IdA string | IdB string | labels int64 | mechanism string | effect string | score float64 | sentence string | signor_id string |
|---|---|---|---|---|---|---|---|
Q00535 | Q8IXJ6 | 1 | phosphorylation | up-regulates activity | 0.397 | Cdk5 phosphorylation-induced SIRT2 nuclear translocation promotes the death of dopaminergic neurons in Parkinson's disease.|Moreover, the cyclin-dependent kinase 5 (Cdk5)-mediated phosphorylation of SIRT2 at the Ser331 and Ser335 sites appears to be necessary for such nuclear translocation. | SIGNOR-279684 |
P17677 | O95372 | 0 | deacetylation | down-regulates quantity by destabilization | 0.477 | Acyl-protein thioesterase 2 catalyzes the deacylation of peripheral membrane-associated GAP-43. In this work, we investigated the deacylation of growth-associated protein-43 (GAP-43), a dually acylated protein at cysteine residues 3 and 4. Thus, the results demonstrate that APT-2 is the protein thioesterase involved in the acylation/deacylation cycle operating in GAP-43 subcellular distribution.we demonstrated that the reduction in the protein level was abrogated when cells were also treated with proteasome inhibitors (chloroquine, MG132 and lactacystin) which strongly suggest that GAP-43 deacylation is an early and necessary step for its later ubiquitination and degradation by the proteasome. In addition, it also suggests that acyl-protein thioesterase levels not only regulate palmitate turnover but also global protein turnover of GAP-43. | SIGNOR-266768 |
Q02156 | P10636-2 | 1 | phosphorylation | down-regulates activity | 0.271 | We have studied the relationship between the phosphorylation oftau by several kinases (MARK, PKA, MAPK, GSK3) and its assembly into PHFs. By contrast, MARK and PKA phosphorylate several sites within the repeats (notably theKXGS motifs including Ser262, Ser324, and Ser356, plus Ser320); in addition PKA phosphorylates somesites in the flanking domains, notably Ser214. This type of phosphorylation strongly reduces tau’s affinityfor microtubules, and at the same time inhibits tau’s assembly into PHFs. | SIGNOR-275444 |
Q96HZ4 | P68400 | 0 | phosphorylation | up-regulates activity | 0.498 | Hes6 inhibits the interaction of Hes1 with its transcriptional corepressor Gro/TLE. Moreover, it promotes proteolytic degradation of Hes1. This effect is maximal when both Hes1 and Hes6 contain the WRPW motif and is reduced when Hes6 is mutated to eliminate a conserved site (Ser183) that can be phosphorylated by protein kinase CK2. | SIGNOR-250890 |
P42224 | Q13555 | 0 | phosphorylation | up-regulates activity | 0.507 | For maximal gene activation, S727 in the transcription activation domain of Stat1 also is inducibly phosphorylated by IFN-gamma. We previously purified a group of nuclear proteins that interact specifically with the Stat1 transcription activation domain. In this report, we identified one of them as the multifunctional Ca(2+)/calmodulin-dependent kinase (CaMK) II. We demonstrate that IFN-gamma mobilizes a Ca(2+) flux in cells and activates CaMKII. CaMKII can interact directly with Stat1 and phosphorylate Stat1 on S727 in vitro. Inhibition of Ca(2+) flux or CaMKII results in a lack of S727 phosphorylation and Stat1-dependent gene activation, suggesting in vivo phosphorylation of Stat1 S727 by CaMKII. | SIGNOR-250706 |
P49841 | P30291 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.329 | Serine 211 phosphorylation occurred under control conditions in the absence of CK1δ and in the presence of GSK3-β (Fig. 5, D and E). | SIGNOR-276632 |
Q16539 | P46734 | 0 | phosphorylation | up-regulates activity | 0.728 | Two human MAP kinase kinases (MKK3 and MKK4) were cloned that phosphorylate and activate p38 MAP kinase. | SIGNOR-232156 |
P06493 | P12830 | 1 | phosphorylation | up-regulates activity | 0.368 | We show that adequate accumulation of Cin8 and Kip1 requires inactivation of the anaphase promoting complex-activator Cdh1 through sequential phosphorylation by Cdk1 and polo kinase.|We show that adequate accumulation of Cin8 and Kip1 requires inactivation of the anaphase-promoting complex-activator Cdh1 through sequential phosphorylation by Cdk1 and polo kinase. | SIGNOR-280204 |
P03951 | P01008 | 0 | cleavage | down-regulates activity | 0.657 | Antithrombin (AT), a member of the serine protease inhibitor (SERPIN) superfamily, is a major circulating inhibitor of blood coagulation proteases such as factor (F) IIa (known as thrombin), FXa and, to a lesser extent, FIXa, FXIa and FXIIa. SERPINC1, which encodes AT in humans, is located on chromosome 1q25.1 | SIGNOR-264137 |
Q07820 | P06493 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.461 | Mcl-1 is phosphorylated at two sites in mitosis, ser64 and thr92. Phosphorylation of thr92 by cyclin-dependent kinase 1 (cdk1)-cyclin b1 initiates degradation of mcl-1 in cells arrested in mitosis by microtubule poisons. | SIGNOR-165867 |
Q9BXM7 | Q9Y2N7 | 1 | phosphorylation | down-regulates activity | 0.347 | Here we show that IPAS is a key molecule involved in neuronal cell death in Parkinson's disease (PD). IPAS was ubiquitinated by Parkin for proteasomal degradation following carbonyl cyanide m-chlorophenyl hydrazone treatment. Phosphorylation of IPAS at Thr12 by PTEN-induced putative kinase 1 (PINK1) was required for ubiquitination to occur. | SIGNOR-263090 |
P43378 | P04626 | 1 | dephosphorylation | down-regulates activity | 0.304 | Conversely, increasing expression of PTPN9 wild type (WT) inhibits tyrosyl phosphorylation of ErbB2 and EGFR.|Protein-tyrosine phosphatase PTPN9 negatively regulates ErbB2 and epidermal growth factor receptor signaling in breast cancer cells. | SIGNOR-277170 |
P10636 | Q5S007 | 0 | phosphorylation | down-regulates | 0.528 | Lrrk2 directly phosphorylates tubulin-associated tau, but not free tau;(iii) lrrk2 phosphorylates tau at thr181 as one of the target sites;. furthermore, we revealed that lrrk2-mediated phosphorylation of tau reduces its tubulin-binding ability. | SIGNOR-195756 |
Q15418 | P29317 | 1 | phosphorylation | up-regulates activity | 0.292 | These comprehensive analyses indicate that high matrix stiffness activates ERK/RSK1-mediated EPHA2 non-canonical signalling to induce LYN activation, TWIST1 nuclear localization, and cell invasion (Fig. 6M).|We next knocked down the most abundant RSK family members and found that loss of RSK1, but not RSK2 or RSK3, drastically inhibited EPHA2 S897 phosphorylation, prevented ECM stiffness-induced LYN activation and recruitment to EPHA2, and inhibited cell EMT and invasion induced by increasing rigidities (Fig. 6F\u2013I and S6H\u2013L). | SIGNOR-280113 |
P61586 | P36897 | 0 | null | up-regulates activity | 0.64 | Thus, TGF-_1 rapidly stimulates activity of both RhoA and Rac1 and this activation requires ALK5/T_RI kinase activity. | SIGNOR-227499 |
O15350 | P17252 | 0 | phosphorylation | up-regulates activity | 0.2 | Here, we report that p73 is able to induce cell cycle arrest independently of its amino-terminal transactivation domain, whereas this domain is crucial for p73 proapoptotic functions. its activity is regulated throughout the cell cycle and modified by protein kinase C-dependent phosphorylation at serine residue 388. | SIGNOR-276235 |
Q9Y625 | Q13469 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.354 | NFAT transcriptionally regulates GPC6 induction in breast cancer cells and binds to three regulatory elements in the GPC6 proximal promoter. Expression of GPC6 in response to NFAT signalling promotes invasive migration, whereas GPC6 silencing with shRNA (small-hairpin RNA) potently blocks this phenotype. | SIGNOR-264021 |
P03217 | O60603 | 1 | post transcriptional regulation | down-regulates quantity by repression | 0.2 | The RNA degradation induced by EBV BGLF5 can affect immunologically relevant proteins, including TLR2. Alkaline exonuclease involved in host shutoff, downregulates TLR2. | SIGNOR-266741 |
Q05682 | Q00535 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.341 | Together, these data demonstrate that phosphorylation of caldesmon on Ser527 by Cdk5 serves to down regulate its stability. | SIGNOR-280215 |
O14757 | Q9Y294 | 1 | phosphorylation | up-regulates activity | 0.414 | Chk1 activated by ataxia telangiectasia mutated (ATM) kinase on DNA breaks in G1 promotes NHEJ through direct phosphorylation of ASF1A at Ser-166. ASF1A phosphorylated at Ser-166 interacts with the repair protein MDC1 and thus enhances MDC1's interaction with ATM and the stable localization of ATM at DNA breaks. | SIGNOR-277620 |
P15514 | Q9Y222 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Notably, amphiregulin (Areg), thrombospondin-1 (Tsp-1), JunB, Egr1, adrenomedullin (Adm), Bcl-3 and methyl-CpG binding domain protein 1 (Mbd1) were downregulated in the lungs from Dmp1-null mice while Gas1 and Ect2 genes were upregulated. | SIGNOR-261582 |
Q9Y210 | P12931 | 0 | phosphorylation | up-regulates activity | 0.435 | TRPC6 Y31 and Y284 are phosphorylated by Src family kinase in isolated glomeruli. | SIGNOR-279659 |
Q13351 | O95600 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.25 | Here we report that Klf8 is repressed by Klf3 in vivo and is up-regulated by Klf1. Transcript analysis indicates that Klf8 has two promoters, both containing multiple CACCC elements. Transactivation assays and chromatin immunoprecipitation experiments indicate that Klf3 represses Klf8 directly and that Klf1 activates Klf8 directly. | SIGNOR-266050 |
P67775 | Q9Y243 | 1 | 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 |
Q04206 | Q05513 | 0 | phosphorylation | up-regulates | 0.555 | Rela is phosphorylated at: ser276 by the catalytic subunit of protein kinase a (pkac), msk1 and msk2; at ser311 by the atypical pkczeta; at ser468 by ikkbeta, ikkepsilon and glycogen-synthase kinase-3beta (gsk3beta); at ser529 by ck2; and at ser536 by ikkbeta, ikkalfa, ikkepsilon, nf-kb activating kinase (nak, also known as tank-binding kinase-1 tbk1)) and rsk1 (also known as p90 ribosomal protein s6 kinase (p90s6k) | SIGNOR-151432 |
O00311 | Q13148 | 1 | phosphorylation | up-regulates activity | 0.2 | Among these, CDC7 directly phosphorylates TDP-43 on serines 409 and 410 both in vitro and in vivo . | SIGNOR-278256 |
P54646 | Q15831 | 0 | phosphorylation | up-regulates | 0.627 | We demonstrated that lkb1 phosphorylates ampk on the activation loop threonine (thr172) within the catalytic subunit and activates ampk in vitro. Here, we have investigated whether lkb1 corresponds to the major ampkk activity present in cell extracts. Ampkk purified from rat liver corresponds to lkb1, and blocking lkb1 activity in cells abolishes ampk activation in response to different stimuli | SIGNOR-122725 |
Q14974 | Q19QW5 | 0 | relocalization | down-regulates activity | 0.2 | ORF6 also retained KPNB1 at the ER/Golgi membrane in complex with KPNA2. Deletion of the N terminus of KPNA2, which binds KPNB1, no longer retained KPNB1 at the ER/Golgi membrane in the presence of ORF6 and did not antagonize STAT1 nuclear import in response to IFN-beta | SIGNOR-260275 |
Q9H422 | Q00613 | 1 | phosphorylation | up-regulates activity | 0.335 | We show that Yak1 directly phosphorylates Hsf1 in vitro, leading to the increase in DNA binding activity of Hsf1. | SIGNOR-279054 |
P19784 | P52655 | 1 | phosphorylation | up-regulates activity | 0.374 | We now show that human TFIIA is phosphorylated in vivo on serine residues that are partially conserved between yeast and human TFIIA large subunits. Alanine substitution mutation of serine residues 316 and 321 in TFIIA alphabeta reduced TFIIA phosphorylation significantly in vivo. Additional alanine substitutions at serines 280 and 281 reduced phosphorylation to undetectable levels. Mutation of all four serine residues reduced the ability of TFIIA to stimulate transcription in transient transfection assays with various activators and promoters, indicating that TFIIA phosphorylation is required globally for optimal function. | SIGNOR-250996 |
Q96J02 | Q12778 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.258 | Mechanistically, Itch ubiquitinates Foxo1 for proteasomal degradation. | SIGNOR-278698 |
P78362 | Q99538 | 1 | phosphorylation | up-regulates activity | 0.2 | Here we report that serine-arginine protein kinase 2 (SRPK2) phosphorylates delta-secretase and enhances its enzymatic activity. SRPK2 phosphorylates serine 226 on delta-secretase and accelerates its autocatalytic cleavage, leading to its cytoplasmic translocation and escalated enzymatic activities. | SIGNOR-273569 |
Q99942 | Q86WV6 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | The ubiquitin ligase RNF5 regulates antiviral responses by mediating degradation of the adaptor protein MITA. RNF5 targeted MITA at Lys150 for ubiquitination and degradation after viral infection. | SIGNOR-271484 |
P17612 | Q07955 | 1 | phosphorylation | up-regulates | 0.2 | Here, we show that pka phosphorylates srsf1 on serine 119 in vitro. Phosphorylation of srsf1 on this site enhanced the rna binding capacity of srsf1 in vivo | SIGNOR-196397 |
Q04206 | P48729 | 0 | phosphorylation | up-regulates activity | 0.2 | These data strongly suggested that CKI phosphorylated Ser-316 of p65. Our data suggested that phosphorylation of p65 on Ser-316 controls the activity and function of NF-κB. Importantly, we found that phosphorylation at the novel Ser-316 site and other two known phosphorylation sites, Ser-529 and Ser-536, either individually or cooperatively, regulated distinct groups of NF-κB-dependent genes, suggesting the unique role of each individual phosphorylation site on NF-κB-dependent gene regulation. | SIGNOR-276916 |
Q96Q27 | P28482 | 0 | phosphorylation | up-regulates activity | 0.265 | Indeed, using mass spectrometry, we showed for the first time that ASB2a is phosphorylated and that phosphorylation of serine-323 (Ser-323) of ASB2a is crucial for the targeting of the actin-binding protein filamin A (FLNa) to degradation. |Moreover, inhibition of the extracellular signal-regulated kinases 1 and 2 (Erk1/2) activity reduced ASB2a-mediated FLNa degradation. | SIGNOR-272240 |
Q06187 | P31749 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.296 | The activated serine/threonine kinase Akt/protein kinase B (PKB) phosphorylated Btk on two sites prior to 14-3-3ζ binding. The interaction sites were mapped to phosphoserine pS51 in the pleckstrin homology domain and phosphothreonine pT495 in the kinase domain. | SIGNOR-276466 |
Q16829 | P28482 | 1 | dephosphorylation | down-regulates | 0.797 | Pyst2 preferentially dephosphorylates and inactivates p42 map kinase in vitro and in vivo | SIGNOR-60871 |
P23469 | P12931 | 1 | dephosphorylation | up-regulates activity | 0.402 | PTPepsilonM activated c-Src kinase probably by directly dephosphorylating phospho-Tyr527, a negative regulatory site of c-Src. | SIGNOR-238074 |
Q9UNN5 | P68400 | 0 | phosphorylation | down-regulates activity | 0.326 | We previously identified the Fas-associated factor FAF1 as an in vitro substrate of protein kinase CK2 and determined Ser289 and Ser291 as phosphorylation sites.|Therefore we assume that CK2‐mediated FAF1 phosphorylation influences the nuclear localization of FAF1 | it implies that the major function of FAF1 might not be in the cytoplasm as an interacting partner of Fas. | SIGNOR-250864 |
P36888 | Q9NTG7 | 1 | phosphorylation | down-regulates activity | 0.2 | We also hypothesize that, besides activating ACAT1 through Y407 phosphorylation (Fan et al., 2016), FLT3 might simultaneously phosphorylate and regulate SIRT3. Our mutational studies on all of the seven tyrosine sites of SIRT3 revealed that purified rFLT3 directly phosphorylated purified rSIRT3 in an in vitro kinase assay, leading to decreased SIRT3 deacetylase activity that was assessed by ability to deacetylate K413 of mIDH2 (Figure 4H, first three samples in left, middle, and right panels), whereas replacement of Y226 completely abolished inhibition of SIRT3 by FLT3 (Figure 4H, right). | SIGNOR-267631 |
Q00532 | P42772 | 1 | phosphorylation | up-regulates activity | 0.2 | We demonstrated that depletion of CDKL1 notably upregulated the protein expression of P15. P15 is shown to be a target of CDKL1 in CRC, either direct or indirect. | SIGNOR-273862 |
P56817 | P05067 | 1 | cleavage | up-regulates activity | 0.794 | Beta-secretase 1 (BACE1) cleaves the type-I transmembrane protein APP to form the N-terminus of Aβ. | SIGNOR-255480 |
Q00535 | O14936 | 1 | phosphorylation | up-regulates activity | 0.288 | Cdk5 promotes synaptogenesis by regulating the subcellular distribution of the MAGUK family member CASK.|We found that Cdk5 phosphorylates and regulates CASK distribution to membranes. | SIGNOR-280216 |
Q9H2X6 | Q8IUQ4 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.514 | Here we demonstrate that HIPK2 is an unstable protein that colocalizes and interacts with the E3 ubiquitin ligase Siah-1 in unstressed cells. Siah-1 knockdown increases HIPK2 stability and steady-state levels, whereas Siah-1 expression facilitates HIPK2 polyubiquitination, degradation and thereby inactivation. | SIGNOR-276166 |
Q13315 | Q8WYQ5 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.27 | Specifically, radiation-induced ATM-dependent phosphorylation of DGCR8 at serine 677 facilitates USP51 to bind, deubiquitinate, and stabilize DGCR8, which leads to the recruitment of DGCR8 and DGCR8's binding partner RNF168 to MDC1 and RNF8 at DSBs. | SIGNOR-277307 |
Q13433 | P43403 | 0 | phosphorylation | up-regulates activity | 0.2 | To summarize, upon TCR triggering Zap70 activates Zip6, which is localized to the IS, through phosphorylation of tyrosine residues likely located in the long cytoplasmic loop.|Zip6 Is Phosphorylated by Zap70 in Response to TCR Stimulation. | SIGNOR-280165 |
O60341 | Q04759 | 0 | phosphorylation | down-regulates activity | 0.259 | Inhibiting PKC-theta also increased the H3K4 demethylase activity of LSD1, indicating that active PKC-theta may prevent LSD1 from demethylating H3K4 and subsequently causing gene repression.|PKC-theta directly phosphorylates LSD1 at serine 111 and regulates its repressive activity and nuclear localization. | SIGNOR-279104 |
P09238 | Q14586 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.39 | Furthermore, ZNF267 binds to the MMP-10 promoter region as demonstrated by chromatin immunoprecipitation assays. In conclusion, our results suggest that ZNF267 as a negative transcriptional regulator of MMP-10 | SIGNOR-266211 |
P28482 | Q13115 | 0 | dephosphorylation | down-regulates activity | 0.762 | Dephosphorylation and Inactivation of ERKs|A single protein kinase, MEK, activates ERK2 by phosphorylating threonine 183 and tyrosine 185 | SIGNOR-248718 |
Q13131 | Q9Y297 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Glucose deprivation activates AMPK kinase to phosphorylate β-TrCP1 and promotes the subsequent ubiquitination and degradation of β-TrCP1 by β-TrCP2, but does not promote β-TrCP2 degradation by β-TrCP1. | SIGNOR-277475 |
P30307 | P68400 | 0 | phosphorylation | down-regulates | 0.302 | Inhibition of protein kinase ck2 enzyme activity in vivo resulted in an enhanced nuclear localization of cdc25c. Thus, phosphorylation of cdc25c at threonine 236 is an important signal for the retention of cdc25c in the cytoplasm | SIGNOR-123713 |
Q12857 | P23352 | 1 | transcriptional regulation | down-regulates quantity | 0.2 | By integrating transcriptomic profiling (RNA-seq) of Nfia- and Nfix-deficient GNPs with epigenomic profiling (ChIP-seq against NFIA, NFIB and NFIX, and DNase I hypersensitivity assays), we reveal that these transcription factors share a large set of potential transcriptional targets, suggestive of complementary roles for these NFI family members in promoting neural development | SIGNOR-268872 |
P19484 | O15297 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | As expected, we found that glucose deprivation induced the binding of TFEB (Figure S4C) and ACSS2 (Figure S4D) to the promoter regions of MAP1LC3B, ATG3, and WIPI-1 as well as mRNA (Figure 3H) and protein (Figure 3I) expression of these genes; | SIGNOR-276557 |
P49841 | Q9UKT5 | 1 | phosphorylation | up-regulates | 0.2 | Gsk3beta-mediated phosphorylation of fbx4 ser12 during the g1/s transition regulates fbx4 dimerization, which in turn governs fbx4-driven e3 ligase activity. | SIGNOR-171648 |
Q6DJT9 | P63279 | 0 | sumoylation | down-regulates | 0.277 | Sumoylation decreases the transcriptional activity of plag1 / plag1 is sumoylated at 2 specific lysine residues (lys-244 and lys-263) | SIGNOR-126048 |
Q13148 | O00311 | 0 | phosphorylation | up-regulates activity | 0.2 | Among these, CDC7 directly phosphorylates TDP-43 on serines 409 and 410 both in vitro and in vivo . | SIGNOR-278256 |
P17612 | P19838 | 1 | phosphorylation | up-regulates | 0.509 | In this study, we demonstrate that the phosphorylation of p50 and p65 by the catalytic subunit of protein kinase a (pkac) is essential for nf-kappab dna binding and transactivation activity. treatment with h89 and knockdown of pkac in cells led to the inhibition of phosphorylation at p50 ser(337) and p65 ser(276) and loss of dna binding by nf-kappab. | SIGNOR-158595 |
Q9UQ13 | P28482 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.322 | Here, we showed that SHOC2, a RAS activator, is a FBXW7 substrate. Growth stimuli trigger SHOC2 phosphorylation on Thr507 by the mitogen-activated protein kinase (MAPK) signal, which facilitates FBXW7 binding for ubiquitylation and degradation. | SIGNOR-277442 |
Q99538 | Q6R6M4 | 0 | deubiquitination | down-regulates quantity by destabilization | 0.309 | We demonstrate that TRAF6 ubiquitinates the proform of AEP through K63-linked polyubiquitin, reversible by USP17, and forms a complex with HSP90α to subsequently promote pro-AEP intracellular stability as well as secretion. We now present evidence that AEP is a substrate for TRAF6 ubiquitination, resulting in AEP/TRAF6/HSP90α complex formation. | SIGNOR-272854 |
Q14653 | P42684 | 0 | 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 |
P99999 | P53701 | 0 | chemical modification | up-regulates activity | 0.44 | Cytochrome c oxidase catalyzes the reduction of molecular oxygen to water, a process in which four electrons, four protons, and one molecule of oxygen are consumed. The reaction is coupled to the pumping of four additional protons across the membrane. According to the currently accepted concept, the pumping of all four protons occurs after the binding of oxygen to the reduced enzyme and is exclusively coupled to the last two electron transfer steps. | SIGNOR-280296 |
Q96EB6 | P15172 | 1 | null | down-regulates activity | 0.621 | Sir2 forms a complex with the acetyltransferase PCAF and MyoD and, when overexpressed, retards muscle differentiation | SIGNOR-241963 |
P68400 | O43395 | 1 | phosphorylation | up-regulates | 0.2 | Our findings provide new insights into the biology of hprp3p and suggest that the loss of hprp3p phosphorylation at thr494 is a key step for initiating thr494met aberrant interactions within u4/u6 snrnp complex and that these are likely linked to the rp18 phenotype. | SIGNOR-158319 |
Q15139 | Q92934 | 1 | 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 |
Q96D96 | Q05655 | 0 | phosphorylation | up-regulates activity | 0.2 | HVCN1S is phosphorylated more by PKC-δ than HVCN1L. PKC-δ in vitro kinase assay showing phosphorylation of HVCN1 | SIGNOR-273827 |
P07384 | P49841 | 1 | cleavage | up-regulates activity | 0.297 | Thus, it has been shown that calpain cleaves the inhibitory domain of GSK3 generating two fragments of 40 and 30 kDa. This cleavage enhanced activity of the kinase | SIGNOR-251586 |
P08047 | O43497 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.261 | Consistent with this, Sp1 over-expression enhanced promoter activity while siRNA-mediated Sp1 silencing significantly decreased the level of CaV 3.1 protein and reduced the amplitude of whole-cell T-type Ca(2+) currents expressed in the N1E-115 cells. These results provide new insights into the molecular mechanisms that control CaV 3.1 channel expression. | SIGNOR-264034 |
Q13224 | Q13554 | 0 | phosphorylation | up-regulates activity | 0.606 | By peptide mapping, automated sequencing, and mass spectrometry, we identified the major site of phosphorylation on the fusion protein as Ser-383, corresponding to Ser-1303 of full-length NR2B. The Km for phosphorylation of this site in the fusion protein was approximately 50 nM, much lower than that of other known substrates for CaM kinase II, suggesting that the receptor is a high affinity substrate. We show that serine 1303 in the full-length NR2B and/or the cognate site in NR2A is a major site of phosphorylation of the receptor both in the postsynaptic density fraction and in living hippocampal neurons. | SIGNOR-250688 |
Q14289 | O43150 | 1 | phosphorylation | up-regulates activity | 0.525 | Tyrosine phosphorylation of Pap by Pyk2 or Src kinases. We have identified a new Pyk2 binding protein designated Pap. Pap is a multidomain protein composed of an N-terminal alpha-helical region with a coiled-coil motif, followed by a pleckstrin homology domain, an Arf-GAP domain, an ankyrin homology region, a proline-rich region, and a C-terminal SH3 domain. We demonstrate that Pap forms a stable complex with Pyk2 and that activation of Pyk2 leads to tyrosine phosphorylation of Pap in living cells. | SIGNOR-269704 |
O00206 | Q16539 | 1 | phosphorylation | up-regulates activity | 0.416 | Binding of S100A9 to TLR4 stimulates the phosphorylation of JNK, ERK1/2, and p38 MAPK, which leads to the activation of c-Jun, CREB, and NF-κB. Activation of neutrophils by S100A9 also proceeds via p38 MAPK, JNK, and ERK1/2 phosphorylation. | SIGNOR-263652 |
P05023 | P17252 | 0 | phosphorylation | down-regulates activity | 0.329 | Parathyroid hormone (PTH) inhibits Na+,K+-ATPase activity through protein kinase C- (PKC) and extracellular signal-regulated kinase- (ERK) dependent pathways and increases serine phosphorylation of the α1-subunit. These results suggest that PTH regulates Na(+),K(+)-ATPase by PKC and ERK-dependent alpha(1)-subunit phosphorylation and that the phosphorylation requires the expression of a serine at the 11 position of the Na(+),K(+)-ATPase alpha(1)-subunit. | SIGNOR-262941 |
O43293 | O14974 | 1 | phosphorylation | down-regulates activity | 0.547 | We conclude from our results Par-4 operates through a "padlock" model in which binding of Par-4 to MYPT1 activates MP by blocking access to the inhibitory phosphorylation sites, and inhibitory phosphorylation of MYPT1 by ZIPK requires "unlocking" of Par-4 by phosphorylation and displacement of Par-4 from the MP complex.|We have also demonstrated that Par-4 is required for agonist induced, ZIPK mediated inhibition of MYPT1 and thus is an important amplifier of inputs to MP. | SIGNOR-279030 |
Q02447 | P14210 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Furthermore, in transient cotransfection assays, overexpression of Sp1 and/or Sp3 stimulated HGF promoter activity independently and additively through binding to the Sp1 binding site in the HGF gene promoter region. | SIGNOR-251741 |
Q9NRW4 | P03372 | 1 | dephosphorylation | down-regulates activity | 0.261 | These results strongly suggest that DUSP22 acts as a negative regulator of the ERalpha-mediated signaling pathway|whereas E2-induced phosphorylation and activation of ERalpha was suppressed by overexpression of DUSP22 but not catalytically inactive mutants. | SIGNOR-248827 |
P49840 | Q13144 | 1 | phosphorylation | down-regulates activity | 0.368 | We identify multiple phosphorylation sites in the largest, catalytic, subunit (epsilon) of mammalian eIF2B. Glycogen synthase kinase 3 (GSK3) is responsible for phosphorylating Ser535. This regulatory phosphorylation event requires both the fourth site (Ser539) and a distal region, which acts to recruit GSK3 to eIF2Bepsilon in vivo. eIF2Bϵ from mammals or insects is a substrate for glycogen synthase kinase 3 (GSK3), and this inhibits the activity of eIF2B | SIGNOR-251215 |
P17612 | P35611 | 1 | phosphorylation | down-regulates activity | 0.311 | Protein kinase A phosphorylates -adducin at three sites in the neck domain (Ser-408, ’436, and ’481) in addition to the MARCKS-related domain of both subunits. Phosphorylation by PKA, in contrast to PKC, reduced affinity of erythrocyte adducin for spectrin-F-actin complexes as well as activity of adducin in promoting binding of spectrin to F-actin. | SIGNOR-250331 |
Q05469 | P17612 | 0 | phosphorylation | up-regulates activity | 0.602 | HSL activity is known to be regulated by phosphorylation (3). PKA increases HSL activity via phosphorylation at Ser563, Ser659, and Ser660 (14,15), although phosphorylation at Ser565 by glycogen synthase kinase, AMP-dependent protein kinase, or Ca2+/calmodulin-dependent protein kinase II has been reported to prevent activation of the enzyme | SIGNOR-249202 |
P06493 | O95835 | 1 | phosphorylation | up-regulates | 0.389 | Warts is a serine/threonine kinase and a dynamic component of the mitotic apparatus. We have found that cdc2/cyclin b forms a complex with a fraction of warts in the centrosome and phosphorylates the ser613 site of warts during mitosisit can be speculated that phosphorylation of warts by cdc2/cyclin b promotes a protein complex formation on the mitotic apparatus at early mitosis, which may be required for subsequent activation of warts kinase at the metaphase-anaphase transition. | SIGNOR-94160 |
O60237 | Q13464 | 0 | phosphorylation | down-regulates | 0.586 | Phosphorylation of ppp1r12b on threonine 646 by rho kinase inhibits the activity of the pp1c-ppp1r12b complex. | SIGNOR-198812 |
O15554 | P17612 | 0 | phosphorylation | down-regulates activity | 0.2 | Mutating the single PKA site (S334A) in human KCa3.1 abolished the PKA-dependent regulation. CaM-affinity chromatography showed that CaM binding to KCa3.1 was decreased by PKA-dependent phosphorylation of S334, and this regulation was absent in the S334A mutant.The results above indicate that PKA activation led to a phosphorylation event that inhibited KCa3.1 channel activity | SIGNOR-276855 |
P06241 | Q15438 | 1 | phosphorylation | up-regulates activity | 0.394 | Fyn directly binds, phosphorylates, and activates cytohesin-1. | SIGNOR-280015 |
P59637 | O00560 | 1 | relocalization | up-regulates activity | 0.2 | Overall, these results support the hypothesis that the interaction of E protein PBM with syntenin facilitates the recruitment of syntenin in the cytosol and leads to p38 MAPK activation. | SIGNOR-260752 |
Q9UNE7 | P55036 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.421 | S5a/Rpn10 is a ubiquitin (Ub)-binding protein that is a subunit of the 26S proteasome but also exists free in the cytosol. It binds poly-Ub chains through its two Ub-interacting motifs (UIMs). We discovered that, unlike typical substrates of Ub ligases (E3s), S5a can be ubiquitinated by all E3s tested including multimeric and monomeric Ring finger E3s (MuRF1, Siah2, Parkin, APC, and SCF(betaTRCP1)), the U-box E3, CHIP, and HECT domain E3s (E6AP and Nedd4) when assayed with UbcH5 or related Ub-conjugating enzymes.The short half-life of S5a presumably is because of the presence of the UIM domain and reflects the ubiquitination of free S5a by many E3s. | SIGNOR-272752 |
Q9BZL6 | Q01105 | 1 | phosphorylation | down-regulates activity | 0.2 | In conclusion, the roles of protein kinase D2 and its substrate SET in T cell activation were investigated and we found that protein kinase D2 phosphorylates Ser171 of SET, which resulted in the reduction of its inhibitory effect on PP2A phosphatase activity. | SIGNOR-279560 |
Q05923 | Q16539 | 1 | dephosphorylation | down-regulates | 0.623 | We show that the in vivo substrate specificities of individual phosphatases are unique. Pac1, mkp-2, and mkp-1 recognize erk and p38, erk and jnk, and erk, p38, and jnk, respectively | SIGNOR-40918 |
P41240 | P16284 | 1 | phosphorylation | up-regulates activity | 0.55 | We demonstrated that phosphorylation of PECAM-1 by Src or Csk family kinases was sufficient to trigger its association with SHP-2. Moreover, it was able to promote binding of PECAM-1 to SHP-1, a SHP-2-related protein-tyrosine phosphatase expressed in hemopoietic cells. Taken together, these findings indicated that the Src and Csk families of kinases are strong candidates for mediating tyrosine phosphorylation of PECAM-1 and triggering its association with SH2 domain-containing phosphatases under physiological circumstances. | SIGNOR-262741 |
O15534 | P49674 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.842 | We show here that mPer proteins, negative limbs of the autoregulatory loop, are specific substrates for CKIepsilon and CKIdelta. The CKI phosphorylation of mPer1 and mPer3 proteins results in their rapid degradation, which is dependent on the ubiquitin-proteasome pathway. | SIGNOR-267997 |
Q00987 | P49137 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.364 | Hdm2 phosphorylation by mapkap kinase 2 enhances hdm2 activity and promote the degradation of p53. | SIGNOR-133560 |
Q969H0 | P01106 | 1 | ubiquitination | down-regulates quantity | 0.762 | We now show that the F-box protein Fbw7 interacts with and thereby destabilizes c-Myc in a manner dependent on phosphorylation of MB1. Whereas wild-type Fbw7 promoted c-Myc turnover in cells, an Fbw7 mutant lacking the F-box domain delayed it. | SIGNOR-243545 |
Q9C0H5 | P63000 | 1 | gtpase-activating protein | down-regulates activity | 0.501 | 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-260494 |
Q8N884 | P43405 | 0 | phosphorylation | up-regulates activity | 0.2 | Mechanistically, viral infection or foreign DNA transfection triggers recruitment of the spleen tyrosine kinase (SYK) and cGAS to the endosomal vacuolar H+ pump (V-ATPase), where SYK is activated and then phosphorylates human cGASY214/215 (mouse cGasY200/201) to prime its activation. | SIGNOR-277844 |
Q13627 | P16220 | 1 | phosphorylation | up-regulates activity | 0.487 | Regarding to the functional role of Dyrk1A, active Dyrk1A phosphorylates the transcription factor cAMP response element -binding protein (CREB), which subsequently leads to the stimulation of cAMP response element-mediated gene transcription during neuronal differentiation ( ). | SIGNOR-279989 |
Q13627 | Q14814 | 1 | phosphorylation | down-regulates activity | 0.411 | DYRK1A phosphorylates MEF2D and decreases its transcriptional activity | SIGNOR-277901 |
P01106 | P68400 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.504 | Together, our findings provide evidence for CK1α-mediated destruction of c-Myc and identify c-Myc S252 as a crucial CK1α phosphorylation site for c-Myc degradation. | SIGNOR-276388 |
Q04206 | Q09472 | 0 | acetylation | up-regulates activity | 0.822 | Using acetylation assays, p300 was found to effectively acetylate RelA/p65 across the amino-acid region containing 1317 | SIGNOR-238778 |
P35637 | P00519 | 0 | phosphorylation | down-regulates activity | 0.325 | Abl kinase-mediated FUS Tyr526 phosphorylation alters nucleocytoplasmic FUS localization in FTLD-FUS. | SIGNOR-280168 |
P36894 | A6ND36 | 1 | phosphorylation | up-regulates activity | 0.374 | These results indicate that ALK3 phosphorylates PAWS1 predominantly at Ser610 but can also phosphorylate at Ser614 and Ser616 in vitro. |Here, we report the discovery and characterization of PAWS1/FAM83G as a novel SMAD1 interactor. PAWS1 forms a complex with SMAD1 in a SMAD4-independent manner, and BMP signalling induces the phosphorylation of PAWS1 through BMPR1A. The phosphorylation of PAWS1 in response to BMP is essential for activation of the SMAD4-independent BMP target genes NEDD9 and ASNS. Our findings identify PAWS1 as the first non-SMAD substrate for type I BMP receptor kinases and as a novel player in the BMP pathway. | SIGNOR-264766 |
Q05397 | P23634-6 | 1 | phosphorylation | up-regulates activity | 0.2 | Results of co-immunoprecipitation, treatment with tyrosine kinase inhibitors and integrin inhibition experiments suggest that FAK is responsible for PMCA4b tyrosine phosphorylation during platelet activation. equence analysis indicates that Y(1176) is a likely substrate for focal adhesion kinase (FAK), while Y(1122) is not located in a tyrosine phosphorylation motif. | SIGNOR-263194 |
Q8IXI1 | Q9BXM7 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.719 | PINK1 phosphorylates Miro, a component of the primary motor/adaptor complex that anchors kinesin to the mitochondrial surface. The phosphorylation of Miro activates proteasomal degradation of Miro in a Parkin-dependent manner. in Miro1, Ser156 (homologous to Ser182 in Drosophila) and Thr298, 299 (homologous to Ser324, 325 in Drosophila, Figure 6C). | SIGNOR-272727 |
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