IdA string | IdB string | labels int64 | mechanism string | effect string | score float64 | sentence string | signor_id string |
|---|---|---|---|---|---|---|---|
P27348 | P30307 | 1 | relocalization | down-regulates | 0.575 | Cdc25c: nuclear exclusion/cytoplasmic sequestration via binding to 14-3-3 proteins. | SIGNOR-163237 |
Q7Z5G4 | P01111 | 1 | palmitoylation | up-regulates activity | 0.396 | Covalent lipid modifications mediate the membrane attachment and biological activity of Ras proteins. All Ras isoforms are farnesylated and carboxyl-methylated at the terminal cysteine; H-Ras and N-Ras are further modified by palmitoylation. Here we report that H- and N-Ras are palmitoylated by a human protein palmito... | SIGNOR-261354 |
O15409 | P08581 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.416 | FOXP2 binds directly to the 5' regulatory region of MET, and overexpression of FOXP2 results in transcriptional repression of MET. The expression of MET in restricted human neocortical regions, and its regulation in part by FOXP2, is consistent with genetic evidence for MET contributing to ASD risk. | SIGNOR-269054 |
O15105 | P49910 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.2 | ZNF165 drives the unrestrained activation of transforming growth factor β (TGFβ) signalling by directly inactivating the expression of negative feedback pathway regulators, SMURF2, SMAD7 and PMEPA1. | SIGNOR-266093 |
Q96CV9 | Q8IYU2 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.401 | Here we report that tumor suppressor HACE1, a ubiquitin ligase, ubiquitylates OPTN and promotes its interaction with p62 and SQSTM1 to form the autophagy receptor complex, thus accelerating autophagic flux.|Ubiquitylation of Autophagy Receptor Optineurin by HACE1 Activates Selective Autophagy for Tumor Suppression.|HAC... | SIGNOR-278748 |
P59595 | P15336 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | The transcription factors c-Fos, FosB, CREB-1, and ATF2 were all activated by the addition of SARS-CoV N protein to the sample well | SIGNOR-260727 |
Q00536 | Q00535 | 0 | phosphorylation | up-regulates activity | 0.335 | Taken together, our findings demonstrate that Pctaire1 interacts with p35, both in vitro and in vivo, and that phosphorylation of Pctaire1 by Cdk5 enhances its kinase activity. | SIGNOR-279149 |
P24941 | Q8WZ60 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | We confirmed the formation of ubiquitin and CDK2 by different systems and further identified the E3 ligase KLHL6 as a mediator of the ubiquitination and degradation of CDK2. | SIGNOR-272310 |
P00519 | P01106 | 1 | phosphorylation | up-regulates activity | 0.469 | Altogether, our data demonstrate that Pin1 and Abl cooperate to enhance the interaction of Myc with p300 and its resulting acetylation.|These experiments confirmed that Myc Y74 is phosphorylated by Abl, and provided us with a reagent to detect this form of Myc in cells (see below). | SIGNOR-278196 |
P19474 | P34897 | 1 | ubiquitination | down-regulates quantity | 0.2 | The expression of TRIM21, but not the expression of the ligase-dead (LD) mutant TRIM21 (C16A, C31A and H33W) 36, increased SHMT2 ubiquitylation, which suggests that TRIM21 is the E3 ligase for SHMT2 and that the E3 ligase activity of TRIM21 is required for SHMT2 ubiquitylation.|We found that the overexpression of TRIM2... | SIGNOR-278792 |
Q05397 | P35968 | 0 | null | up-regulates activity | 0.496 | Here we show that genetic or pharmacological FAK inhibition in ECs prevents VEGF-stimulated permeability downstream of VEGF receptor or Src tyrosine kinase activation in vivo. VEGF promotes tension-independent FAK activation | SIGNOR-261945 |
Q96D59 | P05026 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | RNF183 promotes the degradation of Na, K-ATPas. We confirmed that RNF183 interacted with both α1 and β1 subunits; however, we found that RNF183 ubiquitinated only the β1 subunit, not the α1 subunit. | SIGNOR-272218 |
P67775 | Q08999 | 1 | dephosphorylation | up-regulates | 0.581 | Pocket protein family consists of the retinoblastoma tumor suppressor protein (prb) and the functionally and structurally related proteins p107 and p130./dephosphorylation of p130 and p107 in cell extracts is inhibited by concentrations of okadaic acid known to inhibit pp2a, but not pp1. Finally, the pp2a catalytic sub... | SIGNOR-129752 |
P49841 | Q6PGQ7 | 1 | phosphorylation | up-regulates | 0.258 | It suggests that gsk3_ activity is required for hbora-mediated mitotic entry through ser274 and ser278 phosphorylation | SIGNOR-201519 |
P52735 | P61586 | 1 | guanine nucleotide exchange factor | up-regulates activity | 0.75 | 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... | SIGNOR-260582 |
Q96QB1 | Q15139 | 0 | phosphorylation | down-regulates | 0.371 | The tumor suppressor protein dlc1 is regulated by pkd-mediated gap domain phosphorylation.Our results thus show that pkd-mediated phosphorylation of dlc1 on serine 807 negatively regulates dlc1 cellular function. | SIGNOR-169994 |
Q16763 | P12956 | 0 | relocalization | up-regulates activity | 0.347 | As shown in Figure 4, we found that Ku70 (Figure 4b) and Ku80 (Figure 4c) co-immunoprecipitated with UBE2S.>Taken together, these results demonstrate that ETO enhances the UBE2S–Ku70 interaction, and UBE2S can be recruited to the same sites of DSBs with Ku70 upon ETO treatment. | SIGNOR-265079 |
P07202 | O00358 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.382 | TSH regulates TPO expression through the cAMP pathway and acts with thyroid-specific transcription factors such as TTF-1, TTF-2 and Pax-8 | SIGNOR-267279 |
Q12772 | Q12770 | 0 | relocalization | up-regulates activity | 0.901 | SCAP contains two domains: an NH2-terminal membrane attachment domain with eight membrane-spanning helices (Nohturfft et al., 1998b) and a long COOH-terminal extension that contains multiple copies of a WD40 repeat sequence, which forms a propeller-like structure that binds to the COOH-terminal domains of the SREBPs, t... | SIGNOR-267502 |
Q13200 | P11309 | 0 | phosphorylation | up-regulates activity | 0.2 | Seven of these kinases (PIM1/2/3, MAP4K1/2, PKA, and NEK6) directly and robustly phosphorylated recombinant GST-Rpn1 at S361 in vitro (Fig. 3D and SI Appendix, Fig. S3 A and B). | SIGNOR-273895 |
Q13131 | O95239 | 1 | phosphorylation | up-regulates activity | 0.2 | We found that the strong direct substrate KIF4A is phosphorylated by AMPK at Ser801.Using in vitro kinase assays, we found that active AMPK and Aurora B phosphorylated KIF4A at Ser801 and Thr799 respectively in a time-dependent manner (Figure 5D). KIF4A is phosphoregulated by AMPK and Aurora B. Although AMPK phosphory... | SIGNOR-265991 |
P24941 | Q99708 | 1 | phosphorylation | up-regulates | 0.617 | Collectively, these findings thereby provided strong support for ctip thr-847 indeed being a cdk target. it is established that both cdk-dependent and checkpoint-dependent phosphorylations are required for activation of sae2/ctip in vivo | SIGNOR-183840 |
P31749 | Q00987 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.811 | Mitogen-induced activation of phosphatidylinositol 3-kinase (pi3-kinase) and its downstream target, the akt/pkb serine-threonine kinase, results in phosphorylation of mdm2 on serine 166 and serine 186. Phosphorylation on these sites is necessary for translocation of mdm2 from the cytoplasm into the nucleus.Both akt exp... | SIGNOR-116270 |
Q15653 | O43318 | 0 | phosphorylation | down-regulates | 0.515 | Overexpression oftak1together with its activator protein,tak1binding protein 1 (tab1), induced thenucleartranslocation of nf-kappa b p50/p65 heterodimer accompanied by the degradation of i kappa b alpha and i kappa b beta, and the expression of kappa b-dependent reporter gene. | SIGNOR-55719 |
P13674 | Q16665 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.314 | Hypoxia upregulates P4HA1 expression in PDAC PDOs through HIF1α. Our results show that the treatment of PDO4 and PDO11 cells with 10 μmol/L of PX-478 for 24 hours reduced the levels of P4HA1 in hypoxia (Fig. 2F), suggesting P4HA1 expression in hypoxia is regulated by HIF1α expression. | SIGNOR-279840 |
P15056 | P36507 | 1 | phosphorylation | up-regulates | 0.75 | We show that, consequently, b-raf interacts with mek-1 and mek-2 with a better affinity than does c-raf-1, thus strengthening the notion that b-raf is a stronger mek activator than c-raf-l. | SIGNOR-42664 |
O95139 | P06493 | 0 | 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 phosphoryla... | SIGNOR-275589 |
P27361 | P14921 | 1 | phosphorylation | up-regulates | 0.672 | We found that hgf/sf activates the erk1 map kinase, leading to the phosphorylation of the threonine 38 residue of ets1 | SIGNOR-116494 |
P23458 | Q13546 | 1 | phosphorylation | up-regulates activity | 0.2 | In addition , our results suggest JAK1 could be recruited to TNF-RSC to modulate RIPK1 activity .|In this study, we show that non-receptor tyrosine kinases JAK1 and SRC could phosphorylate RIPK1 on tyrosine 384 (Y384) in human RIPK1 (Y383 in mouse RIPK1), and serve as essential regulators of RIPK1 in the TNFR1 signalin... | SIGNOR-278948 |
P17252 | P35503 | 1 | phosphorylation | up-regulates activity | 0.2 | Curcumin and calphostin C suppressed the activity and phosphorylation of recombinant UGT1A3 expressed in Sf9 cells. These results indicate that UGT1A3 undergoes phosphorylation, which is required for its catalytic activity. Calphostin C is a highly specific protein kinase C (PKC) inhibitor, so three predicted PKC phosp... | SIGNOR-273823 |
P07948 | Q8N6F7 | 1 | phosphorylation | up-regulates activity | 0.245 | Herein, we demonstrate phosphorylation of HGAL by Syk and Lyn kinases at tyrosines Y80, Y86, Y106Y107, Y128, and Y148. Y148 (in black) was already phosphorylated before the addition of kinases. We demonstrate that Grb2 facilitates HGAL and Syk binding following BCR stimulation but does not affect the HGAL-mediated in... | SIGNOR-273560 |
P53396 | P17612 | 0 | phosphorylation | up-regulates activity | 0.309 | Phosphorylation of Recombinant Human ATP:Citrate Lyase by cAMP-Dependent Protein Kinase Abolishes Homotropic Allosteric Regulation of the Enzyme by Citrate and Increases the Enzyme Activity. Ser 454, which is phosphorylated by the catalytic subunit of cAMP-dependent protein kinase (PKA) | SIGNOR-250328 |
O60674 | P54764 | 0 | phosphorylation | up-regulates activity | 0.281 | EphA4 phosphorylates JAK2.|These findings suggest that EphA4 activates not only growth hormone receptor, as shown above, but also JAK2 by direct phosphorylation. | SIGNOR-279040 |
Q9Y297 | P19838 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.589 | Here we demonstrate that following IkappaB kinase (IkappaK)-mediated phosphorylation, the C-terminal domain of p105 (residues 918-934) serves as a recognition motif for the SCF(beta)(-TrCP) ubiquitin ligase.In vitro, SCF(beta)(-TrCP) specifically conjugates and promotes processing of phosphorylated p105. | SIGNOR-272570 |
P49841 | Q13485 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.398 | In the presence of FGF, Wnt potentiates TGF-β signaling by preventing Smad4 GSK3 phosphorylations that inhibit a transcriptional activation domain located in the linker region. | SIGNOR-276440 |
P68400 | P35638 | 1 | phosphorylation | down-regulates activity | 0.344 | CHOP transcription factor phosphorylation by casein kinase 2 inhibits transcriptional activation. | The serine to alanine substituted site CHOP mutant was not phosphorylated by CK2, indicating that serines 14–15 and 30–31 of CHOP are the CK2 phosphoacceptor sites | SIGNOR-250850 |
Q15349 | P25963 | 1 | phosphorylation | down-regulates | 0.267 | Rsk2 is activated by treatment with tumor necrosis factor-alfa (tnf-alfa) and directly phosphorylates ikbalfa at ser-32, leading to ikbalfa degradation. | SIGNOR-164790 |
Q9Y4H2 | P08069 | 0 | phosphorylation | up-regulates | 0.802 | Our results reveal that igf-1 receptors promote beta-cell development and survival through the irs-2 signalling pathway. | SIGNOR-70477 |
Q96GX5 | O43768 | 1 | phosphorylation | up-regulates activity | 0.732 | We identified cyclic adenosine monophosphateregulated phosphoprotein 19 (Arpp19) and -Endosulfine as two substrates of Gwl that, when phosphorylated by this kinase, associate with and inhibit PP2A, thus promoting mitotic entry. | SIGNOR-243690 |
P01106 | Q9ULJ6 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.362 | The N-terminal domain (NTD) of Zmiz1 is important for driving Myc transcription and proliferation […] Zmiz1 directly interacted with Notch1 via a tetratricopeptide repeat domain at a special class of Notch-regulatory sites. | SIGNOR-263939 |
P26358 | Q9H9S0 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.432 | Oct4 and Nanog upregulate Dnmt1 through direct binding to its promoter, thereby leading to the repressed expression of p16 and p21 and genes associated with development and lineage differentiation | SIGNOR-253157 |
P48730 | P12830 | 1 | phosphorylation | down-regulates activity | 0.27 | Casein kinase 1 is a novel negative regulator of E-cadherin-based cell-cell contacts|CK1 colocalizes with E-cadherin and phosphorylates the cytoplasmic domain of E-cadherin in vitro and in a cell culture system. We show that the major CK1 phosphorylation site of E-cadherin is serine 846 | SIGNOR-274046 |
P98177 | Q13043 | 0 | phosphorylation | up-regulates | 0.427 | The other major signaling modules that directly regulate the activity of the foxo factors include the stress-activated jun-n-terminal kinase (jnk), the mammalian ortholog of the ste20-like protein kinase (mst1), and the deacetylase sirt1 | SIGNOR-178193 |
P12931 | P18031 | 0 | dephosphorylation | up-regulates activity | 0.781 | Incubation of the inactivated c-Src with PTP1B results in a dose-dependent reactivation of c-Src tyrosine kinase activity. Incubation of c-Src with 2 or 10 g of PTP1B results in partial or full restoration of c-Src kinase activity, respectively. The activation is accompanied by dephosphorylation of c-Src, both of Tyr-4... | SIGNOR-245299 |
Q13451 | Q9H3Y6 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.267 | SRMS binds FKBP51 and phosphorylates tyrosine 54. Under nutrient-replete conditions, SRMS phosphorylates the PHLPP scaffold FK506-binding protein 51 (FKBP51), disrupts the FKBP51-PHLPP complex, and promotes FKBP51 degradation through the ubiquitin-proteasome pathway. | SIGNOR-277564 |
Q00535 | Q9ULW0 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.272 | CDK5-mediated phosphorylation and stabilization of TPX2 promotes hepatocellular tumorigenesis | SIGNOR-265100 |
Q15672 | P68400 | 0 | phosphorylation | up-regulates | 0.2 | Further investigation revealed that il-6 stabilizes twist in scchn cell lines through casein kinase 2 (ck2) phosphorylation of twist residues s18 and s20, and that this phosphorylation inhibits degradation of twist. | SIGNOR-173668 |
Q15831 | Q13153 | 1 | phosphorylation | down-regulates | 0.247 | Lkb1 suppresses p21-activated kinase-1 (pak1) by phosphorylation of thr109 in the p21-binding domain. | SIGNOR-164814 |
Q9BV73 | Q15154 | 0 | relocalization | up-regulates | 0.551 | Recruitment of nek2 and c-nap1 to the centrosome is dependent on pcm-1 | SIGNOR-133334 |
Q9Y281 | P53667 | 0 | phosphorylation | down-regulates activity | 0.703 | Cofilin is known to be a potent regulator of actin filament dynamics, and its ability to bind and depolymerize actin is abolished by phosphorylation of serine residue at 3;. Here we show that lim-kinase 1 (limk-1), a serine/threonine kinase containing lim and pdz domains, phosphorylates cofilin at ser 3, both in vitro ... | SIGNOR-58596 |
P18031 | Q16620 | 1 | dephosphorylation | down-regulates activity | 0.38 | Collectively, these data establish a direct enzyme-substrate interaction between PTP1B and phosphorylated Y705/706 (p-Y705/706) TRKB, the critical autophosphorylation sites that mediate BDNF-induced signaling.| Therefore, the data are consistent with a role of PTP1B as an inhibitor of BDNF/TRKB signaling | SIGNOR-264554 |
Q9UHC7 | Q8N726 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.366 | Biochemical analyses confirmed that MKRN1 targets p14ARF for ubiquitination and subsequent proteasome-dependent degradation.The Skp1-Cul1-F-box-protein44 (SCF(FBXO44)) complex ubiquitinates full-length BRCA1 in vitro. | SIGNOR-272036 |
Q14247 | Q05655 | 0 | phosphorylation | up-regulates activity | 0.246 | Together these findings demonstrate that phosphorylation of cortactin on S405 and S418 residues is required for its interaction with WAVE2 in MCP1-induced cytoskeleton remodeling, facilitating HASMC migration. In addition, the MCP1-induced cortactin phosp | SIGNOR-260890 |
O14757 | Q96E09 | 1 | phosphorylation | down-regulates activity | 0.2 | Knockout of FAM122A results in activation of PP2A-B55α, a phosphatase that dephosphorylates the WEE1 protein and rescues WEE1 from ubiquitin-mediated degradation. in tumor cells with oncogene-driven replication stress, CHK1 can directly phosphorylate FAM122A, leading to activation of the PP2A-B55α phosphatase and incre... | SIGNOR-266380 |
P49918 | P31749 | 0 | phosphorylation | down-regulates | 0.447 | Cdk inhibitor p57 (kip2) is downregulated by akt during her2-mediated tumorigenicityakt phosphorylates p57 on ser 282 or thr310. Akt activity results in destabilization of p57 by accelerating turnover rate of p57 and enhancing p57 ubiquitination | SIGNOR-252535 |
Q99459 | O00311 | 0 | phosphorylation | down-regulates activity | 0.344 | During SPOC, Dbf4 binds to Cdc5 and promotes Cdc7-mediated phosphorylation of Cdc5, which then presumably prevents Cdc5 from recognizing its substrates in the MEN pathway . | SIGNOR-280203 |
P50750 | P04637 | 1 | phosphorylation | up-regulates | 0.535 | We recently demonstrated that through their physical interaction, cdk9 phosphorylates p53 on ser-392, leading to p53 stability and accumulation | SIGNOR-201935 |
Q02447 | Q9UKX5 | 1 | null | up-regulates quantity by expression | 0.2 | We speculate that the "mesenchymal signature" of alpha11 integrin gene expression is controlled by the activity of Sp1/Sp3, fibroblast-specific combinations of Ets family members and yet unidentified enhancer-binding transcription factors. | SIGNOR-253351 |
O94901 | Q9H3D4 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Here we show that in the developing skin, epidermal progenitor cells of mice lacking p63 transcription factor display alterations in the nuclear shape accompanied by a marked decrease in expression of several nuclear envelope-associated components (Lamin B1, Lamin A/C, Sun1, Nesprin-3, Plectin) compared with controls. ... | SIGNOR-263278 |
P25490 | Q96GD4 | 0 | phosphorylation | up-regulates | 0.368 | Aurora b kinase phosphorylates yy1 on serine 184 and to a lesser extent serine 180 at the g2/m stage of the cell cycle (fig. 7). We show that yy1 is rapidly dephosphorylated as the cells exit mitosis, likely by pp1. Also, our data indicates that phosphorylation at serine 180 and serine 184 can affect the dna binding ac... | SIGNOR-200079 |
Q9NQC7 | O15111 | 0 | phosphorylation | up-regulates activity | 0.544 | The phosphorylation of cyld was completely abolished by the combined mutations of the entire serine cluster (m4, lane 5). Similar results were obtained with the ikk holoenzyme (fig. 4c, panel 1), recombinant ikk_ (panel 2), and recombinant ikk_cyld phosphorylation may serve as a mechanism to inactivate its traf2 deubiq... | SIGNOR-204692 |
P10276 | P17612 | 0 | phosphorylation | down-regulates activity | 0.405 | Mutagenesis of serine 219 (S219) and S369 at the PKA sites on RARA to either double alanines or double glutamic acids showed that both PKA sites are important for RARA activity. | SIGNOR-276281 |
P60953 | Q3KRB8 | 0 | gtpase-activating protein | down-regulates activity | 0.49 | 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... | SIGNOR-260468 |
P60484 | Q13882 | 1 | dephosphorylation | down-regulates activity | 0.416 | PTEN inhibits PTK6 activity and downstream signaling in prostate cancer cells.|Using an in vitro phosphatase assay, we observed that PTEN was able to dephosphorylate PTK6 at tyrosine residue 342 in a dose dependent manner. | SIGNOR-276975 |
O14965 | Q13153 | 0 | phosphorylation | up-regulates | 0.417 | The upstream pak1 kinase can phosphorylate aurora a at t288, autophosphorylation appears to be the essential mode of activation. Our experiments suggest that phosphorylation of t288 is important for regulation of the aurora2 kinase both for its activity and its stability | SIGNOR-205110 |
P50552 | Q9C026 | 0 | 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 |
P06493 | Q16659 | 1 | phosphorylation | up-regulates | 0.484 | Using ms analysis, we identified four novel phosphorylation sites, ser684, ser688, thr698 and ser705, located at the extreme c-terminus of erk3. All four sites are followed by a proline residue. We have shown that purified cyclin b-cdk1 (cyclindependent kinase 1) phosphorylates these sitesalanine substitution of the fo... | SIGNOR-164499 |
P35626 | P30411 | 1 | phosphorylation | down-regulates activity | 0.2 | Ligand-induced phosphorylation is found at Ser339 and Ser346/Ser348 that could be executed by several G protein-coupled receptor kinases. 32P labeling of peptide 3 containing pS346/pS348 was enhanced 1.5–3-fold as compared with mock-transfected cells in the order GRK6 < GRK5 < GRK2 < GRK4α < GRK3. several endogenous GR... | SIGNOR-251462 |
P11309 | Q16665 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.2 | PIM1 kinase directly phosphorylates HIF-1α at threonine 455, a previously uncharacterized site within its oxygen-dependent degradation domain. This phosphorylation event disrupts the ability of prolyl hydroxylases to bind and hydroxylate HIF-1α, interrupting its canonical degradation pathway and promoting constitutive ... | SIGNOR-277311 |
Q15746 | P10916 | 1 | phosphorylation | up-regulates activity | 0.72 | MLCK directly phosphorylates MLC2 and is a substrate for ERK1/2 ( ), thus providing a direct link between the Raf-MEK1/2-ERK1/2 module and MLC2.|These findings strongly suggest that the phosphorylation of MLC2 stimulated by MLCK and ROCK1/2 is an integral component of the biochemical signal transduction program that pr... | SIGNOR-279233 |
Q86VP1 | Q15025 | 0 | relocalization | up-regulates activity | 0.45 | ABIN1 interacted with the A20 regulatory molecule TAX1BP1 and was essential for the recruitment of TAX1BP1 and A20 to the noncanonical IkappaB kinases TBK1 and IKKi in response to poly(I:C) transfection. ABIN1 and TAX1BP1 together disrupted the interactions between the E3 ubiquitin ligase TRAF3 and TBK1/IKKi to attenua... | SIGNOR-275735 |
Q9Y6K1 | P42658 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | In the absence of Dnmt3b, Dnmt3a was associated with Dpp6 gene promoter and regulated its expression and methylation in P19 cells. | SIGNOR-268962 |
O60664 | P20645 | 1 | relocalization | up-regulates activity | 0.73 | TIP47 is present in cytosol and on endosomes and is required for MPR transport from endosomes to the trans-Golgi network in vitro and in vivo. TIP47 recognizes a phenylalanine/tryptophan signal in the tail of the cation-dependent MPR that is essential for its proper sorting within the endosomal pathway. These data sugg... | SIGNOR-253093 |
Q02790 | P68400 | 0 | phosphorylation | down-regulates activity | 0.343 | Thr-143 in the hinge I region was identified as the major phosphorylation site for CK2. | Most importantly, CK2-phosphorylated FKBP52 did not bind to HSP90 | SIGNOR-250865 |
Q9BSJ6 | Q13492 | 1 | relocalization | down-regulates | 0.2 | The cats interaction domain of calm was mapped to aa 221-335 of calm. This domain is contained in the calm/af10 fusion protein. Cats localizes to the nucleus and shows a preference for nucleoli. Expression of cats was able to markedly increase the nuclear localization of calm and of the leukemogenic fusion protein calm... | SIGNOR-144680 |
P22415 | O14672 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.27 | The promoter region of ADAM10 contains several transcription factor binding sites that can stimulate its transcription. These include binding sites for transcription factors SP1 and USF, and the spliced form of the X-box binding protein (XBP)-1 as well as a retinoic acid-responsive element | SIGNOR-259837 |
P48436 | Q05086 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.261 | We show that E6-AP ubiquitinates SOX9 in vitro and in vivo and that SOX9 levels are enhanced after addition of the proteasome inhibitor bortezomib. Similar, siRNA knockdown of E6-AP and the E2 ligase Ubc9 increased cellular SOX9 amounts, supporting the notion that SOX9 may be ubiquitinated in hypertrophic chondrocytes ... | SIGNOR-272134 |
Q9Y297 | P35222 | 1 | ubiquitination | down-regulates | 0.872 | Here we show that fwd1 (the mouse homologue of slimb/betatrcp), an f-box/wd40-repeat protein, specifically formed a multi-molecular complex with beta-catenin, axin, gsk-3beta and apc. Mutations at the signal-induced phosphorylation site of beta-catenin inhibited its association with fwd1. Fwd1 facilitated ubiquitinatio... | SIGNOR-67374 |
Q12888 | P06493 | 0 | phosphorylation | down-regulates activity | 0.599 | Nuclear import of 53BP1 is required for proper localization of 53BP1 and maintenance of genome integrity. 53BP1 has a classical bipartite nuclear localization signal (NLS) of sequence 1666-GKRKLITSEEERSPAKRGRKS-1686. Ser1678 within the 53BP1 NLS can be phosphorylated by CDK1/cyclin B, and a phosphomimetic substitution ... | SIGNOR-264412 |
P0DP23 | P00533 | 0 | phosphorylation | down-regulates | 0.404 | Phosphorylation of calmodulin by the epidermal-growth-factor-receptor tyrosine kinase. Phosphorylated calmodulin does not exhibit the characteristic ca2+ shift normally observed with calmodulin in electrophoretic gels, an observation that is consistent with this modification affecting the biological activity of the mol... | SIGNOR-24778 |
P31946 | Q05513 | 0 | phosphorylation | down-regulates activity | 0.368 | Our results with the 14-3-3 mutants indirectly imply a new phosphorylation site, 130Ser (and to a lesser extent 141Thr), in 14-3-3b that regulates the association}dissociation of 14-3-3b and PKC-f. | SIGNOR-249035 |
P11309 | Q99814 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.2 | PIM1 kinase directly phosphorylates HIF-1α at threonine 455, a previously uncharacterized site within its oxygen-dependent degradation domain. This phosphorylation event disrupts the ability of prolyl hydroxylases to bind and hydroxylate HIF-1α, interrupting its canonical degradation pathway and promoting constitutive ... | SIGNOR-277310 |
Q05513 | P08047 | 1 | phosphorylation | up-regulates | 0.484 | Here we have used a variety of approaches to identify 3 amino acids (thr668, ser670, and thr681) in the zinc finger domain of sp1 that are modified by pkc-zeta angiotensin ii, which activates pkc-? Phosphorylation (at thr410) via the angiotensin ii type 1 receptor, stimulates sp1 phosphorylation and increases sp1 bindi... | SIGNOR-160774 |
P00533 | P51692 | 1 | phosphorylation | up-regulates | 0.829 | Novel activation of stat5b in response to epidermal growth factor. novel activation of stat5b in response to epidermal growth factor. | SIGNOR-113393 |
P53041 | P08183 | 1 | dephosphorylation | down-regulates activity | 0.2 | Protein phosphatase complex PP5/PPP2R3C dephosphorylates P-glycoprotein/ABCB1 and down-regulates the expression and function|P-gp is known to be phosphorylated at Ser667, Ser671, and Ser683 by PKA; at Ser661, Ser667, and Ser671 by PKC; and at Ser683 by Pim-1|simultaneous expression of PP5 and PPP2R3C reduced the phosph... | SIGNOR-272507 |
P12931 | P07355 | 1 | phosphorylation | up-regulates | 0.547 | Translocation requires the presence of the annexin 2 binding partner p11 (s100a10) and the phosphorylation of annexin 2 at tyr23 through a src-like tyrosine kinase-dependent mechanism both in vitro and in vivo. | SIGNOR-127872 |
Q00526 | Q14934 | 1 | phosphorylation | up-regulates activity | 0.369 | CDK3 enhances the transactivation and transcription activity of NFAT3.|NFAT3 can be phosphorylated by CDK3 at Ser259, which is critical for its transactivation activity and cell transformation. | SIGNOR-278511 |
P48730 | O15055 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.869 | Human casein kinase Idelta phosphorylation of human circadian clock proteins period 1 and 2. We have now extended our previous studies to show that human casein kinase Idelta (hCKIdelta), the closest homologue to hCKIepsilon, associates with and phosphorylates hPER1 and causes protein instability. Furthermore, we obser... | SIGNOR-268000 |
P04637 | Q92630 | 0 | phosphorylation | up-regulates | 0.67 | Here, we demonstrate that the dual-specificity tyrosine-phosphorylation-regulated kinase 2 (dyrk2) directly phosphorylates p53 at ser46. these findings indicate that dyrk2 regulates p53 to induce apoptosis in response to dna damage. | SIGNOR-153544 |
Q15831 | P49841 | 1 | phosphorylation | down-regulates activity | 0.378 | In this regard, it was shown that LKB1 physically associates with PKC-zeta, which is known to inhibit GSK3beta kinase activity by promoting its phosphorylation.|Thus, inhibitory phosphorylation of GSK3beta by LKB1 and/or AKT may be a cardinal event leading to constitutive activation of Wnt and beta-catenin signaling (X... | SIGNOR-280148 |
P01112 | Q9P212 | 0 | guanine nucleotide exchange factor | up-regulates | 0.578 | The presence of a rasgef motif in the n terminus of plcepsilon suggests that plcepsilon can activate ras by acting as an exchange factor by promoting the exchange of gtp for bound gdp. | SIGNOR-82859 |
Q9NP77 | Q96GD4 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.254 | Here we report that Aurora B kinase directly interacts with and phosphorylates Ssu72, a new cohesin-binding phosphatase, at Ser 19 in vitro and in vivo. The Aurora B-mediated phosphorylation of Ssu72 causes the structural modification of Ssu72 protein, downregulates phosphatase activity and triggers the ubiquitin-depen... | SIGNOR-275529 |
O14757 | O00311 | 1 | phosphorylation | up-regulates | 0.734 | Chk1 directly phosphorylates essential s-phase kinases cdc7. | SIGNOR-163161 |
P37173 | O75604 | 1 | phosphorylation | up-regulates activity | 0.2 | Here, we report the role of USP2a in promoting metastasis by facilitating TGF-β-triggered signaling. USP2a interacts with TGFBR1 and TGFBR2 upon TGF-β stimulation and removes K33-linked polyubiquitin chains from Lys502 of TGFBR1, promoting the recruitment of SMAD2/3. Simultaneously, TGFBR2 phosphorylates Ser207/Ser225 ... | SIGNOR-273604 |
Q05655 | P28329 | 1 | phosphorylation | up-regulates quantity | 0.311 | Finally, basal ChAT phosphorylation in neurons is mediated predominantly by PKC at Ser-476, with PKC activation increasing phosphorylation at Ser-440 and enhancing ChAT activity. | SIGNOR-249272 |
Q04206 | Q96L73 | 0 | methylation | up-regulates | 0.463 | Fbxl11 and nsd1 have opposite effects on nf-kb; both bind to p65 subunit after activation of nf-kb. / nsd1 activates nf-kb and reverses the inhibitory effect of fbxl11 / these data confirm that fbxl11 and nsd1 constitute an enzyme pair that methylates and demethylates p65 on k218 and 221 in response to cytokine stimula... | SIGNOR-163454 |
O15344 | P67775 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.453 | MID1, mutated in Opitz syndrome, encodes an ubiquitin ligase that targets phosphatase 2A for degradation | SIGNOR-271467 |
Q15796 | Q92831 | 0 | acetylation | up-regulates | 0.578 | We demonstrate that both smad2 and smad3 are acetylated by the coactivators p300 and cbp in a tgfbeta-dependent manner. Smad2 is also acetylated by p/caf. The acetylation of smad2 was significantly higher than that of smad3. Lys(19) in the mh1 domain was identified as the major acetylated residue in both the long and s... | SIGNOR-150273 |
Q9UKI8 | P68431 | 1 | phosphorylation | up-regulates activity | 0.2 | Purified tlk1b phosphorylated histone h3 at s(10) with high specificity both in a mix of core histones and in isolated chromatin, suggesting that histone h3 is a physiological substrate for tlk1b. Phosphorylation of H3 has been linked to the activation of the immediate-early genes upon mitogenic stimulation, and to chr... | SIGNOR-107037 |
O43602 | P49841 | 0 | phosphorylation | up-regulates activity | 0.271 | Gsk3b phosphorylates dcx at the distinct site of ser327 and thereby contributes to dcx function in the restriction of axon branching. Together, our data define a jip3-regulated gsk3_/dcx signaling pathway that restricts axon branching in the mammalian brain.Gsk3_ induces the phosphorylation of dcx at ser327, which cont... | SIGNOR-170755 |
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