IdA string | IdB string | labels int64 | mechanism string | effect string | score float64 | sentence string | signor_id string |
|---|---|---|---|---|---|---|---|
Q13882 | Q9UGK3 | 1 | phosphorylation | up-regulates activity | 0.724 | Our previous studies revealed that STAP-2 binds to signal transducer and activator of transcription 3 (STAT3) and STAT5, and regulates the signaling pathways downstream of them. In the present study, we identified tyrosine-250 (Tyr250) in STAP-2 as a major site of phosphorylation by Brk, using a series of STAP-2 YF mutants and anti-phospho-STAP-2 Tyr250 antibody. Furthermore, overexpression of the STAP-2 Y250F mutant protein affected Brk-mediated STAT3 activation. | SIGNOR-247067 |
Q8NEL9 | P68400 | 0 | phosphorylation | down-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-262977 |
Q96P20 | P07948 | 0 | phosphorylation | down-regulates | 0.29 | Lyn phosphorylates NLRP3 at Tyr 918 and controls NLRP3 ubiquitination.|Therefore, our data collectively indicate that Lyn inhibits the NLRP3 inflammasome in vivo. | SIGNOR-278485 |
P18031 | O75886 | 1 | dephosphorylation | up-regulates quantity by stabilization | 0.472 | Together, the results presented here demonstrate that PTP1B can influence RTK signaling in a previously unrecognized manner. We show that PTP1B directly targets STAM2, part of the ESCRT-0 endosomal sorting complex, and we provide the first evidence that tyrosine phosphorylation affects STAM localization and function. This regulatory mechanism could impact signaling downstream of numerous cell surface receptors that are ubiquitinated and recognized by this conserved sorting machinery. | SIGNOR-248406 |
P31749 | P54578 | 1 | phosphorylation | up-regulates activity | 0.424 | Phosphorylation and activation of ubiquitin-specific protease-14 by Akt regulates the ubiquitin-proteasome system|These results suggested S432 as a major and S143 as a minor phosphorylation site of Akt. | SIGNOR-265056 |
P49674 | O14640 | 1 | phosphorylation | up-regulates activity | 0.637 | Phenotypic analysis of mutant mDvl-1 indicates that phosphorylation of these sites stimulates the Dvl-activated beta-catenin-dependent Wnt signaling pathway in both cell culture and in Xenopus development. | SIGNOR-217849 |
P30304 | P04049 | 1 | dephosphorylation | down-regulates | 0.395 | Cdc25a can act on substrates other than cdks, since it dephosphorylates the homeodomain transcription factor cut and interacts with and dephosphorylates the proto-oncogene raf-1, resulting in a significant decrease in raf-1 kinase activity | SIGNOR-32548 |
P17600 | P17612 | 0 | phosphorylation | down-regulates activity | 0.338 | Synapsin phosphorylation in the A domain, at the only phosphorylation site shared by all synapsins, dissociates synapsins from synaptic vesicles.This site is located in the N-terminal A domain and is a substrate for both PKA and CaM Kinase I | SIGNOR-250058 |
Q13315 | Q96S59 | 1 | phosphorylation | up-regulates activity | 0.439 | We demonstrate that ATM phosphorylates RanBP9 in response to Ionizing Radiation and mediates its nuclear accumulation. | SIGNOR-279005 |
Q9UHD2 | P31749 | 1 | phosphorylation | up-regulates | 0.407 | Upon mitogen stimulation, triggering of the innate immune response, re-exposure to glucose, or oncogene activation, tbk1 is recruited to the exocyst, where it activates akt. Akt is a direct tbk1 substrate that connects tbk1 to prosurvival signaling. | SIGNOR-252608 |
Q15118 | P11362 | 0 | phosphorylation | up-regulates | 0.347 | Mitochondrial pdhk1 is tyrosine phosphorylated and activated by fgfr1 in cancer cells further mass spectrometric analysis identified three tyrosine residues of pdhk1, including y136, y243 and y244, that are phosphorylated by fgfr1 | SIGNOR-193454 |
P63279 | P05412 | 1 | sumoylation | down-regulates activity | 0.42 | 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-263001 |
P17612 | P20020 | 1 | phosphorylation | up-regulates activity | 0.451 | The ATPase is phosphorylated only at this site by the cAMP-dependent protein kinase, and the phosphorylation is inhibited by calmodulin. The effect of the phosphorylation is to decrease the Km for Ca2+ of the purified ATPase from about 10 microM to about 1.4 microM and to increase the Vmax of ATP hydrolysis about 2-fold. | SIGNOR-262694 |
P60510 | P53350 | 1 | dephosphorylation | down-regulates activity | 0.416 | PPP4C dephosphorylated PLK1 at the S137 site, negatively regulating its activity in the DSB response in early embryonic cells. | SIGNOR-277076 |
P55283 | O60610 | 0 | null | up-regulates activity | 0.2 | Taken together, data obtained from MCF10A cells were consistent with the idea that Rho signaling to Dia1 and profilin-1 was essential for R-cadherin adherens junction formation. | SIGNOR-253110 |
P23396 | Q05655 | 0 | phosphorylation | up-regulates activity | 0.2 | Here we show that PKCδ phosphorylates rpS3 resulting in its mobilization in the nucleus to repair damaged DNA | SIGNOR-260895 |
Q05655 | P31431 | 1 | phosphorylation | up-regulates activity | 0.528 | The phosphorylation state of Ser(183) in the cytoplasmic tail of syndecan-4 determines the binding affinity of the cytoplasmic tail to phosphatidylinositol 4,5-bisphosphate (PIP(2)), the capacity of the tail to multimerize, and its ability to activate protein kinase C (PKC) alpha. We sought to identify the kinase responsible for this phosphorylation and to determine its downstream effects on PKCalpha activity and on endothelial cell function. Among several PKC isoenzymes tested, only PKCalpha and -delta were able to specifically phosphorylate Ser(183) in vitro. However, studies in cultured endothelial cells showed that the phosphorylation level of syndecan-4 was significantly reduced in endothelial cells expressing a dominant negative (DN) PKCdelta but not a DN PKCalpha mutant. | SIGNOR-116265 |
P50613 | P11802 | 1 | phosphorylation | up-regulates | 0.587 | Phosphorylation of cdk4 on threonine 172 by a cdk-activating kinase (cak). therefore, formation of the cyclin d-cdk4 complex and phosphorylation of the bound catalytic subunit are independently regulated, and in addition to the requirement for cak activity, serum stimulation is required to promote assembly of the complexes in mammalian cells. | SIGNOR-36549 |
Q99607 | O15550 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.279 | Our findings reveal a dual role for UTX in suppressing acute myeloid leukaemia via repression of oncogenic ETS and upregulation of tumor suppressive GATA programs. several ETS transcription factors, including Elf4, Etv6, Erg, Fli1, Ets2, Spi1 and Elk3 were upregulated immediately after Utx loss in the preleukaemic phase | SIGNOR-260031 |
P23443 | P49959 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | MRE11 is highly unstable in PTEN-deficient cells but stability can be significantly restored by inhibiting mTORC1 or p70S6 kinase (p70S6K), downstream kinases whose activities are stimulated by AKT, or by mutating a residue in MRE11 that we show is phosphorylated by p70S6K in vitro. | SIGNOR-265944 |
P62805 | O94874 | 0 | ubiquitination | up-regulates activity | 0.2 | Here we report that UFM1 specific ligase 1 (UFL1), an ufmylation E3 ligase, is important for ATM activation. | SIGNOR-265072 |
P23471 | P35222 | 1 | dephosphorylation | up-regulates activity | 0.378 | PTPRZ1 constitutively promotes the tyrosine dephosphorylation of \u03b2-catenin, and thus \u03b2-catenin participation in TCF-mediated transcription. | SIGNOR-277044 |
O00311 | P33993 | 1 | phosphorylation | up-regulates | 0.942 | We propose that phosphorylation of mcm4/6 s/tp sites, which are already phosphorylated in g1, allows initial mcm2-7 phosphorylation by ddk and initiation from the first origins of replication ( fig. 7ai ). | SIGNOR-169506 |
P25963 | P68400 | 0 | phosphorylation | down-regulates | 0.581 | Casein kinase ii phosphorylates i kappa b alpha at s-283, s-289, s-293, and t-291 and is required for its degradation. | SIGNOR-40502 |
Q05655 | P05107 | 1 | phosphorylation | up-regulates | 0.329 | In this study, we present evidence that pkc isoforms are the major protein kinases that phosphorylate the c terminus of the integrin cd18 chain in leukocytes. Ser-745 is identified as a novel phosphorylation site in the integrin cytoplasmic domain. Additionally, we show that a thr-758-phosphorylated integrin peptide can interact with 14-3-3 proteins in leukocyte lysates | SIGNOR-178897 |
Q15366 | P27361 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.323 | We also identified 4 hnRNP-E2 MAPKERK1/2 phosphorylation sites and demonstrated that hnRNP-E2 is a bona fide MAPKERK1/2 substrate and that MAPKERK1/2-dependent phosphorylation of hnRNP-E2 at these amino acid residues is essential for increased hnRNP-E2 expression in BCR/ABL-expressing cells. Serine/threonine to alanine substitution abolishes hnRNP-E2 phosphorylation and markedly decreases its stability in BCR/ABL-expressing myeloid precursors. Consistent with the existence of a BCR/ABL-MAPK pathway that posttranslationally regulates hnRNP-E2 expression, sequence analysis of hnRNP-E2 revealed the presence of 4 consensus ERK phosphorylation sites (S/T-P)35,36 at amino acid residues 173, 189, 213, and 272 (Figure 2B). | SIGNOR-262916 |
P12931 | P17813 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.385 | We identified epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) as Src-activators that induce endoglin turnover following (612)YIY(614) phosphorylation. | SIGNOR-276654 |
Q8TE12 | O14529 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.285 | Lmx1a drives Cux2 expression in the cortical hem through activation of a conserved intronic enhancer. Lmx1a knockdown abolishes activation of the Cux2 enhancer in the cortical hem | SIGNOR-263961 |
Q9UM73 | P50750 | 1 | phosphorylation | up-regulates activity | 0.296 | We report that anaplastic lymphoma kinase (ALK) directly phosphorylates CDK9 at tyrosine-19 to promote homologous recombination (HR) repair and PARP inhibitor resistance. Phospho-CDK9-Tyr19 increases its kinase activity and nuclear localization to stabilize positive transcriptional elongation factor b and activate polymerase II-dependent transcription of HR-repair genes. | SIGNOR-277607 |
P42224 | Q9BYW2 | 0 | methylation | up-regulates activity | 0.266 | SETD2 enhances antiviral immunity by directly methylating STAT1 on K525. Mechanistically, SETD2 directly mediates STAT1 methylation on lysine 525 via its methyltransferase activity, which reinforces IFN-activated STAT1 phosphorylation and antiviral cellular response. | SIGNOR-269091 |
P00519 | P15498 | 1 | phosphorylation | up-regulates | 0.401 | Thus, the c-terminal tail of vav serves as a direct substrate of bcr-abl in vitro. | SIGNOR-114091 |
P49795 | P28482 | 0 | phosphorylation | up-regulates | 0.474 | Phosphorylation of gaip by erk2 were abrogated when serine at position 151 in the rgs domain was substituted by an alanine residue using site-directed mutagenesis. Furthermore, the lysosomal-autophagic pathway was not stimulated in s151a-gaip mutant-expressing cells when compared with wild-type gaip-expressing cells. These results demonstrate that the gtpase-activating protein activity of gaip is stimulated by erk2 phosphorylation. | SIGNOR-129883 |
Q5JPH6 | 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 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress. | SIGNOR-269402 |
P17612 | Q06124 | 1 | phosphorylation | down-regulates activity | 0.451 | We identified two key amino acids in Shp2 that are phosphorylated by PKA. Thr-73 contributes a helix cap to helix αB within the N-terminal SH2 domain of Shp2, whereas Ser-189 occupies an equivalent position within the C-terminal SH2 domain. Utilizing double mutant PKA phosphodeficient (T73A/S189A) and phosphomimetic (T73D/S189D) constructs, in vitro binding assays, and phosphatase activity assays, we demonstrate that phosphorylation of these residues disrupts Shp2 interaction with tyrosine-phosphorylated ligands and inhibits its protein-tyrosine phosphatase activity. | SIGNOR-276891 |
P17252 | P08034 | 1 | phosphorylation | up-regulates activity | 0.362 | Phosphorylation of connexin-32 by protein kinase C prevents its proteolysis by mu-calpain and m-calpain. |In agreement with other authors (see Saez et al., 1990b), we have found that phosphorylation of connexin-32 by protein kinase A and protein kinase C occurs in serine residues, although we have detected trace amounts of phosphothreonine in connexin-32 phosphorylated by protein kinase C (results not shown). Indeed, Se233 has been shown to be the major phosphorylation site catalyzed by protein kinase A. However, Ser233, Ser239, and perhaps other serines are phosphorylated by protein kinase C (Saez et al., 1990b). | SIGNOR-248919 |
Q76N32 | O95613 | 1 | relocalization | up-regulates activity | 0.34 | We also found that Cep68 forms a complex with Cep215 (also known as Cdk5Rap2) and PCNT (also known as pericentrin), two PCM (pericentriolar material) proteins involved in centriole engagement. |Cep68 stabilization increases the amount of PCNT at metaphase centrosomes, but does not affect its removal at the end of mitosis | SIGNOR-275623 |
P68400 | P56270 | 1 | phosphorylation | up-regulates | 0.447 | Site-specific mutagenesis of maz revealed that the serine residue at position 480 was the major site of phosphorylation by ckii both in vitro and in vivo. Phosphorylation of maz by ckii at this serine residue was required for maximum binding of maz to the pyrimidine-rich dna of the nuclease-hypersensitive element (nhe) in the 5'-end promoter region of the c-myc gene. Mutation of serine at position 480 to alanine eliminated the dna-binding activity of maz to this element. | SIGNOR-70082 |
P84077 | Q92538 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.719 | GBF1 Stimulates Production of Arf-GTP In Vivo | SIGNOR-277400 |
Q9UHD2 | O75688 | 0 | dephosphorylation | down-regulates activity | 0.352 | PPM1B dephosphorylates TBK1 in vivo and in vitro.|These results demonstrate that PPM1B inhibits TBK1 mediated antiviral signaling by directly dephosphorylating TBK1 at Ser172. | SIGNOR-276985 |
P38936 | O15119 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.304 | TBX2 and TBX3 function as transcriptional repressors and both have been shown to inhibit myogenesis (Carlson et al, 2002; Zhu et al, 2014). Abnormal expression of TBX2 has been reported in several cancers including breast, pancreas, and melanoma, where it has been shown to drive proliferation (reviewed in Abrahams et al (2010)). As has been previously shown in other cell types, TBX2 was found to induce a downregulation of p14/19ARF and function as a direct repressor of p21 in RMS | SIGNOR-249602 |
P35568 | O14733 | 0 | phosphorylation | down-regulates activity | 0.369 | Tyrosine phosphorylation of IRS-1 initiates insulin signaling, whereas serine/threonine phosphorylation alters the ability of IRS-1 to transduce the insulin signalInsulin increased the phosphorylation of Ser312, Ser616, Ser636, Ser892, Ser1101, and Ser1223 Ser312 can be phosphorylated by kinases, such as c-jun NH2-terminal kinase and inhibitor of _B kinase | SIGNOR-217920 |
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 at S664 or double S664A/S540A mutagenesis resulted in a marked reduction in TSC2 phosphorylation to a similar extent. In contrast, S540A substitution only moderately impaired TSC2 phosphorylation (Figure 3D), corroborating the notion that in vivo S664 is the most relevant residue for Erk-mediated phosphorylation. | SIGNOR-249457 |
O75030 | P10415 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.475 | MITF directly occupies the BCL2 promoter in vivo and this suggest that BCL2 may be a direct transcriptional target of MITF | SIGNOR-249618 |
P12931 | O15357 | 1 | phosphorylation | up-regulates | 0.535 | Ship2 could be phosphorylated in vitro by recombinant src kinase and tyrosines 986-987 in the npxy motif of ship2 appear to be the major sites of phosphorylation for src both in vitro and in vivo. | SIGNOR-92935 |
P15923 | Q16539 | 0 | phosphorylation | up-regulates activity | 0.48 | Here we show that p38 mapk, whose activity is essential for myogenesis, regulates myod/e47 heterodimerization. Phosphorylation of e47 at ser140 by p38 induces myod/e47 association and activation of muscle-specific transcription | SIGNOR-134194 |
P49674 | P25054 | 1 | phosphorylation | up-regulates activity | 0.614 | Apc can be phosphorylated by ck1epsilon at ser1279 and ser1392. Mutation of conserved serine residues in the beta-catenin regulatory motifs of APC interfered with both axin-dependent phosphorylation and phosphorylation by CKIepsilon and impaired the ability of APC to regulate beta-catenin. | SIGNOR-109664 |
Q16667 | P24941 | 1 | dephosphorylation | down-regulates activity | 0.714 | The CDK-interacting protein phosphatase KAP dephosphorylates phosphoThr-160 (pThr-160) of the CDK2 activation segment, the site of regulatory phosphorylation that is essential for kinase activity. | SIGNOR-248724 |
Q03112 | Q02763 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | We finally observed that the forced expression of Evi1 induced GATA-2 expression in a hematopoietic cell line, EML C1, along with GATA-1, Ang-1, Ang-2 and Tie2 | SIGNOR-266063 |
P19419 | P17252 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.442 | The luciferase reporter assay results revealed that the presence of both MZF-1 and Elk-1 significantly contributed to the upregulation of PKCα gene transcription activity. | SIGNOR-256336 |
P49366 | P63241 | 1 | post translational modification | up-regulates activity | 0.933 | Deoxyhypusine synthase (DHPS) utilizes spermidine and NAD as cofactors to incorporate a hypusine modification into the eukaryotic translation initiation factor 5A (eIF5A). Hypusine is essential for eIF5A activation, which, in turn, plays a key role in regulating protein translation of selected mRNA that are associated with the synthesis of oncoproteins, thereby enhancing tumor cell proliferation. | SIGNOR-266374 |
Q15080 | P17252 | 0 | phosphorylation | up-regulates activity | 0.2 | In murine and guinea pig neutrophils, PKCδ is required for the phosphorylation of p40phox, a subunit of the NADPH oxidase complex (Li et al., 2016; Someya et al., 1999). In particular, it mediates phosphorylation of the threonine 154 (T154) residue of p40phox, a key regulatory step in the activation of the NADPH oxidase complex in peripheral neutrophils and B cells, in both mice and humans. In conclusion, the EBV-B cells of patients with PKCδ deficiency have impaired ROS production, associated with lower levels of phosphorylation of the cytosolic NADPH oxidase subunit p40phox by PKCδ. | SIGNOR-277628 |
O00238 | Q15797 | 1 | phosphorylation | up-regulates | 0.643 | Two types of bmp-induced signaling pathways are known, the smad and p38 mapk pathways. In the former case, bmpr1 phosphorylates smad-1,-5,-8, which forms a complex with smad4 that translocates into the nucleus and regulates gene expression. | SIGNOR-187190 |
P31749 | Q13188 | 1 | phosphorylation | down-regulates | 0.356 | We determined that mst2 phosphorylation by akt limits mst2 activity in two ways: first, by blocking its binding to rassf1a and by promoting its association into the raf-1 inhibitory complex, and second, by preventing homodimerization of mst2, which is needed for its activation. we identified t117 and t384 as akt phosphorylation sites in mst2. | SIGNOR-163533 |
Q86Y13 | Q71UI9 | 1 | monoubiquitination | up-regulates activity | 0.2 | 2A-HUB catalyzes monoubiquitination of H2A at lysine 119, functioning as a combinatoric component of the repression machinery required for specific gene regulation programs. Thus, 2A-HUB mediates a selective repression of a specific set of chemokine genes in macrophages, critically modulating migratory responses to TLR activation. H2A monoubiquitination acts to prevent FACT recruitment at the transcriptional promoter region, blocking RNA polymerase II release at the early stage of elongation. | SIGNOR-271756 |
P67775 | P23396 | 1 | dephosphorylation | down-regulates | 0.427 | We identified that pp2a interacts with wild-type rps3, but not with mutants (s6a/t221a) (fig. 8), and that it associates with the n-terminal region of rps3 (fig. 2). From our results presented here, we conclude that pp2a is involved in the dephosphorylation of phosphorylated rps3 by pkc, and that serine 6 on the n-terminal region of rps3 appears to mediate the pp2a recruitment. | SIGNOR-137963 |
P28482 | P10415 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.552 | Phosphorylation of the map kinase sites in bcl-2, thr56, thr74, and ser87, is sufficient to inhibit tnf--induced degradation. | SIGNOR-74931 |
P68366 | Q5SQI0 | 0 | acetylation | up-regulates quantity by stabilization | 0.262 | Alpha-Tubulin acetyltransferase (alphaTAT1) is the major α-tubulin lysine-40 (K40) acetyltransferase in mammals, nematodes, and protozoa, and its activity plays a conserved role in several microtubule-based processes.|The tubulin subunits of microtubules are acetylated, and lysine-40 (K40) of the alpha-tubulin subunit has been identified as an important conserved site of microtubule acetylation (6–8). This modification is considered a hallmark of stable, long-lived microtubules | SIGNOR-272249 |
P06241 | Q9H204 | 1 | phosphorylation | up-regulates | 0.446 | To unravel the cellular functions of magicin, we used a yeast two-hybrid system and identified fyn tyrosine kinase as a specific binding partner for magicin. Fyn phosphorylates magicin in vitro. | SIGNOR-148700 |
Q8IXJ6 | Q13627 | 0 | phosphorylation | up-regulates activity | 0.293 | This Minibrain/Dyrk1a kinase phosphorylates and activates the Silent information regulator 2/Sirtuin1 deacetylase, which in turn deacetylates and activates the FOXO transcription factor. | SIGNOR-279990 |
P42574 | Q92934 | 1 | cleavage | up-regulates activity | 0.536 | Casp3 cleaves bad at asp-61. In addition, caspases convert bad(l) into a pro-death fragment that resembles the short splice variant. | SIGNOR-126727 |
P53805 | P49841 | 0 | phosphorylation | up-regulates activity | 0.484 | Consensus phosphorylation sites for p42/44 MAPK and GSK-3 are present in the SP repeat of MCIP1 at serine 112 and serine 108, respectively |Several endogenous proteins are capable of inhibiting the catalytic activity of calcineurin. Modulatory calcineurin interacting protein 1 (MCIP1) is unique among these proteins on the basis of its pattern of expression and its function in a negative feedback loop to regulate calcineurin activity. Here we show that MCIP1 can be phosphorylated by MAPK and glycogen synthase kinase-3 and that phosphorylated MCIP1 is a substrate for calcineurin. | SIGNOR-249359 |
P00748 | P50281 | 0 | cleavage | down-regulates quantity by destabilization | 0.331 | The data presented in this study show for the first time the degradation of Factor XII of the blood clotting system by matrix metalloproteinases. MMP-12, MMP-13, and MMP-14 cleave at Gly376Leu377|However, no activity of Factor XII can be observed after MMPinduced cleavage. | SIGNOR-263610 |
Q8NAP3 | Q7Z6E9 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.423 | Thus, RBBP6 induces ZBTB38 protein degradation, and this depends on the activity of the proteasome.We next tested whether RBBP6 might directly ubiquitinate ZBTB38.|We show that ZBTB38 is directly ubiquitinated by RBBP6 in human and mouse cells, in a process that is independent of p53 and MDM2, and leads to proteasomal degradation. | SIGNOR-278594 |
P12931 | P49023 | 1 | phosphorylation | up-regulates activity | 0.808 | Here, we demonstrate that Src kinase directly phosphorylates Y88 paxillin|In this study, we also show how pY88 paxillin transduces a signal to activate Akt | SIGNOR-263977 |
P49715 | P27361 | 0 | phosphorylation | down-regulates | 0.371 | Ccaat/enhancer-binding protein alpha (c/ebpalpha) is one of the key transcription factors that mediate lineage specification and differentiation of multipotent myeloid progenitors into mature granulocytes.Here we report that inducers of monocyte differentiation inhibit the alternate cell fate choice, that of granulopoiesis, through inhibition of c/ebpalpha. This inhibition is mediated by extracellular signal-regulated kinases 1 and/or 2 (erk1/2), which interact with c/ebpalpha through an fxfp docking site and phosphorylate serine 21. | SIGNOR-120570 |
Q16539 | P30307 | 1 | phosphorylation | down-regulates activity | 0.439 | P38 binds and phosphorylates Cdc25B at serines 309 and 361, and Cdc25C at serine 216; phosphorylation of these residues is required for binding to 14-3-3 proteins. | SIGNOR-250091 |
P26358 | P06493 | 0 | phosphorylation | up-regulates | 0.3 | We report that cyclin-dependent kinases (cdks) 1, 2 and 5 can phosphorylate ser154 of human dnmt1 in vitro. Further evidence of phosphorylation of endogenous dnmt1 at position 154 by cdks is also found in 293 cells treated with roscovitine, a specific inhibitor of cdk1, 2 and 5 | SIGNOR-173677 |
O94811 | P28482 | 0 | phosphorylation | down-regulates activity | 0.354 | Here we show that TPPP induces tubulin self-assembly into intact frequently bundled microtubules, and that the phosphorylation of specific sites distinctly affects the function of TPPP. The phosphorylation sites Thr(14), Ser(18), Ser(160) for Cdk5; Ser(18), Ser(160) for ERK2, and Ser(32) for PKA were identified by mass spectrometry. The phosphorylation by ERK2 or Cdk5 resulted in the loss of microtubule-assembling activity of TPPP. | SIGNOR-262928 |
Q9Y6H6 | Q05655 | 0 | phosphorylation | up-regulates activity | 0.2 | Currents mediated by the complex formed by KCNQ1 and the mutant KCNE3-S82A β-subunit (mutation of the site for PKCdelta-promoted phosphorylation and modulation of the activity of KCNE3) showed rapid run-down and insensitivity to E2. | SIGNOR-275964 |
P03956 | Q99075 | 1 | cleavage | up-regulates activity | 0.33 | We have recently reported that HB-EGF is a substrate of MT1-MMP and that removal of the N-terminal fragment of HB-EGFby MT1-MMP converts the former into a hyperactive growthfactor that does not require heparin as a co-factor. | SIGNOR-278096 |
P31749 | P07550 | 1 | phosphorylation | down-regulates | 0.354 | Akt mediates sequestration of the beta(2)-adrenergic receptor in response to insulin. Phosphorylation studies of the c-terminal cytoplasmic domain of the beta(2)-adrenergic receptor by akt in vitro identified ser(345) and ser(346) within a consensus motif for akt phosphorylation. | SIGNOR-252470 |
P12931 | O14744 | 1 | phosphorylation | down-regulates activity | 0.261 | Here, we demonstrate that PRMT5 is phosphorylated at residue Y324 by Src kinase, a negative regulator of its activity. | SIGNOR-277523 |
Q8N103 | P61586 | 1 | gtpase-activating protein | down-regulates activity | 0.447 | 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-260523 |
P51692 | P17706 | 0 | dephosphorylation | down-regulates activity | 0.733 | In the previous study, we demonstrated that the nuclear isoform of T-cell protein-tyrosine phosphatase (TC-PTP) dephosphorylated and deactivated signal transducer and activator of transcription 5a (STAT5a) and STAT5b, thereby negatively regulating prolactin (PRL)-mediated signaling pathway. | SIGNOR-277126 |
Q9Y385 | P49137 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.334 | Endoplasmic reticulum-associated ubiquitin-conjugating enzyme Ube2j1 is a novel substrate of MK2 (MAPKAP kinase-2) involved in MK2-mediated TNFα production. These findings strongly suggest that MK2 directly phosphorylates Ube2j1 at Ser(184) upon p38-activating stress in vivo. | SIGNOR-263091 |
Q9UQM7 | P16615 | 1 | phosphorylation | up-regulates activity | 0.397 | SERCA2 and SERCA2 mutants S38A, S167A, and S531A were expressed in HEK-293 cells and tested for phosphorylation with CaM kinase. Mutant S38A was not phosphorylated, while mutants S167A and S531A were phosphorylated, suggesting that Ser38 is the site of CaM kinase phosphorylation in SERCA2. This conclusion was supported by the observation that phosphorylation of SERCA2 and mutants S167A and S531A by CaM kinase increased the Vmax for Ca2+ transport, while the Vmax for Ca2+ transport by mutant S38A was unaffected by exposure to a phosphorylation reaction mix. | SIGNOR-250616 |
P22681 | P12931 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.738 | Cbl-b also targets active Src for degradation in cells, and Nedd4 similarly reverses Cbl mediated Src degradation.|Cbl-b also targets active Src for degradation in cells, and Nedd4 similarly reverses Cbl-mediated Src degradation | SIGNOR-278539 |
P23396 | P67775 | 0 | dephosphorylation | down-regulates | 0.427 | We identified that pp2a interacts with wild-type rps3, but not with mutants (s6a/t221a) (fig. 8), and that it associates with the n-terminal region of rps3 (fig. 2). From our results presented here, we conclude that pp2a is involved in the dephosphorylation of phosphorylated rps3 by pkc, and that serine 6 on the n-terminal region of rps3 appears to mediate the pp2a recruitment. | SIGNOR-137963 |
P17542 | Q96AE4 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | TAL1 directly activates the FUBP1 promoter, leading to increased FUBP1 expression during erythroid differentiation. | SIGNOR-259131 |
P31749 | P48431 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.532 | In contrast, phosphorylation of Sox2 by AKT1 at T118 blocks K119me by Set7 and stabilizes Sox2. | SIGNOR-279003 |
Q08289 | P17612 | 0 | 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 |
P16220 | Q13627 | 0 | phosphorylation | up-regulates activity | 0.487 | Regarding to the functional role of Dyrk1A, active Dyrk1A phosphorylates the transcription factor cAMP response element -binding protein (CREB), which subsequently leads to the stimulation of cAMP response element-mediated gene transcription during neuronal differentiation ( ). | SIGNOR-279989 |
Q9BYT3 | O75969 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.2 | Differential phosphoproteomic analysis and in vitro kinase assay identified novel phosphorylation substrates of STK33, fibrous sheath components AKAP3 and AKAP4, whose expression levels decreased in testis after deletion of Stk33. | SIGNOR-272955 |
Q9NPD5 | P10276 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Taken together, these findings suggest that the LPS-induced down-regulation of Oatp4 is likely due to reduction in the binding of HNF1alpha, C/EBP, HNF3, and RXR:RAR to the Oatp4 promoter. | SIGNOR-268989 |
P02461 | Q8NBJ5 | 0 | glycosylation | up-regulates activity | 0.404 | Recombinant GLT25D1 and GLT25D2 enzymes showed a strong galactosyltransferase activity toward various types of collagen and toward the serum mannose-binding lectin MBL, which contains a collagen domain. Amino acid analysis of the products of GLT25D1 and GLT25D2 reactions confirmed the transfer of galactose to hydroxylysine residues. | SIGNOR-261154 |
O43524 | P28482 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.717 | Here, we show that erk downregulates forkhead box o 3a (foxo3a) by directly interacting with and phosphorylating foxo3a at ser 294, ser 344 and ser 425, which consequently promotes cell proliferation and tumorigenesisMDM2 is required for ERk-mediated FOXO3a degradation. | SIGNOR-160415 |
P17252 | Q14469 | 1 | phosphorylation | down-regulates activity | 0.329 | Endogenous HES-1 DNA-binding activity is post-translationally inhibited during NGF signaling in vivo, and phosphorylation of PKC consensus sites in the HES-1 DNA-binding domain inhibits DNA binding by purified HES-1 in vitro. | SIGNOR-248993 |
Q13200 | Q86V86 | 0 | phosphorylation | up-regulates activity | 0.2 | Seven of these kinases (PIM1/2/3, MAP4K1/2, PKA, and NEK6) directly and robustly phosphorylated recombinant GST-Rpn1 at S361 in vitro (Fig. 3D and SI Appendix, Fig. S3 A and B). | SIGNOR-273897 |
P07948 | P46527 | 1 | phosphorylation | down-regulates | 0.553 | We previously reported that y88 phosphorylation of p27(kip1) by oncogenic tyrosine kinases impairs p27(kip1)-mediated cdk inhibition, and initiates its ubiquitin-dependent proteasomal degradation. | SIGNOR-172904 |
P04637 | Q13131 | 0 | phosphorylation | up-regulates | 0.48 | Ampk activation induces phosphorylation of p53 on serine 15, and this phosphorylation is required to initiate ampk-dependent cell-cycle arrest | SIGNOR-135960 |
P12931 | P15311 | 1 | phosphorylation | up-regulates | 0.648 | Src phosphorylates ezrin at tyrosine 477 and induces a phosphospecific association between ezrin and a kelch-repeat protein family member | SIGNOR-132907 |
P20671 | Q86Y13 | 0 | monoubiquitination | up-regulates activity | 0.2 | 2A-HUB catalyzes monoubiquitination of H2A at lysine 119, functioning as a combinatoric component of the repression machinery required for specific gene regulation programs. Thus, 2A-HUB mediates a selective repression of a specific set of chemokine genes in macrophages, critically modulating migratory responses to TLR activation. H2A monoubiquitination acts to prevent FACT recruitment at the transcriptional promoter region, blocking RNA polymerase II release at the early stage of elongation. | SIGNOR-271753 |
P24941 | P17096 | 1 | phosphorylation | down-regulates | 0.264 | Here, we found that hipk2 phosphorylates hmga1a at ser-35, thr-52, and thr-77, and hmga1b at thr-41 and thr-66. In addition, we demonstrated that cdc2, which is known to phosphorylate hmga1 proteins, could induce the phosphorylation of hmga1 proteins at the same ser/thr sites. we found that the hipk2-phosphorylated hmga1a reduced the binding affinity of hmga1a to human germ line promoter, and the drop in binding affinity induced by hipk2 phosphorylation was lower than that introduced by cdc2 phosphorylation. | SIGNOR-158612 |
P14778 | P53779 | 1 | phosphorylation | up-regulates activity | 0.2 | Il-1 binding to its receptor triggers a cascade of signaling events, including activation of the stress-activated mitogen-activated protein (map) kinases, c-jun nh2-terminal kinase (jnk) and p38 map kinase, as well as transcription factor nuclear factor kappab (nf-kappab | SIGNOR-249515 |
P68400 | Q8NEL9 | 1 | phosphorylation | down-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-262977 |
Q99714 | O60260 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.2 | This study identifies the multifunctional PD-related mitochondrial matrix enzyme 17-β hydroxysteroid dehydrogenase type 10 (HSD17B10) as a new Parkin substrate. | SIGNOR-272823 |
Q70YC5 | P04637 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.29 | Here, analysis of p53-regulated genes activated in the setting of telomere dysfunction identified Zfp365 (ZNF365 in humans) as a direct p53 target that promotes genome stability| Our study identified ZNF365 as a necessary target whose activation by p53 in the presence of critically short telomeres contributes to genomic stability. We provide evidence that loss of ZNF365 leads to increased expression of CFS and dysfunctional telomeres, aberrant sister telomere recombination, and increased aneuploidy | SIGNOR-272476 |
Q13315 | Q86U44 | 1 | phosphorylation | up-regulates activity | 0.2 | Here, we report that, in response to DSBs, the RNA methyltransferase METTL3 is activated by ATM-mediated phosphorylation at S43. | SIGNOR-265969 |
P37231 | Q14469 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.248 | CREB inhibits hepatic PPAR-gamma expression in the fasted state by stimulating the expression of the Hairy Enhancer of Split (HES-1) gene, a transcriptional repressor that is shown here to be a mediator of fasting lipid metabolism in vivo | SIGNOR-253584 |
Q6ZUJ8 | Q7Z570 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | ZNF804A has been implicated in susceptibility to schizophrenia by several genome-wide association studies (GWAS), follow-up association studies and meta-analyses. ZNF804A was identified as a schizophrenia-associated gene by GWAS and was predicted to play a role in DNA binding and transcription To identify the genes that are affected by ZNF804A, we manipulated the expression of the ZNF804A protein in HEK293 human embryonic kidney cell lines and performed a cDNA microarray analysis followed by qPCR. We found that ZNF804A-overexpression up-regulated four genes (ANKRD1, INHBE, PIK3AP1, and DDIT3) and down-regulated three genes (CLIC2, MGAM, and BIRC3). | SIGNOR-269463 |
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