IdA string | IdB string | labels int64 | mechanism string | effect string | score float64 | sentence string | signor_id string |
|---|---|---|---|---|---|---|---|
Q01484 | Q9UJW0 | 1 | relocalization | up-regulates quantity | 0.625 | We present evidence for an ankyrin-based mechanism for sarcolemmal localization of dystrophin and beta-DG. Ankyrin-B thus is an adaptor required for sarcolemmal localization of dystrophin, as well as dynactin-4. | SIGNOR-266713 |
Q12923 | P06213 | 1 | dephosphorylation | down-regulates | 0.26 | We demonstrate that ptpl1, like ptp1b, interacts with and dephosphorylates a bis-phosphorylated insulin receptor peptide more efficiently than monophosphorylated peptides, indicating that ptpl1 may down-regulate the phosphatidylinositol 3-kinase pathway, by dephosphorylating insulin or growth factor receptors that contain tandem phosphotyrosines. | SIGNOR-132555 |
Q92529 | Q9UM73 | 0 | phosphorylation | up-regulates | 0.44 | Anaplastic lymphoma kinase (alk), which turned out to be one of these phosphoproteins, was constitutively activated and associated with the ptb domain of shcc in three neuroblastoma cells. In vitro kinase assay revealed that shcc is a potent substrate of the activated alk kinase. The alk gene locus was significantly amplified in both of these cell lines, suggesting that gene amplification leads to constitutive activation of the alk kinase, which results in hyperphosphorylation of shcc. | SIGNOR-91537 |
P04908 | Q9H3R0 | 0 | demethylation | down-regulates activity | 0.2 | As one member of the Jumonji-C histone demethylase family, JMJD2C has the ability to demethylate tri- or di-methylated histone 3 and 2 in either K9 (lysine residue 9) or K36 (lysine residue 36) sites by an oxidative reaction, thereby affecting heterochromatin formation, genomic imprinting, X-chromosome inactivation, and transcriptional regulation of genes.JMJD2C has been proved to be a demethylase for H3K9 methylation, in the manner of catalyzing the demethylation of H3K9me3/me2 (the known repressive markers of gene regulation), a histone mark found in heterochromatin associated with euchromatic transcriptional silencing and heterochromatin formation | SIGNOR-263862 |
P60321 | P46934 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.2 | We find that NEDD4 targets an RNA-binding protein, NANOS2, in spermatogonia to destabilize it, leading to cell differentiation.|To examine whether complex formation of NEDD4 and NDFIP2 promotes NANOS2 ubiquitination in vivo, FLAG tagged NANOS2 was expressed in HEK293 cells with or without MYC-NEDD4 and MYC-NDFIP2. | SIGNOR-278770 |
O43781 | Q96B36 | 1 | phosphorylation | down-regulates | 0.34 | When dyrk3 is active, it allows stress granule dissolution, releasing mtorc1 for signaling and promoting its activity by directly phosphorylating the mtorc1 inhibitor pras40 | SIGNOR-201002 |
Q12888 | O15264 | 0 | phosphorylation | down-regulates activity | 0.2 | Here we show that 53BP1 is phosphorylated during mitosis on two residues, T1609 and S1618, located in its well-conserved ubiquitination-dependent recruitment (UDR) motif.|Dephosphorylation enables the recruitment of 53BP1 to double-strand DNA breaks |phosphorylation of T1609 is likely to be mediated by p38 MAPK | SIGNOR-264449 |
Q13131 | Q9UBK2 | 1 | phosphorylation | up-regulates activity | 0.575 | Ampk phosphorylates pgc-1alpha directly both in vitro and in cells. These direct phosphorylations of the pgc-1alpha protein at threonine-177 and serine-538. | SIGNOR-156780 |
Q9Y243 | P67775 | 0 | dephosphorylation | down-regulates activity | 0.738 | Protein phosphatase 2A negatively regulates insulin's metabolic signaling pathway by inhibiting Akt (protein kinase B) activity in 3T3-L1 adipocytes | SIGNOR-248654 |
P15923 | Q15759 | 0 | phosphorylation | up-regulates | 0.436 | 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, while the nonphosphorylatable e47 mutant ser140ala fails to heterodimerize with myod and displays impaired myogenic potentia | SIGNOR-134190 |
P11171 | P00533 | 0 | phosphorylation | down-regulates | 0.4 | The phosphorylation site has been localized to the 8-kda domain, which has one tyrosine, tyrosine-418. The 8-kda region is required for the assembly of the spectrin/actin complex, and phosphorylation by egfr reduced the ability of protein 4.1 to promote the assembly of the spectrin/actin/protein 4.1 ternary complex | SIGNOR-20452 |
P17858 | O15294 | 0 | glycosylation | down-regulates activity | 0.277 | O-GlcNAcylation was induced at serine 529 of phosphofructokinase 1 (PFK1) in response to hypoxia. Glycosylation inhibited PFK1 activity and redirected glucose flux through the pentose phosphate pathway| O-GlcNAc transferase (OGT) catalyzes the transfer of N-acetylglucosamine from uridine diphospho-N-acetylglucosamine (UDP-GlcNAc) to serine or threonine residues | SIGNOR-267585 |
O15182 | Q15154 | 0 | relocalization | up-regulates | 0.297 | Rna silencing of pcm-1 leads to reduced assembly of centrin, pericentrin, and ninein at the centrosome | SIGNOR-95016 |
O75385 | Q7Z3C6 | 1 | phosphorylation | up-regulates activity | 0.582 | Src phosphorylates mATG9 at Tyr8 to maintain its endocytic and constitutive trafficking in unstressed conditions. In response to starvation, phosphorylation of mATG9 at Tyr8 by Src and at Ser14 by ULK1 functionally cooperate to promote interactions between mATG9 and the AP1/2 complex, leading to redistribution of mATG9 from the plasma membrane and juxta-nuclear region to the peripheral pool for autophagy initiation. | SIGNOR-266369 |
P04150 | P49716 | 1 | transcriptional regulation | up-regulates quantity | 0.315 | We conclude that glucocorticoid-induced adipogenesis from bone marrow stromal cells is mediated through a reaction cascade in which dexamethasone transcriptionally activates C/EBPδ; C/EBPδ then binds to PPARγ2 promoter and transactivates PPARγ2 gene expression. | SIGNOR-253061 |
P10415 | Q86UR1 | 0 | null | down-regulates activity | 0.2 | BH3-only proteins containing only a single BH domain and including Puma, Noxa, Bid and Bad as well as other factors are particularly important for such neutralisation, binding and regulating the anti-apoptotic Bcl-2 proteins to promote apoptosis | SIGNOR-209684 |
Q9Y2U5 | P45985 | 1 | phosphorylation | up-regulates activity | 0.612 | Both mekk2 and mekk3 are able to activate the jun kinase pathway in vivo. However, following routine immunoprecipitation in triton x-100, mekk2 but not mekk3 is able to effectively phosphorylate both sek-1 and mek-1 and to undergo autophosphorylation | SIGNOR-107695 |
Q9Y6Q9 | O15111 | 0 | phosphorylation | up-regulates | 0.395 | Herein, we report the successful identification of six functional in vivo src-3 phosphorylation sites. | SIGNOR-196953 |
P30305 | O14757 | 0 | phosphorylation | down-regulates activity | 0.785 | Here, we show that cdc25b is phosphorylated by chk1 in vitro on multiple residues, including s230 and s563.We show that the s230-phosphorylated form of cdc25b is located at the centrosome from early s phase until mitosis. Furthermore, mutation of s230 to alanine increases the mitotic-inducing activity of cdc25b | SIGNOR-149898 |
Q13568 | P07948 | 0 | phosphorylation | down-regulates activity | 0.329 | Lyn Kinase Suppresses the Transcriptional Activity of IRF5. Here, we found that Lyn physically interacted with IRF5 to inhibit ubiquitination and phosphorylation of IRF5 in the TLR-MyD88 pathway, thereby suppressing the transcriptional activity of IRF5 in a manner independent of Lyn's kinase activity. | SIGNOR-277247 |
P30307 | P38398 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.464 | BRCA1 mediates cyclin B and Cdc25C ubiquitination.|Thus, BRCA1 dependent proteasomal degradation of cyclin B and Cdc25C precede the subsequent BRCA1 dependent cell cycle arrest. | SIGNOR-278623 |
P52945 | P11168 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.522 | In conclusion, Pdx1 confers the expression of pancreatic β-cell-specific genes, such as genes encoding insulin, islet amyloid polypeptide, Glut2, and Nkx6.1. | SIGNOR-255540 |
P06493 | O00429 | 1 | phosphorylation | up-regulates activity | 0.466 | Drp1 is phosphorylated at the Ser616 position and activated predominantly by CDK1. | SIGNOR-279394 |
P20248 | Q86T82 | 0 | deubiquitination | up-regulates quantity by stabilization | 0.581 | USP37 Binds, Deubiquitinates, and Stabilizes Cyclin A | SIGNOR-265052 |
Q13873 | Q9HCE7 | 0 | ubiquitination | down-regulates | 0.56 | Smurf1 and smurf2 are e3 ubiquitin ligases known to suppress tgf-beta signaling through degradation of smads and receptors for tgf-beta and bmps. | SIGNOR-153402 |
P04637 | P38936 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.876 | The ability of p53 to activate transcription from specific sequences suggests that genes induced by p53 may mediate its biological role as a tumor suppressor. Using a subtractive hybridization approach, we identified a gene, named WAF1, whose induction was associated with wild-type but not mutant p53 gene expression in a human brain tumor cell line. The WAF1 gene was localized to chromosome 6p21.2, and its sequence, structure, and activation by p53 was conserved in rodents. | SIGNOR-37145 |
O76064 | O14773 | 1 | ubiquitination | up-regulates activity | 0.302 | Our data demonstrate that RNF8 directly ubiquitylates and stabilizes TPP1 at telomeres.|Taken together, these results suggest that RNF8 dependent K63 linked, but not K48 linked ubiquitin chain formation on TPP1 is required to promote TPP1 stability and function at telomeres. | SIGNOR-278574 |
Q71DI3 | Q9Y4C1 | 0 | demethylation | up-regulates activity | 0.2 | Using a biochemical assay coupled with chromatography, we have purified a JmjC domain-containing protein, JHDM2A, which specifically demethylates mono- and dimethyl-H3K9. | SIGNOR-276844 |
O15534 | Q92973 | 0 | relocalization | up-regulates activity | 0.268 | The non-classical nuclear import carrier Transportin 1 modulates circadian rhythms through its effect on PER1 nuclear localization | SIGNOR-262102 |
Q86U86 | Q13049 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.2 | TRIM32 ubiquitination of PB1 leads to its protein degradation. | SIGNOR-278735 |
P29350 | P14618 | 1 | dephosphorylation | down-regulates activity | 0.2 | SHP-1 dephosphorylates PKM2 at Y105 to inhibit nuclear function of PKM2 and determines the efficacy of targeted drugs.|SHP-1 directly dephosphorylated PKM2 at Y105 and further decreased the proliferative activity of PKM2; similar effects were found in sorafenib-treated hepatocellular carcinoma cells.|SHP-1 dephosphorylates p-PKM2Y105 and further affects the nucleus-related cell proliferation. | SIGNOR-276997 |
Q9H2G2 | P41161 | 1 | phosphorylation | up-regulates activity | 0.2 | Here, we report that the direct activation of the three mammalian ERMs by the Ste20-like kinase (SLK) is crucial for guiding the mitotic spindle toward the expected orientation in two mammalian models of oriented cell division: micropatterned cells and apical progenitors of the mouse neocortex.|SLK directly phosphorylates mammalian ERMs and controls their cortical activation in mitosis. | SIGNOR-280126 |
P25098 | Q8IXH6 | 1 | phosphorylation | down-regulates activity | 0.2 | In conclusion, experimental results demonstrate that GRK2 chronically downregulates DOR functional competence at the PM in peripheral sensory neurons, as well as peripheral DOR anti-nociception in vivo.|These data demonstrate that BK does not affect GRK2 mediated phosphorylation of DOR at its primary desensitization site. | SIGNOR-279739 |
O15111 | P49815 | 1 | phosphorylation | down-regulates | 0.296 | Insulin activation of mtor requires akt in a manner that involves ikkalpha, preferentially to ikkbeta, and tsc2 phosphorylation | SIGNOR-178664 |
Q86Y13 | P16104 | 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-271752 |
P23409 | Q14814 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.573 | Myogenin and MEF2 function synergistically to activate the MRF4 promoter during myogenesis. | SIGNOR-238715 |
P12931 | Q08050 | 1 | phosphorylation | up-regulates activity | 0.324 | Hence, c-Src-dependent phosphorylation of MPP2 could be part of a negative feedback loop within the circuitry that modulates c-Src activity by MPP2. | SIGNOR-279117 |
Q969H0 | P41743 | 0 | phosphorylation | down-regulates activity | 0.267 | Here, we report that Fbw7α, the only Fbw7 isoform detected in eggs, is phosphorylated by PKC (protein kinase C) at a key residue (S18) in a manner coincident with Fbw7α inactivation. | SIGNOR-277250 |
P31749 | O43521 | 1 | phosphorylation | down-regulates activity | 0.567 | Recombinant Akt could directly phosphorylate a GST-Bim(EL) fusion protein and identified the Akt phosphorylation site in the Bim(EL) domain as Ser(87). Further, we demonstrated that cytokine stimulation promotes Bim(EL) binding to 14-3-3 proteins. Finally, we show that mutation of Ser(87) dramatically increases the apoptotic potency of Bim(EL). | SIGNOR-252487 |
P00533 | Q9HD43 | 0 | dephosphorylation | down-regulates activity | 0.288 | We further found that PTPRH and PTPRB directly dephosphorylate EGFR and repress its downstream signaling. | SIGNOR-277090 |
Q8TD19 | P06493 | 0 | phosphorylation | up-regulates activity | 0.482 | We now identify Plk1 as Nek9 direct activator and propose a two-step activation mechanism that involves Nek9 sequential phosphorylation by CDK1 and Plk1. while CDK1 activity is necessary for Nek9 phosphorylation in mitosis and the resulting change in electrophoretical mobility, Nek9 Thr210 phosphorylation and mitotic activation requires both CDK1 and Plk1. | SIGNOR-273889 |
P50222 | O60315 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.318 | ZEB2 represses GAX transcription through multiple up- stream consensus binding sites. | SIGNOR-268951 |
Q13554 | P16949 | 1 | phosphorylation | down-regulates | 0.515 | Stimulation via cd2 activated multiple signal transduction pathways, resulting in phosphorylation of distinct sites of stathmin. Ser16 of recombinant human stathmin was phosphorylated also by purified cam kinase ii, and in vivo, cam kinase ii activity was indeed stimulated in cd2-triggered jurkat cells. | SIGNOR-59358 |
Q13043 | P26927 | 0 | phosphorylation | up-regulates | 0.524 | We directly show that okadaic acid induces phosphorylation in the activation loop of mst, and, once phosphorylated, mst is rapidly translocated to the nucleus. when thr183 in mst1 was mutated to ala, no band could be detected by oa treatment,2 indicating that thr183 was the site of phosphorylation. | SIGNOR-114289 |
P04049 | Q9NQU5 | 0 | phosphorylation | up-regulates activity | 0.2 | PAK5 phosphorylates Raf-1 on serine 338 and stimulates Raf-1 activity. | SIGNOR-278971 |
P21817 | P17612 | 0 | phosphorylation | up-regulates activity | 0.326 | PKA-mediated hyperphosphorylation of a conserved serine, Ser-2843 in skeletal RyR and Ser-2809 in cardiac RyR, results in an aberrant SR function during heart failure. hyperphosphorylated RyRs are leaky and therefore lead to a reduced SR Ca2+ load and impaired contractile function in heart failure | SIGNOR-250078 |
P14635 | Q14774 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | In this study, we have identified cell cycle regulatory genes as downstream targets of the homeobox gene HLX in cultured trophoblast cells, namely RB1, MYC, EGR1, CDKN1C, ELK1, CCNB1, and JUN. RB1 and MYC mRNA expression was increased with HLX inactivation, whereas EGR1, CDKN1C, ELK1, CCNB1, and JUN mRNA expression was decreased compared with mock-transfected control cells. | SIGNOR-261619 |
Q00535 | P35712 | 1 | phosphorylation | down-regulates quantity | 0.366 | GST-Sox6 was phosphorylated in vitro by Cdk5 and p35 (XREF_FIG).|Inhibition of Cdk5 activity by DN Cdk5 and roscovitine increases the Sox6 expression in primary cortical neurons. | SIGNOR-279365 |
P09917 | P17612 | 0 | phosphorylation | down-regulates activity | 0.335 | These results indicate that PKA phosphorylates 5-LO on Ser-523, which inhibits the catalytic activity of 5-LO and reduces cellular LT generation. | SIGNOR-264410 |
P09467 | P17010 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.2 | For instance, nucleophosmin (NPM1) and zinc-finger protein X-linked (ZFX) bind to the E-box and ZFX binding site on the FBP1 promoter, respectively, and restrain FBP1 expression to facilitate aerobic glycolysis in PDAC and melanoma | SIGNOR-267595 |
P17252 | P14136 | 1 | phosphorylation | down-regulates activity | 0.366 | Glial fibrillary acidic protein (GFAP), the intermediate filament component of astroglial cells, can serve as an excellent substrate for both cAMP-dependent protein kinase and protein kinase C, in vitro. GFAP phosphorylated by each protein kinase does not polymerize, and the filaments that do polymerize tend to depolymerize after phosphorylation. Dephosphorylation of phospho-GFAP by phosphatase led to a recovery of the polymerization competence of GFAP. Most of the phosphorylation sites for cAMP-dependent protein kinase and protein kinase C on GFAP are the same, Ser-8, Ser-13, and Ser-34. cAMP-dependent protein kinase has one additional phosphorylation site, Thr-7. | SIGNOR-248862 |
P78527 | P09874 | 1 | phosphorylation | down-regulates activity | 0.525 | Therefore, through its interaction with Ku70/80 in the presence of dsDNA , DNA-PK phosphorylated PARP-1 at its catalytic CTD. | SIGNOR-280093 |
Q07812 | P49841 | 0 | phosphorylation | up-regulates | 0.376 | Glycogen synthase kinase-3beta phosphorylates bax and promotes its mitochondrial localization during neuronal apoptosis. Gsk-3beta directly phosphorylated bax(alpha) on ser163 | SIGNOR-130141 |
P02686 | P09543 | 0 | null | down-regulates activity | 0.455 | We provide evidence that CNP directly associates with and organizes the actin cytoskeleton, thereby providing an intracellular strut that counteracts membrane compaction by myelin basic protein (MBP). | SIGNOR-269269 |
O43795 | P29323 | 0 | phosphorylation | up-regulates activity | 0.2 | EphB2 kinase activity is required for Myo1b-EphB2 interaction and induced Myo1b phosphorylation. | SIGNOR-279171 |
P68104 | P36897 | 0 | phosphorylation | down-regulates | 0.343 | Phosphorylation of eEF1A1 at Ser300 by T_R-I results in inhibition of mRNA translation | SIGNOR-167943 |
P10644 | Q00536 | 0 | phosphorylation | up-regulates activity | 0.272 | PCTK1 regulates spindle orientation in a kinase-dependent manner. Phosphoproteomic analysis together with an RNA interference screen revealed that PCTK1 regulates spindle orientation through phosphorylation of Ser83 on KAP0, a regulatory subunit of protein kinase A (PKA) | SIGNOR-273018 |
Q92990 | P08581 | 0 | relocalization | down-regulates | 0.331 | Significantly, nonphosphorylated hgf receptor prevents fap68 from stimulating p70s6k. fap68 binding to met requires the last 30 amino acids of the c-terminal tail, which are unique to the hgf receptor. | SIGNOR-110726 |
P22607 | Q9UPZ9 | 1 | phosphorylation | down-regulates activity | 0.2 | FGF signaling partially abolished ICK's kinase activity, through FGFR-mediated ICK phosphorylation at conserved residue Tyr15, which interfered with optimal ATP binding. | SIGNOR-277436 |
Q13009 | P48729 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.309 | Phosphorylation of Ser329, Ser334, and Thr340 in Tiam1 is required for its interaction with βTrCP1. The proteolysis of Tiam1 is prevented by βTrCP silencing, inhibition of CK1 and MEK, or mutation of the Tiam1 degron site. | SIGNOR-276673 |
P49336 | P84243 | 1 | 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-273173 |
Q05682 | Q9UQM7 | 0 | phosphorylation | down-regulates | 0.2 | Smooth muscle caldesmon was phosphorylated by smooth muscle calmodulin-dependent protein kinase. Ii | SIGNOR-22635 |
Q9UBS0 | P42345 | 0 | phosphorylation | up-regulates | 0.834 | In response to insulin and nutrients, mtorc1, consisting of mtor, raptor (regulatory-associated protein of mtor), and mlst8, is activated and phosphorylates eukaryotic initiation factor 4e-binding protein (4ebp) and p70 s6 kinase to promote protein synthesis and cell size. | SIGNOR-154821 |
P22087 | Q9NRC8 | 0 | deacetylation | up-regulates activity | 0.271 | Here, we show that FBL is acetylated at several lysine residues by the acetyltransferase CBP and deacetylated by SIRT7.|hyperacetylation impairs the interaction of FBL with histone H2A and chromatin, thereby compromising H2AQ104 methylation (H2AQ104me) and rDNA transcription. SIRT7-dependent deacetylation of FBL ensures H2AQ104me and high levels of rRNA synthesis during interphase. |Global acetylome studies have shown that FBL is acetylated at four conserved lysine residues (K102, K121, K205, and K206) | SIGNOR-275894 |
P00519 | Q9Y6Q9 | 1 | phosphorylation | up-regulates | 0.348 | Tyrosine phosphorylation of the nuclear receptor coactivator aib1/src-3 is enhanced by abl kinase and is required for its activity in cancer cellstyrosine kinase directly phosphorylates aib1/src-3 at y1357 and modulates the association of aib1 with c-abl, eralpha, the transcriptional cofactor p300, | SIGNOR-180571 |
P49841 | P54132 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.259 | We now provide evidence that BLM undergoes K48-linked ubiquitylation and subsequent degradation during mitosis due to the E3 ligase, Fbw7α. Fbw7α carries out its function after GSK3β- and CDK2/cyclin A2-dependent phosphorylation events on Thr171 and Ser175 of BLM which lies within a well-defined phosphodegron, a sequence which is conserved in all primates. | SIGNOR-276906 |
Q9NV58 | P41180 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.381 | Coexpression with dorfin decreased the amount of total CaR protein and increased CaR ubiquitination, whereas a dominant negative fragment of dorfin had opposite effects. dorfin-mediated proteasomal degradation of immature CaR occurs from the endoplasmic reticulum. Because endogenous CaR in Madin-Darby canine kidney cells is also subject to degradation from the endoplasmic reticulum, dorfin-mediated ubiquitination may contribute to a general mechanism for CaR quality control during biosynthesis. | SIGNOR-271456 |
O15379 | P12830 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.257 | GATA1 is a new substrate of p21-activated kinase 5 (PAK5), which is phosphorylated on serine 161 and 187 (S161 and S187). GATA1 recruits HDAC3/4 to E-cadherin promoter, which is reduced by GATA1 S161A S187A mutant. These data indicate that phosphorylated GATA1 recruits more HDAC3/4 to promote transcriptional repression of E-cadherin, leading to the EMT of breast cancer cells. | SIGNOR-275662 |
P24941 | O60318 | 1 | phosphorylation | up-regulates activity | 0.2 | To study the inducible regulation of GANP DNA-primase during cell activation, we examined phosphorylation induced by various kinds of kinases.We observed that the cell cycle-associated kinase Cdks induced phosphorylation of GANP in vitro. Examination of immunoprecipitates of Cdk2 from B cells revealed phosphorylation of GANP-PD at a consensus sequence of Cdk phosphorylation at Ser502 (S/T-P-X-K/R) (Fig. (Fig.1C1C Left; ref. 22). | SIGNOR-262734 |
Q13131 | Q8IWQ3 | 0 | phosphorylation | up-regulates | 0.291 | Ampka1 activators increased phosphorylation level and cytoplasmic localization (reduced nuclear/cytoplasmic ratio). Ampka1 activators reduced rna synthesis in the nucleoli. | SIGNOR-176594 |
Q9HAU4 | P49910 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.268 | ZNF165 drives the unrestrained activation of transforming growth factor β (TGFβ) signalling by directly inactivating the expression of negative feedback pathway regulators, SMURF2, SMAD7 and PMEPA1. | SIGNOR-266095 |
P17252 | Q96RI1 | 1 | phosphorylation | up-regulates | 0.325 | Phosphorylation of farnesoid x receptor by protein kinase c promotes its transcriptional activity. pkcalpha phosphorylates in vitro fxr in its dna-binding domain on s135 and s154. | SIGNOR-180537 |
Q96RR4 | Q00535 | 0 | phosphorylation | down-regulates | 0.2 | Cdk5 and gsk3 phosphorylate ser-129, ser-133, and ser-137. Mutation of ser-129, ser-133, and ser-137 increases autonomous activity with little change in ca2 /cam-dependent activity. | SIGNOR-198111 |
Q16620 | P19174 | 1 | phosphorylation | up-regulates activity | 0.647 | Both Shc and PLCgamma1 are phosphorylated by TrkB, thereby initiating Shc/Ras/MAP kinase and PLCgamma1 signaling respectively.|We conclude that activation of pY783 PLCgamma1 is due mainly to TrkB activation in these models and that TrkB induced PLCgamma1 signaling promotes limbic epileptogenesis. | SIGNOR-279241 |
P0C0L5 | O00187 | 0 | cleavage | up-regulates activity | 0.798 | MASP-2 cleaves C4 releasing C4a and generating C4b, which attaches covalently to the pathogen surface upon exposure of its reactive thioester. C2 binds to C4b and is also cleaved by MASP-2 to form the C3 convertase (C4b2a). | SIGNOR-263422 |
P24941 | P23511 | 1 | phosphorylation | up-regulates activity | 0.439 | Cdk2 phosphorylates two serine residues near the DNA-binding domain of the YA subunit of NF-Y. Cyclin A-cdk2 appears to associate with NF-Y both in vitro and in vivo. Furthermore, YA protein is phosphorylated in parallel with a cell cycle-dependent activation of cdk2 kinase and cyclin A expression. YA phosphorylation is unnecessary for heterotrimer formation with the YB-YC dimer. However, NF-Y containing a phosphorylation-deficient mutant form of YA, YA-aa, has its DNA binding activity impaired. \ To examine whether cdk2 phosphorylates the two serine residues at positions 320 and 326 in YA, we replaced either or both with alanine by site-directed mutagenesis. In a kinase assay using purified GST fusion proteins in vitro, cdk2 phosphorylated the wild type and both of the single-mutant proteins (YA-as and -sa), but not the double-mutant protein (YA-aa) | SIGNOR-250742 |
P13349 | P23759 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.492 | Together, these experiments indicate that Pax7 enforces satellite cell commitment by recruiting a HMT complex to Myf5, resulting in transcriptional activation. | SIGNOR-255641 |
Q96QB1 | Q00535 | 0 | phosphorylation | up-regulates activity | 0.2 | The CDK5 kinase phosphorylates four serines in DLC1 located N-terminal to the Rho-GAP domain. When not phosphorylated, this N-terminal region functions as an autoinhibitory domain that places DLC1 in a closed, inactive conformation by efficiently binding to the Rho-GAP domain. CDK5 phosphorylation reduces this binding and orchestrates the coordinate activation DLC1, including its localization to focal adhesions, its Rho-GAP activity, and its ability to bind tensin and talin. | SIGNOR-276444 |
P42684 | Q14653 | 1 | phosphorylation | up-regulates activity | 0.2 | The data in this study show that IRF3 is physically associated with c-Abl in vivo and directly binds to c-Abl in vitro. IRF3 is phosphorylated by c-Abl and c-Abl-related kinase, Arg, mainly at Y292. | SIGNOR-277441 |
Q16512 | Q9NYL2 | 1 | phosphorylation | up-regulates | 0.2 | Phosphorylation of mltkalpha by pknalpha enhances its kinase activity | SIGNOR-152768 |
Q96SW2 | Q9UKT9 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.581 | IMiD compounds cause selective ubiquitination and degradation of IKZF1 in CD34+ cells by the CRBN E3 ubiquitin ligase. | SIGNOR-272319 |
O43318 | O14920 | 1 | phosphorylation | up-regulates activity | 0.755 | Tak1 become activated and then phosphorylates and activates ikk2 which in turn now phosphorylates ikba, marking it for k48-ubiquitination and proteasomal degradation. tak1 kinase complex phosphorylates and activates ikk in a manner that depends on traf6 and ubc13-uev1a our studies suggests that tak1_ acts as an upstream activating kinase for ikkbeta. | SIGNOR-109490 |
Q07812 | Q9ULZ3 | 0 | relocalization | up-regulates | 0.353 | Asc directly induces bax-mediated apoptosis. Asc induces the translocation of bax to the mitochondria, bax-dependent cycs release from the mitochondria and casp9 activation. | SIGNOR-149522 |
P45984 | P14778 | 0 | phosphorylation | up-regulates activity | 0.281 | 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-249514 |
P41180 | Q9NV58 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.381 | Coexpression with dorfin decreased the amount of total CaR protein and increased CaR ubiquitination, whereas a dominant negative fragment of dorfin had opposite effects. dorfin-mediated proteasomal degradation of immature CaR occurs from the endoplasmic reticulum. Because endogenous CaR in Madin-Darby canine kidney cells is also subject to degradation from the endoplasmic reticulum, dorfin-mediated ubiquitination may contribute to a general mechanism for CaR quality control during biosynthesis. | SIGNOR-271456 |
Q09472 | Q9UK32 | 0 | phosphorylation | down-regulates activity | 0.253 | Figure 2G shows that Ser89 phosphorylation of p300, an event that inhibits p300’s acetyltransferase activity (13), was decreased in RSK4-silenced A549 and T24 cells. Consequently, RSK4 may regulate the activity of the NFκB pathway by direct phosphorylation of p300, as recombinant RSK4 phosphorylates p300 on Ser89 in vitro | SIGNOR-275796 |
P30874 | P15884 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.358 | Activation of somatostatin receptor II expression by transcription factors MIBP1 and SEF-2 in the murine brain. | SIGNOR-261618 |
P22612 | P46019 | 1 | phosphorylation | down-regulates activity | 0.325 | Phosphorylation of the alpha and beta subunits by the 3',5'-cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) also relieves inhibition of the gamma subunit and thereby activates the enzyme. | SIGNOR-267414 |
P09619 | P17706 | 0 | dephosphorylation | down-regulates activity | 0.564 | The PDGF beta receptor is negatively regulated by protein tyrosine phosphatases (PTPs).|In summary, our findings identify TC-PTP as a previously unrecognized negative regulator of PDGF beta receptor signaling and support the general notion that PTPs display site selectivity in their action on tyrosine kinase receptors.The fact that two of the investigated PDGF β receptor sites, Y1021 and Y771, displayed a larger increase in phosphorylation than Y579 and Y751 in TC-PTP ko MEFs indicated that these two sites are preferred substrates for TC-PTP. | SIGNOR-248389 |
P53602 | P31749 | 0 | phosphorylation | up-regulates activity | 0.2 | Akt modulated the pathway by phosphorylating mevalonate diphosphate decarboxylase (MDD) at Ser96. These data suggest that Akt regulates Rac1 activity by directly phosphorylating MDD at Ser96, which augments Rac1 geranylgeranylation. | SIGNOR-265891 |
Q13153 | Q70Z35 | 1 | phosphorylation | down-regulates activity | 0.367 | P21-activated Kinases (PAKs) Mediate the Phosphorylation of PREX2 Protein to Initiate Feedback Inhibition of Rac1 GTPase. PAK-mediated phosphorylation of PREX2 reduced GEF activity toward Rac1 by inhibiting PREX2 binding to PIP3 and Gβγ. | SIGNOR-277181 |
Q02127 | P01106 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.346 | PPAT, catalyzing the first step of purine synthesis, and DHODH, an enzyme generating uridine in the middle of the pyrimidine synthesis pathway, were validated as direct c-MYC target genes by all criteria. | SIGNOR-267382 |
P27361 | P35228 | 1 | phosphorylation | up-regulates | 0.354 | Erk phosphorylated inos on ser745. Mutation of ser745 to ala did not affect basal inos activity but eliminated inos phosphorylation and activation in response to b1r agonist. | SIGNOR-157711 |
Q14790 | Q5T447 | 0 | polyubiquitination | down-regulates activity | 0.336 | HECTD3, a new E3 ubiquitin ligase, interacts with caspase-8 death effector domains and ubiquitinates caspase-8 with K63-linked polyubiquitin chains that do not target caspase-8 for degradation but decrease the caspase-8 activation. HECTD3 ubiquitinates caspase-8 with K63-linked polyubiquitin chains at K215. | SIGNOR-272077 |
P60953 | Q96N96 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.718 | 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-260576 |
Q13148 | O14920 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.2 | IκB kinase phosphorylates cytoplasmic TDP-43 and promotes its proteasome degradation. Furthermore, we identified IKKβ-induced phosphorylation sites of TDP-43 and found that phosphorylation at Thr8 and Ser92 is important for the reduction of TDP-43 by IKK. | SIGNOR-277860 |
Q86V86 | Q13200 | 1 | 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 |
Q8TD16 | P49792 | 0 | relocalization | up-regulates quantity | 0.505 | We show that the dynein/dynactin adaptor BICD2 is specifically recruited to the NPC in G2phase through a direct interaction with the NPC componentRanBP2. | SIGNOR-259122 |
Q12879 | Q00535 | 0 | phosphorylation | up-regulates activity | 0.525 | Here, we demonstrate that cyclin dependent kinase-5 (Cdk5) associates with and phosphorylates NR2A subunits at Ser-1232 in vitro and in intact cells. Moreover, we show that roscovitine, a selective Cdk5 inhibitor, blocks both long-term potentiation induction and NMDA-evoked currents in rat CA1 hippocampal neurons. These results suggest that Cdk5 plays a key role in synaptic transmission and plasticity through its up-regulation of NMDARs. | SIGNOR-250666 |
P35222 | P16591 | 0 | phosphorylation | down-regulates activity | 0.72 | Interaction of beta-catenin with alpha-catenin is regulated by the phosphorylation of beta-catenin Tyr-142. This residue can be phosphorylated in vitro by Fer or Fyn tyrosine kinases. Transfection of these kinases to epithelial cells disrupted the association between both catenins. | SIGNOR-251131 |
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