IdA string | IdB string | labels int64 | mechanism string | effect string | score float64 | sentence string | signor_id string |
|---|---|---|---|---|---|---|---|
Q96KB5 | P45983 | 1 | phosphorylation | up-regulates activity | 0.303 | Taken together, these findings showed that TOPK positively modulated UVB-induced JNK1 activity and played a pivotal role in JNK1-mediated cell transformation induced by H-Ras.|We showed that TOPK associated with and phosphorylated JNK1 following UVB irradiation in vitro or in vivo. | SIGNOR-280061 |
P03372 | P17612 | 0 | phosphorylation | down-regulates | 0.486 | Phosphorylation of human estrogen receptor alpha by protein kinase a regulates dimerizationeralpha is phosphorylated by protein kinase a (pka) on serine-236 within the dna binding domain. Mutation of serine-236 to glutamic acid prevents dna binding by inhibiting dimerization by eralpha | SIGNOR-63984 |
Q13131 | P17612 | 0 | phosphorylation | down-regulates activity | 0.423 | These agents also enhanced phosphorylation of alpha-Ser(485/491) by the cAMP-dependent protein kinase. AMPK alpha-Ser(485/491) phosphorylation was necessary but not sufficient for inhibition of AMPK activity in response to forskolin/isobutylmethylxanthine. | SIGNOR-256112 |
P84022 | Q16539 | 0 | phosphorylation | up-regulates activity | 0.537 | Smad3 was phosphorylated at both Ser203 and Ser207 in untreated MCF10CA1h cells and the p38 and ROCK inhibitors each down-regulated phosphorylation at these sites. we demonstrate that phosphorylation at Ser203 and Ser207 residues is required for the full transactivation potential of Smad3, and that these residues are targets of the p38 and Rho/ROCK pathways. | SIGNOR-250112 |
Q6UUV9 | P57059 | 0 | phosphorylation | down-regulates | 0.494 | These results suggested that sik1 could phosphorylate all torcs and thereby repress their transactivation activities. | SIGNOR-147669 |
P00533 | O00750 | 1 | phosphorylation | up-regulates | 0.44 | The n-terminal region of pi3k-c2beta was found to selectively interact with the egf receptor in vitro, suggesting that it mediates the association of this pi3k with the receptor. | SIGNOR-77195 |
P55072 | P26045 | 0 | dephosphorylation | down-regulates activity | 0.478 | Identification of VCP as a substrate of PTPH1in vivo.|The tyrosines (Tyr796 and Tyr805) at the C terminus of VCP have been reported to be the major sites of phosphorylation, with Tyr805 accounting for more than 90% of the tyrosine phosphorylation on the protein |The Y796F/Y805F VCP mutant was not associated with any of the PTPH1 constructs. | SIGNOR-248460 |
P78352 | Q9NZ94 | 0 | relocalization | up-regulates activity | 0.755 | Like NRXNs, NLGNs bind to intracellular PDZ-domain proteins, but in contrast to NRXNs, NLGNs bind to class I PDZ domains such as those contained in PSD95, a postsynaptic MAGUK protein65. PSD95 and its homologues are centrally involved in recruiting glutamate receptors at postsynaptic sites66. Similarly to CASK, PSD95 binds to intracellular adaptor proteins, and especially to GKAP (a protein that binds to the guanylate-kinase domain of PSD95), which, in turn, binds to SHANK proteins (Fig. 1b). A possible role of these interactions is to recruit postsynaptic adaptor proteins to the site of synaptic junctions. | SIGNOR-264189 |
Q9UIJ5 | P24588 | 1 | palmitoylation | up-regulates activity | 0.331 | Here, we report that the recycling endosome-resident palmitoyl acyltransferase DHHC2 interacts with and palmitoylates AKAP79/150 to regulate these plasticity signaling mechanisms | SIGNOR-261289 |
Q9BXW9 | Q9NS91 | 0 | ubiquitination | up-regulates activity | 0.521 | In summary, these findings suggest a model, where Rad18 promotes monoubiquitination of FANCD2, and associates with a functional complex involving Rad51, BRCA2, and FANCD2 in the repair of CPT induced stalled or collapsed forks.|In this study we focused on the role of Rad18 mediated activation of FANCD2 and its functional relationship with BRCA2 and Rad51 proteins in repair of CPT induced lesions. | SIGNOR-278712 |
A7MCY6 | Q9BWT7 | 1 | relocalization | up-regulates activity | 0.2 | TBKBP1 recruits TBK1 to protein kinase C-theta (PKCθ) through a scaffold protein, CARD10. This enables PKCθ to phosphorylate TBK1 at Ser 716, a crucial step for TBK1 activation | SIGNOR-272470 |
Q9BZL4 | P54646 | 0 | phosphorylation | down-regulates | 0.259 | Ampk-induced phosphorylation is necessary for ppp1r12c interaction with 14-3-3 and phosphorylation of myosin regulatory light chain. Both ampk activity and ppp1r12c phosphorylation are increased in mitotic cells and are important for mitosis completion. The interaction between ppp1r12c and 14-3-3_ may inactivate the ppp1r12c-containing phosphatase complex in vivo. | SIGNOR-195148 |
Q12955 | P11532 | 1 | relocalization | up-regulates quantity | 0.367 | We present evidence for an ankyrin-based mechanism for sarcolemmal localization of dystrophin and beta-DG. Ankyrin-B thus is an adaptor required for sarcolemmal localization of dystrophin, as well as dynactin-4. | SIGNOR-266715 |
Q96KS0 | O43524 | 1 | hydroxylation | down-regulates activity | 0.287 | Prolyl hydroxylation by EglN2 destabilizes FOXO3a by blocking its interaction with the USP9x deubiquitinase.|Here we report that EglN2 can hydroxylate FOXO3a on two specific prolyl residues in vitro and in vivo. Hydroxylation of these sites prevents the binding of USP9x deubiquitinase, thereby promoting the proteasomal degradation of FOXO3a. | SIGNOR-261998 |
P10909 | P10244 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.274 | Here we show that the human ApoJ/Clusterin gene contains a Myb binding site in its 5' flanking region, which interacts with bacterially synthesized B-MYB protein and mediates B-MYB-dependent transactivation of the ApoJ/Clusterin promoter in transient transfection assays. Endogenous ApoJ/Clusterin expression is induced in mammalian cell lines following transient transfection of a B-MYB cDNA. | SIGNOR-269800 |
P31749 | Q7L5N1 | 1 | phosphorylation | up-regulates | 0.282 | Mechanistic studies show that akt causes csn6 phosphorylation at ser 60, which, in turn, reduces ubiquitin-mediated protein degradation of csn6. | SIGNOR-252532 |
P29597 | P40763 | 1 | phosphorylation | up-regulates | 0.687 | Since Jak-STAT pathway primarily activated in IL-15-me- diated cell proliferation, we tested whether it is also participates in IL-15-mediated proliferation of FAPs. Interestingly, we found the expression of phospho-Jak3 and phospho-Tyk2, as well as their downstream, phospho- STAT3 and phospho-STAT5, was significantly upregulated | SIGNOR-256255 |
P62136 | O15169 | 1 | dephosphorylation | down-regulates activity | 0.333 | The data suggest that PP1 controls Wnt signaling through interaction with, and regulated dephosphorylation of, axin| Axin phosphorylation markedly enhances the binding of glycogen synthase kinase 3, leading to a more active beta-catenin destruction complex. Wnt-regulated changes in axin phosphorylation, mediated by PP1, may therefore determine beta-catenin transcriptional activity| Four sites, S80, S82, S222, and S473, were identified to be PP1 regulated | SIGNOR-248551 |
Q13308 | P12931 | 0 | phosphorylation | up-regulates activity | 0.279 | Because Ptk7 lacks intrinsic kinase activitiy, we suggest a positive feedback model in which pre-existing active Src phosphorylates PTK7 enabling it to interact with the SH2 domain of additional Src molecules to result in further activation. | SIGNOR-279123 |
P11802 | Q92879 | 1 | phosphorylation | up-regulates activity | 0.398 | These studies showed that both the increased levels of CUGBP1 and cdk4-mediated hyper-phosphorylation of CUGBP1 are involved in the age-associated induction of the CUGBP1-eIF2 complex. The CUGBP1-eIF2 complex is bound to C/EBPbeta mRNA in the liver of old animals, and this binding correlates with the increased amounts of liver-enriched activator protein and liver-enriched inhibitory protein. | SIGNOR-262735 |
P53367 | Q15139 | 0 | phosphorylation | up-regulates | 0.385 | We report that arfaptins contain an amphipathic helix (ah) preceding the bar domain, which is essential for their binding to phosphatidylinositol 4-phosphate (pi(4)p)-containing liposomes and the tgn of mammalian cells. The binding of arfaptin1, but not arfaptin2, to pi(4)p is regulated by protein kinase d (pkd) mediated phosphorylation at ser100 within the ah. We also found that only arfaptin1 is required for the pkd-dependent trafficking of chromogranin a by the regulated secretory pathway. | SIGNOR-202101 |
Q9UL51 | Q13237 | 0 | phosphorylation | down-regulates activity | 0.2 | Here, we show for the first time that in the HCN2 channel cGMP can also exert an inhibitory effect on gating via cGMP-dependent protein kinase II (cGKII)-mediated phosphorylation.We identify the proximal C-terminus of HCN2 as binding region of cGKII and show that cGKII phosphorylates HCN2 at a specific serine residue (S641) in the C-terminal end of the CNBD. The cGKII shifts the voltage-dependence of HCN2 activation to 2-5 mV more negative voltages and, hence, counteracts the stimulatory effect of cGMP on gating. | SIGNOR-263185 |
O43451 | Q7Z570 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.2 | ZNF804A has been implicated in susceptibility to schizophrenia by several genome-wide association studies (GWAS), follow-up association studies and meta-analyses. ZNF804A was identified as a schizophrenia-associated gene by GWAS and was predicted to play a role in DNA binding and transcription To identify the genes that are affected by ZNF804A, we manipulated the expression of the ZNF804A protein in HEK293 human embryonic kidney cell lines and performed a cDNA microarray analysis followed by qPCR. We found that ZNF804A-overexpression up-regulated four genes (ANKRD1, INHBE, PIK3AP1, and DDIT3) and down-regulated three genes (CLIC2, MGAM, and BIRC3). | SIGNOR-269466 |
P29317 | P19174 | 1 | phosphorylation | up-regulates activity | 0.276 | EphA2 activates PLC\u03b31 in human lung cancer cells.|The result here showed that only wild-type EphA2, but not K646M\nor Y588F mutants, could phosphorylate PLC\u03b31, demonstrating that\nPLC\u03b31 phosphorylation is dependent on the kinase activity of EphA2. | SIGNOR-279708 |
O00141 | O00213 | 1 | phosphorylation | down-regulates activity | 0.345 | In the present study, we demonstrated that phosphorylation of FE65 Ser 610 by SGK1 attenuates the interaction between FE65 and APP (XREF_FIG).|In this regard, we demonstrated that phosphorylation of FE65 Ser 610 by SGK1 abolishes the effect of FE65 on APP processing and the amount of secreted Abeta is comparable to APP + Mock control (XREF_FIG). | SIGNOR-278220 |
P06493 | P27361-3 | 1 | phosphorylation | up-regulates activity | 0.314 | We found that CDK1 phosphorylates Ser343 of ERK1c, thereby allowing the binding of phosphorylated ERK1c to a complex that consists of PI4KIIIβ (also known as PI4KB) and the 14-3-3γ dimer (encoded by YWHAB). | SIGNOR-277185 |
O00327 | Q9UBK2 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.519 | Transcriptional coactivator PGC-1α integrates the mammalian clock and energy metabolism. Here we show that PGC-1alpha (Ppargc1a), a transcriptional coactivator that regulates energy metabolism, is rhythmically expressed in the liver and skeletal muscle of mice. PGC-1alpha stimulates the expression of clock genes, notably Bmal1 (Arntl) and Rev-erbalpha (Nr1d1), through coactivation of the ROR family of orphan nuclear receptors. | SIGNOR-268031 |
Q9UI33 | Q96PU5 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.288 | The control of Nav density at the cell membrane is crucial to ensuring normal neuronal excitability. Navs are subject to posttranslational modifications that may influence their cell membrane availability. Ubiquitylation is a key process that orchestrates the internalization and subsequent degradation or recycling of Navs. This is accomplished by ubiquitin protein ligases, such as NEDD4-2 (neuronal precursor cell expressed developmentally downregulated-4 type 2). | SIGNOR-253462 |
P11831 | P78527 | 0 | phosphorylation | up-regulates activity | 0.406 | The carboxyl-terminal transcription activation domain was mapped within a 71-amino acid region that contains both DNA-PK phosphorylation sites. Amino acid substitutions that interfered with phosphorylation by DNA-PK at Ser-435/446 in GAL4-SRF fusion proteins were reduced in transactivation potency. From these data we suggest that DNA-PK phosphorylation may modulate SRF activity in vivo. | SIGNOR-248922 |
P06396 | Q14289 | 0 | phosphorylation | down-regulates activity | 0.527 | Our results demonstrate that PYK2 inhibits this EGTA stable gelsolin-actin monomer association.|PYK2 phosphorylates gelsolin at tyrosine residues and regulates gelsolin bioactivity, including decreasing gelsolin binding to actin monomer and increasing gelsolin binding to phosphatidylinositol lipids. | SIGNOR-278325 |
O15519 | P22681 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.2 | We therefore conclude that c-cbl is a e3 ubiquitin ligase for flips and that the interaction of flips with c-cbl requires phosphorylation of both ser4 and tyr211 of flips.This interaction triggered proteasomal degradation of FLIP(S), which promoted activation of caspase-8 and apoptosis. | SIGNOR-186998 |
P35568 | P49841 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.454 | HG activates GSK3beta, which phosphorylates IRS1 at serine 332, leading to the ubiquitination and proteasome mediated degradation of IRS1. | SIGNOR-279183 |
Q6N021 | Q13131 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.2 | We identify the tumour suppressor TET2 as a substrate of the AMP-activated kinase (AMPK), which phosphorylates TET2 at serine 99, thereby stabilizing the tumour suppressor. Increased glucose levels impede AMPK-mediated phosphorylation at serine 99, which results in the destabilization of TET2 followed by dysregulation of both 5-hydroxymethylcytosine (5hmC) and the tumour suppressive function of TET2 in vitro and in vivo | SIGNOR-256134 |
O15234 | Q9NTX7 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.262 | Here, we identify RNF146, a RING-domain E3 ubiquitin ligase, as a positive regulator of Wnt signalling. RNF146 promotes Wnt signalling by mediating tankyrase-dependent degradation of axin. Mechanistically, RNF146 directly interacts with poly(ADP-ribose) through its WWE domain, and promotes degradation of PARsylated proteins. Using proteomics approaches, we have identified BLZF1 and CASC3 as further substrates targeted by tankyrase and RNF146 for degradation. | SIGNOR-263339 |
P17612 | Q96SB3 | 1 | phosphorylation | down-regulates activity | 0.31 | Spinophilin is phosphorylated in vitro by protein kinase A (PKA). two major sites of phosphorylation, Ser-94 and Ser-177, that are located within the actin-binding domain of spinophilin. Phosphorylation of spinophilin by PKA modulated the association between spinophilin and the actin cytoskeleton. phosphorylation of spinophilin reduced the stoichiometry of the spinophilin-actin interaction. In contrast, the ability of spinophilin to bind to PP1 remained unchanged. | SIGNOR-250035 |
P22681 | O15519 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | We therefore conclude that c-cbl is a e3 ubiquitin ligase for flips and that the interaction of flips with c-cbl requires phosphorylation of both ser4 and tyr211 of flips.This interaction triggered proteasomal degradation of FLIP(S), which promoted activation of caspase-8 and apoptosis. | SIGNOR-186998 |
O60291 | Q99816 | 1 | monoubiquitination | up-regulates activity | 0.492 | In the present study, we identified the first substrate of the Mahogunin E3 ubiquitin–protein ligase: TSG101, a key component of the endosomal sorting ESCRT machinery.We find that Mahogunin interacts with the ubiquitin E2 variant (UEV) domain of TSG101 via its PSAP motif and that it catalyzes monoubiquitylation of TSG101 both in vivo and in vitro. Consistent with the results of the biochemical characterization and subcellular localization studies of Mahogunin, our functional studies provide direct evidence that Mahogunin plays an essential role in regulation of endosome-to-lysosome trafficking. We found that siRNA-mediated depletion of Mahogunin in HeLa cells causes enlargement and clustering of EEA1-positive endosomes and LAMP2-positive late endosomes/lysosomes (Figure 8B) and inhibits the endosomal trafficking of internalized EGF–EGFR complexes to lysosomes for degradation (Figures 9 and and10,10, A and B). These results are strikingly similar to the phenotypes that resulted from depletion of TSG101 | SIGNOR-271635 |
Q8TBB1 | P49757 | 1 | ubiquitination | down-regulates | 0.74 | Lnx functions as a ring type e3 ubiquitin ligase that targets the cell fate determinant numb for ubiquitin-dependent degradation. | SIGNOR-112201 |
P04049 | P06400 | 1 | phosphorylation | down-regulates activity | 0.578 | Further, Raf-1 was able to phosphorylate Rb in vitro quite efficiently.|Raf-1 can inactivate Rb function and can reverse Rb mediated repression of E2F1 transcription and cell proliferation efficiently. | SIGNOR-279481 |
P31749 | P54253 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.411 | Interaction of Ataxin-1 and 14-3-3 Requires Akt Phosphorylation at S776. 14-3-3 protein, a multifunctional regulatory molecule, mediates the neurotoxicity of ataxin-1 by binding to and stabilizing ataxin-1, thereby slowing its normal degradation. | SIGNOR-252561 |
P68400 | O15266 | 1 | phosphorylation | up-regulates | 0.338 | We show also that casein kinase ii phosphorylates shox on serine 106 efficiently in vitro. S106a shox mutant, defective in phosphorylation, does not activate transcription and fails to induce cell-cycle arrest and apoptosis | SIGNOR-142875 |
O15550 | P31271 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.285 | 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-260022 |
Q05655 | Q8TCJ0 | 1 | phosphorylation | up-regulates activity | 0.271 | 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.|Accordingly, PRKCD-induced phosphorylation of Hax-1 at Ser210 and Fbxo25 at Ser178 was associated with decreased expression of Hax-1 in control cells, | SIGNOR-275561 |
P35568 | Q05513 | 0 | phosphorylation | down-regulates activity | 0.723 | Extensive studies have provided evidence that phosphorylation of Ser307 in IRS-1 inhibits IR/IRS-1 complex formation and IRS-1 tyrosine phosphorylation after prolonged insulin-stimulation similar to our results. | SIGNOR-236760 |
P40763 | P52333 | 0 | phosphorylation | up-regulates | 0.792 | Since Jak-STAT pathway primarily activated in IL-15-me- diated cell proliferation, we tested whether it is also participates in IL-15-mediated proliferation of FAPs. Interestingly, we found the expression of phospho-Jak3 and phospho-Tyk2, as well as their downstream, phospho- STAT3 and phospho-STAT5, was significantly upregulated | SIGNOR-256254 |
Q96BD8 | Q96GD4 | 0 | phosphorylation | up-regulates activity | 0.736 | Aurora B directly phosphorylated Ska1 and Ska3 in vitro, and expression of phosphomimetic mutants of Ska1 and Ska3 impaired Ska KT recruitment and formation of stable KT-MT fibers (K-fibers), disrupting mitotic progression. We propose that Aurora B phosphorylation antagonizes the interaction between the Ska complex and the KMN network, thereby controlling Ska recruitment to KTs and stabilization of KT-MT attachments. | SIGNOR-262662 |
Q9Y463 | P13807 | 1 | phosphorylation | down-regulates activity | 0.258 | DYRK Family Protein Kinases Phosphorylate and Inactivate Glycogen Synthase. both protein kinases phosphorylate site 3a but no other sites that affect glycogen synthase activity. | SIGNOR-260633 |
P50750 | O96019 | 1 | phosphorylation | up-regulates activity | 0.323 | Collectively, these results suggest that the cdk9 and Cyclin T complex more efficiently phosphorylates Baf53 in vitro. | SIGNOR-279689 |
Q13554 | P14921 | 1 | phosphorylation | down-regulates activity | 0.309 | Increased Transactivation of the GM-CSF Promoter/Enhancer by Ets1 with Mutated CaMK II Sites | Significantly, phosphorylation of Ets1 by Ca2+-dependent pathways is thought to inhibit DNA binding in vitro. To analyze the role of these four serines, S251, S257, S282, and S285, in transcription, we constructed three mutant derivatives of human Ets1 | SIGNOR-250684 |
Q16539 | O00418 | 1 | phosphorylation | down-regulates activity | 0.334 | Inhibition of eEF2 kinase resulting from phosphorylation of Ser-396 by SAPK2a p38 was approx.25%. | SIGNOR-249707 |
P27361 | Q07866 | 1 | phosphorylation | down-regulates | 0.264 | Phosphorylation of kinesin light chain 1 at serine 460 modulates binding and trafficking of calsyntenin-1mutation of klc1ser460 to an alanine residue, to preclude phosphorylation, increased the binding of calsyntenin-1, whereas mutation to an aspartate residueklc1ser460 is a predicted mitogen-activated protein kinase (mapk) target site, and we show that extracellular-signal-regulated kinase (erk) phosphorylates this residue in vitro. | SIGNOR-172642 |
Q9UEW8 | P55011 | 1 | phosphorylation | up-regulates activity | 0.6 | This phosphorylation event activates PASK, which in turn phosphorylates and activates NKCC1 | SIGNOR-264642 |
Q8NBJ5 | P02452 | 1 | glycosylation | up-regulates activity | 0.41 | Recombinant GLT25D1 and GLT25D2 enzymes showed a strong galactosyltransferase activity toward various types of collagen and toward the serum mannose-binding lectin MBL, which contains a collagen domain. Amino acid analysis of the products of GLT25D1 and GLT25D2 reactions confirmed the transfer of galactose to hydroxylysine residues. | SIGNOR-261152 |
P78527 | Q9UGP5 | 1 | phosphorylation | up-regulates activity | 0.467 | We show that Polλ is efficiently phosphorylated by DNA-PKcs in vitro and predominantly by ATM after DSB induction with ionizing radiation (IR) in vivo. We identify threonine 204 (T204) as a main target for ATM/DNA-PKcs phosphorylation on human Polλ, and establish that its phosphorylation may facilitate the repair of a subset of IR-induced DSBs and the efficient Polλ-mediated gap-filling during NHEJ. | SIGNOR-273835 |
P30291 | Q8IY84 | 0 | phosphorylation | down-regulates activity | 0.48 | Furthermore, purified bacterially produced Nim1 kinase directly phosphorylates and inactivates Wee1 in vitro.|Phosphorylation and inactivation of the mitotic inhibitor Wee1 by the nim1 and cdr1 kinase. | SIGNOR-279238 |
O43524 | P31751 | 0 | phosphorylation | down-regulates activity | 0.751 | Akt-dependent phosphorylation of foxo3a (thr32, ser253, and ser315 for human foxo3) enhances foxo3a/14-3-3 Interaction and promotes foxo3a nuclear export to the cytoplasm, resulting in the repression of foxo3a transcriptional function akt phosphorylates members of the foxo factors (forkhead family of transcription factors), leading to binding of 14-3-3 proteins and cytoplasmic localisation. In particular, akt phosphorylates foxo1 on thr24, ser256 and ser319. Foxo 3alfa and foxo4 are phosphorylated on equivalent sites. | SIGNOR-236671 |
P23458 | Q06124 | 1 | phosphorylation | up-regulates activity | 0.768 | Tyrosine residues 304 and 327 in shp-2 are phosphorylated by jaks, and phosphorylated shp-2 can associate with the downstream adapter protein grb2 | SIGNOR-236274 |
P04150 | Q16649 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.296 | GR directly regulates transcription of circadian clock components in mouse and human primary MSCs. Per2, E4bp4, Per1, and Timeless rapidly respond to glucocorticoid stimulation. Primary glucocorticoid receptor (GR) target genes are those at which GR occupies a nearby genomic glucocorticoid response element (GRE) and regulates target gene transcription | SIGNOR-268051 |
P36897 | P84022 | 1 | phosphorylation | up-regulates activity | 0.812 | A major event leading to Smad3 activation is the TGF-beta-induced, TbetaRI-mediated phosphorylation at two C-terminal serine residues, Ser-423 and Ser-425, which triggers dissociation of Smad3 from its receptors to form a complex with Smad4 and accumulate in the nucleus | SIGNOR-235380 |
P00734 | P25116 | 1 | cleavage | up-regulates | 0.887 | The par1 receptor subtype is activated when the n terminus is proteolytically cleaved by the serine protease thrombin, resulting in an irreversible activation of the receptor. Thrombin activates platelets by binding and cleaving protease-activated receptors 1 and 4 (par1 and par4). | SIGNOR-199007 |
Q9BYX4 | Q6PJ69 | 0 | ubiquitination | up-regulates activity | 0.448 | These results indicate that TRIM65 promotes MDA5 ubiquitination at lysine 743, which is important for MDA5 activation. | SIGNOR-278535 |
P04637 | Q9BXM7 | 0 | phosphorylation | up-regulates activity | 0.321 | Our studies thus indicated that mitophagy\npositively regulated hepatic CSCs by suppressing p53, which otherwise would be activated by\nPINK1 to suppress the expression of NANOG and hepatic CSCs.|These results indicated that the phosphorylation of p53 at S392 by\nPINK1 likely took place on mitochondria. | SIGNOR-278418 |
Q05086 | Q8IXH7 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.326 | In this paper, we identify here trihydrophobin 1 (TH1), an integral subunit of the human negative transcription elongation factor (NELF) complex, as a novel E6-AP interaction protein and a target of E6-AP-mediated degradation. Overexpression of E6-AP results in degradation of TH1 in a dose-dependent manner, whereas knock-down of endogenous E6-AP elevates the TH1 protein level. | SIGNOR-271404 |
Q99801 | P60484 | 0 | dephosphorylation | up-regulates quantity by stabilization | 0.441 | Loss of PTEN Accelerates NKX3.1 Degradation to Promote Prostate Cancer Progression.|PTEN was also able to dephosphorylate NKX3.1 at threonine 179, a target of protein kinase C, but not threonine residues 89 and 93, targeted by casein kinase 2 . | SIGNOR-277026 |
P28482 | P07949 | 0 | phosphorylation | up-regulates | 0.423 | We hypothesized that ret could directly phosphorylate fak and erk. erk 2 could be phosphorylated at y187 (y204 in erk1). | SIGNOR-140294 |
P11233 | P62714 | 0 | dephosphorylation | down-regulates | 0.289 | Pp2a abeta-containing complexes dephosphorylate rala at ser183 and ser194, inactivating rala and abolishing its transforming function | SIGNOR-155349 |
P29474 | P54760 | 0 | phosphorylation | up-regulates activity | 0.311 | These results suggest that activation of Eph-B4 with Ephrin-B2/Fc stimulates eNOS phosphorylation in vitro (XREF_FIG), eg, eNOS may be a downstream mediator of Eph-B4 signaling in endothelial cells. | SIGNOR-279172 |
P15056 | O00141 | 0 | phosphorylation | down-regulates activity | 0.344 | Serum- and glucocorticoid-inducible kinase SGK phosphorylates and negatively regulates B-Raf.|We observed that SGK inhibits B-Raf activity. | SIGNOR-279110 |
P41134 | Q9UQM7 | 0 | phosphorylation | up-regulates activity | 0.2 | Here we show that CaMKII can directly phosphorylate Beclin 1 at Ser90 to promote K63-linked ubiquitination of Beclin 1 and activation of autophagy. | SIGNOR-277367 |
Q13535 | O75943 | 1 | phosphorylation | up-regulates activity | 0.858 | Here we demonstrate that atr but not atm phosphorylates the human rad17 (hrad17) checkpoint protein on ser(635) and ser(645) in vitro.The rfc-related checkpoint protein rad17, a phosphorylation substrate of atr, is critical for atr-mediated checkpoint signaling and cell survival. | SIGNOR-111248 |
Q9Y6E0 | Q15208 | 1 | phosphorylation | up-regulates | 0.381 | Ndr1/ndr2 protein kinase is activated by phosphorylation on the activation loop phosphorylation site ser281/ser282 and the hydrophobic motif phosphorylation site thr444/thr442. Autophosphorylation of ndr is responsible for phosphorylation on ser281/ser282, whereas thr444/thr442 is targeted by an upstream kinase. Here we show that mst3, a mammalian ste20-like protein kinase, is able to phosphorylate ndr protein kinase at thr444/thr442. In vitro, mst3 selectively phosphorylated thr442 of ndr2, resulting in a 10-fold stimulation of ndr activity. | SIGNOR-142467 |
P31269 | O15550 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.323 | 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-260025 |
O94916 | P29350 | 0 | dephosphorylation | down-regulates activity | 0.343 | We confirmed that SHP-1 is inhibitory by overexpressing it, which reduces TonEBP/OREBP transcriptional activity at 500 mosmol/kg. SHP-1 dephosphorylates TonEBP/OREBP at a known regulatory site, Y143, both in vivo and in vitro. It inhibits TonEBP/OREBP by both reducing TonEBP/OREBP nuclear localization, which is Y143 dependent, and by lowering high NaCl-induced TonEBP/OREBP transactivating activity | SIGNOR-248467 |
Q92823 | Q01484 | 1 | relocalization | up-regulates quantity | 0.737 | Neurofascin, L1, NrCAM, NgCAM, and neuroglian are membrane-spanning cell adhesion molecules with conserved cytoplasmic domains that are believed to play important roles in development of the nervous system. This report presents biochemical evidence that the cytoplasmic domains of these molecules associate directly with ankyrins, a family of spectrin-binding proteins located on the cytoplasmic surface of specialized plasma membrane domains. | SIGNOR-266719 |
P01116 | Q07889 | 0 | guanine nucleotide exchange factor | up-regulates | 0.828 | Because the KRAS-GDP to KRAS-GTP transition catalyzed by the GEF, son of sevenless 1 (SOS1), represents the rate-limiting step for nucleotide exchange, disrupting the activating SOS1/KRAS protein interaction has also been the focus of drug development efforts | SIGNOR-141647 |
P62140 | 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-248576 |
P17612 | Q13936 | 1 | phosphorylation | up-regulates activity | 0.498 | These findings reveal an essential role for _1C phosphorylation at Ser1928 in stimulating CaV1.2 channel activity and vasoconstriction by AKAP-targeted PKA upon exposure to increased glucose and in diabetes | SIGNOR-251709 |
Q13131 | Q13085 | 1 | phosphorylation | down-regulates activity | 0.7 | We have isolated and purified from rat livers a novel kinase that phosphorylates and inactivates the carboxylase Ser1200 isphosphorylated by both CAMP-dependent protein kinase and AMP-activated protein kinase | SIGNOR-250400 |
Q06124 | Q14289 | 1 | dephosphorylation | down-regulates activity | 0.725 | We demonstrate that RAFTK is a direct substrate of SHP2 both in vitro and in vivo, and that Tyr(906) in the C-terminal domain of RAFTK mediates its interaction with SHP2. |We demonstrate that RAFTK is a direct substrate of SHP2 both in vitro and in vivo, and that Tyr(906) in the C-terminal domain of RAFTK mediates its interaction with SHP2. Moreover, overexpression of dominant negative SHP2 blocked the protective effect of IL-6 against Dex-induced apoptosis. These findings demonstrate that SHP2 mediates the anti-apoptotic effect of IL-6 and suggest SHP2 as a novel therapeutic target in MM..... 1) RAFTK is a substrate of SHP2 in vitro and 2) dephosphorylation of RAFTK by SHP2 inhibits its kinase activity. | SIGNOR-277084 |
Q96EP1 | O14965 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.471 | Chfr, a mitotic stress checkpoint, plays an important role in cell cycle progression, tumor suppression and the processes that require the E3 ubiquitin ligase activity mediated by the RING finger domain. Chfr stimulates the formation of polyubiquitin chains by ub-conjugating enzymes, and induces the proteasome-dependent degradation of a number of cellular proteins including Plk1 and Aurora A. | SIGNOR-271463 |
Q86T82 | P20248 | 1 | deubiquitination | up-regulates quantity by stabilization | 0.581 | USP37 Binds, Deubiquitinates, and Stabilizes Cyclin A | SIGNOR-265052 |
P40189 | P07947 | 1 | phosphorylation | up-regulates activity | 0.2 | Binding of LIF to the LIFR-gp130 receptor complex has been previously shown to activate YES and YAP/TAZ-TEAD -dependent transcription, which is required to maintain self-renewal in embryonic stem cells | SIGNOR-278033 |
Q9UKB1 | Q13485 | 1 | ubiquitination | up-regulates | 0.2 | We have identified scf(beta-trcp1), a ubiquitin (e3) ligase, as a critical determinant for the protein degradation of smad4 protein. | SIGNOR-123060 |
P04637 | P50613 | 0 | phosphorylation | up-regulates | 0.458 | The cdk7-cych-p36 complex of transcription factor iih phosphorylates p53, enhancing its sequence-specific dna binding activity in vitro. serines 371, 376, 378, and 392 may be the potential sites for this kinase. | SIGNOR-51292 |
Q9Y2A9 | Q9NZQ7 | 1 | glycosylation | up-regulates activity | 0.2 | These results further suggested that B3GNT3 mediates PD-L1 and PD-1 interaction through N-linked glycosylation instead of O-linked glycosylation | SIGNOR-275389 |
P26678 | P17612 | 0 | 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 |
P51812 | P16104 | 1 | phosphorylation | up-regulates activity | 0.2 | Herein, we found that ribosomal S6 kinase 2 (RSK2) directly phosphorylates histone H2AX at Ser139 and also at a newly discovered site, Ser16.|Phosphorylated RSK2 and histone H2AX colocalized in the nucleus following EGF treatment, and the phosphorylation of histone H2AX by RSK2 enhanced the stability of histone H2AX and prevented cell transformation induced by EGF. | SIGNOR-279349 |
Q14469 | P15172 | 1 | transcriptional regulation | down-regulates activity | 0.294 | Notch signaling up-regulated HES1 mRNA expression within 1 h and subsequently reduced expression of MyoD mRNA | SIGNOR-243181 |
P55211 | P27361 | 0 | phosphorylation | down-regulates activity | 0.535 | Inhibition of caspase-9 through phosphorylation at thr 125 by erk mapk | SIGNOR-101548 |
Q9HC98 | Q13200 | 1 | phosphorylation | up-regulates activity | 0.2 | Seven of these kinases (PIM1/2/3, MAP4K1/2, PKA, and NEK6) directly and robustly phosphorylated recombinant GST-Rpn1 at S361 in vitro (Fig. 3D and SI Appendix, Fig. S3 A and B). | SIGNOR-273894 |
O14920 | O43318 | 0 | phosphorylation | up-regulates activity | 0.755 | Tak1 become activated and then phosphorylates and activates ikk2 which in turn now phosphorylates ikba, marking it for k48-ubiquitination and proteasomal degradation. tak1 kinase complex phosphorylates and activates ikk in a manner that depends on traf6 and ubc13-uev1a our studies suggests that tak1_ acts as an upstream activating kinase for ikkbeta. | SIGNOR-109490 |
P84243 | Q92831 | 0 | acetylation | down-regulates activity | 0.2 | The HAT module within the SAGA and ADA complexes acetylates histone H3, mainly on residues K9 and K14. | SIGNOR-269620 |
O14733 | Q9Y2U5 | 0 | phosphorylation | up-regulates activity | 0.603 | MEKK2 can phosphorylate and activate MAP2K proteins MKK7 and MEK5, thereby promoting activation of JNK and ERK5, respectively [ xref ]. | SIGNOR-279212 |
P21453 | P31749 | 0 | phosphorylation | up-regulates activity | 0.704 | Activated akt binds to edg-1 and phosphorylates the third intracellular loop at the t(236) residue. Transactivation of edg-1 by akt is not required for g(i)-dependent signaling but is indispensable for rac activation, cortical actin assembly, and chemotaxis | SIGNOR-252467 |
P35575 | P04150 | 0 | transcriptional regulation | up-regulates quantity | 0.2 | Further, CRTC2 is required for the glucocorticoid-associated cooperative mRNA expression of the glucose-6-phosphatase, a rate-limiting enzyme for hepatic gluconeogenesis, by facilitating the attraction of GR and itself to its promoter region already occupied by CREB | SIGNOR-256104 |
Q86UZ6 | P23219 | 1 | 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 |
P21860 | Q00535 | 0 | phosphorylation | up-regulates activity | 0.341 | We demonstrated that Cdk5 phosphorylated Ser-1176 in the neuregulin receptor ErbB2 and phosphorylated Thr-871 and Ser-1120 in the ErbB3 receptor. We identified the Ser-1120 sequence RSRSPR in ErbB3 as a novel phosphorylation consensus sequence of Cdk5. Finally, we found that Cdk5 activity is involved in neuregulin-induced Akt activity and neuregulin-mediated neuronal survival. | SIGNOR-250663 |
Q86TM6 | Q16236 | 1 | 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 |
Q9HCK8 | Q9HD90 | 1 | transcriptional regulation | down-regulates quantity | 0.2 | Many of the most significantly up-regulated genes in Chd8+/− and Chd8−/− NPCs are involved in later stages of neuronal development, including Ascl1 [a central driver of neural reprogramming (29)], Dcx, Map2, Nefm, Neurod4, and Neurog1 (Fig. 2 E and F). Additionally, we found that Sox3 is derepressed in both Chd8+/− and Chd8−/− NPCs, and several other Sox TF members (Sox2, Sox7, and Sox11) became derepressed in the Chd8−/− cells | SIGNOR-268918 |
P10636 | P19525 | 0 | phosphorylation | up-regulates quantity | 0.2 | Interestingly, PKR phosphorylated tau directly and no detectable labeling occurred when tau was incubated with 32 P\u2010ATP alone (Figure\u00a0 xref right).|PKR kinase directly regulates tau expression and Alzheimer's disease-related tau phosphorylation. | SIGNOR-279735 |
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