IdA string | IdB string | labels int64 | mechanism string | effect string | score float64 | sentence string | signor_id string |
|---|---|---|---|---|---|---|---|
P22891 | P38435 | 0 | carboxylation | up-regulates activity | 0.507 | Gamma-carboxylation is essential in the activation and proper functioning of multiple VK-dependent proteins (VKDP), the most well-known of which are involved in blood clotting, including coagulation factors (FII, FVII, FIX and FX) and natural anti-clotting agents (protein C, protein S (ProS; OMIM*176880) and protein Z | SIGNOR-265926 |
Q92736 | Q15772 | 0 | phosphorylation | down-regulates activity | 0.248 | Conclusions : Unlike other kinases (PKA, CaMKII) that increase RyR2 activity, SPEG phosphorylation reduces RyR2 mediated SR Ca 2+ -release.|Further, we show that SPEG phosphorylates RyR2 at a previously uncharacterized serine (S2367) located in the central domain of the channel. xref Importantly, in contrast to previously studied phosphorylation sites that activate RyR2 (e.g. S2808, S2814), we show that SPEG mediated RyR2-S2367 phosphorylation suppresses pathogenic diastolic SR Ca 2+ -leak. | SIGNOR-279114 |
P45983 | Q92934 | 1 | phosphorylation | down-regulates | 0.686 | Jnk phosphorylates bad at threonine 201, thereby inhibiting bad association with the antiapoptotic molecule bcl-x(l) | SIGNOR-121940 |
Q8WZ64 | P60953 | 1 | gtpase-activating protein | down-regulates activity | 0.495 | 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-260455 |
P16220 | P31749 | 0 | phosphorylation | up-regulates activity | 0.769 | When overexpressed in serum-stimulated cells, Akt/PKB potently induced Ser-133 phosphorylation of CREB and promoted recruitment of CBP. Correspondingly, Akt/PKB stimulated target gene expression via CREB in a phospho(Ser-133)-dependent manner. | SIGNOR-252549 |
Q9Y2K6 | Q13535 | 0 | phosphorylation | down-regulates activity | 0.306 | On the other hand, USP20 is phosphorylated by ATR, which disrupts the interaction between USP20 and HERC2, resulting in USP20 stabilization.|USP20 phosphorylation by ATR is important for its stabilization and checkpoint activation. | SIGNOR-278393 |
P78536 | P01135 | 1 | cleavage | up-regulates activity | 0.489 | ADAM17 is involved in the release and activation of several growth factors and cytokine receptor ligands. Among the growth factors activated by ADAM17 are TGF-alpha, amphiregulin, epiregulin and HB-EGF | SIGNOR-259841 |
P11413 | Q05655 | 0 | phosphorylation | up-regulates | 0.2 | A pkc activator, significantly increased g6pd phosphorylation and activity, whereas single (s210a, t266a) and double (s210a/t266a) mutations at sites flanking the g6pd active site significantly inhibited phosphorylation, shifted the isoelectric point, and reduced enzyme activity. | SIGNOR-167053 |
Q12772 | Q14703 | 0 | cleavage | up-regulates activity | 0.594 | We present evidence that SKI-1 processes peptides mimicking the cleavage sites of the SKI-1 prosegment, pro-brain-derived neurotrophic factor, and the sterol regulatory element-binding protein SREBP-2 | SIGNOR-267496 |
P23443 | Q15633 | 1 | phosphorylation | up-regulates activity | 0.322 | We demonstrate that S6 kinases can phosphorylate the extended C-terminal domain of TRBP and interact with TRBP in situ in primary cells. TRBP serines 283/286 are essential for S6K-mediated TRBP phosphorylation, optimal expression of TRBP, and the S6K-TRBP interaction in human primary cells. | SIGNOR-274068 |
P28482 | P01106 | 1 | phosphorylation | up-regulates activity | 0.735 | Transactivation of gene expression by myc is inhibited by mutation at the phosphorylation sites thr-58 and ser-62. | SIGNOR-235700 |
P42658 | Q9UBC3 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.327 | Dnmt3b was responsible for transcriptional silencing of Dpp6 gene as depletion of Dnmt3b resulted in increased mRNA and protein expression of Dpp6. | SIGNOR-268963 |
Q7Z2G1 | 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-265387 |
P40763 | Q9NZQ7 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.464 | STAT3 and HIF-1α cooperatively enhance PD-L1 expression in EML4-ALK-translocated pADC cells under hypoxia.The protein-DNA binding assay revealed that pSTAT3 was bound to the PD-L1 promoter region in H23 cells transfected with EML4-ALK. | SIGNOR-259188 |
Q12800 | P67775 | 0 | dephosphorylation | up-regulates | 0.2 | We previously established that phosphorylation of lsf in early g1 at ser-291 and ser-309 inhibits its transcriptional activity and that dephosphorylation later in g1 is required for its reactivation. This predominant cis conformation would also limit dephosphorylation of ser-291 and ser-309 by phosphatases such as pp2a | SIGNOR-167385 |
Q9Y6K9 | P49841 | 0 | phosphorylation | down-regulates quantity | 0.431 | For analysis of phosphorylation of NEMO on Ser8 and Ser17 by GSK-3, we generated phospho-specific antibodies (anti-phospho-NEMO-Ser8 and anti-phospho-NEMO-Ser17) while anti-phospho-NEMO-Ser31 and anti-phospho-NEMO-Ser43 were commercially available. Indeed, GSK-3\u03b2 was able to phosphorylate all four serines of rhNEMO in a time-dependent manner in an in vitro kinase assay (Fig. 3a).|In this study, we identified NEMO as a GSK-3\u03b2 substrate that is phosphorylated at several serine residues located within the N-terminal domain.|The kinase forms a complex with wild-type NEMO while point mutations of NEMO at the specific serines abrogated GSK-3β binding and subsequent phosphorylation of NEMO resulting in its destabilization | SIGNOR-279527 |
P01106 | P34896 | 1 | 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 |
Q9HC78 | P25963 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.259 | ChIP and next generation high-throughput DNA sequencing assay showed that ZBTB20 specifically bound to IκBα gene promoter (+1 to +60 region) after TLR activation. ZBTB20 could inhibit IκBα gene transcription, govern IκBα protein expression, and then promote NF-κB activation. Therefore, transcriptional repressor ZBTB20 is needed to promote full activation of TLR signaling and TLR-triggered innate immune response by selectively suppressing the suppressor IκBα gene transcription. | SIGNOR-266868 |
O15198 | P36894 | 0 | phosphorylation | up-regulates activity | 0.706 | To ascertain whether overexpression of BMPr1A can initiate adipocyte lineage commitment in the absence of its BMP ligand, constitutively active (CA)-BMPr1A and CA-BMPr1B were expressed in C3H10T1/2 stem cells using a mouse stem cell virus (MSCV) retroviral system. […]Thus, their overexpression provoked a substantial rise in the phosphorylation of Smad1/5/8 and p38 MAPK, known downstream phosphorylated intermediates in the BMP signaling pathway. | SIGNOR-255772 |
P22681 | P16234 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.478 | Cbl overexpression in nih3t3 cells enhanced the ubiquitination and degradation of the platelet-derived growth factor receptor-alpha (pdgfralpha) | SIGNOR-68024 |
Q53H47 | O14757 | 0 | phosphorylation | down-regulates activity | 0.49 | We previously found that Chk1 phosphorylation of Metnase on S495 enhanced its DNA DSB repair activity but decreased its ability to re-start stalled replication forks. Here we show that phosphorylated Metnase feeds back to increase the half-life of Chk1. Chk1 half-life is regulated by DDB1 targeting it to Cul4A for ubiquitination and destruction. Metnase decreases Chk1 interaction with DDB1, and decreases Chk1 ubiquitination. | SIGNOR-273610 |
P15976 | Q9P286 | 0 | phosphorylation | up-regulates activity | 0.2 | In addition, we defined GATA1 Ser161, Ser187 were the main phosphorylation sites by PAK5. | SIGNOR-278297 |
P46937 | P07947 | 0 | phosphorylation | up-regulates activity | 0.721 | Yes directly phosphorylates YAP and TAZ, resulting in their increased nuclear localization and transcriptional activity.Analysis by mass spectrometry identified Tyr391 and Tyr407 as the two phosphorylation sites of YAP, whereas Tyr305 was the sole phosphorylated residue of TAZ (Fig. 5F and fig. S4, A to C). | SIGNOR-277653 |
P50613 | P49736 | 1 | phosphorylation | up-regulates activity | 0.299 | Taken together, these results indicate that Cdc7/Dbf4 phosphorylation of MCM2 is essential for the initiation of DNA replication in mammalian cells. | Because MCM2 was phosphorylated in vivo at Ser27, Ser41, and Ser139, which were phosphorylated by Cdc7/Dbf4 in vitro, the results suggested that Ser27, Ser41, and Ser139 are in vivo Cdc7/Dbf4 phosphorylation sites in MCM2. | SIGNOR-259849 |
P15907 | P20273 | 1 | glycosylation | down-regulates activity | 0.471 | CD22-ligand interaction is regulated by the activity of a b-galactoside a2,6- sialyltransferase that can inactivate CD22-mediated binding by sialylating the CD22 receptor itself. These observations suggest that N-linked glycosylation sites on the CD22 molecule may play a role in the regulation of CD22-mediated adhesion. | SIGNOR-261741 |
P10912 | P26045 | 0 | dephosphorylation | down-regulates activity | 0.43 | PTPH1 only bound Tyr534, whereas PTP1B and TC-PTP bound multiple phosphopeptides. Earlier work suggests that Tyr332, Tyr487, Tyr534, Tyr566, and Tyr627 are all phosphorylated after GH stimulation (21). Apart from Tyr627, all of these also appear good PTP substrates | SIGNOR-248459 |
P38936 | P28482 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.364 | Extracellular signal-regulated kinase 2-dependent phosphorylation induces cytoplasmic localization and degradation of p21cip1.|Phosphopeptide analysis of in vitro ERK2-phosphorylated p21(Cip1) revealed two phosphorylation sites, Thr57 and Ser130. | SIGNOR-185215 |
O43597 | P12931 | 0 | phosphorylation | up-regulates | 0.565 | Activation of signalling by fibroblast growth factor receptor leads to phosphorylation of the signalling attenuator human sprouty 2 (hspry2) on residue y55. we show that hspry2 is a direct substrate for src family kinases, including src itself.Phosphorylation of hspry2 is required for hspry2 to inhibit activation of the extracellular signal-regulated kinase pathway. | SIGNOR-131189 |
P09958 | P04275 | 1 | cleavage | up-regulates activity | 0.481 | Like PACE,PACE4 was able to process pro-vWF to its mature form, and efficient cleavage required both the P4 arginine and the P2 lysine | SIGNOR-260368 |
P23588 | Q14004 | 0 | phosphorylation | up-regulates activity | 0.251 | CDK13 directly phosphorylates 4E-BP1 at Thr46 and eIF4B at Ser422; genetically or pharmacologically inhibiting CDK13 disrupts mRNA translation. | SIGNOR-273115 |
P07948 | Q92835 | 1 | phosphorylation | up-regulates activity | 0.509 | In this line, Lyn has been demonstrated to tyrosine-phosphorylate and activate SHIP1, thereby constituting a negative feedback control of PI3K-mediated signals. | SIGNOR-279060 |
P11362 | P54764 | 0 | phosphorylation | up-regulates activity | 0.402 | EphA4 and FGFR1 heterodimer promotes FGFR1 signaling in glioma cell line.|Ligand stimulation of EphA4 stimulates FGFR1 phosphorylation and signaling. | SIGNOR-280007 |
P35222 | P06241 | 0 | phosphorylation | down-regulates activity | 0.851 | Interaction of beta-catenin with alpha-catenin is regulated by the phosphorylation of beta-catenin Tyr-142. This residue can be phosphorylated in vitro by Fer or Fyn tyrosine kinases. Transfection of these kinases to epithelial cells disrupted the association between both catenins. | SIGNOR-251162 |
P29317 | Q15418 | 0 | phosphorylation | up-regulates activity | 0.292 | These comprehensive analyses indicate that high matrix stiffness activates ERK/RSK1-mediated EPHA2 non-canonical signalling to induce LYN activation, TWIST1 nuclear localization, and cell invasion (Fig. 6M).|We next knocked down the most abundant RSK family members and found that loss of RSK1, but not RSK2 or RSK3, drastically inhibited EPHA2 S897 phosphorylation, prevented ECM stiffness-induced LYN activation and recruitment to EPHA2, and inhibited cell EMT and invasion induced by increasing rigidities (Fig. 6F\u2013I and S6H\u2013L). | SIGNOR-280113 |
O43426 | Q9NQU5 | 0 | phosphorylation | up-regulates activity | 0.2 | We identified two novel Pak5 substrates, Pacsin1 and Synaptojanin1, proteins that directly interact with one another to regulate synaptic vesicle endocytosis and recycling. Pacsin1 and Synaptojanin1 were phosphorylated by Pak5 and the other group II Paks in vitro, and Pak5 phosphorylation promoted Pacsin1-Synaptojanin1 binding both in vitro and in vivo. | SIGNOR-263022 |
Q9UPU5 | Q92466 | 1 | deubiquitination | up-regulates | 0.703 | Usp24-mediated ddb2 deubiquitination prevents ddb2 degradation | SIGNOR-199731 |
P10636-2 | Q13131 | 0 | phosphorylation | down-regulates activity | 0.2 | We have studied the relationship between the phosphorylation oftau by several kinases (MARK, PKA, MAPK, GSK3) and its assembly into PHFs. By contrast, MARK and PKA phosphorylate several sites within the repeats (notably theKXGS motifs including Ser262, Ser324, and Ser356, plus Ser320); in addition PKA phosphorylates somesites in the flanking domains, notably Ser214. This type of phosphorylation strongly reduces tau’s affinityfor microtubules, and at the same time inhibits tau’s assembly into PHFs. | SIGNOR-275438 |
Q04206 | P47710 | 0 | phosphorylation | up-regulates | 0.2 | Phosphorylation of serine 529 of p65 is mediated by casein kinase ii, but is prevented in nonstimulated cells by the interaction with ikba | SIGNOR-171222 |
O60216 | P23769 | 1 | relocalization | down-regulates activity | 0.325 | Large-scale AML genome re-sequencing efforts have identified novel recurrently mutated genes, including the members of the cohesin complex (RAD21, SMC3, SMC1A, and STAG2), implicated in the pathogenesis of this disease.Using ATAC-seq, we determined that mutant cohesin lead to a state of elevated chromatin accessibility and higher predicted binding at transcription factor binding sites for ERG, GATA2, and RUNX1. Moreover, using ChIP-Seq, we formally demonstrated increased binding of GATA2 and RUNX1 to these sites. Finally, we demonstrated that knockdown of these three TFs in human HSPC can revert the differentiation block induced by mutant cohesin. These results support a model in which mutant cohesin impairs hematopoietic differentiation and enforces stem cell programs through the modulation of ERG, GATA2, and RUNX1 chromatin accessibility, expression, and activity. | SIGNOR-261513 |
P45983 | P31946 | 1 | phosphorylation | down-regulates | 0.2 | The c-jun n-terminal kinase (jnk) protein is activated in the cellular response to dna damage and phosphorylates 14-3-3 on ser 184 these results support a role for 14-3-3 proteins in inhibiting c-abl-mediated apoptosis by sequestering c-abl into the cytoplasm. these findings support a model in which jnk phosphorylation of 14-3-3 proteins induces dissociation of the c-abl_14-3-3 complex and thereby targeting of c-abl to the nucleus. | SIGNOR-133875 |
P00519 | P15172 | 1 | phosphorylation | down-regulates activity | 0.286 | We have found that c-Abl can phosphorylate MyoD at a conserved N-terminal tyrosine (Tyr30) that is located within the transactivation domain. Mutation of Tyr30 to Phe does not interfere with the function of MyoD, but theTyr30Phe mutant becomes resistant to the inhibitory effect of DNA damage. | SIGNOR-253055 |
Q9Y6Q9 | O14920 | 0 | phosphorylation | up-regulates activity | 0.378 | We demonstrated the in vitro phosphorylation of SRC-3 by the two catalytic subunits of the IKK complex, IKKα and IKKβ. IKK kinase activity is required for synergistic activation with SRC-3 | SIGNOR-251298 |
P28482 | P35398 | 1 | phosphorylation | down-regulates | 0.26 | We identified the extracellular signal-regulated kinase 2 (erk-2) as roralpha4 phosphorylating kinase in vitro. The primary sequence of roralpha4 contains an erk-2 recognition motif (p-l-t(128)-p) within the hinge domain, and mutation of thr-128 to ala prevents roralpha4 phosphorylation by erk. The roralpha4-t128a mutant exhibits an increased dna-binding affinity, an increased transcriptional activity | SIGNOR-154914 |
Q8NFZ5 | Q96J02 | 0 | ubiquitination | down-regulates | 0.268 | Here we show that tnfa-mediated jnk activation accelerates turnover of the NF-kappaBinduced antiapoptotic protein c-flip, an inhibitor of caspase-8. This is not due to direct c-flip phosphorylation but depends on jnk-mediated phosphorylation and activationof the e3ubiquitin ligaseitch, which speci?cally Ubiquitinates c-flip and induces its proteasomal degradation. | SIGNOR-144453 |
P15169 | P69905 | 1 | cleavage | down-regulates activity | 0.2 | Both human plasma carboxypeptidase N (CPN) and membrane-bound carboxypeptidase M (CPM) released the C-terminal arginine (alpha-Arg141) of the alpha chain of human adult hemoglobin. Thus, the hydrolysis of hemoglobin by CPM and CPN demonstrated the contribution of the alpha-Arg141 residue to sustaining the tetrameric structure of hemoglobin and its normal oxygen affinity and vasoactivity. | SIGNOR-256508 |
Q8IVT5 | Q7KZI7 | 0 | phosphorylation | down-regulates activity | 0.315 | In vivo, MARK2 appears to negatively regulate KSR1 in insulin sensitivity.|These data suggest that MARK2 phosphorylates KSR1 on Ser392, which has been shown previously to function as a negative regulatory site xref . | SIGNOR-279343 |
P09917 | P28482 | 0 | phosphorylation | up-regulates activity | 0.381 | Intriguingly, a significant difference in the potency of nonredox-type inhibitors (but not of BWA4C) was determined between wild-type 5-LO and the mutant S271A/S663A-5-LO (lacking phosphorylation sites for ERK1/2 and MAPKAPK-2) in HeLa cells. Collectively, our data suggest that compared with Ca2+-mediated 5-LO product formation, enzyme activation involving 5-LO phosphorylation events specifically and strongly alters the susceptibility of 5-LO toward nonredox-type inhibitors in intact cells. | SIGNOR-264409 |
P15923 | P12830 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.31 | The p21-activated kinase 5 (PAK5) is overexpressed in advanced cancer and the transcription factor E47 is a direct repressor of E-cadherin and inducer of epithelial-mesenchymal transition (EMT). |In this study, we found that PAK5-mediated E47 phosphorylation promoted EMT in advanced colon cancer. PAK5 interacted with E47 and phosphorylated E47 on Ser39 under hepatocyte growth factor (HGF) stimulation | SIGNOR-275654 |
P04637 | Q9NRC8 | 0 | deacetylation | down-regulates | 0.498 | We found that sirt7 interacts with p53 and efficiently deacetylates p53 in vitro, which corresponds to hyperacetylation of p53 in vivo. | SIGNOR-160539 |
Q9Y6X9 | Q13153 | 0 | phosphorylation | up-regulates activity | 0.366 | We demonstrate that PAK1-mediated MORC2 phosphorylation promotes cell cycle progression, defective phosphorylation of MORC2-S677A results in attenuated cell proliferation and tumorigenicity of gastric cancer cells, which is significantly enhanced in overexpression of phospho-mimic MORC2-S677E form, suggesting the importance of MORC2 phosphorylation in tumorigenesis. | SIGNOR-273714 |
P17612 | Q16790 | 1 | phosphorylation | up-regulates | 0.2 | Here, we report that thr443 phosphorylation at the intracellular domain of ca ix by protein kinase a (pka) is critical for its activation in hypoxic cells, with the fullest activity of ca ix also requiring dephosphorylation of ser448. | SIGNOR-176973 |
P78352 | Q9UIJ5 | 0 | palmitoylation | up-regulates activity | 0.379 | Plasma membrane targeting of DHHC2 palmitoyltransferase rapidly recruited PSD-95 to the plasma membrane and proved essential for postsynaptic nanodomain formation. | SIGNOR-261290 |
Q96PV0 | Q9UQM7 | 0 | phosphorylation | up-regulates activity | 0.429 | Here we show that phosphorylation of synGAP by Ca(2+)/calmodulin-dependent protein kinase II increases its Ras GTPase-activating activity by 70-95%. The Major Phosphorylation Sites, Serines 764/765, 1058, and 1123, All Contribute to Regulation of GAP Activity of synGAP by CaMKII | SIGNOR-262687 |
P17612 | Q9Y698 | 1 | phosphorylation | down-regulates activity | 0.432 | phosphorylation of stargazin at T321 by PKA inhibits its interaction with PSD-95. | SIGNOR-250342 |
P27361 | P17676 | 1 | phosphorylation | up-regulates | 0.668 | Thr235 phosphorylation occurs in nuclei of differentiated macrophages, but not in monocytes. | SIGNOR-184917 |
P21860 | Q01973 | 0 | phosphorylation | up-regulates activity | 0.343 | Here we show that NKX2-1 induces the expression of the receptor tyrosine kinase-like orphan receptor 1 (ROR1), which in turn sustains a favorable balance between prosurvival PI3K-AKT and pro-apoptotic p38 signaling, in part through ROR1 kinase-dependent c-Src activation, as well as kinase activity-independent sustainment of the EGFR-ERBB3 association, ERBB3 phosphorylation, and consequential PI3K activation.|ROR1 knockdown decreased phosphorylations of ERBB3, c-Src, and AKT in NKX2-1 + / ROR1 + NCI-H1975, SK-LC-5, and NCI-H358 cells. | SIGNOR-279279 |
Q2TAL8 | P23381 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress. | SIGNOR-269410 |
Q15831 | Q7KZI7 | 1 | phosphorylation | up-regulates activity | 0.588 | 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-276165 |
P06241 | P09619 | 0 | phosphorylation | up-regulates activity | 0.58 | PDGF-induced phosphorylation of Tyr28 in the N-terminus of Fyn affects Fyn activation. We show here that Fyn, a member of the Src family, is phosphorylated on Tyr28 in the unique N-terminal part of the molecule after interaction with the intracellular domain of the PDGF beta-receptor. Activated Fyn furthermore undergoes autophosphorylation on Tyr30, Tyr39 and Tyr420. When Fyn mutants with Tyr28, Tyr30 or Tyr39 replaced with phenylalanine residues were transfected into NIH3T3 cells a decreased activation after PDGF stimulation was seen, suggesting a functional importance of the N-terminal tyrosine phosphorylation of Fyn. | SIGNOR-250253 |
Q9NR30 | Q92793 | 0 | acetylation | down-regulates activity | 0.245 | Significantly, the activity of DDX21 is regulated by acetylation. Acetylation by CBP inhibits DDX21 activity, while deacetylation by SIRT7 augments helicase activity and overcomes R-loop-mediated stalling of RNA polymerases.|acetylation of K18, K137, and K600 impairs the helicase activity of DDX21. | SIGNOR-275904 |
P51452 | Q05397 | 1 | dephosphorylation | down-regulates activity | 0.326 | Deficiency in VHR/DUSP3, a suppressor of focal adhesion kinase, reveals its role in regulating cell adhesion and migration.|In vitro assays proved that recombinant VHR directly dephosphorylated FAK and paxillin. | SIGNOR-277033 |
P50613 | P19447 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.895 | These results led us to propose a model that spironolactone may trigger the phosphorylation of XPB at Ser90 by CDK7, which promotes the recognition and polyubiquitination of XPB by SCFFBXL18 for proteasomal degradation. | SIGNOR-277433 |
P06493 | O14757 | 1 | phosphorylation | up-regulates | 0.411 | Chk1 itself is also subject to cdk-mediated phosphorylation at serines 286 and 301 (s286 and 301). We show that chk1 s301 phosphorylation increases as cells progress through s and g2 and that both cdk1 and cdk2 are likely to contribute to this modification in vivo. We also find that substitution of s286 and s301 with non-phosphorylatable alanine residues strongly attenuates dna damage-induced chk1 activation and g2 checkpoint proficiency | SIGNOR-175071 |
Q96P48 | P63000 | 1 | gtpase-activating protein | down-regulates activity | 0.455 | 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-260451 |
Q13191 | Q6EIG7 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | Furthermore, we found that Cbl-b, an E3 ubiquitin ligase, mediates the ubiquitination and degradation of the activated Dectin-2 and Dectin-3 to negatively regulate CLR mediated innate immune responses against fungal infections. | SIGNOR-278625 |
Q8WXX7 | Q16650 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.359 | Tbr1 implements frontal identity in part by direct promoter binding and activation of Auts2, a frontal cortex gene implicated in autism. | SIGNOR-266836 |
Q9UGI0 | Q15672 | 1 | deubiquitination | down-regulates activity | 0.331 | Trabid inhibits Twist1 activity by cleaving RNF8-mediated Twist1 K63-linked ubiquitination | SIGNOR-273502 |
Q9BXL7 | Q04759 | 0 | phosphorylation | up-regulates activity | 0.775 | NF-kappaB activation is triggered by PKCteta-dependent phosphorylation of Carma1 after TCR/CD28 co-stimulation. PKCteta-phosphorylated Carma1 was suggested to function as a molecular scaffold that recruits preassembled Bcl10-Malt1 complexes to the membrane|we demonstrate that PP2A removes PKCteta-dependent phosphorylation of Ser645 in Carma1, and show that maintenance of this phosphorylation is correlated with increased T-cell activation. | SIGNOR-249193 |
O75581 | P48729 | 0 | phosphorylation | up-regulates | 0.552 | We show that wnt induces sequential phosphorylation of lrp6 by gsk3 and casein kinase 1, and this dual phosphorylation promotes the engagement of lrp6 with the scaffolding protein axin.Site ii, like site i, was phosphorylated, as detected by means of a phospho-specific antibody (ab1493, for phosphorylated t1493 in lrp6) | SIGNOR-143034 |
Q02388 | P13497 | 0 | cleavage | up-regulates quantity | 0.604 | We show that bone morphogenetic protein-1 (BMP-1), which exhibits procollagen C-proteinase activity, cleaves the C-terminal propeptide from human procollagen VII. The cleavage occurs at the BMP-1 consensus cleavage site SYAA/DTAG within the NC-2 domain. Proteinases of the bone morphogenetic protein-1 family convert procollagen VII to mature anchoring fibril collagen. | SIGNOR-256338 |
Q05655 | P30086 | 1 | phosphorylation | up-regulates | 0.301 | Here we show that the raf kinase inhibitor protein (rkip) is a physiological inhibitor of grk-2. After stimulation of gpcr, rkip dissociates from its known target, raf-1 (refs 6-8), to associate with grk-2 and block its activity. This switch is triggered by protein kinase c (pkc)-dependent phosphorylation of the rkip on serine 153. | SIGNOR-119551 |
O60282 | P53779 | 0 | phosphorylation | down-regulates activity | 0.32 | Mass spectrometry identified a residue in the kinesin-1 motor domain that was phosphorylated by JNK3 and this modification reduced kinesin-1 binding to microtubules. JNK3 phosphorylates kinesin-1 at Ser176 | SIGNOR-262950 |
P36888 | P06241 | 0 | phosphorylation | up-regulates activity | 0.292 | FYN phosphorylates FLT3 on tyrosine residues (A\u2013B) COS1 cells were transfected with plasmids expressing FLT3 wild-type and FYN wild-type or mutants.|It was not completely unexpected that FYN associates wild-type FLT3 in the absence of ligand stimulation in COS-1 cells, as overexpression of wild-type FLT3 results in ligand independent activation of FLT3 (data not shown). | SIGNOR-279715 |
Q9UNE7 | P29034 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.318 | S100 protein itself is ubiquitinated by CHIP in a Ca2+-dependent manner.Ubiquitylated S100 proteins are shown as (Ub)n-S100A2 and (Ub)n-S100P. The association of the S100 proteins with CHIP provides a Ca2+-dependent regulatory mechanism for the ubiquitination and degradation of intracellular proteins by the CHIP-proteasome pathway. | SIGNOR-272918 |
Q13555 | O60266 | 1 | phosphorylation | down-regulates activity | 0.353 | Phosphorylation and inhibition of type III adenylyl cyclase by calmodulin-dependent protein kinase II in vivo. | Site-directed mutagenesis of a CaM kinase II consensus site (Ser-1076 to Ala-1076) in III-AC greatly reduced Ca2+-stimulated phosphorylation and inhibition of III-AC in vivo. | SIGNOR-250691 |
O75914 | Q9UM54 | 1 | phosphorylation | up-regulates activity | 0.336 | P21-activated kinase 3 phosphorylated myosin VI, and the site was identified as Thr(406). The phosphorylation of myosin VI significantly facilitated the actin-translocating activity of myosin VI. | SIGNOR-250244 |
O15350 | P05771 | 0 | phosphorylation | up-regulates activity | 0.2 | Here, we report that p73 is able to induce cell cycle arrest independently of its amino-terminal transactivation domain, whereas this domain is crucial for p73 proapoptotic functions. its activity is regulated throughout the cell cycle and modified by protein kinase C-dependent phosphorylation at serine residue 388. | SIGNOR-276234 |
Q92934 | P22694 | 0 | phosphorylation | down-regulates | 0.429 | Ser-155 is the major phosphoacceptor site for pka on bad, but that pka also phosphorylates ser-112 and ser-136. | SIGNOR-81141 |
P84243 | Q7LBC6 | 0 | demethylation | down-regulates activity | 0.2 | We have purified a JmjC domain-containing protein, JHDM2A, which specifically demethylates mono- and dimethyl-H3K9. JHDM2A exhibits hormone-dependent recruitment to androgen-receptor target genes, resulting in H3K9 demethylation and transcriptional activation. Thus, our work identifies a histone demethylase and links its function to hormone-dependent transcriptional activation. | SIGNOR-266636 |
P62380 | O96017 | 0 | phosphorylation | down-regulates activity | 0.291 | In vitro, TRF2 was phosphorylated by recombinant Chk2 ( Figure\u00a04 C) on residues located in the first 350 aa ( Figure\u00a0S11 ).|To evaluate whether Chk2 activity affected the binding of TRF2 for telomeric TTAGGG repeats in duplex DNA, electrophoretic mobility shift assays (EMSA) were performed in the presence of ATP to allow phosphorylation and found that in contrast to Chk2 KD, Chk2 WT decreased the binding of TRF2 to DNA. | SIGNOR-280227 |
P18850 | P17861-2 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.654 | Apart from ER protein chaperones, ATF6 also induces the expression of CHOP and XBP1, thereby connecting the three UPR branches into an integrated signaling network | SIGNOR-260184 |
Q9NRP7 | P29372 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | Here, we show that MID1 catalyzes the ubiquitination and proteasomal cleavage of the GLI3 regulator Fu. | SIGNOR-272466 |
Q93008 | P42566 | 1 | deubiquitination | down-regulates activity | 0.271 | We identify the endocytic protein Eps15 as one of the critical substrates of USP9X | SIGNOR-245052 |
Q06830 | P11802 | 0 | phosphorylation | down-regulates | 0.226 | Peroxiredoxin (prx) i is a member of the peroxiredoxin family of peroxidases and contains a consensus site (thr(90)-pro-lys-lys) for phosphorylation by cyclin-dependent kinases (cdks). This protein has now been shown to be phosphorylated specifically on thr(90) by several cdks, including cdc2, in vitro. Phosphorylation of prx i on thr(90) reduced the peroxidase activity of this protein by 80%.Prx i was also phosphorylated, with an efficiency similar to that observed with cdc2, when incubated in vitro with cdk2, cdk4, or cdk6 that had been immunoprecipitated from hela cell lysates with specific antibodies (data not shown). | SIGNOR-87105 |
P49841 | P22415 | 1 | phosphorylation | up-regulates activity | 0.286 | Both MITF and USF1 were activated by glycogen synthase kinase (GSK) 3, with GSK3 phosphorylation sites on USF1 identified as the previously described activating site threonine 153 as well as serine 186. | SIGNOR-276355 |
Q9GZV5 | Q4VCS5 | 0 | relocalization | down-regulates | 0.678 | Yap/taz and angiomotin (amot) family proteins were shown to interact, resulting in yap/taz localization to tight junctions and inhibition through phosphorylation-dependent and -independent mechanisms. | SIGNOR-201132 |
Q92949 | Q9UI46 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.368 | FOXJ1 expression in basal cells induced the expression of a panel of cilia-associated genes, including centrin 2 (CETN2); dynein, axonemal, heavy chain 11 (DNAH11); dynein, axonemal, intermediate chain 1 (DNAI1); dynein, axonemal, light intermediate chain 1 (DNALI1); EF-hand domain, C-terminal, containing 1 (EFHC1); sperm associated antigen 6 (SPAG6); tektin 1 (TEKT1), TEKT2 and tubulin, alpha 1a (TUBA1A; Figure 3C and Additional file 2: Table S1). | SIGNOR-266932 |
Q96C90 | Q13418 | 0 | phosphorylation | up-regulates activity | 0.398 | We conclude that ILK may activate smooth-muscle contraction both directly, via phosphorylation of myosin, and indirectly, via phosphorylation and activation of CPI-17 and PHI-1, leading to inhibition of MLCP.|CPI-17 and PHI-1 thiophosphorylated by ILK at Thr(38) or Thr(57) respectively inhibited myosin light-chain phosphatase (MLCP) activity bound to myosin | SIGNOR-265741 |
O60716 | Q9HCE7 | 0 | monoubiquitination | down-regulates activity | 0.2 | Upon TGFβ treatment, activated extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylates T900 of p120-catenin to promote its interaction with Smurf1 and subsequent monoubiquitination. TGFβ promotes monoubiquitination of p120-catenin through Smurf1 to induce junction dissociation. | SIGNOR-277507 |
P42226 | P45983 | 0 | phosphorylation | down-regulates | 0.353 | Deactivation of stat6 through serine 707 phosphorylation by jnk. | SIGNOR-170153 |
P55957 | P45984 | 0 | phosphorylation | up-regulates activity | 0.406 | (c) The phosphorylation of recombinant Bid by JNK2 (in vitro kinase assay) prevents its cleavage by caspase-8 | SIGNOR-279220 |
O14746 | P31749 | 0 | phosphorylation | up-regulates | 0.732 | Akt kinase enhances human telomerase activity through phosphorylation of htert subunit as one of its substrate proteins. | SIGNOR-67313 |
P56817 | Q9UNE7 | 0 | ubiquitination | down-regulates quantity | 0.378 | This result establishes that CHIP negatively regulates BACE1 stability.|Thus, both deletion mutants of CHIP could not enhance the ubiquitination of BACE1, suggesting that both domains of CHIP were essential for ubiquitination and degradation of BACE1. | SIGNOR-278719 |
Q13049 | P01106 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.456 | TRIM32 ubiquitinates and degrades the transcription factor c-Myc but also binds Argonaute-1 and thereby increases the activity of specific microRNAs. | SIGNOR-278676 |
O14980 | P04637 | 1 | relocalization | down-regulates activity | 0.549 | We identify the major poly(ADP-ribosyl)ated sites of p53 by PARP-1 and find that PARP-1-mediated poly(ADP-ribosyl)ation blocks the interaction between p53 and the nuclear export receptor Crm1, resulting in nuclear accumulation of p53. These findings molecularly link PARP-1 and p53 in the DNA-damage response, providing the mechanism for how p53 accumulates in the nucleus in response to DNA damage.|PARP-1 is super-activated by binding to damaged DNA, and poly(ADP-ribosyl)ates p53. Poly(ADP-ribosyl)ation probably induces a structural change that mask the NES, and thus Crm1 can no longer target p53 to the nuclear export machinery, resulting in accumulation of p53 in the nucleus. | SIGNOR-260067 |
Q9UJU2 | P48730 | 0 | phosphorylation | down-regulates | 0.25 | Cki_/_ binds and phosphorylates lef-1, and this phosphorylation disrupts lef-1_-catenin interaction | SIGNOR-134494 |
P51812 | P18846 | 1 | phosphorylation | up-regulates activity | 0.318 | ATF1 and CREB can be phosphorylated by Rsk2 which is a protein kinase directly activated by Erk MAP kinase. These results suggest a signaling pathway in which Erk MAP kinase activates the c-fos enhancer by direct phosphorylation of p62TCF and by activation of Rsk related kinases that phosphorylate ATF1 and CREB.|ATF1 and CREB can be phosphorylated by Rsk2 which is a protein kinase directly activated by Erk MAP kinases. | SIGNOR-280117 |
P14778 | P45984 | 1 | phosphorylation | up-regulates activity | 0.281 | Il-1 binding to its receptor triggers a cascade of signaling events, including activation of the stress-activated mitogen-activated protein (map) kinases, c-jun nh2-terminal kinase (jnk) and p38 map kinase, as well as transcription factor nuclear factor kappab (nf-kappab | SIGNOR-249514 |
Q5SQI0 | Q6PEY2 | 1 | acetylation | up-regulates quantity by stabilization | 0.267 | 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-272248 |
P03372 | Q99728 | 0 | ubiquitination | down-regulates quantity | 0.427 | As shown in xref , both FOXK2 and BARD1 enhanced the ubiquitination of ER\u03b1, with the extent of ubiquitination being enhanced when both FOXK2 and BARD1 were overexpressed.|These findings suggested that FOXK2 might act as a negative regulator of Estrogen receptor\u03b1, and its association with both Estrogen receptor\u03b1 and BRCA1/BARD1 could lead to the down-regulation of Estrogen receptor\u03b1 transcriptional activity, effectively regulating the function of Estrogen receptor\u03b1. | SIGNOR-278803 |
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