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 |
|---|---|---|---|---|---|---|---|
Q00987 | O75417 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | DNA polymerase eta is targeted by Mdm2 for polyubiquitination and proteasomal degradation in response to ultraviolet irradiation | SIGNOR-272729 |
Q05655 | P25054 | 1 | phosphorylation | down-regulates activity | 0.2 | APC is Phosphorylated by PKCdelta in Intact RKO Cells. | SIGNOR-279650 |
P27695 | P01266 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | In co-transfection experiments, Ref-1 increases the Pax-8 activating effect on thyroglobulin promoter. | SIGNOR-271694 |
O60260 | Q16665 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | These results indicate that Parkin inhibits HIF-1alpha transcriptional activity.|Ubiquitination of HIF-1alpha at lysine 477 by Parkin. | SIGNOR-278542 |
P37198 | P23258 | 1 | binding | up-regulates activity | 0.2 | Furthermore, we found interactions and co-localization with γ-tubulin and SAS-6. Our results also point to a potential role of Nup62 in targeting gamma-tubulin and SAS-6 to the centrioles. | SIGNOR-261257 |
Q8N2H9 | Q15306 | 1 | ubiquitination | down-regulates activity | 0.2 | Peli3 induces the degradation of IRF4 through K48‐mediated ubiquitination |To detect the direct interaction of Peli3 and IRF4, Peli3 and IRF4 DNA constructs were transfected into HEK293 cells. | SIGNOR-280453 |
Q14289 | Q02535 | 1 | phosphorylation | up-regulates quantity | 0.2 | Taken together these findings demonstrated that Pyk2 mediates the expression of ID3 protein.|Together these findings from the combined MS+MS/MS data confirm that Flag tagged ID3 is phosphorylated by active recombinant Pyk2 kinase; and support the phospho-Tyr band that was detected at the corresponding MW ~ 13 kDA for Flag-ID3 by immunoblot. | SIGNOR-278496 |
P13674 | P04035 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | In this study, we found that the prolyl 4-hydroxylase (P4H) subunit P4HA1 protects NPC cells from erastin-induced ferroptosis by activating HMGCS1, a key enzyme in the mevalonate pathway. Our results show that HMGCS1 and HMGCR are regulated by P4HA subunits at the transcriptional level (Fig. S4). | SIGNOR-279854 |
P68400 | O43395 | 1 | phosphorylation | up-regulates | 0.2 | Our findings provide new insights into the biology of hprp3p and suggest that the loss of hprp3p phosphorylation at thr494 is a key step for initiating thr494met aberrant interactions within u4/u6 snrnp complex and that these are likely linked to the rp18 phenotype. | SIGNOR-158319 |
Q6P1N0 | O60216 | 1 | binding | up-regulates activity | 0.2 | Akt kinase-interacting protein 1 (Aki1)/Freud-1/CC2D1A is localized in the cytosol, nucleus, and centrosome. Aki1 plays distinct roles depending on its localization. | In the centrosome, it regulates spindle pole localization of the cohesin subunit Scc1, thereby mediating centriole cohesion during mitosis. | SIGNOR-268294 |
Q9BZL6 | Q9BZL6 | 2 | phosphorylation | up-regulates | 0.2 | The addition of phorbol 12,13-dibutyrate in the presence of dioleoylphosphatidylserine stimulated the autophosphorylation of pkd2 in a synergistic fashion.In addition, we could identify the c-terminal ser(876) residue as an in vivo phosphorylation site within pkd2. Phosphorylation of ser(876) of pkd2 correlated with the activation status of the kinase. | SIGNOR-83834 |
Q2M2I8 | Q9BXS5 | 1 | phosphorylation | up-regulates | 0.2 | Aak1 is enriched at presynaptic terminals, whereas in nonneuronal cells it colocalizes with clathrin and ap2 in clathrin-coated pits and at the leading edge of migrating cells. Aak1 specifically phosphorylates the mu subunit in vitro, and stage-specific assays for endocytosis show that mu phosphorylation by aak1 results in a decrease in ap2-stimulated transferrin internalization. Together, these results provide strong evidence that aak1 is the endogenous mu 2 kinase and plays a regulatory role in clathrin-mediated endocytosis. | SIGNOR-115589 |
P49674 | P15923 | 1 | phosphorylation | up-regulates | 0.2 | Tcf3 is a substrate for both glycogen synthase kinase (gsk) 3 and casein kinase (ck) 1epsilon, and phosphorylation of tcf3 by ckiepsilon stimulates its binding to beta-catenin, an effect reversed by gsk3. | SIGNOR-110056 |
P23470 | P23470 | 2 | binding | down-regulates activity | 0.2 | The main regulatory mechanism of RPTP activity consists of the reversible transition from a homodimeric inactive form to a monomeric active form. PTPRG is constitutively expressed on monocyte plasma membrane as a homodimer with the WD involved in catalytic domain blockade. | SIGNOR-254737 |
P17252 | O75144 | 1 | phosphorylation | up-regulates activity | 0.2 | PKCα and PKCβ are required for phosphorylation of ICOSL and ICOSL-mediated cytokine induction. Therefore, S285 is required for PKC substrate (serine) phosphorylation of ICOSL, and each of the upstream arginines is similarly required for this phosphorylation. | SIGNOR-273798 |
P19525 | P10636 | 1 | phosphorylation | up-regulates quantity | 0.2 | Interestingly, PKR phosphorylated tau directly and no detectable labeling occurred when tau was incubated with 32 P\u2010ATP alone (Figure\u00a0 xref right).|PKR kinase directly regulates tau expression and Alzheimer's disease-related tau phosphorylation. | SIGNOR-279735 |
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 |
O00398 | 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-257287 |
O00712 | 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-268912 |
O75914 | O75914 | 2 | phosphorylation | up-regulates activity | 0.2 | Both in vivo and in vitro analyses demonstrate that, although most phosphorylation events in the PAK N-terminal regulatory domain play no direct role in activation, a phosphorylation of alphaPAK serine 144 or betaPAK serine 139, which lie in the kinase inhibitory domain, significantly contribute to activation. | SIGNOR-250245 |
O95644 | Q03405 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Inducible podocyte-specific expression of constitutively active NFATc1 increased podocyte uPAR expression by binding to the Plaur gene promoter (encoding uPAR) in chromatin immunoprecipitation assays. | SIGNOR-253336 |
Q6UB99 | P23560 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Neurite growth-related genes such as Trkb, Bdnf, Gap43, Coronin 1B, and Rab13 are downregulated in ANKRD11-deficient neurons. | SIGNOR-266732 |
Q9Y5H9 | Q9UN71 | 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-265679 |
P30291 | O43660 | 1 | phosphorylation | down-regulates activity | 0.2 | These results indicate that WEE1 promotes PRL1 phosphorylation.|WEE1 promotes PRL1 degradation . | SIGNOR-279579 |
O75151 | P84243 | 1 | demethylation | up-regulates activity | 0.2 | PHF2, a jmjC demethylase, is enzymatically inactive by itself, but becomes an active H3K9Me2 demethylase through PKA-mediated phosphorylation. This modification leads to targeting of the PHF2–ARID5B complex to its target promoters, where it removes the repressive H3K9Me2 mark. | SIGNOR-264518 |
P00533 | P25098 | 1 | phosphorylation | up-regulates activity | 0.2 | Previous studies showed that EGFR activation results in association of GRK2 with the EGFR and subsequent phosphorylation of GRK2 at three tyrosine residues (Tyr 13, -86, and -92), resulting in activation of GRK2.|We propose that GRK2 activation by EGFR leads to GRK2 phosphorylation of Mst2 at these sites, which, in turn, regulates the Mst2-Nek2A-PP1\u03b3 complex ( xref ). | SIGNOR-279368 |
Q14493 | Q5TEC6 | 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-265415 |
Q04771 | Q96JC1 | 1 | binding | up-regulates activity | 0.2 | TLP interacts with TGF-β and activin receptors in vivo. Endogenous TLP associates with both active and kinase-deficient TGF-beta and activin type II receptors, but interacts with the common-mediator Smad4 only in the presence of TGF-beta/activin signaling. | SIGNOR-261376 |
P20794 | P20794 | 2 | phosphorylation | up-regulates activity | 0.2 | We conclude that dual phosphorylation on the TDY motif is crucial for MAK activity, and that the autokinase activity is required for this phosphorylation | SIGNOR-260779 |
P00519 | Q8IWL8 | 1 | phosphorylation | up-regulates activity | 0.2 | STH interacts with tau and Abl, and Abl phosphorylates STH on its single tyrosine residue. | SIGNOR-279353 |
P11362 | O15530 | 1 | phosphorylation | up-regulates activity | 0.2 | Y105 phosphorylation of PKM2, which is involved in FGFR1-regulated PDHK1 expression, appears to be an upstream event that precedes FGFR1-dependent phosphorylation and activation of PDHK1 in cancer cell metabolism. | SIGNOR-279174 |
P18848 | Q9NP81 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress. | SIGNOR-269425 |
P06748 | P09467 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | For instance, nucleophosmin (NPM1) and zinc-finger protein X-linked (ZFX) bind to the E-box and ZFX binding site on the FBP1 promoter, respectively, and restrain FBP1 expression to facilitate aerobic glycolysis in PDAC and melanoma | SIGNOR-267594 |
Q9BZL6 | Q13563 | 1 | phosphorylation | up-regulates activity | 0.2 | Here, we report the identification of a previously unrecognized phosphorylation site within the polycystin-2 C terminus (Ser801), and we demonstrate that it is phosphorylated by protein kinase D. These results suggest that growth factor-stimulated, protein kinase D-mediated phosphorylation of polycystin-2 is essential for its ER channel function and links extracellular stimuli to its effects on cell growth and intracellular calcium regulation. | SIGNOR-276284 |
Q86Y13 | Q16777 | 1 | monoubiquitination | up-regulates activity | 0.2 | 2A-HUB catalyzes monoubiquitination of H2A at lysine 119, functioning as a combinatoric component of the repression machinery required for specific gene regulation programs. Thus, 2A-HUB mediates a selective repression of a specific set of chemokine genes in macrophages, critically modulating migratory responses to TLR activation. H2A monoubiquitination acts to prevent FACT recruitment at the transcriptional promoter region, blocking RNA polymerase II release at the early stage of elongation. | SIGNOR-271754 |
Q09472 | Q9UPG8 | 1 | acetylation | up-regulates | 0.2 | Plag1 and plagl2 are also regulated by acetylation. They are acetylated and activated by p300 and deacetylated and repressed by hdac7. | SIGNOR-140947 |
P17676 | P17174 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | In cotransfection experiments, the C/EBP beta protein trans-activated 10-15-fold the cAspAT gene promoter in HepG2 cells. Deletion studies revealed that regions P2 and P4 are critical for promoter activity. In gel retardation experiments, the P4 region bound different C/EBP-related proteins in different tissues | SIGNOR-254051 |
Q12834 | P23497 | 1 | binding | down-regulates quantity by destabilization | 0.2 | Cdc20 is a co-activator of the anaphase-promoting complex/cyclosome (APC/C complex), which recruits substrates at particular phases of the cell cycle and mediates their degradation. Overexpression of Cdc20 resulted in decreased levels of both endogenous Sp100 protein and overexpressed Sp100 mRNA in HEK 293 cells. Our results suggested that sp100 is a novel substrate of Cdc20 and it is degraded by the ubiquitination pathway. The intact D-box of Sp100 was necessary for this process. | SIGNOR-272724 |
Q96LB1 | 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-256930 |
P40189 | P07947 | 1 | phosphorylation | up-regulates activity | 0.2 | Binding of LIF to the LIFR-gp130 receptor complex has been previously shown to activate YES and YAP/TAZ-TEAD -dependent transcription, which is required to maintain self-renewal in embryonic stem cells | SIGNOR-278033 |
Q96LB2 | O95837 | 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-257433 |
Q14331 | Q4FZB7 | 1 | binding | down-regulates activity | 0.2 | Here we show that, when over-expressed, FRG1 binds and interferes with the activity of the histone methyltransferase Suv4-20h1 both in mammals and Drosophila. Accordingly, FRG1 over-expression or Suv4-20h1 knockdown inhibits myogenesis. | SIGNOR-266639 |
Q92824 | P01178-PRO_0000020496 | 1 | cleavage | up-regulates quantity | 0.2 | Oxytocin-extended form is further cleaved by enzymatic activity to yield the nine-amino-acid active peptide, OT. The proteolysis may involve several pro-hormone convertases, convertase 2 (PC2) (20p11-1-11.2) and convertase 5 (PC5) (9q21.3) (Gabreels et al 1998). Both enzymes are found in OT neurosecretory vesicles and are a part of a family of subtilisen/kexinlike convertases (Seidah et al 1994). It is a product of the OT gene located at human gene locus 20p13 (Rao et al 1992). The processing cascade results in the production of neurophysin I and OT extended form (OT-X), which is OT with a C-terminal, three-amino-acid extension. | SIGNOR-270336 |
O60260 | Q8IWA4 | 1 | ubiquitination | down-regulates quantity | 0.2 | Parkin and PINK1 are required for ubiquitination of MFN-1 and MFN-2. Decreases in MFN-1 and MFN-2 protein levels seen at later timepoints are difficult to interpret as it is unclear whether this is due to degradation by the proteasome and/or loss of whole mitochondria by mitophagy. | SIGNOR-272779 |
Q9Y5H9 | 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-265687 |
O14905 | P02708 | 1 | binding | up-regulates | 0.2 | We identified five wnts (wnt9a, wnt9b, wnt10b, wnt11, and wnt16) that are able to stimulate achr clustering, of which wnt9a and wnt11 are expressed abundantly in developing muscles. | SIGNOR-195978 |
Q9Y243 | P55265 | 1 | phosphorylation | down-regulates activity | 0.2 | AKT-dependent phosphorylation of the adenosine deaminases ADAR-1 and -2 inhibits deaminase activity. Coimmunoprecipitation studies and in vitro kinase assays revealed that AKT-1, -2, and -3 interact with both ADAR1p110 and ADAR2 and phosphorylate these RNA editases. Using site-directed mutagenesis of suspected AKT phosphorylation sites, AKT was found to primarily phosphorylate ADAR1p110 and ADAR2 on T738 and T553, respectively | SIGNOR-276191 |
Q9NS75 | P08754 | 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-256746 |
Q9NQU5 | P53667 | 1 | phosphorylation | up-regulates activity | 0.2 | PAK6 bound to LIMK1 and activated it via phosphorylation at Thr-508.|These data indicated that PAK6 directly phosphorylated LIMK1 at Thr-508. | SIGNOR-278970 |
Q14493 | Q99878 | 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-265404 |
P17612 | Q9Y6X9 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.2 | Mechanistically, GPER1 activates PRKACA (protein kinase cAMP-activated catalytic subunit alpha), which in turn phosphorylates MORC2 at threonine 582 (T582). Phosphorylated MORC2 decreases its interaction with HSPA8 (heat shock protein family A [Hsp70] member 8) and LAMP2A (lysosomal associated membrane protein 2A), two core components of the chaperone-mediated autophagy (CMA) machinery, thus protecting MORC2 from lysosomal degradation by CMA. | SIGNOR-273781 |
O15111 | P06748 | 1 | phosphorylation | up-regulates activity | 0.2 | S125A and a delta form lacking the aa 119-195 region completely abolished NPM phosphorylation by IKKalpha (XREF_FIG), suggesting that IKKalpha phosphorylates S125 of NPM.|We found that TNFalpha treatment induced IKKalpha phosphorylation and increased NPM hexamers, which were correlated with increased NPM phosphorylation (XREF_FIG). | SIGNOR-279405 |
P29322 | P29322 | 2 | phosphorylation | up-regulates activity | 0.2 | Tyr-615 and Tyr-838 are major autophosphorylation sites of the EphA8 receptor. phosphorylation of Tyr-615 is critical for determining the association with Fyn whereas the integrity of Tyr-838 phosphorylation is required for efficient phosphorylation at Tyr-615 as well as other major sites. | SIGNOR-251121 |
Q68D86 | Q96CN5 | 1 | binding | up-regulates activity | 0.2 | CCDC102B is recruited to the centrosome by C-Nap1 (also known as CEP250) and interacts with the centrosome linker components rootletin and LRRC45. CCDC102B decorates and facilitates the formation of rootletin filaments. Furthermore, CCDC102B is phosphorylated by Nek2A (an isoform encoded by NEK2) and is disassociated from the centrosome at the onset of mitosis. | SIGNOR-275627 |
P16220 | P35575 | 1 | transcriptional regulation | up-regulates quantity | 0.2 | Further, CRTC2 is required for the glucocorticoid-associated cooperative mRNA expression of the glucose-6-phosphatase, a rate-limiting enzyme for hepatic gluconeogenesis, by facilitating the attraction of GR and itself to its promoter region already occupied by CREB | SIGNOR-256105 |
P49321 | Q9Y4K3 | 1 | binding | down-regulates activity | 0.2 | SNASP inhibits TLR4-induced NF-κB activation through TRAF6.Reciprocal immunoprecipitation and Western blot analyses confirmed that endogenous sNASP binds to TRAF6 in human monocyte cell line THP-1 (Figure 1B).Here, we show that somatic nuclear autoantigenic sperm protein (sNASP) binds to TRAF6 to prevent TRAF6 autoubiquitination in unstimulated macrophages. Following LPS stimulation, a complex consisting of sNASP, TRAF6, IRAK4, and casein kinase 2 (CK2) is formed. CK2 phosphorylates sNASP at serine 158, allowing sNASP to dissociate from TRAF6. Free TRAF6 is then autoubiquitinated, followed by activation of downstream signaling pathways. | SIGNOR-273655 |
Q16665 | Q9H3R0 | 2 | 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-271570 |
Q9Y5I2 | Q9Y5G7 | 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-265716 |
Q9P2K6 | Q16537 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | PPP2R5ϵ is a KLHL42 substrate and affects TGF-β signaling in SSc. Lys-84 is a candidate ubiquitin acceptor site within PPP2R5ϵ. | SIGNOR-272205 |
P16220 | Q9Y2T3 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | In addition, exposure of the neurons to BDNF increased CREB binding to the cypin promoter and, in line with these data, expression of a dominant negative form of CREB blocked BDNF-promoted increases in cypin protein levels and proximal dendrite branches. | SIGNOR-268968 |
Q02952 | P17612 | 2 | relocalization | up-regulates activity | 0.2 | A-kinase-anchoring protein 250 (AKAP250; gravin) acts as a scaffold that binds protein kinase A (PKA), protein kinase C and protein phosphatases, associating reversibly with the beta(2)-adrenergic receptor. | SIGNOR-271835 |
O14647 | Q13426 | 1 | relocalization | up-regulates quantity | 0.2 | CHD2 Promotes the Recruitment of Core NHEJ Factors. overexpression of ATPase-dead CHD2 (K515R; Figure S5F), but not wild-type CHD2, also reduced the recruitment of XRCC4 (Figure 5E). Together, these findings suggest that the chromatin remodeling activity of CHD2 promotes the efficient assembly of NHEJ complexes at DSBs. | SIGNOR-264528 |
P53778 | P05787 | 1 | phosphorylation | up-regulates | 0.2 | Keratin 8 (k8) serine 73 occurs within a relatively conserved type ii keratin motif . Here we show that ser-73 is exclusively phosphorylated in vitro by p38 mitogen-activated protein kinase. The ser-73 --> ala-associated filament reorganization defect is rescued by a ser-73 --> asp mutation. Also, disease-causing keratin mutations can modulate keratin phosphorylation and organization, which may affect disease pathogenesis. | SIGNOR-114067 |
P51812 | Q99990 | 1 | phosphorylation | down-regulates activity | 0.2 | Site-directed mutagenesis and immunoprecipitation experiments revealed that RSK2 phosphorylated VGLL1 at S84 in the presence of TGF-β. Mutation of VGLL1 at S84 suppressed VGLL1-TEAD4 binding and the subsequent transcriptional activation of matrix metalloprotease 9 (MMP9). | SIGNOR-273842 |
P17612 | Q96PU5 | 1 | phosphorylation | down-regulates | 0.2 | Nedd4-2 was a substrate for phosphorylation by pka in vitro and in cells;three nedd4-2 residues were phosphorylated by pka and were required for camp to inhibit nedd4-2 (relative functional importance ser-327 > ser-221 > thr-246). | SIGNOR-128429 |
O43638 | P98177 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | Fkhl18 suppressed the transcriptional activity of FoxO3a and FoxO4. | SIGNOR-261611 |
P49840 | Q9BYG3 | 1 | phosphorylation | up-regulates activity | 0.2 | The forkhead-associated (FHA) domain of human Ki67 interacts with the human nucleolar protein hNIFK, recognizing a 44-residue fragment, hNIFK226-269, phosphorylated at Thr234. Here we show that high-affinity binding requires sequential phosphorylation by two kinases, CDK1 and GSK3, yielding pThr238, pThr234 and pSer230. phosphorylation of Thr234 by GSK3 proceeds only after Thr238 is already phosphorylated by CDK1. | SIGNOR-262697 |
P61328 | 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-253424 |
P49841 | Q99612 | 1 | phosphorylation | up-regulates activity | 0.2 | Functionally, GSK3beta enhanced KLF6 mediated growth suppression, which was abrogated by the KLF6-4A phosphomutant.|These data establish that GSK3\u03b2 directly phosphorylates KLF6, which augments its induction of p21 and resultant growth suppression. | SIGNOR-279373 |
P07384 | P49840 | 1 | cleavage | up-regulates activity | 0.2 | Thus, it has been shown that calpain cleaves the inhibitory domain of GSK3 generating two fragments of 40 and 30 kDa. This cleavage enhanced activity of the kinase | SIGNOR-251585 |
Q96A26 | P21796 | 1 | binding | up-regulates activity | 0.2 | HGTD-P was coprecipitated with VDAC but not with ANT or cyclophilin D (Fig. 7A, left upper panel).|However, it is not clear at present whether HGTD-P participates directly in channel formation in association with VDAC or modulates its channel-forming activity. | SIGNOR-260293 |
O75688 | Q6WCQ1 | 1 | dephosphorylation | down-regulates activity | 0.2 | Ppm1b prevents Rip3 auto-activation in resting cells.|Together, these data demonstrate that Ppm1b dephosphorylates Rip3 and thus negatively regulates TNF induced necroptosis in L929 cells. | SIGNOR-277019 |
P25098 | P30989 | 1 | phosphorylation | up-regulates activity | 0.2 | Here we report the unique phosphorylation\nof NTSR1 by GRK2 and GRK5, which belong to the GRK2 and GRK4 subfamilies,\nrespectively. | SIGNOR-278280 |
Q92914 | Q9UI33 | 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-253438 |
Q13131 | O75925 | 1 | phosphorylation | up-regulates activity | 0.2 | Mechanically, we found that AMPKα1 directly phosphorylated protein inhibitor of activated STAT-1 (PIAS1), the SUMO E3-ligase of Runx2, at serine 510, to promote its SUMO E3-ligase activity. Finally, mutation of protein inhibitor of activated STAT-1 at serine 510 suppressed m | SIGNOR-259866 |
Q86Y13 | P0C0S8 | 1 | monoubiquitination | up-regulates activity | 0.2 | 2A-HUB catalyzes monoubiquitination of H2A at lysine 119, functioning as a combinatoric component of the repression machinery required for specific gene regulation programs. Thus, 2A-HUB mediates a selective repression of a specific set of chemokine genes in macrophages, critically modulating migratory responses to TLR activation. H2A monoubiquitination acts to prevent FACT recruitment at the transcriptional promoter region, blocking RNA polymerase II release at the early stage of elongation. | SIGNOR-271749 |
P49593 | O95835 | 1 | dephosphorylation | down-regulates activity | 0.2 | POPX2 is capable of dephosphorylating LATS1 at Thr1079 (Figure xref ), which is a residue critical for LATS1 activity.|POPX2 might negatively regulate the activities of MST1 and LATS1 through dephosphorylation.|We found that POPX2 could dephosphorylate LATS1 on Threonine-1079, leading to inactivation of LATS1 kinase. | SIGNOR-276989 |
P49841 | P49841 | 2 | phosphorylation | up-regulates activity | 0.2 | Phosphorylation of the residue Tyrosine in 216 position results in the constitutive activity of GSK-3beta and believed to be important target for signal transduction. | SIGNOR-217865 |
O00418 | O00418 | 2 | phosphorylation | down-regulates | 0.2 | The combination of eef2k autophosphorylation (targeting ser445) and a yet to be identified kinase (targeting ser441) would be needed to generate the eef2k phosphodegron specifically in response to dna damage. | SIGNOR-197725 |
Q7Z3C6 | P62258 | 1 | binding | up-regulates activity | 0.2 | Our data suggest that the localization of mammalian Atg9A to autophagosomes requires phosphorylation on the C terminus of Atg9A at S761, which creates a 14-3-3ζ docking site. Under basal conditions, this phosphorylation is maintained at a low level and is dependent on both ULK1 and AMPK. | SIGNOR-266368 |
Q86YJ5 | Q12913 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | MARCH9, a member of the RING-CH family of transmembrane E3 ubiquitin ligases, down-regulates CD4, major histocompatibility complex-I (MHC), and ICAM-1 in lymphoid cells. To identify novel MARCH9 substrates, we used high throughput flow cytometry and quantitative mass spectrometry by stable isotope labeling by amino acids in cell culture (SILAC) to determine the differential expression of plasma membrane proteins in a MARCH9-expressing B cell line. This combined approach identified 13 potential new MARCH9 targets. | SIGNOR-271535 |
P31749 | Q5XUX0 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Here we show that the low levels of FBXO31 are maintained through proteasomal degradation by anaphase-promoting complex/cyclosome (APC/C). We find that the APC/C coactivators CDH1 and CDC20 bind to a destruction-box (D-box) motif present in FBXO31 to promote its polyubiquitination and degradation in a cell-cycle-regulated manner, which requires phosphorylation of FBXO31 on serine-33 by the prosurvival kinase AKT. | SIGNOR-277376 |
O60260 | P55036 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | S5a/Rpn10 is a ubiquitin (Ub)-binding protein that is a subunit of the 26S proteasome but also exists free in the cytosol. It binds poly-Ub chains through its two Ub-interacting motifs (UIMs). We discovered that, unlike typical substrates of Ub ligases (E3s), S5a can be ubiquitinated by all E3s tested including multimeric and monomeric Ring finger E3s (MuRF1, Siah2, Parkin, APC, and SCF(betaTRCP1)), the U-box E3, CHIP, and HECT domain E3s (E6AP and Nedd4) when assayed with UbcH5 or related Ub-conjugating enzymes.The short half-life of S5a presumably is because of the presence of the UIM domain and reflects the ubiquitination of free S5a by many E3s. | SIGNOR-272749 |
P06493 | Q9UPU5 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Epidermal growth factor (EGF) treatment, and the KrasG12D and EGFRL858R mutations decrease USP24 protein stability via EGF- or CDK1-mediated phosphorylation at Ser1616, Ser2047 and Ser2604. | SIGNOR-275605 |
Q14469 | P53805 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | Increased Calcineurin/NFAT activity by Notch signaling involves downregulation of Calcipressin, an endogenous Calcineurin inhibitor, through a HES-1-dependent mechanism .... Chromatin immunoprecipitation (ChIP) analysis of keratinocytes overexpressing HES-1 showed that this protein can bind to the HES binding sites present in both distal and proximal promoters | SIGNOR-252026 |
Q7Z589 | P83916 | 1 | binding | up-regulates activity | 0.2 | The binding sites for HP1β and BS69 with EMSY abut each other, and are found directly adjacent to the ENT domain of EMSY. This demonstrates that EMSY has the capacity to contact directly at least two proteins which contain a Royal Family domain. Since this domain is found in proteins with a chromatin connection, we assume that EMSY functions, at least partly, in the regulation of chromatin. | SIGNOR-263917 |
P48729 | Q99873 | 1 | phosphorylation | up-regulates activity | 0.2 | CSNK1a1 directly bound and phosphorylated PRMT1 to control its genomic targeting to PRMT1-sustained proliferation genes as well as PRMT1-suppressed differentiation genes.|Taken together, these data support a provisional model in which CSNK1a1 directs PRMT1 to genomic targets that promote self-renewal and suppress terminal differentiation.In the context of transcription regulation, PRMT1 has been generally considered as a transcriptional co-activator. | SIGNOR-279733 |
Q5SGD2 | Q9Y5P4 | 1 | dephosphorylation | up-regulates activity | 0.2 | The expression of PP2Cepsilon also enhanced the association between CERT and VAPA.|These results suggest that CERT is a physiological substrate of PP2Cepsilon and that dephosphorylation of CERT by PP2Cepsilon may play an important role in the regulation of ceramide trafficking from the ER to the Golgi apparatus. | SIGNOR-277113 |
P09341 | P17612 | 1 | binding | down-regulates | 0.2 | 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-152594 |
P29350 | Q14247 | 1 | dephosphorylation | down-regulates activity | 0.2 | Shp1 interacts with cortactin and reduces cortactin phosphorylation at tyrosine 421; 3.|induction of Shp1-cortactin complex formation impairs cortactin scaffolding-activity and negatively affects invadopodia behaviour; 4. | SIGNOR-277003 |
Q969V5 | Q86WV6 | 1 | ubiquitination | up-regulates activity | 0.2 | Identification of MUL1 as an essential activator of dsDNA mediated STING dependent pathway.|We further report that the mitochondrial E3 ubiquitin protein ligase 1 (MUL1, also known as GIDE/MAPL/MULAN/RNF218) ubiquitinates STING on K224 via K63-linked polyubiquitination, which facilitates optimal STING trafficking and the transcription of host defense genes. | SIGNOR-278634 |
P25105 | 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-257329 |
Q15796 | Q15796 | 2 | binding | up-regulates activity | 0.2 | Smad2 and Smad3 form homo-oligomers upon phosphorylation by the constitutively active TGF-beta type I receptor, and this oligomerization does not require Smad4 | SIGNOR-232149 |
P11309 | Q99814 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.2 | PIM1 kinase directly phosphorylates HIF-1α at threonine 455, a previously uncharacterized site within its oxygen-dependent degradation domain. This phosphorylation event disrupts the ability of prolyl hydroxylases to bind and hydroxylate HIF-1α, interrupting its canonical degradation pathway and promoting constitutive transcription of HIF-1 target genes. Moreover, phosphorylation of the analogous site in HIF-2α (S435) stabilizes the protein through the same mechanism, indicating post-translational modification within the oxygen-dependent degradation domain as a mechanism of regulating the HIF-α subunits. | SIGNOR-277310 |
P29371 | 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-256937 |
Q9BXM7 | O60260 | 1 | phosphorylation | up-regulates | 0.2 | We show that human pink1 is specifically activated by mitochondrial membrane potential (??m) depolarization, enabling it to phosphorylate parkin at ser(65). We further show that phosphorylation of parkin at ser(65) leads to marked activation of its e3 ligase activity that is prevented by mutation of ser(65) or inactivation of pink1. | SIGNOR-197976 |
P24941 | Q12800 | 1 | phosphorylation | down-regulates | 0.2 | In vitro, lsf is phosphorylated by cyclin e/cyclin-dependent kinase 2 (cdk2), cyclin c/cdk2, and cyclin c/cdk3, predominantly on s309. Phosphorylation by cyclin c/cyclin-dependent kinase 2 following mitogenic stimulation of murine fibroblasts inhibits transcriptional activity of lsf during g1 progression | SIGNOR-184160 |
P36873 | O95786 | 1 | dephosphorylation | up-regulates activity | 0.2 | We identified PP1alpha and PP1gamma as primary phosphatases responsible for MDA5 and RIG-I dephosphorylation, leading to their activation.|endogenous RIG-I and MDA5 that interacted with PP1 exhibited markedly decreased phosphorylation levels at S8 and S88, respectively | SIGNOR-264580 |
Q13043 | P52945 | 1 | phosphorylation | down-regulates activity | 0.2 | MST1 directly phosphorylated PDX1 at Thr11, resulting in its ubiquitination, degradation and impaired insulin secretion.|Thus, kinase activity is required for MST1 induced PDX1 degradation. | SIGNOR-278303 |
P28482 | O00562 | 1 | phosphorylation | up-regulates | 0.2 | Both cdk1 and erk2 induced phosphorylation of the wild-type nir2. Substitution of t794 by alanine reduced the phosphorylation by erk2, whereas the double mutations t794/1223a completely abolished it. The requirement of multiple nir2 phosphorylation sites for plk1 binding may provide a mechanism that sets a threshold for the nir2-plk1 interaction during mitosis. | SIGNOR-124646 |
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