IdA stringlengths 6 21 | IdB stringlengths 6 21 | labels float64 0 2 | mechanism stringclasses 40 values | effect stringclasses 10 values | score float64 0.1 0.99 ⌀ | sentence stringlengths 10 1.63k ⌀ | signor_id stringlengths 12 14 |
|---|---|---|---|---|---|---|---|
P35968 | P35968 | 2 | phosphorylation | up-regulates | 0.2 | Binding of vegf to the receptor induces dimerisation and autophosphorylation of specific intracellular tyrosine residues. Activation of intracellular cascades results in proliferation, migration, survival and increased permeability. | SIGNOR-157093 |
P11362 | Q9Y2J4 | 1 | phosphorylation | up-regulates activity | 0.2 | These data support an idea that Amotl2 Tyr-103 can be phosphorylated by FGF receptor tyrosine kinase activity. We then determined whether Amotl2 Tyr-103 is required for its interaction with c-Src. |Amotl2 promotes MAPK/ERK activation via c-Src, which is dependent on phosphorylation of tyrosine residue at position 103 but independent of the C-terminal PDZ-binding domain. | SIGNOR-271869 |
Q9UGL1 | P68431 | 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-264302 |
O14842 | Q03113 | 1 | binding | up-regulates activity | 0.2 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-257338 |
P53350 | Q53GL7 | 1 | phosphorylation | up-regulates activity | 0.2 | PLK1, an important regulator for cell mitosis, directly interacts with and phosphorylates PARP10 at T601. PARP10 phosphorylation at T601 significantly decreases its binding to NEMO and disrupts its inhibition to NEMO ubiquitination, thereby enhancing the transcription activity of NF-κB toward multiple target genes and promoting HCC development. | SIGNOR-273728 |
P53671 | O43791 | 1 | phosphorylation | down-regulates activity | 0.2 | LIMK2 phosphorylates SPOP at S59, S171 and S226.|Together, these results depict that LIMK2-mediated SPOP degradation is a key mechanism that regulates AR stability. | SIGNOR-278338 |
P29375 | 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-264300 |
P59595 | P01100 | 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-260726 |
P0C6X7-PRO_0000037311 | Q13114 | 1 | deubiquitination | down-regulates activity | 0.2 | Overexpressing PLPro of SARS-CoV or MERS-CoV significantly reduced the expression of IFN-β and proinflammatory cytokines in MDA5-stimulated 293T cells (83).Also, SARS-CoVPLPro catalyzed deubiquitination of TNF-receptor-associated factor3 (TRAF3) and TRAF6, thereby suppressing IFN-I and proinflammatory cytokines induced by TLR7 agonist (63). The deubiquitinating activity of SARS-CoV PLPro also suppressed a constitutively active phosphomimetic IRF3, suggesting its involvement in the postactivation signaling of IRF3 | SIGNOR-260246 |
O00712 | P54764 | 1 | transcriptional regulation | up-regulates quantity | 0.2 | For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8) | SIGNOR-268901 |
Q9UNE7 | O14654 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | IRS4 was phosphorylated at Ser859 by CK1γ2 in vitro and in vivo, which promoted the polyubiquitination and degradation of IRS4 through the ubiquitin/lysosome pathway by the carboxyl terminus of Hsc70-interacting protein(CHIP). | SIGNOR-277616 |
P30530 | Q14511 | 1 | phosphorylation | up-regulates activity | 0.2 | Mechanistically, AXL phosphorylates NEDD9, leading to its binding to CRKII which in turn associates with and orchestrates the phosphorylation of the pseudo-kinase PEAK1.|These results reveal NEDD9 as a specific AXL substrate.We next validated whether AXL promotes canonical NEDD9 signaling. | SIGNOR-278905 |
P49841 | P52945 | 1 | phosphorylation | down-regulates quantity | 0.2 | We show that glucose levels modulate PDX1 protein phosphorylation at a novel C-terminal GSK3 consensus that maps to serines 268 and 272. A decrease in glucose levels triggers increased turnover of the PDX1 protein in a GSK3-dependent manner, such that PDX1 phosphomutants are refractory to the destabilizing effect of low glucose | SIGNOR-255566 |
Q13547 | O95471 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | ChIP assays revealed that SNAI1P is recruited on the CLDN7 gene promoter along with the co-repressor CtBP1 and the effector HDAC1.|These data further suggest that HDAC1 is involved in the SNAI1P-mediated repression of the human CLDN7 gene promoter. | SIGNOR-254106 |
P17612 | P25098 | 1 | phosphorylation | up-regulates activity | 0.2 | PKA directly phosphorylates GRK2 on serine 685. This modification increases G subunit binding to GRK2 and thus enhances the ability of the kinase to translocate to the membrane and phosphorylate the receptor. | SIGNOR-250334 |
Q05655 | Q96C90 | 1 | phosphorylation | up-regulates activity | 0.2 | Recombinant tagged PHI-1 was phosphorylated by protein kinase C at two sites, one a Ser and one a Thr; phosphorylation enhanced inhibitory potency 50-fold. | SIGNOR-265739 |
P28482 | O15067 | 1 | phosphorylation | up-regulates | 0.2 | T619 in PFAS is required to mediate ERK2-dependent purine synthesis stimulation. We demonstrate that ERK2, but not ERK1, phosphorylates the purine synthesis enzyme PFAS (phosphoribosylformylglycinamidine synthase) at T619 in cells to stimulate de novo purine synthesis. The expression of nonphosphorylatable PFAS (T619A) decreases purine synthesis, RAS-dependent cancer cell-colony formation, and tumor growth. Thus, ERK2-mediated PFAS phosphorylation facilitates the increase in nucleic acid synthesis required for anabolic cell growth and proliferation. | SIGNOR-267306 |
Q04759 | Q9UHD2 | 1 | phosphorylation | up-regulates activity | 0.2 | TBKBP1 recruits TBK1 to protein kinase C-theta (PKCθ) through a scaffold protein, CARD10. This enables PKCθ to phosphorylate TBK1 at Ser 716, a crucial step for TBK1 activation | SIGNOR-272472 |
P45984 | Q13526 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.2 | Mechanistically, the JNK kinases directly bind to and phosphorylate PIN1 at Ser115, and this phosphorylation prevents PIN1 mono-ubiquitination at Lys117 and its proteasomal degradation. | SIGNOR-277563 |
P51608 | O00548 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | As the first step to reveal how MeCP2 phosphorylation may regulate Notch signaling, we conducted chromatin immunoprecipitation (ChIP) experiment to determine whether the phosphor-mutant MeCP2 protein has altered promoter occupancy at the promoters of Dll1 and Notch1. We found increased binding of the phosphor-mutant protein at the promoters of both Dll1 and Notch1 | SIGNOR-264674 |
Q14469 | P36888 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | We then found that Hes1 directly bound to the promoter region of the FMS-like tyrosine kinase 3 (FLT3) gene and downregulated the promoter activity. | SIGNOR-261563 |
Q9NRC8 | Q9NR31 | 1 | deacetylation | up-regulates activity | 0.2 | SIRT7 interacts with the helicase DDX21. Deacetylation by SIRT7 is required for DDX21 activity and R-loop unwinding | SIGNOR-260978 |
O95819 | P42336 | 1 | phosphorylation | down-regulates activity | 0.2 | MST1/2 and HGK inhibit catalytic activity of p110α through phosphorylation at T1061 | SIGNOR-277921 |
O15111 | Q9Y261 | 1 | phosphorylation | down-regulates | 0.2 | Here, we show that ikk_, an important downstream kinase of tnf_, interacts with and phosphorylates foxa2 at s107/s111, thereby suppressing foxa2 transactivation activity and leading to decreased numb expression | SIGNOR-195316 |
Q13131 | Q13363 | 1 | phosphorylation | down-regulates | 0.2 | We found that an activated amp-activated protein kinase (ampk) phosphorylates ctbp1 on ser-158 upon metabolic stresses. Moreover, ampk-mediated phosphorylation of ctbp1 (s158) attenuates the repressive function of ctbp1 | SIGNOR-200250 |
P78317 | P25208 | 1 | binding | up-regulates activity | 0.2 | Coactivator RNF4 is involved in the GCH gene expression. Through serial deletion and mutagenesis studies of the GCH promoter, we defined the RNF4-responsive element on GCH proximal promoter as a CCAAT box. RNF4 did not possess specific DNA binding activity toward this CCAAT box, which suggests that RNF4 may be a coactivator of the CCAAT boxbinding protein nuclear factor Y (NF-Y). RNF4 is a coactivator for nuclear factor Y on GTP cyclohydrolase I proximal promoter. | SIGNOR-252230 |
Q96P68 | P63092 | 1 | binding | up-regulates activity | 0.2 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ‚â• -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ‚â• -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ‚â• -1.0. | SIGNOR-256770 |
Q99677 | P09471 | 1 | binding | up-regulates activity | 0.2 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-257258 |
P45452 | P02675 | 1 | cleavage | down-regulates quantity by destabilization | 0.2 | Matrix metalloproteinases collagenase-2, macrophage elastase, collagenase-3, and membrane type 1-matrix metalloproteinase impair clotting by degradation of fibrinogen and factor XII| We have now investigated the role of collagenase-2 (MMP-8), macrophage elastase (MMP-12), collagenase-3 (MMP-13), and membrane type 1-matrix metalloproteinase (MT1-MMP, MMP-14) in the degradation of fibrinogen and Factor XII of the plasma clotting system.|MMP-13 27YVATRDN g-chain| 20ADSGEGD a-chain| 124RNSVDXLNXN b-chain| 442LRTGKEKV a-chain | SIGNOR-263615 |
Q92831 | P0DPK2 | 1 | acetylation | down-regulates activity | 0.2 | The HAT module within the SAGA and ADA complexes acetylates histone H3, mainly on residues K9 and K14. | SIGNOR-269614 |
P08047 | Q92820 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Overexpression of Sp1 led to enhanced GGH promoter activity and GGH mRNA expression in allele-specific manners. These findings suggested that Sp1 acted as a positive regulator of human GGH transcription through the rs3758149 polymorphism in CEM/C1 cells. | SIGNOR-261350 |
O95382 | O95382 | 2 | phosphorylation | up-regulates activity | 0.2 | These results suggested that the induction of ASK2 phosphorylation in the presence of ASK1 is the consequence of autophosphorylation of ASK2. ASK1 thus appears to not only support the effective protein expression but also confer the kinase activity to ASK2. | SIGNOR-260774 |
P19525 | P19525 | 2 | phosphorylation | up-regulates activity | 0.2 | PKR autophosphorylates on Y101, Y162, and Y293 in vitro. Site-specific tyrosine phosphorylation is essential for efficient dsRNA-binding, dimerization, kinase activation and eIF2alpha phosphorylation of PKR. | SIGNOR-260784 |
Q8NFU7 | Q96SR6 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Furthermore, TET1 catalytic domain possessed demethylase activity in cancer cells, being able to inhibit the CpG methylation of tumor suppressor gene (TSG) promoters and reactivate their expression, such as SLIT2, ZNF382 and HOXA9. | SIGNOR-259095 |
Q9Y5X2 | O14920 | 1 | binding | up-regulates activity | 0.2 | IFNγ induced JAK1-mediated phosphorylation of SNX8 at Tyr95 and Tyr126, which promoted the recruitment of IKKβ to the JAK1 complex. | SIGNOR-273646 |
Q05655 | P21730 | 1 | phosphorylation | down-regulates | 0.2 | Whole cell phosphorylation assays with specific inhibitors as well as in vitro phosphorylation assays with recombinant enzymes and peptide substrates revealed that phosphorylation of ser-334 is regulated by protein kinase c-beta this study is among the first to analyze in a detailed manner, using a non-mutational approach, modifications of a defined phosphorylation site in a g protein-coupled receptor and to correlate these findings with functional parameters of receptor deactivation. | SIGNOR-73967 |
Q13882 | Q13017 | 1 | phosphorylation | up-regulates | 0.2 | Breast tumor kinase phosphorylates p190rhogap to regulate rho and ras and promote breast carcinoma growth, migration, and invasion. Brk phosphorylates p190 at the y(1105) residue both in vitro and in vivo, thereby promoting the association of p190 with p120rasgap (p120). As a consequence, brk stimulates p190 and attenuates p120 functions, leading to rhoa inactivation and ras activation, respectively. | SIGNOR-181452 |
P24941 | Q6PKG0 | 1 | phosphorylation | up-regulates activity | 0.2 | CDK2 phosphorylates LARP1 protein, regulates TOP-protein expression and LARP1\u2019s translational activity. | SIGNOR-279015 |
P23443 | Q16873 | 1 | phosphorylation | down-regulates activity | 0.2 | Here, we identified Ser(36) as the major p70S6k phosphorylation site, along with a low frequency site at Thr(40), using an in vitro phosphorylation assay combined with mass spectrometry. Cellular LTC4S activity is suppressed by PKC-mediated phosphorylation, and recently a downstream p70S6k was shown to play an important role in this process. | SIGNOR-277256 |
Q13131 | Q06210 | 1 | phosphorylation | down-regulates | 0.2 | Amp-activated protein kinase phosphorylates glutamine : fructose-6-phosphate amidotransferase 1 at ser243 to modulate its enzymatic activityhe 2-dg induced phosphorylation of gfat1 . The assay of the gfat enzymatic activity in the cell lysates indicated that the 2-dg-treatment inhibited the enzymatic activity | SIGNOR-183528 |
P54762 | P54762 | 2 | phosphorylation | up-regulates activity | 0.2 | Co-immunoprecipitation was used to confirm the interaction of Grb7 with the cytoplasmic domain of EphB1 as well as the full-length receptor in intact cells. This interaction is mediated by the SH2 domain of Grb7 and requires tyrosine autophosphorylation of EphB1. We also found that EphB1 could phosphorylate Grb7 and mutation of either Tyr-928 or Tyr-594 to Phe decreased this activity. | SIGNOR-251123 |
Q02447 | P07288 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | We characterized four Sp1/Sp3 binding sites in the proximal promoter of the PSA gene. In a luciferase assay, these sites contributed to the basal promoter activity in prostate cancer cells. In an electrophoretic mobility shift assay and chromatin immunoprecipitation assay, we confirmed that Sp1 and Sp3 bind to these sites. Overexpression of wild-type Sp1 and Sp3 further upregulated the promoter activity, whereas overexpression of the Sp1 dominant-negative form or addition of mithramycin A significantly reduced the promoter activity and the endogenous mRNA level of PSA. | SIGNOR-253665 |
P17252 | O95243 | 1 | phosphorylation | up-regulates activity | 0.2 | Phosphorylation of MBD4 promotes 5-meC glycosylase activity Further evidence emerged to support the involvement of MBD4 in active demethylation. Protein-kinase C phosphorylation of MBD4 at two specific serine residues (165 and 262) following parathyroid hormone stimulation was shown to promote demethylation within the CYP27B1 gene promoter [12] | SIGNOR-275672 |
O60729 | Q93008 | 1 | dephosphorylation | down-regulates quantity by destabilization | 0.2 | Here, we find that CDC14B antagonizes CDK1-mediated activating mitotic phosphorylation of the deubiquitinase USP9X at serine residue 2563, which we show to be essential for USP9X to mediate mitotic survival. Starting from an unbiased proteome-wide screening approach, we specify Wilms' tumor protein 1 (WT1) as the relevant substrate that becomes deubiquitylated and stabilized by serine 2563-phosphorylated USP9X in mitosis. | SIGNOR-275613 |
P48730 | Q02880 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Specifically, DNA damage signal, triggered by teniposide (VM-26) treatment, activates ATM, cooperating with CK1 to phosphorylate TOP2β on Ser1134 and Ser1130, respectively, in a canonical degron motif to facilitate β-TrCP binding and subsequent degradation.CK1 binds with and phosphorylates TOP2β at Ser1130 to promote its degradation by VM-26. | SIGNOR-277509 |
P68400 | Q12913 | 1 | phosphorylation | up-regulates activity | 0.2 | CK2-dependent phosphorylation of DEP-1 T1318 promotes Y1320 phosphorylation and Src activation upon VEGF stimulation. | SIGNOR-277876 |
P51812 | Q8IX03 | 1 | phosphorylation | up-regulates | 0.2 | Moreover, we found that rsk1/2 specifically phosphorylates kibra at two highly conserved sites (thr(929) and ser(947)) in vitro and in cells. Rsk-mediated phosphorylation is required for kibra binding to rsk1, but not rsk2. | SIGNOR-203302 |
Q14493 | Q71DI3 | 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-265414 |
Q5T0W9 | P48730 | 1 | binding | up-regulates quantity | 0.2 | We identified members of the FAM83 family of proteins as partners of CK1 in cells. All eight members of the FAM83 family (FAM83A–H) interacted with the α and α-like isoforms of CK1; FAM83A, -B, -E, and -H also interacted with the δ and ε isoforms of CK1. The intrinsic catalytic activity of CK1 is not affected by or required for the association of CK1 with FAM83 proteins. Our findings imply that the DUF1669 domains of FAM83 proteins anchor CK1 α, α-like, δ, and ε isoforms in specific subcellular compartments and potentially mediate their association with substrates. | SIGNOR-273766 |
P03209 | P01574 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | Epstein-Barr Virus BRLF1 Inhibits Transcription of IRF3 and IRF7 and Suppresses Induction of Interferon-β. These results suggest that EBV Rta is capable of regulating the activation of the IFN-β promoter. | SIGNOR-266646 |
Q96M91 | Q8TE73 | 1 | binding | up-regulates activity | 0.2 | CFAP53 likely facilitates the transport of TTC25 and the dyneins into cilia. CFAP53 at the centriolar satellites may form a complex with TTC25 and ODAs, including DNAH5 and DNAH11, and regulate their trafficking into the cilium (Fig 10B). | SIGNOR-265544 |
Q9H1B7 | P35222 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | FOXF2 directly bound the promoter of E3 ligase interferon regulatory factor 2-binding protein-like (IRF2BPL) and induced its transcriptional expression. IRF2BPL in turn interacted with β-catenin, increasing its ubiquitination and degradation. | SIGNOR-267153 |
Q9UQM7 | P15036 | 1 | phosphorylation | down-regulates | 0.2 | Camkii caused ets-2 phosphorylation.Serine 246, 310, and 313 were the targets. Camkii to phosphorylates ets-2, thus altering ets-2 binding to its downstream promoters | SIGNOR-183596 |
Q99835 | P62879 | 1 | binding | up-regulates | 0.2 | Consistent with its predicted topology, smo couples to a specific family of inhibitory g protein (gis) to regulate hh signaling. | SIGNOR-199177 |
Q8IXQ9 | P38117 | 1 | methylation | down-regulates activity | 0.2 | Accordingly, we found that METTL20-mediated methylation of ETFβ in vitro reduced its ability to receive electrons from the medium chain acyl-CoA dehydrogenase and the glutaryl-CoA dehydrogenase. In conclusion, the present study establishes METTL20 as the first human KMT localized to mitochondria and suggests that it may regulate cellular metabolism through modulating the interaction between its substrate ETFβ and dehydrogenases. | SIGNOR-269450 |
P05129 | P43629 | 1 | phosphorylation | down-regulates | 0.2 | Functional studies of the wild-type receptor and serine/threonine mutants indicated that phosphorylation of ser(394) by protein kinase c slightly suppresses kir3dl1 inhibitory function, and reduces receptor internalization and turnover. | SIGNOR-158133 |
P49674 | Q13541 | 1 | phosphorylation | down-regulates | 0.2 | Mechanistic investigations showed that ck1_ interacted with and phosphorylated 4e-bp1 at two novel sites t41 and t50, which were essential for 4e-bp1 inactivation along with increased mrna translation and cell proliferation. | SIGNOR-203240 |
P43320 | P43320 | 2 | binding | up-regulates activity | 0.2 | βB2-crystallin is the major component of β-crystallin and is a dimer at low concentrations. At high concentrations or in the lens, βB2-crystallin forms hetero-oligomers with other β-crystallins. These oligomeric β-crystallins further participate in the formation of a supramolecular assembly that is important in lens function-lens transparency. | SIGNOR-252154 |
P53350 | P49959 | 1 | phosphorylation | down-regulates activity | 0.2 | Plk1 phosphorylates Mre11 at S649.Mre11 phosphorylation at S649/S688 inhibits its binding to dsDNA and antagonizes the ATM signaling. | SIGNOR-265943 |
P49840 | P49840 | 2 | phosphorylation | up-regulates | 0.2 | Gsk3a is activated by phosphorylation at tyr-279. | SIGNOR-180035 |
Q15139 | P35236 | 1 | phosphorylation | up-regulates activity | 0.2 | HePTP is phosphorylated by PKC isozymes at Ser-225 in vitro. While all isozymes phosphorylated Ser-225 predominantly and Ser-113 to a lesser extent (Fig. (Fig.5),5), they differed strikingly in how much 32P they incorporated into HePTP during the 30-min assay. PKC θ was the most efficient, while PKC ζ and PKC μ were clearly less potent; PKC δ, ɛ, and η were quite inefficient. | SIGNOR-276046 |
P49674 | P49674 | 2 | phosphorylation | down-regulates activity | 0.2 | Amino acids Ser-323, Thr-325, Thr-334, Thr-337, Ser-368, Ser-405, Thr-407, and Ser-408 in the carboxyl-terminal tail of CKIepsilon were identified as probable in vivo autophosphorylation sites. A recombinant CKIepsilon protein with serine and threonine to alanine mutations eliminating these autophosphorylation sites was 8-fold more active than wild-type CKIepsilon using IkappaBalpha as a substrate. T | SIGNOR-250813 |
P00533 | Q92952 | 1 | phosphorylation | up-regulates activity | 0.2 | These results demonstrate the novel information that hSKCa1 channels are inhibited by genistein, T25 and AG556 via EGFR tyrosine kinase inhibition, which is related to the phosphorylation of Tyr(109) in the N-terminus. | SIGNOR-276490 |
P16519 | P01189-PRO_0000024969 | 1 | cleavage | up-regulates quantity | 0.2 | POMC is post-translationally cleaved by prohormone convertase enzymes 1 and 2 (PC1, PC2) into ACTH, an N-terminal glycopeptide | SIGNOR-268725 |
P15289 | P68871 | 1 | acetylation | up-regulates activity | 0.2 | ASA acetylates hemoglobin. Purified acetylated hemoglobin had a slightly increased oxygen affinity and decreased heme-heme interaction. | SIGNOR-251772 |
Q9UN74 | P05556 | 1 | binding | up-regulates activity | 0.2 | The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion. | SIGNOR-265665 |
O15550 | P68431 | 1 | demethylation | down-regulates activity | 0.2 | Ubiquitously Transcribed Tetratricopeptide Repeat on chromosome X (UTX) and Jumonji D3 (JMJD3) as novel histone demethylases that catalyze the removal of di- and trimethyl groups on histone H3 lysine 27, thereby promoting target gene activation. | SIGNOR-260017 |
P04637 | Q9C0B5 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Mechanistic investigations revealed that mutant p53 transcriptionally upregulated ZDHHC5 along with the nuclear transcription factor NF-Y | SIGNOR-261150 |
O75582 | O75582 | 2 | phosphorylation | up-regulates activity | 0.2 | Msk1 can autophosphorylate on at least six sites: ser-212, ser-376, ser-381, ser-750, ser-752 and ser-758. Of these sites, the n-terminal t-loop residue ser-212 and the 'hydrophobic motif' ser-376 are phosphorylated by the c-terminal kinase domain of msk1, and their phosphorylation is essential for the catalytic activity of the n-terminal kinase domain of msk1 and therefore for the phosphorylation of msk1 substrates in vitro. | SIGNOR-131395 |
Q5D1E8 | P23769 | 1 | post transcriptional regulation | up-regulates quantity | 0.2 | Here, we show that Regnase-1 regulates self-renewal of HSPCs through modulating the stability of Gata2 and Tal1 mRNA | SIGNOR-259943 |
P17252 | P32004 | 1 | phosphorylation | down-regulates activity | 0.2 | CKII phosphorylates T1172 of the L1 CD and phosphorylation of T1172 is responsible for loss of 2C2 signal. | SIGNOR-276283 |
P11802 | P19484 | 1 | phosphorylation | up-regulates activity | 0.2 | CDK4 and CDK6 phosphorylate TFEB and TFE3. | SIGNOR-279450 |
Q9UKI8 | Q8IW41 | 1 | phosphorylation | up-regulates activity | 0.2 | We established that TLK1 phosphorylates MK5 on three residues (S160, S354 and S386), resulting in MK5 activation, and additionally, mobility shifts of MK5 also supported its phosphorylation by TLK1 in transfected HEK 293 cells. | SIGNOR-276747 |
Q9Y5I2 | Q9Y5G6 | 1 | binding | up-regulates activity | 0.2 | The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion. They also form oligomers with Pcdh-gamma proteins at the same membrane sites. | SIGNOR-265709 |
P18075 | P18075 | 2 | binding | up-regulates | 0.2 | Bmps are dimeric proteins with a single inter-chain disulfide bond. The dimeric conformation is an absolute requirement for the biological action and interac- tion with receptors | SIGNOR-236172 |
P83916 | P84243 | 1 | binding | up-regulates activity | 0.2 | A core characteristic of heterochromatin is its association with heterochromatin protein 1 (HP1) proteins, a highly conserved family of chromosomal proteins that bind to di- and trimethylated H3K9 via a conserved N-terminal domain called the chromodomain (CD) HP1 proteins are a highly conserved family of eukaryotic proteins that bind to methylated histone H3 lysine 9 (H3K9) and are required for heterochromatic gene silencing. | SIGNOR-264491 |
Q14493 | Q6NXT2 | 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-265420 |
Q6ZP65 | O43896 | 1 | binding | up-regulates activity | 0.2 | BICDR-1 interacts with the dynein/dynactin motor complex. In young neurons, BICDR-1 accumulates Rab6 secretory vesicles around the centrosome, restricts anterograde secretory transport and inhibits neuritogenesis. Later during development, BICDR-1 expression is strongly reduced, which permits anterograde secretory transport required for neurite outgrowth. These results indicate an important role for BICDR-1 as temporal regulator of secretory trafficking during the early phase of neuronal differentiation. These results show that BICDR-1 regulates recruitment and/or activity of the anterograde kinesin motor Kif1C on Rab6 secretory carriers. | SIGNOR-266876 |
Q13153 | Q13153 | 2 | phosphorylation | up-regulates activity | 0.2 | Cdc42 and Rac1 cause alpha-PAK autophosphorylation and kinase activation. | SIGNOR-250219 |
Q9UPZ9 | Q9UPZ9 | 2 | phosphorylation | up-regulates | 0.2 | Ick is activated by dual phosphorylation of the tdy motif. Phosphorylation of tyr-159 in the tdy motif requires ick autokinase activity | SIGNOR-138424 |
Q9UPS6 | P84243 | 1 | methylation | down-regulates activity | 0.2 | SETD1B encodes a lysine-specific methyltransferase that assists in transcriptional activation of genes by depositing H3K4 methyl marks. | SIGNOR-265578 |
Q92570 | Q9BXH1 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Over-expression of NR4A3 attenuated proliferation of cancer cells and promoted apoptosis by augmenting the expression of pro-apoptotic genes, PUMA and Bax. | SIGNOR-259396 |
Q15139 | P48426 | 1 | phosphorylation | down-regulates | 0.2 | We conclude that the type ii pip kinases are physiological targets for pkd phosphorylation, and that this modification is likely to regulate inositol lipid turnover by inhibition of these lipid kinases. | SIGNOR-145370 |
Q9NRC8 | Q5TEC6 | 1 | deacetylation | up-regulates activity | 0.2 | Besides confirming the previously reported histone H3K18 deacylation activity, our results revealed that SIRT7 has an astonishingly high activity to catalyze deacylation of H3K36 and is also catalytically active to deacylate H3K37. | SIGNOR-275883 |
Q13315 | Q15109 | 1 | phosphorylation | up-regulates activity | 0.2 | RAGE is phosphorylated at Serine 376 and Serine 389 by the ATM kinase and is recruited to the site of DNA-DSBs via an early DNA damage response. | SIGNOR-278907 |
Q8NEV1 | Q99250 | 1 | phosphorylation | up-regulates activity | 0.2 | We found that the ankyrin-binding motif of Na(v)1.2 that determines channel concentration at the AIS depends on a glutamate residue (E1111), but also on several serine residues (S1112, S1124, and S1126). We showed that phosphorylation of these residues by protein kinase CK2 (CK2) regulates Na(v) channel interaction with ankyrins. | inhibition of CK2 activity reduced sodium channel accumulation at the AIS of neurons. In conclusion, CK2 contributes to sodium channel organization by regulating their interaction with ankyrin G. | SIGNOR-275755 |
P63279 | O95243 | 1 | sumoylation | up-regulates activity | 0.2 | MBD4 is sumoylated at three main sites: K137, K215 and K377.|Sumoylation increases the G:T repair activity of MBD4 in cell extracts.|we conducted an in vitrosumoylation assay, employing recombinant activating E1 (Aos1-Uba2) and conjugating E2 (Ubc9) enzymes, along with recombinant YFP-SUMO1 and MBD4 or, as positive control for sumoylation, TDG (Fig. 2D). These results indicate that MBD4 is sumoylated in vivo and in vitro. | SIGNOR-275678 |
P11308 | P04628 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Interestingly, our data showed that ERG drastically induced Wnt ligand gene expression. | SIGNOR-261597 |
P47900 | P38405 | 1 | binding | up-regulates activity | 0.2 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-256943 |
P04792 | P30793 | 1 | binding | up-regulates quantity by stabilization | 0.2 | GTP cyclohydrolase I (GCH), an oligomeric protein composed of 10 identical subunits, is required for the synthesis of neurotransmitters; mutations in GCH are associated with dopa-responsive dystonia (DRD) and hyperphenylalaninemia. Mutated GCH proteins are unstable and prone to dominant-negative effect. We show herein that expression of the GCH mutant GCH-201E or the splicing variant GCH-II caused intracellular inclusion bodies. When Hsp27 was expressed together with the GCH mutants, Hsp27 expression decreased the formation of inclusion bodies by GCH (as assessed by immunofluorescence) and decreased the amount of insoluble GCH mutant proteins (as assessed by Western blot). we demonstrated that Hsp27 increases the expression of the wild-type GCH protein, causes the appearance of the soluble GCH-II protein, and decreases the quantities of insoluble mutated GCH protein. Therefore, it is likely that Hsp27 improves the folding of mutated GCH proteins, so they can stay in free cytosolic compartment. | SIGNOR-252222 |
Q9HAZ1 | Q13285 | 1 | phosphorylation | up-regulates activity | 0.2 | Immunoblotting analyses showed that the phosphorylation status of NR5A1 at Ser203 was attenuated by the CLK1/4 inhibitor. | SIGNOR-274117 |
P17252 | Q8TD43 | 1 | phosphorylation | up-regulates | 0.2 | Phorbol ester-induced activation of protein kinase c (pkc) increased the ca(2+) sensitivity of wild-type trpm4 but not of two mutants mutated at putative pkc phosphorylation sites. | SIGNOR-132243 |
Q9UBI6 | Q9P212 | 1 | binding | up-regulates | 0.2 | In the non-canonical wntpathway, frizzled uses galfaq or galfai and gbetagamma dimers to activate phospholipase c (plc), resulting in protein kinase c (pkc) activation and calcium mobilization that regulates the transcription factor nfat, and frizzled also signals through the small gtpases rho and rac to c-jun n-terminal kinase (jnk), which activates the ap1 transcription factor | SIGNOR-152612 |
Q5S007 | Q9P2J5 | 1 | phosphorylation | down-regulates activity | 0.2 | In this study, we elucidated that leucyl-tRNA synthetase (LRS) was an LRRK2 kinase substrate and identified T293 as an LRRK2 phosphorylation site. LRRK2-meidated LRS phosphorylation or G2019S can lead to impairment of LRS editing, increased ER stress, and accumulation of autophagy markers. | SIGNOR-277417 |
P00519 | O15269 | 1 | phosphorylation | down-regulates | 0.2 | We demonstrated that the er-resident human protein serine palmitoyltransferase long chain-1 (sptlc1), which is the first enzyme of sphingolipid biosynthesis, is phosphorylated at tyr(164) by the tyrosine kinase abl. this occurred through the specific abl-mediated phosphorylation of sptlc1 on tyr164, leading to the attenuation of its activity. | SIGNOR-202003 |
Q9Y653 | Q03113 | 1 | binding | up-regulates activity | 0.2 | Binding of collagen III to ADGRG1 provides a canonical example of adhesion GPCR interactions with ECM proteins (Luo et al., 2011). Identified by an in vitro biotinylation/proteomics approach, extracellular interactions with collagen III were subsequently proven capable of activating ADGRG1-mediated signaling via Gα12/13 followed by RhoA activation to regulate corticogenesis | SIGNOR-272344 |
Q9NX47 | Q9NX47 | 2 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | Rapid degradation of MITOL by autoubiquitination activity. Taken together, these results suggested that MITOL strictly controls its protein expression level by rapid degradation of MITOL through the PHD-dependent autoubiquitination activity. | SIGNOR-271895 |
Q9UIF8 | P68431 | 1 | binding | down-regulates activity | 0.2 | The BAZ2B bromodomain has been shown to bind to acetylated H3K14 (H3K14ac), whose presence at promoter regions is generally associated with gene activation. This suggests a potential role for BAZ2B in transcriptional activation. | SIGNOR-266622 |
Q8IYT8 | P19367 | 1 | phosphorylation | up-regulates activity | 0.2 | Here, we demonstrate that, during deprivation of amino acid and growth factors, ULK1/2 directly phosphorylate key glycolytic enzymes including hexokinase (HK), phosphofructokinase 1 (PFK1), enolase 1 (ENO1), and the gluconeogenic enzyme fructose-1,6-bisphosphatase (FBP1).Phosphorylation of these enzymes leads to enhanced HK activity to sustain glucose uptake but reduced activity of FBP1 to block the gluconeogenic route and reduced activity of PFK1 and ENO1 to moderate drop of glucose-6-phosphate and to repartition more carbon flux to pentose phosphate pathway (PPP), maintaining cellular energy and redox homeostasis at cellular and organismal levels.Similar results were also obtained using ULK2 as the kinase (data not shown). | SIGNOR-274042 |
Q05655 | P53004 | 1 | phosphorylation | up-regulates activity | 0.2 | LC-MS/MS analysis of PKCdelta-activated intact hBVR identified phosphorylated serine positions 21, 33, 230, and 237, corresponding to the hBVR Src homology-2 domain motif (Ser(230) and Ser(237)), flanking the ATP-binding motif (Ser(21)) and in PHPS sequence (Ser(33)) as targets of PKCdelta. |PKCdelta potentiated hBVR reductase activity and accelerated the rate of bilirubin formation. | SIGNOR-275525 |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.