phosphorylation and Src activation upon VEGF stimulation. | SIGNOR-277876 |
P49715 | P63279 | 0 | sumoylation | down-regulates activity | 0.2 | C/EBPalpha interacts directly with the E2 SUMO-conjugating enzyme Ubc9 and can be SUMOylated in vitro using purified recombinant components. Our results indicate that SUMO modification of SC motifs provides a means to rapidly control higher order interactions among transcription factors and suggests that SUMOylation may be a general mechanism to limit transcriptional synergy. | SIGNOR-256334 |
P43405 | P02730 | 1 | phosphorylation | up-regulates | 0.451 | Our findings suggest that, upon phosphorylation by p72syk, y8 and y21 act as docking sites for the sh2 domain of lyn, which subsequently phosphorylates band 3 at additional secondary sites. | SIGNOR-80792 |
O60716 | P52735 | 2 | binding | up-regulates | 0.61 | We demonstrate that p120-catenin participates in the stimulation of rac1 activity, binding directly to this protein. In addition we show that vav2 also binds to p120-catenin and is required for rac1 activation and for beta-catenin translocation to the nucleus.Vav2 And rac1 association with p120-catenin was modulated by phosphorylation of this protein, which was stimulated upon serine/threonine phosphorylation by ck1 and inhibited by tyrosine phosphorylation by src or fyn | SIGNOR-198941 |
P10276 | Q8IZD2 | 2 | binding | up-regulates activity | 0.334 | MLL5 binds to retinoic acid receptor α (RARα) and induces transcriptional activation of RARα target genes by methylation of lysine residues of histone H3. | SIGNOR-260041 |
P63092 | O75084 | 2 | binding | up-regulates activity | 0.2 | Wnt7a binding to fzd7 activates pi3k through a g protein alpha s- dependent mechanism. | SIGNOR-198831 |
P62140 | Q96C90 | 2 | binding | down-regulates activity | 0.286 | We conclude that ILK may activate smooth-muscle contraction both directly, via phosphorylation of myosin, and indirectly, via phosphorylation and activation of CPI-17 and PHI-1, leading to inhibition of MLCP.|CPI-17 and PHI-1 thiophosphorylated by ILK at Thr(38) or Thr(57) respectively inhibited myosin light-chain phosphatase (MLCP) activity bound to myosin | SIGNOR-265743 |
P29322 | Q12857 | 0 | transcriptional regulation | up-regulates quantity | 0.2 | For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8) | SIGNOR-268896 |
Q00535 | P54646 | 1 | phosphorylation | down-regulates activity | 0.216 | In vitro, the results show that murine wild-type AMPK-alpha2 was phosphorylated by Cdk5 at a (S/T) PX (K/H/R) phosphorylation consensus sequence, which was associated with decreased AMPK-alpha2 activity.|Inactivated AMPK-alpha2 promotes the progression of diabetic brain damage by Cdk5 phosphorylation at Thr485 site. | SIGNOR-280218 |
P19174 | O60260 | 0 | ubiquitination | down-regulates quantity | 0.2 | In order to address the functional role of parkin ubiquitination of PLCgamma1, we investigated PLC activity in human neuroblastoma SH-SY5Y cell lines stably transfected with either WT, or mutant R42P or G328E parkin.|WT parkin expression significantly reduced the levels of PLCgamma1 in human neuroblastoma. | SIGNOR-278592 |
Q9UGK3 | O60674 | 0 | phosphorylation | up-regulates activity | 0.343 | To examine this possibility, STAP-2 was co-transfected with constitutively active tyrosine kinases in HEK-293 cells. STAP-2 was strongly phosphorylated by various tyrosine kinases, including v-Src (Fig.2 A-a), a JAK2 tyrosine kinase |On the other hand, the phosphorylation levels of Y22F, Y310F, and Y322F by GST-JH1 were reduced to 8060% of the levels of wild-type STAP-2, which suggests that these three are potential phosphorylation sites by activated JAK2. | SIGNOR-249372 |
P06730 | Q13541 | 2 | binding | down-regulates activity | 0.939 | The rate-limiting factor for translation is eukaryotic translation initiation factor 4E (eIF4E), which is negatively regulated by eIF4E-binding protein 1 (4E-BP1). | SIGNOR-167176 |
O60353 | P04628 | 2 | binding | up-regulates activity | 0.692 | Distinctly, wnt1 signals through fzd receptors 1 and 6 in the epaxial domain of the somite, to regulate myf5 expression via the canonical bcatenin pathway. | SIGNOR-198846 |
Q01844 | Q15637 | 2 | binding | down-regulates | 0.418 | Here we report that zfm1 also interacts withews / overexpression of zfm1 in hepg2 cells represses the transactivation of reporter gene expression driven by gal4-ews-ntd fusion protein and this repression correlates with zfm1 binding to ews. | SIGNOR-58928 |
P16220 | P59595 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | The transcription factors c-Fos, FosB, CREB-1, and ATF2 were all activated by the addition of SARS-CoV N protein to the sample well | SIGNOR-260729 |
P48729 | P10070 | 1 | phosphorylation | down-regulates | 0.568 | Gli2 can also be phosphorylated directly by ck-1 at the non-optimal sites | SIGNOR-146112 |
P24821 | P14921 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Sp1 and Ets1 are potent transactivators of the TN-C promoter. | SIGNOR-261599 |
Q13363 | P45983 | 0 | phosphorylation | down-regulates | 0.358 | In this study, we found that c-jun nh2-terminal kinase 1 activation triggered ctbp phosphorylation on ser-422 and subsequent degradation, | SIGNOR-149721 |
P16949 | P45983 | 0 | phosphorylation | down-regulates | 0.316 | Involved in the regulation of the microtubule (mt) filament system by destabilizing microtubules. Prevents assembly and promotes disassembly of microtubules. Here we show that in response to hyperosmotic stress, jnk phosphorylates a key cytoplasmic microtubule regulatory protein, stathmin (stmn), on conserved ser-25 and ser-38 residues. In in vitro biochemical studies, we identified stmn ser-38 as the critical residue required for efficient phosphorylation by jnk and identified a novel kinase interaction domain in stmn required for recognition by jnk. We revealed that jnk was required for microtubule stabilization in response to hyperosmotic stress. | SIGNOR-166694 |
P23760 | P54727 | 2 | binding | down-regulates activity | 0.294 | Monoubiquitinated Pax3 was shuttled to the intrinsic proteasomal protein S5a by interacting specifically with the ubiquitin-binding protein Rad23B. | SIGNOR-237667 |
P19793 | P10589 | 2 | binding | up-regulates | 0.549 | Arp-1/rxr, coup-tfi/rxr, and arp-1/coup-tfi heterodimers bound the fp330-3' site | SIGNOR-79440 |
P36544 | P61586 | 2 | binding | up-regulates activity | 0.2 | Here, we demonstrate a role for α7 nAChR/G protein interaction in the activation of the small (monomeric) RhoA GTPase leading to cytoskeletal changes during neurite growth. Treatment of PC12 cells with the α7 nAChR agonist choline or PNU-282987 was associated with an increase in RhoA activity and an inhibition in neurite growth. | SIGNOR-253985 |
P19174 | P09619 | 0 | phosphorylation | up-regulates | 0.859 | Tyrosine phosphorylation has been shown to increase the enzymatic activity of plc-? / we show that the human pdgf ?- And ?-Receptors differ quantitatively in their abilities to associate with and phosphorylate plc-? And to stimulate inositol phosphate production. | SIGNOR-28179 |
P35638 | O75807 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.454 | ATF4 also induces another bZIP protein C/EBP-homologous protein (CHOP), which is responsible for triggering apoptosis in cells under prolonged ER stress. ATF4 and CHOP further induce growth arrest and DNA damage–inducible protein 34 (GADD34),a regulatory subunit of protein phosphatase 1 (PP1) that dephosphorylates eIF2α. This negative feedback mechanism enables protein synthesis to resume after resolution of ER stress. | SIGNOR-260173 |
P10415 | Q92934 | 0 | relocalization | down-regulates activity | 0.801 | Apoptosis is initiated when Bcl-2 and its prosurvival relatives are engaged by proapoptotic BH3-only proteins via interaction of its BH3 domain with a groove on the Bcl-2-like proteins. These interactions have been considered promiscuous, but our analysis of the affinity of eight BH3 peptides for five Bcl-2-like proteins has revealed that the interactions vary over 10,000-fold in affinity, and accordingly, only certain protein pairs associate inside cells. Bim and Puma potently engaged all the prosurvival proteins comparably. Bad, however, bound tightly to Bcl-2, Bcl-xL, and Bcl-w but only weakly to A1 and not to Mcl-1. | SIGNOR-133756 |
Q9Y6K1 | P01106 | 2 | binding | up-regulates activity | 0.712 | Based on one of these publications, we here showed that the interaction of Dnmt3a with c-myc promote the specific methylation of CG dinucleotides localized in c-myc boxes of promoter regions of CDKN2a, CCND1 and TIMP2 genes. Acellular experiments corroborated and complemented these results by revealing that the specificity of consensus sequence for DNA methylation of Dnmt3a is increased in presence of c-myc. | SIGNOR-255806 |
P52306 | P61224 | 2 | binding | up-regulates | 0.414 | Smggds has been previously shown to activate a wide variety of small gtpases, including the ras family members rap1a, rap1b, and k-ras, as well as the rho family members cdc42, rac1, rac2, rhoa, and rhob | SIGNOR-171552 |
P48163 | Q96PY6 | 0 | phosphorylation | down-regulates activity | 0.2 | PGAM5-mediated dephosphorylation of malic enzyme 1 (ME1) at S336 allows increased ACAT1-mediated K337 acetylation, leading to ME1 dimerization and activation, both of which are reversed by NEK1 kinase-mediated S336 phosphorylation. SIRT6 deacetylase antagonizes ACAT1 function in a manner that involves mutually exclusive ME1 S336 phosphorylation and K337 acetylation. | SIGNOR-275570 |
P0CG47 | P45974 | 0 | cleavage | up-regulates quantity | 0.767 | Here we provide data suggesting that two of the four mammalian ubiquitin precursors, UBA52 and UBA80, are processed mostly post-translationally whereas the other two, UBB and UBC, probably undergo a combination of co- and post-translational processing. Using an unbiased biochemical approach we found that UCHL3, USP9X, USP7, USP5 and Otulin/Gumby/FAM105b are by far the most active DUBs acting on these precursors. | SIGNOR-270821 |
Q86UY5 | P48730 | 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-273765 |
Q9NX47 | O95140 | 1 | ubiquitination | up-regulates activity | 0.2 | Taken together, these results suggested that MITOL regulates endoplasmic reticulum tethering to mitochondria by activating Mfn2 via K192 ubiquitination.|Therefore, MITOL specifically ubiquitinates mitochondrial Mfn2. | SIGNOR-278553 |
P11802 | P38936 | 2 | binding | down-regulates | 0.941 | P21cip1 is a cyclin-dependent kinase (cdk) inhibitor that is transcriptionally activated by p53 in response to dna damage.We Have explored the interaction of p21 with the currently known cdks. p21 effectively inhibits cdk2, cdk3, cdk4, and cdk6 kinases. | SIGNOR-29957 |
P20810 | P68400 | 0 | phosphorylation | up-regulates activity | 0.2 | We also showed that casein kinase 2, a pro-survival kinase overexpressed in many cancer types, phosphorylated calpastatin at Ser-633. Our results indicate that calpastatin phosphorylation promotes radiation resistance in GBM cells by increasing the activity of calpain proteases, which are known to promote survival and invasion in cancer. | SIGNOR-277388 |
Q04206 | P42224 | 2 | binding | down-regulates | 0.518 | Acetylated stat1 is able to interact with nf-kappab p65. As a consequence, p65 dna binding, nuclear localization, and expression of anti-apoptotic nf-kappab target genes decrease. | SIGNOR-144561 |
Q05655 | P07108 | 1 | phosphorylation | up-regulates | 0.2 | Acyl coenzyme a-binding protein (acbp) is phosphorylated following protein kinase c activation. | SIGNOR-160393 |
Q5H9F3 | Q13363 | 2 | binding | up-regulates activity | 0.437 | BCoR-L1 also interacts with the CtBP corepressor through a CtBP-interacting motif in its amino terminus. Furthermore, BCoR-L1 is located on the E-cadherin promoter, a known CtBP-regulated promoter, and represses the E-cadherin promoter activity in a reporter assay. | SIGNOR-259193 |
P68431 | P49336 | 0 | phosphorylation | down-regulates activity | 0.2 | However, within T/G-Mediator, cdk8 phosphorylates serine-10 on histone H3, which in turn stimulates H3K14 acetylation by GCN5L within the complex. Tandem phosphoacetylation of H3 correlates with transcriptional activation, and ChIP assays demonstrate co-occupancy of T/G-Mediator components at several activated genes in vivo. | SIGNOR-273171 |
O00187 | O75636 | 2 | binding | up-regulates activity | 0.517 | In the lectin pathway, mannose-binding lectin (MBL) and ficolins bind to pathogens and activate MBL-associated serine protease-2 (MASP-2) | SIGNOR-263412 |
O75182 | Q5VTB9 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.429 | Here we identify RNF220 (RING finger protein 220) as a novel ubiquitin ligase for Sin3B. RNF220 specifically interacts with Sin3B both in vitro and in vivo. Sin3B can be regulated by the ubiquitin-proteasome system. Co-expression of RNF220 promotes the ubiquitination and proteasomal degradation of Sin3B. | SIGNOR-271943 |
P17612 | Q13131 | 1 | phosphorylation | down-regulates activity | 0.423 | These agents also enhanced phosphorylation of alpha-Ser(485/491) by the cAMP-dependent protein kinase. AMPK alpha-Ser(485/491) phosphorylation was necessary but not sufficient for inhibition of AMPK activity in response to forskolin/isobutylmethylxanthine. | SIGNOR-256112 |
O15169 | O95271 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.774 | Both tankyrase isoforms interact with a highly conserved domain of axin and stimulate its degradation through the ubiquitin-proteasome pathway. | SIGNOR-187972 |
Q15139 | P22059 | 1 | phosphorylation | down-regulates | 0.444 | Pkd attenuates the function of both cert and osbp by phosphorylation at their respective ser(132) and ser(240) residues (phosphorylation inhibition) | SIGNOR-171756 |
Q8N163 | P19784 | 0 | phosphorylation | up-regulates activity | 0.2 | CK2alphawas bound to DBC1 and phosphorylated DBC1. The phosphorylation of DBC1 by CK2alphawas evidenced by co-immunoprecipitation of CK2alphaand DBC1 in a GST pull-down assay, an in vitro kinase assay, and immunofluorescence staining. |In our results, CK2alpha affected the|These results suggest that DBC1 may be involved in the progression of gastric carcinoma by inducing the EMT and that it is closely associated with CK2alpha-mediated phosphorylation of DBC1. phosphorylation of Thr454 on DBC1 | SIGNOR-267667 |
P17252 | P04637 | 1 | phosphorylation | up-regulates activity | 0.437 | Here, we demonstrate that cotransfection of p53 with either PKC alpha or PKC zeta increases p53's transcriptional activity. Mutagenesis of p53 indicates that serine 371 is the major site for phosphorylation by PKC alpha in vitro. | SIGNOR-248999 |
P67775 | Q8NEL9 | 1 | dephosphorylation | up-regulates activity | 0.2 | Here we incubated a recombinant preparation of the phospholipase in vitro with several enzymes including protein kinase CK2 (CK2), extracellular signal-regulated kinase 2 (ERK2), and protein phosphatase 2A (PP2A) to identify effects that might be of regulatory importance in vivo.Major findings were that 1) CK2 phosphorylated the phospholipase on serines 93, 105, and 716; 2) ERK2 phosphorylated the enzyme on serine 730; 3) there was cross-antagonism between the reactions that phosphorylated serines 716 and 730; 4) PP2A selectively hydrolyzed phosphate groups that were esterified to serines 716 and 730. The results of two independent experiments with each type of assay indicated that the incubation caused a 50% loss of phospholipase activity (TableV). These results differed from those of corresponding incubation experiments with PA-PLA1α plus ERK2 and MgATP (see “Experimental Procedures”), which provided no evidence for complex formation or phosphorylation-dependent loss of phospholipase activity | SIGNOR-262975 |
Q8N1W1 | P61586 | 1 | guanine nucleotide exchange factor | up-regulates activity | 0.755 | 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-260546 |
P16949 | P05771 | 0 | phosphorylation | down-regulates | 0.2 | Op18 is multisite phosphorylated on four ser residues during mitosis;two of these ser residues, ser-25 and ser-38, are targets for cyclin-dependent protein kinases. our findings suggest that stathmin phosphorylation in reh6 cells could be in part mediated by pkc activation. | SIGNOR-50598 |
Q96J02 | O95999 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.276 | The HECT domain ubiquitin ligases NEDD4 and Itch promote ubiquitination and degradation of Bcl10, thus downmodulating NF-kappa B activation. | SIGNOR-271414 |
P31751 | Q92934 | 1 | phosphorylation | down-regulates | 0.525 | Ser-136 is the major phosphoacceptor site for akt;akt can weakly phosphorilate ser-155. | SIGNOR-81114 |
O14936 | Q00535 | 0 | phosphorylation | up-regulates activity | 0.288 | Cdk5 promotes synaptogenesis by regulating the subcellular distribution of the MAGUK family member CASK.|We found that Cdk5 phosphorylates and regulates CASK distribution to membranes. | SIGNOR-280216 |
Q92824 | P01178-PRO_0000020495 | 1 | cleavage | up-regulates quantity | 0.2 | Oxytocin-extended form is further cleaved by enzymatic activity to yield the nine-amino-acid active peptide, OT. The proteolysis may involve several pro-hormone convertases, convertase 2 (PC2) (20p11-1-11.2) and convertase 5 (PC5) (9q21.3) (Gabreels et al 1998). Both enzymes are found in OT neurosecretory vesicles and are a part of a family of subtilisen/kexinlike convertases (Seidah et al 1994). It is a product of the OT gene located at human gene locus 20p13 (Rao et al 1992). The processing cascade results in the production of neurophysin I and OT extended form (OT-X), which is OT with a C-terminal, three-amino-acid extension. | SIGNOR-270334 |
Q05513 | Q13164 | 1 | 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 |
P04792 | P31751 | 0 | phosphorylation | down-regulates | 0.289 | First, the akt1, akt2, and akt3 isoforms can bind directly to hsp27 and can be found in a complex with p38 mapk, mk2, and hsp27 [98_100]. Second, rane and colleagues showed that akt could phosphorylate hsp27 at ser-82, but not ser-15 or ser-78, in vitro, while co-expression of an active akt mutant and hsp27 in hek cells resulted in hsp27 phosphorylation at the same residue. | SIGNOR-186776 |
Q13976 | Q9Y613 | 1 | phosphorylation | up-regulates | 0.354 | Pkgi also directly phosphorylates fhod1, and studies with wild-type and mutant fhod1-derived peptides identify ser-1131 in the fhod1 c terminus as the unique pkgi phosphorylation site in fhod1. phosphorylation of three conserved residues within the dad domain activates fhod1 while binding to rac regulates fhod1 subcellular localization | SIGNOR-123646 |
P49407 | Q14940 | 1 | relocalization | down-regulates activity | 0.401 | Internalization of the Na(+)/H(+) exchanger NHE5 into recycling endosomes is enhanced by the endocytic adaptor proteins beta-arrestin1 and -2, best known for their preferential recognition of ligand-activated G protein-coupled receptors (GPCRs) | SIGNOR-275505 |
P42574 | Q13464 | 1 | cleavage | up-regulates | 0.734 | Rock i is cleaved by casp3 at a conserved detd1113/g sequence and its carboxy-terminal inhibitory domain is removed, resulting in deregulated and constitutive kinase activity. | SIGNOR-106546 |
Q02156 | P40763 | 1 | phosphorylation | up-regulates | 0.399 | Abrogation of pkcdelta activity inhibited insulin-induced stat3 phosphorylation, pkcdelta-stat3 association and nuclear translocation. | SIGNOR-143832 |
Q96J92 | Q96J92 | 2 | phosphorylation | down-regulates activity | 0.2 | Elimination of the catalytic activity (D321A or D321K-K186D) or the autophosphorylation site (S335A) in mutant WNK4-L322F abrogated the positive effect on NCC. | SIGNOR-276871 |
P30307 | P24941 | 0 | phosphorylation | up-regulates | 0.754 | The cyclin e/cdk2 complex phosphorylates cdc25c on ser(214), leading to its premature activation, which coincides with higher cyclin b/cdk1 and polo-like kinase 1 (plk1) activities in an s-phase-enriched population that result in faster mitotic entry. | SIGNOR-165872 |
Q02156 | P59047 | 1 | phosphorylation | up-regulates activity | 0.2 | MATER protein as substrate of PKCepsilon in human cumulus cells. we performed coimmunoprecipitation experiments using HEK293T cells expressing human MATER; a similar approach was then followed in human cumulus/follicular cells. In MATER(+)HEK293T cells, we observed that this protein acts as a phosphorylation substrate of PKCepsilon. Since PKCepsilon is known to collaborate with antiapoptotic signalling pathways, this suggests a novel mechanism for the function of MATER in follicular maturation. | SIGNOR-263175 |
Q8N884 | Q8WV44 | 0 | ubiquitination | up-regulates activity | 0.2 | Our finding that RINCK positively regulates cGAS activation by mediating the monoubiquitination of cGAS uncovers the function of RINCK in cGAS mediated innate immunity.|Together, these data suggest that RINCK mediates cGAS monoubiquitination. | SIGNOR-278794 |
P36956 | P53350 | 0 | phosphorylation | up-regulates activity | 0.441 | As illustrated in , the turnover of nuclear SREBP1a was attenuated in the presence of Plk1, confirming that Plk1 stabilizes nuclear SREBP1 by reducing its degradation.|Figure 2.Plk1 phosphorylates threonine 424, serine 467 and serine 486 in nuclear SREBP1 during mitosis. (A) In vitro kinase assay with recombinant nuclear SREBP1a and Plk1. | SIGNOR-279382 |
P49840 | Q13144 | 1 | phosphorylation | down-regulates activity | 0.368 | We identify multiple phosphorylation sites in the largest, catalytic, subunit (epsilon) of mammalian eIF2B. Glycogen synthase kinase 3 (GSK3) is responsible for phosphorylating Ser535. This regulatory phosphorylation event requires both the fourth site (Ser539) and a distal region, which acts to recruit GSK3 to eIF2Bepsilon in vivo. eIF2Bϵ from mammals or insects is a substrate for glycogen synthase kinase 3 (GSK3), and this inhibits the activity of eIF2B | SIGNOR-251215 |
O43781 | Q96EB6 | 1 | phosphorylation | up-regulates activity | 0.502 | DYRK1A and DYRK3 directly phosphorylate SIRT1 at Thr (522), promoting deacetylation of p53.|DYRK1A and DYRK3 promote cell survival through phosphorylation and activation of SIRT1. | SIGNOR-279705 |
P51812 | Q13164 | 0 | phosphorylation | up-regulates activity | 0.561 | This suggested that ERK5 may directly activate RSKs.|In vitro active ERK5 also phosphorylated RSK2 that had been immunoprecipitated from transfected cells using an anti-HA antibody ( Fig. 2 B).|Phosphorylation of RSK2 by ERK5 in vitro increased its activity towards GST-S6 as much as 8-fold (Figs. 2 C and E). | SIGNOR-279216 |
P07948 | P46934 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.459 | These findings suggest that LMP2A recruits Nedd4-like ubiquitin-protein ligases and B-cell signal transduction molecules, resulting in the degradation of LMP2A and Lyn by a ubiquitin-dependent mechanism. | SIGNOR-272558 |
Q00987 | Q6PCD5 | 2 | binding | up-regulates activity | 0.364 | RFWD3 is a positive regulator of p53 abundance and regulates the G1 checkpoint in response to IR. We found that an E3 ubiquitin ligase RFWD3 (RNF201/FLJ10520) forms a complex with Mdm2 and p53 to synergistically ubiquitinate p53 and is required to stabilize p53 in the late response to DNA damage. | SIGNOR-271945 |
P17612 | Q01668 | 1 | phosphorylation | up-regulates activity | 0.396 | We recently demonstrated that PKA activation led to increased alpha(1D) Ca(2+) channel activity in tsA201 cells by phosphorylation of the channel protein. Western blotting showed that the N terminus and C terminus were phosphorylated. Serines 1743 and 1816, two PKA consensus sites, were phosphorylated by PKA and identified by mass spectrometry. | SIGNOR-263109 |
P55212 | O60285 | 0 | phosphorylation | down-regulates activity | 0.483 | ARK5 negatively regulates procaspase-6 by phosphorylation at Ser257, leading to resistance to the FasL/Fas system. | SIGNOR-250209 |
Q13554 | Q9NQC7 | 1 | phosphorylation | up-regulates | 0.2 | Purified camkii phosphorylates cyld on at least three residues (s-362, s-418, and s-772 on the human cyld protein q9nqc7-1) and promotes its deubiquitinase activity. | SIGNOR-91403 |
Q9HD43 | P00533 | 1 | dephosphorylation | down-regulates activity | 0.288 | We further found that PTPRH and PTPRB directly dephosphorylate EGFR and repress its downstream signaling. | SIGNOR-277090 |
P04626 | P30530 | 0 | phosphorylation | down-regulates activity | 0.316 | Blockade of Axl function abrogated phosphorylation of ERBB2 (Her-2 and neu) at the Tyr877 residue, indicative of receptor crosstalk.|We have demonstrated that either pharmacological or genetic inhibition of Axl function abrogates phosphorylation of ERBB2 at the critical Tyr877 residue and sensitizes OE33 cells to lapatinib in vitro. | SIGNOR-280193 |
P63092 | Q99527 | 2 | binding | up-regulates activity | 0.377 | GPCRs transduce their signal via G-protein heterotrimers (αβγ) that dissociate in free Gα-subunit protein and Gβγ-subunit protein complexes following ligand stimulation; the activated receptor induces a conformational change in the associated G protein α-subunit leading to release of GDP followed by binding of GTP and α-subunit dissociation from the receptor. | SIGNOR-251102 |
Q9UM11 | O00429 | 1 | ubiquitination | down-regulates quantity | 0.349 | Here we demonstrate that changes in mitochondrial dynamics as cells exit mitosis are driven in part through ubiquitylation of Drp1 catalyzed by the APC/Ccdh1 (anaphase-promoting complex/cyclosome and its coactivator (Cdh1) E3 ubiquiting ligase complex | SIGNOR-274127 |
P31323 | P22694 | 2 | binding | down-regulates activity | 0.894 | Inactive PKA exists as a holoenzyme, comprised of two regulatory (R) subunits and two catalytic subunits . In the presence of cAMP, the holoenzyme becomes active by binding two cAMP molecules cooperatively to each R subunit, resulting in a conformational change in the R subunits, thus releasing the two C subunits to phosphorylate downstream targets | SIGNOR-258758 |
Q96FW1 | P04637 | 1 | deubiquitination | up-regulates quantity by stabilization | 0.565 | Furthermore, although OTUB1 dramatically induced p53 deubiquitination, its mutant (S16A) and deletion mutant did not have this effec | SIGNOR-276528 |
P49336 | P36956 | 1 | phosphorylation | up-regulates activity | 0.474 | Biochemical analyses reveal that SREBP-1c can be directly phosphorylated by CDK8 at the conserved Threonine-402 residue (T402) in vitro and in cultured mammalian cells ( xref ).|Therefore, the mechanism of CDK8 regulating SREBP functions is primarily through the phosphorylation initiated control of nuclear SREBP-1 protein stability. | SIGNOR-279688 |
P62820 | O75385 | 1 | relocalization | up-regulates activity | 0.532 | C9orf72 acts as an effector of Rab1a that recruits active Rab1a to theULK1 complex to promote translocation of the ULK1 complex to thephagophore during autophagy initiation | SIGNOR-261299 |
O60479 | P17252 | 0 | phosphorylation | down-regulates activity | 0.307 | Dlx3 is primarily phosphorylated by PKC alpha. By deletion and mutational analysis, we show that the serine residue S(138), located in the homeodomain of Dlx3 protein, was specifically phosphorylated by PKC. The phosphorylation of purified Dlx3 proteins by PKC partially inhibited formation of complexes between Dlx3 protein and DNA. These results suggest that Dlx3 protein can be directly phosphorylated by PKC and this affects the DNA binding activity of Dlx3. | SIGNOR-249096 |
Q14164 | P05412 | 1 | phosphorylation | up-regulates activity | 0.316 | Indeed, using an in vitro kinase assay, we demonstrated that both JNK and IKKepsilon phosphorylated c-Jun (XREF_FIG and XREF_SUPPLEMENTARY). | SIGNOR-279621 |
Q86VS8 | P21757 | 2 | binding | down-regulates | 0.333 | We have identified a microtubule-binding protein, hook3, as a novel interacting partner of sr-a. / by transfecting small interfering rna targeting hook3, total and surface expression, receptor-mediated ligand uptake and protein stability of sr-a were significantly promoted, whereas the protein synthesis and maturation were not altered. We propose for the first time that hook3 may participate in the turnover of the endocytosed scavenger receptor | SIGNOR-152314 |
Q92974 | Q9ULJ8 | 2 | binding | up-regulates activity | 0.341 | The Rho Family GEF Lfc Interacts with Neurabin and Spinophilin. Neurabin and spinophilin are homologous protein phosphatase 1 and actin binding proteins that regulate dendritic spine function. The results obtained in the present study suggest a mechanism by which neurabin or spinophilin contributes to the organization of the F-actin cytoskeleton in dendritic spines, and in turn to the regulation of spine morphology, via the activity-dependent recruitment of the Rho-specific GEF Lfc | SIGNOR-269177 |
Q92997 | P63000 | 2 | binding | up-regulates | 0.467 | Wnt/fz activation of rac and rho is inhibited by rac-n17 and rho-n19, respectively (figs. _(figs.1d,1d, _d,5c,d;5c,d;habas et al. 2001), and requires different dvl domains wnt signaling induces complex formation between dvl and rac. | SIGNOR-97409 |
Q99962 | O75116 | 0 | phosphorylation | down-regulates | 0.439 | We identified the phosphorylation site of endophilin a1 at thr-14 endophilin t14d inhibited egf receptor internalization. Furthermore, phosphorylation of endophilin by rho-kinase inhibited the binding to cin85. | SIGNOR-140466 |
O00230 | Q96LB1 | 2 | binding | up-regulates | 0.511 | The mrgx2 receptor has been shown to be activated by the peptides cortistatin and proadrenomedullin n-terminal peptides (pamp) | SIGNOR-139855 |
P06213 | P23470 | 0 | dephosphorylation | up-regulates activity | 0.365 | PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity. | SIGNOR-254703 |
P49841 | P50219 | 1 | phosphorylation | down-regulates | 0.295 | Here we show that gsk-3_ inactivates the proapoptotic activity of hlxb9 by phosphorylating hlxb9 at ser-78/ser-80 (phlxb9). | SIGNOR-203657 |
O00303 | P59594 | 2 | binding | down-regulates activity | 0.2 | Coronavirus spike protein inhibits host cell translation by interaction with eIF3f | SIGNOR-260255 |
Q8IUQ4 | P67809 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.244 | Here, we identified that SIAH1 which was downregulated in chemoresistant EOC samples and cell lines functioned as novel E3 ligases to trigger degradation of YBX-1 at cytoplasm by RING finger domain.|SIAH1 ubiquitinated YBX-1 at its K304 through the RING domain. | SIGNOR-278780 |
Q13363 | O95471 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | ChIP assays revealed that SNAI1P is recruited on the CLDN7 gene promoter along with the co-repressor CtBP1 and the effector HDAC1. | SIGNOR-254105 |
P10276 | P19793 | 2 | binding | up-regulates | 0.725 | Here we report that the transcriptional activity of rar and rxr can be reciprocally modulated by direct interactions between the two proteins | SIGNOR-16433 |
O15146 | O96014 | 2 | binding | up-regulates | 0.456 | Like ror, musk has an extracellular region with homolgogy to the frizzled crd, binding of which by wnt11 stimulates a pcp-like pathway during neuromuscular development | SIGNOR-199518 |
O14867 | P09601 | 1 | transcriptional regulation | down-regulates quantity | 0.361 | These results indicate that ho-1 regulation involves a competition between the activator Nrf2 and the Bach1 repressor for interactions with the small Maf proteins. | SIGNOR-259336 |
P60484 | Q9UDY6 | 0 | ubiquitination | down-regulates quantity | 0.2 | Collectively, these results indicate that TRIM10 may lead to ubiquitination and degradation of PTEN, which could be an underlying reason for AKT signalling inhibition in cardiac hypertrophy processes (Figure\u00a05D).4\n\nDISCUSSION.|In addition, we found that the effect regulated by TRIM10 was mediated by interactions with phosphatase and tensin homolog (PTEN); specifically, TRIM10 promoted PTEN ubiquitination, thus leading to AKT signalling activation.|The results showed that TRIM10 overexpression decreased PTEN expression, and MG132 reversed the reduction in PTEN (Figure\u00a05C). | SIGNOR-278729 |
Q12923 | P25963 | 1 | dephosphorylation | up-regulates quantity by stabilization | 0.442 | Identification of IkappaBalpha as a substrate of Fas-associated phosphatase-1|A full-length FAP-1 protein preferentially dephosphorylates Tyr-42 of IkBa|Moreover, other studies have shown that tyrosine phosphorylation of IkBa on Tyr-42 (which occurs with Fas ligand binging) protected against inducible degradation both in vitro [30] and in vivo [38] | SIGNOR-248712 |
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