IdA string | IdB string | labels int64 | mechanism string | effect string | score float64 | sentence string | signor_id string |
|---|---|---|---|---|---|---|---|
Q13315 | Q16204 | 1 | phosphorylation | up-regulates | 0.274 | Phosphorylation of ccdc6 at thr434 by atm during dna damage response prevents fbxw7-mediated ccdc6 degradation. | SIGNOR-199276 |
P12821 | P01019-PRO_0000032458 | 1 | cleavage | up-regulates quantity | 0.2 | Ang I is subsequently converted into the major RAS effector peptide Ang II or Ang (1–8), through activity of the zinc-dependent protease ACE, which hydrolyzes two amino acids from the carboxy terminus of Ang I | SIGNOR-260236 |
P49915 | P19474 | 0 | ubiquitination | down-regulates | 0.326 | Cytoplasmic sequestration of gmps requires ubiquitylation by trim21, a ubiquitin ligase associated with autoimmune disease. | SIGNOR-204478 |
P17861-2 | Q96EB6 | 0 | deacetylation | down-regulates activity | 0.379 | P300 increases the acetylation and protein stability of XBP1s, and enhances its transcriptional activity, whereas SIRT1 deacetylates XBP1s and inhibits its transcriptional activity.. The mRNA encoding the active spliced form of XBP1 (XBP1s) is generated from the unspliced form by IRE1 (inositol-requiring enzyme 1) during the UPR. | SIGNOR-260430 |
O95863 | Q92626 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | TGF-β1 induced Snai1 binding to the PXDN promoter (as assessed by chromatin immunoprecipitation-PCR) and significantly repressed luciferase reporter gene expression, as did Snai1 overexpression. | SIGNOR-265249 |
Q00987 | P31751 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.56 | Mitogen-induced activation of phosphatidylinositol 3-kinase (pi3-kinase) and its downstream target, the akt/pkb serine-threonine kinase, results in phosphorylation of mdm2 on serine 166 and serine 186. Phosphorylation on these sites is necessary for translocation of mdm2 from the cytoplasm into the nucleus.. Both akt expression and serum treatment induced phosphorylation of mdm2 at ser186. | SIGNOR-109732 |
Q99661 | P06493 | 0 | phosphorylation | down-regulates | 0.686 | We show here that cyclin-dependent kinase 1 (cdk1) phosphorylates t537 in the core domain of mcak and attenuates its microtubule-destabilizing activity in vitro and in vivo. Phosphorylation of mcak by cdk1 promotes the release of mcak from centrosomes and is required for proper spindle formation. | SIGNOR-164761 |
P19793 | P28482 | 0 | phosphorylation | down-regulates activity | 0.534 | In colon cancer cells, the Ras/mitogen‐activated protein kinase (MAPK) pathway phosphorylates RXRalpha, which impairs its function as a heterodimeric partner for PPARgamma|A point‐mutated RXRalpha T82A/S260A, which mimics the unphosphorylated form of RXRalpha, can form a heterodimer with PPARgamma and thereby activate target gene expression by binding to the PPRE | SIGNOR-262958 |
P56524 | Q9Y2K2 | 0 | phosphorylation | down-regulates activity | 0.411 | They find that SIK3 phosphorylates and inhibits HDAC4 during feeding states.|They find that SIK3 phosphorylates and inhibits HDAC4 during feeding\nstates. | SIGNOR-279430 |
P24666 | Q05397 | 1 | dephosphorylation | down-regulates activity | 0.276 | Lymphocyte function-associated antigen-1-mediated T cell adhesion is impaired by low molecular weight phosphotyrosine phosphatase-dependent inhibition of FAK activity. 4000254={CellProcess=4107155 CellType=10000184}}|Moreover, in these conditions LMW-PTP causes FAK dephosphorylation, thus preventing the activation of FAK downstream pathways. | SIGNOR-277064 |
P19793 | P27361 | 0 | phosphorylation | down-regulates activity | 0.523 | In colon cancer cells, the Ras/mitogen‐activated protein kinase (MAPK) pathway phosphorylates RXRalpha, which impairs its function as a heterodimeric partner for PPARgamma|A point‐mutated RXRalpha T82A/S260A, which mimics the unphosphorylated form of RXRalpha, can form a heterodimer with PPARgamma and thereby activate target gene expression by binding to the PPRE | SIGNOR-88662 |
Q5JUK2 | P60852 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Cotransfection of a mouse Sohlh1 expression vector with E box-containing promoter regions of mouse Lhx8, Zp1, and Zp3 fused to luciferase resulted in significant transactivation . Mutation of the E box sequences abolished SOHLH1-dependent stimulation. Thus, Lhx8, Zp1, and Zp3 are likely direct downstream target genes of SOHLH1 through the E box elements in their promoters. | SIGNOR-266077 |
P56945 | Q14289 | 0 | phosphorylation | up-regulates activity | 0.782 | Pyk2 knockdown also decreased p130Cas.|p130Cas and paxillin can be phosphorylated by Fak or Pyk2, and bind directly to these kinases. | SIGNOR-280100 |
Q9UJU2 | Q9UBE8 | 0 | phosphorylation | down-regulates | 0.76 | Regulation of lymphoid enhancer factor 1/t-cell factor by mitogen-activated protein kinase-related nemo-like kinase-dependent phosphorylation in wnt/beta-catenin signaling.Nlk phosphorylates lef-1/tcf on two serine/threonine residues located in its central region. Mutation of both residues to alanine enhanced lef-1 transcriptional activity and rendered it resistant to inhibition by nlk. | SIGNOR-97812 |
Q15637 | Q13976 | 0 | phosphorylation | down-regulates activity | 0.438 | PKG phosphorylates SF1 at Ser20, which inhibits the SF1-U2AF65 interaction leading to a block of pre-spliceosome assembly. Mutation of Ser20 to Ala or Thr also inhibits the interaction with U2AF65, indicating that Ser20 is essential for binding. | SIGNOR-249018 |
P24941 | P31749 | 0 | phosphorylation | up-regulates | 0.328 | Akt phosphorylates cdk2 at threonine 39 residue both in vitro and in vivo. Although cdk2 threonine 39 phosphorylation mediated by akt enhances cyclin-a binding, it is dispensable for its basal binding and the kinase activity. | SIGNOR-178058 |
P48431 | O95071 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.256 | We identified UBR5 as a major ubiquitin E3 ligase that induces SOX2 degradation through ubiquitinating SOX2 at lysine 115. | SIGNOR-277446 |
O14757 | P30304 | 1 | phosphorylation | down-regulates | 0.857 | The signal for ubiquitination after uv and ir exposure is created by phosphorylation of cdc25a mediated by chk1 and chk2, respectively. Chk1 is a major kinase phosphorylating cdc25a (ser76/124) and cdc25c (ser216). | SIGNOR-163134 |
P09327 | P12931 | 0 | phosphorylation | up-regulates activity | 0.363 | These data suggest that phosphorylation of villin by c-src is involved in the actin cytoskeleton remodeling necessary for cell migration.To further investigate the role of tyrosine phosphorylated villin in cell migration, we used phosphorylation site mutants (tyrosine to phenylalanine or tyrosine to glutamic acid) in HeLa cells. We determined that tyrosine phosphorylation at residues 60, 81, and 256 of human villin played an essential role in cell migration as well as in the reorganization of the actin cytoskeleton | SIGNOR-247441 |
P01112 | Q92565 | 0 | guanine nucleotide exchange factor | up-regulates | 0.508 | Gefs catalyse the transition from gdp-bound, inactive ras to gtp-bound, active ras. | SIGNOR-183732 |
Q7L590 | P09884 | 1 | relocalization | up-regulates quantity by stabilization | 0.862 | Mcm10 is an essential eukaryotic protein required for the initiation and elongation phases of chromosomal replication. Specifically, Mcm10 is required for the association of several replication proteins, including DNA polymerase alpha (pol alpha), with chromatin. | SIGNOR-261271 |
P31749 | P56178 | 1 | phosphorylation | up-regulates | 0.264 | Akt, a member of the ser-ine/threonine-specific protein kinase, was found to phosphorylate osx and dlx5. akt interacts with and phosphorylates dlx5. In addition, we provide evidences that akt kinase activity is important for akt to enhance the protein stability and transcriptional activity of dlx5. | SIGNOR-252513 |
P68400 | P12830 | 1 | phosphorylation | up-regulates activity | 0.401 | Casein kinase II phosphorylation of E-cadherin increases E-cadherin/beta-catenin interaction and strengthens cell-cell adhesion. | Under these conditions, phosphorylation of the E-cadherin double mutant S853A/S855A was reduced by 25% as compared with wt E-cadherin. | Expression of the E-cadherin double mutant S853A/S855A in NIH3T3 cells expressing Wnt-1 reduces cell-cell adhesion. | SIGNOR-250840 |
O00631 | Q9UQM7 | 0 | phosphorylation | down-regulates activity | 0.241 | SLN is also phosphorylated by CaMKII at Thr 5, and a phosphorylation mimic (Thr5Glu mutation) abolishes the inhibitory function of ectopically expressed SLN in adult rat ventricular myocytes| Thr 5 interacts with SERCA Trp 932, and phosphorylation at this site would cause a steric clash that destabilizes binding | SIGNOR-264778 |
Q14653 | Q9BYM8 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.325 | Here we show that the E3 ubiquitin ligase RBCC protein interacting with PKC1 (RBCK1) catalyzes the ubiquitination and degradation of IRF3. We transfected 293 cells with expression plasmids for Flag-IRF3, HA-ubiquitin, and HA-RBCK1. Coimmunoprecipitation and western blot analysis indicated that RBCK1 significantly polyubiquitinated IRF3 (Figure 4D). | SIGNOR-271737 |
Q15424 | Q13043 | 0 | phosphorylation | down-regulates activity | 0.2 | In the present study, we demonstrate that the chromatin scaffold protein SAFB1 interacts with and is phosphorylated by MST1 and is a novel regulator of AR capable of integrating signaling between the AR and MST1 networks. | SIGNOR-279296 |
O15169 | P36894 | 1 | ubiquitination | down-regulates | 0.331 | Other proteins, such as the serine/threonine kinase fused (fu), can function in concert with the e3 ligase smurf to regulate ubiquitination and proteolysis of the bmp receptor | SIGNOR-195552 |
P17858 | O60502 | 0 | deglycosylation | up-regulates activity | 0.2 | Our previous investigation on O-GlcNAcylation of PFK1 has demonstrated that O-GlcNAcylation inhibits PFK1 enzyme activity|In cells, a single set of antagonistic enzymes-O-GlcNAc transferase (OGT) and O-GlcNAc hydrolase are responsible for the addition and removal of GlcNAc moiety, respectively. | SIGNOR-267608 |
Q9UJX2 | P06493 | 0 | phosphorylation | up-regulates | 0.636 | Apc activation is thought to depend on apc phosphorylation and cdc20 binding. We have identified 43 phospho_sites on apc of which at least 34 are mitosis specific. Of these, 32 sites are clustered in parts of apc1 and the tetratricopeptide repeat (tpr) subunits cdc27, cdc16, cdc23 and apc7. In vitro, at least 15 of the mitotic phospho_sites can be generated by cyclin_dependent kinase 1 (cdk1), and 3 by polo_like kinase 1 (plk1). Apc phosphorylation by cdk1, but not by plk1, is sufficient for increased cdc20 binding and apc activation | SIGNOR-119821 |
O75113 | P46934 | 0 | monoubiquitination | up-regulates activity | 0.448 | This observation, together with the monoubiquitination of Nedd4-BP1 by the ubiquitin ligase Nedd4 suggests that the NYN domain proteins of eukaryotes are regulated by monoubiquitination. Given the localization of Nedd4-BP1 to punctuate nuclear bodies, it is likely that they are parts of nuclear RNA-processing complexes that are dependent on monoubiquitination for their assembly. | SIGNOR-272626 |
P61586 | Q92888 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.831 | We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2). | SIGNOR-260528 |
P19784 | Q13351 | 1 | phosphorylation | up-regulates activity | 0.343 | Regulation of erythroid Krppel-like factor (EKLF) transcriptional activity by phosphorylation of a protein kinase casein kinase II site within its interaction domain. the transactivation capability of EKLF is augmented by co-transfection of CKIIalpha. in vitro assays demonstrate that CKIIalpha interacts with EKLF, and that the EKLF interaction domain is phosphorylated by CKII only at Thr-41 | SIGNOR-241365 |
P06493 | Q9C0C7 | 1 | phosphorylation | up-regulates activity | 0.2 | CDK1 phosphorylates AMBRA1 at T1209 and S1223. |CDK1-mediated phosphorylation primes PLK1 phosphorylation on AMBRA1|In this work, we show that AMBRA1 is sequentially phosphorylated at mitosis by CDK1 and PLK1 on multiple sites. In particular, CDK1 is responsible for the early phosphorylations on T1209 and S1223, and it promotes additional late phosphorylation events by PLK1 on AMBRA1. Altogether, these phosphorylation events are critical for proper spindle function and orientation. Indeed, phosphorylated AMBRA1 can interact with NUMA1 and is responsible for NUMA1 proper localization at the cell cortex. Moreover, we observe that loss of AMBRA1 leads to PLK1 protein stabilization and to an increase in phospho-NUMA1 levels which, in turn, contributes to spindle orientation defects. | SIGNOR-272968 |
O14641 | Q6VVB1 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.462 | We have also found that malin enhances K48- and K63-linked ubiquitination of dishevelled2 that could lead to its degradation through both proteasome and autophagy. Altogether, our results indicate that malin regulates Wnt signaling pathway through the degradation of dishevelled2 and suggest possible deregulation of Wnt signaling in Lafora disease. | SIGNOR-272005 |
P01137 | P01222 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | TGF-β inhibits thyroid-stimulated hormone (TSH)-induced NIS mRNA and protein levels in a dose-dependent manner. This effect takes place at the transcriptional level, as TGF-β inhibits TSH-induced transcription | SIGNOR-251991 |
P49768 | P05771 | 0 | phosphorylation | up-regulates activity | 0.2 | A phosphorylation site at serine residue 346 was identified that is selectively phosphorylated by PKC but not by PKA. This site is localized within a recognition motif for caspases, and phosphorylation strongly inhibits proteolytic processing of PS1 by caspase activity during apoptosis. | SIGNOR-249237 |
Q9P0J1 | P00519 | 0 | phosphorylation | down-regulates activity | 0.268 | Here we report that phosphorylation at another tyrosine residue, Tyr-94, inhibits PDP1 by reducing the binding ability of PDP1 to lipoic acid, which is covalently attached to the L2 domain of dihydrolipoyl acetyltransferase (E2) to recruit PDP1 to PDC. We found that multiple oncogenic tyrosine kinases directly phosphorylated PDP1 at Tyr-94, and Tyr-94 phosphorylation of PDP1 was common in diverse human cancer cells and primary leukemia cells from patients. | SIGNOR-276641 |
P06493 | Q9NZI6 | 1 | phosphorylation | up-regulates activity | 0.2 | In addition, overexpression of TFCP2L1 and CDK1 in T24 cells increased clonogenic activity in a clonogenic limiting dilution assay (Fig\u00a05H), confirming the importance of CDK1\u2010TFCP2L1 pathways for the stemness features of BC cells.High levels of co\u2010expression of p\u2010TFCP2L1 and CDK1 were associated with distant metastasis in our cohort of BC patients (Table\u00a01).|Tfcp2l1 Thr177 phosphorylation by CDK1 is essential for proliferation and cell cycle progression of ESCs.|Tfcp2l1 is phosphorylated at Thr177 by CDK1. | SIGNOR-278472 |
P67775 | O95997 | 1 | dephosphorylation | up-regulates quantity by stabilization | 0.295 | CaMKII phosphorylates securin at PP2A substrate site(s).Securin is destabilized by phosphorylation and stabilized by PP2A-dependent dephosphorylation on separase | SIGNOR-276376 |
P51608 | P61278 | 1 | post transcriptional regulation | up-regulates quantity by expression | 0.297 | MeCP2 binds to the promoter region of six target genes. ChIP with anti-MeCP2 antibody shows that MeCP2 binds to the promoter regions of activated targets Sst, Oprk1, Gamt, and Gprin1, and repressed targets Mef2c and A2bp1. | SIGNOR-264676 |
P05412 | Q9UBF6 | 0 | ubiquitination | down-regulates activity | 0.324 | SAG (Sensitive to Apoptosis Gene), also known as RBX2 (RING box protein 2), ROC2 (Regulator of Cullins 2), or RNF7 (RING Finger Protein 7), was originally cloned in our laboratory as a redox inducible antioxidant protein and later characterized as the second member of the RBX/ROC RING component of the SCF (SKP1-CUL-F-box Proteins) E3 ubiquitin ligase. by forming a complex with other components of the SCF E3 ligase, SAG promotes ubiquitination and degradation of a number of protein substrates, including c-JUN, DEPTOR, HIF-1α, IκBα, NF1, NOXA, p27, and procaspase-3, thus regulating various signaling pathways and biological processes. | SIGNOR-271452 |
P28482 | Q9BZI1 | 1 | phosphorylation | up-regulates activity | 0.2 | We tested the transcriptional properties of Irx2 by dividing it into amino- and carboxy terminal parts and found that Mek1-mediated phosphorylation activates and derepresses the amino and carboxyl parts, respectively. When Ser46 and Ser65 were mutated to alanine (S46A and S65A), phosphorylation was reduced, whereas substitution of Ser83 and Ser103 (S83A and S103A) did not affect phosphorylation. | SIGNOR-263052 |
Q8IZL9 | Q15910 | 1 | phosphorylation | up-regulates activity | 0.2 | In addition to the transcriptional feedback loop, we also identified a feed-forward loop in which CCRK induces EZH2 phosphorylation, thereby promoting p-EZH2 Ser21 -AR physical interaction for CCRK promoter co-occupancy and transcriptional activation. | SIGNOR-279017 |
P12931 | P37173 | 1 | phosphorylation | up-regulates | 0.281 | Tbetarii can also be phosphorylated by src, a non-rtk, on y284, which can serve as a docking site for the recruitment of grb2 and shc, thereby bridging tbetarii to mapk activation. | SIGNOR-182963 |
Q05513 | Q96RI1 | 1 | phosphorylation | up-regulates | 0.38 | The effect of fic1 on fxr phosphorylation and nuclear localization and its effects on bsep promoter activity could be blocked with protein kinase c zeta (pkc zeta) inhibitors (pseudosubstrate or small interfering rna silencing). Recombinant pkc zeta directly phosphorylated immunoprecipitated fxr. The mutation of threonine 442 of fxr to alanine yielded a dominant negative protein, | SIGNOR-179771 |
P12931 | P40337 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.29 | We have found that elevated Src can trigger a drastic reduction in VHL stability even under normoxic conditions, through phosphorylation of VHL tyrosine residue 185, leading to ubiquitination and proteasome mediated degradation of VHL. | SIGNOR-279125 |
P19784 | Q01105-2 | 1 | phosphorylation | down-regulates | 0.259 | Ckii-mediated phosphorylation at ser9 hinders nuclear import of set | SIGNOR-200802 |
P23975 | Q13153 | 0 | phosphorylation | down-regulates activity | 0.2 | PAK1 negatively regulates the activity of the Rho exchange factor NET1.|Specifically, PAK1 phosphorylates NET1 on three sites in vitro : serines 152, 153, and 538. | SIGNOR-280054 |
Q15835 | Q13009 | 1 | phosphorylation | down-regulates activity | 0.2 | For example, RhoK phosphorylates and inhibits TIAM1, STEF, and PAR3; disrupts the polarity complex; and prevents Rac activation ( xref ). | SIGNOR-279995 |
O43318 | Q5SGD2 | 0 | dephosphorylation | down-regulates activity | 0.585 | Co-immunoprecipitation experiments indicated that PP2Cepsilon associates stably with TAK1 and attenuates the binding of TAK1 to MKK4 or MKK6.|PP2Cepsilon dephosphorylated TAK1 in vitro. | SIGNOR-277114 |
Q13563 | Q15139 | 0 | phosphorylation | up-regulates activity | 0.458 | Here, we report the identification of a previously unrecognized phosphorylation site within the polycystin-2 C terminus (Ser801), and we demonstrate that it is phosphorylated by protein kinase D. Phosphorylation at this site was significantly increased in response to serum and epidermal growth factor stimulation.We confirmed previous studies showing that PC2 mediated Ca2+ release from the ER can be stimulated by ATP.Phosphorylation at Ser801 seems to be permissive for this activity without altering the subcellular localization nor homophilic and heterophilic (with PC1) interactions of wild-type PC2. | SIGNOR-259829 |
Q8IXT1 | Q9UNE7 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.322 | HSP70 recruits DDIAS to the CHIP E3 ligase, whereas CHIP promotes the ubiquitination of DDIAS.|However, the findings clearly demonstrated that HSP70 was solely involved in CHIP mediated proteasomal degradation of DDIAS. | SIGNOR-278784 |
P05129 | P49840 | 1 | phosphorylation | down-regulates | 0.324 | Convergence of multiple signaling cascades at glycogen synthase kinase 3: edg receptor-mediated phosphorylation and inactivation by lysophosphatidic acid through a protein kinase c-dependent intracellular pathway. | SIGNOR-115726 |
Q14005 | P19784 | 0 | phosphorylation | up-regulates activity | 0.326 | We now show that N-terminal to the NLS domain of pro-IL-16 are protein kinase CK2 substrate and cdc2 kinase substrate sites which, along with the NLS, constitute a dual phosphorylation-regulated CcN motif which regulates nuclear localization of pro-IL-16. In addition, we demonstrate that mutation of either site is associated with impairment of the N-terminal domain's ability to induce G(0)/G(1) cell cycle arrest. | Thus, we confirm that the N-terminal (42SLNEE46) sequence of pro-IL-16 is in fact a site for protein kinase CK2 phosphorylation. | SIGNOR-251009 |
Q8NEZ5 | O43474 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.365 | F-box protein FBXO22 mediates polyubiquitination and degradation of KLF4 to promote hepatocellular carcinoma progression | SIGNOR-273444 |
P29350 | P06241 | 0 | phosphorylation | up-regulates activity | 0.551 | By contrast, receptor multivalent aggregation induced a Fyn-dependent SHP-1 S591 phosphorylation (Fig.\u00a0 xref ).|Fyn simultaneously activates the PI3K-PKC\u03b1 pathway, leading to SHP-1 phosphorylation on serine 591. | SIGNOR-279716 |
Q16665 | P48730 | 0 | phosphorylation | down-regulates | 0.324 | In this work, we investigate the phosphorylation of the n-terminal heterodimerization (pas) domain of hif-1alpha and identify ser247 as a major site of in vitro modification by casein kinase 1delta (ck1delta). Mutation of this site to alanine, surprisingly, enhanced the transcriptional activity of hif-1alpha | SIGNOR-167476 |
Q13554 | P35222 | 1 | phosphorylation | down-regulates | 0.289 | Camkii represses transcriptionally active _-catenin to mediate acute ethanol neurodegeneration and can phosphorylate _-catenincamkii can directly phosphorylate _-catenin. Using targeted mutagenesis we identified camkii phosphorylation sites within human _-catenin at t332, t472, and s552. | SIGNOR-202833 |
O96017 | P67775 | 0 | dephosphorylation | up-regulates activity | 0.432 | Protein phosphatase 2A interacts with Chk2 and regulates phosphorylation at Thr-68 after cisplatin treatment of human ovarian cancer cells|In response to DNA damage, Chk2 is initially phosphorylated at Thr-68, which leads to its full activation. | SIGNOR-248617 |
Q12888 | Q8N2W9 | 0 | sumoylation | up-regulates | 0.637 | Pias1 and pias4 are recruited to dna-damage sites and mediate 53bp1 recruitment and sumoylation | SIGNOR-162167 |
Q9BXW9 | Q13315 | 0 | phosphorylation | up-regulates | 0.789 | These results suggest that s222 and either s1401, s1404, or s1408 are sites of atm-dependent phosphorylation in vitro.Phosphorylation Of fancd2 is required for activation of an s phase checkpoint | SIGNOR-90117 |
O75376 | Q96EB6 | 0 | null | up-regulates | 0.621 | In differentiated adipocyte cell lines, SIRT1 inhibits adipogenesis and enhances fat mobilization through lipolysis by suppressing the activity of PPARγ. SIRT1 achieves this by promoting the assembly of a corepressor complex, involving NCoR1 and SMRT, on the promoters of PPARγ target genes to repress their transcription. | SIGNOR-253505 |
P35626 | P51681 | 1 | phosphorylation | down-regulates activity | 0.2 | Serine residues at positions 336, 337, 342, and 349 represent GRK phosphorylation sites on CCR5. CCR5 phosphorylation and desensitization through a GRK-mediated mechanism | SIGNOR-251463 |
P03230 | Q92985 | 1 | sumoylation | down-regulates activity | 0.2 | One mechanism by which LMP1 regulates cellular activation is through the induction of protein posttranslational modifications. We have now identified a specific target of LMP1-induced sumoylation, interferon regulatory factor 7 (IRF7). We hypothesize that during EBV latency, LMP1 induces the sumoylation of IRF7, limiting its transcriptional activity and modulating the activation of innate immune responses. | SIGNOR-266951 |
Q99933 | O75807 | 1 | null | down-regulates activity | 0.444 | Human BAG-1 proteins bind to the cellular stress response protein GADD34 and interfere with GADD34 functions.|BAG-1 negatively modulates GADD34-bound PP1 activity, and the expression of BAG-1 isoforms can also mask GADD34-mediated inhibition of colony formation and suppression of transcription. Our findings suggest that BAG-1 may function to suppress the GADD34-mediated cellular stress response and support a role for BAG-1 in the survival of cells undergoing stress. | SIGNOR-254117 |
Q14511 | Q06124 | 0 | dephosphorylation | down-regulates activity | 0.488 | In this study we demonstrated that SHP-2 inhibits tyrosine phosphorylation of Cas-L, and negatively regulates the cell migration induced by Cas-L.|These results show that both SH2 domains of SHP-2 are necessary for the interaction with Cas-L.\nIn this study we demonstrated that SHP-2 inhibits tyrosine phosphorylation of Cas-L, and negatively regulates the cell migration induced by Cas-L. Furthermore, our data raise the possibility that Cas-L is a direct substrate for SHP-2, although SHP-2 may inhibit Cas-L phosphorylation indirectly by regulating kinase activity. | SIGNOR-277083 |
P19784 | O95786 | 1 | phosphorylation | down-regulates activity | 0.2 | Phosphorylation of RIG-I by casein kinase II inhibits its antiviral response.Threonine at amino acid (aa) 770 and serine at aa 854 to 855 of RIG-I are phosphorylated by casein kinase II (CK2) in the resting state of the cell and dephosphorylated when cells are infected by RNA virus. | SIGNOR-276285 |
P46527 | Q13616 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.642 | Furthermore, c-myc activation can also promote the degradation of p27kip1 protein by directly activating the cul1 gene, which encodes a critical component of the ubiquitin ligase scfskp2 | SIGNOR-102725 |
Q16819 | Q99626 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.471 | TNF-α-induced down-regulation of CDX2 suppresses MEP1A expression in colitis| | SIGNOR-253965 |
P61073 | Q15139 | 0 | phosphorylation | down-regulates quantity | 0.2 | Inhibition of PKD activity restores membrane expression of CXCR4 and migration towards CXCL12 in BCR responsive cells in vitro.|This cascade consisted on a novel BCR dependent pathway in which PI3K-delta phosphorylates PKD, which in turn phosphorylates CXCR4 at Ser 324/325. | SIGNOR-279263 |
O75475 | P42574 | 0 | cleavage | down-regulates | 0.348 | Ledgf/ p75 has a cooh-terminally truncated splice variant, p52 / during apoptosis, caspase-3 cleaved p52 to generate a p38 fragment that lacked the nh2-terminal pwwp domain and failed to transactivate the hsp27 promoter in reporter assays. However, p38 retained chromatin association properties and repressed the transactivation potential of ledgf/p75 | SIGNOR-180144 |
P12830 | P56545 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.381 | Overexpression of the CtBP2 protein enhanced the repression activity of the E-cadherin promoter in a dose-dependent manner, whereas overexpression of ataxin-1 increased the activity of the E-cadherin promoter in a dose-dependent manner | SIGNOR-261578 |
Q13315 | Q9UGP5 | 1 | phosphorylation | up-regulates activity | 0.354 | 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-273836 |
P27816 | O14757 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.2 | MAP4 is a novel target of FBXW7 via the phosphorylated threonine T521 modified by CHEK1 in ESCC. The threonine T521 of MAP4, which was phosphorylated by CHEK1, played a key role in the FBXW7-related degradation system. | SIGNOR-277846 |
P31749 | P26678 | 1 | phosphorylation | down-regulates activity | 0.289 | Akt interacts with and phosphorylates PLN at Thr(17), the Ca(2+)-calmodulin-dependent kinase IIdelta site, whereas silencing Akt signaling, through the knock-out of phosphatidylinositol-dependent kinase-1, resulted in reduced phosphorylation of PLN at Thr(17). | SIGNOR-252578 |
P04626 | Q96PG8 | 1 | phosphorylation | down-regulates activity | 0.281 | These results show for the first time that PUMA can be phosphorylated at tyrosine residues directly by HER2.|Together, our results demonstrate, for the first time, that PUMA can be tyrosine phosphorylated and that HER2-mediated phosphorylation destabilizes PUMA protein. | SIGNOR-278224 |
Q13627 | P46531 | 1 | phosphorylation | down-regulates | 0.396 | Dyrk1a physically interacts with the nicd inducing its phosphorylation in the ankyrin domain, thereby attenuating notch . | SIGNOR-185494 |
Q9P0L0 | Q92953 | 0 | relocalization | up-regulates quantity | 0.2 | Confirmation that Kv2.1 and -2.2 bind VAPA and VAPB employed colocalization/redistribution, siRNA knockdown, and Förster resonance energy transfer (FRET)-based assays.|As Kv2.1 accumulates on the surface it begins to bind ER VAPs and form the large and stable membrane junctions. | SIGNOR-262124 |
P17252 | P09211 | 1 | phosphorylation | up-regulates activity | 0.2 | Peptide phosphorylation analyses and both phosphorylation and enzyme kinetic studies with GSTP1 proteins mutated at candidate amino acid residues established Ser-42 and Ser-184 as putative phospho-acceptor residues for both kinases in the GSTP1 protein. Together, these findings show PKA- and PKC-dependent phosphorylation as a significant post-translational mechanism of regulation of GSTP1 function. Together, these results further support S42 and S184 as major phosphor-acceptor residues for PKA and PKC and suggest that the increased activity of the phospho-GSTP1 was not simply a consequence of the negative charge introduced in the GSTP1 protein by the phosphate group.All eight PKC isoforms, PKC-α, PKC-βI, PKC-βII, PKC-ε, PKC-γ, PKC-η, and PKC-ζ phosphorylated the GSTP1 protein efficiently | SIGNOR-276024 |
Q06187 | Q04206 | 1 | phosphorylation | up-regulates activity | 0.403 | Btk induces the phosphorylation of NF-\u03baB p65 which can be induced by the expression of inflammation cytokines [ ].|Btk induces the phosphorylation of NF-\u03baB p65 which can be induced by the expression of inflammation cytokines [ xref ]. | SIGNOR-280197 |
P02452 | P01137 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.485 | COL1A1 expression is regulated by upstream genes and the binding of regulatory elements at multiple binding sites upstream of its promoter. During cancer progression, CAFs reorganize and cross-link COL1A1, which accumulates and stiffens in the tumor stroma [12], [18]. This process may involve fibrogenic factors, especially transforming growth factor-beta (TGF-β1). Indeed, a TGF-β1 response sequence was identified 174 nucleotides upstream of the COL1A1 transcription start site, and was shown to up-regulate COL1A1 promoter activity | SIGNOR-277678 |
P04049 | P01111 | 0 | relocalization | up-regulates | 0.87 | The raf family of proteins (raf-1, a-raf, and b-raf) bind to the effector region of ras-gtp, thus inducing translocation of the protein to the plasma membrane. Once there, raf proteins are activated and phosphorylated by different protein kinases. | SIGNOR-175231 |
Q13309 | O75874 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | During the cell cycle S phase, Cyclin A-CDK2 phosphorylates IDH1 on its Threonine 157 residue (Threonine 197 in IDH2) to facilitate its recognition and ubiquitination by Skp2 E3 ubiquitin, followed by degradation through 26S proteasome | SIGNOR-267625 |
O75298 | Q9C037 | 0 | ubiquitination | down-regulates quantity | 0.2 | 2: TRIM4 ubiquitinates and degrades the NSP2 protein.|Mechanistic studies showed that TRIM4 ubiquitinated modified NSP2 and down-regulated NSP2 expression. | SIGNOR-278793 |
P27361 | P49418 | 1 | phosphorylation | down-regulates activity | 0.274 | Thus, we propose that mapk phosphorylation of amphiphysin1 controls ngf receptor/trka-mediated endocytosis by terminating the amphiphysin1-ap-2 interaction.Our results indicate that phosphorylation of amphiphysin 1 at ser-285 and/or ser-293 affects the function of amphiphysin1.Mapk phosphorylation of ser-285 and ser-293 could modulate the interaction between prd and ap-2, resulting in the dissociation of amphiphysin1 from ap-2. | SIGNOR-126867 |
Q8IYU2 | P63000 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.367 | The CNF1 toxin of pathogenic Escherichia coli addresses Rac1 to ubiquitin-proteasome system (UPS). We report the essential role of the tumor suppressor HACE1, a HECT-domain containing E3 ubiquitin-ligase, in the targeting of Rac1 to UPS. HACE1 binds preferentially GTP-bound Rac1 and catalyzes its polyubiquitylation | SIGNOR-255538 |
P49841 | Q7KZI7 | 1 | phosphorylation | down-regulates activity | 0.349 | MARK family kinases can be activated by phosphorylation of a conserved threonine (Thr-208 in MARK2), and inactivated by phosphorylation of a serine (Ser-212), both in the activation loop of the catalytic domain. Activation is achieved by the kinases MARKK/TAO1 or LKB1, although the inactivating kinase was unknown. We show here that GSK3beta serves the role of the inhibitory kinase. | SIGNOR-276163 |
P68400 | P11387 | 1 | phosphorylation | up-regulates activity | 0.383 | In vitro kinase assays demonstrated that Ser(10) can be phosphorylated by casein kinase II, Ser(21) can be phosphorylated by protein kinase Calpha, and Ser(112) and Ser(394) can be phosphorylated by Cdk1.Collectively these results indicate that topo I is phosphorylated during mitosis at multiple sites, one of which enhances DNA relaxation activity in vitro and interaction with DNA in cells. | SIGNOR-276155 |
Q9NZQ7 | Q8IZR5 | 0 | stabilization | up-regulates quantity by stabilization | 0.353 | Furthermore, the observations that (i) CMTM6 affects PD-L1 protein stability at late time points after biosynthesis; (ii) CMTM6, CMTM4 and PD-L1 interact, as shown by co-immunoprecipitation; and that (iii) CMTM6 is largely located at the cell surface, collectively suggest a model in which CMTM6 interacts with PD-L1 at the tumour cell surface and thereby protects it from degradation | SIGNOR-274981 |
P49768 | Q14790 | 0 | cleavage | up-regulates activity | 0.368 | Remarkably, the caspases acting on PS1 could be subdivided in two groups. One group, containing caspase-8, -6 and -11, cleaved PS1 after residues ENDD329 and to a lesser extent after residues AQRD341. A second group consisting of caspase-3, -7 and -1 acted uniquely on AQRD341. Importantly, these two cleavage sites were also recognized by caspases in the C-terminal PS1 fragment produced by constitutive proteolysis. | SIGNOR-261760 |
P25098 | P30989 | 1 | phosphorylation | up-regulates activity | 0.2 | Here we report the unique phosphorylation\nof NTSR1 by GRK2 and GRK5, which belong to the GRK2 and GRK4 subfamilies,\nrespectively. | SIGNOR-278280 |
P00519 | Q05209 | 0 | dephosphorylation | down-regulates activity | 0.439 | Several experiments suggest that the pest-type ptps negatively regulate c-abl activity: c-abl was hyperphosphorylated in ptp-pest-deficient cells dephosphorylation of c-abl by pest-type ptp represents a novel mechanism by which c-abl activity is regulated. | SIGNOR-235568 |
Q14938 | P23352 | 1 | transcriptional regulation | down-regulates quantity | 0.2 | By integrating transcriptomic profiling (RNA-seq) of Nfia- and Nfix-deficient GNPs with epigenomic profiling (ChIP-seq against NFIA, NFIB and NFIX, and DNase I hypersensitivity assays), we reveal that these transcription factors share a large set of potential transcriptional targets, suggestive of complementary roles for these NFI family members in promoting neural development | SIGNOR-268884 |
P31749 | Q09472 | 1 | phosphorylation | up-regulates | 0.697 | We find that suberoylanilide hydroxamic acid stimulates akt activity, which is required to phosphorylate p300 at ser(1834). Akt-mediated phosphorylation of p300 dramatically increases its acetyltransferase activity | SIGNOR-148983 |
Q9UQD0 | Q96PU5 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.325 | 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-253461 |
Q6FI13 | Q86Y13 | 0 | monoubiquitination | up-regulates activity | 0.2 | 2A-HUB catalyzes monoubiquitination of H2A at lysine 119, functioning as a combinatoric component of the repression machinery required for specific gene regulation programs. Thus, 2A-HUB mediates a selective repression of a specific set of chemokine genes in macrophages, critically modulating migratory responses to TLR activation. H2A monoubiquitination acts to prevent FACT recruitment at the transcriptional promoter region, blocking RNA polymerase II release at the early stage of elongation. | SIGNOR-271755 |
P84022 | P49841 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.488 | Mechanistically, axin facilitates gsk3-beta-mediated phosphorylation of smad3 at thr66, which triggers smad3 ubiquitination and degradation. | SIGNOR-160318 |
P54762 | Q8WXD9 | 1 | phosphorylation | up-regulates activity | 0.283 | EphB1 phosphorylates Caskin1 on tyrosine 296 and 336. Tyrosine phosphorylated Caskin1 then likely promotes reorganization of the actin cytoskeleton leading to spine formation. | SIGNOR-262861 |
P01112 | P49356 | 0 | null | up-regulates activity | 0.46 | Major investments have been made to target Ras through indirect routes. Inhibition of farnesyl transferase to block Ras maturation has failed in large clinical trials. | SIGNOR-242565 |
Q9UHD2 | A5D8V6 | 1 | phosphorylation | down-regulates activity | 0.366 | We have identified that TBK1 may target and phosphorylate VPS37C, a structural component of ESCRT-I complex, and serve as a ratelimiting factor in the control of PTAP-dependent (HIV-1, MLV/p6, and EIAV/PTAP), but not PPPY-dependent (MLV, EIAV/PPPY) retrovirus budding, independent of its role in IFN-I signaling. | SIGNOR-279768 |
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