IdA string | IdB string | labels int64 | mechanism string | effect string | score float64 | sentence string | signor_id string |
|---|---|---|---|---|---|---|---|
Q8N137 | P51955 | 0 | phosphorylation | down-regulates activity | 0.35 | The opposite outcomes in NEK2- and centrobin-depleted cells suggest that NEK2 antagonizes biological functions of centrobin.|These results suggest that NEK2 phosphorylates specific sites of centrobin, which are distinct from the PLK1 phosphorylation sites. | SIGNOR-279545 |
P63096 | P17948 | 0 | phosphorylation | up-regulates activity | 0.257 | RTKs directly phosphorylate Gαi on Y154, 155, and Y320. | SIGNOR-277230 |
P05787 | P18031 | 0 | dephosphorylation | down-regulates activity | 0.2 | Keratin 8 phospho-Tyr-267 is dephosphorylated by PTP1B and promotes insolubility and filament organization, as does the paralogous GFAP tyrosine. | SIGNOR-265495 |
O43524 | P67775 | 0 | dephosphorylation | up-regulates | 0.402 | Protein phosphatase 2a reactivates foxo3a through a dynamic interplay with 14-3-3 and aktpp2a-mediated dephosphorylation of t32/s253 is required for dissociation of 14-3-3, nuclear translocation, and transcriptional activation of foxo3a. | SIGNOR-163680 |
O43464 | P31751 | 0 | phosphorylation | down-regulates | 0.2 | Akt attenuation of the serine protease activity of htra2/omi through phosphorylation of serine 212 | SIGNOR-153327 |
O43379 | O14965 | 0 | phosphorylation | up-regulates activity | 0.352 | AURKA activity promotes WDR62 spindle localization|We next purified recombinant full-length WDR62 (GST–WDR62-FL) for in vitro kinase assays with active AURKA and demonstrated that WDR62 was a direct phosphorylation target of AURKA|In addition, our quantitative phosphoproteomic analysis of in-vitro-phosphorylated WDR62 identified S32 and S33 as significantly phosphorylated in the presence of active AURKA|Alanine replacement of the five putative phosphorylation sites (S32/S33/S49/T50/S52-AAAAA) of WDR62 attenuated interphase microtubule association induced by AURKA coexpression | SIGNOR-271713 |
Q99626 | Q07654 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.391 | The transcription of human TFF3 reporter genes was significantly up-regulated by the transient overexpression of CDX2 in COS-7 cells and AGS gastric cells. | SIGNOR-253967 |
Q13131 | P41235 | 1 | phosphorylation | down-regulates activity | 0.285 | Here we demonstrate that ampk directly phosphorylates hnf4 and represses its transcriptional activity. Ampk-mediated phosphorylation of hnf4 on serine 304 had a 2-fold effect | SIGNOR-101101 |
Q8IVM0 | P06239 | 0 | phosphorylation | down-regulates activity | 0.2 | We found that Ymer was considerably phosphorylated on tyrosine residues also via Src family kinases such as Lck. A luciferase reporter assay showed that mutation of tyrosines on Ymer (YmerY217/279/304F) results in loss of the inhibitory activity for NF-kappaB signaling. | SIGNOR-262855 |
Q9BUB5 | Q9NP80 | 1 | phosphorylation | up-regulates activity | 0.2 | Constitutively active MNK1 activates and phosphorylates iPLA2γ. Thus, complement-mediated activation of iPLA(2)γ is mediated via ERK and p38 pathways, and phosphorylation of Ser-511 and/or Ser-515 plays a key role in the catalytic activity and signaling of iPLA(2)γ. | SIGNOR-273677 |
P04637 | Q9BRQ8 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.503 | The p53 tumor suppressor protein induces cell cycle arrest or apoptosis in response to cellular stresses. We have identified PRG3 (p53-responsive gene 3), which is induced specifically under p53-dependent apoptotic conditions in human colon cancer cells, and encodes a novel polypeptide of 373 amino acids with a predicted molecular mass of 40.5 kDa. these results support the hypothesis that the expression of the PRG3 gene in cells undergoing p53‐dependent apoptosis involves direct activation of its promoter by p53. | SIGNOR-261808 |
Q92888 | P61586 | 1 | guanine nucleotide exchange factor | up-regulates activity | 0.831 | 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-260528 |
P41970 | Q16539 | 0 | phosphorylation | up-regulates | 0.379 | Tcf sap-1a is efficiently phosphorylated by p38 map kinase in vitro and in vivo on the homologous residues ser381 and ser387. Mutation of these sites to alanine severely reduces c-fos sre-dependent transcription mediated by sap-1a and p38 map kinase. | SIGNOR-47685 |
P02458 | P45452 | 0 | cleavage | down-regulates quantity by destabilization | 0.544 | Although it appears that MMP-1 and MMP-13 both cleave type II collagen initially at the same site, MMP-13 affects a secondary cleavage to produce a 1/4-size collagen fragment with an NH2 terminus three amino acids removed from the primary cleavage site.The present work has demonstrated expression of MMP-13 in human osteoarthritic cartilage and shown that MMP-13 has significant type II collagen degrading activity. | SIGNOR-256340 |
P15735 | P11217 | 1 | phosphorylation | up-regulates activity | 0.55 | It is well-characterized that GP is activated by PhK-mediated serine phosphorylation at Ser-15 | SIGNOR-267400 |
P32004 | Q15418 | 0 | phosphorylation | up-regulates activity | 0.506 | Western blot analysis demonstrated that the L1 kinase activity from PC12 cells that phosphorylated this site was co-eluted with the S6 kinase, p90(rsk). Moreover, S6 kinase activity and p90(rsk) immunoreactivity co-immunoprecipitate with L1 from brain, and metabolic labeling studies have demonstrated that Ser1152 is phosphorylated in vivo in the developing rat brain. | These data demonstrate that the membrane-proximal 15 amino acids of the cytoplasmic domain of L1 are important for neurite outgrowth on L1, and the interactions it mediates may be regulated by phosphorylation of Ser1152. | SIGNOR-248948 |
P37231 | P20393 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.277 | Mutations of the 5' or 3' half-sites of the response element totally abrogated PPARgamma binding and transcriptional activation, identifying this site as a novel type of functional PPARgamma response element. Finally, ectopic expression of Rev-Erbalpha in 3T3-L1 preadipocytes potentiated adipocyte differentiation induced by the PPARgamma ligand rosiglitazone. These results identify Rev-Erbalpha as a target gene of PPARgamma in adipose tissue and demonstrate a role for this nuclear receptor as a promoter of adipocyte differentiation. | SIGNOR-268022 |
P63279 | P58012 | 1 | sumoylation | up-regulates | 0.698 | Foxl2 is sumoylated by ubc9, and this ubc9-mediated sumoylation is essential to the transcriptional activity of foxl2 on the star promoter. / the sumoylation site was identified at lysine 25 of foxl2 | SIGNOR-187901 |
P43405 | P02730 | 1 | phosphorylation | up-regulates | 0.451 | Our findings suggest that, upon phosphorylation by p72syk, y8 and y21 act as docking sites for the sh2 domain of lyn, which subsequently phosphorylates band 3 at additional secondary sites. | SIGNOR-80792 |
P06241 | Q03135 | 1 | phosphorylation | down-regulates activity | 0.721 | Caveolin-1 is phosphorylated on tyr(14) in response to both oxidative and hyperosmotic stress. In the present paper, we show that this phosphorylation requires activation of the src family kinase fyn.Therefore, | SIGNOR-118003 |
Q9H2X6 | Q13363 | 1 | phosphorylation | down-regulates | 0.47 | Homeodomain-interacting protein kinase-2 mediates ctbp phosphorylation and degradation in uv-triggered apoptosishipk2 phosphorylates ctbp at ser-422 | SIGNOR-134040 |
P14859 | P78527 | 0 | phosphorylation | down-regulates | 0.33 | Through a similar strategy, t226 and s232 were characterized as the dna-pk phosphorylation sites | SIGNOR-53258 |
Q06187 | P43405 | 0 | phosphorylation | up-regulates activity | 0.589 | We have demonstrated that BLNK mediates Syk-dependent Btk activation. In a reconstitution cell system, coexpression of BLNK allows Syk to phosphorylate Btk on its tyrosine 551, leading to the enhancement of Btk activity. | SIGNOR-247586 |
P10276 | P78396 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.244 | RARα is involved in the regulation of cyclin A1. Further studies using ligands selective for various retinoic acid receptors suggested that cyclin A1 expression is negatively regulated by activated RARα. | SIGNOR-249636 |
O15534 | P04150 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.268 | GR directly regulates transcription of circadian clock components in mouse and human primary MSCs. Per2, E4bp4, Per1, and Timeless rapidly respond to glucocorticoid stimulation. Primary glucocorticoid receptor (GR) target genes are those at which GR occupies a nearby genomic glucocorticoid response element (GRE) and regulates target gene transcription | SIGNOR-268050 |
Q92934 | O14920 | 0 | phosphorylation | down-regulates | 0.263 | Ikk phosphorylates bad at serine-26 (ser26) and primes it for inactivation. | SIGNOR-192614 |
P53778 | Q6JBY9 | 1 | phosphorylation | down-regulates activity | 0.504 | Peptide T2 was sequenced and shown to comprise residues 79–112 of CapZIP, phosphorylated at Ser-108 (Figure 2B). The identity of peptide T1 is unknown. These experiments established that the SAPK3/p38γ substrate was CapZIP. Using this antibody, we showed by immunoblotting that bacterially expressed CapZIP was phosphorylated at Ser-108 by SAPK4/p38δ, JNK1α1 and ERK2 in vitro, as well as by SAPK3/p38γ (results not shown). An important clue to the function of CapZIP and its phosphorylation came from the finding that it binds to the actin-capping protein CapZ (Figure 7A), and that cellular stresses trigger the dissociation of these two proteins (Figure 7B).Such an effect is presumably lost when CapZIP is phosphorylated and dissociates from CapZ. | SIGNOR-263083 |
P55085 | P07477 | 0 | cleavage | up-regulates activity | 0.388 | Mass spectrometry studies of PAR2E predicted activation of PAR2 by trypsin through cleavage at the Arg36-Ser37 site, no effect of thrombin, and inactivation of the receptor by plasmin, calpain and leukocyte elastase, cathepsin G, and proteinase 3. | SIGNOR-263602 |
P78563 | Q9Y243 | 0 | phosphorylation | down-regulates activity | 0.2 | AKT-dependent phosphorylation of the adenosine deaminases ADAR-1 and -2 inhibits deaminase activity. Coimmunoprecipitation studies and in vitro kinase assays revealed that AKT-1, -2, and -3 interact with both ADAR1p110 and ADAR2 and phosphorylate these RNA editases. Using site-directed mutagenesis of suspected AKT phosphorylation sites, AKT was found to primarily phosphorylate ADAR1p110 and ADAR2 on T738 and T553, respectively | SIGNOR-276195 |
Q96A00 | Q15139 | 0 | phosphorylation | up-regulates activity | 0.2 | A major kinase for GPCR‐induced CPI‐17 phosphorylation is PKC which is activated by the PLCbeta‐produced signaling messenger diacylglycerol (DAG). It phosphorylates CPI‐17 at Thr38 residue that directly docks at the active site of MLCP, thereby inhibiting its activity and promoting an increase of phosphorylation of myosin and of other MLCP. | SIGNOR-249260 |
P15336 | Q16539 | 0 | phosphorylation | up-regulates | 0.793 | On the other hand, sapks such as jnks and p38 phosphorylate atf-2 at thr-69, thr-71, and ser-90 which lie close to the n-terminal transcriptional activation domain and stimulate itstrans-activating capacity our results indicate that atf-2 not only directly binds to smad3/4 hetero-oligomers but also that atf-2 is phosphorylated by tgf- signaling via tak1 and p38. | SIGNOR-65597 |
O75460 | Q5SGD2 | 0 | dephosphorylation | up-regulates activity | 0.309 | Overall, our study establishes that PP2Ce mediated IRE1 regulation in ER stress signaling is a potentially important molecular basis for its genetic contribution to metabolic syndrome.Lin et al. [36] have reported that different durations and composition of ER stress signaling pathways can dictate cell fate and the balance between survival and death.|Recombinant wildtype PP2Ce, but not a phosphatase-dead mutant (PP2Ce-D302A), effectively dephosphorylated the phosphor-Ser724 site of IRE1\u03b1 protein (p-IRE1\u03b1) (A). | SIGNOR-277074 |
Q03112 | P68400 | 0 | phosphorylation | up-regulates activity | 0.2 | We also identified EVI1 phosphorylation sites by MS analysis and showed that Ser538 and Ser858 can be phosphorylated and dephosphorylated by two EVI1 interactome proteins, casein kinase II and protein phosphatase-1α. Finally, mutations that impair EVI1 phosphorylation at these sites reduced EVI1 DNA binding through its C-terminal zinc finger domain and induced cancer cell proliferation. | SIGNOR-273427 |
P31040 | P12931 | 0 | phosphorylation | up-regulates activity | 0.267 | Phosphorylation-site analysis selects c-Src targets, including NDUFV2 (NADH dehydrogenase [ubiquinone] flavoprotein 2) at Tyr(193) of respiratory complex I and SDHA (succinate dehydrogenase A) at Tyr(215) of complex II. The phosphorylation of these sites by c-Src is supported by an in vivo assay using cells expressing their phosphorylation-defective mutants. | SIGNOR-276420 |
P13051 | P49840 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Here we show that glycogen synthase kinase 3 (GSK-3) interacts with and phosphorylates UNG2 at Thr60 and that Thr60 phosphorylation requires a Ser64 priming phosphorylation event.|phosphorylation of Thr60 and Ser64 creates a cyclin E/c-Myc-like phosphodegron that promotes polyubiquitylation and proteasome-mediated degradation | SIGNOR-264886 |
P06730 | Q13490 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.401 | We found that endogenous eIF4E was ubiquitinated by cIAP1, and ubiquitinated eIF4E accumulated upon MG132 treatment. | SIGNOR-278741 |
P06127 | P05129 | 0 | phosphorylation | up-regulates | 0.341 | Cd5 is a good pkc substrate. Phosphorylation of cd5 is necessary for cd5-mediated lipid second messenger generation. | SIGNOR-85183 |
O14649 | P51812 | 0 | phosphorylation | up-regulates activity | 0.2 | The chaperone protein, 14-3-3, binds to a critical phosphorylated serine in the channel c termini of k2p3.1 and k2p9.1 (ser(393) and ser(373), respectively) and overcomes retention in the endoplasmic reticulum by ?COP. We sought to identify the kinase responsible for phosphorylation of the terminal serine in human and rat variants of k2p3.1 and k2p9.1. Adopting a bioinformatic approach, three candidate protein kinases were identified: camp-dependent protein kinase, ribosomal s6 kinase, and protein kinase c. | SIGNOR-172470 |
O14920 | Q9NQC7 | 1 | phosphorylation | down-regulates activity | 0.548 | Thus, serine 418 is phosphorylated in vivo.Cyld phosphorylation may serve as a mechanism to inactivate its traf2 deubiquitination activity. | SIGNOR-204716 |
P17706 | P42224 | 1 | dephosphorylation | down-regulates activity | 0.734 | Upon ligand binding, IL-2R , IL-6R or LeptinR , IFN-_R , IFN-_R and PRLR or growth hormone (GH) receptor associated JAKs become activated. These JAKs mediate phosphorylation of specific tyrosine residues and recruit STATs. Activated STATs are released from the receptor and translocate to the nucleus. PTP1B dephosphorylates JAK2, TYK2 and STAT5 . The 45-kDa form of TC-PTP was shown to dephosphorylate JAK1 and JAK3 as well as STAT1, STAT3 and STAT5. | SIGNOR-133279 |
Q86Y07 | Q9UHP3 | 1 | phosphorylation | down-regulates activity | 0.294 | Here, we report that USP25 is a novel TRiC interacting protein that is also phosphorylated by VRK2. USP25 catalyzed deubiquitination of the TRiC protein and stabilized the chaperonin, thereby reducing accumulation of misfolded polyglutamine protein aggregates. Notably, USP25 deubiquitinating activity was suppressed when VRK2 phosphorylated the Thr(680), Thr(727), and Ser(745) residues. | SIGNOR-273579 |
P42262 | P54829 | 0 | dephosphorylation | down-regulates activity | 0.412 | One study showed that stimulation of the metabotrophic glutamate receptor mGluR5 leads to a STEP mediated tyrosine dephosphorylation of GluA2 and internalization of GluA1 and GluA2, although the tyrosine residue on GluA2 that is dephosphorylated by STEP remains unidentified. | SIGNOR-277040 |
Q13882 | Q07666 | 1 | phosphorylation | up-regulates | 0.748 | Sik/brk is the first identified tyrosine kinase that can phosphorylate sam68 and regulate its activity within the nucleus, where it resides during most of the cell cycle | SIGNOR-80020 |
Q86Y13 | Q8IUE6 | 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-271758 |
P06493 | Q8TEM1 | 1 | phosphorylation | up-regulates activity | 0.549 | In vitro phosphorylation of GST fusion protein containing the carboxyl-terminal domain of gp210 by cyclin B-p34cdc2 protein kinase generates a phosphopeptide that comigrates with a mitosis-specific phosphopeptide. Ser1880 Is the Mitotic Phosphorylation Site of Gp210. | SIGNOR-262699 |
P12644 | P19838 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.2 | The effect of TNF-alpha on the Bmp4 promoter is mediated through NF-kB. | SIGNOR-266086 |
Q5VWQ8 | P01116 | 1 | gtpase-activating protein | down-regulates activity | 0.518 | The GAP domain of DAB2IP is homologous to other Ras-GAPs, such as GAP120 and neurofibromin (NF1), and can stimulate the GTPase activity of RAS proteins both in vitro and in cancer cell lines. DAB2IP is able to stimulate in vitro and in vivo the GTPase activity of RAS proteins (H-Ras, K-Ras, and N-Ras) facilitating GTP hydrolysis to GDP. | SIGNOR-254746 |
P17612 | P03372 | 1 | phosphorylation | down-regulates | 0.486 | Phosphorylation of human estrogen receptor alpha by protein kinase a regulates dimerizationeralpha is phosphorylated by protein kinase a (pka) on serine-236 within the dna binding domain. Mutation of serine-236 to glutamic acid prevents dna binding by inhibiting dimerization by eralpha | SIGNOR-63984 |
P40337 | O14965 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.406 | Conversely, AURKA can phosphorylate VHL at serine 72, a priming phosphorylation for GSK3beta, which regulates VHL 's role in microtubule stability. | SIGNOR-279800 |
O15530 | O14920 | 1 | phosphorylation | up-regulates activity | 0.474 | We found that PDK1 directly phosphorylates IKKbeta at the Ser(181) residue in the activation loop, leading to NF-kappaB nuclear translocation and NF-kappaB-dependent anti-apoptotic gene expression. | SIGNOR-279088 |
P18848 | P41250 | 1 | 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-269426 |
Q6PEY2 | Q5SQI0 | 0 | acetylation | up-regulates quantity by stabilization | 0.267 | 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-272248 |
O94768 | P05129 | 0 | phosphorylation | down-regulates activity | 0.2 | These results suggest that phosphorylation of Ser350 plays an essential role in regulating translocation of DRAK2 to the nucleus from the cytoplasm, possibly by affecting the activity of the NLS. Ectopic expression of PKC-gamma induced cytoplasmic localization of DRAK2 and PKC-gamma phosphorylated Ser350 flanking the NLS. | SIGNOR-263178 |
P56945 | P12931 | 0 | phosphorylation | up-regulates activity | 0.803 | Cas is a member of the focal adhesion complex. Phosphorylation of Cas by Src is an important event leading to cell transformation. Using mass spectrometry, we have mapped 11 sites in Cas that are phosphorylated by Src. These sites are all located between residues 132 and 414 of CasBased on these data, 11 tyrosine residues (132, 169, 183, 196, 238, 253, 271, 291, 301, 391, and 414) were phosphorylated by Src|the biological activity of Cas depends on its phosphorylation by Src (16–18). After phosphorylation, Cas associates with a number of proteins, including Crk, Src, phosphatidylinositol 3-kinase, Nck, and phospholipase Cgamma, via SH2 binding motifs | SIGNOR-246393 |
Q5D1E8 | P17542 | 1 | post transcriptional regulation | up-regulates quantity | 0.2 | Here, we show that Regnase-1 regulates self-renewal of HSPCs through modulating the stability of Gata2 and Tal1 mRNA | SIGNOR-259944 |
P23469 | P28482 | 1 | dephosphorylation | down-regulates activity | 0.39 | The effect of PTP epsilon on ERKs is at least in part indirect because phosphorylation of the threonine residue in the ERK activation loop is reduced in the presence of PTP epsilon. Nonetheless, PTP epsilon is present in a molecular complex with ERK, providing PTP epsilon with opportunity to act on ERK proteins also directly. We conclude that PTP epsilon is a physiological inhibitor of ERK signaling|These enzymes are joined by the large family of dual-specificity phosphatases, which are structurally similar to tyrosine phosphatases but which can dephosphorylate both residues of the activation loop | SIGNOR-248448 |
Q9Y2R2 | Q96P20 | 1 | dephosphorylation | up-regulates activity | 0.356 | Further, this explains how loss of PTPN22 and subsequent enhanced NLRP3 phosphorylation mediate a decrease in NLRP3 inflammasome activation.|Upon NLRP3 activation, PTPN22 dephosphorylates NLRP3 and thereby protects it from degradation, allowing robust inflammasome activity (summarized in Fig.S6). | SIGNOR-277056 |
P07948 | Q13568 | 1 | 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 |
O43353 | Q13489 | 0 | polyubiquitination | up-regulates activity | 0.787 | CIAP1/2 are direct E3 ligases conjugating diverse types of ubiquitin chains to receptor interacting proteins kinases 1 to 4 (RIP1-4).Together, our results demonstrate that depleting cIAP1/2 inhibits RIP1-4 mediated NF-kB activation without affecting RIP auto-phosphorylation. | SIGNOR-272715 |
P17252 | P49802 | 1 | phosphorylation | down-regulates activity | 0.364 | TNF-α rapidly increases the concentration of functionally active RGS7 protein through two mechanisms. TNF-induced dephosphorylation of serine 434 liberates RGS7 from 14-3-3 binding and inhibition. , PKC α catalyzes the incorporation of phosphate into a truncation of RGS7 fused to maltose-binding protein (MBP.RGS7315–469). | SIGNOR-263165 |
P49841 | Q9UPN3 | 1 | phosphorylation | down-regulates activity | 0.435 | We discovered that GSK3β, a kinase inhibited by Wnt signaling, directly phosphorylates ACF7, a > 500 kDa microtubule-actin crosslinking protein abundant in hair follicle stem cells (HF-SCs). We map ACF7's GSK3β sites to the microtubule-binding domain and show that phosphorylation uncouples ACF7 from microtubules. | SIGNOR-264428 |
P14138 | P23946 | 0 | cleavage | up-regulates activity | 0.374 | Chymase from human mast cells selectively cleaved big endothelins (ETs) at the Tyr31-Gly32 bond and produced novel trachea-constricting 31-amino acid-length endothelins, ETs(1-31), without any further degradation products. | SIGNOR-256355 |
P04083 | P05771 | 0 | phosphorylation | up-regulates | 0.2 | The authors identified several phosphorylated residues by a combination of peptide mapping and sequence analysis and showed that recombinant pp60c-src phosphorylates annexin a1 near its amino terminus, at tyrosine 21 (tyr21). Also polyoma virus middle t/pp60c-src complex, recombinant pp50v-abl, and the egf receptor/kinase phosphorylated the same tyrosine residue. It was also shown that serine 27 residue of anxa1 is the primary site phosphorylated by protein kinase c (pkc). In the same study, the threonine 41 residue has been identified as a pkc substrate as well. The adenosine cyclic 3_,5_-phosphate dependent protein kinase a (pka) phosphorylates anxa1 in its carboxyl-terminal core at the threonine 216 residue (thr216) [2].The phosphorylation of serine 27 is essential for annexin a1 membrane localization. | SIGNOR-202784 |
Q2Q1W2 | P17612 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.2 | These observations suggested that LINK-A expression potentially inhibits PKA phosphorylation/activity and PKA-mediated phosphorylation of TRIM71 at Ser3. | SIGNOR-277454 |
P20749 | P49840 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.392 | In this report, we show that BCL-3 is a substrate for the protein kinase GSK3 and that GSK3-mediated BCL-3 phosphorylation, which is inhibited by Akt activation, targets its degradation through the proteasome pathway. | SIGNOR-276011 |
P10636 | O95155 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.2 | Ubiquitination and degradation of Tau by UBE4B and STUB1 in mammalian neuroblastoma cells. | SIGNOR-278682 |
Q05516 | Q8WXG1 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Promoter regions from the PLZF-regulated transcripts Rsad2 and Ifit2 were fused to luciferase and activity was measured after IFN treatment. Overexpression of PLZF in RCC1 or ACHN cells produced a dose-dependent induction of the reporter promoters. | SIGNOR-261023 |
P53778 | P10636 | 1 | phosphorylation | down-regulates activity | 0.525 | Phosphorylation of tau by SAPK3 and SAPK4 markedly reduced the ability of tau to promote microtubule assembly. SAPK3 (also called ERK6 and p38) and SAPK4 phosphorylate recombinant tau protein at multiple Ser/Thr-Pro sites that are hyperphosphorylated in PHF-tau, with SAPK4 and SAPK3 being the most effective. | SIGNOR-250087 |
P49841 | O75030 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.435 | We also show that the MITF protein was stabilized by Wnt signaling, through the novel C-terminal GSK3 phosphorylations identified here. | SIGNOR-276476 |
P12931 | Q14693 | 1 | phosphorylation | up-regulates activity | 0.2 | Obesity-associated microenvironmental factors and other Src-activating growth factors, including the epidermal growth factor, activate Src and promote Src-mediated lipin-1 phosphorylation on Tyr398, Tyr413 and Tyr795 residues. The tyrosine phosphorylation of lipin-1 markedly increases its PAP activity, accelerating the synthesis of glycerophospholipids and triglyceride. | SIGNOR-277291 |
Q92574 | O14920 | 0 | phosphorylation | down-regulates | 0.642 | Here we show that ikkbeta, a major downstream kinase in the tnfalpha signaling pathway, physically interacts with and phosphorylates tsc1 at ser487 and ser511, resulting in suppression of tsc1phosphorylation of tsc2 (by akt and erk;refs. 28, 29) and tsc1(by ikkbeta;ref. 30) results in the disruption of the tsc1/2 complex, and thereby activates the oncogenic mtor signaling contributing to tumor progression. | SIGNOR-157296 |
O95831 | Q9P286 | 0 | phosphorylation | down-regulates activity | 0.2 | Our results show that PAK5 can phosphorylate Thr-281 of AIF, which is included in its NLS1 sequence.|These results suggested that PAK5 inhibited AIF from entering the nucleus through phosphorylation of AIF T281 site, thus inhibiting cell apoptosis. | SIGNOR-279085 |
Q9Y3E5 | Q15139 | 0 | phosphorylation | up-regulates | 0.3 | Overexpression of constitutively active pkd or pkd activation by treatment with phorbol 12-myristate 13-acetate results in phosphorylation of two serine residues (ser5 and ser87) in a form of bit1 that is confined to the cytoplasm and concomitantly increases the apoptotic activity of cytoplasmic bit1 | SIGNOR-180085 |
Q16649 | P04150 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.296 | GR directly regulates transcription of circadian clock components in mouse and human primary MSCs. Per2, E4bp4, Per1, and Timeless rapidly respond to glucocorticoid stimulation. Primary glucocorticoid receptor (GR) target genes are those at which GR occupies a nearby genomic glucocorticoid response element (GRE) and regulates target gene transcription | SIGNOR-268051 |
Q96J02 | Q8NFZ5 | 1 | ubiquitination | down-regulates | 0.268 | Here we show that tnfa-mediated jnk activation accelerates turnover of the NF-kappaBinduced antiapoptotic protein c-flip, an inhibitor of caspase-8. This is not due to direct c-flip phosphorylation but depends on jnk-mediated phosphorylation and activationof the e3ubiquitin ligaseitch, which speci?cally Ubiquitinates c-flip and induces its proteasomal degradation. | SIGNOR-144453 |
Q9UQM7 | P35372 | 1 | phosphorylation | down-regulates | 0.2 | The decrease in mu-opioid receptor activity after chronic agonist exposure (1 microm [d-ala(2),n-mephe(4),gly-ol(5)]-enkephalin) is largely due to kinase-mediated phosphorylation of intracellular receptor domains. We have recently shown that the substitution of two putative ca(2+)/calmodulin-dependent protein kinase ii (camk ii) phosphorylation sites, s261 and s266, by alanines in the third intracellular loop of the rat mu-opioid receptor (rmor1) confers resistance to camk ii-induced receptor desensitization. | SIGNOR-79682 |
Q13315 | Q7LG56 | 1 | phosphorylation | up-regulates | 0.512 | Atm-mediated serine 72 phosphorylation stabilizes ribonucleotide reductase small subunit p53r2 protein against mdm2 to dna damage | SIGNOR-182423 |
P07711 | P0DTC2 | 1 | cleavage | up-regulates activity | 0.2 | SARS-2-S can use both CatB/L as well as TMPRSS2 for priming in these cell lines. | SIGNOR-260737 |
Q13541 | Q13315 | 0 | phosphorylation | down-regulates | 0.512 | Here we report that atm... phosphorylates 4e-bp1 at ser 111cells lacking atm kinase activity exhibit a significant decrease in the insulin-induced dissociation of 4e-bp1 from eif-4e. | SIGNOR-85619 |
Q15303 | Q96JA1 | 0 | ubiquitination | down-regulates | 0.608 | We report upregulation of lrig1 transcript and protein upon egf stimulation, and physical association of the encoded protein with the four egfr orthologs of mammals. Upregulation of lrig1 is followed by enhanced ubiquitylation and degradation of egfr. The underlying mechanism involves recruitment of c-cbl, an e3 ubiquitin ligase that simultaneously ubiquitylates egfr and lrig1 and sorts them for degradation. | SIGNOR-139954 |
Q6ZN04 | O95149 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.556 | HOTAIR associates with E3 ubiquitin ligases bearing RNA-binding domains, Dzip3 and Mex3b, as well as with their respective ubiquitination substrates, Ataxin-1 and Snurportin-1. In this manner, HOTAIR facilitates the ubiquitination of Ataxin-1 by Dzip3 and Snurportin-1 by Mex3b in cells and in vitro, and accelerates their degradation. | SIGNOR-272079 |
O60341 | P78347 | 0 | relocalization | up-regulates activity | 0.405 | Moreover, the inhibitory effect of TFII-I on transcription is mediated by its ability to recruit corepressor complexes, including histone deacetylase 3 (HDAC3) (25, 133), histone H3K4-specific demethylase LSD1 (48), and components of the polycomb repressor complex | SIGNOR-268540 |
O14757 | Q99638 | 1 | phosphorylation | up-regulates activity | 0.669 | Chk1 inhibition with small interfering RNA (siRNA) reduces Rad9A stabilization and accumulation.|In the case of DNA damage, an activated Chk1 phosphorylates Rad9A or other proteins (TLK1) as a feedback mechanism to prevent Rad9A (poly) ubiquitination and degradation. | SIGNOR-279503 |
Q15139 | O95863 | 1 | phosphorylation | down-regulates activity | 0.466 | Pkd1 phosphorylates ser(11) (s11) on transcription factor snail, a master emt regulator and repressor of e-cadherin expression, triggering nuclear export of snail via 14-3-3_ binding. Pkd1 regulates the expression of e-cadherin at the promoter level through direct phosphorylation of the transcriptional repressor snai1. Pkd1-mediated phosphorylation of snai1 occurs in the nucleus and generates a nuclear, inactive dna/snai1 complex that shows decreased interaction with its co-repressor ajuba. | SIGNOR-168537 |
Q13153 | Q00535 | 0 | phosphorylation | down-regulates activity | 0.54 | Our previous work revealed that the neuronal p35/Cdk5 kinase associates with Pak1 in a RacGTP-dependent manner, causing hyperphosphorylation and down-regulation of Pak1 kinase activity. We have now demonstrated direct phosphorylation of Pak1 on threonine 212 by the p35/Cdk5 kinase. | SIGNOR-249328 |
P46934-4 | P12931 | 0 | phosphorylation | up-regulates activity | 0.417 | Activation of c-Src by epidermal growth factor (EGF) also promoted tyrosine phosphorylation and enhanced the activity of NEDD4. | SIGNOR-276860 |
Q8N2H9 | O43353 | 1 | ubiquitination | up-regulates activity | 0.374 | Pellino3 directly bound to the kinase RIP2 and catalyzed its ubiquitination | SIGNOR-280452 |
P08047 | P62136 | 0 | dephosphorylation | down-regulates activity | 0.266 | Transcription factors Sp1 and Sp3 activate alpha-ENaC2 transcription through a GC-rich element (Sp1-binding site) in the promoter. Sp1 and Sp3 are essential for alpha-ENaC2 transcription in lung epithelial cells and that dephosphorylation of the Sp transcription factors by PP1 suppresses alpha-ENaC2 expression. | SIGNOR-251952 |
O14980 | Q15208 | 0 | phosphorylation | up-regulates activity | 0.2 | We further uncover that STK38 modulates XPO1 export activity by phosphorylating XPO1 on serine 1055, thus regulating its own nuclear exit. | SIGNOR-277483 |
Q9Y4B6 | Q99878 | 1 | phosphorylation | up-regulates activity | 0.2 | Here we report that VprBP possesses an intrinsic protein kinase activity and is capable of phosphorylating histone H2A on threonine 120 (H2AT120p) in a nucleosomal context. Functional studies reveal that H2AT120p by VprBP is sufficient to repress chromatin transcription. | SIGNOR-279884 |
O96013 | O14713 | 1 | phosphorylation | down-regulates activity | 0.2 | We further demonstrate that p21 activated kinase 4 (PAK4) can phosphorylate ICAP1 at Ser 10 both in vitro and in cultured cells, and that active PAK4 inhibits ICAP1 nuclear accumulation in a Ser-10-dependent manner.|We further demonstrate that p21-activated kinase 4 (PAK4) can phosphorylate ICAP1 at Ser-10 both in vitro and in cultured cells, and that active PAK4 inhibits ICAP1 nuclear accumulation in a Ser-10-dependent manner. | SIGNOR-280056 |
P01903 | Q8TCQ1 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | Two E3 ligases, MARCH I and MARCH VIII, have been shown to polyubiquitinate lysine residue 225 in the cytoplasmic tail of I-Abeta and HLA-DRbeta. We show that lysine residue 219 in the cytoplasmic tail of DRalpha is also subject to polyubiquitination. | SIGNOR-271412 |
P68400 | Q01105-2 | 1 | phosphorylation | down-regulates | 0.365 | Ckii-mediated phosphorylation at ser9 hinders nuclear import of set | SIGNOR-200798 |
Q09472 | P17861-2 | 1 | acetylation | up-regulates quantity by stabilization | 0.285 | P300 increases the acetylation and protein stability of XBP1s, and enhances its transcriptional activity, whereas SIRT1 deacetylates XBP1s and inhibits its transcriptional activity.. The mRNA encoding the active spliced form of XBP1 (XBP1s) is generated from the unspliced form by IRE1 (inositol-requiring enzyme 1) during the UPR. | SIGNOR-260429 |
Q13886 | P04150 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.321 | We show that in addition, DEX-bound GR directly promotes the expression of adipogenic TFs, including C/EBPβ, Klf5, Klf9, and C/EBPα | SIGNOR-256119 |
P54646 | O00763 | 1 | phosphorylation | down-regulates activity | 0.649 | The results suggest that the decrease in ACC activity during muscle contraction is caused by an increase in its phosphorylation, most probably due, at least in part, to activation of the alpha2 isoform of AMPK. | SIGNOR-250318 |
Q86YT6 | Q15154 | 1 | ubiquitination | down-regulates | 0.371 | We demonstrate that the E3 ubiquitin ligase MIB1 is a new component of centriolar satellites, which interacts with and ubiquitylates AZI1 and PCM1 and suppresses primary cilium formation. | SIGNOR-272878 |
Q14247 | P23470 | 0 | dephosphorylation | down-regulates activity | 0.2 | PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity. | SIGNOR-254696 |
P68400 | Q13829 | 1 | phosphorylation | up-regulates | 0.2 | It was demonstrated that ck2 could phosphorylate tnfaip1 in vitro and in vivo, which facilitated the distribution of tnfaip1 in nucleus and enhanced its interaction with pcna. It is suggested that the phosphorylation of tnfaip1 may be required for its functions. | SIGNOR-188849 |
P78527 | Q96T60 | 1 | phosphorylation | up-regulates | 0.649 | We demonstrate that pnkp is phosphorylated by the dna-dependent protein kinase (dna-pk) and ataxia-telangiectasia mutated (atm) in vitro. The major phosphorylation site for both kinases was serine 114, with serine 126 being a minor site. Purified pnkp protein with mutation of serines 114 and 126 had decreased dna kinase and dna phosphatase activities and reduced affinity for dna in vitro. | SIGNOR-176020 |
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