IdA string | IdB string | labels int64 | mechanism string | effect string | score float64 | sentence string | signor_id string |
|---|---|---|---|---|---|---|---|
P84022 | P36896 | 0 | phosphorylation | up-regulates activity | 0.741 | ActRIIB, and then partners with a type I receptor, either activin receptor-like kinase 4 (ALK4 or ActRIB) or ALK5 (T²RI), to induce phosphorylation of Smad2/Smad3 and activate a TGF-²-like signaling pathway | SIGNOR-235160 |
O00571 | P35637 | 0 | relocalization | down-regulates activity | 0.256 | We found that ALS mutants of FUS co-localized with Caprin-1, DDX3X, and DHX9 in cytoplasmic inclusions that could lead to the mis-regulation of their respective pathways, providing further clues to the mechanism of ALS pathogenesis.|FUS interacting proteins were sequestered into the cytoplasmic mutant FUS inclusions that could lead to their mis-regulation or loss of function, contributing to ALS pathogenesis. | We also demonstrated the co-localization of DHX9, DDX3X and Caprin-1 with cytoplasmic EGFP-P525L mutant FUS inclusions in primary cortical neurons | SIGNOR-262811 |
Q8IVH8 | P19484 | 1 | phosphorylation | down-regulates activity | 0.25 | However, although our results indicate that MAP4K3 initiates TFEB repression, MAP4K3 also promotes robust mTORC1 activation upon amino acid stimulation - ; hence, MAP4K3 and mTORC1 must ultimately work together to achieve robust suppression of autophagy.|Moreover, MAP4K3 serine 3 phosphorylation of TFEB is required for TFEB interaction with mTORC1-Rag GTPase-Ragulator complex and TFEB cytosolic sequestration. | SIGNOR-278282 |
O95600 | P57682 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.255 | Here we report that Klf8 is repressed by Klf3 in vivo and is up-regulated by Klf1. Transcript analysis indicates that Klf8 has two promoters, both containing multiple CACCC elements. Transactivation assays and chromatin immunoprecipitation experiments indicate that Klf3 represses Klf8 directly and that Klf1 activates Klf8 directly. | SIGNOR-266049 |
P18887 | O96017 | 0 | phosphorylation | up-regulates | 0.515 | Chk2 formed a complex with xrcc1, the ber scaffold protein, and phosphorylated xrcc1 in vivo and in vitro at thr(284). our results are consistent with the phosphorylation of xrcc1 by atm-chk2 facilitating recruitment of downstream ber proteins to the initial damage recognition/excision step to promote ber. | SIGNOR-181816 |
Q6ZWJ1 | P31751 | 0 | phosphorylation | down-regulates activity | 0.42 | Akt2 phosphorylates Synip to regulate docking and fusion of GLUT4-containing vesicles. These data demonstrate that insulin activation of Akt2 specifically regulates the docking/fusion step of GLUT4-containing vesicles at the plasma membrane through the regulation of Synip phosphorylation and Synip-Syntaxin4 interaction.Thus, our data demonstrate that insulin-stimulated Akt2-dependent phosphorylation of Synip on serine residue 99 results in reduced binding interactions between Synip and Syntaxin4. | SIGNOR-262635 |
Q9BYP7 | P55017 | 1 | phosphorylation | up-regulates activity | 0.455 | We have shown that with-no-lysine kinase 3 (WNK3) possesses several properties that suggest it could be the Cl−/volume-sensitive regulatory kinase that, in association with protein phosphatases, reciprocally modifies the phosphorylation/dephosphorylation states of the SLC12 proteins and thus their activities|WNK3 activates NKCC1/2 and NCC and inhibits the KCCs | SIGNOR-264624 |
Q96RU2 | Q13535 | 0 | phosphorylation | up-regulates activity | 0.2 | Here we report that the deubiquitylase USP28 is recruited to sites of DNA damage in cisplatin-treated cells. ATR phosphorylates USP28 and increases its enzymatic activity.|Representative immunoblots of n = 3. C Immunoblotting of total and phosphorylated USP28 at serine 67 and 714 in A431 cells exposed to indicated concentrations of CPPD for 6 h. | SIGNOR-275850 |
P30307 | P45983 | 0 | phosphorylation | down-regulates | 0.411 | Here we show that jnk directly phosphorylates cdc25c at serine 168 during g(2) phase of the cell cycle. Cdc25c phosphorylation by jnk negatively regulates its phosphatase activity and thereby cdk1 activation, enabling a timely control of mitosis onset. | SIGNOR-164089 |
Q9Y5B0 | Q96GX5 | 1 | dephosphorylation | down-regulates activity | 0.433 | Taken together, these data suggest that Fcp1 bound and dephosphorylated Gwl at S90 and S453, and possibly at other Cdk1 dependent sites, during mitosis exit and that Fcp1 catalyzed dephosphorylation lowered Gwl activity towards Ensa and ARPP19, allowing PP2A-B55 to autoactivate.|Together, these data indicate that Fcp1 dependent dephosphorylation greatly reduces S67-Ensa kinase activity of Gwl and that, downstream inactivation of Cdk1, Fcp1 deficit substantially blunts inactivation of Gwl. | SIGNOR-276971 |
O96013 | Q92974 | 1 | phosphorylation | down-regulates activity | 0.518 | PAK4 specifically phosphorylates GefH1, and this is thought to inhibit its ability to activate Rho, consequently inhibiting stress fiber formation. | SIGNOR-279245 |
P31749 | Q16584 | 1 | phosphorylation | down-regulates | 0.4 | Negative regulation of mixed lineage kinase 3 by protein kinase b/akt leads to cell survivalthe expression of activated akt1 inhibits mlk3-mediated cell death in a manner dependent on serine 674 phosphorylation. | SIGNOR-252592 |
Q969R2 | P49840 | 0 | phosphorylation | up-regulates activity | 0.2 | CK1a1, JNK1 and CDK1 had the highest site-specific activity for ORP4L, while CDK1, GSK3a, CK1a1 and GSK3b showed the highest specificity for the site when corrected for background activity with ORP4L-S4A. Because of the complexity of the serine/proline-rich site, we did not determine which serine(s) in ORP4L were phosphorylated by candidate kinases.|We conclude that phosphorylation of a unique serine/proline motif in the ORD induces a conformation change in ORP4L that enhances interaction with vimentin and cholesterol extraction from membranes. | SIGNOR-264875 |
Q05655 | Q9UQ80 | 1 | phosphorylation | up-regulates | 0.509 | Trk receptor activation by both ngf and bdnf induced phosphorylation of ebp1 at the s360 upon the activation of protein kinase c (pkc ) and triggered dissociation of p48 from retinoblastoma (rb | SIGNOR-170348 |
O14757 | Q9HB96 | 1 | phosphorylation | up-regulates | 0.716 | Chk1 directly phosphorylates the fance subunit of the fa core complex on two conserved sites (threonine 346 and serine 374). chk1-mediated phosphorylation of fance is required for the fanconi anemia/brca pathway. | SIGNOR-153023 |
P16066 | P02763 | 1 | phosphorylation | up-regulates activity | 0.2 | On TORC1 inhibition by rapamycin treatment or nutrient limitation, Npr1 phosphorylates and activates Orm1 and Orm2, which in turn promotes synthesis of complex sphingolipids downstream of SPT.|Thus Npr1 directly phosphorylates Orm1 and Orm2 downstream of TORC1. | SIGNOR-278966 |
P28482 | Q17RY0 | 1 | phosphorylation | up-regulates activity | 0.325 | Our results indicate that CPEB4 activation is driven by ERK2- and Cdk1 mediated hyperphosphorylation of at least 12 residues in the intrinsically disordered NTD.|We concluded that, in interphase, unphosphorylated CPEB4 phase separates into liquid like droplets that recruit mRNAs but are inactive for cytoplasmic polyadenylation and translation, whereas in M-phase, CPEB4 is phosphorylated by ERK2 and Cdk1 and recovers its monomeric form, which can drive the cytoplasmic polyadenylation of target mRNAs. | SIGNOR-280021 |
Q15796 | P36897 | 0 | phosphorylation | up-regulates activity | 0.825 | Recently, it was demonstrated that Smad2 interacts transiently with and is a direct substrate of the transforming growth factor-beta (TGF-beta) type I receptor, TbetaRI. Phosphorylation sites on Smad2 were localized to a carboxyl-terminal fragment containing three serine residues at positions 464, 465, and 467. These results indicate that receptor-dependent phosphorylation of Smad2 on serines 465 and 467 is required in mammalian cells to permit association with Smad4 and to propagate TGF-_ signals. | SIGNOR-235995 |
Q05655 | Q16820 | 1 | phosphorylation | down-regulates quantity | 0.307 | These findings suggest that activation of a protein kinase, presumably PKC, mediates PMA-induced hmeprinβ shedding. By labeling COS-1 cells transfected with mutant constructs lacking the potential phosphorylation sites, we identified Ser687 as the main 32P-acceptor. These data provide evidence that the cytoplasmic domain of hmeprinβ can function as a PKC substrate. | SIGNOR-263171 |
Q14863 | O14965 | 0 | phosphorylation | down-regulates activity | 0.2 | Here, we report that Aurora kinase A phosphorylates mPOU at Ser197 and inhibit its DNA-binding ability. | SIGNOR-273546 |
P48058 | Q9UQM7 | 0 | phosphorylation | up-regulates | 0.592 | Receptor internalization, altered;intracellular localization | SIGNOR-97546 |
Q8N4C8 | Q96P20 | 1 | phosphorylation | up-regulates activity | 0.2 | MINK1-mediated NLRP3 phosphorylation at Ser725 is critical for inflammasome activation.|These results suggest that MINK1 promotes NLRP3 inflammasome activation via direct interaction with NLRP3.|To determine whether MINK1 phosphorylated NLRP3 directly, we used Phos-tag SDS\u2013PAGE to detect the phosphorylation of NLRP3. | SIGNOR-280042 |
P38435 | P02818 | 1 | carboxylation | up-regulates activity | 0.687 | Thus, vitamin K acts as a cofactor for GGCX via the vitamin K cycle and exerts physiological effects through its regulation of VKDPs [29]. More than 20 VKDPs have been found. Osteocalcin promotes bone formation, and blood coagulation factors II, VII, IX, and X activate blood coagulation. Matrix Gla protein suppresses cardiovascular calcification, and brain-expressed Gas 6 promotes neural differentiation [29]. GGCX is an enzyme that converts glutamic acid (Glu) residues to Gla residues, so that the Gla-containing proteins can exert various physiological actions such as blood coagulation and bone formation. | SIGNOR-265922 |
Q06124 | P10721 | 0 | phosphorylation | up-regulates activity | 0.684 | SHP2 can be phosphorylated at 2 C-terminal tyrosyl residues by receptor tyrosine kinases, including KIT as well as cytosolic tyrosine kinases, including Src and Abl. The level of tyrosyl phosphorylation of SHP2 has been associated with its recruitment to the receptor.Thus, pharmacologic inhibition of SHP2 phosphatase function might permit SHP2 to return to its inactive conformation resulting in reduced tyrosine phosphorylation. | SIGNOR-256140 |
Q9HCU9 | P68400 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.473 | We show that BRMS1 is posttranslationally regulated by TNF-induced casein kinase 2 catalytic subunit (CK2α') phosphorylation of nuclear BRMS1 on serine 30 (S30), resulting in 14-3-3ε-mediated nuclear exportation, increased BRMS1 cytosolic expression, and ubiquitin-proteasome-induced BRMS1 degradation. | SIGNOR-266407 |
P49593 | Q13153 | 1 | dephosphorylation | down-regulates activity | 0.39 | The p21-activated kinase PAK is negatively regulated by POPX1 and POPX2, a pair of serine/threonine phosphatases of the PP2C family|POPX Can Dephosphorylate and Downregulate PAK| To confirm that POPX2 acts on αPAK phospho-Thr422, a key regulator of activity in the kinase activation loop [9], we used phospho-specific antibodies against αPAK P-Thr422 (Figure 3B, lower panel), which proved to be an excellent substrate for POPX2. Similarly, complete loss of αPAK P-Ser57 with 0.2 μg POPX2 contrasts with the slight loss observed with 1.5 μg PP1. On the basis of these results, we suggest PAK is a substrate of POPX. | SIGNOR-248530 |
P10163 | Q96L73 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.342 | We here demonstrate that NSD1 could bind to the promoter regions of PRB4 and activate promoter activity by reducing the binding of H3K27me2 and increasing the binding of H3K36me2 on PRB4 promoter. | SIGNOR-268459 |
Q9Y6Q9 | P35790 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.2 | First, by using purified recombinant SRC-3 (XREF_FIG) and CKI proteins, we found that CKI is able to phosphorylate SRC-3 (XREF_FIG). | SIGNOR-280229 |
P31948 | P06493 | 0 | phosphorylation | down-regulates activity | 0.264 | Inactivation and phosphorylation mimicking of potential phosphorylation sites in mSTI1 altered the nuclear translocation. Mimicking of phosphorylation at the mSTI1 CKII phosphorylation site (S189E) promoted nuclear localization of mSTI1-EGFP. Mimicking phosphorylation at the cdc2 kinase phosphorylation site (T198E) promoted cytoplasmic localization of mSTI1-EGFP at the G1/S-phase transition,whereas removal of this site (T198A) promoted the nuclear localization of mSTI1-EGFP under the same conditions. | SIGNOR-262729 |
P10070 | P48729 | 0 | phosphorylation | down-regulates | 0.568 | Gli2 can also be phosphorylated directly by ck-1 at the non-optimal sites | SIGNOR-146112 |
P12931 | Q8IW41 | 1 | phosphorylation | up-regulates quantity | 0.372 | These data strongly suggest that PRAK phosphorylation by Src on Y188 and Y216 drives the relocalization of PRAK to focal adhesion structures during cell adhesion. | SIGNOR-279762 |
P48730 | Q9GZV5 | 1 | phosphorylation | down-regulates | 0.366 | LATS1/2-mediated phosphorylation of a conserved serine in this region (Ser311 in human TAZ; Ser397 in human YAP) primes for further phosphorylation by CK1_/_ kinases (Ser314 on human TAZ; Ser400/403 in human YAP) | SIGNOR-234438 |
O15297 | O15151 | 1 | dephosphorylation | up-regulates quantity by stabilization | 0.431 | PPM1D also inhibits p53 activity by dephosphorylating Ser395 and stabilizing MDM2 and by dephosphorylating Ser403 on MDMX | SIGNOR-275491 |
P51813 | P23470 | 0 | dephosphorylation | down-regulates activity | 0.26 | 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-254693 |
P05106 | Q15118 | 0 | phosphorylation | down-regulates activity | 0.306 | PDK1 specifically phosphorylates Thr-753 in 3. Our data argue that phosphorylation of Thr-753, which is conserved in many subunits, reduces the ability of PTB-containing proteins to bind the NXX(pY) motif in 3. | SIGNOR-250264 |
P10636 | Q13627 | 0 | phosphorylation | down-regulates | 0.427 | Dyrk1a phosphorylates tau at least at s202, t212 and s404, but t212 phosphorylation is known to initiate tau hyperphosphorylation by gsk3b (ryoo et al., 2007;woods et al., 2001) and has been demonstrated to have a role in alternative splicing of taumrna | SIGNOR-171030 |
Q13976 | P04792 | 1 | phosphorylation | down-regulates | 0.274 | Purified pkg isoforms ia, ib, and ii all caused incorporation of phosphate in recombinant hsp27 at ser-78, ser-82, and thr-143, but not ser-15.These Studies indicate that hsp27 is a genuine substrate for pkg and that pkg may mediate inhibition of platelet aggregation through phosphorylation of hsp27 and subsequent prevent of actin polymerization | SIGNOR-186784 |
Q6P1N0 | P08908 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.371 | Akt kinase-interacting protein 1 (Aki1)/Freud-1/CC2D1A is localized in the cytosol, nucleus, and centrosome. Aki1 plays distinct roles depending on its localization. In the cytosol, it acts as a scaffold protein in the phosphoinositide 3-kinase (PI3K)/3-phosphoinositide-dependent protein kinase 1 (PDK1)/Akt pathway. In the nucleus, it is a transcriptional repressor of the serotonin-1A (5-HT1A) receptor. | SIGNOR-268295 |
P68400 | P18848 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | By using mutants of ATF4 we identified serine 215 as the main CK2 phosphorylation site. The ATF4 S215A mutant turned out to be more stable than the wild-type form. | SIGNOR-276425 |
P28482 | P55211 | 1 | phosphorylation | down-regulates activity | 0.533 | ERK/MAPK phosphorylates caspase-9 at Thr(125), and this phosphorylation is crucial for caspase-9 inhibition | SIGNOR-148616 |
Q92831 | P78527 | 0 | phosphorylation | up-regulates activity | 0.417 | In response to UV-induced DNA damage, DNA-PK phosphorylates and activates PCAF, and activated PCAF is transferred to photo lesion sites and further acetylates RPA1 at K163. | SIGNOR-280092 |
Q15139 | P35670 | 1 | phosphorylation | up-regulates activity | 0.296 | ATP7B trafficking was markedly reduced by the Ser-478/481/1121/1453 to Ala mutation. We conclude that PKD plays a key role in copper-dependent serine phosphorylation, permitting high levels of ATP7B protein expression and trafficking. | SIGNOR-272295 |
Q9UPW0 | Q06413 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.317 | Foxj3 transcriptionally activates Mef2c and regulates adult skeletal muscle fiber type identity. | SIGNOR-261606 |
Q13131 | Q05469 | 1 | phosphorylation | down-regulates | 0.41 | Phosphorylation of bovine hormone-sensitive lipase by the amp-activated protein kinase. | SIGNOR-58255 |
P24752 | P00533 | 0 | phosphorylation | up-regulates activity | 0.2 | We found that purified EGFR and FGFR1 directly phosphorylate and activate ACAT1 ( xref ).|We found that purified EGFR and FGFR1 directly phosphorylate and activate ACAT1 (XREF_FIG). | SIGNOR-279996 |
Q15311 | P63000 | 1 | gtpase-activating protein | down-regulates activity | 0.582 | 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-260513 |
P31749 | Q9BVI0 | 1 | phosphorylation | down-regulates | 0.552 | Akt phosphorylates phf20 at ser(291) in vitro and in vivo, which results in its translocation from the nucleus to the cytoplasm and attenuation of phf20 function. | SIGNOR-252529 |
P06239 | P29353 | 1 | phosphorylation | up-regulates activity | 0.744 | We show that during TCR signaling, the tyrosines Y239, Y240 and Y317 of Shc are the primary sites of tyrosine phosphorylation. CD4/Lck-dependent tyrosine phosphorylation on Shc was markedly diminished when Y317 was mutated, suggesting a preference of Lck for the Y317 site. tyrosine phosphorylation of Shc may play a key role in T lymphocyte proliferation via interaction of phosphorylated Shc with downstream molecules involved in activation of Ras and Myc proteins | SIGNOR-251388 |
P62820 | Q08379 | 1 | relocalization | up-regulates activity | 0.718 | Here, we demonstrate that the cis ‐Golgi tethering protein GM130, complexed with GRASP65 and other proteins, forms a novel Rab1 effector complex that interacts with activated Rab1‐GTP in a p115‐independent manner and is required for coat protein II vesicle targeting/fusion with the cis ‐Golgi | SIGNOR-261285 |
Q9C0H2 | Q96PU5 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | Our data indicate that Nedd4-2 binds to two family members, TTYH2 and TTYH3, which contain consensus PY ((L/P)PXY) binding sites for HECT type E3 ubiquitin ligases, but not to TTYH1, which lacks this motif. Consistently, Nedd4-2 ubiquitinates both TTYH2 and TTYH3. Importantly, we have shown that endogenous TTYH2 and Nedd4-2 are binding partners and demonstrated that the TTYH2 PY motif is essential for these interactions. We have also shown that Nedd4-2-mediated ubiquitination of TTYH2 is a critical regulator of cell surface and total cellular levels of this protein. | SIGNOR-272633 |
Q14493 | P58876 | 1 | translation regulation | up-regulates quantity by expression | 0.2 | Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control. | SIGNOR-265378 |
P19793 | P45984 | 0 | phosphorylation | down-regulates activity | 0.246 | Under stress conditions, hyperphosphorylated by activated jnk on ser-56, ser-70, thr-82 and ser-260. These findings indicate that inflammation-mediated cell signaling leads to rapid and profound reductions in nuclear rxralpha levels, via a multistep, jnk-dependent mechanism involving ser260, nuclear export, and proteasomal degradation. | SIGNOR-145301 |
C9JLW8 | P27361 | 0 | phosphorylation | down-regulates activity | 0.2 | When phosphorylated by ERK, MCRIP1 dissociates from CtBP, allowing CtBP to interact with ZEB1. In this manner, the CtBP co-repressor complex is recruited to, and silences, the E-cadherin promoter by inducing chromatin modifications.| While substitution of S4 or S18 with Ala did not affect the phosphorylation of MCRIP1 by ERK, substitution of either S21 or T30 significantly reduced MCRIP1 phosphorylation | SIGNOR-264772 |
Q96GD4 | Q92974 | 1 | phosphorylation | down-regulates activity | 0.25 | The mitotic kinases Aurora A/B and Cdk1/Cyclin B phosphorylate GEF-H1, thereby inhibiting GEF-H1 catalytic activity. | SIGNOR-276062 |
P06241 | Q16539 | 1 | phosphorylation | up-regulates | 0.489 | T cell src family kinases and zap70 activate p38 by phosphorylating tyr323. | SIGNOR-134293 |
P06493 | Q9NZH5 | 1 | phosphorylation | up-regulates activity | 0.291 | HPTTG is phosphorylated by Cdc2 at Ser165. we show that hPTTG is phosphorylated during mitosis. The direct phosphorylation of hPTTG by Cdc2 is interesting in itself since the substrates of this master mitotic kinase are supposed to play important roles in the initiation and progression of mitosis. | SIGNOR-262700 |
Q9Y4H2 | P06213 | 0 | phosphorylation | down-regulates activity | 0.757 | Tyr624 and Tyr628 are involved in the interaction between the IR and the KRLB domain of IRS-2, including tyrosine phosphorylation, and Tyr628 seems to be more important than Tyr624 in this process. the binding between the insulin receptor and the KRLB domain of IRS-2 results in tyrosine phosphorylation of the KRLB domain, and this leads to decreased binding of IRS-2 to the insulin receptor. | SIGNOR-251319 |
Q9H0D6 | P50613 | 0 | phosphorylation | up-regulates activity | 0.247 | CDKs and Xrn2 phosphorylation promote transcription termination. | Cdk7 phosphorylated Xrn2-Thr439 but was less efficient than Cdk9. | | SIGNOR-259851 |
Q86UR1 | P17612 | 0 | phosphorylation | down-regulates | 0.324 | We identified ser-282 as target of mapk and ser-172 as target of pkc and pka in vitro and in a transfected human embryonic kidney 293 (hek293) cell model using site directed mutagenesis and phosphopeptide mapping analysis. In hek293 cells, phosphorylation of these sites occurred at a basal level and down-regulated constitutive nox1 activity. I | SIGNOR-163663 |
Q2T9J0 | Q15067 | 1 | cleavage | up-regulates activity | 0.694 | Here, we demonstrate that Tysnd1, a previously uncharacterized protein, is responsible both for the removal of the leader peptide from PTS2 proteins and for the specific processing of PTS1 proteins. All of the identified Tysnd1 substrates catalyze peroxisomal β-oxidation. In vitro cleavage of Acox1, Scp2 and prethiolase by recombinant Tysnd1. | SIGNOR-261057 |
P25098 | P15311 | 1 | phosphorylation | up-regulates | 0.2 | Grk2 phosphorylates glutathione s-transferase (gst)-ezrin, but not an ezrin fusion protein lacking threonine 567 (t567), in vitro. These results suggest that t567, the regulatory phosphorylation site responsible for maintaining ezrin in its active conformation, represents the principle site of grk2-mediated phosphorylation. | SIGNOR-135622 |
Q9P209 | Q96SN8 | 1 | relocalization | up-regulates activity | 0.663 | By bringing CDK5RAP2 to the centrosome, the centriolar satellite proteins CEP72 and SPAG5 are required for the centrosomal localization of the other three MCPH proteins despite not interacting with them biochemically. | SIGNOR-271720 |
Q9H0M0 | O15350 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.283 | WWP1 in complex with WWP2 specifically regulates ΔNp73. In our study, we identified WWP2, an E3 ligase, as a novel p73-associated protein that ubiquitinates and degrades p73. In contrast, WWP2 heterodimerizes with another E3 ligase, WWP1, which specifically ubiquitinates and degrades ΔNp73. | SIGNOR-272232 |
P61586 | P26038 | 1 | phosphorylation | up-regulates activity | 0.61 | Rev-erbα interacted with OPHN-1, promoted RhoA activity and phosphorylation of ERM. etection of phosphorylated ezrin (Thr567)/radixin (Thr564)/moesin (Thr558)(p-ERM) in Rev-erbαfl/flCre− and Rev-erbαfl/flPF4Cre+ platelets using phospho-specific antibodies. | SIGNOR-268431 |
Q9HC78 | P02771 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.44 | Zinc finger and BTB domain-containing 20 (ZBTB20), a member of BTB/POZ family, functions in neurogenesis and represses α-fetoprotein gene transcription in liver. | SIGNOR-266867 |
P52564 | P46108 | 1 | phosphorylation | up-regulates | 0.2 | Mapkk6 was shown to phosphorylate and specifically activate the p38/mpk2 sub-family of the mitogen-activated protein kinase superfamily. | SIGNOR-42384 |
P04637 | O96017 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.791 | Chk1/chk2 and atm/atr also phosphorylate the effector p53, increasing its stability.We Have demonstrated that the human homologs of the checkpoint kinases, chk1 and chk2/hcds1, phosphorylate at least three dna damage-inducible phosphorylation sites in p53. | SIGNOR-74831 |
P49593 | Q16566 | 1 | dephosphorylation | down-regulates activity | 0.348 | Calmodulin-dependent protein kinase phosphatase (CaMKP) dephosphorylates and concomitantly deactivates multifunctional Ca(2+)/calmodulin-dependent protein kinases , such as CaMKI, CaMKII, and CaMKIV. | SIGNOR-277157 |
P78368 | Q13330 | 1 | phosphorylation | up-regulates activity | 0.344 | CKI-gamma2 could further potentiate the ER corepressive function of metastasis-associated protein-1 short form.|These findings identified metastasis-associated protein-1 short form as a target of CKI-gamma2, and provided new evidence to suggest that CKI-gamma2 phosphorylates and modulates the functions of metastasis-associated protein-1 short form, and that these extranuclear effects of estrogen might have important implications in regulating the functions of metastasis-associated protein-1 short form in human mammary epithelial and cancer cells. | SIGNOR-280236 |
P62736 | P17481 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.2 | Results from these experiments demonstrated that in 10T1/2 cells Hoxa10-1 increased the activity of the telokin promoter 3-fold without affecting the activity of the other promoters analyzed (Fig. 2A). Similar results were also observed in A10 SMC (data not shown). In contrast, Hoxb8 significantly repressed the activity of the telokin, smooth muscle α-actin, and SM22α promoters by 70, 50, and 70%, respectively | SIGNOR-261641 |
Q99683 | P30307 | 0 | dephosphorylation | down-regulates activity | 0.288 | At the interval CDC25C inhibits ASK1, dephosphorylating pThr838 in its activation loop.|CDC25C dephosphorylates ASK1 to inhibit its activity during the interphase. | SIGNOR-277100 |
Q16236 | P05771 | 0 | phosphorylation | up-regulates | 0.418 | Phosphorylation of nrf2 at ser-40 by protein kinase c regulates antioxidant response element-mediated transcription / recently we reported evidence for the involvement of protein kinase c (pkc) in phosphorylating nrf2 and triggering its nuclear translocation in response to oxidative stress | SIGNOR-91830 |
P41091 | Q14232 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.694 | EIF2B converts the protein synthesis initiation factor 2 (eIF2) from an inactive GDP-bound form to an active eIF2-GTP complex owing to its guanine nucleotide exchange factor (GEF) activity. | SIGNOR-269134 |
P78352 | P06241 | 0 | phosphorylation | up-regulates | 0.562 | Psd-95 is phosphorylated either by purified src/fyn kinases in vitro or by co-expression of constitutively active src/fyn in cos7 cells. psd-95 tyr(523) phosphorylation contributes to the post-ischaemic over-activation of nmda receptors. | SIGNOR-180449 |
Q15139 | Q9GZY8 | 1 | phosphorylation | up-regulates activity | 0.2 | PKD directly phosphorylates MFF on serines 155, 172, and 275 | SIGNOR-277559 |
P01178 | P16519 | 0 | cleavage | down-regulates quantity | 0.265 | Oxytocin-extended form is further cleaved by enzymatic activity to yield the nine-amino-acid active peptide, OT. The proteolysis may involve several pro-hormone convertases, convertase 2 (PC2) (20p11-1-11.2) and convertase 5 (PC5) (9q21.3) (Gabreels et al 1998). Both enzymes are found in OT neurosecretory vesicles and are a part of a family of subtilisen/kexinlike convertases (Seidah et al 1994). It is a product of the OT gene located at human gene locus 20p13 (Rao et al 1992). The processing cascade results in the production of neurophysin I and OT extended form (OT-X), which is OT with a C-terminal, three-amino-acid extension. | SIGNOR-270328 |
P49841 | P60484 | 1 | phosphorylation | down-regulates activity | 0.424 | Gsk3beta Phosphorylates pten at thr-366 in intact cells phosphorylation of pten at thr-366 reduces the activity of pten in cells | SIGNOR-236641 |
Q9NRM7 | P60891 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Recruitment of TRAF2 to PRPS1/2 requires phosphorylation of PRPS1 S285 or PRPS2 T285, which is mediated by low stiffness-activated large tumor suppressor (LATS)1/2 kinases.LATS1/2-dependent S/T285 phosphorylation is required for PRPS1/2 ubiquitination and degradation at low stiffness. | SIGNOR-276504 |
P24941 | Q8WXE1 | 1 | phosphorylation | up-regulates | 0.579 | Atrip is a cdk2 substrate, and cdk2-dependent phosphorylation of s224 regulates the ability of atr-atrip to promote cell cycle arrest in response to dna damage./ One possibility is s224 phosphorylation creates a binding site for another protein involved in the g2-m checkpoint response | SIGNOR-156928 |
Q13315 | Q15910 | 1 | phosphorylation | down-regulates quantity | 0.458 | Enhancer of zeste homolog 2 (EZH2), a core catalytic component of polycomb repressive complex 2, is a new ATM kinase target, and ATM-mediated phosphorylation of EZH2 on Ser734 reduces protein stability.|We verified that S734 is the predominant ATM site on EZH2 by performing ATM in vitro kinase assays using GST-EZH2 fusion proteins as substrates (Fig. 2b). The phosphorylation signal was nearly lost when the EZH2-S734A mutant was used as substrate | SIGNOR-279586 |
Q13464 | Q8N264 | 1 | phosphorylation | up-regulates activity | 0.433 | ROCK phosphorylates FilGAP, and this phosphorylation stimulates its RacGAP activity and is a requirement for FilGAP-mediated bleb formation. | As shown in Fig. 5b, ROCK stimulated the incorporation of phosphate into FilGAP. We identified seven potential phosphorylation sites in FilGAP that was isolated by preparative SDSPAGE and subjected to trypsin digestion and mass spectrometry: Ser 391, Ser 402, Ser 413, Ser 415, Ser 437, Thr 452, and a cluster of serine and threonine residues (SSTTT) at position 573577 (see Supplementary Information, Table S2). | SIGNOR-249302 |
P16220 | Q9UQM7 | 0 | phosphorylation | down-regulates | 0.594 | Phosphorylation of creb1 at ser142 and ser143 is selectively activated by ca(2+) influx;phosphorylation of ser142 and ser143, disrupts the interaction of creb with its cofactor cbp. Phosphorylation of serine 142 in creb by camkii leads to dissociation of the creb dimer. | SIGNOR-82501 |
O60664 | P35790 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.2 | In addition, as a protein kinase, CHKα2 phosphorylates PLIN2 at Tyrosine 232 and PLIN3 at Tyrosine 251. Phosphorylated PLIN2 and PLIN3 are separated from lipid droplets and degraded by Hsc70-mediated autophagy, thereby promoting lipid droplet lipolysis, fatty acid oxidation and glioblastoma growth | SIGNOR-267650 |
P53350 | P37840 | 1 | phosphorylation | down-regulates activity | 0.351 | Polo-like kinase (plk) family (plk1, plk2, and plk3) phosphorylate alpha-syn and beta-syn specifically at ser-129 and ser-118, respectively. Polo-like kinase 2 (plk2) phosphorylates alpha-synuclein at serine 129 in central nervous system. The membrane association of pd-linked mutant alpha -synuclein, but not wild-type -synuclein, was increased by serine 129 phosphorylation. | SIGNOR-189045 |
Q01105-2 | P67870 | 0 | phosphorylation | down-regulates | 0.246 | Ckii-mediated phosphorylation at ser9 hinders nuclear import of set | SIGNOR-200806 |
Q13627 | O43597 | 1 | phosphorylation | down-regulates | 0.304 | We identify dyrk1a as one of the protein kinases of sprouty2. We show that dyrk1a interacts with and regulates the phosphorylation status of sprouty2. Moreover, we identify thr75 on sprouty2 as a dyrk1a phosphorylation site in vitro and in vivo. | SIGNOR-179828 |
P53779 | P61978 | 1 | phosphorylation | up-regulates activity | 0.339 | JNK Phosphorylation of HnRNP K Increases Its Transcriptional Activity. the primary site for JNK phosphorylation consists of serines 216 and 353 on the K protein. | SIGNOR-250083 |
Q13261 | P29597 | 1 | null | up-regulates | 0.245 | Since Jak-STAT pathway primarily activated in IL-15-me- diated cell proliferation, we tested whether it is also participates in IL-15-mediated proliferation of FAPs. Interestingly, we found the expression of phospho-Jak3 and phospho-Tyk2, as well as their downstream, phospho- STAT3 and phospho-STAT5, was significantly upregulated | SIGNOR-256253 |
P35968 | P18031 | 0 | dephosphorylation | down-regulates activity | 0.418 | This led to increased PTPN1 (PTP1b)-mediated dephosphorylation of VEGFR2 at Y 1175 , the site involved in activating ERK signaling. | SIGNOR-277011 |
Q15831 | Q9P0L2 | 1 | phosphorylation | up-regulates | 0.41 | Lkb1 is a master kinase that activates 13 kinases of the ampk subfamily, including mark/par-1we recently demonstrated that the lkb1 tumour suppressor kinase, in complex with the pseudokinase strad and the scaffolding protein mo25, phosphorylates and activates amp-activated protein kinase (ampk). A total of 12 human kinases (nuak1, nuak2, brsk1, brsk2, qik, qsk, sik, mark1, mark2, mark3, mark4 and melk) are related to ampk. Here we demonstrate that lkb1 can phosphorylate the t-loop of all the members of this subfamily, apart from melk, increasing their activity >50-fold | SIGNOR-122545 |
P03372 | P24385 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.754 | Ikkalpha in conjunction with eralpha and aib1/src-3, is important in activating the transcription of estrogen-responsive genes, including cyclin d1. | SIGNOR-135053 |
P67775 | Q12933 | 1 | dephosphorylation | down-regulates activity | 0.2 | We show that the Thr117 residue in TRAF2 is phosphorylated following TNFalpha stimulation. This phosphorylation process is modulated by PP2A and is required for TRAF2 functional activity. | SIGNOR-248640 |
O15259 | Q14289 | 0 | phosphorylation | up-regulates activity | 0.461 | Pyk2 Induces Tyrosine Phosphorylation of NPHP1 at Tyr 46, Tyr 349, and Tyr 721.|The expression of wild-type Pyk2 enhances the amount of co-precipitating PACS-1 with wild-type NPHP1 compared with the presence of the kinase-dead variant of Pyk2. | SIGNOR-278272 |
P09211 | P24723 | 0 | 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-276014 |
P78396 | P10276 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.244 | RARα is involved in the regulation of cyclin A1. Further studies using ligands selective for various retinoic acid receptors suggested that cyclin A1 expression is negatively regulated by activated RARα. | SIGNOR-249636 |
O94804 | P26038 | 1 | phosphorylation | up-regulates activity | 0.385 | Evidence in jurkat cells that lok phosphorylates erm and that erm phosphorylation impedes migration. | SIGNOR-184433 |
P22736 | Q15349 | 0 | phosphorylation | down-regulates activity | 0.367 | Phosphorylation of a residue in the DNA-binding region (Ser-350 of NGFI-B and 354 of Nur77) has been described in detail to have effect on the transcriptional function of the protein [11, 24]. Growth-related kinase pp90rsk, but not ERK1 (pp44mapk), was shown to phosphorylate recombinant Nur77 in vitro in the DNA binding domain, but not the amino-terminus, using an immune complex kinase as- say [11]. | SIGNOR-249429 |
P12931 | P41240 | 0 | phosphorylation | down-regulates | 0.569 | The catalytic activity of the src family of tyrosine kinases is suppressed by phosphorylation on a tyrosine residue located near the c terminus (tyr 527 in c-src), which is catalyzed by c-terminal src kinase (csk). | SIGNOR-179417 |
P17612 | Q6J4K2 | 1 | phosphorylation | up-regulates activity | 0.2 | However, the PDE2-inhibitory effect is eliminated when the mitochondrial S258A NCLX mutant that mimics a non-PKA phosphorylated state of NCLX is expressed. Altogether, our findings indicate that NCLX is regulated by the mitochondrial PDE2A2 form.|We show that caffeine, by inhibiting PDE2, enhances PKA phosphorylation leading to mitochondrial NCLX activation, thereby reducing neuronal excitotoxicity and enhancing learning in mice. |Moreover, PDE2 acts by diminishing mitochondrial cAMP, thus promoting NCLX phosphorylation at its PKA site. | SIGNOR-275727 |
O43683 | P06493 | 0 | phosphorylation | up-regulates | 0.861 | The plk1-bub1 interaction requires the polo-box domain (pbd) of plk1 and is enhanced by cyclin-dependent kinase 1 (cdk1)-mediated phosphorylation of bub1 at t609 | SIGNOR-147065 |
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