IdA string | IdB string | labels int64 | mechanism string | effect string | score float64 | sentence string | signor_id string |
|---|---|---|---|---|---|---|---|
Q06413 | Q15759 | 0 | phosphorylation | up-regulates activity | 0.538 | In this study, we demonstrate that among the different Mitogen-activated protein kinases, the MADS-box transcription factors MEF2A and MEF2C are preferentially phosphorylated and activated by the p38 subfamily members p38alpha and p38beta2. | SIGNOR-280025 |
P68400 | Q9UNN4 | 1 | phosphorylation | up-regulates activity | 0.424 | ALF was able to stabilize the binding of TBP to DNA, but it could not stabilize TBP mutants A184E, N189E, E191R, and R205E nor could it facilitate binding of the TBP-like factor TRF2/TLF to a consensus TATA element. However, phosphorylation of ALF with casein kinase II resulted in the partial restoration of complex formation using mutant TBPs. | Because the residues involved (Ser-280, Ser-281, Ser-316, and Ser-321) are conserved in ALF (Ser-356, Ser-357, Ser-418, and Ser-423), we tested whether its activity might also be affected by this modification. We first showed that ALF and TFIIAα/β polypeptides incubated with casein kinase II and [γ-32P]ATP could be labeled. | SIGNOR-250873 |
P60484 | P42229 | 1 | dephosphorylation | down-regulates | 0.439 | The forced expression of pten in the eol-1r cells dephosphorylated akt, erk and stat5 /eol-1r cells showed epigenetic silencing of the phosphatase and tensin homolog deleted on chromosome ten (pten) gene. Exposure of eol-1r cells to imatinib failed to dephosphorylate akt, erk and stat5, although pdgfr? Was effectively inactivated. The forced expression of pten negatively regulated these signal pathways and sensitized eol-1r cells to imatinib. | SIGNOR-166481 |
Q02790 | Q9H3Y6 | 0 | phosphorylation | down-regulates activity | 0.267 | Together, these data indicate that SRMS inhibits the scaffolding function of its endogenous substrate FKBP51, thus antagonizing FKBP51-dependent inactivation of AKT (S4E Fig).|We demonstrate that SRMS phosphorylates FKBP51 to inhibit its scaffolding activity and promote its degradation through the ubiquitin-proteasome pathway. | SIGNOR-279764 |
Q9NYV6 | P68400 | 0 | phosphorylation | down-regulates | 0.206 | Here we show that ck2 phosphorylates the transcription initiation factor tif-ia at serines 170 and 172 (ser170/172), and this phosphorylation triggers the release of tif-ia from pol i after transcription initiation. | SIGNOR-178943 |
P60510 | Q13263 | 1 | dephosphorylation | down-regulates activity | 0.358 | PP4 dephosphorylated pKAP1 in vitro. | SIGNOR-277163 |
P24752 | P36888 | 0 | phosphorylation | up-regulates activity | 0.2 | We previously reported that the mitochondrial fraction of FLT3 activates acetyl-CoA acetyltransferase ACAT1 in mitochondria via Y407 phosphorylation to acetylate and inhibit mitochondrial pyruvate dehydrogenase A (PDHA) and PDH phosphatase 1 (PDP1) | SIGNOR-267628 |
Q00987 | Q9NQU5 | 0 | phosphorylation | up-regulates activity | 0.2 | We also showed that PAK6 phosphorylates Mdm2 on Thr-158 and Ser-186, which is critical for AR ubiquitin-mediated degradation. | SIGNOR-276428 |
Q13888 | P03372 | 1 | phosphorylation | up-regulates activity | 0.257 | TFIIH Phosphorylates Human Estrogen Receptor α at Serine 118 | We report here that Cdk7 overexpression stimulates transcription activation by ERα by stimulating phosphorylation of S118 in a ligand-dependent manner. | SIGNOR-260817 |
Q15139 | Q13671 | 1 | phosphorylation | down-regulates | 0.402 | Rin1 also binds to 14-3-3 proteins through a sequence including serine 351. Mutation of this residue abolished the 14-3-3 binding capacity of rin1 and led to more efficient blockade of ras-mediated transformation. The mutant protein, rin1(s351a), showed a shift in localization to the plasma membrane. Serine 351 is a substrate for protein kinase d (pkd [also known as pkcmu]) in vitro and in vivo. These data suggest that the normal localization and function of rin1, as well as its ability to compete with raf, are regulated in part by 14-3-3 binding, which in turn is controlled by pkd phosphorylation. | SIGNOR-113960 |
Q16695 | Q9BY66 | 0 | demethylation | up-regulates activity | 0.2 | KDM5 subfamily is capable of removing tri‐ and di‐ methyl marks from lysine 4 on histone H3 (H3K4). Depending on the methylation site, its effect on transcription can be either activating or repressing. | SIGNOR-264309 |
P48740 | P0C0L4 | 1 | cleavage | up-regulates activity | 0.606 | The classical complement activation pathway, like the MELinitiated pathway, involves the generation of a C3-converting complex, C4b2b, through enzymatic activation of C4 and C2. In the C1 complex (C1qr2s2), this specific protease activity is exhibited by C1s after activation of this enzyme by C1r. When C4 is activated, its reactive thiol ester is exposed and C4b binds covalently to nearby amino or hydroxyl groups. The C4-activating abilities of MASP-1 and MASP-2 were compared.|Activation of C4 by Ct sand MASP-2 on western blots. | SIGNOR-263438 |
O43182 | P61586 | 1 | gtpase-activating protein | down-regulates activity | 0.581 | 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-260462 |
Q16539 | P78356 | 1 | phosphorylation | down-regulates | 0.2 | Inhibition of pip4kbeta activity occurs through the direct phosphorylation of pip4kbeta at ser326 by the p38 stress-activated protein kinase. | SIGNOR-149359 |
O00429 | P48454 | 0 | dephosphorylation | up-regulates activity | 0.262 | When mitochondrial depolarization is associated with sustained cytosolic Ca(2+) rise, it activates the cytosolic phosphatase calcineurin that normally interacts with Drp1. Calcineurin-dependent dephosphorylation of Drp1, and in particular of its conserved serine 637, regulates its translocation to mitochondria as substantiated by site directed mutagenesis. | SIGNOR-248506 |
P46527 | P31751 | 0 | phosphorylation | down-regulates | 0.53 | Akt-induced t157 phosphorylation causes retention of p27(kip1) in the cytoplasm, precluding p27(kip1)-induced g1 arrest.[__]Thus, cytoplasmic relocalization of p27(kip1), secondary to akt-mediated phosphorylation, is a novel mechanism whereby the growth inhibitory properties of p27(kip1) are functionally inactivated and the proliferation of breast cancer cells is sustained. | SIGNOR-93122 |
P49840 | Q96BR1 | 0 | phosphorylation | down-regulates activity | 0.354 | Phosphorylation of GSK3 by PKB or SGK1 inhibits GSK3 activity|estern blotting using an antibody specific for the PKB/SGK1 consensus phosphorylation site in GSK3a/beta (serine 21 and 9 respectively) revealed an increase in GSK3a/beta phosphorylation in human embryonic kidney 293 (HEK293) cells overexpressing wild type SGK1, constitutively active SGK1, but not catalytically inactive SGK1.|The effect of SGK1 was mimicked by PKB and SGK3. | SIGNOR-249165 |
Q5VTR2 | Q13315 | 0 | phosphorylation | up-regulates | 0.522 | E3 ubiquitin ligase, a heterodimeric complex of the ringfinger rfn20/rfn40 is phosphorylated by atm. | SIGNOR-174949 |
Q5VWC8 | P49327 | 1 | chemical activation | up-regulates activity | 0.2 | Very long-chain fatty acids are produced through a four-step cycle. However, the 3-hydroxyacyl-CoA dehydratase catalyzing the third step in mammals has remained unidentified. Mammals have four candidates, HACD1-4, based on sequence similarities to the recently identified yeast Phs1, although HACD3 and HACD4 share relatively weak similarity. We demonstrate that all four of these human proteins are indeed 3-hydroxyacyl-CoA dehydratases, | SIGNOR-267763 |
Q8N6T3 | P84077 | 1 | gtpase-activating protein | up-regulates activity | 0.862 | The ARFGAP molecule binds to switch 2 and helix α3 to orient ARF1 residues for catalysis, but it supplies neither arginine nor other amino acid side chains to the GTPase active site. | SIGNOR-261915 |
P15336 | Q15759 | 0 | phosphorylation | up-regulates | 0.756 | Our results indicate that atf-2 not only directly binds to smad3/4 hetero-oligomers but also that atf-2 is phosphorylated by tgf-beta signaling via tak1 and p38. The two pathways, smad and tak1, synergistically enhance the activity of atf-2 which acts as their common nuclear target | SIGNOR-65586 |
P24863 | P46531 | 1 | phosphorylation | down-regulates | 0.48 | Purified recombinant cycc:cdk8 phosphorylates the notch icd within the tad and pest domains, and expression of cycc:cdk8 strongly enhances notch icd hyperphosphorylation and pest-dependent degradation by the fbw7/sel10 ubiquitin ligase in vivo. | SIGNOR-130592 |
P33981 | P04637 | 1 | phosphorylation | up-regulates | 0.499 | Ttk/hmps1 mediates the p53-dependent postmitotic checkpoint by phosphorylating p53 at thr18. phosphorylation at thr18 enhances p53-dependent activation of not only p21 but also lats2, two mediators of the postmitotic checkpoint. | SIGNOR-184931 |
P12532 | P00519 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.2 | Here, we show that oncogenic HER2 tyrosine kinase signaling induces phosphorylation of mitochondrial creatine kinase 1 (MtCK1) on tyrosine 153 (Y153) in an ABL-dependent manner in breast cancer cells. Y153 phosphorylation, which is commonly upregulated in HER2+ breast cancers, stabilizes MtCK1 to increase the phosphocreatine energy shuttle and promote proliferation. | SIGNOR-277406 |
Q86YT6 | P53355 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.437 | Transient expression of DIP-1 in HeLa cells antagonizes the anti-apoptotic function of DAPK to promote a caspase-dependent apoptosis. These studies also demonstrate that DAPK is an in vitro and in vivo target for ubiquitination by DIP-1, thereby providing a mechanism by which DAPK activities can be regulated through proteasomal degradation. | SIGNOR-272602 |
P27361 | P15056 | 1 | phosphorylation | down-regulates | 0.645 | Erk-induced phosphorylation of b-raf on t753 promoted the disassembly of raf heterodimers, and the mutation of t753 prolonged growth factor-induced heterodimerization. The b-raf t753a mutant enhanced differentiation of pc12 cells, which was previously shown to be dependent on sustained erk signaling. Site is critical for v-src dependent modulation of slk kinase activity. | SIGNOR-144827 |
Q9UI47 | P43694 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.25 | GATA-4 and MEF2C are known to bind to the GATA box 2 in the major promoter of CTNNA3 and this element is essential in directly regulating expression of CTNNA3 in cardiac muscle cells. The co-transfection of GATA-4 with MEF2C leads to a synergistic activation of the CTNNA3 promoter | SIGNOR-265490 |
P53355 | P19105 | 1 | phosphorylation | up-regulates activity | 0.275 | DAPK Phosphorylates Myosin II RLC in Vitro and in Vivo. Together these results show that similar to the conventional MLCKs, Ser-19 is the primary RLC residue phosphorylated by DAPK and that phosphorylation of Thr-18 is also possible. | SIGNOR-262842 |
P06493 | O60610 | 1 | phosphorylation | down-regulates activity | 0.2 | In this study, we found that Cdk1 phosphorylated DIAPH1, which inhibited the interaction between DIAPH1 and profilin1 (PFN1) during metaphase.|Thus, the results suggest that the level of cortical F-actin has to be finely maintained by Cdk1 mediated positive and negative regulation of DIAPH1. | SIGNOR-279598 |
P09619 | P63096 | 1 | phosphorylation | up-regulates activity | 0.2 | RTKs directly phosphorylate Gαi on Y154, 155, and Y320. | SIGNOR-277232 |
Q15021 | P51955 | 0 | phosphorylation | down-regulates activity | 0.269 | Nek2 phosphorylates C-Nap1, rootletin and beta-catenin to regulate centrosome separation. | SIGNOR-279234 |
P01112 | P05412 | 1 | phosphorylation | up-regulates activity | 0.5 | c-Jun was first shown to be phosphorylated in its transactivation domain (Ser-63 and Ser-73) by ERKs and p54-JNK. This is consistent with other studies which show that PD98059 inhibits up-regulation of c-Jun protein in Ras-transformed NIH-3T3 cells | SIGNOR-235522 |
O43524 | P46527 | 1 | transcriptional regulation | up-regulates quantity | 0.747 | AFX transcriptionally activates p27kip1, resulting in increased protein levels. | SIGNOR-238610 |
Q13153 | P04049 | 1 | phosphorylation | up-regulates | 0.602 | P21-activated protein kinases (paks) are serine/threonine protein kinases that phosphorylate raf-1 at ser-338 and ser-339. | SIGNOR-180808 |
P63000 | P52735 | 0 | guanine nucleotide exchange factor | up-regulates | 0.761 | Vav2 activates rac1 / vav2 is an exchange factor for rho family gtpases. | SIGNOR-81645 |
O95835 | Q13188 | 0 | phosphorylation | up-regulates | 0.62 | Since the N-terminal half of Lats1 (residues 1588) was dispensable for the activation of Lats1 by Mst2, mass spectrometry was used to identify phosphorylation sites within the C-terminal domain of Lats1. | SIGNOR-132927 |
Q9H6Z9 | O43521-1 | 1 | hydroxylation | up-regulates quantity by stabilization | 0.254 | EglN3 hydroxylase stabilizes BIM-EL linking VHL type 2C mutations to pheochromocytoma pathogenesis and chemotherapy resistance|EglN3 Hydroxylates BIM-EL at the Proline67/70 Residues | SIGNOR-262003 |
Q92565 | P01116 | 1 | guanine nucleotide exchange factor | up-regulates | 0.436 | Gefs catalyse the transition from gdp-bound, inactive ras to gtp-bound, active ras. | SIGNOR-183735 |
Q15796 | Q9GZU7 | 0 | dephosphorylation | down-regulates activity | 0.515 | SCP1 Dephosphorylates Smad2/3 in the Linkers|MAPK-mediated linker phosphorylation appears to have a dual role in Smad2/3 regulation. Mitogens and hyperactive Ras result in extracellular signal-regulated kinase (ERK)-mediated phosphorylation of Smad3 at Ser-204, Ser-208, and Thr-179 and of Smad2 at Ser-245/250/255 and Thr-220. Mutation of these sites increases the ability of Smad3 to activate target genes, suggesting that MAPK phosphorylation of Smad3 is inhibitory (11, 12). However, in contrast, ERK-dependent phosphorylation of Smad2 at Thr-8 enhances its transcriptional activity | SIGNOR-248795 |
P37198 | P53778 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.2 | We further show that imidazole propionate impairs insulin signaling at the level of insulin receptor substrate through the activation of p38γ MAPK, which promotes p62 phosphorylation and, subsequently, activation of mechanistic target of rapamycin complex 1 (mTORC1). | SIGNOR-277416 |
P56817 | P40818 | 0 | deubiquitination | up-regulates quantity by stabilization | 0.45 | Accordingly, we reported that BACE1 is ubiquitinated at lysine 501 and that lack of ubiquitination at lysine 501 produces BACE1 stabilization.Our findings demonstrate that USP8 plays a key role in the trafficking and degradation of BACE1 by deubiquitinating lysine 501. | SIGNOR-259101 |
P06241 | Q07666 | 1 | phosphorylation | up-regulates activity | 0.544 | The tyrosine kinase Fyn modulates Sam68 mediated alternative splicing of Bcl-x mRNA.|Tyrosine phosphorylation of Sam68 by Fyn inverted this effect and favored the Bcl-x(L) splice site selection. | SIGNOR-279462 |
P11802 | Q92830 | 1 | phosphorylation | up-regulates activity | 0.36 | Activated cyclin D1-Cdk4 kinase phosphorylates and activates GCN5|GCN5 T272A/S372A (AA) phosphorylation by cyclin D1-CDK4 kinase is diminished compared to GCN5 wild-type (WT) | SIGNOR-275494 |
P06241 | Q9NPH5 | 1 | phosphorylation | down-regulates activity | 0.271 | We found that direct phosphorylation of tyrosine 566 on NOX4 was critical for this FYN-mediated negative regulation. | SIGNOR-277273 |
P06493 | O15392 | 1 | phosphorylation | up-regulates | 0.686 | Survivin is a member of the inhibitor of apoptosis gene family that has been implicated in both apoptosis inhibition and regulation of mitosisin synchronized cultures, cytosolic survivin abruptly increased at mitosis, physically associated with p34(cdc2), and was phosphorylated by p34(cdc2) on thr(34), in vivo | SIGNOR-115129 |
Q15554 | P31943 | 0 | post transcriptional regulation | down-regulates quantity | 0.334 | During neuronal differentiation, use of an alternative splice site on the rat telomere repeat-binding factor 2 (TRF2) mRNA generates a short TRF2 protein isoform (TRF2-S) capable of derepressing neuronal genes. However, the RNA-binding proteins (RBPs) controlling this splicing event are unknown. Here, using affinity pull-down analysis, we identified heterogeneous nuclear ribonucleoproteins H1 and H2(HNRNPH) as RBPs specifically capable of interacting with the spliced RNA segment (exon 7) of Trf2 pre-mRNA. HNRNPH proteins prevent the production of the short isoform of Trf2 mRNA, as HNRNPH silencing selectively elevates TRF2-S levels. | SIGNOR-266807 |
P28482 | P62714 | 0 | dephosphorylation | down-regulates activity | 0.479 | Inactivation of p42 MAP kinase by protein phosphatase 2A and a protein tyrosine phosphatase, but not CL100, in various cell lines|Protein phosphatase-2A was the only vanadate-insensitive phosphatase acting on Thr 183 of p42mapk or on MAPKK to be detected in PC12 cell extracts. | SIGNOR-248590 |
O14965 | P06730 | 1 | phosphorylation | up-regulates activity | 0.278 | In this study, we demonstrated for the first time that AURKA can phosphorylate and activate EIF4E. | SIGNOR-279495 |
Q14192 | P61586 | 0 | relocalization | up-regulates | 0.348 | Here, we show that stimulation of the rho pathway induces translocation of the transcriptional lim-only coactivator fhl2 to the nucleus and subsequent activation of fhl2- and androgen receptor-dependent genes. | SIGNOR-114071 |
P68400 | P13569 | 1 | phosphorylation | down-regulates | 0.278 | Cftr possesses two ck2 phosphorylation sites (s422 and t1471) the t1471 residue, previously described as a site for cftr phosphorylation by ck2 (25), seems to be critical for cftr turnover and processing. | SIGNOR-176627 |
P15172 | Q969P5 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.56 | Here we present evidence that mafbx targets myod for degradation in several models of skeletal muscle atrophy. | SIGNOR-184861 |
P01100 | P63279 | 0 | sumoylation | down-regulates activity | 0.365 | We report here that lysine 265 of c-Fos is conjugated by the peptidic posttranslational modifiers SUMO-1, SUMO-2, and SUMO-3 and that c-Jun can be sumoylated on lysine 257 as well as on the previously described lysine 229. Sumoylation of c-Fos preferentially occurs in the context of c-Jun/c-Fos heterodimers.|Inhibition of c-Fos and c-Jun sumoylation stimulates AP-1-dependent transcription activity. | SIGNOR-263013 |
Q05086 | P54725 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.486 | Here we report the identification of HHR23A, one of the human homologues of the yeast DNA repair protein Rad23, as an E6-independent target of E6AP. E6AP-mediated ubiquitination and degradation of HHR23A and HHR23B. | SIGNOR-272550 |
O95229 | Q96GD4 | 0 | phosphorylation | up-regulates activity | 0.651 | Zwint-1 is a novel Aurora B substrate required for the assembly of a dynein-binding platform on kinetochores|During prometaphase, AurB phosphorylation of zwint-1 is required for recruitment of ZW10-, pT89 dynein-, and RZZ-dependent proteins to kinetochores. This is defective after AurB inhibition or after expression of the triple-A zwint-1 mutant. Triple-E mutant zwint-1 mimics phospho–zwint-1 in RZZ recruitment, even after AurB inhibition | SIGNOR-265010 |
P49407 | P28482 | 0 | phosphorylation | down-regulates | 0.727 | Erk1 and erk2 phosphorylate beta-arrestin1 at ser-412 in vitro. . in the resting state, cytosolic arrestin1 proteins are constitutively phosphorylated by extracellular signal-regulated kinase (erk) at ser412, located within their distal c terminus. erk-phosphorylated arrestin1 is unable to associate with clathrin cages, whereas this constraint is removed upon its dephosphorylation | SIGNOR-67630 |
P06493 | Q09472 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.404 | In this study, we found that p300 was highly phosphorylated and its level was decreased during mitosis and tumorigenesis. In vitro and in vivo experiments aimed showed that cyclin-dependent kinase 1 (CDK1) and ERK1/2 phosphorylated p300 on Ser1038 and Ser2039. Mutations of Ser1038 and Ser2039 increased p300 protein stability and levels. | SIGNOR-276457 |
P23443 | P62753 | 1 | phosphorylation | up-regulates activity | 0.937 | A knockin mouse carrying mutations at all phosphorylation sites in the primary s6k substrate, ribosomal protein s6 (rps6), has provided insight into the physiological role of this protein phosphorylation event. Of the many known substrates of s6k1, it is rps6 that has been shown to be directly involved, via its phosphorylation, in controlling cell size. | SIGNOR-135176 |
P17252 | P10721 | 1 | phosphorylation | down-regulates | 0.531 | Phosphorylation of kit/scfr by pkc-_ in vitro: identification of ser-741 and ser-746 as the major phosphorylation sites for pkc / pkc, which acts in an scf-stimulated feedback loop, that negatively controls kit/scfr kinase activity | SIGNOR-28605 |
P49137 | Q01860 | 1 | phosphorylation | up-regulates activity | 0.2 | MK2 mediated OCT4 transcriptional activation is a novel mechanism for activating the MYC oncogene in progressive disease neuroblastoma that provides a therapeutic target.|OCT4 phosphorylation at the S111 residue by MK2 was upstream of MYC transcriptional activation. | SIGNOR-279542 |
P17612 | Q08289 | 1 | phosphorylation | up-regulates activity | 0.43 | Voltage-dependent L-type calcium (Ca) channels are heteromultimeric proteins that are regulated through phosphorylation by cAMP-dependent protein kinase (PKA) Mutagenesis of a single residue at Ser459 resulted in the loss of one site of phosphorylation by PKA, and mutagenesis of two residues at Ser478/479 resulted in the loss of approximately two sites of PKA-mediated phosphorylation | SIGNOR-250341 |
P57073 | Q01167 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.288 | We showed for the first time that Aurora-A interacts directly with SOX8 and phosphorylates the protein at Ser327 to further regulate the SOX8/FOXK1 axis, which modulates cell senescence and glycolysis, ultimately leading to cisplatin resistance.. Our results showed that SOX8 targets FOXK1, thereby regulating its transcription, which has significant impacts on senescence, glycolysis and chemoresistance in ovarian cancer. | SIGNOR-273613 |
P04626 | Q8NEM2 | 1 | phosphorylation | up-regulates activity | 0.2 | Blocking HER2 activation using trastuzumab effectively abolished EGF-induced nuclear localization of SHCBP1 in gastric cancer cells [7].|In addition, nuclear translocation of SHCBP1 is a downstream consequence of HER2 activation, which is dependent on phosphorylation of SHCBP1 at the Ser273 site. | SIGNOR-280009 |
P46934 | P68036 | 0 | ubiquitination | up-regulates activity | 0.544 | Only UbcH5 and Related Class I E2s Support Ubiquitination of S5a—UbcH5 belongs to the Class I family of E2s which contains a catalytic core (UBC domain) without a distinct Ub binding domain (38). To test whether other Class I E2s can also support ubiquitination of S5a, we assayed the ubiquitination of S5a with UbcH7 and the E3s, Nedd4, or Parkin. With either of these E3s, UbcH7 supported ubiquitination of S5a (Fig. 8, A and B). In addition, another Class I E2, Ubc4, a close homolog of UbcH5, supported ubiquitination of S5a by the APC, a multimeric Ring finger E3 responsible for cell cycle progression through mitosis (39) (Fig. 8C). Thus, multiple Class I E2s can support ubiquitination of S5a by various types of E3s (Table 1). | SIGNOR-272735 |
Q13233 | Q02750 | 1 | phosphorylation | up-regulates activity | 0.661 | Phosphorylation at ser-218 and ser-222 by map kinase kinase kinases (raf or mekk1) positively regulates mek1 kinase activity. | SIGNOR-235587 |
Q16665 | P13500 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.403 | These findings suggest that both MCP-1 and MCP-5 are HIF-1 target genes and that HIF-1α is involved in transcriptional induction of these two chemokines in astrocytes by hypoxia. | SIGNOR-251719 |
Q9H2K2 | O15234 | 1 | ADP-ribosylation | down-regulates quantity by destabilization | 0.2 | Here, we identify RNF146, a RING-domain E3 ubiquitin ligase, as a positive regulator of Wnt signalling. RNF146 promotes Wnt signalling by mediating tankyrase-dependent degradation of axin. Mechanistically, RNF146 directly interacts with poly(ADP-ribose) through its WWE domain, and promotes degradation of PARsylated proteins. Using proteomics approaches, we have identified BLZF1 and CASC3 as further substrates targeted by tankyrase and RNF146 for degradation. | SIGNOR-263382 |
O14733 | Q99683 | 0 | phosphorylation | up-regulates | 0.594 | Ask1 is a member of a mapkkk family and functions as an upstream kinase engaged in c-jun nh2-terminal kinase (jnk)/p38 signaling via the phosphorylation and activation of mapkks, such as mkk3, -4, -6, and -7 | SIGNOR-161766 |
P30411 | P12931 | 0 | phosphorylation | up-regulates | 0.262 | Here we demonstrate that egf is capable of inducing src-mediated phosphorylation of the tyrosine residues 177 and 347 of bkr. Their replacement by phenylalanine led to bkr mutants which are unable to activate the camp pathway. | SIGNOR-141103 |
Q9NZQ7 | Q99720 | 0 | stabilization | up-regulates quantity by stabilization | 0.2 | We propose that Sigma1 is a ligand-operated scaffolding protein that promotes the stability, processing, assembly, and trafficking of specific proteins in the secretory pathway of cancer cells. In support of this hypothesis, we found that siRNA-mediated knockdown of Sigma1 resulted in a significant decrease in PD-L1 protein levels in triple-negative MDA-MB-231 breast cancer and androgen-independent PC3 prostate cancer cells | SIGNOR-274974 |
P17252 | P24844 | 1 | phosphorylation | down-regulates | 0.278 | Rlc can also be phosphorylated at ser1/ser2/thr9 by protein kinase c (pkc). Biophysical studies show that phosphorylation at these sites leads to an increase in the km of myosin light chain kinase (mlck) for rlc, thereby indirectly inhibiting myosin ii activity | SIGNOR-192792 |
P30305 | P24941 | 1 | dephosphorylation | up-regulates activity | 0.767 | CDC25B is also able to dephosphorylate and activate CDK2-Cyclin A and CDK2-Cyclin E complexes [ xref \u2013 xref ]. | SIGNOR-277140 |
Q7Z6M2 | O00303 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | Mediation of eIF3-f polyubiquitination by the SCFMAFbx. The association of MAFbx with the essential Skp1, Roc 1 and Cul1 proteins, specific components of an E3 ubiquitin–protein ligase (SCFMAFbx), was previously described. Here, we present evidence that during muscle atrophy MAFbx targets the eukaryotic initiation factor 3 subunit 5 (eIF3-f) for ubiquitination and degradation by the proteasome. | SIGNOR-271768 |
O96017 | P04637 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.791 | Chk1/chk2 and atm/atr also phosphorylate the effector p53, increasing its stability.We Have demonstrated that the human homologs of the checkpoint kinases, chk1 and chk2/hcds1, phosphorylate at least three dna damage-inducible phosphorylation sites in p53. | SIGNOR-74831 |
P06401 | Q9Y618 | 0 | acetylation | down-regulates | 0.588 | In this study we assessed the effect of smrt and dax-1 on ar and pr activity in the presence of both agonists and partial antagonists. We show that smrt and dax-1 repress agonist-dependent activity of both receptors, and the mechanism of repression includes disruption of the receptor dimer interactions rather than recruitment of histone deacetylases. | SIGNOR-101289 |
P48729 | A8MYZ6 | 1 | phosphorylation | down-regulates | 0.2 | Additionally, ck1, dyrk1a, and cdk2 also phosphorylate foxos at various sites to inhibit foxos activity. | SIGNOR-183667 |
P36871 | Q16512 | 0 | phosphorylation | up-regulates | 0.2 | Pak1-mediated phosphorylation of pgm selectively on threonine 466 significantly increased pgm enzymatic activity | SIGNOR-128722 |
O43707 | Q05397 | 0 | phosphorylation | down-regulates | 0.558 | Phosphorylation at y12 by fak reduces _-actinin1's affinity for actin [25] and [27]. _-actinin4 is phosphorylated at y4, y31, and y265. Phosphorylation at y4 or y31 decreases its binding to actin [28] while phosphorylation of y265 increases its affinity for actin | SIGNOR-192195 |
P28482 | Q8N122 | 1 | phosphorylation | up-regulates activity | 0.518 | We found three proline-directed residues within raptor, ser(8), ser(696), and ser(863), which are directly phosphorylated by erk1/2. Expression of phosphorylation-deficient alleles of raptor revealed that phosphorylation of these sites by erk1/2 normally promotes mtorc1 activity and signaling to downstream substrates, such as 4e-bp1. | SIGNOR-188916 |
P17252 | P55273 | 1 | phosphorylation | up-regulates | 0.2 | Cdk2 and pka were found to participate in p19ink4d phosphorylation process and that they would mediate serine 76 and threonine 141 modifications respectively. Nuclear translocation of p19ink4d induced by dna damage was shown to be dependent on serine 76 phosphorylation. | SIGNOR-197285 |
O95817 | P27361 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.312 | We further demonstrated BAG3, a HSP70 co-chaperone, is a bona fide substrate of SCFFBXO22. FBXO22 mediates BAG3 ubiquitination and degradation that requires ERK-dependent BAG3 phosphorylation at S377. | SIGNOR-277318 |
P06748 | Q9NYY3 | 0 | phosphorylation | up-regulates | 0.536 | Phosphorylated at ser-4 by plk1 and plk2. Phosphorylation at ser-4 by plk2 in s phase is required for centriole duplication and is sufficient to trigger centriole replication. Phosphorylation at ser-4 by plk1 takes place during mitosis. | SIGNOR-125720 |
Q9HAV4 | Q13526 | 0 | isomerization | down-regulates activity | 0.2 | Here we show that ERK suppresses pre-miRNA export from the nucleus through phosphorylation of exportin-5 (XPO5) at T345/S416/S497. After phosphorylation by ERK, conformation of XPO5 is altered by prolyl isomerase Pin1, resulting in reduction of pre-miRNA loading. | SIGNOR-263015 |
Q9BPZ7 | P23443 | 0 | phosphorylation | down-regulates activity | 0.565 | Consistently, we detected in vivo Sin1 phosphorylation triggered by S6K1 and to a lesser extent, Akt1, but not other characterized AGC kinases (XREF_FIG and XREF_SUPPLEMENTARY).|Here we report that phosphorylation of Sin1 at Thr 86 and Thr 398 suppresses mTORC2 kinase activity by dissociating Sin1 from mTORC2. | SIGNOR-279568 |
P31749 | P78527 | 0 | phosphorylation | up-regulates activity | 0.754 | DNA-PK phosphorylates HM Ser473 of PKB. However, we also noted similar patterns in T loop Thr308 phosphorylation after _-IR []his function is apparently restricted to the PKBalpha isoform | SIGNOR-252431 |
Q07666 | P12931 | 0 | phosphorylation | up-regulates activity | 0.825 | 26 In particular, Sam68 was shown to play a scaffold role in Src kinase activated pathways, 16,27 and tyrosine phosphorylation of Sam68 by Src kinases triggers the release of bound RNA and might allow translational activation. | SIGNOR-279121 |
P51812 | P05114 | 1 | phosphorylation | down-regulates activity | 0.364 | We report here that the NBD of the HMGN1 and -N2 protein family is highly and specifically phosphorylated during mitosis and that this phosphorylation has a major functional consequence: it abolishes the interaction of the proteins with its chromatin targets. | SIGNOR-249100 |
Q04759 | O60341 | 1 | phosphorylation | down-regulates activity | 0.259 | Inhibiting PKC-theta also increased the H3K4 demethylase activity of LSD1, indicating that active PKC-theta may prevent LSD1 from demethylating H3K4 and subsequently causing gene repression.|PKC-theta directly phosphorylates LSD1 at serine 111 and regulates its repressive activity and nuclear localization. | SIGNOR-279104 |
Q07889 | P01116 | 1 | guanine nucleotide exchange factor | up-regulates | 0.828 | Because the KRAS-GDP to KRAS-GTP transition catalyzed by the GEF, son of sevenless 1 (SOS1), represents the rate-limiting step for nucleotide exchange, disrupting the activating SOS1/KRAS protein interaction has also been the focus of drug development efforts | SIGNOR-141647 |
Q12913 | P35222 | 1 | dephosphorylation | up-regulates activity | 0.519 | Our data demonstrate that CD148 promotes E-cadherin cell adhesion by regulating Rac1 activity, concomitant with modulation of p120, \u03b2-catenin, and Src tyrosine phosphorylation, and that this effect requires E-cadherin and p120 association.|Taken together, it is likely that CD148 dephosphorylation of \u03b2-catenin enhances the cadherin cell adhesion independent of Rho family GTPases. | SIGNOR-276992 |
Q9UNN5 | Q14164 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.283 | Upon virus infection, the kinase IKKɛ directly phosphorylates FAF1 at Ser556 and triggers FAF1 de-aggregation. Moreover, Ser556 phosphorylation promotes FAF1 lysosomal degradation, consequently relieving FAF1-dependent suppression of MAVS. | SIGNOR-277618 |
O00311 | P33991 | 1 | phosphorylation | up-regulates | 0.958 | Activation of the eukaryotic replicative dna helicase, the mcm2-7 complex, requires phosphorylation by cdc7/dbf4 (dbf4-dependent kinase or ddk), which, in turn, depends on prior phosphorylation of mcm2-7 by an unknown kinase (or kinases).we propose that the resulting mec1 modification of mcm4 and mcm6 further activates ddk phosphorylation of mcm2-7 ( fig. 7aii ). | SIGNOR-169453 |
Q05195 | Q15418 | 0 | phosphorylation | down-regulates | 0.315 | In this study, we showed that mad1 is a substrate of p90 ribosomal kinase (rsk) and p70 s6 kinase (s6k). Both rsk and s6k phosphorylate serine 145 of mad1 upon serum or insulin stimulation. Ser-145 phosphorylation of mad1 accelerates the ubiquitination and degradation of mad1 through the 26s proteasome pathway | SIGNOR-178586 |
Q9H3R0 | P19525 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.2 | In the absence of Wnt3a, protein kinase R phosphorylated KDM4C at Ser918, inducing KDM4C ubiquitination and degradation. | SIGNOR-277497 |
P55957 | Q96J02 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.352 | The ubiquitin ligase Itch mediates the antiapoptotic activity of epidermal growth factor by promoting the ubiquitylation and degradation of the truncated C-terminal portion of Bid | SIGNOR-271415 |
Q9HAV4 | P27361 | 0 | phosphorylation | down-regulates activity | 0.312 | Here we show that ERK suppresses pre-miRNA export from the nucleus through phosphorylation of exportin-5 (XPO5) at T345/S416/S497. After phosphorylation by ERK, conformation of XPO5 is altered by prolyl isomerase Pin1, resulting in reduction of pre-miRNA loading. | SIGNOR-262985 |
Q14765 | P52564 | 0 | phosphorylation | up-regulates activity | 0.342 | MKK6, phosphorylate STAT4 on serine 721. IL-12 induces STAT4 phosphorylation on serine 721 and that mutation of serine 721 interferes with STAT4 transcriptional activity. | SIGNOR-251425 |
P00519 | P43405 | 1 | phosphorylation | up-regulates activity | 0.253 | Abl kinases modulate Syk kinase activation.|Expression of constitutively active Abl (AblPP) increased Syk Y346 phosphorylation, whereas the phosphorylation was unaffected in cells expressing kinase inactive form of Abl (AblKR) (XREF_FIG). | SIGNOR-279665 |
Q58EX7 | P60953 | 1 | guanine nucleotide exchange factor | up-regulates activity | 0.36 | 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-260564 |
P51813 | Q06187 | 0 | phosphorylation | up-regulates | 0.335 | Tec family protein tyrosine kinases (tfks) play a central role in hematopoietic cellular signaling. Initial activation takes place through specific tyrosine phosphorylation situated in the activation loop. Further activation occurs within the sh3 domain via a transphosphorylation mechanism. | SIGNOR-98028 |
O43524 | Q8IW41 | 0 | phosphorylation | up-regulates activity | 0.475 | Analysis of mutant alleles of FoxO3a showed that MK5 phosphorylated FoxO3a predominantly at S215, but that mutation of four of the identified sites was required to essentially abolish phosphorylation of FoxO3a by MK5 (\u201c4A\u201d) ( Figure\u00a04 C and data not shown).|MK5 phosphorylates and activates the transcription factor FoxO3a and potentially other FoxO factors. | SIGNOR-279469 |
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