IdA string | IdB string | labels int64 | mechanism string | effect string | score float64 | sentence string | signor_id string |
|---|---|---|---|---|---|---|---|
Q8N122 | Q9UIK4 | 0 | phosphorylation | down-regulates activity | 0.354 | DAPK2 phosphorylates raptor in vitro on Ser721. | SIGNOR-278243 |
Q15418 | Q8N122 | 1 | phosphorylation | up-regulates | 0.546 | Ser719, ser721, and ser722 are the predominant rsk-dependent phosphorylation sites in raptor raptor phosphorylation regulates mtorc1 activity | SIGNOR-180466 |
P06493 | P12272 | 1 | phosphorylation | down-regulates | 0.2 | Phosphorylation at the cyclin-dependent kinases site (thr85) of parathyroid hormone-related protein negatively regulates its nuclear localization | SIGNOR-68544 |
P00533 | P43115 | 0 | relocalization | up-regulates quantity | 0.332 | These results demonstrate that PGE2 -mediated EGFR nuclear translocation requires the EP3 receptor. | SIGNOR-278884 |
P63167 | Q15139 | 0 | phosphorylation | down-regulates activity | 0.2 | We now provide evidence that PKD phosphorylates an additional site in DLC1, namely serine 807 within the GAP domain, adding another layer of complexity to PKD-mediated negative regulation of the DLC1 tumor suppressor protein.|We previously reported that PKD inhibits DLC1 cellular function through phosphorylation of serines 327 and 431 [10]. | SIGNOR-279265 |
O75602 | Q92949 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.447 | 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-266935 |
P19419 | Q14774 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | In this study, we have identified cell cycle regulatory genes as downstream targets of the homeobox gene HLX in cultured trophoblast cells, namely RB1, MYC, EGR1, CDKN1C, ELK1, CCNB1, and JUN. RB1 and MYC mRNA expression was increased with HLX inactivation, whereas EGR1, CDKN1C, ELK1, CCNB1, and JUN mRNA expression was decreased compared with mock-transfected control cells. | SIGNOR-261622 |
Q99102 | P14921 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Through promoter screening, overexpressing methods and luciferase reporter studies, we found that transcription factors CREB, Ets-1, Elk-1 and STAT1 can positively regulate MUC4 expression at the promoter and mRNA level. | SIGNOR-254098 |
P46531 | Q9UQ52 | 0 | relocalization | up-regulates | 0.588 | Here, we establish that nb-3, a member of the f3/contactin family, acts as a novel notch ligand to participate in oligodendrocyte generation. Nb-3 triggers nuclear translocation of the notch intracellular domain and promotes oligodendrogliogenesis from progenitor cells and differentiation of oligodendrocyte precursor cells via deltex1. | SIGNOR-124151 |
P15884 | P01106 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.371 | Association of c-Jun, β-catenin, and TCF4 specifically with the downstream enhancer underlies mitogen stimulation of c-Myc transcription. | SIGNOR-253324 |
Q9UMX1 | P10070 | 1 | relocalization | down-regulates activity | 0.909 | We demonstrate here that Su(fu) prevents the nuclear accumulation of Gli1 and Gli2 through multiple mechanisms | SIGNOR-129065 |
P36873 | P36897 | 1 | dephosphorylation | down-regulates | 0.469 | We found smad7 interacts with growth arrest and dna damage protein, gadd34, a regulatory subunit of the protein phosphatase 1 (pp1) holoenzyme, which subsequently recruits catalytic subunit of pp1 (pp1c) to dephosphorylate t?RI. | SIGNOR-121277 |
Q06609 | P15374 | 0 | deubiquitination | up-regulates activity | 0.325 | Here we report that ubiquitination of RAD51 hinders RAD51-BRCA2 interaction, while deubiquitination of RAD51 facilitates RAD51-BRCA2 binding and RAD51 recruitment and thus is critical for proper HR. | UCHL3, in turn, deubiquitinates RAD51 and promotes the binding between RAD51 and BRCA2.|Our results suggested that three lysine sites (56, 57, and 63) on RAD51 that are close to E59 are deubiquitinated by UCHL3. | SIGNOR-275908 |
Q86TM6 | P60484 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | Secondly, HRD1 promotes PTEN ubiquitination and degradation. | SIGNOR-278724 |
Q9Y2H0 | Q9Y566 | 1 | relocalization | up-regulates activity | 0.696 | SHANK proteins are ‘master’ scaffolding proteins that tether and organize intermediate scaffolding proteins. They are located at excitatory synapses, where they are crucial for proper synaptic development and function. SAPAP proteins subsequently bind to the PDZ domain of members of the SHANK protein family. SHANK proteins then bind to the actin cytoskeleton and to Homer protein, which in turn interacts with mGluRs. Through these extended links, PSD95, SAPAP, SHANK and Homer proteins form a quaternary complex that brings together mGluR and NMDAR complexes in the PSD (FIG. 3). | SIGNOR-264595 |
Q13085 | P17612 | 0 | phosphorylation | down-regulates activity | 0.2 | TC1 = Ser-2Ser(P)-Met-3Ser(P)-Gly-Leu; TC2 = Arg-Met-1Ser(P)-Phe- Cyclic-AMP-dependent protein kinase phosphorylates sites 1 and 2 exclusively, whereas the AMP-activated protein kinase phosphorylates sites 1 and 3, plus at least one other minor site.[…]The results suggest that phosphorylation of site 3 is primarily responsible for the large decrease in Vmax produced by the AMP-activated protein kinase, while phosphorylation of site 1 may be primarily responsible for the increase in A0.5 for citrate and more modest depression of Vmax produced by cyclic-AMP-dependent protein kinase and ACK2 | SIGNOR-267714 |
Q9H2X6 | P29590 | 1 | phosphorylation | up-regulates | 0.438 | In response to dna damage, hipk2 phosphorylates pml at serines 8 and 38. he n-terminal phosphorylation sites contribute to the dna damage-induced pml sumoylation and are required for the ability of pml to cooperate with hipk2 for the induction of cell death. | SIGNOR-182428 |
Q8N6U8 | O75386 | 0 | relocalization | up-regulates activity | 0.608 | Upon knockdown of Tulp3 using siRNA in IMCD3 cells, ciliary localization of Gpr161 was severely reduced | SIGNOR-259938 |
P31749 | P10275 | 1 | phosphorylation | down-regulates activity | 0.586 | Akt suppresses androgen-induced apoptosis by phosphorylating and inhibiting androgen receptor. Here, we demonstrate that akt phosphorylates the androgen receptor (ar) at ser-210 and ser-790 | SIGNOR-108508 |
P29590 | Q6ZNA4 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.355 | Upon TGF-β induction, interaction of Arkadia with phosphorylated Smad2 triggers degradation of SnoN, whereas upon arsenic treatment, interaction of Arkadia with poly-SUMO in PML nuclear bodies induces degradation of polysumoylated PML together with RNF4. | SIGNOR-272883 |
Q9NP71 | Q13131 | 0 | phosphorylation | down-regulates | 0.451 | Ampk has also been suggested to phosphorylate the glucose-sensitive transcription factor chrebpthe dna binding activity, as assayed in a gel-shift assay of the truncated chrebp, was gradually inactivated with time by treatment with ampk | SIGNOR-176494 |
P01222 | P23769 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.39 | Pit-1, is necessary but not sufficient to allow basal transcription of the mTSHβ gene.The analysis of the mTSHβ gene described in this report provides evidence for the participation of a zinc finger factor, GATA-2, with a POU homeodomain partner, Pit-1, on a such a composite element.In summary, we have shown the requirement for at least two different classes of transcription factors to regulate mTSHβ gene expression. Both GATA-2 and Pit-1 can bind independently to the P1 region of the promoter, form a heteromeric complex with DNA, and functionally synergize to activate TSHβ promoter activity. | SIGNOR-267253 |
Q99835 | P48729 | 0 | phosphorylation | up-regulates | 0.521 | We demonstrate that mammalian Smo (mSmo) is activated through multi-site phosphorylation of its carboxyl-terminal tail by CK1α and GRK2. Phosphorylation of mSmo induces its active conformation and simultaneously promotes its ciliary accumulation. | SIGNOR-174542 |
P07948 | Q05655 | 1 | phosphorylation | down-regulates activity | 0.557 | Src, Fyn, or Lyn are the essential kinases that tyrosine phosphorylate and inactivate PKC δ. Lyn phosphorylates tyrosine residue 565 in vitro | SIGNOR-251407 |
P35367 | Q9UQM7 | 0 | phosphorylation | down-regulates | 0.282 | As we have shown previously, human h1r can be phosphorylated in vitro by several kinases includingpka, pkc, pkg, and camk ii in summary, these data suggest that thr140, thr142, ser396, ser398, and thr478 can be phosphorylated by the kinases described above (table 2). | SIGNOR-124348 |
Q96EB6 | P58012 | 1 | deacetylation | down-regulates | 0.501 | We find that foxl2 activity is repressed by the sirt1 deacetylase. | SIGNOR-182306 |
P33981 | Q9Y6D9 | 1 | phosphorylation | up-regulates activity | 0.819 | Furthermore, although catalytically inactive Mps1 can restore kinetochore localization of Mad1, only the active kinase restores Mad2 localization.|Indeed, Mps1 can phosphorylate Mad1 in vitro. | SIGNOR-279000 |
Q15797 | P49841 | 0 | phosphorylation | down-regulates | 0.504 | Phosphorylation at the gsk3 sites represses the transcriptional activity of smad1 by enhancing proteasomal degradation of psmad1cter | SIGNOR-159484 |
Q14938 | P41161 | 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-268886 |
Q14012 | Q9UQL6 | 1 | phosphorylation | down-regulates | 0.419 | Camk phosphorylates serines -259 and -498 in hdac5, which subsequently serve as docking sites for 14-3-3. Our studies suggest that 14-3-3 binding to hdac5 is required for camk-dependent disruption of mef2hdac complexes and nuclear export of hdac5, and implicate 14-3-3 as a signal-dependent regulator of muscle cell differentiation. | SIGNOR-85022 |
P67775 | Q16549 | 0 | phosphorylation | up-regulates | 0.2 | This together with the rapid kinetics of pp1-pp2a activation following p38 activation suggests that pp1 and/or pp2a complexes are direct targets for p38-mediated phosphorylation | SIGNOR-105783 |
Q16555 | O75116 | 0 | phosphorylation | up-regulates | 0.383 | Rho-kinase phosphorylated crmp-2 at thr-555 in vitro.we demonstrated that crmp-2 is phosphorylated by rho-kinase in drg neurons during lpa-induced growth cone collapse. | SIGNOR-77543 |
Q15208 | P46937 | 1 | phosphorylation | down-regulates activity | 0.383 | We show that mammalian NDR1/2 kinases phosphorylate YAP1 on S127 and thereby negatively regulate YAP1 activity in tissue-cultured cells. | SIGNOR-259855 |
P37840 | P62714 | 0 | dephosphorylation | down-regulates activity | 0.276 | α-Synuclein (α-Syn) is a key protein that accumulates as hyperphosphorylated aggregates in pathologic hallmark features of Parkinson's disease (PD) and other neurodegenerative disorders. Phosphorylation of this protein at serine 129 is believed to promote its aggregation and neurotoxicity, suggesting that this post-translational modification could be a therapeutic target. Here, we demonstrate that phosphoprotein phosphatase 2A (PP2A) dephosphorylates α-Syn at serine 129 | SIGNOR-248592 |
P46937 | Q9UL68 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.2 | Myt1 and Myt1l transcription factors limit proliferation in GBM cells by repressing YAP1 expression. Examination of the gene expression changes in cells expressing Myt1 or Myt1l suggests that both repress expression of the YAP1 transcriptional coactivator, which functions primarily in the Hippo signaling pathway. Expression of YAP1 and its target genes is reduced in Myt-expressing cells, and there is an inverse correlation between YAP1 and MYT1/MYT1L expression in human brain cancer datasets. Together, our data suggest that Myt1 and Myt1l directly repress expression of YAP1, a protein which promotes proliferation and GBM growth. | SIGNOR-266778 |
Q969R2 | P45983 | 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-264876 |
Q15831 | P43268 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.622 | LKB1 phosphorylated PEA3 and promoted its degradation through a proteasome-mediated mechanism. | SIGNOR-279293 |
Q9NVW2 | O43679 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.452 | Here we identify RLIM as a ubiquitin protein ligase that is able to target CLIM cofactors for degradation through the 26S proteasome pathway. | SIGNOR-272616 |
O60858 | P22736 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | These results suggest that Trim13 activity mediates Nur77 ubiquitination, leading to its degradation. | SIGNOR-278564 |
O95819 | Q12933 | 1 | phosphorylation | down-regulates quantity | 0.521 | A key finding of our study is that HGK induces lysosomal degradation of TRAF2 by directly phosphorylating TRAF2 Ser35.|Conversely, TRAF2 levels were decreased by ectopically expressed HGK in an overexpression system (XREF_FIG). | SIGNOR-279536 |
P28482 | Q07889 | 1 | phosphorylation | down-regulates activity | 0.714 | In this report, we describe the identification of five map kinase sites (s-1137, s-1167, s-1178, s-1193, and s-1197) on hsos1Replacing the MAP kinase phosphorylation sites with alanine residues results in an increase in the binding affinity of Grb2 to hSos1 | SIGNOR-235929 |
P49023 | Q13882 | 0 | phosphorylation | up-regulates activity | 0.63 | It was also observed that the attenuation of BRK phosphorylation in turn inhibits BRK mediated activation of its direct targets, STAT3, SAM68, and Paxillin.|The EGF pathway also stimulates BRK 's phosphorylation of paxillin to promote migratory and invasive characteristics in breast cancer cells. | SIGNOR-280102 |
O75030 | P27361 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.542 | More interestingly, ERK-dependent phosphorylation of MITF at Ser 73 is essential for MITF ubiquitinilation and degradation (87). Putting together all these findings, it can be proposed that MAPK activation inhibits melanogenesis due to an increased MITF degradation which is dependent on the MAPK-induced MITF phosphorylation and ubiquitinilation. In summary, although the phosphorylation of MITF at Ser73 increases its intrinsic transcriptional activity, this phosphorylation also targets MITF to the proteasome for its degradation. Consequently, the decrease in MITF levels leads to a down-regulation of melanogenic enzymes expression and to an inhibition of melanogenesis. | SIGNOR-249620 |
P01106 | Q13049 | 0 | 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 |
Q13464 | P14136 | 1 | phosphorylation | down-regulates activity | 0.312 | We report here that aurora-b phosphorylates gfap and desmin in vitro, and this phosphorylation leads to a reduction in filament forming ability. The sites phosphorylated by aurora-b;thr-7/ser-13/ser-38 of gfap, and thr-16 of desmin are common with those related to rho-associated kinase (rho-kinase), which has been reported to phosphorylate gfap and desmin at cleavage furrow during cytokinesis. We identified ser-59 of desmin to be a specific site phosphorylated by aurora-b in vitro. | SIGNOR-100192 |
P08581 | P17706 | 0 | dephosphorylation | down-regulates | 0.501 | We have identified ptp1b and tcptp as negative regulators of the hepatocyte growth factor receptor, the met receptor-tyrosine kinase. In vivo, loss of ptp1b or tcptp enhances hepatocyte growth factor-mediated phosphorylation of met. | SIGNOR-181331 |
P0C0S8 | O75582 | 0 | phosphorylation | up-regulates | 0.2 | We found that msk1 phosphorylated histone h2a on serine 1, and mutation of serine 1 to alanine blocked the inhibition of transcription by msk1. | SIGNOR-123383 |
Q8N9I0 | Q9H4A3 | 0 | phosphorylation | up-regulates activity | 0.603 | Endogenous WNK1 and Syt2 coimmunoprecipitate and colocalize on a subset of secretory granules in INS-1 cells. Phosphorylation by WNK1 increases the amount of Ca2+ required for Syt2 binding to phospholipid vesicles; mutation of threonine 202, a WNK1 phosphorylation site, partially prevents this change. These findings suggest that phosphorylation of Syts by WNK1 can regulate Ca2+ sensing and the subsequent Ca2+-dependent interactions mediated by Syt C2 domains. . In contrast, WNK1 phosphorylated Syt2 on T202 and T386 within the C2 domains (Figure 6B). | SIGNOR-263049 |
P22612 | Q6PIY7 | 1 | phosphorylation | down-regulates activity | 0.2 | We found that Gld2 activity is regulated by site-specific phosphorylation in its disordered N-terminal domain. We identified two phosphorylation sites (S62, S110) where phosphomimetic substitutions increased Gld2 activity and one site (S116) that markedly reduced activity. Using mass spectrometry, we confirmed that HEK 293 cells readily phosphorylate the N-terminus of Gld2. We identified protein kinase A (PKA) and protein kinase B (Akt1) as the kinases that site-specifically phosphorylate Gld2 at S116, abolishing Gld2-mediated nucleotide addition. | SIGNOR-259404 |
Q15746 | Q13555 | 0 | phosphorylation | down-regulates activity | 0.331 | Phosphorylation of MLC kinase by CaM protein kinase II increased the dissociation constant of MLC kinase for calmodulin about 10 times without changing the Vmax. The location of the phosphorylation sites was identified by isolating and sequencing the tryptic phosphopeptides of MLC kinase. The preferred site was identified as serine 512 and the second site as serine 525. These sites are the same as the sites phosphorylated by cAMP-dependent protein kinase. | SIGNOR-250700 |
Q13470 | Q96L34 | 0 | phosphorylation | down-regulates activity | 0.2 | We also discover a MARK-mediated phosphorylation on TNK1 at S502 that promotes an interaction between TNK1 and 14-3-3, which sequesters TNK1 and inhibits its kinase activity.Phosphorylation of TNK1 at S502 within the proline rich domain is required for TNK1 binding to 14-3-3.MARKs mediate phosphorylation at S502 and 14-3-3 binding to TNK1, which restrains the movement of TNK1 into heavy membrane-associated clusters. | SIGNOR-273865 |
P52735 | Q16620 | 0 | phosphorylation | up-regulates activity | 0.302 | Finally, the TrkB kinase dependent increase in P-Y172 Vav2 was largely independent of the Vav2 SH2 domain (XREF_FIG, right), which was previously shown to be important for activation by Eph receptors.|These findings reveal a strong kinase independent binding mechanism between Vav and TrkB in cells, and suggest that activation of TrkB kinase activity stimulates Vav2 tyrosine phosphorylation and GEF activity. | SIGNOR-280050 |
P63000 | Q05397 | 0 | phosphorylation | up-regulates activity | 0.574 | Both Src and FAK phosphorylate Rac1 at tyrosine 64.|Our investigations of direct interactions between Rac1, Src, and FAK were motivated by our previous insights into FAK augmentation of Rac1 activation during cell spreading, and the Cerione lab 's work on the interactions between Src and Cdc42 , . | SIGNOR-279652 |
P28482 | P03372 | 1 | phosphorylation | up-regulates | 0.671 | In several estrogen response element-containing genes, the s118a mutation strongly reduced induction by e(2), and u0126 did not further reduce expression. Here, we show that serines 104 (s104) and 106 (s106) are also phosphorylated by mapk in vitro and upon stimulation of mapk activity in vivo. | SIGNOR-156856 |
Q92844 | Q14164 | 0 | phosphorylation | down-regulates activity | 0.743 | IKK-i phosphorylates I-TRAF. In vitro kinase assays demonstrate that IKK‐i phosphorylates I‐TRAF in the middle portion that associates with TRAF2. Interestingly, TRAF2 is freed from the I‐TRAF/TRAF2 complex after I‐TRAF phosphorylation. TRAF2 isdistributed throughout the cytoplasm, in the formof inactive an I-TRAF/TRAF2 complex | SIGNOR-262722 |
P68400 | P30291 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.408 | In the present study, we show that phosphorylation of S123 (pS123) by CDK promoted the binding of Wee1A to beta-TrCP through three independent mechanisms. S123 phosphorylation creates a PBD-binding motif and accelerates S53 phosphorylation by Plk1. | SIGNOR-276038 |
P53350 | P33981 | 1 | phosphorylation | up-regulates activity | 0.381 | Here, we demonstrate that Plk1 promotes checkpoint signaling at kinetochores through the phosphorylation of at least two Mps1 substrates, including KNL-1 and Mps1 itself. As a result, Plk1 activity enhances Mps1 catalytic activity as well as the recruitment of the SAC components Mad1:C-Mad2 and Bub3:BubR1 to kinetochores. Plk1 Targets Mps1 Autophosphorylation Sites In Vitro | SIGNOR-276199 |
Q00987 | Q9BRP0 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | In breast cancer cells, MDM2 overexpression or p53 KD reduced OVOL2 protein expression, and the proteasome inhibitor MG132 blocked the MDM2 overexpression\u2010 or p53 KD\u2010mediated reduction in OVOL2 expression (Figure\u00a06B,C).|The E3 ubiquitin ligase MDM2 ubiquitinates and degrades the OVOL2 protein. | SIGNOR-278826 |
O60331 | Q00535 | 0 | phosphorylation | down-regulates | 0.364 | The interaction of talin with phosphatidylinositol(4) phosphate 5 kinase type i gamma (pipki gamma) regulates pi(4,5)p2 synthesis at synapses and at focal adhesions. Here, we show that phosphorylation of serine 650 (s650) within the talin-binding sequence of human pipki gamma blocks this interaction. At synapses, s650 is phosphorylated by p35/cdk5 and mitogen-activated protein kinase at rest, and dephosphorylated by calcineurin upon stimulation. | SIGNOR-134455 |
P43405 | Q7Z6Z7 | 1 | phosphorylation | up-regulates activity | 0.2 | Collectively, these data suggest that TNF induced tyrosine phosphorylation of Mule by Syk contributes to its E3 ligase activity. | SIGNOR-280150 |
P42575 | P78527 | 0 | phosphorylation | up-regulates | 0.297 | Here we show that dna damage induced by gamma-radiation triggers the phosphorylation of nuclear caspase-2 at the s122 site within its prodomain, leading to its cleavage and activation. This phosphorylation is carried out by the nuclear serine/threonine protein kinase dna-pkcs | SIGNOR-183895 |
P08069 | O14654 | 1 | phosphorylation | up-regulates | 0.657 | Insulin-like growth factor i acting through its receptor was as effective as insulin in eliciting tyrosine phosphorylation of irs-4. | SIGNOR-56604 |
P42685 | P60484 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.599 | Rak phosphorylates PTEN on Tyr 336 to prevent its protein degradation. In this study, we demonstrate that the Rak tyrosine kinase physically interacts with PTEN and phosphorylates PTEN on Tyr336. Knockdown of Rak enhanced the binding of PTEN to its E3 ligase NEDD4-1 and promoted PTEN polyubiquitination, leading to PTEN protein degradation. | SIGNOR-275458 |
O00220 | Q5T0T0 | 0 | ubiquitination | down-regulates quantity | 0.2 | The collective data indicate that endogenous MARCH-8 ubiquitinates TRAIL-R1 to attenuate its cell surface expression. | SIGNOR-278570 |
P09467 | P06748 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.2 | For instance, nucleophosmin (NPM1) and zinc-finger protein X-linked (ZFX) bind to the E-box and ZFX binding site on the FBP1 promoter, respectively, and restrain FBP1 expression to facilitate aerobic glycolysis in PDAC and melanoma | SIGNOR-267594 |
P49840 | P07384 | 0 | cleavage | up-regulates activity | 0.2 | Thus, it has been shown that calpain cleaves the inhibitory domain of GSK3 generating two fragments of 40 and 30 kDa. This cleavage enhanced activity of the kinase | SIGNOR-251585 |
P38435 | P04070 | 1 | carboxylation | up-regulates activity | 0.572 | 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-265925 |
Q9NR19 | P10619 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Nucleus-Translocated ACSS2 Promotes Gene Transcription for Lysosomal Biogenesis and Autophagy|A chromatin immunoprecipitation (ChIP) assay with antibodies against TFEB or ACSS2 demonstrated that glucose deprivation results in the binding of TFEB (Figure 3D) and ACSS2 (Figure 3E) to the promoter regions of CTSA, GBA, GUSB, and LAMP1|These results indicated that TFEB and ACSS2 are mutually required for their binding to the promoter regions of lysosomal genes. In line with these findings, glucose deprivation induced mRNA (Figure 3F) and protein (Figure 3G) expression for these lysosomal genes, which was largely abrogated by knockin of ACSS2 mutants | SIGNOR-276550 |
Q9HC16 | P46934 | 0 | ubiquitination | up-regulates activity | 0.284 | APOBEC3G ubiquitination by Nedd4-1 favors its packaging into HIV-1 particles|This could be explained in at least two ways : first, endogenous Nedd4 is naturally expressed at a level largely sufficient to target APOBEC3G into the VLP or virions. | SIGNOR-278635 |
P15941 | P78536 | 0 | cleavage | down-regulates | 0.308 | These characteristics along with studies conducted with cell lines genetically deficient in various adams (for a disintegrin and metalloprotease) identified tumor necrosis factor-alpha converting enzyme (tace)/adam 17 as a muc1 sheddase. | SIGNOR-95630 |
P12931 | P52757 | 1 | phosphorylation | down-regulates | 0.2 | Here we report that beta2-chimaerin is tyrosine-phosphorylated by src-family kinases (sfks) upon cell stimulation with epidermal growth factor (egf). Mutational analysis identified tyr-21 in the n-terminal regulatory region as a major phosphorylation site. these results suggest tyr-21 phosphorylation as a novel, sfk-dependent mechanism that negatively regulates beta2-chimaerin rac-gap activity. | SIGNOR-155713 |
Q9C026 | P50552 | 1 | ubiquitination | down-regulates quantity | 0.345 | TRIM9 ubiquitinates VASP but not Mena or EVL.|Thus TRIM9 negatively regulates VASP localization to filopodia tips, whereas netrin promotes VASP tip localization. | SIGNOR-278580 |
P52292 | Q19QW5 | 0 | relocalization | down-regulates activity | 0.2 | Taken together, these data support a direct interaction between KPNA2 and ORF6 in the context of virus infection.|SARS-CoV, but not SARSdeltaORF6, retains KPNA2 at the ER/Golgi membrane. | SIGNOR-260272 |
Q9HCK8 | O96020 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.417 | In order to identify CHD8 target genes, we performed a transcriptomic analysis of CHD8-depleted cells, finding out that CHD8 controls the expression of cyclin E2 (CCNE2) and thymidylate synthetase (TYMS), two genes expressed in the G1/S transition of the cell cycle. CHD8 was also able to co-activate the CCNE2 promoter in transient transfection experiments. Chromatin immunoprecipitation experiments demonstrated that CHD8 binds directly to the 5' region of both CCNE2 and TYMS genes. | SIGNOR-268804 |
P42574 | O76075 | 1 | cleavage | up-regulates | 0.684 | Casp3_ cleaves the 45 kda subunit at two sites to generate an active factor that produces_ dna_ fragmentation | SIGNOR-47419 |
Q9NQC7 | Q13554 | 0 | phosphorylation | up-regulates | 0.2 | Purified camkii phosphorylates cyld on at least three residues (s-362, s-418, and s-772 on the human cyld protein q9nqc7-1) and promotes its deubiquitinase activity. | SIGNOR-91403 |
Q15714 | P23582 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.257 | TSC-22 significantly enhanced CNP promoter activity in GH3 cells. | SIGNOR-266226 |
P14316 | P33076 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.525 | In addition to IRF-1, IRF-2, another member of the IRF family, also activates the human CIITA type IV promoter, and IRF-2 cooperates with IRF-1 to activate the promoter in transient transfection assays. | SIGNOR-271681 |
Q13535 | O43542 | 1 | phosphorylation | up-regulates activity | 0.464 | HXRCC3 S225 phosphorylation is mediated by ATR via an ATM-dependent signaling pathway. These data clearly indicate that ATR mediates the late activation of XRCC3 following DSB accumulation. | SIGNOR-262666 |
P36896 | P27037 | 0 | phosphorylation | up-regulates | 0.687 | In this complex, the actrii??/Iib kinase phosphorylates alk4 within a glycine- and serine-rich region called the gs domain, and this phosphorylation event activates the alk4 kinase | SIGNOR-99995 |
P06493 | P56181 | 1 | phosphorylation | up-regulates activity | 0.2 | Here, we show that a fraction of cyclin B1/Cdk1 proteins localizes to the matrix of mitochondria and phosphorylates a cluster of mitochondrial proteins, including the complex I (CI) subunits in the respiratory chain. Cyclin B1/Cdk1-mediated CI phosphorylation enhances CI activity, whereas deficiency of such phosphorylation in each of the relevant CI subunits results in impairment of CI function.|These results were confirmed by generating phosphorylation defective forms of the five CI subunits through substitutions of S/T residues with Alanine (A) on either Cdk1 optimal or minimal consensus motifs (T383 on NDUFV1, S105 on NDUFV3, S364 on NDUFS2, S55/S29/T5 on NDUFB6, and T142/T120 on NDUFA12). The mutation of Cdk1 consensus motifs severely diminished their phosphorylation | SIGNOR-275593 |
P07101 | Q8IW41 | 0 | phosphorylation | up-regulates | 0.2 | Recombinant human tyrosine hydroxylase (hth1) was found to be phosphorylated by mitogen and stress-activated protein kinase 1 (msk1) at ser40 and by p38 regulated/activated kinase (prak) on ser19. Phosphorylation of both ser40 and ser19 induced a high-affinity binding of 14-3-3 proteins, but only the interaction of 14-3-3 with ser19 increased the hth1 activity. | SIGNOR-95479 |
P41229 | Q16695 | 1 | demethylation | up-regulates activity | 0.2 | KDM5 subfamily is capable of removing tri†and di†methyl marks from lysine 4 on histone H3 (H3K4). Depending on the methylation site, its effect on transcription can be either activating or repressing. | SIGNOR-264306 |
Q8WW12 | Q96PU4 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.451 | Ubiquitination of PEST containing nuclear protein (PEST) by NIRF (Np95/ICBP90‐like RING finger protein) in the nuclear core of the cell: Ubiquitin‐like domain in the N‐terminus and a RING finger motif in the C‐terminus of NIRF confirm the ubiquitin ligase function of NIRF. PCNP acts as a substrate for NIRF mediated proteasome activity. | SIGNOR-271501 |
Q13507-3 | Q13976 | 0 | phosphorylation | down-regulates | 0.408 | The present study demonstrates that human trpc3 expressed in hek293 cells forms store-operated ca2+ influx channels, the activity of which is inhibited by pkg. The inhibition is due to a direct phosphorylation of pkg on trpc3 channels at position t11 and s263. | SIGNOR-142957 |
O14920 | P35813 | 0 | dephosphorylation | down-regulates | 0.308 | Using a functional genomic approach, we have identified two protein serine/threonine phosphatases, ppm1a and ppm1b, as ikkbeta phosphatases. Overexpression of ppm1a or ppm1b results in dephosphorylation of ikkbeta at ser177 and ser181 and termination of ikkbeta-induced nf-kappab activation | SIGNOR-181659 |
Q19QW5 | P52292 | 1 | relocalization | down-regulates activity | 0.2 | Taken together, these data support a direct interaction between KPNA2 and ORF6 in the context of virus infection.|SARS-CoV, but not SARSdeltaORF6, retains KPNA2 at the ER/Golgi membrane. | SIGNOR-260272 |
Q14693 | O95476 | 0 | dephosphorylation | up-regulates activity | 0.78 | Dullard significantly dephosphorylates mouse lipin 1b only in BHK cells (Fig. 5A). This is most clearly seen by using the antibody prepared against the phosphorylation site Ser-106.|Dephosphorylation of lipin results in its translocation to the nuclear envelope and endoplasmic reticulum membranes from the cytosol and generation of diacylglycerol | SIGNOR-248346 |
P49841 | O15033 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.316 | These experiments suggested that GSK3beta phosphorylation of FIEL1 is required for PIAS4 targeting, and FIEL1 residues P779 and phosphorylated T783 are both required for PIAS4 interaction |FIEL1 T783A mutant overexpression completely failed to decrease PIAS4 protein level. | SIGNOR-275528 |
P40763 | P43378 | 0 | dephosphorylation | down-regulates activity | 0.432 | Results are presented as mean \u00b1 SD from three independent experiments. (B) PTPMeg2 inhibits STAT3-mediated transcriptional activity in a dose dependent manner.|These results indicate that PTPMeg2 inhibits STAT3 activation with certain specificity.|In this study, we demonstrated that PTPMeg2 dephosphorylates STAT3 at the Tyr705 residue by a direct interaction. | SIGNOR-276976 |
P28482 | Q07343-2 | 1 | phosphorylation | up-regulates activity | 0.268 | The short-form PDE4B2 isoenzyme was activated by Erk2 phosphorylation. These functional changes in PDE activity were mimicked by mutation of the target serine for Erk2 phosphorylation to the negatively charged amino acid, aspartic acid. | SIGNOR-275971 |
P10276 | Q9NPD5 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Taken together, these findings suggest that the LPS-induced down-regulation of Oatp4 is likely due to reduction in the binding of HNF1alpha, C/EBP, HNF3, and RXR:RAR to the Oatp4 promoter. | SIGNOR-268989 |
P99999 | Q16611 | 0 | relocalization | up-regulates | 0.566 | Allosteric activation of bak induces its intramembranous oligomerization into a proposed pore for cytochrome c efflux | SIGNOR-105206 |
P05198 | Q14232 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.83 | 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-269124 |
O15123 | Q03112 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | We finally observed that the forced expression of Evi1 induced GATA-2 expression in a hematopoietic cell line, EML C1, along with GATA-1, Ang-1, Ang-2 and Tie2 | SIGNOR-266060 |
O14654 | P06213 | 0 | phosphorylation | up-regulates activity | 0.518 | The binding of insulin to the subunit of IR not only concentrates insulin at its site of action, but also induces conformational changes in the receptor, which in turn stimulates the tyrosine kinase activity intrinsic to the _ subunit of the IR and triggers the signaling cascades (Fig. 3). Insulin receptors trans phosphorylate several immediate substrates (on Tyr residues) including IRS1-4, Shc, and Gab 1, Cbl, APS, and P60dok. | SIGNOR-217897 |
Q9Y2T1 | P53350 | 0 | phosphorylation | up-regulates activity | 0.486 | Plk1 phosphorylates axin2 at Ser311. | SIGNOR-277180 |
P48431 | Q9HCK8 | 0 | transcriptional regulation | down-regulates quantity | 0.318 | Many of the most significantly up-regulated genes in Chd8+/− and Chd8−/− NPCs are involved in later stages of neuronal development, including Ascl1 [a central driver of neural reprogramming (29)], Dcx, Map2, Nefm, Neurod4, and Neurog1 (Fig. 2 E and F). Additionally, we found that Sox3 is derepressed in both Chd8+/− and Chd8−/− NPCs, and several other Sox TF members (Sox2, Sox7, and Sox11) became derepressed in the Chd8−/− cells | SIGNOR-268921 |
Q86Y97 | P62805 | 1 | methylation | down-regulates activity | 0.2 | SUV420H1 and SUV420H2 are two highly homologous enzymes that methylate lysine 20 of histone H4 (H4K20), a mark that has been implicated in transcriptional regulation. | SIGNOR-266650 |
P30048 | Q5S007 | 0 | phosphorylation | down-regulates activity | 0.413 | Here, we show that LRRK2 interacts with human peroxiredoxin 3 (PRDX3), a mitochondrial member of the antioxidant family of thioredoxin (Trx) peroxidases. Importantly, mutations in the LRRK2 kinase domain significantly increased phosphorylation of PRDX3 compared to wild-type. The increase in PRDX3 phosphorylation was associated with decreased peroxidase activity and increased death in LRRK2-expressing but not in LRRK2-depleted or vector-transfected neuronal cells. | SIGNOR-262891 |
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