IdA string | IdB string | labels int64 | mechanism string | effect string | score float64 | sentence string | signor_id string |
|---|---|---|---|---|---|---|---|
Q9Y2H0 | Q9BYB0 | 1 | relocalization | up-regulates activity | 0.2 | SHANK proteins are ‘master’ scaffolding proteins that tether and organize intermediate scaffolding proteins. They are located at excitatory synapses, where they are crucial for proper synaptic development and function. SAPAP proteins subsequently bind to the PDZ domain of members of the SHANK protein family. SHANK proteins then bind to the actin cytoskeleton and to Homer protein, which in turn interacts with mGluRs. Through these extended links, PSD95, SAPAP, SHANK and Homer proteins form a quaternary complex that brings together mGluR and NMDAR complexes in the PSD (FIG. 3). | SIGNOR-264597 |
P43405 | P09769 | 0 | phosphorylation | up-regulates activity | 0.594 | Fgr associates with Fc\u03b5RI and phosphorylates Syk in antigen-stimulated mast cells.|The overexpression of Fgr stimulates Syk, Syk dependent signaling molecules, and degranulation in RBL-2H3 cells and BMMCs. | SIGNOR-279332 |
Q05397 | Q9H9S0 | 1 | phosphorylation | up-regulates activity | 0.274 | In addition, FAK directly phosphorylates Nanog in a dose-dependent manner by in vitro kinase assay and in cancer cells in vivo. The site-directed mutagenesis of Nanog tyrosines, Y35F and Y174F, blocked phosphorylation and binding by FAK. | SIGNOR-276410 |
Q7L7L0 | Q14493 | 0 | translation regulation | up-regulates quantity by expression | 0.2 | Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control. | SIGNOR-265409 |
Q14289 | P12931 | 0 | phosphorylation | up-regulates | 0.624 | These data indicate that pyk2 activation via phosphorylation at tyr-402 requires ?V?3 Ligation and src activity. | SIGNOR-133870 |
O15530 | Q02156 | 1 | phosphorylation | up-regulates | 0.573 | In the present study, we analysed the contribution of the phosphoinositide-dependent kinase 1 (pdk-1) and pkcepsilon kinase activity in controlling the phosphorylation of thr(566) and ser(729). pdk-1 phosphorylation of the activation loop triggers autophosphorylation of the hydrophobic motif | SIGNOR-117320 |
P35611 | Q00535 | 0 | phosphorylation | up-regulates activity | 0.255 | We found that Cdk5 directly phosphorylated the actin-binding protein adducin-1 (ADD1) at T724 in vitro and in intact cells. | SIGNOR-277487 |
Q8IW41 | P12931 | 0 | phosphorylation | up-regulates quantity | 0.372 | These data strongly suggest that PRAK phosphorylation by Src on Y188 and Y216 drives the relocalization of PRAK to focal adhesion structures during cell adhesion. | SIGNOR-279762 |
Q9H2X6 | P00519 | 0 | phosphorylation | up-regulates activity | 0.403 | The Tyrosine Kinase c-Abl Promotes Homeodomain-interacting Protein Kinase 2 (HIPK2) Accumulation and Activation in Response to DNA Damage | SIGNOR-260936 |
Q06124 | P31260 | 1 | dephosphorylation | up-regulates | 0.373 | We also identified hoxa10 as a substrate for shp2 in undifferentiated myeloid cells, an effect that diminished during myelopoiesis. However, a constitutively active form of shp2 dephosphorylated hoxa10 throughout ex vivo myelopoiesis and sustained repression of hoxa10 target genes involved in phagocyte effector functions. | SIGNOR-182475 |
O15524 | P51451 | 0 | phosphorylation | down-regulates activity | 0.2 | These findings show that SOCS1 phosphorylation by the SRC family inhibits its tumor-suppressive activity, indicating that patients with increased SOCS1 phosphorylation may benefit from SRC family kinase inhibitors. | SIGNOR-277889 |
Q9NSD9 | Q2TAL8 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress. | SIGNOR-269404 |
P12931 | Q9C0H9 | 1 | phosphorylation | up-regulates activity | 0.496 | Phosphorylation of multiple tyrosine-containing motifs found on Sin correlated with c-Crk and cellular phosphoprotein binding to Sin as well as increased c-Src activity. These data suggest that (1) SH2 and SH3 ligand sites on Sin cooperatively activate the signaling potential of c-Src, (2) Sin acts as both an activator and a substrate for c-Src, and (3) phosphorylated Sin may serve as a signaling effector molecule for Src by binding to multiple cellular proteins. | SIGNOR-263196 |
Q8TCJ0 | O00165 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.331 | FBXO25 encodes an orphan F-box protein that determines the substrate specificity of the SCF (SKP1-CUL1-F-box)(FBXO25) ubiquitin ligase complex. An unbiased screen uncovered the prosurvival protein HCLS1-associated protein X-1 (HAX-1) as the bona fide substrate of FBXO25 that is targeted after apoptotic stresses. Protein kinase Cdelta (PRKCD) initiates this process by phosphorylating FBXO25 and HAX-1, thereby spatially directing nuclear FBXO25 to mitochondrial HAX-1. | SIGNOR-275563 |
P55036 | Q9UNE7 | 0 | 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 |
P49279 | P12931 | 0 | phosphorylation | up-regulates activity | 0.281 | In this study, we provide evidence that SLC11A1 is phosphorylated by Src family kinases at tyrosine 15 present in a conserved tyrosine-based motif (YGSI) among all species. | SIGNOR-278500 |
Q13233 | P00519 | 0 | phosphorylation | up-regulates activity | 0.258 | Moreover, c-Abl activates MEKK-1 in vitro and in response to DNA damage.|The results demonstrate that the nuclear c-Abl binds to MEKK-1 and that c-Abl phosphorylates MEKK-1 in vitro and in vivo. | SIGNOR-279672 |
P18031 | P42226 | 1 | dephosphorylation | down-regulates activity | 0.327 | Phosphorylated STAT6 may also serve as a cytoplasmic substrate for PTP1B since overexpression of PTP1B leads to STAT6 dephosphorylation and the suppression of STAT6 transcriptional activity, whereas PTP1B deficiency increases IL-4-induced STAT6 signaling in B-cells. | SIGNOR-277122 |
Q14004 | P23588 | 1 | phosphorylation | up-regulates activity | 0.251 | CDK13 directly phosphorylates 4E-BP1 at Thr46 and eIF4B at Ser422; genetically or pharmacologically inhibiting CDK13 disrupts mRNA translation. | SIGNOR-273115 |
O60869 | P17252 | 0 | phosphorylation | down-regulates activity | 0.301 | EDF-1 was phosphorylated in vitro by PKC in the presence of Ca2+ and phospholipids | This results shows that introduction of a single negative charge by phosphorylation at Thr-91 inhibited CaM-EDF-1 interactions. | SIGNOR-249041 |
Q12968 | Q08209 | 0 | dephosphorylation | up-regulates | 0.538 | Calcineurin directly dephosphorylates nfat resulting in the nuclear import of nfat. | SIGNOR-176376 |
P35354 | P07948 | 0 | phosphorylation | up-regulates activity | 0.385 | We report that FYN phosphorylates human COX2 on Tyr 446, and while corresponding phospho-mimetic COX2 mutation promotes COX2 activity, the phosphorylation blocking mutation prevents FYN-mediated increase in COX2 activity. FYN and LYN kinases phosphorylate COX2 on two distinct residues in vitro. | SIGNOR-276643 |
P21127 | Q07955 | 1 | phosphorylation | up-regulates activity | 0.283 | In comparison, CLK1 expression leads to speckle dissolution and diffuse GFP-SRSF1 localization in the nucleus.|We showed that CLK1 phosphorylates SRSF1 at approximately 18 sites inducing a gel shift from 35 to about 38 kDa on SDS-PAGE (XREF_FIG, upper panel). | SIGNOR-279499 |
P49715 | P49675 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.335 | Electrophoretic mobility shift assay demonstrated that this region of the StAR promoter was bound by C/EBPalpha, C/EBPbeta, and CREB. Forced expression of either C/EBPalpha or C/EBPbeta alone was sufficient to up-regulate StAR promoter activity whereas PGE(2) was needed to induce StAR promoter activity in CREB-overexpressed cells. | SIGNOR-254043 |
Q5S007 | Q9P2J5 | 1 | phosphorylation | down-regulates activity | 0.2 | In this study, we elucidated that leucyl-tRNA synthetase (LRS) was an LRRK2 kinase substrate and identified T293 as an LRRK2 phosphorylation site. LRRK2-meidated LRS phosphorylation or G2019S can lead to impairment of LRS editing, increased ER stress, and accumulation of autophagy markers. | SIGNOR-277417 |
Q9UPZ9 | P22607 | 0 | phosphorylation | down-regulates activity | 0.2 | FGF signaling partially abolished ICK's kinase activity, through FGFR-mediated ICK phosphorylation at conserved residue Tyr15, which interfered with optimal ATP binding. | SIGNOR-277436 |
Q9H2S1 | Q05086 | 0 | ubiquitination | up-regulates activity | 0.286 | UBE3A directly ubiquitinates SK2 in the C-terminal domain, which facilitates endocytosis. | SIGNOR-278527 |
Q5S007 | P10636 | 1 | 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 |
Q8IYA7 | Q7RTU7 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.415 | MKX is a meniscus-enriched transcription factor. In human meniscus cells, MKX regulates the expression of meniscus marker genes, OA-related genes, and other transcription factors, including Scleraxis (SCX), SRY Box 5 (SOX5), and Runt domain-related transcription factor 2 (RUNX2). | SIGNOR-267213 |
P42684 | P17676 | 1 | phosphorylation | up-regulates | 0.274 | The y79 amino acid residue of c/ebpbeta was phosphorylated by c-abl or arg. The phosphorylation of c/ebpbeta resulted in an increased c/ebpbeta stability and a potentiation of c/ebpbeta transcription activation activity in cells | SIGNOR-186427 |
P53350 | P43487 | 1 | phosphorylation | up-regulates activity | 0.359 | Here, we demonstrated in vitro and in vivo phosphorylation of RanBP1 by Plk1 as well as the importance of phosphorylation of RanBP1 in the interaction between Plk1 and Ran during early mitosis. | SIGNOR-279751 |
P10415 | P28482 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.552 | Phosphorylation of the map kinase sites in bcl-2, thr56, thr74, and ser87, is sufficient to inhibit tnf--induced degradation. | SIGNOR-74931 |
Q04206 | O75582 | 0 | phosphorylation | up-regulates | 0.718 | Transcriptional activation of the nf-kappab p65 subunit by mitogen- and stress-activated protein kinase-1 (msk1)mutational analysis of p65 revealed ser276 as a target for phosphorylation and transactivation in response to tnf. Moreover, we identified msk1 as a nuclear kinase for p65, since msk1 associates with p65 in a stimulus-dependent way and phosphorylates p65 at ser276. | SIGNOR-99210 |
P28482 | Q08499 | 1 | phosphorylation | down-regulates | 0.353 | Long pde4d forms are inhibited by erk2 phosphorylation | SIGNOR-77574 |
Q92819 | P54646 | 0 | phosphorylation | down-regulates activity | 0.2 | We found that AMPK phosphorylated Thr-110 of human HAS2, which inhibits its enzymatic activity. | SIGNOR-276299 |
P17612 | Q96PU5 | 1 | phosphorylation | down-regulates | 0.2 | Nedd4-2 was a substrate for phosphorylation by pka in vitro and in cells;three nedd4-2 residues were phosphorylated by pka and were required for camp to inhibit nedd4-2 (relative functional importance ser-327 > ser-221 > thr-246). | SIGNOR-128429 |
O60285 | P31749 | 0 | phosphorylation | up-regulates | 0.262 | Ser(600) in ark5 was found to be phosphorylated by active akt resulting in the activation of kinase activity. | SIGNOR-252591 |
Q14457 | O60674 | 0 | phosphorylation | up-regulates activity | 0.297 | Mechanistically, IL-6 triggers the interaction between JAK2 and BECN1, where JAK2 phosphorylates BECN1 at Y333. We demonstrate that BECN1 Y333 phosphorylation is crucial for BECN1 activation and IL-6-induced autophagy by regulating PI3KC3 complex formation. | SIGNOR-277567 |
P12931 | P29317 | 1 | phosphorylation | up-regulates activity | 0.454 | SRC phosphorylates EPHA2 on Tyr594|. It is therefore likely that this phosphorylation site is included in the binding motif of an additional signalling molecule required for cell transformation. | SIGNOR-246104 |
P51813 | Q08881 | 0 | phosphorylation | up-regulates activity | 0.334 | Itk phosphorylated Bmx-SH3 to a low extent. pY positions correspond to the residues Y215 and Y223 in Bmx. Tec family protein tyrosine kinases (TFKs) play a central role in hematopoietic cellular signaling. Initial activation takes place through specific tyrosine phosphorylation situated in the activation loop. | SIGNOR-251331 |
P05771 | P04083 | 1 | 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 |
P38435 | P00734 | 1 | carboxylation | up-regulates activity | 0.669 | We analyzed the number of glutamic acid (Glu) residues and their positions in the Gla domain (GD) of DCP to investigate the gamma-carboxylation mechanism of VK-dependent carboxylase. Several DCPs were found in each subject studied. The 10 Gla residues of human prothrombin were carboxylated in order from the N-terminal (residues 26, 25, 16, 29, 20, 19, 14, 32, 7 and 6)|In the absence of VK or in the presence of VK antagonists, hepatic VKdependent carboxylase activity is inhibited and des-g-carboxyprothrombin (abnormal prothrombin or PIVKA; protein induced by vitamin K antagonist, prothrombin) is released into the blood. | SIGNOR-263676 |
Q9UL54 | Q13043 | 1 | phosphorylation | up-regulates | 0.279 | In addition, the thousand-and-one (tao) amino acids kinase or taok1 3 has been shown to directly phosphorylate and activate hpo or mst1/2 | SIGNOR-201330 |
P11802 | P28749 | 1 | phosphorylation | up-regulates activity | 0.807 | Here we assessed the effects of alanine substitution at the individual or combined Cdk4(6)-specific sites in p130, compared with homologous sites in p107 (Thr(369)/Ser(650)/Ser(964)). In U-2-OS cells, the triple p107(DeltaCdk4)* mutant strongly inhibited E2F-4 activity and imposed a G(1) arrest resistant to cyclin D1 coexpression. | SIGNOR-250764 |
O60716 | P07333 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.27 | In our study, CSF-1R induced the tyrosine phosphorylation of p120 Y904 and Y228 in a SRC-dependent manner ( xref ). | SIGNOR-278929 |
Q14493 | Q96KK5 | 1 | translation regulation | up-regulates quantity by expression | 0.2 | Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control. | SIGNOR-265402 |
Q6ZNA4 | P12757 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.723 | Upon TGF-β induction, interaction of Arkadia with phosphorylated Smad2 triggers degradation of SnoN, whereas upon arsenic treatment, interaction of Arkadia with poly-SUMO in PML nuclear bodies induces degradation of polysumoylated PML together with RNF4. | SIGNOR-272885 |
P01106 | Q15208 | 0 | phosphorylation | down-regulates activity | 0.282 | Previously, we demonstrated that STK38 kinase mediates MYC phosphorylation.|STK38-WT overexpression dramatically reduced MYC half-life (4-fold), compared to control un induced cells (XREF_FIG), while STK38-KD overexpression led to increased MYC half-life (1.7 fold), illustrating an involvement in MYC protein turnover regulation (XREF_FIG). | SIGNOR-280142 |
Q9Y2N7 | O60260 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.2 | 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-263089 |
P41145 | P51608 | 0 | post transcriptional regulation | up-regulates quantity by expression | 0.272 | MeCP2 binds to the promoter region of six target genes. ChIP with anti-MeCP2 antibody shows that MeCP2 binds to the promoter regions of activated targets Sst, Oprk1, Gamt, and Gprin1, and repressed targets Mef2c and A2bp1. | SIGNOR-264677 |
P05230 | Q05655 | 0 | phosphorylation | up-regulates quantity | 0.2 | Translocated FGF1 can be phosphorylated by PKC\u03b4 on serine 130. | SIGNOR-278451 |
Q92934 | P28482 | 0 | phosphorylation | down-regulates activity | 0.461 | The rapid phosphorylation of bad following il-3 connects a proximal survival signal with the bcl-2 family, modulating this checkpoint for apoptosis.phosphorylatedBAD is bound to 14-3-3 within the cytosol, while only nonphosphorylated BAD is heterodimerized with membrane-bound BCL-XL. | SIGNOR-44858 |
O60260 | Q99714 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | This study identifies the multifunctional PD-related mitochondrial matrix enzyme 17-β hydroxysteroid dehydrogenase type 10 (HSD17B10) as a new Parkin substrate. | SIGNOR-272823 |
Q05209 | P29353 | 1 | dephosphorylation | down-regulates | 0.675 | The shc adaptor protein is highly phosphorylated at conserved, twin tyrosine residues (y239/240) that mediate protein-protein interactions. | SIGNOR-44361 |
Q99626 | P24941 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.476 | Phosphorylation of the homeotic tumor suppressor Cdx2 mediates its ubiquitin-dependent proteasome degradation|We found that cyclin-dependent kinase 2 phosphorylated Cdx2 in vitro and in vivo. | SIGNOR-250729 |
O14965 | Q8TEW0 | 1 | phosphorylation | up-regulates | 0.35 | Aurora a interacts directly with the atypical protein kinase c binding domain of par3 and phosphorylates it at serine 962. The phosphorylation of par3 at serine 962 contributes to its function in the establishment of neuronal polarity. | SIGNOR-188398 |
Q05513 | P49768 | 1 | phosphorylation | up-regulates activity | 0.337 | A phosphorylation site at serine residue 346 was identified that is selectively phosphorylated by PKC but not by PKA. This site is localized within a recognition motif for caspases, and phosphorylation strongly inhibits proteolytic processing of PS1 by caspase activity during apoptosis. | SIGNOR-249239 |
P49841 | P14921 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.2 | Here, we show that ETS1 forms a complex with glycogen synthase kinase-3β (GSK3β). Specifically, GSK3β-mediated phosphorylation of ETS1 at threonine 265 and serine 269 promoted protein stability, induced the transcriptional activation of matrix metalloproteinase (MMP)-9, and increased cell migration. | SIGNOR-277560 |
Q96LA5 | Q86YJ5 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.2 | MARCH9, a member of the RING-CH family of transmembrane E3 ubiquitin ligases, down-regulates CD4, major histocompatibility complex-I (MHC), and ICAM-1 in lymphoid cells. To identify novel MARCH9 substrates, we used high throughput flow cytometry and quantitative mass spectrometry by stable isotope labeling by amino acids in cell culture (SILAC) to determine the differential expression of plasma membrane proteins in a MARCH9-expressing B cell line. This combined approach identified 13 potential new MARCH9 targets. | SIGNOR-271543 |
P62136 | P42575 | 1 | dephosphorylation | up-regulates activity | 0.2 | nutrient-replete oocytes inhibit C2 via S135 phosphorylation catalyzed by calcium/calmodulin-dependent protein kinase II. We now show that C2 phosphorylated at S135 binds 14-3-3zeta, thus preventing C2 dephosphorylation. Moreover, we determined that S135 dephosphorylation is catalyzed by protein phosphatase-1 (PP1), which directly binds C2. | SIGNOR-248564 |
P36897 | Q9HAU4 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.71 | Smad7 Recruits Smurf2 to the TGFβ Receptor Complex. Here, we identify Smurf2, a C2-WW-HECT domain ubiquitin ligase and show that Smurf2 associates constitutively with Smad7. Smurf2 is nuclear, but binding to Smad7 induces export and recruitment to the activated TGF beta receptor, where it causes degradation of receptors and Smad7 via proteasomal and lysosomal pathways. | SIGNOR-272938 |
Q14191 | P00519 | 0 | phosphorylation | up-regulates | 0.41 | We thus hypothesized that wrn may interact with the abl tyrosine kinase in the dna damage response. Here, we provide evidence for a functional and physical interaction between wrn and c-abl, including wrn relocalization in response to dna damage, suggesting that this protein-protein interaction participates in a shared pathway of genome surveillance. | SIGNOR-86497 |
P19086 | Q13153 | 0 | phosphorylation | up-regulates | 0.2 | Phosphorylation of either ser(16) by pak1 or ser(27) by pkc decreased the affinity of galpha(z) for gbetagamma;phosphorylation of both residues by pkc caused no further effect. Pak1 thus regulates galpha(z) function by attenuating the inhibitory effects of both gaps and gbetagamma. | SIGNOR-48673 |
P24941 | Q16204 | 1 | phosphorylation | up-regulates | 0.2 | Serine 244 phosphorylation is required for h4 apoptotic function. | SIGNOR-121198 |
Q13541 | Q05655 | 0 | phosphorylation | down-regulates activity | 0.2 | As shown for serum, phosphorylation of 4E-BP1 by PKCdelta inhibits the interaction between 4E-BP1 and eIF4E and stimulates cap-dependent translation.|Here we demonstrate that protein kinase Cdelta (PKCdelta) associates with RAFT1 and that PKCdelta is required for the phosphorylation and inactivation of 4E-BP1. | SIGNOR-279100 |
P20671 | Q14493 | 0 | translation regulation | up-regulates quantity by expression | 0.2 | Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control. | SIGNOR-265399 |
Q9UQM7 | Q13224 | 1 | phosphorylation | up-regulates activity | 0.7 | 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-250630 |
Q96P20 | Q9BZY9 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.489 | Taken together, these data indicated that TRIM31 directly induced the K48-linked ubiquitination of NLRP3 through its E3 ligase activity.|Taken together, these results indicated that TRIM31 could promote proteasomal degradation of NLRP3. | SIGNOR-278603 |
Q86UX7 | P17252 | 0 | phosphorylation | up-regulates activity | 0.2 | PKC-induced phosphorylation events, as we have shown kindlin-3 to be a PKC phosphorylation target (Fig. 6C), are often followed by rapid activation of phosphatases (38). | SIGNOR-266415 |
Q9Y2Y9 | P45984 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.2 | TGF-β-mediated downregulation of KLF13 by HDAC-mediated epigenetic silencing and JNK-induced phosphorylation abrogates the latter’s inhibitory effect on TGF-β signaling. | SIGNOR-277809 |
P24941 | P38398 | 1 | phosphorylation | up-regulates | 0.677 | However, shrna-mediated depletion of cdk1 alone or small molecule cdk1 inhibition abrogated s phase cell-cycle arrest and the phosphorylation of a subset of atr/atm targets after dna damage. Loss of dna damage-induced checkpoint control was caused by a reduction in formation of brca1-containing foci. Mutation of brca1 at s1497 and s1189/s1191 resulted in loss of cdk1-mediated phosphorylation and also compromised formation of brca1-containing foci. | SIGNOR-187607 |
P06241 | Q13322 | 1 | phosphorylation | down-regulates | 0.38 | Grb10 tyrosine phosphorylation was stimulated by expression of constitutively active src or fyn in cells and by incubation with purified src or fyn in vitro. The insulin stimulated or src/fyn-mediated tyrosine phosphorylation in vivo was significantly reduced when grb10 tyrosine 67 was changed to glycine. This mutant form of grb10 bound with higher affinity to the ir in cells than that of the wild-type protein, suggesting that tyrosine phosphorylation of grb10 may normally negatively regulate its binding to the ir. | SIGNOR-78702 |
P30291 | P68400 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.408 | In the present study, we show that phosphorylation of S123 (pS123) by CDK promoted the binding of Wee1A to beta-TrCP through three independent mechanisms. S123 phosphorylation creates a PBD-binding motif and accelerates S53 phosphorylation by Plk1. | SIGNOR-276038 |
P15056 | Q92911 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | The BRAFV600E oncogene induces transforming growth factor beta secretion leading to sodium iodide symporter repression and increased malignancy in thyroid cancer. BRAF induces TGFβ secretion leading to NIS repression in a MEK-ERK–independent manner but cooperating with the MEK-ERK pathway to induce strong tumor invasion, two major traits acquired during PTC progression. | SIGNOR-251989 |
P49450 | P06493 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.68 | Here, we report that the phosphorylation of CENP-A Ser68 primes the ubiquitin-proteasome-mediated proteolysis of CENP-A during mitotic phase in human cultured cells.the mitotic CENP-A degradation specifically depends on Cdk1 activity. | SIGNOR-277576 |
Q05655 | Q9NRY6 | 1 | phosphorylation | up-regulates | 0.457 | Ad198-activated pkc-delta induces phosphorylation of mitochondrial pls3 at thr21;pls3 is a critical downstream effector of pkc-delta in ad198-induced apoptosis. | SIGNOR-140759 |
Q9NP71 | Q13085 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.435 | The present study provides evidence for a direct and dominant role of ChREBP in the glucose regulation of two key liver lipogenic enzymes, acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) | SIGNOR-267946 |
P11308 | P48729 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Using in vitro kinase assays, we further demonstrated that deletion of degron 1 largely abolished CKI-mediated phosphorylation of ERG (Figure S5B), indicating that serine residues within degron 1 are the major CKI phosphorylation sites. | SIGNOR-276935 |
P51828 | Q05655 | 0 | phosphorylation | up-regulates activity | 0.555 | Immunoprecipitation data indicated that PKCdelta could bind and directly phosphorylate AC7. | SIGNOR-279258 |
O95835 | Q4VCS5 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.523 | Here low serum and high LATS1 activity are found to enhance the levels of the 130-kDa isoform of angiomotin (Amot130) through phosphorylation by LATS1/2 at serine 175, which then forms a binding site for 14-3-3. Such phosphorylation, in turn, enables the ubiquitin ligase atrophin-1 interacting protein (AIP)4 to bind, ubiquitinate, and stabilize Amot130 | SIGNOR-275843 |
O15550 | P09630 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.26 | Evidence for direct involvement of UTX in regulation of HOX gene activity was demonstrated through UTX knockdown experiments in HEK293T cells in which loss of UTX induced transcriptional repression of HOXA and HOXC clusters. | SIGNOR-260028 |
Q13131 | Q9NYV6 | 1 | phosphorylation | down-regulates | 0.2 | We show that ampk down-regulates rrna synthesis under glucose restriction by phosphorylating the rna polymerase i (pol i)-associated transcription factor tif-ia at a single serine residue (ser-635). | SIGNOR-188403 |
P38398 | P06493 | 0 | phosphorylation | up-regulates | 0.497 | However, shrna-mediated depletion of cdk1 alone or small molecule cdk1 inhibition abrogated s phase cell-cycle arrest and the phosphorylation of a subset of atr/atm targets after dna damage. Loss of dna damage-induced checkpoint control was caused by a reduction in formation of brca1-containing foci. Mutation of brca1 at s1497 and s1189/s1191 resulted in loss of cdk1-mediated phosphorylation and also compromised formation of brca1-containing foci. | SIGNOR-72087 |
Q8IXL6 | Q9NP70 | 1 | phosphorylation | up-regulates activity | 0.664 | Disruption of Fam20C completely eliminated AMBN phosphorylation, suggesting that Fam20C is the kinase that phosphorylates enamel matrix proteins in vivo (XREF_FIG). | SIGNOR-280010 |
P17612 | P26678 | 1 | phosphorylation | up-regulates activity | 0.492 | Phospholamban (PLB) can be phosphorylated at Ser(16) by cyclic AMP-dependent protein kinase. phosphorylation of Ser(16) is sufficient for mediating the maximal cardiac responses to beta-adrenergic stimulation. | SIGNOR-250030 |
P46527 | Q00536 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.333 | In vitro kinase assays showed PCTAIRE1 phosphorylates p27 at Ser10. PCTAIRE1 silencing modulated Ser10 phosphorylation on p27 and led to its accumulation in cancer cells but not in nontransformed cells.|Together our findings reveal an unexpected role for PCTAIRE1 in regulating p27 stability, mitosis, and tumor growth, suggesting PCTAIRE1 as a candidate cancer therapeutic target. | SIGNOR-273016 |
P06493 | O00571 | 1 | phosphorylation | down-regulates | 0.297 | Thr204 to glu204 ddx3 mutant protein lost its function, suggesting that phosphorylation at thr204 affects ddx3 function. Thr204 was phosphorylated by cyclin b/cdc2. Thr323 in motif ib was also phosphorylated by cyclin b/cdc2 kinase. We propose a novel function of cyclin b/cdc2 kinase in mitosis, which is to cause a loss of ddx3 function to repress cyclin a expression and to decrease ribosome biogenesis and translation during mitosis. | SIGNOR-141569 |
P68400 | P08473 | 1 | phosphorylation | down-regulates | 0.323 | The cytoplasmic n-terminal domain of nep interacts with the phosphatase and tensin homologue deleted on chromosome 10 (pten) thereby regulating intracellular signaling via akt. Ser 6 is efficiently phosphorylated by protein kinase ck2. The phosphorylation of the cytoplasmic domain of nep inhibits its interaction with pten. | SIGNOR-168673 |
P17612 | P46020 | 1 | phosphorylation | up-regulates activity | 0.432 | Phosphorylation of the alpha and beta subunits by the 3',5'-cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) also relieves inhibition of the gamma subunit and thereby activates the enzyme. | SIGNOR-267411 |
O95235 | Q9HC98 | 0 | phosphorylation | down-regulates activity | 0.347 | We show that Nek9, Nek6, and the kinesin Mklp2 form a signaling module, which is required for Mklp2 to localize to the central spindle in anaphase. Nek6 also phosphorylates Mklp2 at Ser244, inhibiting its bundling activity until anaphase onset. | SIGNOR-273891 |
Q99426 | Q13618 | 0 | ubiquitination | down-regulates quantity | 0.245 | Gigaxonin is the substrate-specific adaptor for a new Cul3-E3-ubiquitin ligase family that promotes the proteasome dependent degradation of its partners MAP1B, MAP8 and tubulin cofactor B. | SIGNOR-268945 |
P42345 | Q9Y6M1 | 1 | phosphorylation | up-regulates activity | 0.2 | IGF2BP2 can be activated by mTOR and promotes its binding to IGF2 mRNA of IGF2 thereby leading to diabetes mellitus [ xref , xref ].|In addition, phosphorylation of IGF2BP2 in the linker region between RRM2 and KH1 by mTOR promotes its binding to the IGF leader 3 mRNA 5\u2032-UTR, enhancing the initiation of IGF2 translation through eIF-4E- and 5\u2032 cap-independent internal ribosomal entry [ xref ]. | SIGNOR-280046 |
Q96SB4 | P54793 | 1 | phosphorylation | up-regulates activity | 0.2 | Phosphorylation by SRPK1 drives ASF from the cytosol to the nucleus.|Phosphorylation of ASF by SR protein kinase 1 (SRPK1) in the cytosol results in ASF relocation to the nucleus, whereas phosphorylation of ASF by Clk and Sty releases ASF from speckles and recruits it into nascent transcripts where ASF regulates alternative splicing. | SIGNOR-279765 |
P06748 | Q7Z419 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.2 | NPMc degradation was mediated by the ubiquitin-proteasome pathway involving the IBR-type RING-finger E3 ubiquitin ligase IBRDC2, and genetic correction of FA-A or FA-C lymphoblasts prevented NPMc ubiquitination. As shown in Fig. 4C, knockdown of IBRDC2, an IBR-type RING-finger E3 ubiquitin ligase (21), significantly reduced NPMc ubiquitination and restored NPMc stability in FA-A cells | SIGNOR-271490 |
P62136 | P40763 | 1 | dephosphorylation | down-regulates activity | 0.329 | Avicins dephosphorylate Stat3 in a variety of human tumor cell lines, leading to a decrease in the transcriptional activity of Stat3.| However, PD98059, an inhibitor of MEK1/2, had no significant effects on avicin-induced dephosphorylation of Stat3 (Ser 727) | SIGNOR-248563 |
Q9UQM7 | P10636 | 1 | phosphorylation | down-regulates activity | 0.596 | We found that when tau was first phosphorylated by A-kinase, C-kinase, cdk5, or CaM kinase II and then by GSK-3, its binding to microtubules was inhibited by 45, 61, 78, and 79%, respectively. Further, the kinase combinations cdk5/GSK-3 and CaM kinase II/GSK-3 rapidly phosphorylated the sites Thr 231 and Ser 235. When these sites were individually replaced by Ala and the phosphorylation experiments repeated, tau binding to microtubules was inhibited by 54 and 71%, respectively. By comparison, when Ser 262 was replaced by Ala, tau binding to microtubules was inhibited by only 8% after phosphorylation by CaM kinase II. | SIGNOR-249315 |
Q4VCS5 | Q9NRM7 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.516 | Here low serum and high LATS1 activity are found to enhance the levels of the 130-kDa isoform of angiomotin (Amot130) through phosphorylation by LATS1/2 at serine 175, which then forms a binding site for 14-3-3. Such phosphorylation, in turn, enables the ubiquitin ligase atrophin-1 interacting protein (AIP)4 to bind, ubiquitinate, and stabilize Amot130 | SIGNOR-275846 |
Q96SN8 | O60566 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.27 | These data indicate that CDK5RAP2 is a positive regulator of both the BUBR1 promoter and the MAD2 promoter | SIGNOR-260312 |
O76083 | O76050 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | Neuralized family member NEURL1 is a ubiquitin ligase for the cGMP-specific phosphodiesterase 9A. We also demonstrate that NEURL1 can promote polyubiquitination of PDE9A that leads to its proteasome-mediated degradation mainly via lysine residue K27 of ubiquitin. | SIGNOR-272305 |
O00238 | Q99717 | 1 | phosphorylation | up-regulates activity | 0.68 | Two types of bmp-induced signaling pathways are known, the smad and p38 mapk pathways. In the former case, bmpr1 phosphorylates smad-1,-5,-8, which forms a complex with smad4 that translocates into the nucleus and regulates gene expression. | SIGNOR-255260 |
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