IdA stringlengths 6 21 | IdB stringlengths 6 21 | labels int64 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 |
|---|---|---|---|---|---|---|---|
P04637 | O95831 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.351 | P53 regulates basal expression of AIF and SCO2 and facilitates oxidative phosphorylation. The expression of GLUT1, GLUT4, and HK2 is negatively regulated by p53, whereas TIGAR expression is induced by p53. The net result of p53-mediated regulation of these glycolytic enzymes is the suppression of glycolysis. In addition, p53 directly binds and inhibits G6PD activity and downregulates the pentose phosphate pathway. | SIGNOR-267462 |
Q15121 | O43464 | 2 | binding | down-regulates | 0.485 | Htra2 promotes cell death by binding and degrading the anti-apoptotic protein pea15 | SIGNOR-126966 |
P01303 | P49146 | 2 | binding | up-regulates | 0.837 | Analogs of npy and pyy have been synthesized that contain a proline residue in position 34 of the molecule, i.e., [leu31, pro34]npy (fuhlendorff et al., 1990) or [pro34]pyy (grandt et al., 1994b), and are much more potent at y1 than y2receptors. | SIGNOR-56568 |
P53350 | P25490 | 1 | phosphorylation | up-regulates | 0.392 | More recently, we identified and mapped multiple phosphorylation sites in yy1, including, threonine 39, serine 118, serine 247, threonine 348 and threonine 378. The first kinase proven to phosphorylate yy1 in vivo was plk1, which phosphorylates threonine 39 during g2/m stage of the cell cycle [25]. Ck2_ is another kinase identified as constitutively phosphorylating yy1 at serine 118. This modification protects yy1 cleavage by caspase 7 during apoptosis | SIGNOR-200087 |
P16885 | P38936 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.2 | Phosphorylation at Ser-146 by PKCδ increases p21 stability | SIGNOR-262963 |
Q9UBS5 | P28482 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.2 | We found that, in addition to CaMKIIβ, also ERK1/2 is involved in the degradation pathway of GABAB receptors under physiological and ischemic conditions. In contrast to our previous view, CaMKIIβ does not appear to directly phosphorylate S867. Instead, the data support a mechanism in which CaMKIIβ activates ERK1/2, which then phosphorylates S867 and T872 in GABAB1. | SIGNOR-277857 |
P16112 | P08254 | 0 | cleavage | down-regulates quantity by destabilization | 0.738 | Aggrecan Degradation in Human Cartilage Evidence for both Matrix Metalloproteinase and Aggrecanase Activity in Normal, Osteoarthritic, and Rheumatoid Joints|Stromelysin-1 (MMP-3), as well as other MMPs, cleave aggrecan in the interglobular domain between Asn341 and Phe342 to generate a G1 fragment with the COOH terminus VDIPEN341 (11–13). This fragment has been isolated and identified by NH2-terminal sequence analysis from human OA cartilage (11). A second proteolytic activity identified as “aggrecanase” also cleaves aggrecan in the interglobular domain, but between Glu373 and Ala374 (19–24), generating a G1 fragment with a COOH terminus of NITEGE374 | SIGNOR-266986 |
Q8N2Q7 | P58400 | 2 | binding | up-regulates activity | 0.84 | Pre- and postsynaptic plasma membranes are always precisely aligned, and are separated by a synaptic cleft of ~20 nm. The cleft contains an undefined proteinaceous material in the middle, and is presumably bridged by synaptic cell-adhesion molecules such as Nrxns and Nlgns that align the pre- and postsynaptic elements and mediate trans-synaptic signaling.|Nlgns bind to both alpha- and beta-Nrxns with nanomolar affinities; binding involves the sixth LNS-domain of alpha-Nrxns which corresponds to the only LNS-domain of beta-Nrxns52. The binding affinities differ characteristically between various pairs of Nlgns and Nrxns, and are controlled by alternative splicing of both Nrxns and Nlgns (Figure 1c) | SIGNOR-264149 |
Q8N6P7 | Q6X9E4 | 2 | binding | down-regulates quantity by destabilization | 0.342 | FBXW12 causes depletion of endogenous and plasmid-derived IL-22R in lung epithelia, binds the E3 ligase constituent Skp-1, and facilitates ubiquitination of IL-22R in vitro. | SIGNOR-272426 |
Q9UKX5 | P08047 | 0 | 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-253350 |
P18031 | P35222 | 1 | dephosphorylation | up-regulates activity | 0.66 | PTP1B modulates the association of beta-catenin with N-cadherin through binding to an adjacent and partially overlapping target site.|The nonreceptor tyrosine phosphatase PTP1B associates with the cytoplasmic domain of N-cadherin and may regulate cadherin function through dephosphorylation of beta-catenin.|Thus, interaction of PTP1B with N-cadherin is essential for its association with beta-catenin, stable expression at the cell surface, and consequently, cadherin function. | SIGNOR-277121 |
Q9UBY5 | P09471 | 2 | binding | up-regulates activity | 0.25 | 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-257141 |
P15498 | P22681 | 2 | binding | up-regulates | 0.692 | Hese data imply that c-cbl is a molecular adapter that regulates the function of vav | SIGNOR-49188 |
P54821 | O15525 | 2 | binding | down-regulates activity | 0.338 | Hoxd12 and MHox, that interact with v-/c-Maf, using the phage display method. The Hox proteins also could associate with the other Maf protein family members, MafB, MafK, MafF, and MafG, but not with Jun and Fos. The Hox proteins negatively regulated the DNA binding, transactivation and cell-transforming abilities of Maf. | SIGNOR-221961 |
Q99661 | P06493 | 0 | phosphorylation | down-regulates | 0.686 | We show here that cyclin-dependent kinase 1 (cdk1) phosphorylates t537 in the core domain of mcak and attenuates its microtubule-destabilizing activity in vitro and in vivo. Phosphorylation of mcak by cdk1 promotes the release of mcak from centrosomes and is required for proper spindle formation. | SIGNOR-164761 |
P43405 | P37840 | 1 | phosphorylation | down-regulates | 0.532 | Here, we show that alpha-synuclein (alpha-syn) is an outstanding substrate for the protein tyrosine kinase p72syk (syk), which phosphorylates three tyrosyl residues in its c-terminal domain (y-125, y-133, and y-136), here, we show that _-syn is an outstanding substrate for syk and that once it is tyrosine phosphorylated, it loses the ability to form oligomers. | SIGNOR-113065 |
P09471 | Q8TDV5 | 2 | binding | up-regulates activity | 0.25 | 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-257241 |
Q15173 | P10415 | 1 | dephosphorylation | down-regulates | 0.323 | Pp2a directly interacts with the bh4 domain of bcl2 as a docking site to potentially bridge pp2a to bcl2's flexible loop domain containing the target serine 70 phosphorylation site. | SIGNOR-181559 |
P35568 | P06213 | 0 | phosphorylation | up-regulates activity | 0.914 | All known IRS proteins contain multiple YXXM motifs that upon phosphorylation by activated insulin receptors A previous study using phosphopeptides suggested that tyrosine-phosphorylated YXXM motifs at positions 608 and 939 in rat IRS-1 bind with high affinity to SH2 domains of p85, and motifs at positions 460 and 987 bind with lower affinity (10). | SIGNOR-235975 |
Q9Y6R4 | P52564 | 1 | phosphorylation | up-regulates activity | 0.657 | When truncated mapkkk4 (deltamapkkk4) was overexpressed in hek293 cells, it was constitutively activeco-expressed map kinase kinase (mkk)-1, mkk-4, mkk-3 and mkk-6 were activated in vivo by deltamapkkk4. All of the above mkks purified from escherichia coli were phosphorylated and activated by deltamapkkk4 immunoprecipitates in vitro. | SIGNOR-62372 |
Q9NP62 | P49841 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.2 | We demonstrated that GSK-3beta mediates phosphorylation of GCM1 on Ser322, which is recognized by the F-box protein, FBW2, to promote GCM1 ubiquitination and degradation. | SIGNOR-278940 |
Q7Z570 | Q6ZUJ8 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | ZNF804A has been implicated in susceptibility to schizophrenia by several genome-wide association studies (GWAS), follow-up association studies and meta-analyses. ZNF804A was identified as a schizophrenia-associated gene by GWAS and was predicted to play a role in DNA binding and transcription To identify the genes that are affected by ZNF804A, we manipulated the expression of the ZNF804A protein in HEK293 human embryonic kidney cell lines and performed a cDNA microarray analysis followed by qPCR. We found that ZNF804A-overexpression up-regulated four genes (ANKRD1, INHBE, PIK3AP1, and DDIT3) and down-regulated three genes (CLIC2, MGAM, and BIRC3). | SIGNOR-269463 |
Q9UBI6 | P17612 | 2 | binding | down-regulates | 0.4 | As pka suppresses the activity of gli, smo might use the stimulation of pi3k by galfai and gbetagamma subu- nits to block pka in cells that have high levels of camp. | SIGNOR-152615 |
P06850 | P51608 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.466 | Collectively, these results point to a specific association between WT MeCP2 and the methylated promoter region of Crh in vivo. In contrast, the MeCP2308 protein was not detected at the Crh promoter. | Thus, the results of seqChIP indicate that MeCP2 preferentially associates with a transcriptionally inactive, dimethyl-histone H3 Lys-9-rich form of the Crh promoter in mice. | SIGNOR-264548 |
O00398 | Q14344 | 2 | 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-257348 |
Q01094 | P17612 | 0 | phosphorylation | up-regulates activity | 0.2 | We confirmed the phosphorylation of T130, S235, and S364 by developing monoclonal antibodies against phospho-specific forms of these sites and showed that their phosphorylation is cell cycle-dependent. According to our results, PKA-mediated phosphorylation of E2F1 by PKA inhibits proliferation and glucose uptake and induces caspase-3 activation and senescence. | SIGNOR-277537 |
Q00535 | Q8IWU2 | 1 | phosphorylation | up-regulates | 0.497 | Here, we demonstrate that lmtk2 is phosphorylated on serine-1418 (lmtk2ser ) by cdk5/p35 and present evidence that this regulates its ability to phosphorylate pp1cthr __ | SIGNOR-195329 |
Q14623 | Q9Y6C5 | 2 | binding | down-regulates activity | 0.791 | Biochemical analysis of ptch and ptch2 shows that they both bind to all hedgehog family members with similar affinity and that they can form a complex with smo.Current models suggest that binding of Shh to PTCH prevents the normal inhibition of the seven-transmembrane-protein Smoothened (SMO) by PTCH. | SIGNOR-61314 |
O15527 | O14529 | 2 | binding | up-regulates activity | 0.2 | CUX2 Interacts Directly with OGG1 and Stimulate Its Binding to DNA Containing 8-OxoG | SIGNOR-263960 |
P11309 | Q01196 | 1 | phosphorylation | up-regulates activity | 0.269 | Furthermore, catalytically active Pim-1 kinase was able to phosphorylate Runx1 and Runx3 proteins and enhance the transactivation activity of Runx1 in a dose-dependent fashion.|Pim-1 potentiates transcriptional activity of the RUNX1 transcription factor. | SIGNOR-278976 |
Q9H2S1 | P17612 | 0 | phosphorylation | down-regulates | 0.2 | Mutagenesis and mass spectrometry studies identified four pka phosphorylation sites: ser465 (minor site) and three amino acid residues ser568, ser569, and ser570 (major sites) within the carboxyl-terminal region. pka activation decreased sk2 surface localization | SIGNOR-145040 |
Q96J87 | P38936 | 1 | post transcriptional regulation | up-regulates quantity by stabilization | 0.2 | CELF6 binds to the 3'UTR of p21 transcript and increases its mRNA stability. Depletion of CELF6 promotes cell cycle progression, cell proliferation and colony formation whereas overexpression of CELF6 induces G1 phase arrest. | SIGNOR-269044 |
Q9UHD2 | Q7Z434 | 2 | binding | up-regulates activity | 0.913 | After ligand binding, cGAS and RIG-I signal through respective adaptor proteins STING and MAVS to recruit the kinases IKK and TBK1, which then activate the transcription factors NF-κB and interferon regulatory factor 3 (IRF3), respectively. | SIGNOR-260145 |
Q8NFZ4 | P78352 | 1 | relocalization | up-regulates activity | 0.759 | Like NRXNs, NLGNs bind to intracellular PDZ-domain proteins, but in contrast to NRXNs, NLGNs bind to class I PDZ domains such as those contained in PSD95, a postsynaptic MAGUK protein65. PSD95 and its homologues are centrally involved in recruiting glutamate receptors at postsynaptic sites66. Similarly to CASK, PSD95 binds to intracellular adaptor proteins, and especially to GKAP (a protein that binds to the guanylate-kinase domain of PSD95), which, in turn, binds to SHANK proteins (Fig. 1b). A possible role of these interactions is to recruit postsynaptic adaptor proteins to the site of synaptic junctions. | SIGNOR-264193 |
P04150 | P0DMV8 | 2 | binding | down-regulates | 0.633 | Interestingly, FKBP51 forms complexes in mitochondria with the glucocorticoid receptor and the Hsp90/Hsp70-based chaperone heterocomplex | SIGNOR-251668 |
O43541 | Q99717 | 0 | transcriptional regulation | up-regulates quantity | 0.599 | Chromatin immunoprecipitation (ChIP) revealed a subset of the BIG (BMP4 induced genes) signature, including Satb2, Smad6, Hand1, Gadd45γ and Gata3, that was bound by Smad1/5 in the developing mandible, revealing direct Smad-mediated regulation | SIGNOR-268940 |
P67775 | P28749 | 1 | dephosphorylation | up-regulates | 0.623 | 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 subunit pp2a/c) specifically interacts with both p130 and p107 / the cell cycle repressor activity of pocket proteins is inactivated by cdk mediated phosphorylation. | SIGNOR-129749 |
Q93077 | Q14493 | 0 | translation regulation | up-regulates quantity by expression | 0.2 | Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control. | SIGNOR-265400 |
P62136 | P04150 | 1 | dephosphorylation | up-regulates activity | 0.291 | The current study assessed whether PP1\u03b1 can stimulate GR function and tested two different hypotheses: First, that PP1\u03b1 regulates GR activity through suppression of MDM2 activity by dephosphorylating it at Ser166, thereby reducing the MDM2-mediated ubiquitination of GR and the subsequent proteasomal degradation of the receptor, as shown for the MR and AR ( xref ; xref ); and second, that PP1\u03b1 directly dephosphorylates the GR at a particular site to relieve functional repression as demonstrated for PP2A and PP5 ( xref ; xref ; xref ).|The involvement of GR-Ser211 phosphorylation supports the assumption that altered subcellular trafficking is a mechanism less likely contributing to the PP1\u03b1-dependent GR activation. | SIGNOR-277161 |
Q16695 | Q9UGL1 | 0 | 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-264303 |
P09630 | P09429 | 2 | binding | up-regulates activity | 0.298 | We show that HMG1 interacts with proteins encoded by the HOX gene family by establishing protein-protein contacts between the HMG box domains and the HOX homeodomain. The functional role of these interactions was studied using the transcriptional activity of the human HOXD9 protein as a model. HMG1 enhances, in a dose-dependent fashion, the sequence-specific DNA binding activity in vitro, and the transcriptional activation in a co-transfection assay in vivo, of the HOXD9 protein. | SIGNOR-219937 |
O75807 | O15105 | 2 | binding | up-regulates | 0.679 | 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-121280 |
P15531 | Q8IVT5 | 1 | phosphorylation | down-regulates | 0.543 | Autophosphorylated recombinant nm23-h1 phosphorylated ksr in vitro. Using site-directed mutagenesis, we found that nm23-h1 phosphorylated ksr serine 392, a 14-3-3-binding site, consistent with the recent identification of c-tak1 as a kinase for this site. | SIGNOR-90390 |
Q13085 | Q8NHY2 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.2 | TRB3 appears to inhibit ACC activity by functioning as an adaptor for COP1. Taken together, these results suggest that TRB3 may promote loss of fat by mediating the COP1-dependent ubiquitination and inactivation of ACC. Taking these results together, we propose that TRB3 may protect against diet-induced obesity by stimulating fatty acid oxidation in adipose during fasting through the COP1-mediated ubiquitination and degradation of ACC (Fig. 4D). | SIGNOR-271598 |
P04150 | P17676 | 2 | binding | up-regulates activity | 0.46 | The differentiation of 3T3-L1 preadipocytes is regulated in part by a cascade of transcriptional events involving activation of the CCAAT/enhancer-binding proteins (C/EBPs) and peroxisome proliferator-activated receptor gamma (PPARgamma) by dexamethasone (DEX), 3-isobutyl-1-methylxanthine (MIX), and insulin | SIGNOR-250566 |
Q14703 | P36956 | 1 | cleavage | up-regulates activity | 0.561 | We present evidence that SKI-1 processes peptides mimicking the cleavage sites of the SKI-1 prosegment, pro-brain-derived neurotrophic factor, and the sterol regulatory element-binding protein SREBP-2 | SIGNOR-267497 |
P08581 | P14210 | 2 | binding | up-regulates | 0.928 | Hgf is the ligand for p190met, the receptor tyrosine kinase encoded by the met proto-oncogene. | SIGNOR-38429 |
P78536 | P12931 | 0 | phosphorylation | up-regulates activity | 0.458 | These data suggests that Src mediates TACE activation in mechanically stressed cardiomyocytes and this mechanism could be exploited for specific blockade of TNFalpha secretion and its detrimental effects in congestive heart failure.|We found that the non receptor tyrosine kinase Src mediates TACE activation in mechanically stretched rat cardiomyocytes by phosphorylating the Tyr 702 residue within the intracellular tail of TACE. | SIGNOR-279115 |
Q14289 | Q9UHD2 | 1 | phosphorylation | up-regulates activity | 0.266 | Mechanistically, we demonstrate that PTK2B directly phosphorylates residue Tyr591 of TBK1, which increases TBK1 oligomerization and activation. | SIGNOR-277910 |
O43613 | P50148 | 2 | binding | up-regulates activity | 0.466 | 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-257220 |
P03206 | Q02548 | 2 | binding | down-regulates activity | null | ... we demonstrate that Pax5 inhibits Z-mediated lytic viral gene expression and the release of infectious viral particles in latently infected epithelial cell lines. Conversely, we found that shRNA-mediated knockdown of endogenous Pax5 in a Burkitt lymphoma B-cell line leads to viral reactivation. Furthermore, we show that Pax5 reduces Z activation of early lytic viral promoters in reporter gene assays and inhibits Z binding to lytic viral promoters in vivo. We confirm that Pax5 and Z directly interact | SIGNOR-269082 |
Q13322 | P08069 | 2 | binding | down-regulates | 0.739 | Grb10 negatively regulates growth factor signaling. It binds the insulinand insulin-like growth factor 1 (igf-1) receptors, and mice without grb10 are larger and exhibit enhanced insulin sensitivity | SIGNOR-174062 |
P18848 | P51812 | 0 | phosphorylation | up-regulates | 0.633 | Here, we show that rsk2 is required for osteoblast differentiation and function. We identify the transcription factor atf4 as a critical substrate of rsk2 that is required for the timely onset of osteoblast differentiation, for terminal differentiation of osteoblasts, and for osteoblast-specific gene expression | SIGNOR-124436 |
Q8WZ75 | O94813 | 2 | binding | up-regulates | 0.634 | We show that robo4 binds slit and inhibits cellular migration in a heterologous expression system, analogous to the role of known robo receptors in the nervous system. | SIGNOR-86380 |
Q9GZV5 | O95835 | 0 | phosphorylation | down-regulates | 0.791 | In response to high cell densities, activated LATS1/2 phosphorylates the WW-domain containing transcriptional co-activators YAP at Ser127 and TAZ at Ser89, promoting 14-3-3 binding and thereby inhibiting their translocation into the nucleus. | SIGNOR-197643 |
P00403 | P0C6X7-PRO_0000037317 | 2 | binding | down-regulates activity | 0.2 | This result suggests that the nsp10 protein could affect the activities of NADH and cytochrome oxidase II via a direct interaction while being involved in viral replication. | SIGNOR-260254 |
P04083 | P25090 | 2 | binding | up-regulates activity | 0.643 | We show that the mimetic N-terminal annexin 1 peptide Ac1-25 is able to activate and desensitize not only FPR but also FPRL1 and FPRL2. | SIGNOR-259437 |
Q06609 | Q96B01 | 2 | binding | up-regulates activity | 0.771 | Homologous recombination (HR) repairs chromosome damage and is indispensable for tumor suppression in humans. RAD51 mediates the DNA strand-pairing step in HR. RAD51 associated protein 1 (RAD51AP1) is a RAD51-interacting protein whose function has remained elusive. Biochemical and cytological results show that RAD51AP1 functions at a step subsequent to the assembly of the RAD51-ssDNA nucleoprotein filament. Purified RAD51AP1 binds both dsDNA and a D loop structure and, only when able to interact with RAD51, greatly stimulates the RAD51-mediated D loop reaction. | SIGNOR-261962 |
P01100 | O75534 | 0 | post transcriptional regulation | down-regulates quantity | 0.295 | By testing different classes of mammalian poly(A) nucleases, we identified CCR4 as a poly(A) nuclease involved in the mCRD-mediated rapid deadenylation in viv | SIGNOR-261145 |
Q9UQM7 | Q96PM5 | 1 | phosphorylation | down-regulates | 0.296 | Phosphorylation of pirh2 by calmodulin-dependent kinase ii impairs its ability to ubiquitinate p53 | SIGNOR-156064 |
Q9H2B2 | P45983 | 0 | phosphorylation | up-regulates activity | 0.411 | JNK phosphorylates Syt 4 at Ser135 in vitro and in vivo. | SIGNOR-273673 |
P60520 | O95352 | 2 | binding | up-regulates activity | 0.905 | Three human atg8 (hatg8) homologs, lc3, gabarap, and gate-16, have been characterized as modifiers in reactions mediated by hatg7 (an e1-like enzyme) and hatg3 (an e2-like enzyme). | SIGNOR-142002 |
P56524 | Q06413 | 2 | binding | down-regulates | 0.713 | We discovered that mef2 interacts with histone deacetylases (hdacs) 4 and 5, resulting in repression of the transcriptional activity of mef2. | SIGNOR-76234 |
P23760 | P22455 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.365 | FGFR4 is a transcriptional target of PAX3 and the PAX3-FOXO1 fusion protein found in ARMS. | SIGNOR-251572 |
P63096 | Q08828 | 2 | binding | down-regulates activity | 0.552 | GTP-bound, active WT Gαi1 acts to inhibit AC, resulting in a decreased concentration of intracellular cAMP. | SIGNOR-256498 |
P29597 | Q8IU57 | 2 | binding | up-regulates | 0.559 | Despite signaling through distinct receptor complexes, type i ifns and ifn-_s activate similar signaling events and biological activities, consistent with their common ability to mediate an antiviral state in cells (fig. 6). In both cases, receptor engagement leads via the activation of the jak kinases jak1 and tyk2 | SIGNOR-124483 |
P41240 | P12931 | 1 | phosphorylation | down-regulates | 0.569 | The catalytic activity of the src family of tyrosine kinases is suppressed by phosphorylation on a tyrosine residue located near the c terminus (tyr 527 in c-src), which is catalyzed by c-terminal src kinase (csk). | SIGNOR-179417 |
O95786 | P68400 | 0 | phosphorylation | down-regulates | 0.2 | Threonine at amino acid (aa) 770 and serine at aa 854 to 855 of rig-i are phosphorylated by casein kinase ii (ck2) in the resting state of the cell and dephosphorylated when cells are infected by rna virus. Mutation at aa position 770 or 854 to 855 of rig-i renders it constitutively active | SIGNOR-169404 |
Q9NQC7 | Q96LD4 | 0 | ubiquitination | down-regulates quantity | 0.2 | CYLD is progressively degraded upon interaction with the E3 ligase TRIM47 in proportion to NASH severity | SIGNOR-266443 |
P38398 | P30307 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.464 | BRCA1 mediates cyclin B and Cdc25C ubiquitination.|Thus, BRCA1 dependent proteasomal degradation of cyclin B and Cdc25C precede the subsequent BRCA1 dependent cell cycle arrest. | SIGNOR-278623 |
P05771 | Q96D31 | 1 | phosphorylation | down-regulates | 0.2 | We propose that pkc suppresses soce and crac channel function by phosphorylation of orai1 at n-terminal serine residues ser-27 and ser-30. | SIGNOR-166040 |
P49767 | P35916 | 2 | binding | up-regulates | 0.935 | Vegf-c, was isolated as a ligand for the tyrosine kinase vegfr-3 (flt4) | SIGNOR-55205 |
P01871 | Q9UPW6 | 0 | transcriptional regulation | up-regulates quantity | 0.2 | The SATB2 protein was shown to bind MAR sequences flanking the enhancer of the endogenous immunoglobulin μ heavy chain (IgH) gene in vivo, and this binding was found to correlate with an increase in the expression of a transfected rearranged μ wild-type gene | SIGNOR-268933 |
P29972 | P17252 | 0 | phosphorylation | up-regulates | 0.2 | Activation of protein kinase c (pkc) by 1-oleoyl-2-acetyl-sn-glycerol (oag) induced a marked increase of aqp1-dependent water permeability. This regulation was abolished in mutated aqp1 channels lacking both consensus pkc phosphorylation sites thr(157) and thr(239) (termed aqp1 deltapkc). | SIGNOR-155106 |
P07195 | Q9NXA8 | 0 | deacetylation | up-regulates activity | 0.2 | In colorectal cancer, SIRT5 binds to lactate dehydrogenase B (LDHB) to deacetylate it at Lysine 329, thereby increasing its enzymatic activity. | SIGNOR-267645 |
Q9H3R0 | P19525 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.2 | In the absence of Wnt3a, protein kinase R phosphorylated KDM4C at Ser918, inducing KDM4C ubiquitination and degradation. | SIGNOR-277497 |
P51149 | P60484 | 0 | dephosphorylation | up-regulates activity | 0.373 | PTEN dephosphorylates Rab7 on two conserved residues S72 and Y183, which are necessary for GDP dissociation inhibitor (GDI)-dependent recruitment of Rab7 on to late endosomes and subsequent maturation. | SIGNOR-276960 |
Q13131 | P46527 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.267 | P27Kip1-Mediated Cell Survival Is Dependent on AMPK-Specific Thr198 Phosphorylation|AMPK-dependent phosphorylation of p27Kip1 on Thr198 promotes p27Kip1 protein stability, resulting in more autophagy and less apoptosis. | SIGNOR-259859 |
P56524 | P49841 | 0 | phosphorylation | down-regulates | 0.364 | The double mutation of serines 298/302 into alanines, but also the sole mutation of serine 302, abolishes hdac4 phosphorylation by gsk3_we have shown that cells lacking gsk3_ are unable to degrade hdac4 after serum starvation | SIGNOR-170144 |
P15882 | Q15078 | 2 | binding | up-regulates | 0.337 | _-chimaerin was identified to interact with the p35 activator of cdk5. The complex of _-chimaerin, cdk5 and p35 is enzymatically functional | SIGNOR-123439 |
Q13884 | P53778 | 2 | binding | down-regulates | 0.368 | Basal localization of the p38g/p-Carm1 complex in muscle stem cells occurs via binding to the dystrophin-glycoprotein complex (DGC) through b1-syntrophin. In dystrophin-deficient muscle stem cells undergoing asymmetric division, p38g/b1-syntrophin interactions are abrogated, resulting in enhanced Carm1 phosphorylation | SIGNOR-255901 |
Q99497 | O60260 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.2 | Together, these results demonstrate that parkin selectively recognizes and ubiquitinates misfolded DJ-1 in vivo. | SIGNOR-278526 |
Q9Y463 | P61962 | 2 | binding | up-regulates activity | 0.728 | Two isoforms of DYRK, DYRK1A and DYRK1B, co-immunoprecipitate with HAN11 when coexpressed in COS cells indicating that the proteins interact in mammalian cells. HAN11 might target DYRKs to cytosolic locations for regulation of specific cellular functions. | SIGNOR-260631 |
P05412 | P00519 | 0 | phosphorylation | up-regulates activity | 0.526 | Active nuclear Abl efficiently phosphorylate c-Jun. After phosphorylation of c-Jun by Abl on Tyr170, both proteins interacted via the SH2 domain of Abl. | SIGNOR-251428 |
Q8WXI2 | P04049 | 2 | binding | up-regulates | 0.767 | We show cnk2 interacts with raf. cnk2 interacts with the gef domain of rlf and with both the regulatory and catalytic domains of raf. The raf interaction was also mapped to the carboxyl-terminal half of cnk2. Overexpression of cnk2 results in inhibition of the mapk signaling pathway. | SIGNOR-119039 |
P46937 | O15350 | 2 | binding | up-regulates | 0.716 | Yap also interacts with p73, a p53 family pro-apoptotic transcription factor, to induce expression of genes such as bax, puma and pml. | SIGNOR-175934 |
Q13323 | Q07817 | 2 | binding | down-regulates | 0.808 | We have identified a novel cellular protein, bik, that interacts with the cellular survival-promoting proteins, bcl-2 and bcl-xl in transient transfection assays, bik promotes cell death in a manner similar to the death-promoting members of the bcl-2 family, bax and bak. | SIGNOR-26453 |
P06493 | P46937 | 1 | phosphorylation | up-regulates activity | 0.425 | Our evidence suggested that these YAP sites (Ser138, Thr143, and Ser367) were CDK1 phosphorylation sites.|These data demonstrate that the YAP phosphorylation sites Ser138, Thr143, and Ser367 are important for proper mitosis and cytokinesis. | SIGNOR-276587 |
Q9BYB0 | P42261 | 2 | binding | up-regulates quantity | 0.2 | 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-264601 |
Q04206 | P68400 | 0 | phosphorylation | up-regulates activity | 0.443 | We demonstrate that casein kinase II (CKII) interacts with p65 in vivo and can phosphorylate p65 at serine 529 in vitro. A CKII inhibitor (PD144795) inhibited TNFalpha-induced p65 phosphorylation in vivo. Furthermore, our results indicate that the association between IkappaBalpha and p65 inhibits p65 phosphorylation by CKII and that degradation of IkappaBalpha allows CKII to phosphorylate p65 to increase NF-kappaB transactivation potential. | SIGNOR-250942 |
A7KAX9 | P04629 | 0 | relocalization | up-regulates | 0.602 | Grit translocation was regulated by receptor stimulation | SIGNOR-95809 |
Q16539 | O95382 | 0 | phosphorylation | up-regulates activity | 0.2 | These data indicate that MKK6 phosphorylates p38 MAP kinase on Thr-180 and Tyr-182, the sites of phosphorylation that activate p38 MAP kinase | SIGNOR-260916 |
Q15172 | P19525 | 0 | phosphorylation | up-regulates | 0.328 | Phosphorylation of serine 28 by pkr promotes mitochondrial localization of b56alpha, because wild-type but not mutant s28a b56alpha promoted mitochondrial pp2a activity. | SIGNOR-181793 |
O96014 | O75581 | 2 | binding | up-regulates activity | 0.572 | Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation. | SIGNOR-131637 |
P20226 | Q12947 | 2 | binding | up-regulates activity | 0.408 | The human forkhead protein FREAC-2 contains two functionally redundant activation domains and interacts with TBP and TFIIB. | SIGNOR-220373 |
P37231 | Q15596 | 2 | binding | up-regulates | 0.77 | Collectively, our data provide the first evidence that erbeta-deficiency protects against diet-induced ir and glucose intolerance which involves an augmented ppargamma signaling in adipose tissue. Moreover, our data suggest that the coactivators src1 and tif2 are involved in this interaction. | SIGNOR-179175 |
Q8IZL8 | P04150 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.553 | MNAR functionally interacts with both NH2- and COOH-terminal GR domains to modulate transactivation | SIGNOR-251681 |
P09471 | O43614 | 2 | binding | up-regulates activity | 0.253 | 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-257008 |
P00751 | P08603 | 2 | binding | down-regulates activity | 0.518 | As a regulator of the alternative pathway, FH binds to C3b and inhibits the binding of factor B to C3b, acts as a cofactor for the factor I-mediated cleavage of C3b to iC3b (cofactor activity), and accelerates the decay of C3bBb, the alternative pathway C3 convertase (decay-accelerating activity) | SIGNOR-252142 |
Q9NVI1 | O94782 | 0 | deubiquitination | down-regulates activity | 0.666 | Phosphorylation of FANCI may also turn the ubiquitinated ID complex into a poor substrate for deubiquitination by the USP1–UAF1 complex, resulting in increased levels of monoubiquitinated FANCD2. | SIGNOR-263272 |
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