IdA string | IdB string | labels int64 | mechanism string | effect string | score float64 | sentence string | signor_id string |
|---|---|---|---|---|---|---|---|
Q16236 | Q86TM6 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.2 | NRF2 is negatively regulated by three E3 ubiquitin ligase complexes: the KEAP1-CUL3-RBX1 complex, the β-TrCP-SKP1-CUL1-RBX1 complex, and HRD1. | SIGNOR-267360 |
Q14289 | P56945 | 1 | phosphorylation | up-regulates activity | 0.782 | Pyk2 knockdown also decreased p130Cas.|p130Cas and paxillin can be phosphorylated by Fak or Pyk2, and bind directly to these kinases. | SIGNOR-280100 |
P46734 | O43318 | 0 | phosphorylation | up-regulates activity | 0.505 | Taken together, our data indicate that TAK1 and TAB1 play a pivotal role as upstream signal transducers activating the MKK3-p38 MAPK signaling cascade that leads to the induction of type I collagen expression by TGF-beta(1). In addition, our findings also suggest that TAK1 has a novel function in regulation of the steady-state protein levels of MKK3 and p38 MAPK. | SIGNOR-42402 |
P05412 | Q8TD08 | 0 | phosphorylation | up-regulates | 0.428 | Up-regulation of c-jun mrna in cardiac myocytes requires the extracellular signal-regulated kinase cascade, but c-jun n-terminal kinases are required for efficient up-regulation of c-jun protein. these data suggest that erks, rather than jnks, are required for c- jun up-regulation. | SIGNOR-91375 |
O75688 | P37231 | 1 | dephosphorylation | up-regulates activity | 0.372 | Furthermore we show that PPM1B can directly dephosphorylate PPARgamma, both in intact cells and in vitro.|In addition PPM1B increases PPARγ-mediated transcription via dephosphorylation of Ser(112).|The serine/threonine phosphatase PPM1B (PP2Cbeta) selectively modulates PPARgamma activity. | SIGNOR-277073 |
P29350 | P21854 | 1 | dephosphorylation | down-regulates | 0.623 | Our work clearly identifies cd72 as both an shp-1 binding protein (figure 1,figure 2) and a direct substrate for shp-1 in vivo (figure 3). As tyrosine phosphorylation of cd72 strongly correlates with the ability of the bcr to deliver growth-inhibitory/apoptosis-inducing signals (figure 4), our results suggest that shp-1-catalyzed dephosphorylation of cd72 may antagonize these signals. | SIGNOR-60155 |
O14578 | Q96GD4 | 0 | phosphorylation | down-regulates activity | 0.283 | Finally, Aurora B phosphorylates CIT-K to control its localization and interaction with central spindle partners.|Together these findings indicate that CIT-K is an Aurora B substrate and that Aurora B phosphorylation at S699 dampens the association of CIT-K with KIF23 and the chromosomal passenger complex in order to reduce CIT-K accumulation at the spindle midzone in early cytokinesis. | SIGNOR-279140 |
Q16539 | Q06330 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.247 | P38 MAPK phosphorylates RBP-Jk at Thr339 by physical binding, which subsequently induces the degradation and ubiquitylation of the RBP-Jk protein. | SIGNOR-276403 |
Q99501 | P51955 | 0 | phosphorylation | up-regulates activity | 0.2 | Nek2A mediates G2/M phosphorylation of GAS2L1. GAS2L1 and its Ser352 phosphorylation are required for proper spindle organization and chromosome segregation. | SIGNOR-273683 |
O15530 | P36507 | 1 | phosphorylation | up-regulates | 0.256 | The identified pdk1 phosphorylation sites in mek1 and mek2 are ser222 and ser226, respectively, and are known to be essential for full activation. | SIGNOR-125176 |
Q13683 | P29692 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.2 | alpha7 Integrin Expression Is Negatively Regulated by deltaEF1 during Skeletal Myogenesis | SIGNOR-241773 |
O14757 | O60566 | 1 | phosphorylation | up-regulates activity | 0.447 | Nonetheless, in our experimental system a Chk1-dependent BubR1 phosphorylation was also observed after Noc treatment.|Possible requirement of Chk1 in U2OS cells to activate the mitotic spindle checkpoint proteins Mad2 and BubR1. | SIGNOR-280223 |
P63000 | Q6ZUM4 | 0 | gtpase-activating protein | down-regulates activity | 0.589 | 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-260482 |
P00519 | Q13148 | 1 | phosphorylation | up-regulates quantity | 0.2 | The phosphorylation of tyrosine 43 of TDP-43 by c-Abl led to increased TDP-43 levels in the cytoplasm and increased the formation of G3BP1-positive stress granules in SH-SY5Y cells. | SIGNOR-279135 |
Q92934 | Q15139 | 0 | phosphorylation | down-regulates | 0.307 | Pkcs phosphorylate bad under in vitro conditions, and the association of phosphorylated bad with pkc-mu or pkc-epsilon, as shown by immunoprecipitation, indicated direct involvement of pkcs in bad phosphorylation. To confirm these results, cells overexpressing pegfp-n1, wt-bad, or bad with a single site mutated (ser112ala;ser136ala;ser155ala), two sites mutated (ser(112/136)ala;ser(112/155)ala;ser(136/155)ala), or the triple mutant were tested. Igf-i protected completely against rapamycin-induced apoptosis in cells overexpressing wt-bad and mutants having either one or two sites of phosphorylation mutated | SIGNOR-163920 |
Q15349 | P32004 | 1 | phosphorylation | up-regulates activity | 0.515 | 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-248949 |
P46108 | P00519 | 0 | phosphorylation | down-regulates activity | 0.76 | Negative regulation of crk by abl is essential for the antitumorigenic effects of ephrinb2,similar pathways may operate for crkl | SIGNOR-175135 |
P15311 | O94804 | 0 | phosphorylation | up-regulates activity | 0.473 | Ezrin activation by LOK phosphorylation involves a PIP 2 -dependent wedge mechanism.|The specificity of kinases depends on local peptide consensus sequences, which in the case of ezrin phosphorylation by LOK involves the hydrophobic residue Y565 positioned -2 residues from T567. | SIGNOR-278204 |
Q13315 | Q00535 | 0 | phosphorylation | up-regulates | 0.415 | Here we show that cdk5 (cyclin-dependent kinase 5), activated by dna damage, directly phosphorylates atm at ser 794 in post-mitotic neurons. Phosphorylation at ser 794 precedes, and is required for, atm autophosphorylation at ser 1981, and activates atm kinase activity | SIGNOR-183454 |
P46937 | O95835 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.84 | We show that YAP is phosphorylated by Lats on Ser 381 in one of the HXRXXS motifs, and this phosphorylation provides the priming signal for CK1delta/epsilon to phosphorylate a phosphodegron in YAP. The phosphorylated phosphodegron recruits beta-TRCP, leading to YAP ubiquitination and degradation under conditions of elevated Hippo pathway activity, such as cell contact inhibition | SIGNOR-218034 |
Q02750 | P49841 | 1 | phosphorylation | up-regulates activity | 0.343 | In vitro kinase assay was carried out using a recombinant human active mek1 and we found that gsk-3beta was phosphorylated on tyr(216) by this kinase in a dose- and time-dependent manner. Further, the pretreatment of fibroblasts with u0126 inhibited serum-induced nuclear translocation of gsk-3beta. These results suggested that mek1/2 induces tyrosine phosphorylation of gsk-3beta and this cellular event might induce nuclear translocation of gsk-3beta. | SIGNOR-236622 |
Q9Y478 | Q8N122 | 1 | phosphorylation | down-regulates | 0.466 | Ampk in turn inactivates mtorc1 directly by phosphorylating raptor and indirectly by phosphorylating tsc2. | SIGNOR-173041 |
Q02447 | P07288 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | We characterized four Sp1/Sp3 binding sites in the proximal promoter of the PSA gene. In a luciferase assay, these sites contributed to the basal promoter activity in prostate cancer cells. In an electrophoretic mobility shift assay and chromatin immunoprecipitation assay, we confirmed that Sp1 and Sp3 bind to these sites. Overexpression of wild-type Sp1 and Sp3 further upregulated the promoter activity, whereas overexpression of the Sp1 dominant-negative form or addition of mithramycin A significantly reduced the promoter activity and the endogenous mRNA level of PSA. | SIGNOR-253665 |
Q969H0 | Q96KS0 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.349 | Mechanistically, we further show that FBW7, an E3 ligase complex component that is frequently downregulated in TNBC, negatively regulates EglN2 protein stability. | SIGNOR-261997 |
Q00610 | O14976 | 0 | phosphorylation | up-regulates activity | 0.857 | Clathrin heavy chain (CHC) was phosphorylated at T606 by its association partner cyclin G-associated kinase (GAK). This phosphorylation was required for proper cell proliferation and tumor growth of cells implanted into nude mice. | SIGNOR-275448 |
Q16539 | Q9UIG0 | 1 | phosphorylation | up-regulates | 0.2 | Moreover, this region (wac domain) was also phosphorylated by recombinant proteins of p38_? And jnk2_? But not by akt1 | SIGNOR-188160 |
P54274 | Q13315 | 0 | phosphorylation | up-regulates activity | 0.571 | Telomeric protein pin2/trf1 as an important atm target in response to double strand dna breaks. activated atm directly phosphorylated pin2/trf1 preferentially on the conserved ser(219)-gln site in vitro and in vivo. | SIGNOR-108419 |
P45983 | P19793 | 1 | phosphorylation | down-regulates activity | 0.464 | Under stress conditions, hyperphosphorylated by activated jnk on ser-56, ser-70, thr-82 and ser-260. These findings indicate that inflammation-mediated cell signaling leads to rapid and profound reductions in nuclear rxralpha levels, via a multistep, jnk-dependent mechanism involving ser260, nuclear export, and proteasomal degradation. | SIGNOR-145297 |
P42566 | Q93008 | 0 | deubiquitination | down-regulates activity | 0.271 | We identify the endocytic protein Eps15 as one of the critical substrates of USP9X | SIGNOR-245052 |
O95835 | O60285 | 0 | phosphorylation | down-regulates | 0.389 | Moreover, we show that nuak1 phosphorylates lats1 at s464 and this has a role in controlling its stabilitycells that constitutively express nuak1 suffer gross aneuploidies and show diminished expression of the genomic stability regulator lats1 | SIGNOR-161792 |
P45983 | Q01094 | 1 | phosphorylation | down-regulates activity | 0.277 | JNK1 phosphorylates E2F1 in vitro, and co-transfection of JNK1 reduces the DNA binding activity of E2F1 | SIGNOR-279218 |
P28482 | P23467 | 0 | dephosphorylation | down-regulates | 0.382 | Expression of rptp-beta inhibits both mek1/2 and erk1/2 phosphorylation. | SIGNOR-173000 |
Q12913 | P68400 | 0 | phosphorylation | up-regulates activity | 0.2 | CK2-dependent phosphorylation of DEP-1 T1318 promotes Y1320 phosphorylation and Src activation upon VEGF stimulation. | SIGNOR-277876 |
P12931 | Q13263 | 1 | phosphorylation | down-regulates activity | 0.2 | Among SFKs, Src strongly induces tyrosine phosphorylation of KAP1.|Immunostaining and chromatin fractionation show that Src and Lyn decrease the association of KAP1 with heterochromatin in a kinase activity-dependent manner. | SIGNOR-280137 |
Q13131 | Q12778 | 1 | phosphorylation | up-regulates | 0.446 | The energy sensor amp-activated protein kinase (ampk) has been shown to directly phosphorylate foxo factors at six regulatory sites that are distinct from the akt. | SIGNOR-157941 |
Q9C0C7 | P06493 | 0 | phosphorylation | up-regulates activity | 0.2 | CDK1 phosphorylates AMBRA1 at T1209 and S1223. |CDK1-mediated phosphorylation primes PLK1 phosphorylation on AMBRA1|In this work, we show that AMBRA1 is sequentially phosphorylated at mitosis by CDK1 and PLK1 on multiple sites. In particular, CDK1 is responsible for the early phosphorylations on T1209 and S1223, and it promotes additional late phosphorylation events by PLK1 on AMBRA1. Altogether, these phosphorylation events are critical for proper spindle function and orientation. Indeed, phosphorylated AMBRA1 can interact with NUMA1 and is responsible for NUMA1 proper localization at the cell cortex. Moreover, we observe that loss of AMBRA1 leads to PLK1 protein stabilization and to an increase in phospho-NUMA1 levels which, in turn, contributes to spindle orientation defects. | SIGNOR-272968 |
Q7Z2Z1 | O14757 | 0 | phosphorylation | down-regulates activity | 0.432 | In principle, phosphorylation of Treslin by Chk1 may alter its conformation or directly affect its interactions with other proteins to preclude helicase activation.|The fact that the TRCT domain blocks the binding of Chk1 to Treslin suggests that Chk1 suppresses the initiating function of Treslin. | SIGNOR-278924 |
O15355 | Q93009 | 1 | dephosphorylation | down-regulates quantity by destabilization | 0.51 | We find that stabilization of Mdm2, and correspondingly p53 downregulation in unstressed cells, is accomplished by a specific isoform of USP7 (USP7S), which is phosphorylated at serine 18 by the protein kinase CK2. |After ionizing radiation, dephosphorylation of USP7S by the ATM-dependent protein phosphatase PPM1G leads to USP7S downregulation, followed by Mdm2 downregulation and accumulation of p53. | SIGNOR-276531 |
Q96KB5 | Q96S44 | 1 | phosphorylation | up-regulates activity | 0.418 | In this study, we provide evidence showing that TOPK promotes metastasis of colorectal carcinoma, which is mediated through its phosphorylation of PRPK at Ser250.|Therefore, we conclude that TOPK directly promotes metastasis of colorectal cancer by modulating PRPK. | SIGNOR-278236 |
P23219 | Q86UZ6 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | ZBTB46 acts as a transcriptional coactivator that binds to the promoter of prostaglandin-endoperoxide synthase 1 (PTGS1) and transcriptionally regulated PTGS1 levels. | SIGNOR-277991 |
P84243 | Q9UGL1 | 0 | demethylation | up-regulates activity | 0.2 | KDM5 subfamily is capable of removing tri‐ and di‐ methyl marks from lysine 4 on histone H3 (H3K4). Depending on the methylation site, its effect on transcription can be either activating or repressing. | SIGNOR-264304 |
Q12923 | P04626 | 1 | dephosphorylation | down-regulates activity | 0.332 | Since a previous report showed PTPN13 may dephosphorylate ErbB2 directly, we also examined levels of phospho-ErbB2 (tyr 1248), and we also observed a small effect in the presence of wild-type PTPN13 (XREF_FIG).|The fact that both ErbB2 and H-RasV12 were potentiated by PTPN13 loss and PTPN13 inhibited MAP kinase signaling downstream of multiple oncogenes (ErbB2, EGFR, H-RasV12), suggest that the phosphatase target that inhibits MAP kinase signaling may not only be limited to ErbB2 tyrosine 1248. | SIGNOR-277087 |
P48729 | Q9Y4G8 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Here, we report that in response to factors that promote cell motility, the Rap guanine exchange factor RAPGEF2 is rapidly phosphorylated by I-kappa-B-kinase-β and casein kinase-1α and consequently degraded by the proteasome via the SCF(βTrCP) ubiquitin ligase. | SIGNOR-276604 |
Q5JTZ9 | P18848 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.244 | 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-269415 |
Q8N6D2 | P27449 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.466 | The data indicated that RNF182 targeted ATP6V0C for degradation by the ubiquitin-proteosome pathway. | SIGNOR-271771 |
P29353 | P36888 | 0 | phosphorylation | up-regulates activity | 0.446 | Intracellular FLT3 signaling involves tyrosine phosphorylation of several cytoplasmic proteins including SHC. We have found that upon FLT3 activation SHC phosphorylation occurs at tyrosine 239/240 and 313. | SIGNOR-251147 |
P10275 | P11309 | 0 | phosphorylation | up-regulates activity | 0.381 | PIM1 phosphorylates the AR and 14-3-3 ζ and coordinates their interaction. PIM1 phosphorylation of the AR and 14-3-3 ζ enhances their interaction and shifts their occupancy on chromatin, resulting in 14-3-3 ζ co-regulation of AR, likely by recruiting other AR co-regulators such as hnRNPK and TRIM28. | SIGNOR-277575 |
P19838 | Q5XPI4 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.397 | Here, we identify KPC1 as the Ub ligase (E3) that binds to the ankyrin repeats domain of p105, ubiquitinates it, and mediates its processing both under basal conditions and following signaling. | SIGNOR-272221 |
P02679 | P50281 | 0 | cleavage | down-regulates quantity by destabilization | 0.2 | Matrix metalloproteinases collagenase-2, macrophage elastase, collagenase-3, and membrane type 1-matrix metalloproteinase impair clotting by degradation of fibrinogen and factor XII| We have now investigated the role of collagenase-2 (MMP-8), macrophage elastase (MMP-12), collagenase-3 (MMP-13), and membrane type 1-matrix metalloproteinase (MT1-MMP, MMP-14) in the degradation of fibrinogen and Factor XII of the plasma clotting system.|MMP-14 27YVATRDN g-chain| 105XDAATLKSR g-chain | 92LTYNPDES g-chain |105LTTNIXEXL a-chain|433LVTSKGDKE a-chain| 117FXSANNRD a-chain | SIGNOR-263616 |
Q13131 | Q9NRC8 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Here, the authors show that energy stress induces an AMPK-dependent phosphorylation of Sirt7, which promotes its ubiquitin-independent degradation by REGγ, resulting in the down-regulation of rRNA transcription and cell survival.|These results strongly suggest that the phosphorylation status of SirT7 at T153 plays a crucial role in determining its subcellular distribution, degradation and binding to REGγ. | SIGNOR-275864 |
P00748 | P39900 | 0 | cleavage | down-regulates quantity by destabilization | 0.33 | 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-263611 |
P24941 | P01106 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.749 | Cdk2 phosphorylates c-Myc at Ser62 to suppress its ubiquitination modification/degradation, resulting in enhanced stability of c-Myc [ xref ]. | SIGNOR-279808 |
P01308 | P52945 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.643 | 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-255541 |
P29376 | Q9HCU5 | 1 | phosphorylation | down-regulates activity | 0.2 | Furthermore, we show that LTK interacts with and phosphorylates Sec12. Expression of a phosphoablating mutant of Sec12 reduces the efficiency of ER export. Thus, LTK-to-Sec12 signaling represents the first example of an ER-resident signaling module with the potential to regulate proteostasis.Altogether, we propose that Sec12 is phosphorylated in a manner dependent on LTK and that this phosphorylation affects ERES function. | SIGNOR-273650 |
P06493 | P05783 | 1 | phosphorylation | up-regulates | 0.338 | We identified k18 ser33 as an interphase phosphorylation site, which increases its phosphorylation during mitosis in cultured cells and regenerating liver, and as an in vitro cdc2 kinase phosphorylation site. K18 ser33 phosphorylation dictates binding to 14_3_3 proteins | SIGNOR-55994 |
Q13315 | Q15797 | 1 | phosphorylation | up-regulates | 0.2 | On genotoxic stress, atm phosphorylates bmps-activated smad1 in the nucleus on s239, which disrupts smad1 interaction with protein phosphatase ppm1a, leading to enhanced activation and upregulation of smad1. | SIGNOR-197533 |
P35637 | O00571 | 1 | relocalization | down-regulates activity | 0.256 | We found that ALS mutants of FUS co-localized with Caprin-1, DDX3X, and DHX9 in cytoplasmic inclusions that could lead to the mis-regulation of their respective pathways, providing further clues to the mechanism of ALS pathogenesis.|FUS interacting proteins were sequestered into the cytoplasmic mutant FUS inclusions that could lead to their mis-regulation or loss of function, contributing to ALS pathogenesis. | We also demonstrated the co-localization of DHX9, DDX3X and Caprin-1 with cytoplasmic EGFP-P525L mutant FUS inclusions in primary cortical neurons | SIGNOR-262811 |
Q5BJF6 | P06493 | 0 | phosphorylation | up-regulates activity | 0.543 | Phosphorylation of hCenexin1 at S796 is critical for the hCenexin1-Plk1 interaction.Here we show that a splice variant of hODF2 called hCenexin1, but not hODF2 itself, efficiently localizes to somatic centrosomes via a variant-specific C-terminal extension and recruits Plk1 through a Cdc2-dependent phospho-S796 motif within the extension. This interaction and Plk1 activity were important for proper recruitment of pericentrin and gamma-tubulin, and, ultimately, for formation of normal bipolar spindles. | SIGNOR-273584 |
Q13237 | P49841 | 1 | phosphorylation | down-regulates activity | 0.258 | These data indicate that hypertrophic differentiation of growth plate chondrocytes during skeletal growth is promoted by phosphorylation and inactivation of GSK-3beta by cGKII. | SIGNOR-280095 |
Q12933 | O43318 | 1 | ubiquitination | up-regulates activity | 0.597 | Tumor necrosis factor receptor-associated factors 2 and 6 (traf2 and -6) act as the ubiquitin e3 ligases to mediate lys63-linked tak1 polyubiquitination at the lys158 residue in vivo and in vitro. Lys(63)-linked TAK1 polyubiquitination at the Lys(158) residue is required for TAK1-mediated IKK complex recruitment. | SIGNOR-162638 |
Q9Y5B0 | P30291 | 1 | dephosphorylation | up-regulates activity | 0.382 | At mitosis exit, Fcp1 promoted inhibitory Cdk1 phosphorylation by dephosphorylating Wee1, and ubiquitin dependent cyclin B degradation by dephosphorylating Cdc20 and USP44.|This lead us to hypothesize that, during prolonged mitosis in AMCDs treated cancer cells, progressive Fcp1 induced Wee1 reactivation might lead to progressive loss of Cdk1 activity that weakens the SAC to a point in which the mitotic state could not be sustained . | SIGNOR-277142 |
Q13428 | P68400 | 0 | phosphorylation | up-regulates activity | 0.305 | Phosphorylated Thr 210 in Treacle is the major interaction site for NBS1|A purified GST fragment of this region was efficiently phosphorylated by CK2 in vitro (Supplementary Fig. 4; T-2) and this fragment pulled down the MRN complex from Hela nuclear extracts only when previously phosphorylated by CK2 | SIGNOR-265086 |
Q8TEA8 | O00311 | 0 | phosphorylation | up-regulates activity | 0.321 | Here we show that DUE-B is de-phosphorylated in M phase and phosphorylated in G1/S phase. Phosphorylated DUE-B forms homodimers, whereas de-phosphorylated DUE-B interacts with the Mcm2–7 complex and aminoacyl-tRNA synthetases. We find that CKII can prime DUE-B for Cdc7 phosphorylation. Confirming the importance of DUE-B phosphorylation in replication initiation, a C-terminal Ser/Thr to Ala mutant blocks Cdc45 and RPA loading on sperm chromatin and inhibits DNA replication. DUE-B C-terminal phosphorylation sites (serine 179, 181, 182, 194, 196, 197, 204, 205, and threonine 187) were mutated to unphosphorylatable alanine (DUE-B(S/T)-A) or phosphomimic aspartic acid (DUE-B(S/T)-D). | SIGNOR-273967 |
Q9UMX1 | P17612 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.467 | We report that Sufu is phosphorylated at Ser-342 and Ser-346 by GSK3? and cAMP-dependent protein kinase A (PKA), respectively, and phosphorylation at this dual site stabilizes Sufu against Shh signaling-induced degradation | SIGNOR-172003 |
P46734 | Q99683 | 0 | phosphorylation | up-regulates activity | 0.599 | Ask1 is a member of a mapkkk family and functions as an upstream kinase engaged in c-jun nh2-terminal kinase (jnk)/p38 signaling via the phosphorylation and activation of mapkks, such as mkk3, -4, -6, and -7 | SIGNOR-161763 |
Q03468 | P38398 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.441 | BRCA1 polyubiquitinates CSB and this polyubiquitination and subsequent degradation of CSB occur following UV irradiation, even in the absence of Cockayne syndrome A (CSA) protein. | SIGNOR-272754 |
Q8N3J5 | P12694 | 1 | dephosphorylation | up-regulates activity | 0.783 | BCKD is inhibited by phosphorylation of its E1alpha subunit at Ser293, which is catalyzed by BCKD kinase. During BCAA excess, phosphorylated Ser293 (pSer293) becomes dephosphorylated through the concerted inhibition of BCKD kinase and the activity of an unknown intramitochondrial phosphatase. Using unbiased, proteomic approaches, we have found that a mitochondrial-targeted phosphatase, PP2Cm, specifically binds the BCKD complex and induces dephosphorylation of Ser293 in the presence of BCKD substrates | SIGNOR-248758 |
P23946 | P05305 | 1 | cleavage | up-regulates activity | 0.472 | 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-256356 |
Q7KZI7 | Q9BXM7 | 1 | phosphorylation | up-regulates activity | 0.367 | MARK2 phosphorylated and activated the cleaved form of PINK1 (DeltaN-PINK1 | SIGNOR-278975 |
P60953 | P35125 | 1 | relocalization | up-regulates | 0.359 | In quiescent cells, tre17 is localized to intracellular filamentous and punctate structures in the cytoplasm, folded in an inactive conformation. Upon growth factor addition, cdc42 and rac1 become activated and recruit tre17 to the plasma membrane. Stable membrane localization of tre17 also requires polymerized actin. This recruitment process leads to a conformational change in tre17, such that the n-terminal portion of the molecule further stimulates the accumulation of cortical actin. | SIGNOR-98935 |
P14921 | P01100 | 1 | transcriptional regulation | up-regulates quantity | 0.718 | Furthermore, the possible involvement of an Ets protein in the control of c-fos has interesting implications for proto-oncogene cooperation in cellular growth control. | SIGNOR-256495 |
Q92886 | Q15784 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.278 | Based on these results, we concluded that the transactivation of the NDRF gene by ngn1 is mediated through the E4 box, suggesting that the E4 box and its binding bHLH protein(s) may play an important role in the transcriptional regulation of the NDRF gene. | SIGNOR-266235 |
Q02156 | P43629 | 1 | phosphorylation | down-regulates | 0.2 | Functional studies of the wild-type receptor and serine/threonine mutants indicated that phosphorylation of ser(394) by protein kinase c slightly suppresses kir3dl1 inhibitory function, and reduces receptor internalization and turnover. | SIGNOR-158129 |
Q9BU19 | Q13131 | 0 | phosphorylation | down-regulates | 0.2 | Arebp is phosphorylated at ser(470) by ampk. Phosphorylation reduces the dna-binding activity of arebp. | SIGNOR-150590 |
P17612 | Q13526 | 1 | phosphorylation | down-regulates activity | 0.2 | Pka and pkc readily phosphorylated pin1 and its ww domain in summary, we have demonstrated that phosphorylation of the pin1 ww domain on ser16 regulates its ability to function as a pser/thr-binding module. |To examine the importance of Ser16 of Pin1, it was mutated to Glu to mimic pSer, and the mutant Pin1S16E failed to bind mitotic phosphoproteins | SIGNOR-112164 |
P06239 | P09693 | 1 | phosphorylation | up-regulates activity | 0.56 | Last, we demonstrate directly that members of the CD3 complex, including the gamma, delta, and epsilon chains, as well as a putative zeta subunit, can be phosphorylated at tyrosine residues by the CD4/CD8.p56lck complex. | SIGNOR-259931 |
P15036 | Q9UQM7 | 0 | phosphorylation | down-regulates | 0.2 | Camkii caused ets-2 phosphorylation.Serine 246, 310, and 313 were the targets. Camkii to phosphorylates ets-2, thus altering ets-2 binding to its downstream promoters | SIGNOR-183596 |
Q9Y4D8 | P10275 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | We identified several E3 ligases as strong candidates responsible for AR and MYC protein loss as HECTD4, MYCBP2, and TRIM49. HECTD4 and MYCBP2 target AR and MYC for degradation while TRIM49 appears to promote AR and MYC stability. We have shown that these E3 ligases in turn are directly regulated by MYC. MYC in turn represses the expression of ubiquitin ligases, HECTD4 and MYCBP2 that promote AR and MYC protein degradation, further suppressing MYC and AR in a feed forward loop. | SIGNOR-267148 |
P45983 | O15350 | 1 | phosphorylation | up-regulates activity | 0.42 | Therefore, it is likely that p73 recruitment to the \u0394Np73 promoter is mediated by its JNK-1-dependent phosphorylation. | SIGNOR-279219 |
O15530 | Q9HBY8 | 1 | phosphorylation | up-regulates activity | 0.596 | SGK2 and SGK3 are activated in vitro by PDK1, albeit more slowly than SGK1, and their activation is accompanied by the phosphorylation of Thr(193) and Thr(253) respectively. The PDK1-catalysed phosphorylation and activation of SGK2 and SGK3, like SGK1, is greatly potentiated by mutating Ser(356) and Ser(419) respectively to Asp, these residues being equivalent to the C-terminal phosphorylation site of PKB. | SIGNOR-250277 |
P60953 | Q7Z5H3 | 0 | gtpase-activating protein | down-regulates activity | 0.543 | 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-260478 |
Q00536 | P17612 | 0 | phosphorylation | down-regulates | 0.314 | Here, we report that cdk16 is activated by membrane-associated cyclin y (ccny). Treatment of transfected human cells with the protein kinase a (pka) activator forskolin blocked, while kinase inhibition promoted, ccny-dependent targeting of cdk16-green fluorescent protein (gfp) to the cell membrane. Ccny binding to cdk16 required a region upstream of the kinase domain and was found to be inhibited by phosphorylation of serine 153, a potential pka phosphorylation site. | SIGNOR-191623 |
P06493 | O14746 | 1 | phosphorylation | up-regulates activity | 0.324 | Here we report that hTERT is phosphorylated at threonine 249 during mitosis by the serine/threonine kinase CDK1.These observations indicate that phosphorylation at threonine 249 regulates hTERT RdRP and contributes to cancer progression in a telomere independent manner. | SIGNOR-277517 |
P17612 | Q00059 | 1 | phosphorylation | up-regulates | 0.2 | Here, we demonstrate that tfam is phosphorylated within its hmg box 1 (hmg1) by camp-dependent protein kinase in mitochondria. Hmg1 phosphorylation impairs the ability of tfam to bind dna and to activate transcription. | SIGNOR-199934 |
Q9H5J4 | P36956 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.45 | These data demonstrated that Elovl-6 is regulated directly and primarily by SREBP-1c. | SIGNOR-267943 |
Q13237 | P04792 | 1 | phosphorylation | down-regulates | 0.2 | Purified pkg isoforms ia, ib, and ii all caused incorporation of phosphate in recombinant hsp27 at ser-78, ser-82, and thr-143, but not ser-15.These Studies indicate that hsp27 is a genuine substrate for pkg and that pkg may mediate inhibition of platelet aggregation through phosphorylation of hsp27 and subsequent prevent of actin polymerization | SIGNOR-186947 |
Q9H0D6 | P50750 | 0 | phosphorylation | up-regulates activity | 0.278 | Among the RNA processing factors phosphorylated by Cdk9 was the 5'-to-3' "torpedo" exoribonuclease Xrn2, required in transcription termination by Pol II, which we validated as a bona fide P-TEFb substrate in vivo and in vitro. Phosphorylation by Cdk9 or phosphomimetic substitution of its target residue, Thr439, enhanced enzymatic activity of Xrn2 on synthetic substrates in vitro. | SIGNOR-277194 |
Q9UQC2 | P27361 | 0 | phosphorylation | up-regulates | 0.617 | Phosphorylation of grb2-associated binder 2 on serine 623 by erk mapk regulates its association with the phosphatase shp-2 and decreases stat5 activation.We and others have demonstrated that il-2-induced tyrosine phosphorylation of gab2 and its interaction with its sh2 domain-containing partners, shp-2, p85 pi3k, and crkl (5, 26, 27). we report that pretreatment of kit 225 cells with the mek inhibitor u0126, strongly decreased the characteristic shift of gab2 in response to il-2 and increased gab2/shp-2 association, an effect that could be ascribed to erk phosphorylation of serine 623. | SIGNOR-128731 |
P46108 | P42684 | 0 | phosphorylation | down-regulates | 0.695 | Abl2 kinase activity toward crk leads to increased phosphorylation of crk, inhibiting this cytoskeletal regulator by promoting intramolecular over intermolecular associations. | SIGNOR-136958 |
P17252 | P29474 | 1 | phosphorylation | down-regulates activity | 0.3 | The phosphorylation of both S617 and S635 have also been shown to promote increased eNOS-derived NO release (Michell et al., 2002). The phosphorylaiton of S617 can be induced by PKA or Akt activity, and may serve to sensitize eNOS to calmodulin binding and modulate the phosphorylation of other eNOS sites | SIGNOR-251620 |
Q96GD4 | Q02241 | 1 | phosphorylation | down-regulates quantity | 0.727 | Furthermore, reduced turnover of regulatory phosphorylation on another Aurora B substrate MKlp1 was observed, suggesting that PP2A-B56\u03b3 and -\u03b5 play a general role opposing Aurora B at the central spindle.|In anaphase, the KIF4A-targeted pool of B56\u03b3 and -\u03b5 is ideally placed to counteract Aurora B phosphorylations on other central spindle proteins such as MKlp1. | SIGNOR-280192 |
P04637 | Q99986 | 0 | phosphorylation | up-regulates | 0.523 | Vrk1 phosphorylates murine p53 in threonine 18. This threonine is within the p53 hydrophobic loop (residues 13-23) required for the interaction of p53 with the cleft of its inhibitor mdm-2. | SIGNOR-81222 |
O00712 | P54756 | 1 | transcriptional regulation | up-regulates quantity | 0.2 | For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8) | SIGNOR-268902 |
P07949 | P78527 | 1 | phosphorylation | up-regulates activity | 0.27 | Phosphorylation of DNA-PKcs at s2056 is elevated in RET expressing cells and can be reduced by RET inhibition. | SIGNOR-279275 |
Q6UUV9 | Q13233 | 0 | phosphorylation | up-regulates | 0.321 | We report on the activation oftorc1through mekk1-mediated phosphorylation. | SIGNOR-180816 |
O43353 | Q13490 | 0 | polyubiquitination | up-regulates activity | 0.652 | 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-272712 |
Q15678 | P40763 | 1 | dephosphorylation | down-regulates activity | 0.271 | Moreover, dephosphorylation of STAT3 by PTPN14 might occur in the cytoplasm but not in nucleus.|The tyrosine phosphatase PTPN14 inhibits the activation of STAT3 in PEDV infected Vero cells. | SIGNOR-277088 |
Q13882 | P31749 | 1 | phosphorylation | up-regulates | 0.476 | Here we demonstrate that AKT is a direct substrate of PTK6 and that AKT tyrosine residues 315 and 326 are phosphorylated by PTK6. | SIGNOR-252622 |
O75460 | Q99683 | 0 | phosphorylation | up-regulates activity | 0.618 | ASK1 may directly phosphorylate IRE1\u03b1 at sites other than the IRE1\u03b1 autophosphorylation site. | SIGNOR-279213 |
P53350 | Q53EZ4 | 1 | phosphorylation | up-regulates | 0.553 | Upon mitotic entry, centrosome dissociation of cep55 is triggered by erk2/cdk1-dependent phosphorylation at s425 and s428. s425/428 phosphorylation is required for interaction with plk1, enabling phosphorylation of cep55 at s436...enabling it to relocate to the midbody to function in mitotic exit and cytokinesis. | SIGNOR-140898 |
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