IdA string | IdB string | labels int64 | mechanism string | effect string | score float64 | sentence string | signor_id string |
|---|---|---|---|---|---|---|---|
P51532 | Q96EP1 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.333 | Here we report that CHFR interacts with BRG1, SNF5, and BAF60a of the SWI/SNF-like BAF complex and ubiquitinates them to target for degradation through a proteasome-mediated pathway, and that SRG3/mBAF155 stabilizes these components by blocking their interaction with CHFR. These results suggest that CHFR enhances the degradation of the components of the SWI/SNF-like BAF complex by inducing their poly-ubiquitination. | SIGNOR-271457 |
O00560 | P59637 | 0 | 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 |
Q96JP5 | P52597 | 1 | ubiquitination | down-regulates quantity | 0.2 | Collectively, our results indicate that ZFP91 polyubiquitinated hnRNP F at Lys 185.|We found that silencing ZFP91 increased hnRNP F protein levels, but not hnRNP F mRNA levels, while ectopically expressing ZFP91 decreased hnRNP F protein levels, but not hnRNP F mRNA levels. | SIGNOR-278802 |
P21462 | P25098 | 0 | phosphorylation | down-regulates activity | 0.2 | Phosphorylation of the FPR carboxyl terminus by GRK2 is the result of a high affinity interaction and proceeds in a hierarchical manner. sequential mechanism of phosphorylation beginning with residues 328 and/or 329, followed by residues 331 and/or 332, and finally residues 334 through 339. Attenuation of receptor-mediated signal amplification in response to external stimuli, an essential step in the balance of cellular activation, may be mediated by receptor phosphorylation. | SIGNOR-251452 |
Q99708 | P24941 | 0 | phosphorylation | up-regulates | 0.617 | Collectively, these findings thereby provided strong support for ctip thr-847 indeed being a cdk target. it is established that both cdk-dependent and checkpoint-dependent phosphorylations are required for activation of sae2/ctip in vivo | SIGNOR-183840 |
P04150 | O43524 | 1 | transcriptional regulation | up-regulates quantity | 0.415 | We show that FOXO3 is an immediate early glucocorticoid receptor (GR) target, whose transcription is even further enhanced by conditions that mimic metabolic stress. | SIGNOR-255759 |
O14929 | P62805 | 1 | acetylation | down-regulates activity | 0.2 | Histone acetyltransferase 1 is the founding member of the histone acetyltransferase superfamily and catalyzes lysine acetylation of newly synthesized histone H4|Lys12 for direct attack of the acetyl group of the cofactor.| It is postulated that histone acetylation, through charge neutralization of the cationic histone tails, weakens nucleosomal electrostatic interactions with anionic DNA, thus destabilizing internucleosomal contacts and nucleosomal structure and facilitating access to the promoter region for RNA polymerase and transcription factors. | SIGNOR-264790 |
P42226 | O43474 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.345 | STAT6 coordinates and synergizes with both PPAR? and Krppel-like factor 4 (KLF4), a member of a family of proteins that contribute to macrophage function. | SIGNOR-249568 |
Q13976 | P10644 | 1 | phosphorylation | up-regulates activity | 0.234 | In this study, we further examined the potential of RIα phosphorylation to regulate physiologically relevant "desensitization" of PKAc activity. First, the serine 101 site of RIα was validated as a target of PKGIα phosphorylation both in vitro and in cells.These findings suggest that RIα phosphorylation may be a novel mechanism to circumvent the requirement of cAMP stimulus to activate type I PKA in cells. | SIGNOR-277383 |
Q9Y6X9 | P06493 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Mechanically, PTX and VCR activate cyclin-dependent kinase 1, which in turn induces MORC2 phosphorylation at threonine 717 (T717) and T733. Phosphorylated MORC2 enhances its interation with HSPA8 and LAMP2A, two essential components of the chaperone-mediated autophagy (CMA) mechinery, resulting in its autophagic degradation. | SIGNOR-277837 |
P37231 | Q96EB6 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.695 | Interestingly, SIRT1 suppresses PPARγ but activates PGC-1α , and thus affects the clock network through multiple mechanisms. | SIGNOR-268032 |
P04629 | P19174 | 1 | phosphorylation | up-regulates | 0.652 | The nerve growth factor (ngf) receptor/trk associated with and phosphorylated phospholipase c gamma (plc gamma) | SIGNOR-38538 |
Q9UGI0 | Q9P2Y5 | 1 | deubiquitination | up-regulates activity | 0.2 | Here we report that UVRAG is ubiquitinated by SMURF1 at lysine residues 517 and 559, which decreases the association of UVRAG with RUBCN and promotes autophagosome maturation. However, the deubiquitinase ZRANB1 specifically cleaves SMURF1-induced K29 and K33-linked polyubiquitin chains from UVRAG, thereby increasing the binding of UVRAG to RUBCN and inhibiting autophagy flux. | SIGNOR-273651 |
Q9Y566 | Q9P1A6 | 0 | relocalization | up-regulates activity | 0.756 | 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-264589 |
Q92882 | Q15418 | 0 | phosphorylation | down-regulates activity | 0.352 | SH3P2 was phosphorylated on Ser(202) by ribosomal S6 kinase (RSK) in an ERK pathway-dependent manner, and such phosphorylation inhibited the ability of SH3P2 to suppress cell motility. | SIGNOR-273838 |
Q9NXA8 | P31327 | 1 | post translational modification | up-regulates activity | 0.508 | Glutarylation suppresses CPS1 activity, which is targeted by SIRT5 for removal|SIRT5 can catalyze the enzymatic removal of lysine glutarylation | SIGNOR-267643 |
P10275 | P07288 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.822 | TH1 also associates with AR at the active androgen-responsive prostate-specific antigen (PSA) promoter in the nucleus of LNCaP cells. Decrease of endogenous AR protein by TH1 interferes with androgen-induced luciferase reporter expression and reduces endogenous PSA expression. | SIGNOR-253657 |
Q16654 | P08559 | 1 | phosphorylation | down-regulates | 0.686 | Mammalian pyruvate dehydrogenase (?2_2) (e1) is regulated by phosphorylation-dephosphorylation, catalyzed by the e1-kinase and the phospho-e1-phosphatase. | SIGNOR-33201 |
Q96RI1 | P17252 | 0 | phosphorylation | up-regulates | 0.325 | Phosphorylation of farnesoid x receptor by protein kinase c promotes its transcriptional activity. pkcalpha phosphorylates in vitro fxr in its dna-binding domain on s135 and s154. | SIGNOR-180537 |
P84243 | Q09472 | 0 | acetylation | down-regulates activity | 0.2 | These results highlight the substrate and site specificities of hats in cells, demonstrate the distinct roles of gcn5/pcaf- and cbp/p300-mediated histone acetylations in gene activation, and suggest an important role of cbp/p300-mediated h3k18/27ac in nr-dependent transcription. | SIGNOR-170266 |
Q16236 | O96013 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.2 | PAK4 directly phosphorylated Nrf2 at T369, and it led to its nuclear export and proteasomal degradation, all of which impaired antioxidant responses in hepatocytes. | SIGNOR-277583 |
P07237 | Q8IXL6 | 0 | phosphorylation | up-regulates activity | 0.387 | The secretory pathway kinase Fam20C phosphorylates Ser357 of PDI and responds rapidly to various ER stressors. Phosphorylation of Ser357 induces an open conformation of PDI and turns it from a "foldase" into a "holdase", which is critical for preventing protein misfolding in the ER. Phosphorylated PDI also binds to the lumenal domain of IRE1α, a major UPR signal transducer, and attenuates excessive IRE1α activity. | SIGNOR-275574 |
P27448 | Q13470 | 1 | phosphorylation | down-regulates activity | 0.2 | We also discover a MARK-mediated phosphorylation on TNK1 at S502 that promotes an interaction between TNK1 and 14-3-3, which sequesters TNK1 and inhibits its kinase activity.Phosphorylation of TNK1 at S502 within the proline rich domain is required for TNK1 binding to 14-3-3.MARKs mediate phosphorylation at S502 and 14-3-3 binding to TNK1, which restrains the movement of TNK1 into heavy membrane-associated clusters. | SIGNOR-273868 |
Q96MT8 | Q96SN8 | 0 | relocalization | up-regulates activity | 0.692 | Primary microcephaly (MCPH) associated proteins CDK5RAP2, CEP152, WDR62 and CEP63 colocalize at the centrosome. We found that they interact to promote centriole duplication and form a hierarchy in which each is required to localize another to the centrosome, with CDK5RAP2 at the apex, and CEP152, WDR62 and CEP63 at sequentially lower positions. MCPH proteins interact with distinct centriolar satellite proteins; CDK5RAP2 interacts with SPAG5 and CEP72, CEP152 with CEP131, WDR62 with MOONRAKER, and CEP63 with CEP90 and CCDC14. These satellite proteins localize their cognate MCPH interactors to centrosomes and also promote centriole duplication. Consistent with a role for satellites in microcephaly, homozygous mutations in one satellite gene, CEP90, may cause MCPH. The satellite proteins, with the exception of CCDC14, and MCPH proteins promote centriole duplication by recruiting CDK2 to the centrosome. | SIGNOR-271722 |
P04637 | Q66K89 | 0 | ubiquitination | up-regulates activity | 0.608 | E4F1 Has an Intrinsic Ubiquitin E3 Ligase Activity that Drives K48-type Ubiquitylation of p53. These data demonstrate that E4F1 stimulates the ubiquitylation of p53 on the lysine cluster K319–K321, i.e., at sites distinct from those targeted by Hdm2. p53 forms Ubiquitylated by E4F1 Are Localized on Chromatin. In striking contrast with Ub-p53 forms stimulated by Hdm2, which are mainly cytosoluble and targeted to the proteasome, we found that E4F1-stimulated Ub-p53 forms are tightly associated with chromatin, suggesting that they could be involved in transcription. | SIGNOR-271394 |
P45983 | P55957 | 1 | phosphorylation | up-regulates activity | 0.594 | (b) Phosphorylation of Bid at Thr59 by JNK1 and JNK2 (in vitro kinase assay). | SIGNOR-279076 |
Q9Y6K9 | P78527 | 0 | phosphorylation | down-regulates activity | 0.296 | Here, we show that DNA-dependent protein kinase (DNA-PK), an enzyme involved in DNA double-strand break (DSB) repair, triggers the phosphorylation of NEMO by genotoxic stress, thereby enabling shuttling of NEMO through the nucleus with subsequent NF-κB activation. We identified serine 43 of NEMO as a DNA-PK phosphorylation site and point mutation of this serine to alanine led to a complete block of NF-κB activation by ionizing radiation (IR). | SIGNOR-277508 |
O75151 | Q16695 | 1 | demethylation | down-regulates activity | 0.2 | PHF2, a jmjC demethylase, is enzymatically inactive by itself, but becomes an active H3K9Me2 demethylase through PKA-mediated phosphorylation. This modification leads to targeting of the PHF2–ARID5B complex to its target promoters, where it removes the repressive H3K9Me2 mark. | SIGNOR-264520 |
P0C0S5 | 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-265408 |
P07288 | Q9NY61 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Chromatin immunoprecipitation in combination with siRNA-mediated knockdown revealed that recruitment of AATF and ZIPK to the PSA enhancer was dependent on AR, whereas recruitment of TSG101 was dependent on AATF. | SIGNOR-253669 |
P06493 | Q8IXJ6 | 1 | phosphorylation | down-regulates | 0.412 | Here, we demonstrate that sirt2 is phosphorylated both in vitro and in vivo on serine 368 by the cell-cycle regulator, cyclin-dependent kinase 1. Overexpression of sirt2 mediates a delay in cellular proliferation that is dependent on serine 368 phosphorylation. | SIGNOR-154681 |
P48730 | P56645 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.719 | 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-267998 |
P80188 | O94916 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.329 | As expected, the depletion of NFAT5 decreased the S100A4 and LCN2 mRNA levels (Figure 3a). In addition, chromatin immunoprecipitation (ChIP) assay using NFAT5 antibody indicated that NFAT5 was bound to the S100A4 and LCN2 promoters (Figure 3b, Supplementary Figure S3), as expected (Chen et al., 2009). | SIGNOR-274114 |
Q14493 | P68431 | 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-265413 |
Q14493 | P0DPK5 | 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-265416 |
O96013 | Q16236 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | PAK4 directly phosphorylated Nrf2 at T369, and it led to its nuclear export and proteasomal degradation, all of which impaired antioxidant responses in hepatocytes. | SIGNOR-277583 |
Q96P20 | Q13153 | 0 | phosphorylation | up-regulates activity | 0.2 | Pak1 phosphorylates NLRP3 to promote inflammasome activation. | SIGNOR-277547 |
Q00535 | P54646 | 1 | phosphorylation | down-regulates activity | 0.216 | In vitro, the results show that murine wild-type AMPK-alpha2 was phosphorylated by Cdk5 at a (S/T) PX (K/H/R) phosphorylation consensus sequence, which was associated with decreased AMPK-alpha2 activity.|Inactivated AMPK-alpha2 promotes the progression of diabetic brain damage by Cdk5 phosphorylation at Thr485 site. | SIGNOR-280218 |
P12931 | Q14847 | 1 | phosphorylation | up-regulates activity | 0.253 | Integrin-dependent translocation of LASP-1 to the cytoskeleton of activated platelets correlates with LASP-1 phosphorylation at tyrosine 171 by Src-kinase | SIGNOR-271706 |
Q9UHW9 | Q9UEW8 | 0 | phosphorylation | down-regulates activity | 0.569 | We observed that in vitro activated STE20/SPS1-related proline/alanine-rich kinase (SPAK) complexed to its regulatory MO25 subunit phosphorylated KCC3 at Ser-96 and that in Xenopus laevis oocytes Ser-96 of human KCC3 is phosphorylated in isotonic conditions and becomes dephosphorylated during incubation in hypotonicity, leading to a dramatic increase in KCC3 function. | SIGNOR-276597 |
P45984 | Q5JR12 | 1 | phosphorylation | down-regulates | 0.2 | Specific phosphorylation of pp2czeta at ser (92) by stress-activated jnk attenuates its phosphatase activity in cells. | SIGNOR-178934 |
P84243 | P41231 | 0 | demethylation | up-regulates activity | 0.2 | KDM5 subfamily is capable of removing tri‐ and di‐ methyl marks from lysine 4 on histone H3 (H3K4). Depending on the methylation site, its effect on transcription can be either activating or repressing. | SIGNOR-264307 |
P53778 | Q86X55 | 1 | phosphorylation | down-regulates activity | 0.363 | Here, we identify a role for the mitogen-activated protein kinase (MAPK) p38g/MAPK12 as a critical regulator of satellite stem cell fate through phosphorylation of Carm1. | SIGNOR-255897 |
P35222 | P17252 | 0 | phosphorylation | down-regulates | 0.413 | As shown in Fig. 1 B, PKCalpha readily phosphorylated Ser33 and Ser37 / Thr41 on full-length beta-catenin (beta-catenin 1 - 781) and CTD deletion mutant (beta-catenin 1-682).|To examine the effect of the armadillo repeats 1-5 on PKCalpha mediated beta-catenin degradation, DNA constructs expressing beta-catenin 1 - 781 and beta-catenin deletion mutants (beta-catenin 1-422 and beta-catenin 1-138) were transfected into HEK293 cells, followed by treatment with increasing concentrations of A23187 and CGK062, which are known activators of PKCalpha. | SIGNOR-278492 |
Q9UBK2 | P78527 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Mechanistically, PGC1α was phosphorylated at serine (S) 636 by DNA-dependent protein kinase in response to irradiation. Phosphorylation at S636 promoted the degradation of PGC1α by facilitating its binding to the E3 ligase RNF34. | SIGNOR-277911 |
O43683 | Q13315 | 0 | phosphorylation | up-regulates | 0.461 | We also demonstrate that mitotically activated atm phosphorylates bub1, a critical kinetochore protein, on ser314. Atm-mediated bub1 ser314 phosphorylation is required for bub1 activity and is essential for the activation of the spindle checkpoint | SIGNOR-177276 |
P14651 | P32243 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Transactivation of the mouse OTX2 Luc constructs by the human HOXB1, HOXB2, and HOXB3 proteins. | Likewise, the construct pOTX2LucΔ−710 showed an 8-, 12-, and 6-fold increase in transcriptional activity if co-transfected with pSG-HOXB1, -HOXB2, and -HOXB3, respectively | SIGNOR-261635 |
Q16620 | Q92529-2 | 1 | phosphorylation | up-regulates activity | 0.755 | We also obtained tryptic phosphopeptide maps of N-Shc protein phosphorylated in vitro by other tyrosine kinases, TrkB, v-Src and EGFR. The overall patterns of the phosphopeptide maps generated by these tyrosine kinases were similar, although there were some differences among these maps (Figure 4a–d).We performed phosphopeptide mapping analysis using GST-fused N-Shc protein, and found that N-Shc phosphorylated by TrkA in vitro was resolved into at least seven phosphopeptides (Y1 through Y7, Figure 4a). Phosphopeptide mapping revealed that N-Shc has novel tyrosine-phosphorylation sites at Y259/Y260 and Y286; in vivo-phosphorylation of these tyrosines was demonstrated by site-specific anti-pTyr antibodies. Phosphorylated Y286 bound to several proteins, of which one was Crk. The pY221/pY222 site, corresponding to one of the Grb2-binding sites of Shc, also preferentially bound to Crk. The phosphorylation-dependent interaction between N-Shc and Crk was demonstrated in vitro and in vivo. | SIGNOR-273917 |
Q08881 | P10747 | 1 | phosphorylation | up-regulates | 0.69 | We demonstrate that emt can phosphorylate all four tyrosines of the cd28 tail, in contrast to lck, which phosphorylates only tyrosine 173. Together with evidence that in vivo, tyrosines other than tyrosine 173 become phosphorylated following cd28 stimulation, this finding suggests that, like lck, one function of emt during cd28 signaling is phosphorylation of the receptor | SIGNOR-198747 |
P15056 | Q13164 | 1 | phosphorylation | up-regulates quantity | 0.292 | Our data indicate that oncogenic BRAF increases ERK5 protein level, phosphorylation at several residues and kinase activity.|Overexpression of oncogenic BRAF induced ERK5 phosphorylation at Thr218 and Tyr220, although to a lower level than that induced by MEK5DD. | SIGNOR-278353 |
P36956 | P54646 | 0 | phosphorylation | down-regulates | 0.328 | Here we demonstrate that ampk interacts with and directly phosphorylates sterol regulatory element binding proteins (srebp-1c and -2). Ser372 | SIGNOR-173031 |
Q9BXS5 | Q2M2I8 | 0 | phosphorylation | up-regulates | 0.2 | Aak1 is enriched at presynaptic terminals, whereas in nonneuronal cells it colocalizes with clathrin and ap2 in clathrin-coated pits and at the leading edge of migrating cells. Aak1 specifically phosphorylates the mu subunit in vitro, and stage-specific assays for endocytosis show that mu phosphorylation by aak1 results in a decrease in ap2-stimulated transferrin internalization. Together, these results provide strong evidence that aak1 is the endogenous mu 2 kinase and plays a regulatory role in clathrin-mediated endocytosis. | SIGNOR-115589 |
Q14232 | P41091 | 1 | guanine nucleotide exchange factor | up-regulates activity | 0.694 | EIF2B converts the protein synthesis initiation factor 2 (eIF2) from an inactive GDP-bound form to an active eIF2-GTP complex owing to its guanine nucleotide exchange factor (GEF) activity. | SIGNOR-269134 |
P49841 | Q05655 | 0 | phosphorylation | down-regulates activity | 0.271 | In the TFEB activation pathway, activated PKC\u03b4 phosphorylates and inactivates GSK3\u03b2, leading to the reduced phosphorylation of TFEB at Ser134 and Ser138 residues; this reduced phosphorylation is critical for the cytoplasmic sequestration of TFEB.|In the TFEB activation pathway, activated PKCdelta phosphorylates and inactivates GSK3beta, leading to the reduced phosphorylation of TFEB at Ser134 and Ser138 residues; this reduced phosphorylation is critical for the cytoplasmic sequestration of TFEB. | SIGNOR-280084 |
P50552 | P31939 | 1 | phosphorylation | up-regulates activity | 0.342 | ATIC and VASP phosphorylation is dependent on NPM-ALK kinase activity. | SIGNOR-276172 |
P06730 | P42345 | 0 | phosphorylation | down-regulates activity | 0.801 | Mechanistic target of rapamycin complex 1 (mTORC1) phosphorylates and inhibits eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1). | SIGNOR-278963 |
O43524 | Q00534 | 0 | phosphorylation | up-regulates activity | 0.464 | CDK6 and cyclin D3 complex phosphorylates FOXO3 on S325.|Using cycloheximide (CHX), we observed that CDK6 knockdown decreased FOXO3 stability, particularly in platinum treated cells (Fig XREF_FIG A) and that, following platinum treatment, FOXO3 WT was more stable than the non phosphorylatable mutant FOXO3 S325A (Fig XREF_FIG B). | SIGNOR-279023 |
Q68CZ1 | Q04206 | 1 | demethylation | down-regulates | 0.2 | Fbxl11 and nsd1 have opposite effects on nf-kb; both bind to p65 subunit after activation of nf-kb. / nsd1 activates nf-kb and reverses the inhibitory effect of fbxl11 / these data confirm that fbxl11 and nsd1 constitute an enzyme pair that methylates and demethylates p65 on k218 and 221 in response to cytokine stimulation. | SIGNOR-163320 |
Q01484 | P11532 | 1 | relocalization | up-regulates quantity | 0.53 | 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-266712 |
Q92793 | Q13351 | 1 | acetylation | up-regulates activity | 0.49 | EKLF residues acetylated by CREB binding protein (CBP) in vitro map to Lys-288 in its transactivation domain and Lys-302 in its zinc finger domain. | SIGNOR-251826 |
P35568 | P08069 | 0 | phosphorylation | up-regulates | 0.868 | Binding of IGF1 to its receptor leads to activation of its intrinsic tyrosine kinase and autophosphorylation, thus generating docking sites for insulin receptor substrate (IRS), which is also phosphorylated by the IGF1 receptor. | SIGNOR-175665 |
P01116 | Q8N9B8 | 0 | guanine nucleotide exchange factor | up-regulates | 0.427 | Gefs catalyse the transition from gdp-bound, inactive ras to gtp-bound, active ras. | SIGNOR-183826 |
Q96EB6 | P24941 | 0 | phosphorylation | up-regulates activity | 0.465 | Sirt1 is in turn phosphorylated by Cdk2, which may further regulate its activity.|Taken together, these data demonstrate that Cdk2 deletion does not decrease Hif1\u03b1 expression induced by HX, and strongly suggests that the phosphorylation of Sirt1 at Ser47 by Cdk2 requires Sirt1 deacetylase activity. | SIGNOR-279513 |
Q9Y6K9 | Q9BVN2 | 0 | null | up-regulates quantity by stabilization | 0.308 | NESCA interacts with the IKK complex by the N-terminal region of NEMO. This experiment revealed that the overexpression of NESCA completely abolished the TRAF6-mediated polyubiquitination of NEMO, as it appears by using either anti-HA (Fig. 5A) or anti-NEMO (Fig. 5B) antibodies on immunoprecipitated extracts. | SIGNOR-272775 |
Q13627 | O43524 | 1 | phosphorylation | down-regulates | 0.359 | Additionally, ck1, dyrk1a, and cdk2 also phosphorylate foxos at various sites to inhibit foxos activity phosphorylation of foxos by akt, ikk, erk, ck1, cdk2, and dyrk1a universally leads to foxo's inhibition. | SIGNOR-183674 |
Q9Y4A8 | Q13093 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.363 | Moreover, we demonstrated that nuclear factor erythroid 2-related factor 3 (Nrf3) regulates Pla2g7 gene expression through direct binding to the promoter regions of Pla2g7 gene. | SIGNOR-268979 |
O60674 | Q01344 | 0 | phosphorylation | up-regulates activity | 0.602 | Jak 2 is physically associated with the IL-5b receptor. The binding of IL-5 to its receptor results in tyrosine phosphorylation and activation of Jak 2 tyrosine kinase within 1 to 3 min. | SIGNOR-254352 |
Q9Y5U4 | Q8WU17 | 0 | ubiquitination | down-regulates quantity | 0.436 | Induction of TRC8 destabilized the precursor forms of the transcription factors SREBP-1 and SREBP-2. TRC8 destablizes SREBP precursors in a RING and proteasome-dependent manner | SIGNOR-271956 |
Q16695 | O75151 | 0 | demethylation | down-regulates activity | 0.2 | PHF2, a jmjC demethylase, is enzymatically inactive by itself, but becomes an active H3K9Me2 demethylase through PKA-mediated phosphorylation. This modification leads to targeting of the PHF2–ARID5B complex to its target promoters, where it removes the repressive H3K9Me2 mark. | SIGNOR-264520 |
P67870 | Q99250 | 1 | phosphorylation | up-regulates activity | 0.2 | We found that the ankyrin-binding motif of Na(v)1.2 that determines channel concentration at the AIS depends on a glutamate residue (E1111), but also on several serine residues (S1112, S1124, and S1126). We showed that phosphorylation of these residues by protein kinase CK2 (CK2) regulates Na(v) channel interaction with ankyrins. | inhibition of CK2 activity reduced sodium channel accumulation at the AIS of neurons. In conclusion, CK2 contributes to sodium channel organization by regulating their interaction with ankyrin G. | SIGNOR-275752 |
P68400 | Q16623 | 1 | phosphorylation | up-regulates | 0.366 | In this report, we show that syntaxin-1a is phosphorylated in vitro by cki on thr21. Casein kinase ii (ckii) has been shown previously to phosphorylate syntaxin-1a in vitro and we have identified ser14 as the ckii phosphorylation site. the phosphorylation of syntaxin-1a by ckii enhances its capacity to associate with synaptotagmin [21]. Therefore, phosphorylation of ser14 by ckii suggests an important role for this residue in regulating the interaction between syntaxin-1a and synaptotagmin | SIGNOR-114840 |
Q8TB45 | P48729 | 0 | phosphorylation | down-regulates | 0.2 | Phosphorylation of all three serine residues in the deptor degron (ser286, ser287, and ser291) is necessary for - and directly mediates - the interaction with _trcp. ck1 phosphorylated the degron of deptor, as shown by western blotting with the phospho-specific antibody (fig. S3e-f). In contrast, mtor alone was unable to induce phosphorylation of deptor on ser286, ser287, and ser291. | SIGNOR-176871 |
P84243 | P51812 | 0 | phosphorylation | down-regulates activity | 0.2 | Phosphorylation at ser-11 (h3s10ph) by rps6ka4 and rps6ka5 is important during interphase because it enables the transcription of genes following external stimulation, like mitogens, stress, growth factors or uv irradiation and result in the activation of genes, such as c-fos and c-jun. | SIGNOR-138471 |
P48029 | O60674 | 0 | relocalization | down-regulates activity | 0.2 | Janus-activated kinase-2 (JAK2) participates in the regulation of the Na⁺-coupled glucose transporter SGLT1 and the Na⁺-coupled amino acid transporter SLC6A19. JAK2 is a novel regulator of the creatine transporter SLC6A8, which downregulates the carrier, presumably by interference with carrier protein insertion into the cell membrane. | SIGNOR-265781 |
Q9BYH8 | Q16552 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.381 | In cooperation with RORγt and RORα, IκBζ enhances Il17a expression by binding directly to the regulatory region of the Il17a gene. | SIGNOR-266210 |
P06213 | P29122 | 0 | cleavage | up-regulates activity | 0.2 | Here we demonstrate that the two IR isoforms are similarly cleaved by furin, but when this furin-dependent maturation is inefficient, IR proforms move to the cell surface where the proprotein convertase PACE4 selectively supports IRB maturation. | SIGNOR-260366 |
Q09472 | O15105 | 1 | acetylation | up-regulates | 0.464 | Here we present evidence that smad7 interacts with the transcriptional coactivator p300, resulting in acetylation of smad7 on two lysine residues in its n terminus. Acetylation or mutation of these lysine residues stabilizes smad7 and protects it from tgfbeta-induced degradation. we have recently shown that smad7 is acetylated on lysine residues 64 and 70 by p300 | SIGNOR-95169 |
Q13547 | Q96EP1 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.394 | Histone deacetylase 1 (HDAC1), which represses transcription by deacetylating histones, was newly isolated as a Chfr-interacting protein. Chfr binds and downregulates HDAC1 by inducing its polyubiquitylation, both in vitro and in vivo. Together, these results suggest that the ubiquitin ligase activity of Chfr targets HDAC1 for degradation. | SIGNOR-271465 |
Q16539 | Q02078 | 1 | phosphorylation | up-regulates activity | 0.661 | We show that mef2a, but not mef2b or mef2d, is a substrate for p38. Threonines 312 and 319 are the key regulatory phosphorylation sites by p38 in mef2a. Phosphorylation at these sites enhances transcriptional activity of mef2a | SIGNOR-62780 |
Q15139 | P24723 | 0 | phosphorylation | up-regulates | 0.355 | These results provide direct evidence that pkd becomes activated in vivo as a consequence of pkc-mediated phosphorylation of serines 744 and 748. | SIGNOR-66734 |
Q15118 | P00558 | 0 | phosphorylation | up-regulates activity | 0.428 | Mitochondrial PGK1 acts as a protein kinase to phosphorylate pyruvate dehydrogenase kinase 1 (PDHK1) at T338, which activates PDHK1 to phosphorylate and inhibit the pyruvate dehydrogenase (PDH) complex. | SIGNOR-278365 |
P35568 | P28482 | 0 | phosphorylation | down-regulates activity | 0.68 | Rin beta-cells exposed to high glucose exhibited increased c-jun n-terminal kinase (jnk) and erk1/2 activity, which was associated with increased irs-1 phosphorylation at serine (ser)(307) and ser(612), respectively, that inhibits coupling of irs-1 to the insulin receptor and is upstream of the inhibition of irs-1 tyrosine phosphorylation. | SIGNOR-123173 |
Q5VSY0 | O75382 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.248 | Here we identify the RING finger-containing protein TRIM3 as a specific E3 ubiquitin ligase for the PSD scaffold GKAP/SAPAP1. Present in PSD fractions from rat brain, TRIM3 stimulates ubiquitination and proteasome-dependent degradation of GKAP, and induces the loss of GKAP and associated scaffold Shank1 from postsynaptic sites. | SIGNOR-271959 |
Q05655 | P25054 | 1 | phosphorylation | down-regulates activity | 0.2 | APC is Phosphorylated by PKCdelta in Intact RKO Cells. | SIGNOR-279650 |
Q05513 | P55211 | 1 | phosphorylation | down-regulates | 0.348 | Inhibitor sensitivity and interactions with caspase 9 indicate that the predominant kinase that targets ser144 is the atypical protein kinase c isoform zeta (pkczeta). | SIGNOR-141629 |
Q68CJ9 | P49841 | 0 | phosphorylation | down-regulates activity | 0.549 | It is possible that phosphorylation of CREBH by GSK3beta leads to altered CREBH conformation with a resulting decreased affinity toward the COPII coated transport complex.|Similarly, expression of dominant negative GSK3beta can rescue the decreased CREBH cleavage activity in the Bmal1 knockdown hepatocytes under the circadian clock (XREF_FIG), thus confirming that BMAL1 controls circadian regulated CREBH cleavage and activation through AKT and GSK3beta signaling in hepatocytes. | SIGNOR-279785 |
Q9H2P0 | P49711 | 1 | relocalization | down-regulates activity | 0.206 | These results argue against the simultaneous binding of CTCF and ADNP to the same genomic loci. Instead, they support a model in which ADNP counteracts stable association of CTCF with DNA at over 15,000 binding sites in the mouse genome. | SIGNOR-266755 |
P12931 | Q9ULV8 | 1 | phosphorylation | up-regulates | 0.537 | Phosphorylation of a critical tyrosine (tyr-341) in the linker region of cbl-c by src or a phosphomimetic mutation of this tyrosine (y341e) is sufficient to increase the e3 activity of cbl-c. | SIGNOR-165862 |
P49674 | Q9UD71 | 1 | phosphorylation | up-regulates activity | 0.322 | CKIepsilon phosphorylates and activates DARPP-32, a key molecule in various complex signaling pathways, including dopamine and glutamine signaling, which have both been demonstrated to be main pathways in substance dependence. | SIGNOR-279701 |
Q07343 | P28482 | 0 | phosphorylation | up-regulates activity | 0.268 | The short-form PDE4B2 isoenzyme was activated by Erk2 phosphorylation. These functional changes in PDE activity were mimicked by mutation of the target serine for Erk2 phosphorylation to the negatively charged amino acid, aspartic acid. | SIGNOR-275970 |
P05771 | P04004 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.303 | Phosphorylation of vitronectin on Ser362 by protein kinase C attenuates its cleavage by plasmin. | SIGNOR-248963 |
P12931 | Q9Y210 | 1 | phosphorylation | up-regulates activity | 0.435 | TRPC6 Y31 and Y284 are phosphorylated by Src family kinase in isolated glomeruli. | SIGNOR-279659 |
Q6ZMT4 | Q16665 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | To this end, we confirm that KDM3A, KDM4B, KDM4C, KDM5B, KDM5C, and KDM62 are direct targets of HIF-1a while extent the list of known targets to KDM2A, KDM2B, KDM4D, KDM5A, and KDM6A. The results demonstrated that majority of the KDMs were similarly induced (KDM2A, KDM2B, KDM3A, KDM4B, KDM4C, KDM4D, KDM5A, KDM5B, KDM5C, KDM6B, and KDM7A) or repressed (KDM NO66 and KDM1A) by both HIF-1a and HIF-2a. | SIGNOR-271572 |
P49840 | Q96F46 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Glycogen synthase kinase 3 (GSK3) constitutively bound to and phosphorylated IL-17RA at T780, leading to ubiquitination and proteasome-mediated degradation of IL-17RA, thus inhibiting IL-17-mediated inflammation. | SIGNOR-277206 |
Q96GD4 | Q8TF76 | 1 | phosphorylation | up-regulates activity | 0.2 | Phosphorylation by Aurora B is required for full Haspin activity toward H3T3 in mitosis | SIGNOR-262657 |
P31276 | O15550 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.267 | 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-260027 |
P20929 | P49841 | 0 | phosphorylation | down-regulates | 0.306 | Gsk3b is able to phosphorylate nebulin at two ser sites in the c-terminal region of nebulin localized to the z-disk, thus preventing the interaction of nebulin with neuronal wiscott-aldrich syndrome protein (nwasp), a ubiquitously expressed member of the wasp family, which is involved in actin assembly. | SIGNOR-175659 |
P15172 | P38936 | 1 | transcriptional regulation | up-regulates | 0.4 | P21 is regulated by MyoD and myogenin in normal muscle cells and the inactivation of these factors in RMS cells contributes to the silencing of p21 in RMS cells | SIGNOR-251574 |
Q9BXM7 | P49411 | 1 | phosphorylation | down-regulates activity | 0.2 | PINK1 interacts with the autophagy effector TUFm and phosphorylates TUFm at Ser222. These results indicated that p222-hTUFm sequestered more monomer Atg5 and reduced the conjugated Atg5-Atg12 complex to subdue mitophagy. | SIGNOR-266382 |
Q9NWZ3 | P51617 | 1 | phosphorylation | up-regulates activity | 0.687 | In addition, IRAK-4 is able to phosphorylate IRAK-1, and overexpression of dominant-negative IRAK-4 is blocking the IL-1-induced activation and modification of IRAK-1, suggesting a role of IRAK-4 as a central element in the early signal transduction of Toll/IL-1 receptors, upstream of IRAK-1. | SIGNOR-117315 |
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