IdA string | IdB string | labels int64 | mechanism string | effect string | score float64 | sentence string | signor_id string |
|---|---|---|---|---|---|---|---|
P17612 | P04049 | 1 | phosphorylation | down-regulates activity | 0.5 | Protein kinase A blocks Raf-1 activity by stimulating 14-3-3 binding and blocking Raf-1 interaction with Ras. Cyclic AMP (cAMP) blocks Raf-1 activation by stimulating its phosphorylation on serine 43 (Ser43), serine 233 (Ser233), and serine 259 (Ser259). | SIGNOR-250041 |
Q00535 | Q14814 | 1 | phosphorylation | down-regulates activity | 0.415 | In this case, cdk5 phosphorylates MEF2D on Ser444 suppressing its transcriptional activity. | SIGNOR-279509 |
P17612 | Q92917 | 1 | phosphorylation | up-regulates activity | 0.307 | PKA phosphorylates GPKOW at S27 and T316 in vitro. GPKOWs ability to bind RNA is sensitive to mutations of its PKA phosphorylation sites. | SIGNOR-266309 |
Q9UPS6 | Q16695 | 1 | methylation | down-regulates activity | 0.2 | SETD1B encodes a lysine-specific methyltransferase that assists in transcriptional activation of genes by depositing H3K4 methyl marks. | SIGNOR-265577 |
Q5JR12 | P45984 | 0 | phosphorylation | down-regulates | 0.2 | Specific phosphorylation of pp2czeta at ser (92) by stress-activated jnk attenuates its phosphatase activity in cells. | SIGNOR-178934 |
Q86U44 | P28482 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.273 | Mass spectrometry analysis showed that ERK phosphorylates METTL3 at three highly conserved residues: S43, S50, and S525 (Figures 2D and 2E). Mutational analysis further confirmed these three sites as main ERK phosphorylation sites (Figure 2F). Phosphorylation of METTL3 increases interaction with USP5, decreasing ubiquitination to stabilize the m6 A methyltransferase complex. | SIGNOR-265948 |
Q13642 | P12931 | 0 | phosphorylation | up-regulates activity | 0.26 | However, overexpression of Src promoted most of the Flag-FHL1-WT to translocate to the nucleus, whereas the Flag-FHL1-Y149-272F mutant (phosphorylation deficient mutant) remained in the cytoplasm (XREF_FIG).|We found that Src phosphorylates FHL1 at Y149 and Y272, demonstrating that FHL1 is a bona fide novel substrate of Src. | SIGNOR-278213 |
Q15831 | P28482 | 0 | phosphorylation | down-regulates activity | 0.402 | Directly and/or through the activation of p90RSK, ERK phosphorylates LKB-1 at Ser325 and Ser428. The phosphorylation of LKB-1 causes the dissociation of LKB-1 from AMPK, resulting in the impaired activation of AMPK. | SIGNOR-209876 |
Q9H4A3 | P55011 | 1 | phosphorylation | up-regulates activity | 0.491 | Combining these biochemical studies with the live cell imaging data, these results collectively suggest that the entire CTD is necessary for WNK1 to drive optimal SPAK/OSR1 activation and downstream NKCC1/KCC phosphorylation via PS. | SIGNOR-277859 |
Q00535 | A0A1B0GVQ0 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Cdk5 also phosphorylates PSD-95-interacting protein Spine Associated RapGAP (SPAR), resulting in its degradation ([98], Table 2). | SIGNOR-280219 |
P17096 | P24941 | 0 | phosphorylation | down-regulates | 0.264 | Here, we found that hipk2 phosphorylates hmga1a at ser-35, thr-52, and thr-77, and hmga1b at thr-41 and thr-66. In addition, we demonstrated that cdc2, which is known to phosphorylate hmga1 proteins, could induce the phosphorylation of hmga1 proteins at the same ser/thr sites. we found that the hipk2-phosphorylated hmga1a reduced the binding affinity of hmga1a to human germ line promoter, and the drop in binding affinity induced by hipk2 phosphorylation was lower than that introduced by cdc2 phosphorylation. | SIGNOR-158612 |
P17252 | Q13255 | 1 | phosphorylation | down-regulates activity | 0.385 | Furthermore, we demonstrate that the selectivity of PKC action on receptor signaling rests on phosphorylation of a threonine residue located in the G protein-interacting domain of the receptor. Modification at Thr(695) selectively disrupts mGluR1alpha-G(q/11) interaction without affecting signaling through G(s). | SIGNOR-249043 |
O75928 | Q16539 | 0 | phosphorylation | up-regulates activity | 0.316 | The switch between the coactivating and inhibitory actions of PIASxα is controlled, at least in part, through PIASxα phosphorylation. PIASxα is itself phosphorylated by p38 in vitro and in vivo in response to the activation of stress signaling pathways (Figure 2, Figure 3, Figure 4). We identify Ser113 and Ser 116 as two residues that are phosphorylated by p38 and have important functional roles | SIGNOR-262949 |
Q9BX46 | Q15208 | 0 | phosphorylation | up-regulates activity | 0.355 | Phosphorylation of Rbm24 by Stk38 is crucial for the maintenance of cardiac sarcomeric gene expression in cardiac cells.|These results indicated that Stk38 increases Rbm24 protein stability probably by interfering with the ubiquitin-proteasome protein degradation pathway. | SIGNOR-278291 |
P15056 | P27361 | 0 | phosphorylation | down-regulates | 0.645 | Erk-induced phosphorylation of b-raf on t753 promoted the disassembly of raf heterodimers, and the mutation of t753 prolonged growth factor-induced heterodimerization. The b-raf t753a mutant enhanced differentiation of pc12 cells, which was previously shown to be dependent on sustained erk signaling. Site is critical for v-src dependent modulation of slk kinase activity. | SIGNOR-144827 |
P49327 | Q9P035 | 0 | chemical activation | up-regulates activity | 0.2 | Very long-chain fatty acids are produced through a four-step cycle. However, the 3-hydroxyacyl-CoA dehydratase catalyzing the third step in mammals has remained unidentified. Mammals have four candidates, HACD1-4, based on sequence similarities to the recently identified yeast Phs1, although HACD3 and HACD4 share relatively weak similarity. We demonstrate that all four of these human proteins are indeed 3-hydroxyacyl-CoA dehydratases, | SIGNOR-267762 |
Q9NQC7 | O43318 | 1 | deubiquitination | up-regulates activity | 0.636 | Mechanistically, CYLD interacts directly with the kinase TAK1 and removes its K63-linked polyubiquitin chain, which blocks downstream activation of the JNK-p38 cascades. | SIGNOR-266437 |
P19429 | P67775 | 0 | dephosphorylation | down-regulates | 0.401 | The major phosphatase thought to dephosphorylate ctni and phospholamban is type 2a protein phosphatase (pp2a) [61]. Activation of pp2a and ensuing dephosphorylation of regulatory proteins is involved in the anti-adrenergic effects of adenosine and muscarinic receptor activation see also fig2. | SIGNOR-134601 |
Q8WUM4 | P12931 | 0 | phosphorylation | down-regulates activity | 0.393 | Src phosphorylation of Alix/AIP1 modulates its interaction with binding partners and antagonizes its activities. Phosphorylation of Alix by Src caused it to translocate from the membrane and cytoskeleton to the cytoplasm and reduced its interaction with binding partners SETA/CIN85, epidermal growth factor receptor, and Pyk2. | SIGNOR-263201 |
O60216 | Q14674 | 0 | cleavage | down-regulates quantity by destabilization | 0.78 | In order to segregate sister chromatids to opposite poles in anaphase, cohesin has to be removed from chromosomes. In budding yeast, the prevalent mode of cohesin removal is by proteolytic cleavage of the Scc1 subunit at the onset of anaphase by the endopeptidase separase | SIGNOR-275537 |
P67775 | P06730 | 1 | dephosphorylation | down-regulates | 0.347 | A recent study using genetically engineered mouse models has clearly shown that mnk-mediated eif4e phosphorylation is absolutely required for eif4e's oncogenic action. Taken together, we conclude that pp2a negatively regulates eif4e phosphorylation and eif4f complex assembly through dephosphorylation of mnk and eif4e, thus suggesting a novel mechanism by which pp2a exerts its tumor-suppressive function. | SIGNOR-168306 |
P62633 | P01106 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.303 | These data verified that the binding of CNBP with c-myc promoter G-quadruplex can indeed down-regulate its associated gene expression for a certain period of time. This result with human CNBP is somehow consistent with previous reports that c-myc G-quadruplex serves as a silencer of c-myc transcription [7] and CNBP promotes the formation of c-myc G-quadruplex. | SIGNOR-261571 |
Q13535 | Q92900 | 1 | phosphorylation | up-regulates activity | 0.368 | Phosphorylation of UPF1 by the PIKKs SMG1, ATM and ATR is stimulated in response to DNA damage. | SIGNOR-278911 |
Q9Y243 | P35226 | 1 | phosphorylation | up-regulates activity | 0.258 | the polycomb group silencing protein Bmi1 can be phosphorylated by AKT, which enhances its oncogenic potential in PCa. Overexpression of Bmi1 can act in combination with PTEN haploinsufficiency to induce invasive carcinogenic formation in the prostate | SIGNOR-249583 |
P06493 | Q01167 | 1 | phosphorylation | up-regulates | 0.372 | We have mapped two cdk phosphorylation sites, serines 368 and 423, which play a role in defining foxk2 function through regulating its stability and its activity as a transcriptional repressor protein. These two cdk sites appear vital for foxk2 function because expression of a mutant lacking these sites cannot be tolerated and causes apoptosis. | SIGNOR-167826 |
Q9NQB0 | P68400 | 0 | phosphorylation | up-regulates activity | 0.358 | We show here that Tcf-4 can be phosphorylated in vitro by protein kinase CK2 stoichiometrically in amino acids Ser-58-Ser-59-Ser-60. Phosphorylation of these residues does not modify the interaction of Tcf-4 with beta-catenin but reduces its association to plakoglobin. | Experiments performed using a Tcf-4 mutant with decreased interaction to plakoglobin demonstrated that binding to this protein negatively affected the transcriptional activity of Tcf-4. | SIGNOR-250963 |
P34896 | P01106 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.276 | Myc regulates the de novo purine and pyrimidine synthetic genes in multiple biological systems. Intriguingly, MYC was found to directly activate the expression of SHMT1, and SHMT2, which are enzymes involved in single carbon metabolism and are essential for dNTP synthesis | SIGNOR-267379 |
Q13043 | Q96EB6 | 1 | phosphorylation | down-regulates activity | 0.344 | We found that MST1 increases p53 acetylation and transactivation by inhibiting the deacetylation of Sirtuin 1 (Sirt1) and its interaction with p53 and that Sirt1 can be phosphorylated by MST1 leading to the inhibition of Sirt1 activity. | SIGNOR-279574 |
P28482 | P12270 | 1 | phosphorylation | up-regulates | 0.374 | Tpr is phosphorylated by erk2 at four different sites. / because phosphorylation of tpr by activated erk stabilizes their interaction, we hypothesize that this phosphorylation is not part of a signal amplification cascade but rather positions activated erk to perform a continuing function in the nuclear pore. | SIGNOR-181022 |
P01871 | Q9UPW6 | 0 | transcriptional regulation | up-regulates quantity | 0.2 | The SATB2 protein was shown to bind MAR sequences flanking the enhancer of the endogenous immunoglobulin μ heavy chain (IgH) gene in vivo, and this binding was found to correlate with an increase in the expression of a transfected rearranged μ wild-type gene | SIGNOR-268933 |
Q5SQI0 | P68366 | 1 | acetylation | up-regulates quantity by stabilization | 0.262 | Alpha-Tubulin acetyltransferase (alphaTAT1) is the major α-tubulin lysine-40 (K40) acetyltransferase in mammals, nematodes, and protozoa, and its activity plays a conserved role in several microtubule-based processes.|The tubulin subunits of microtubules are acetylated, and lysine-40 (K40) of the alpha-tubulin subunit has been identified as an important conserved site of microtubule acetylation (6–8). This modification is considered a hallmark of stable, long-lived microtubules | SIGNOR-272249 |
Q86VP3 | Q13490 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.303 | Under basal conditions, PACS-2 underwent K48-linked poly-ubiquitination, resulting in PACS-2 proteasomal degradation. Biochemical assays showed cIAP-1 and cIAP-2 interacted with PACS-2 in vitro and co-immunoprecipitation studies demonstrated that the two cIAPs bound PACS-2 in vivo. More importantly, both cIAP-1 and cIAP-2 directly mediated PACS-2 ubiquitination in a cell-free assay. | SIGNOR-272851 |
P35568 | Q6ZMU5 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.477 | Here, we demonstrate that MG53 induces IRS-1 ubiquitination with the help of the E2 enzyme UBE2H during skeletal myogenesis by examining MG53 disrupted skeletal muscle cells and tissues.|The IRS-1 protein level was decreased by MG53 in a concentration dependent manner and was restored by the addition of MG132, a proteasome inhibitor (XREF_FIG; XREF_SUPPLEMENTARY). | SIGNOR-278520 |
P53350 | Q9Y5T5 | 1 | phosphorylation | up-regulates activity | 0.344 | Plk1 phosphorylates and activates Usp16. In vitro phosphorylation of Usp16 with single (S330A, S386A, or S486A) or collective 3A (S330A/S386A/S486A) mutation showed that Plk1 phosphorylated Usp16 at all three sites (Fig. S2 D). | SIGNOR-274015 |
O75151 | P84243 | 1 | demethylation | up-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-264518 |
Q13285 | P60484 | 0 | dephosphorylation | down-regulates activity | 0.256 | The fact that SF-1 and PIP3 is robustly dephosphorylated by PTEN, yet SF-1 and PIP2 is resistant to phosphorylation by p110 PI3-kinases, suggests that nuclear proteins like SF-1 can help decouple PTEN signaling in the nucleus from p110 signaling.|We also showed that PTEN can dephosphorylate the SF-1 and PIP3 product of the IPMK reaction, and that PTEN inhibits SF-1 transcriptional activity. | SIGNOR-277117 |
P36873 | P29474 | 1 | dephosphorylation | up-regulates activity | 0.2 | The increase in eNOS activity coincided with specific dephosphorylation of eNOS-Thr495, known to enhance eNOS activity. Inhibition of protein phosphatase 1 (PP1) by calyculin A, tautomycetin, or siRNA against PP1 reversed NF-induced eNOS-Thr495 dephosphorylation | SIGNOR-248501 |
P40763 | P62136 | 0 | 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 |
P24385 | Q16539 | 0 | phosphorylation | up-regulates | 0.426 | A large number of cytosolic proteins can be phosphorylated by p38 mapks, including phospholipase a2, the microtubule-associated protein tau, nhe-1, cyclin d1, cdk inhibitors, bcl2 family proteins, growth factor receptors or keratins | SIGNOR-166594 |
Q96T88 | P48730 | 0 | phosphorylation | up-regulates | 0.245 | We further show that uhrf1 physically interacts with _-trcp1 in a manner dependent on phosphorylation of serine 108 (s108(uhrf1)) within the dsg degron. Furthermore, we demonstrate that s108(uhrf1) phosphorylation is catalyzed by casein kinase 1 delta (ck1_) and is important for the recognition of uhrf1 by scf(_-trcp). | SIGNOR-200349 |
P23470 | P00533 | 1 | dephosphorylation | down-regulates activity | 0.481 | PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity. | SIGNOR-254699 |
P05305 | P23946 | 0 | cleavage | up-regulates activity | 0.472 | Chymase from human mast cells selectively cleaved big endothelins (ETs) at the Tyr31-Gly32 bond and produced novel trachea-constricting 31-amino acid-length endothelins, ETs(1-31), without any further degradation products. | SIGNOR-256356 |
Q92952 | P00533 | 0 | phosphorylation | up-regulates activity | 0.2 | These results demonstrate the novel information that hSKCa1 channels are inhibited by genistein, T25 and AG556 via EGFR tyrosine kinase inhibition, which is related to the phosphorylation of Tyr(109) in the N-terminus. | SIGNOR-276490 |
P17612 | P35612 | 1 | phosphorylation | down-regulates activity | 0.283 | Ser-726 and Ser-713 in the C-terminal MARCKS-related domains of - and -adducin, respectively, were identified as the major phosphorylation sites common for PKA and PKC. Phosphorylation by PKA, but not PKC, reduced the affinity of adducin for spectrin-F-actin complexes as well as the activity of adducin in promoting binding of spectrin to F-actin. | SIGNOR-250332 |
Q9Y4K3 | P49841 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.479 | TRAF6 was phosphorylated at Thr266 by GSK3B in most clinical CRC, which triggered K48-linked polyubiquitination and degradation of TRAF6 and thereby attenuated its inhibitory activity towards the autophagy-dependent CTNNB1 signaling. | SIGNOR-277438 |
P25116 | P24158 | 0 | cleavage | down-regulates activity | 0.42 | PAR1E and PAR2E (10 microM) were incubated in the presence of the different proteases | The enzymes were used at the following concentrations: 0.5 unit/mL thrombin, 2.5 nM trypsin, 20 nM plasmin, 20 nM cathepsin G, 20 nM elastase, 20 nM proteinase 3, and 2 units/mL calpain I and II|Protease-activated receptors (PARs) mediate cell activation after proteolytic cleavage of their extracellular amino terminus.|Protease-activated receptors (PARs) mediate cell activation after proteolytic cleavage of their extracellular amino terminus.|Plasmin, calpain and leukocyte elastase, cathepsin G, and proteinase 3 cleaved at multiple sites and would be expected to disable PAR1 by cleaving COOH-terminal to the activation site. | SIGNOR-263577 |
P04626 | Q00535 | 0 | phosphorylation | up-regulates activity | 0.274 | Since Tyr-654 is the ERBB2 phosphorylation site on beta-catenin, this result is consistent with our hypothesis that CDK5 activates ERBB2 , which in turn phosphorylates beta-catenin on Tyr-654, leading to a shift of beta-catenin away from the adherens junction and into the nucleus where it can serve as a transcriptional co-activator.|Taken together with the results of our kinase analysis, these observations suggest that CDK5 phosphorylation of both ERBB2 and ERBB3 and AR could drive a feedback loop, in which ERBB2 and ERBB3 promotes beta-catenin transcriptional activity that then contributes to higher expression of ERBB3. | SIGNOR-279155 |
O15530 | P07949 | 0 | phosphorylation | up-regulates activity | 0.2 | Ret/ptc (rearranged in transformation/papillary thyroid carcinomas) tyrosine kinase phosphorylates and activates phosphoinositide-dependent kinase 1 (pdk1) ret/ptc phosphorylates a specific tyrosine (y9) residue located in the n-terminal region of pdk1. | SIGNOR-235863 |
Q9Y6K9 | P25963 | 1 | phosphorylation | down-regulates activity | 0.848 | IκB components are phosphorylated on two amino-terminal serine residues by the IκB kinase (IKK) complex, composed of two catalytic proteins, IKKα and IKKβ, and the regulatory subunit IKKγ (NEMO, IKBKG). This modification targets IκB for degradation by the proteasome, allowing the release and nuclear translocation of NF-κB. | SIGNOR-280462 |
P56178 | Q9Y458 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.307 | the main function of TBX22 as shown in misexpression experiments is to decrease proliferation. We subsequently uncovered three targets of TBX22, DLX5, MSX2, and TBX22 itself. All are downregulated in the presence of viral-derived hTBX22. | SIGNOR-265566 |
P17706 | P00533 | 1 | dephosphorylation | down-regulates | 0.635 | Here, we report that the 45-kda variant of the protein tyrosine phosphatase tcptp (tc45) can recognize delta egfr as a cellular substrate | SIGNOR-132316 |
P16220 | Q9UBK2 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.554 | CREB was found to induce expression of the gluconeogenic programme through the nuclear receptor coactivator PGC-1, which is shown here to be a direct target for CREB regulation in vivo | SIGNOR-256150 |
Q96R06 | P53350 | 0 | phosphorylation | up-regulates activity | 0.394 | Phosphorylation of the astrin N-terminal domain by Plk1 contributes to kinetochore\u2013microtubule attachment stability.|Taken together with the localisation data in XREF_FIG B, these data suggest that the presence of the Plk1 phosphorylated astrin N-terminus promotes the accumulation of the astrin complex at attached kinetochores, without which attachments appear more prone to dissociate. | SIGNOR-279423 |
Q9NYV4 | P50613 | 0 | phosphorylation | up-regulates activity | 0.51 | Although Cdk12/CycK kinase complex lacking T-loop phosphorylation showed some basal activity towards a CTD substrate prephosphorylated at position Ser7, its activity was significantly increased upon coexpression with the CAK from S. cerevisiae (Supplementary Fig. 9a). Mutation of T893 to E to mimic phosphorylation showed no effect on basal kinase activity. Quantitative phosphorylation of a single residue occurred upon coexpression with Cak1, as determined by ESI mass spectrometry (Supplementary Fig. 9b). | SIGNOR-275509 |
P19544 | P17612 | 0 | phosphorylation | down-regulates | 0.341 | Pka phosphorylated wt1 at ser-365 and ser-393 in vitro, as well as at additional sites, and this phosphorylation abolished the dna-binding activity of wt1 in vitro. Using wt1 mutants in which ser-365 and ser-393 were mutated to ala individually and in combination, we showed that phosphorylation of these sites was critical for inhibition of dna binding in vivo. | SIGNOR-53172 |
P67775 | P13639 | 1 | dephosphorylation | up-regulates | 0.404 | Protein phosphatases-2a and -2c (pp-2a and pp-2c) can each efficiently dephosphorylate phosphorylated eef-2 | SIGNOR-38566 |
P23677 | P17252 | 0 | null | down-regulates activity | 0.37 | In contrast, phosphorylation of the A isoform with PKC caused a significant decrease in activity whether assayed in the presence or absence of calcium/calmodulin (to _25% of the unphosphorylated enzyme activity). | SIGNOR-248991 |
O60346 | P23443 | 1 | dephosphorylation | down-regulates activity | 0.572 | Here we report the identification of ribosomal protein S6 kinase 1 (S6K1) as a novel substrate of PHLPP. | SIGNOR-237454 |
Q16695 | O60341 | 0 | demethylation | up-regulates activity | 0.2 | Here, we provide evidence that LSD1 (KIAA0601), a nuclear homolog of amine oxidases, functions as a histone demethylase and transcriptional corepressor. LSD1 specifically demethylates histone H3 lysine 4, which is linked to active transcription. | SIGNOR-264508 |
Q9NQU5 | O95831 | 1 | phosphorylation | down-regulates activity | 0.2 | Furthermore, PAK5 phosphorylates AIF at Thr281 site to inhibit the formation of AIF/importin \u03b13 complex, leading to decrease AIF nuclear translocation.|These results suggested that PAK5 can inhibit AIF from entering the nucleus and prevent caspase- independent apoptosis. | SIGNOR-278969 |
P17612 | O96004 | 1 | phosphorylation | down-regulates activity | 0.296 | In vitro and in vivo phosphorylation studies show that both PKA and PKC can phosphorylate HAND1 and -2. T107; S109 within helix I and S98 within the basic domain, are the phosphorylated residues. We determined that modification of HAND1 at residues 107 and 109 affects dimerization affinities with E-proteins, thus changing the bHLH dimer equilibrium within the cell. These modifications also affect HAND1 function. | SIGNOR-249991 |
O60656 | P20823 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.267 | Using gel shift and functional assays, HNF1alpha was demonstrated to bind to and activate the UGT1A8, -1A9, and -1A10 promoters. In contrast, Cdx2 bound to and activated the UGT1A8 and -1A10 promoters but could not activate the UGT1A9 promoter. | SIGNOR-253973 |
Q14790 | P28482 | 0 | phosphorylation | down-regulates | 0.757 | We demonstrate that perk 1/2 can phosphorylate pro-caspase-8 at s387 by knocking-down the endogenous pro-caspase-8 using rnai and replacing it with its non-phosphorylatable counterpart (s387a), a significant increase in caspase-8 activity | SIGNOR-203473 |
Q00613 | P31751 | 0 | phosphorylation | up-regulates activity | 0.309 | AKT2 also phosphorylated S326 of HSF1 but showed weak ability to activate HSF1.|AKT2 promoted a significant increase in HSF1 activity , but the effect was modest while AKT3 had no significant effect on HSF1 activity ( Fig. 1A-C ) . | SIGNOR-279779 |
P36956 | P14618 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.29 | Well-described targets of srebp-1 and the carbohydrate response element binding protein (chrebp), which include the following: fatty acid synthase (fas), acetyl coa carboxylase (acc1), and liver pyruvate kinase (l-pk) | SIGNOR-166381 |
P29401 | Q86Y07 | 0 | phosphorylation | up-regulates activity | 0.2 | Mechanistically, VRK2 promoted Thr287 phosphorylation of TKT and then recruited FBXL6 to promote TKT ubiquitination and activation. | SIGNOR-277842 |
Q15653 | O14920 | 0 | phosphorylation | down-regulates | 0.765 | We described the purification of a 900 kda protein kinase complex, the ikb kinase (ikk), that phosphorylates ikbalfa and ikbbeta at the sites that mediate their ubiquitination and degradation | SIGNOR-52932 |
P23528 | Q15139 | 0 | phosphorylation | down-regulates activity | 0.334 | PKD1 regulates cofilin S3-phosphorylation|Both, oxidative stress as well as RhoA activation enhanced cofilin phosphorylation at S3, implicating an increased inhibition due to PKD1-mediated signalling events | SIGNOR-275944 |
O15119 | Q9Y243 | 0 | phosphorylation | up-regulates activity | 0.354 | We have identified TBX3 as a key substrate of AKT3 in melanomagenesis. we have identified the AKT3 target site at serine residue 720 in the TBX3 protein and show that this site is phosphorylated in vivo. the phosphorylation at S720 promotes TBX3 protein stability, nuclear localization, transcriptional repression of E-cadherin, and its role in cell migration and invasion. | SIGNOR-223534 |
Q9HCE7 | Q15797 | 1 | ubiquitination | down-regulates | 0.708 | Smurf1 and smurf2 are e3 ubiquitin ligases known to suppress tgf-beta signaling through degradation of smads and receptors for tgf-beta and bmps | SIGNOR-195660 |
Q92888 | P17252 | 0 | phosphorylation | up-regulates activity | 0.439 | We showed that the first and second phase of RhoA activity are dependent on p63 and Ca2+/PKC, respectively, and further identified phosphorylation of serine 240 on p115 RhoGEF by PKC to be the mechanistic link between PKC and RhoA. | SIGNOR-277530 |
P31749 | P03372 | 1 | phosphorylation | up-regulates | 0.765 | Studies using mutants of er-alpha demonstrated that akt increased estrogen receptor activity through the amino-terminal activation function-1 (af-1). Serines s104 s106, s118, and s167 appear to play a role in the activation of er-alpha by akt. | SIGNOR-84963 |
Q92993 | Q16539 | 0 | phosphorylation | up-regulates activity | 0.321 | We found that phosphorylation of Tip60-T158 was increased by p38\u03b1 isolated from Dox- or \u03b3-radiation-treated cells over that from untreated cells (Figure xref ), indicating that DNA damage induces the protein kinase activity of p38\u03b1 towards Tip60-T158. | SIGNOR-278958 |
Q13443 | P21802 | 1 | cleavage | down-regulates quantity by destabilization | 0.257 | Truncated FGFR2 was observed in cells transfected with wild-type ADAM9, but not in those with inactive mutant ADAM9 (Figure 5E). In line with this, cells transfected with wild-type ADAM9 showed reduced pErK1/2 in response to FGF2 as compared to controls or cells expressing mutant ADAM9.|Here we show that MT1-MMP forms a complex with FGFR2 and ADAM9 in osteoblasts and proteolytically inactivates ADAM9, hence protecting FGFR2 from ADAM9-mediated ectodomain shedding on the cell surface. | SIGNOR-260300 |
P31749 | Q9H4A3 | 1 | phosphorylation | up-regulates | 0.393 | Phosphorylation of wnk1 on thr-58 contributes to sgk1 activation. these data suggest that activation of sgk1 by wnk1 requires the catalytic activity of akt. | SIGNOR-252481 |
Q14669 | P35712 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.397 | In this article, we focused on Trip 12, an E3 ubiquitin ligase, which polyubiquitinates Sox6.|Therefore, Sox6 is a specific substrate to Trip12, by which it is polyubiquitinated and degraded. | SIGNOR-278579 |
P30304 | Q9UM11 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.464 | We found that Cdc25 A degradation during mitotic exit and in early G(1) is mediated by the anaphase-promoting complex or cyclosome (APC/C)(Cdh1) ligase, and that a KEN-box motif in the N-terminus of the protein is required for its targeted degradation. | SIGNOR-271388 |
P04626 | Q99952 | 0 | dephosphorylation | down-regulates quantity by destabilization | 0.671 | PTPN18 knockdown selectively enhances the EGF-induced tyrosine phosphorylation of the HER2 Y1112, Y1196 and Y1248 sites. |Whereas the catalytic domain of PTPN18 blocks lysosomal routing and delays the degradation of HER2 by dephosphorylation of HER2 on pY(1112), the PEST domain of PTPN18 promotes K48-linked HER2 ubiquitination and its rapid destruction via the proteasome pathway and an HER2 negative feedback loop. | SIGNOR-262596 |
Q9Y463 | Q02363 | 1 | phosphorylation | down-regulates activity | 0.2 | Phosphorylation of Thr27 of ID2 by DYRK1 blocks ID2-VHL interaction and preserves HIF2α ubiquitylation.|We report that DYRK1A and DYRK1B kinases phosphorylate ID2 on Threonine-27 (T27). | SIGNOR-279033 |
Q7L7X3 | Q13315 | 0 | phosphorylation | up-regulates | 0.42 | The dna damage kinase ataxia telangiectasia mutated (atm) phosphorylates taos in vitro;radiation induces phosphorylation of tao on a consensus site for phosphorylation by the atmprotein kinase in cells. | SIGNOR-154171 |
Q15672 | P31749 | 0 | phosphorylation | up-regulates | 0.438 | Moreover, phosphorylation of twist-1 at ser42 was shown in vivo in various human cancer tissues, suggesting that this post-translational modification ensures functional activation of twist-1 after promotion of survival during carcinogenesis. | SIGNOR-164884 |
P63279 | Q9UKY1 | 1 | sumoylation | up-regulates quantity by stabilization | 0.452 | Here, we report that the SUMO-E2 conjugating enzyme Ubc9 was identified to interact with ZHX1 by an interaction screen using a yeast two-hybrid system. This interaction was confirmed by co-immunoprecipitation and co-localization assays. Further study showed that ZHX1 is SUMOylated by Ubc9 with SUMO1 at the sites K159, K454, and K626. Furthermore, we demonstrated that the SUMOylation of ZHX1 regulated the stability, ubiquitination and transcriptional activity of ZHX1. The sumoylation of zinc‐fingers and homeoboxes 1 (ZHX1) by ubc9 regulates its stability and transcriptional repression activity. However, in the current work, we demonstrated that ZHX1 was only SUMOylated by SUMO1. | SIGNOR-263901 |
P16615 | P49841 | 0 | phosphorylation | down-regulates activity | 0.283 | GSK3β-dependent phosphorylation of SERCA2 at serine 663 in human and mouse hearts. Phosphorylation of SERCA2 at serine 663 regulates SERCA2 activity. | SIGNOR-277886 |
P00533 | P19174 | 1 | phosphorylation | up-regulates | 0.841 | We have identified the sites phosphorylated in vitro by epidermal growth factor (egf) receptor kinase in bovine brain phospholipase c-gamma (plc-gamma). They are tyrosine residues 472, 771, 783, and 1254. we propose, therefore, that the phosphorylation of plc-gamma by egf receptor kinase alters its interaction with putative inhibitory proteins and leads to its activation. | SIGNOR-20984 |
P53350 | Q99708 | 1 | phosphorylation | up-regulates activity | 0.347 | PLK1 targets CtIP to promote microhomology mediated end joining.|We further showed that the DSB repair factor CtIP is jointly phosphorylated by CDK1 and Aurora A and PLK1. | SIGNOR-279253 |
Q9Y5S2 | P26038 | 1 | phosphorylation | up-regulates activity | 0.2 | In this study, we have shown that MRCKb phosphorylated moesin at Thr-558 | We have shown that the phosphorylation is important to the formation of ®lopodia, and that MRCK may regulate this formation through the phosphorylation of ERM proteins at the tip of ®lopodia. | SIGNOR-260802 |
O00327 | P49841 | 0 | phosphorylation | down-regulates | 0.382 | Gsk3beta phosphorylates bmal1 specifically on ser 17 and thr 21 and primes it for ubiquitylation. In the absence of gsk3beta-mediated phosphorylation, bmal1 becomes stabilized and bmal1 dependent circadian gene expression is dampened. | SIGNOR-162786 |
Q9UDY6 | P60484 | 1 | ubiquitination | down-regulates quantity | 0.2 | Collectively, these results indicate that TRIM10 may lead to ubiquitination and degradation of PTEN, which could be an underlying reason for AKT signalling inhibition in cardiac hypertrophy processes (Figure\u00a05D).4\n\nDISCUSSION.|In addition, we found that the effect regulated by TRIM10 was mediated by interactions with phosphatase and tensin homolog (PTEN); specifically, TRIM10 promoted PTEN ubiquitination, thus leading to AKT signalling activation.|The results showed that TRIM10 overexpression decreased PTEN expression, and MG132 reversed the reduction in PTEN (Figure\u00a05C). | SIGNOR-278729 |
Q9H4B4 | Q07817 | 1 | phosphorylation | up-regulates | 0.391 | Polo kinase 3 (plk3) was implicated in bcl-xl(ser49) phosphorylation. These data indicate that, during g2 checkpoint, phospho-bcl-xl(ser49) is another downstream target of plk3, acting to stabilize g2 arrest. | SIGNOR-172230 |
P19235 | O60674 | 0 | phosphorylation | up-regulates activity | 0.812 | JAK2 in turn phosphorylates several tyrosine residues on the EpoR-cytosolic domain and probably on JAK2 itself that serve as docking sites for SH2 or protein tyrosine binding domains of downstream signal transduction proteins such as STAT5, phosphatidylinositol 3-kinase, Shc, and tyrosine phosphatases SHP1 and SHP2 | SIGNOR-251351 |
Q08881 | Q14344 | 1 | phosphorylation | up-regulates activity | 0.2 | This ability of Itk to phosphorylate Galpha13 was abolished in Itk mutants R29C (no longer able to interact with the membrane, and thus unable to interact with Galpha13) and K391M (no kinase activity) (XREF_FIG).|To determine whether Itk is a downstream mediator of Galpha13, we examined whether Galpha13 could interact with Itk when locked in the GDP bound or GTP bound state. | SIGNOR-279623 |
P49137 | P28482 | 0 | phosphorylation | up-regulates | 0.507 | Using novel methodology we demonstrate that activation of mapkap kinase-2 requires the phosphorylation of any two of the three residues thr222, ser272 and thr334. gst-mapkap kinase-2 lacking the n-terminal domain was inactive, but activated fully when phosphorylated at thr222, ser272 and thr334 by p42 mapk or rk. | SIGNOR-44343 |
O75925 | P49137 | 0 | phosphorylation | up-regulates | 0.2 | T he mitogen-activated protein kinase (mapk)-activated protein kinase-2 is a proinflammatory kinase and phosphorylates pias1 at the ser522 residue. Activation of mapk-activated protein kinase-2 enhances p53-sumoylation, but a pias1 phosphorylation mutant, pias1-s522a, abolished this p53-sumoylation, suggesting a critical role for pias1-s522 phosphorylation in its sumo ligase activity. | SIGNOR-199944 |
O15354 | Q86TM6 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.4 | We demonstrated that endogenous HRD1 interacts with Pael-R, and that HRD1 promotes the degradation of Pael-R and protects cell death caused by the accumulation of Pael-R. | SIGNOR-272631 |
Q9BYB0 | Q9Y2H0 | 0 | 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 |
Q13131 | P04637 | 1 | phosphorylation | up-regulates | 0.48 | Ampk activation induces phosphorylation of p53 on serine 15, and this phosphorylation is required to initiate ampk-dependent cell-cycle arrest | SIGNOR-135960 |
Q14524 | Q13555 | 0 | phosphorylation | up-regulates activity | 0.291 | Among the sites identified, only six were previously suggested to be the targets for specific kinases using in silico and/or in vitro analyses: S36 and S525 were attributed to the regulation by PKA; S484 and S664 were assigned to the serum- and glucocorticoid-inducible kinase 3 (SGK3); and S516 and S571 were ascribed to CaMKII (reviewed in Marionneau and Abriel, 2015). In marked contrast, several previously described phosphorylation sites were not detected in the present study, including the PKA-dependent S528, the CaMKII-associated T594, the PKC-dependent S1506, the adenosine monophosphate–activated protein kinase (AMPK)–dependent T101 (Liu et al., 2019), and the six Fyn-dependent tyrosines (Ahern et al., 2005; Iqbal et al., 2018).|The simplest interpretation of these findings is that these three phosphorylation clusters, at positions S457-S460, S483-T486, and S664-S671, are likely involved in regulating the basal and/or gating properties of native cardiac NaV1.5 channels. Conversely, the other phosphorylation sites, with lower stoichiometries, may play spatially or temporally distinct roles in the physiological or more pathophysiological regulation of channel expression or gating. | Remarkably, this MS analysis also revealed that the vast majority of identified phosphorylation sites (at least 26) are clustered, suggesting concomitant phosphorylation and roles in regulating channel expression and/or function. Unexpectedly, however, except for S664, S667, and S671, no apparent effects of phosphomimetic or phosphosilent mutations were observed on heterologously expressed (in HEK-293 cells) NaV1.5 | SIGNOR-275779 |
P25874 | P37231 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.533 | NFIA binds to and activates the brown-fat-specific enhancers even before differentiation and later facilitates the binding of PPARgamma|NFIA has at least three functions on the transcriptional regulation of brown fat [2]. First, NFIA activates adipogenesis per se, through activating the transcription of Pparg, which encodes PPARgamma. Second, NFIA also activates the brown-fat-specific gene expression (such as Ucp1 and Ppargc1a) independent of the degree of adipocyte differentiation, through facilitating the binding of PPARgamma to the brown-fat-specific enhancers. Third, NFIA represses myogenesis through suppression of myogenic transcription factors such as Myod1 as well as Myog, | SIGNOR-263985 |
P17612 | P63104 | 1 | phosphorylation | down-regulates activity | 0.566 | Phosphorylation by pka leads to modulation of 14-3-3zeta dimerization and affect its interaction with partner proteins. Substitution of ser58 to ala completely abolished phosphorylation of 14-3-3zeta by pka. | SIGNOR-143373 |
Q00987 | P62714 | 0 | dephosphorylation | up-regulates activity | 0.4 | cyclin G also binds in vivo and in vitro to Mdm2 and markedly stimulates the ability of PP2A to dephosphorylate Mdm2 at T216. Consistent with these data, cyclin G null cells have both Mdm2 that is hyperphosphorylated at T216 and markedly higher levels of p53 protein when compared to wild-type cells | SIGNOR-248593 |
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