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 |
|---|---|---|---|---|---|---|---|
Q92915 | Q15858 | 1 | binding | down-regulates activity | 0.2 | Sodium channel fast inactivation is modulated by alpha subunit interaction with a family of cytoplasmic proteins termed fibroblast growth factor homologous factors (FHFs). In this paper, we report that all A-type FHFs exert rapid onset long-term inactivation on Nav1.6 and other sodium channels. | SIGNOR-253425 |
Q13153 | O15344 | 1 | phosphorylation | up-regulates activity | 0.2 | Pak1 phosphorylates the N-terminus of Mid1 to promote its association with cortical nodes.|Pak1 promotes Mid1 localization to cortical nodes. | SIGNOR-279307 |
Q13526 | Q9HAV4 | 1 | isomerization | down-regulates activity | 0.2 | Here we show that ERK suppresses pre-miRNA export from the nucleus through phosphorylation of exportin-5 (XPO5) at T345/S416/S497. After phosphorylation by ERK, conformation of XPO5 is altered by prolyl isomerase Pin1, resulting in reduction of pre-miRNA loading. | SIGNOR-263015 |
Q05655 | P13498 | 1 | phosphorylation | up-regulates | 0.2 | Phosphorylation of p22phox on threonine 147 enhances NADPH oxidase activity by promoting p47phox binding. | Threonine 147 of p22phox Is Phosphorylated by PKC-α and PKC-δ in Vitro | SIGNOR-260892 |
O60729 | Q15572 | 1 | dephosphorylation | up-regulates activity | 0.2 | Consistent with prior studies showing that the phosphatase hCdc14B regulates progression through mitosis by counteracting mitotic phosphorylation by Cdk1/cyclin B [ ], hCdc14B dephosphorylates TAFI110, thus promoting its reactivation as cells exit mitosis.|Here we show that hCdc14B, the phosphatase that regulates Cdk1/cyclin B activity and progression through mitosis, promotes reactivation of rDNA transcription by dephosphorylating TAFI110. | SIGNOR-277135 |
Q03112 | Q02763 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | We finally observed that the forced expression of Evi1 induced GATA-2 expression in a hematopoietic cell line, EML C1, along with GATA-1, Ang-1, Ang-2 and Tie2 | SIGNOR-266063 |
Q7Z570 | Q15327 | 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-269461 |
Q9Y5H9 | Q9Y5G0 | 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-265692 |
Q5T0T0 | P79483 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | Two E3 ligases, MARCH I and MARCH VIII, have been shown to polyubiquitinate lysine residue 225 in the cytoplasmic tail of I-Abeta and HLA-DRbeta. We show that lysine residue 219 in the cytoplasmic tail of DRalpha is also subject to polyubiquitination. | SIGNOR-271408 |
Q5T447 | P04049 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | By western blot, we observed robust degradation of endogenous native CRAF in untransformed HEK293 cells treated with control siRNA 24 hr after the addition of AUY922, but this was substantially reduced in cells in which HECTD3 was knocked down, confirming that endogenous CRAF is a bona fide degradation target of HECTD3 | SIGNOR-272328 |
P49715 | P49715 | 2 | transcriptional regulation | up-regulates quantity | 0.2 | Here, we demonstrate that C/EBPα indeed activates its promoter in transient transfection assays in myeloid cells. | SIGNOR-255673 |
P31314 | P06400 | 1 | binding | down-regulates activity | 0.2 | ectopic HOX11 expression resulted in hyperphosphorylation of the retinoblastoma protein (Rb), which correlated with inhibition of the major Rb serine/threonine phosphatase PP1. | SIGNOR-240725 |
Q99814 | Q6ZMT4 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | To this end, we confirm that KDM3A, KDM4B, KDM4C, KDM5B, KDM5C, and KDM62 are direct targets of HIF-1a while extent the list of known targets to KDM2A, KDM2B, KDM4D, KDM5A, and KDM6A. The results demonstrated that majority of the KDMs were similarly induced (KDM2A, KDM2B, KDM3A, KDM4B, KDM4C, KDM4D, KDM5A, KDM5B, KDM5C, KDM6B, and KDM7A) or repressed (KDM NO66 and KDM1A) by both HIF-1a and HIF-2a. | SIGNOR-271587 |
O95863 | Q92626 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | TGF-β1 induced Snai1 binding to the PXDN promoter (as assessed by chromatin immunoprecipitation-PCR) and significantly repressed luciferase reporter gene expression, as did Snai1 overexpression. | SIGNOR-265249 |
P17252 | P49407 | 1 | phosphorylation | up-regulates activity | 0.2 | We demonstrate that β-arrestin-1 recruitment to the TCR, and bystander TCR and CXCR4 downregulation, are mechanistically mediated by the TCR-triggered PKC-mediated phosphorylation of β-arrestin-1 at Ser163. | SIGNOR-276619 |
P46977 | Q9NZQ7 | 1 | glycosylation | up-regulates quantity by stabilization | 0.2 | Together, these results support a notion that the two STT3 isoforms regulate EMT-mediated PD-L1 induction through PD-L1 protein N-glycosylation and stabilization. | SIGNOR-274975 |
Q9UL17 | Q9UL17 | 2 | null | up-regulates | 0.2 | In turn, T-bet is an IFN-gamma activator (Szabo et al., 2000), thus creating an indirect positive feedback. Furthermore, it has been shown that ectopic T-bet is able to induce the transcription of its own gene | SIGNOR-254294 |
Q99558 | P50281 | 1 | phosphorylation | up-regulates activity | 0.2 | A post-transcriptional process is indicated because we observed that NIK increases MT1-MMP phosphorylation and activity, but does not affect MT1-MMP mRNA expression (XREF_FIG and XREF_FIG).|NIK increases MT1-MMP pseudopodial localization and enzymatic activity. | SIGNOR-279631 |
Q14938 | A6NFN3 | 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-268913 |
Q8IYM9 | Q8IYM9 | 2 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | Importantly, TRIM22 was conjugated with poly-ubiquitin chains and stabilized by the proteasome inhibitor in 293T cells, suggesting that TRIM22 targeted itself for proteasomal degradation through the poly-ubiquitylation. We also found that TRIM22 was located in the nucleus, indicating that TRIM22 might function as a nuclear E3 ubiquitin ligase. | SIGNOR-271780 |
Q9C026 | Q9C026 | 2 | ubiquitination | down-regulates quantity by destabilization | 0.2 | Collectively, these results indicated that TRIM9 is an E3 ligase for its self-ubiquitination and that the ubiquitination of TRIM9 likely serves as a signal for proteasomal degradation. As shown in Fig. 1A, TRIM9 was ubiquitinated by itself when incubated with UbcH5b. In contrast, ubiquitination was observed when incubated with other E2 enzymes. These results suggest that TRIM9 cooperates with UbcH5b for its self-ubiquitination. N | SIGNOR-271419 |
P43146 | Q13936 | 1 | null | up-regulates activity | 0.2 | DCC activation by a netrin-1 gradient creates a high-level [Ca2+]i gradient by triggering LCC activity and by stimulating the cAMP–PKA pathway, which further activates LCC in the plasma membrane (PM) and Ca2+ channels in the ER. | SIGNOR-268291 |
P17612 | Q14738 | 1 | phosphorylation | up-regulates | 0.2 | Protein kinase a activates protein phosphatase 2a by phosphorylation of the b56delta subunit. | SIGNOR-153218 |
P08047 | P10645 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Recently, binding of specific protein 1 (Sp1) and cAMP response element binding protein (CREB) to a GC-rich element at -92/-62 has been identified as a critical step in gastrin-dependent regulation of the chromogranin A (CgA) gene in gastric epithelial cells. Here we demonstrate that binding of early growth response protein 1 (Egr-1) to the distal part of the -92/-62 site is also required for gastrin-dependent CgA transactivation. | SIGNOR-254273 |
Q15139 | A6ND36 | 1 | phosphorylation | up-regulates activity | 0.2 | Taken together, these data demonstrate that FAM83G S356 phosphorylation modulates HSP27 phosphorylation and apoptosis regulation and that HSP27 is a counterpart of FAM83G.|an active form of PKD1/PKCm could phosphorylate the FAM83G peptide, including the S356 portion.|We also demonstrated that the phosphorylation of the FAM83G S356 residue was required for the reduction of the live cell number, as the CHO cells were unaffected upon the overexpression of a FAM83G S356A mutant resistant to S356 phosphorylation. | SIGNOR-264764 |
Q14493 | Q99880 | 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-265389 |
Q8TCJ2 | Q9NZQ7 | 1 | glycosylation | up-regulates quantity by stabilization | 0.2 | Together, these results support a notion that the two STT3 isoforms regulate EMT-mediated PD-L1 induction through PD-L1 protein N-glycosylation and stabilization. | SIGNOR-274976 |
O95990 | Q9Y243 | 1 | binding | up-regulates | 0.2 | Full-length tcl1 and its isoforms bind to akt / in in vitro kinase assays using gsk-3_ as a substrate, we found that the presence of any of the tcl1 family proteins (tcl1, mtcp1, or tcl1b) as gst fusion proteins significantly enhanced akt-induced gsk-3_ phosphorylation | SIGNOR-81800 |
Q13185 | Q16695 | 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-264495 |
Q02447 | P08243 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Sp1 and Sp3 Activate Transcription Driven by the AS Promoter | SIGNOR-268020 |
O14965 | P07195 | 1 | phosphorylation | up-regulates activity | 0.2 | Aurora-A-mediated phosphorylation of LDHB serine 162 significantly increases its activity in reducing pyruvate to lactate, which efficiently promotes NAD+ regeneration, glycolytic flux, lactate production and bio-synthesis with glycolytic intermediates. | SIGNOR-277493 |
Q14938 | P41221 | 1 | transcriptional regulation | down-regulates quantity | 0.2 | By integrating transcriptomic profiling (RNA-seq) of Nfia- and Nfix-deficient GNPs with epigenomic profiling (ChIP-seq against NFIA, NFIB and NFIX, and DNase I hypersensitivity assays), we reveal that these transcription factors share a large set of potential transcriptional targets, suggestive of complementary roles for these NFI family members in promoting neural development | SIGNOR-268889 |
P41229 | Q16695 | 1 | demethylation | up-regulates activity | 0.2 | KDM5 subfamily is capable of removing tri†and di†methyl marks from lysine 4 on histone H3 (H3K4). Depending on the methylation site, its effect on transcription can be either activating or repressing. | SIGNOR-264306 |
Q9UBE8 | P15884 | 1 | phosphorylation | down-regulates | 0.2 | Whereas lef-1 and tcf-4 phosphorylation by nlk (nemo-like kinase) leads to less lef/tcf/beta-catenin complex binding to dna and to lef-1/tcf-4 degradation | SIGNOR-24147 |
Q9NX47 | O60260 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | MITOL promotes cell survival by degrading Parkin during mitophagy.|Mechanistically, MITOL mediates ubiquitination of Parkin at lysine 220 residue, which promotes its proteasomal degradation, and thereby fine-tunes mitophagy by controlling the quantity of Parkin. | SIGNOR-278554 |
P12931 | P53801 | 1 | phosphorylation | up-regulates activity | 0.2 | Src induction leads to phosphorylation at PBF residue Y174. Abrogation of this residue results in PM retention and a markedly reduced ability to bind NIS. | SIGNOR-273810 |
P08631 | Q9UHD2 | 1 | phosphorylation | down-regulates activity | 0.2 | The Src family kinases (SFKs) Lck, Hck, and Fgr directly phosphorylate TBK1 at Tyr354/394, to prevent TBK1 dimerization and activation. | SIGNOR-276727 |
Q6PJ69 | Q96P20 | 1 | ubiquitination | down-regulates activity | 0.2 | These results suggest that TRIM65 could inhibit the activation of the NLRP3 inflammasome in response to multiple agonists.|Thus, TRIM65 deficiency impairs NLRP3 ubiquitination and enhances NLRP3 inflammasome activation, but has no effects on AIM2 or IPAF inflammasome activation. | SIGNOR-278566 |
P17481 | Q01995 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | Results from these experiments demonstrated that in 10T1/2 cells Hoxa10-1 increased the activity of the telokin promoter 3-fold without affecting the activity of the other promoters analyzed (Fig. 2A). Similar results were also observed in A10 SMC (data not shown). In contrast, Hoxb8 significantly repressed the activity of the telokin, smooth muscle α-actin, and SM22α promoters by 70, 50, and 70%, respectively | SIGNOR-261642 |
Q9Y5H9 | Q9Y5G2 | 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-265688 |
P51812 | P19525 | 1 | phosphorylation | up-regulates | 0.2 | Our data indicated that phosphorylation of pkr at thr(451) is mediated through erk2 and rsk2, but not through p38 kinase. | SIGNOR-154183 |
P06493 | O75154 | 1 | phosphorylation | up-regulates quantity | 0.2 | FIP3 is phosphorylated on S102 in a cell cycle-dependent manner. We identify four sites of phosphorylation of FIP3 in vivo, S-102, S-280, S-347 and S-450 and identify S-102 as a target for Cdk1-cyclin B in vitro. Of these, we show that S-102 is phosphorylated in metaphase and is dephosphorylated as cells enter telophase. | SIGNOR-273588 |
P17612 | P19793 | 1 | phosphorylation | down-regulates | 0.2 | Serine 27, a human retinoid x receptor alpha residue, phosphorylated by protein kinase a is essential for cyclicamp-mediated downregulation of rxralpha function. | SIGNOR-104954 |
Q14938 | P29322 | 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-268910 |
Q9H765 | O14920 | 2 | ubiquitination | down-regulates quantity by destabilization | 0.2 | In turn, ASB8 facilitated K48-linked ubiquitination and degradation of IKKbeta via the ubiquitin-proteasome pathway, resulting in remarkable inhibition of I-kappa-B-alpha (IkappaBalpha) and of p65 phosphorylation, consequently suppressing NF-kappaB activity. | SIGNOR-272253 |
Q13131 | Q92538 | 1 | phosphorylation | down-regulates | 0.2 | These results indicate that gbf1 is a novel ampk substrate and that the ampk-mediated phosphorylation of gbf1 at thr(1337) has a critical role, presumably by attenuating the function of gbf1, in the disassembly of the golgi apparatus induced under stress conditions that lower the intracellular atp concentration. | SIGNOR-159639 |
Q14493 | P04908 | 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-265397 |
Q9NZJ5 | O15294 | 1 | phosphorylation | up-regulates activity | 0.2 | Collectively, these results indicate that upon cold and \u03b2-adrenergic stimulation PERK-activated OGT catalyzes the O-GlcNAcylation of CK2\u03b1 and TOM70 which enhances MIC19 import into the mitochondria increasing cristae formation and cell respiration (Figure 7I).|Here, we report that the ER-resident kinase PERK is activated upon cold or \u03b2-adrenergic stimulation and directly phosphorylates OGT. | SIGNOR-279736 |
Q14493 | P0C5Y9 | 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-265411 |
P51684 | P14780 | 1 | null | up-regulates activity | 0.2 | We hypothesized that MIP-3alpha promotes pancreatic cancer invasion through the up-regulation of MMP-9, a Type 4 collagenase. | SIGNOR-278042 |
O60502 | P11413 | 1 | deglycosylation | down-regulates activity | 0.2 | O-GlcNAcylation of G6PD promotes the pentose phosphate pathway and tumor growth|O-GlcNAcylation of G6PD activates enzyme activity|G6PD is dynamically modified by O-GlcNAc at serine 84|In cells, a single set of antagonistic enzymes-O-GlcNAc transferase (OGT) and O-GlcNAc hydrolase are responsible for the addition and removal of GlcNAc moiety, respectively. | SIGNOR-267605 |
P05771 | Q12906 | 1 | phosphorylation | up-regulates activity | 0.2 | Upon T cell activation, NF90 translocates from the nucleus into the cytoplasm, where it binds to the AU-rich element-containing 3' untranslated regions of IL-2 mRNA and stabilizes it.|Our results support a model in which PMA stimulation activates PKCβI to phosphorylate NF90-Ser647, and this phosphorylation triggers NF90 relocation to the cytoplasm and stabilize IL-2 mRNA. | SIGNOR-168173 |
Q15645 | P00533 | 2 | binding | up-regulates quantity by stabilization | 0.2 | Mechanistically, TRIP13 enhanced EGFR protein abundance in part by preventing Cbl-mediated ubiquitination and proteasomal degradation. | SIGNOR-265084 |
O43303 | P0DP24 | 1 | binding | up-regulates activity | 0.2 | We report that CP110 interacts with two different Ca2+-binding proteins, calmodulin (CaM) and centrin, in vivo. our data demonstrate a functional role for CaM binding to CP110 and suggest that CP110 cooperates with CaM and centrin to regulate progression through cytokinesis. | SIGNOR-266332 |
Q9NRM7 | P60891 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Recruitment of TRAF2 to PRPS1/2 requires phosphorylation of PRPS1 S285 or PRPS2 T285, which is mediated by low stiffness-activated large tumor suppressor (LATS)1/2 kinases.LATS1/2-dependent S/T285 phosphorylation is required for PRPS1/2 ubiquitination and degradation at low stiffness. | SIGNOR-276504 |
O00398 | P63096 | 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-256726 |
P06241 | P52757 | 1 | phosphorylation | down-regulates | 0.2 | Ere we report that beta2-chimaerin is tyrosine-phosphorylated by src-family kinases (sfks) upon cell stimulation with epidermal growth factor (egf). these results suggest tyr-21 phosphorylation as a novel, sfk-dependent mechanism that negatively regulates beta2-chimaerin rac-gap activity. | SIGNOR-155709 |
Q9H4P4 | O60260 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | Here we further demonstrated that overexpression of Nrdp1 significantly reduced the endogenous Parkin level in an Nrdp1 dosage-dependent and proteasome-dependent manner. More importantly, Nrdp1 ubiquitinated Parkin and catalyzed the poly-ubiquitin chains on Parkin in vitro as well as in cells, indicating Parkin is an Nrdp1 substrate. | SIGNOR-272639 |
P62136 | P29474 | 1 | dephosphorylation | up-regulates activity | 0.2 | The increase in eNOS activity coincided with specific dephosphorylation of eNOS-Thr495, known to enhance eNOS activity. Inhibition of protein phosphatase 1 (PP1) by calyculin A, tautomycetin, or siRNA against PP1 reversed NF-induced eNOS-Thr495 dephosphorylation | SIGNOR-248558 |
Q9Y5W3 | P78509 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | KLF2 transactivates the reelin promoter in K562 cells. | SIGNOR-266048 |
P15056 | Q92911 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | The BRAFV600E oncogene induces transforming growth factor beta secretion leading to sodium iodide symporter repression and increased malignancy in thyroid cancer. BRAF induces TGFβ secretion leading to NIS repression in a MEK-ERK–independent manner but cooperating with the MEK-ERK pathway to induce strong tumor invasion, two major traits acquired during PTC progression. | SIGNOR-251989 |
Q96LB2 | P19086 | 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-257326 |
P15173 | P15173 | 2 | transcriptional regulation | up-regulates | 0.2 | Upon the expression of myogenin, myogenin, mef2d, and brg1 localize to the myogenin promoter to maintain myogenin expression./ Swi/snf chromatin-remodeling activity is required for myogenin expression in differentiated skeletal muscle | SIGNOR-151694 |
Q9NQU5 | O43426 | 1 | phosphorylation | up-regulates activity | 0.2 | We identified two novel Pak5 substrates, Pacsin1 and Synaptojanin1, proteins that directly interact with one another to regulate synaptic vesicle endocytosis and recycling. Pacsin1 and Synaptojanin1 were phosphorylated by Pak5 and the other group II Paks in vitro, and Pak5 phosphorylation promoted Pacsin1-Synaptojanin1 binding both in vitro and in vivo. | SIGNOR-263022 |
Q96RI0 | P19086 | 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-257312 |
Q8TEB7 | P52566 | 1 | polyubiquitination | up-regulates quantity by stabilization | 0.2 | We found that RhoGDIα and RhoGDIβ are ubiquitin E3 substrates of GRAIL. GRAIL uses nonlysine 48-ubiquitin linkage in polyubiquitinating RhoGDI. GRAIL was subsequently demonstrated to bind and ubiquitinate RhoGDI, although GRAIL-mediated ubiquitination of RhoGDI did not result in proteosomal degradation. Our data suggest that ubiquitination of RhoGDI by GRAIL does not result in proteolytic degradation. In fact, GRAIL activity appeared to increase RhoGDI stability. | SIGNOR-271621 |
P46934 | O75896 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | NEDD4 Degrades TUSC2 to Promote Glioblastoma Progression.|NEDD4 E3 ubiquitin ligase polyubiquitinates TUSC2 at residue K71, and the TUSC2-K71R mutant is resistant to NEDD4-mediated proteasomal degradation. | SIGNOR-278638 |
Q96T88 | Q5T3J3 | 1 | ubiquitination | down-regulates activity | 0.2 | In our study, we found the UHRF1 is sufficient to suppress RIF1 accumulation at DSBs in S phase and CtIP functions as a negative regulator of RIF1 only in G2 phase (XREF_FIG; XREF_SUPPLEMENTARY).|UHRF1 ubiquitinates RIF1. | SIGNOR-278604 |
Q9HCK8 | O43602 | 1 | transcriptional regulation | down-regulates quantity | 0.2 | Many of the most significantly up-regulated genes in Chd8+/− and Chd8−/− NPCs are involved in later stages of neuronal development, including Ascl1 [a central driver of neural reprogramming (29)], Dcx, Map2, Nefm, Neurod4, and Neurog1 (Fig. 2 E and F). Additionally, we found that Sox3 is derepressed in both Chd8+/− and Chd8−/− NPCs, and several other Sox TF members (Sox2, Sox7, and Sox11) became derepressed in the Chd8−/− cells | SIGNOR-268915 |
P15036 | P02818 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Ets2 is expressed at high levels during the differentiation and matrix mineralization phases of MC3T3-E1 culture. In addition, several extracellular matrix (ECM) associated gene products are targets of Ets2. Some of these matrix associated genes include: bone sialoprotein, osteonectin, osteocalcin and osteopontin | SIGNOR-259875 |
O15146 | O15146 | 2 | phosphorylation | up-regulates activity | 0.2 | AGRN is released by the nerve and binds to LRP4, which then binds to MuSK. This interaction leads to MuSK autophosphorylation and activation of its kinase function, leading to anterograde signalling by subsequent phosphorylation of DOK7 (not shown), which binds MuSK as a dimer. | SIGNOR-273851 |
P67775 | Q70Z35 | 1 | dephosphorylation | up-regulates activity | 0.2 | PREX2 is dephosphorylated by PP1α and PP2A.PAK-mediated phosphorylation of PREX2 reduced GEF activity toward Rac1 by inhibiting PREX2 binding to PIP3 and Gβγ. | SIGNOR-277184 |
P51955 | P46937 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.2 | NEK2 promotes the migration and proliferation of ESCC via stabilization of YAP1 by phosphorylation at Thr-143 | SIGNOR-276586 |
P54646 | Q9UQB8 | 1 | phosphorylation | down-regulates | 0.2 | Using this approach for ppp1r12c, baiap2, and cdc27, we found that mutation of a single serine to alanine (s452, s366, and s379 respectively) resulted in almost a complete loss of ampk phosphorylation in these proteins. Termination of irsp53 function is suggested to occur following cdc42 dissociation, kinase phosphorylation of t340 and t360, and subsequent 14-3-3 binding, which competes for sh3 partners, thus allowing filopodial retraction | SIGNOR-195102 |
P17252 | Q9H3Q1 | 1 | phosphorylation | down-regulates activity | 0.2 | Cdc42 effector protein-4 (CEP4) was recently identified by our laboratory to be a substrate of multiple PKC isoforms in non-transformed MCF-10A human breast cells. MS/MS analysis verified that Ser(18) and Ser(80) were directly phosphorylated by PKCα in vitro. Phosphorylation of CEP4 severely diminished its affinity for Cdc42 while promoting Rac activation and formation of filopodia (microspikes). | SIGNOR-263160 |
Q9Y222 | P07996 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Notably, amphiregulin (Areg), thrombospondin-1 (Tsp-1), JunB, Egr1, adrenomedullin (Adm), Bcl-3 and methyl-CpG binding domain protein 1 (Mbd1) were downregulated in the lungs from Dmp1-null mice while Gas1 and Ect2 genes were upregulated. | SIGNOR-261587 |
Q01094 | P80370 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Using luciferase reporter assay, ChIP assay and EMSA, we found that the -211/-194 region of the pref-1 promoter is essential for the binding of E2F1 as well as E2F1-dependent transcriptional activation. | SIGNOR-271684 |
P23470 | Q14247 | 1 | dephosphorylation | down-regulates activity | 0.2 | PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity. | SIGNOR-254696 |
Q9BRZ2 | Q86WV6 | 1 | ubiquitination | up-regulates activity | 0.2 | In contrast, we found that TRIM56 preferentially promoted K63 linked ubiquitination of the same lysine residue of STING that was important for the dimer formation and TBK1 activation.|Specifically, TRIM56 induces STING dimerization during dsDNA triggered signaling to potentiate antiviral responses while RNF5 may induce degradation of mitochondrial STING to suppress RLR induced antiviral responses.The findings that TRIM56 failed to interact with dsDNA and that there was no colocalization between TRIM56 and dsDNA within cells suggest that TRIM56 is unlikely to be a dsDNA sensor, and instead facilitates the STING function by ubiquitination. | SIGNOR-278621 |
Q86YT6 | P63162 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | These data indicate that Mib1 reduces SMN protein stability by targeting it for degradation by the proteasome and represents a new modifier of the SMA phenotype.|Through this study, we provide evidence that the E3 ligase Mib1 ubiquitinates and catalyzes SMN protein degradation. | SIGNOR-278632 |
Q15349 | P49959 | 1 | phosphorylation | down-regulates activity | 0.2 | Rsk can phosphorylate the Mre11 protein directly at S676 both in vitro and in intact cells and thereby can inhibit the binding of Mre11 to DNA with DSBs.|ribosomal s6 kinase can phosphorylate the Mre11 protein directly at S676 both in vitro and in intact cells and thereby can inhibit the binding of Mre11 to DNA with double-stranded breaks. | SIGNOR-280116 |
Q14493 | Q16777 | 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-265398 |
P17612 | Q7KZI7 | 1 | phosphorylation | down-regulates activity | 0.2 | Here, we found the disruption of microtubule and neurite outgrowth induced by MARK2 overexpression was blocked by active PKA. The interaction between PKA and MARK2 was confirmed by coimmunoprecipitation and immunocytochemistry both in vitro and in vivo. PKA was found to inhibit MARK2 kinase activity by phosphorylating a novel site, serine 409. | SIGNOR-276870 |
P50613 | O95243 | 1 | phosphorylation | down-regulates activity | 0.2 | The mechanistic basis for the phase-separation of MED1 is not well understood, and we hypothesize that this may be due to the phosphorylation of MED1 by CDK7 in response to growth stimuli or nuclear translocation of steroid hormone receptors, such as AR.|Together, we demonstrate that CDK7 inhibition selectively targets MED1 mediated, AR dependent oncogenic transcriptional amplification, thus representing a potential new approach for the treatment of CRPC. | SIGNOR-279686 |
P16885 | P38936 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.2 | Phosphorylation at Ser-146 by PKCδ increases p21 stability | SIGNOR-262963 |
O96013 | Q16236 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | PAK4 directly phosphorylated Nrf2 at T369, and it led to its nuclear export and proteasomal degradation, all of which impaired antioxidant responses in hepatocytes. | SIGNOR-277583 |
P36544 | P61586 | 1 | binding | up-regulates activity | 0.2 | Here, we demonstrate a role for α7 nAChR/G protein interaction in the activation of the small (monomeric) RhoA GTPase leading to cytoskeletal changes during neurite growth. Treatment of PC12 cells with the α7 nAChR agonist choline or PNU-282987 was associated with an increase in RhoA activity and an inhibition in neurite growth. | SIGNOR-253985 |
Q9UQM7 | Q9Y4D2 | 1 | phosphorylation | down-regulates activity | 0.2 | Activated CaMKII interacted with the C-terminal domain of DGLalpha, phosphorylated two serine residues and inhibited DGLalpha activity. |CaMKIIalpha phosphorylates DGLalpha at Ser808 and Ser782 | SIGNOR-275540 |
Q96PY6 | P48163 | 1 | phosphorylation | down-regulates activity | 0.2 | PGAM5-mediated dephosphorylation of malic enzyme 1 (ME1) at S336 allows increased ACAT1-mediated K337 acetylation, leading to ME1 dimerization and activation, both of which are reversed by NEK1 kinase-mediated S336 phosphorylation. SIRT6 deacetylase antagonizes ACAT1 function in a manner that involves mutually exclusive ME1 S336 phosphorylation and K337 acetylation. | SIGNOR-275570 |
Q9Y4C1 | Q71DI3 | 1 | demethylation | up-regulates activity | 0.2 | Using a biochemical assay coupled with chromatography, we have purified a JmjC domain-containing protein, JHDM2A, which specifically demethylates mono- and dimethyl-H3K9. | SIGNOR-276844 |
O14867 | P04406 | 1 | transcriptional regulation | up-regulates quantity | 0.2 | BACH1 activates transcription of Hexokinase 2 and Gapdh and increases glucose uptake, glycolysis rates, and lactate secretion, thereby stimulating glycolysis-dependent metastasis of mouse and human lung cancer cells. | SIGNOR-259339 |
O60260 | P02788 | 1 | ubiquitination | down-regulates activity | 0.2 | We propose that Parkin ubiquitylation of LTF at K649 perturbs LTF\u2019s ability to accumulate intracellular iron levels and that depletion of Parkin, or substitution of K649 on LTF, allows LTF to accumulate intracellular iron levels.|Parkin dependent ubiquitylation of LTF occurred most often on lysines (K) 182 and 649. | SIGNOR-278641 |
Q9UNE7 | Q9ULG1 | 1 | ubiquitination | up-regulates activity | 0.2 | Then, by an in vivo ubiquitination assay under denaturing conditions (hereafter, all in vivo ubiquitination assays were carried out under denaturing conditions), we determined whether CHIP ubiquitinates Ino80.|We also show that CHIP works together with BAP1 to enhance the stabilization of Ino80, leading to its chromatin binding. | SIGNOR-278646 |
Q00535 | Q8IWR1 | 1 | phosphorylation | up-regulates activity | 0.2 | Here, we identify TRIM59 as a substrate of CDK5. EGFR-activated CDK5 directly binds to and phosphorylates TRIM59, a ubiquitin ligase at serine 308, which recruits PIN1 for cis-trans isomerization of TRIM59, leading to TRIM59 binding to importin α5 and nuclear translocation. | SIGNOR-272929 |
P25098 | Q16581 | 1 | phosphorylation | down-regulates activity | 0.2 | These findings indicated that agonist-induced C3aR phosphorylation by GRK2 promotes C3aR desensitization. | SIGNOR-279044 |
O60260 | O15354 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | Parkin is a protein of 465 amino acids, and its structure includes a ubiquitin homologous domain in its N terminus and two RING finger domains in its C terminus. Molecular studies have determined that parkin is an E3 ubiquitin ligase function, implicating parkin in the ubiquitin-proteasome system, and raising the possibility that mutations in the gene lead to loss or diminished function. Three substrates for the ubiquitin-ligase function of parkin have been identified to date.1. A 22kDa glycosolated form of alpha-synuclei|2. Parkin-associated endothelin receptor-like receptor (Pael-R). | SIGNOR-249706 |
O75398 | Q05925 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Deaf1 is the first transcription factor implicated in the regulation of En1, a critical determinant of eccrine fate, within keratinocytes. | SIGNOR-269062 |
Q9BYW2 | P68431 | 1 | trimethylation | up-regulates activity | 0.2 | Our results suggest that HYPB HMTase may coordinate histone methylation and transcriptional regulation in mammals and open perspective for the further study of the potential roles of HYPB protein in hematopoiesis and pathogenesis of HD. | SIGNOR-269071 |
Q9BQE4 | P55072 | 1 | binding | up-regulates activity | 0.2 | VIMP mediates p97 binding to hDerlin-1. these data suggest that Derlin-1 and VIMP form a membrane protein complex that serves as a receptor for p97. | SIGNOR-261371 |
Q9Y5H9 | Q9Y5H4 | 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-265686 |
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