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 |
|---|---|---|---|---|---|---|---|
P27448 | Q13470 | 1 | phosphorylation | down-regulates activity | 0.2 | We also discover a MARK-mediated phosphorylation on TNK1 at S502 that promotes an interaction between TNK1 and 14-3-3, which sequesters TNK1 and inhibits its kinase activity.Phosphorylation of TNK1 at S502 within the proline rich domain is required for TNK1 binding to 14-3-3.MARKs mediate phosphorylation at S502 and 14-3-3 binding to TNK1, which restrains the movement of TNK1 into heavy membrane-associated clusters. | SIGNOR-273868 |
Q7Z589 | P51587 | 1 | binding | down-regulates activity | 0.2 | The EMSY protein interacts precisely with a highly conserved transactivating region at the N terminus of the breast cancer protein BRCA2, and has endogenous transcriptional repressor activity when recruited to a high basal promoter. We have suggested that the independent activation domain of BRCA2 within exon 3 might have some role in transcription (Milner et al., 1997). The identification of the repressor protein EMSY, which binds and silences this domain, is consistent with such a function. | SIGNOR-263915 |
O15055 | P14859 | 1 | binding | down-regulates activity | 0.2 | This PER2-OCT1 interaction effectively converted OCT1 sites, which normally activate expression, into repressor sites by recruitment of a polycomb repressor complex including EZH2 and SUZ12, as well as HDAC2. | SIGNOR-254148 |
Q8N531 | P29401 | 1 | ubiquitination | up-regulates activity | 0.2 | Mechanistically, VRK2 promoted Thr287 phosphorylation of TKT and then recruited FBXL6 to promote TKT ubiquitination and activation. | SIGNOR-277843 |
P24941 | Q16584 | 1 | phosphorylation | up-regulates activity | 0.2 | Using in vitro kinase assays and phosphomutants, we determined that CDK1 phosphorylates MLK3 on Ser548 and decreases MLK3 activity during mitosis, whereas CDK2 phosphorylates MLK3 on Ser770 and increases MLK3 activity during G1/S and G2 phases. | SIGNOR-277604 |
O94826 | P07900 | 1 | binding | up-regulates activity | 0.2 | The Tom70 receptor is a membrane-localized cochaperone that integrates the Hsp70/Hsp90 chaperones with mitochondrial preprotein targeting and translocation. In mammals, preprotein in the cytosol is associated with both Hsp90 and Hsp70 in a multichaperone complex, and docking of Hsp90 and/or Hsp70 onto Tom70 is essential for preprotein targeting. | SIGNOR-261379 |
Q92785 | P11474 | 1 | binding | down-regulates activity | 0.2 | DPF2 directly bound to ERRalpha and suppressed the transactivation function of nuclear receptors such as androgen receptor. DPF2 was recruited to ERR target gene promoters in myoblast cells, and knockdown of DPF2 derepressed the level of mRNA expressed by target genes of ERRalpha. These results show that DPF2 acts as a nuclear receptor-selective co-repressor for ERRalpha by associating with both acetylated histone H3 and HDAC1. | SIGNOR-239539 |
Q05209 | P52565 | 1 | dephosphorylation | up-regulates activity | 0.2 | Integrin-bound PTP-PEST dephosphorylates RhoGDI1.|Translocation of Src phosphorylated RhoGDI1 to the cell 's leading edge promotes local activation of Rac1 and Cdc42, whereas dephosphorylation of RhoGDI1 by integrin bound PTP-PEST promotes RhoGDI1 release from the membrane and sequestration of inactive Rac1 and Cdc42 in the cytoplasm.|Translocation of Src-phosphorylated RhoGDI1 to the cell's leading edge promotes local activation of Rac1 and Cdc42, whereas dephosphorylation of RhoGDI1 by integrin-bound PTP-PEST promotes RhoGDI1 release from the membrane and sequestration of inactive Rac1/Cdc42 in the cytoplasm. | SIGNOR-277175 |
Q9NQU5 | O95831 | 1 | phosphorylation | down-regulates activity | 0.2 | Furthermore, PAK5 phosphorylates AIF at Thr281 site to inhibit the formation of AIF/importin \u03b13 complex, leading to decrease AIF nuclear translocation.|These results suggested that PAK5 can inhibit AIF from entering the nucleus and prevent caspase- independent apoptosis. | SIGNOR-278969 |
Q9NQU5 | P10275 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Furthermore, AR phosphorylation at Ser-578 by PAK6 promotes AR-E3 ligase murine double minute-2 (Mdm2) association, causing AR degradation upon androgen stimuli. | SIGNOR-279247 |
Q99759 | O43379 | 2 | binding | up-regulates quantity by stabilization | 0.2 | Specifically, we demonstrate that MEKK3 interacts with WDR62 to stabilize WDR62 and regulates JNK activity in a synergic way. On the other hand, JNK activity also regulates the phosphorylation of WDR62 at T1053 in a feedback loop which facilities the recruitment of FBW7 degradation of WDR62 | SIGNOR-271714 |
P35790 | O60664 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | In addition, as a protein kinase, CHKα2 phosphorylates PLIN2 at Tyrosine 232 and PLIN3 at Tyrosine 251. Phosphorylated PLIN2 and PLIN3 are separated from lipid droplets and degraded by Hsc70-mediated autophagy, thereby promoting lipid droplet lipolysis, fatty acid oxidation and glioblastoma growth | SIGNOR-267650 |
Q13535 | Q8IUQ4 | 1 | phosphorylation | down-regulates activity | 0.2 | We have also demonstrated that DNA damage triggers disruption of the HIPK2-Siah-1 complex, resulting in HIPK2 stabilization and activation. Disruption of the HIPK2-Siah-1 complex is mediated by the ATM/ATR pathway and involves ATM/ATR-dependent phosphorylation of Siah-1 at Ser 19. | SIGNOR-276167 |
P10275 | Q86UZ6 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | Our study confirmed a novel positive association between ZBTB46 activity and LIF levels in prostate cancer tissues and cells. Under androgen regulation, low levels of ZBTB46 are an essential transcriptional factor for maintaining LIF-STAT3 signaling, while the loss of androgen signaling or inhibition of AR signaling causes LIF-enhanced therapeutic resistance and CRPC characteristics through the upregulation of ZBTB46. We also found that LIF activation drives malignant progression and NE-like reprogramming in prostate cancer by activating STAT3 signaling. | SIGNOR-277989 |
O00254 | 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-257146 |
P53350 | Q8TF76 | 2 | phosphorylation | up-regulates activity | 0.2 | Phosphorylation by Cyclin B-Cdk1 allows Haspin to bind Plk1-PBD. Phosphorylation of Haspin at T128 and Plk1 target sites is required for full H3T3ph generation and normal Aurora B localization in mitosis. | SIGNOR-275421 |
P48729 | O00257 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | The phosphorylation of CBX4 at T437 by casein kinase 1α (CK1α) facilitated its ubiquitination at both K178 and K280 and subsequent degradation by CHIP, and this phosphorylation of CBX4 could be reduced by TNFα. | SIGNOR-277512 |
P40189 | P40189 | 2 | phosphorylation | up-regulates activity | 0.2 | The biological functions of interleukin-6 (IL-6) are mediated through a signal-transducing component of the IL-6 receptor, gp130, which is associated with the ligand-occupied IL-6 receptor (IL-6R) protein. Binding of IL-6 to IL-6R induced disulfide-linked homodimerization of gp130. Tyrosine kinase activity was associated with dimerized but not monomeric gp130 protein. Substitution of serine for proline residues 656 and 658 in the cytoplasmic motif abolished tyrosine kinase activation and cellular responses but not homodimerization of gp130. | SIGNOR-238625 |
O43865 | Q9NRJ5 | 1 | binding | down-regulates activity | 0.2 | Inositol 1,4,5-triphosphate receptor-binding protein released with inositol 1,4,5-triphosphate (IRBIT) associates with components of the mRNA 3' processing machinery in a phosphorylation-dependent manner and inhibits polyadenylation|In addition to CPSF, IRBIT interacted in vitro with poly(A) polymerase (PAP), which is the enzyme recruited by CPSF to elongate the poly(A) tail, and inhibited PAP activity in a phosphorylation-dependent manner. | SIGNOR-268331 |
Q16659 | Q16659 | 2 | phosphorylation | up-regulates | 0.2 | Ser189 of erk3, which corresponds to thr183, one of the activating phosphorylation sites of erk2, is autophosphorylated in vitro and phosphorylated in vivo. | SIGNOR-40097 |
Q9ULT8 | P07900 | 1 | ubiquitination | down-regulates quantity | 0.2 | We demonstrate that Hectd1 is a functional ubiquitin ligase and that one of its substrates is Hsp90, a chaperone protein with both intra- and extracellular clients. Identification of Hsp90 in both proteomic screens suggested that members of the Hsp90 superfamily may be substrates of Hectd1. Myc-Hectd1ANK and HA-Hsp90bd (the fragment identified in the yeast two-hybrid screen) bind in an in vitro binding assay (Fig. 3 D) and when coexpressed in HEK293T cells. Hectd1 is required for K63-linked Ubn of Hsp90. Together, these results demonstrate that Hectd1-dependent Ubn of Hsp90 targets it away from the membrane and the secretory pathway. | SIGNOR-261199 |
Q9UKI8 | P68431 | 1 | phosphorylation | up-regulates activity | 0.2 | Purified tlk1b phosphorylated histone h3 at s(10) with high specificity both in a mix of core histones and in isolated chromatin, suggesting that histone h3 is a physiological substrate for tlk1b. Phosphorylation of H3 has been linked to the activation of the immediate-early genes upon mitogenic stimulation, and to chromatin condensation during mitotic/meiotic events. | SIGNOR-107037 |
Q14493 | P06899 | 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-265381 |
P25098 | P30411 | 1 | phosphorylation | down-regulates activity | 0.2 | Ligand-induced phosphorylation is found at Ser339 and Ser346/Ser348 that could be executed by several G protein-coupled receptor kinases. 32P labeling of peptide 3 containing pS346/pS348 was enhanced 1.5–3-fold as compared with mock-transfected cells in the order GRK6 < GRK5 < GRK2 < GRK4α < GRK3. several endogenous GRKs may phosphorylate the B2R and that the various GRKs, even without apparent effect on total GPCR phosphorylation levels, may induce distinct phosphorylation patterns with possible functional consequences for receptor desensitization and sequestration. | SIGNOR-251445 |
Q96P68 | 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-256913 |
Q8NFZ3 | Q9ULB1 | 1 | binding | up-regulates activity | 0.2 | 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-264143 |
Q8IWR1 | O75367 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | Nuclear TRIM59 induces ubiquitination and degradation of the tumor suppressive histone variant macroH2A1, leading to enhanced STAT3 signaling activation and tumorigenicity. | SIGNOR-272931 |
Q05513 | O95863 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | APKC kinases phosphorylate S249 of SNAI1, which leads to protein degradation. | SIGNOR-277437 |
P05186 | P10636 | 1 | dephosphorylation | down-regulates activity | 0.2 | TNAP dephosphorylates overphosphorylated tau once it is released upon neuronal death. | SIGNOR-277097 |
Q9Y5Z9 | P01112 | 1 | binding | down-regulates activity | 0.2 | This study show that UBIAD1 interacts with H-Ras, retains H-Ras in the Golgi apparatus, prevents H-Ras trafficking from the Golgi apparatus to the plasma membrane, blocks the aberrant activation of Ras/MAPK signaling, and inhibits the proliferation of bladder cancer cells. | SIGNOR-256206 |
O43312 | P63000 | 1 | binding | up-regulates | 0.2 | Mim-b binds and activates rac via its irsp53/mim domain | SIGNOR-141573 |
Q14493 | P33778 | 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-265385 |
Q13153 | P27694 | 1 | phosphorylation | up-regulates activity | 0.2 | In this article, we found that Ser-135 and Thr-180 of RPA1 are directly phosphorylated by PAK1 in a DOCK7-Rac1/Cdc42-dependent manner.|We further explored the biological role of PAK1 in replication stress and found that depletion of PAK1 resulted in decreased RPA1 and RPA2 chromatin loading and RPA2 foci formation ( Figure 4I-K ) . | SIGNOR-279378 |
Q14980 | Q13885 | 1 | binding | up-regulates | 0.2 | Direct binding of numa to tubulin is mediated by a novel sequence motif in the tail domain that bundles and stabilizes microtubules. | SIGNOR-116936 |
P49137 | Q7L5N7 | 1 | phosphorylation | up-regulates activity | 0.2 | Mass spectrometry and mutagenesis analyses identified Ser34 of LPCAT2 as the phosphorylation site to enhance the catalytic activities. The experiments using inhibitors and siRNA against MAPK cascades demonstrated that LPCAT2 phosphorylation through LPS-TLR4 signaling may directly depend on MAPK-activated protein kinase 2 (MAPKAP kinase 2 or MK2). | SIGNOR-263077 |
Q8TD84 | O43315 | 1 | binding | up-regulates activity | 0.2 | Our findings now further suggest that STAT3 and the adaptor protein SH2D2A interact with tyrosine‐containing motifs within the DSCAM/L1 ICDs. The SH2 domains of both STAT3 and SH2D2A are known to bind to phosphorylated tyrosine residues in the context of such motifs. Thus, the interactions between DSCAMs and SH2‐domain containing proteins seem to play a central and conserved role in Dscam signaling in the context of dynamic changes of tyrosine‐phosphorylation levels. | SIGNOR-264280 |
Q9GZU7 | P78527 | 1 | dephosphorylation | up-regulates activity | 0.2 | CTDSP1 activates DNA-PKcs and enhances DNA-PKcs dependent topoI degradation in response to irinotecan .|Our novel finding indicates that CTDSP1 dephosphorylates DNA-PKcs, changes its kinase activity, and regulates irinotecan-induced topoI degradation. | SIGNOR-277101 |
P01189-PRO_0000024969 | Q01718 | 1 | binding | up-regulates activity | 0.2 | Here, we show that, whereas MRAP was essential for activation of MC2R signaling, MRAP2 was an endogenous inhibitor that competed with MRAP for binding to MC2R and decreased the potency of adrenocorticotropic hormone (ACTH), the endogenous agonist for MC2Rs, in stimulating the production of adenosine 3',5'-monophosphate (cAMP). | SIGNOR-268616 |
P54646 | Q92786 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Furthermore, the Ser79 phosphorylation of PROX1 by AMPK enhances the recruitment of CUL4-DDB1 ubiquitin ligase to promote PROX1 degradation. | SIGNOR-277608 |
Q9NQU5 | Q9BY11 | 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-263021 |
O14529 | O15527 | 1 | binding | up-regulates activity | 0.2 | CUX2 Interacts Directly with OGG1 and Stimulate Its Binding to DNA Containing 8-OxoG | SIGNOR-263960 |
Q9BRS2 | P35579 | 1 | phosphorylation | up-regulates activity | 0.2 | This study demonstrates that SPC25 acts as a molecular scaffold, mediating SPC25/RIOK1/MYH9 complex formation and triggering the RIOK1‐mediated phosphorylation of MYH9 at Ser1943.Taken together, these results suggested that SPC25 increases MYH9 phosphorylation at Ser1943, enhancing the nuclear accumulation of MYH9 and consequently modulating the transcription of CTNNB1. | SIGNOR-278895 |
O95153 | Q86UR5 | 1 | binding | down-regulates activity | 0.2 | SH3 domains of RBPs interact with RIMs. The enhancement of depolarization-induced secretion in PC12 cells by fusion proteins that suppress the associations of RBPs with RIMs and α1 suggests that RBPs may repress RIMs, either directly or through associated proteins. | SIGNOR-264363 |
P08912 | 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-256730 |
P29323 | P29323 | 2 | phosphorylation | up-regulates activity | 0.2 | Our results demonstrate that autophosphorylation tyrosine 611 in the juxtamembrane region of chicken EphB2 is critical for the association of the Src SH2 domain. | SIGNOR-251124 |
P49841 | Q6IA17 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Activation of GSK3beta promotes Sigirr degradation in the proteasome .|Taken together, IL-37-induced Sigirr internalization is dependent on phosphorylation of Sigirr in T372 residue by GSK3\u03b2. | SIGNOR-279053 |
Q9Y6W6 | Q14653 | 1 | dephosphorylation | down-regulates activity | 0.2 | The inactivation of IRF3 by MKP5 is dependent on MKP5 phosphatase activity or its binding to IRF3.|This is confirmed since MKP5 phosphatasedeficient mutant is unable to dephosphorylate IRF3 and MKP5 mutant lacking IRF3 binding motifs fails to suppress IRF3 nuclear translocation upon virus infection. | SIGNOR-277146 |
Q96J92 | Q96J92 | 2 | phosphorylation | down-regulates activity | 0.2 | Elimination of the catalytic activity (D321A or D321K-K186D) or the autophosphorylation site (S335A) in mutant WNK4-L322F abrogated the positive effect on NCC. | SIGNOR-276871 |
Q5JTV8 | P08670 | 1 | binding | up-regulates activity | 0.2 | Co-immune precipitation studies revealed association between vimentin and torsinA in a complex. these studies suggest that mutant torsinA interferes with cytoskeletal events involving vimentin, possibly by restricting movement of these particles/filaments, and hence may affect development of neuronal pathways in the brain. | SIGNOR-261313 |
Q5JU85 | P48058 | 1 | relocalization | up-regulates quantity | 0.2 | BRAG1 increases the synaptic recycling pool of AMPARs.these data suggest that the BRAG1 enhancement of AMPAR transmission is mediated by the increased expression of the recycling pool of synaptic GluA2/3 receptors. | SIGNOR-264915 |
Q8IXL6 | P04275 | 1 | phosphorylation | up-regulates activity | 0.2 | In vitro phosphorylation of von Willebrand factor by FAM20c enhances its ability to support platelet adhesion. | SIGNOR-279331 |
P00533 | P48050 | 1 | phosphorylation | up-regulates activity | 0.2 | These results demonstrate that the EGF receptor tyrosine kinase up-regulates the K(IR) 2.3 channel via phosphorylation of the Y234 residue of the WT protein. | SIGNOR-276322 |
Q05513 | P05023 | 1 | phosphorylation | up-regulates activity | 0.2 | Na,K-ATPase alpha(1) subunit was phosphorylated by PKC in hypoxia-treated AEC. In AEC treated with a PKC-zeta antagonist peptide or with the Na,K-ATPase alpha(1) subunit lacking the PKC phosphorylation site (Ser-18), hypoxia failed to decrease Na,K-ATPase abundance and function. | SIGNOR-263181 |
P17612 | P05549 | 1 | phosphorylation | up-regulates | 0.2 | Recombinant ap-2 was phosphorylated in vitro by protein kinase a (pka) at ser239. Mutation of ser239 to ala abolished in vitro phosphorylation of ap-2 by pka, but not the dna binding activity of ap-2. Cotransfection studies showed that pka stimulated the effect of ap-2 on the apoe promoter, but not that of the s239a mutant. | SIGNOR-64955 |
Q9P1W9 | Q13131 | 1 | phosphorylation | down-regulates activity | 0.2 | Specifically, we found that PIM2 bound to AMPKα1, and directly phosphorylated it on Thr467. Phosphorylation of AMPKα1 by PIM2 led to decreasing AMPKα1 kinase activity, which in turn promoted aerobic glycolysis and tumor growth. | SIGNOR-277471 |
Q05086 | O43324 | 1 | ubiquitination | down-regulates quantity | 0.2 | These results strongly suggest that Ube3a decreases p18 levels via ubiquitination followed by proteasomal degradation.|We demonstrate that Ube3a directly ubiquitinates p18 and targets it for proteasomal degradation, which normally limits mTORC1 signaling and activity dependent synaptic remodeling. | SIGNOR-278680 |
P17612 | P36956 | 1 | phosphorylation | down-regulates | 0.2 | Sterol regulatory element-binding protein 1 is negatively modulated by pka phosphorylation. ser338 of srebp-1a and ser314 of srebp-1c are pka phosphorylation sites. | SIGNOR-143392 |
Q92905 | Q9NZQ7 | 1 | deubiquitination | up-regulates quantity by stabilization | 0.2 | The results suggested that TNF-α upregulates expression of CSN5, which interacts and deubiquitinates PD-L1 for protein stabilization. | SIGNOR-274977 |
Q9Y5I2 | Q9Y5H0 | 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-265699 |
O14647 | P84243 | 1 | relocalization | up-regulates quantity | 0.2 | Non-homologous end-joining (NHEJ) is the dominant DSB repair pathway in human cells, but our understanding of how it operates in chromatin is limited. Here, we define a mechanism that plays a crucial role in regulating NHEJ in chromatin. This mechanism is initiated by DNA damage-associated poly(ADP-ribose) polymerase 1 (PARP1), which recruits the chromatin remodeler CHD2 through a poly(ADP-ribose)-binding domain. CHD2 in turn triggers rapid chromatin expansion and the deposition of histone variant H3.3 at sites of DNA damage. | SIGNOR-264527 |
Q14493 | P62805 | 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-265376 |
Q7Z569 | Q7Z569 | 2 | ubiquitination | down-regulates quantity by destabilization | 0.2 | Here we report on a novel interaction between the E3 ligase BRAP (also referred to as IMP), a negative regulator of the MAPK scaffold protein KSR, and two closely related deubiquitylases, USP15 and USP4. USP15 as well as USP4 oppose the autoubiquitylation of BRAP, whereas BRAP promotes the ubiquitylation of USP15. | SIGNOR-272027 |
P28482 | P23396 | 1 | phosphorylation | up-regulates | 0.2 | Erk phosphorylates threonine 42 residue of ribosomal protein s3. | SIGNOR-137955 |
P19525 | P52564 | 1 | phosphorylation | up-regulates activity | 0.2 | Consistent with this observation, PKR was capable of activating MKK6 as assessed in a coupled kinase assay containing the components of the p38 MAPK pathway.|In vitro kinase assays revealed that MKK6 was efficiently phosphorylated by PKR, and this could be inhibited by 2-aminopurine. | SIGNOR-279707 |
P68400 | Q96G74 | 1 | phosphorylation | up-regulates activity | 0.2 | Here we show that phosphorylation of the human deubiquitinase DUBA (OTUD5) at a single residue, Ser177, is both necessary and sufficient to activate the enzyme. Treatment with CK2 could activate DUBA purified from E. coli, and this activity was associated with a species monophosphorylated at Ser177 (Fig. 1d). | SIGNOR-265872 |
P05771 | Q9H1D0 | 1 | phosphorylation | down-regulates activity | 0.2 | This regulation requires PKC(betaII) and defined phosphorylation sites within the ARD and the C-terminus. Both regulatory sites act synergistically to constitute a novel mechanism by which ATP stabilizes channel activity and acts as a metabolic switch for Ca(2+) influx. Decreases in ATP concentration or activation of PKC(betaII) disable regulation of the channels by ATP, rendering them more susceptible to inactivation and rundown and preventing Ca(2+) overload. | SIGNOR-276265 |
Q13557 | P13688 | 1 | phosphorylation | up-regulates | 0.2 | Camkiid specifically phosphorylates thr-457 on ceacam1-sf, which in turn regulates the process of lumen formation via apoptosis of the central acinar cells. | SIGNOR-203402 |
Q14493 | P0C5Z0 | 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-265407 |
P53567 | P35247 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Cotransfection of C/EBPalpha, C/EBPbeta, or C/EBPdelta cDNA in H441 lung adenocarcinoma cells significantly increased the luciferase activity of a wild-type SP-D promoter construct containing 698 bp of upstream sequence (SS698). Transfection of C/EBP also increased the level of endogenous SP-D mRNA in H441 cells| Thus, interactions among C/EBP elements in the near-distal promoter can modulate the promoter activity of SP-D. | SIGNOR-254058 |
Q05516 | Q8WXG1 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Promoter regions from the PLZF-regulated transcripts Rsad2 and Ifit2 were fused to luciferase and activity was measured after IFN treatment. Overexpression of PLZF in RCC1 or ACHN cells produced a dose-dependent induction of the reporter promoters. | SIGNOR-261023 |
Q13129 | Q13671 | 1 | binding | up-regulates activity | 0.2 | Rit and Rin were found to interact with the known Ras binding proteins RalGDS, Rlf, and AF-6/Canoe. These interactions were GTP and effector domain dependent and suggest that RalGDS, Rlf, and AF-6 are Rit and Rin effectors. | SIGNOR-220920 |
Q92914 | P35499 | 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-253434 |
Q8NFZ3 | P58400 | 1 | binding | up-regulates activity | 0.2 | 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-264148 |
Q13237 | Q9UL51 | 1 | phosphorylation | down-regulates activity | 0.2 | Here, we show for the first time that in the HCN2 channel cGMP can also exert an inhibitory effect on gating via cGMP-dependent protein kinase II (cGKII)-mediated phosphorylation.We identify the proximal C-terminus of HCN2 as binding region of cGKII and show that cGKII phosphorylates HCN2 at a specific serine residue (S641) in the C-terminal end of the CNBD. The cGKII shifts the voltage-dependence of HCN2 activation to 2-5 mV more negative voltages and, hence, counteracts the stimulatory effect of cGMP on gating. | SIGNOR-263185 |
Q13153 | Q9UQ80 | 1 | phosphorylation | up-regulates | 0.2 | We found that pak1 phosphorylated ebp1 in vitro and mapped the phosphorylation site to threonine 261. these studies demonstrate for the first time that ebp1 is a substrate of pak1 and the importance of the pak1 phosphorylation site for the functional activity of ebp1 in breast cancer cells. | SIGNOR-160963 |
Q9Y5I2 | Q9Y5H3 | 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-265704 |
O95600 | P68871 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | These results establish KLF8 as a CACCC-box binding protein that associates with CtBP and represses transcription. | SIGNOR-266052 |
Q15208 | Q96RD6 | 1 | phosphorylation | up-regulates activity | 0.2 | We identified 5 potential NDR1 substrates in the mouse brain and chose two for functional validation. We show that one NDR1 substrate is another kinase, AP-2 associated kinase-1 (AAK1) which regulates dendritic branching as a result of NDR1 phosphorylation. Another substrate is the Rab8 guanine nucleotide exchange factor (GEF) Rabin8 (a Sec2p homolog) which we find is involved in spine synapse formation. | SIGNOR-263032 |
P01019-PRO_0000420660 | P04201 | 1 | binding | up-regulates activity | 0.2 | Recent advances have improved our understanding of the renin-angiotensin system (RAS). These have included the recognition that angiotensin (Ang)-(1-7) is a biologically active product of the RAS cascade. The identification of the ACE homologue ACE2, which forms Ang-(1-7) from Ang II, and the GPCR Mas as an Ang-(1-7) receptor have provided the necessary biochemical and molecular background and tools to study the biological significance of Ang-(1-7). | SIGNOR-260229 |
Q9UHD2 | Q86WV6 | 2 | phosphorylation | up-regulates activity | 0.2 | MITA was phosphorylated by TBK1, which is required for MITA-mediated activation of IRF3. Our results suggest that MITA is a critical mediator of virus-triggered IRF3 activation and IFN expression and further demonstrate the importance of certain mitochondrial proteins in innate antiviral immunity. Consistent with its inability to activate IRF-E, the mutation of S358 to alanine impaired the ability of MITA to interact with TBK1 and to enhance the interaction between TBK1 and IRF3 | SIGNOR-263136 |
O60260 | P19174 | 1 | ubiquitination | down-regulates quantity | 0.2 | In order to address the functional role of parkin ubiquitination of PLCgamma1, we investigated PLC activity in human neuroblastoma SH-SY5Y cell lines stably transfected with either WT, or mutant R42P or G328E parkin.|WT parkin expression significantly reduced the levels of PLCgamma1 in human neuroblastoma. | SIGNOR-278592 |
Q13470 | Q13470 | 2 | phosphorylation | up-regulates activity | 0.2 | We found a similar reduction in the levels of phosphorylation of Tyr277, which corresponds to the predicted major site of autophosphorylation within the activation loop of Tnk1 (Fig. 3C). | SIGNOR-274126 |
Q00535 | O94916 | 1 | phosphorylation | up-regulates | 0.2 | High nacl-induced activation of cdk5 increases phosphorylation of the osmoprotective transcription factor tonebp/orebp at threonine 135, which contributes to its rapid nuclear localization. n hek293 cells, mass spectrometry shows phosphorylation of tonebp/orebp-s120, -s134, -t135, and -s155. | SIGNOR-170886 |
P68400 | Q13829 | 1 | phosphorylation | up-regulates | 0.2 | It was demonstrated that ck2 could phosphorylate tnfaip1 in vitro and in vivo, which facilitated the distribution of tnfaip1 in nucleus and enhanced its interaction with pcna. It is suggested that the phosphorylation of tnfaip1 may be required for its functions. | SIGNOR-188849 |
Q9P0N8 | P13569 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | A catalytically dead MARCH2 RING mutant was unable to promote CFTR degradation.|In vivo ubiquitination assays demonstrated the ubiquitination of CFTR by MARCH2, and overexpression of MARCH2, like that of CAL and STX6, led to a dose dependent degradation of mature CFTR that was blocked by bafilomycin A1 treatment. | SIGNOR-278584 |
Q14493 | Q16778 | 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-265386 |
P0DTD1-PRO_0000449630 | Q9UHD2 | 1 | binding | down-regulates activity | 0.2 | We use unbiased screening to identify SARS-CoV-2 proteins that antagonize type I interferon (IFN-I) response. We found three proteins that antagonize IFN-I production via distinct mechanisms: nonstructural protein 6 (nsp6) binds TANK binding kinase 1 (TBK1) to suppress interferon regulatory factor 3 (IRF3) phosphorylation, nsp13 binds and blocks TBK1 phosphorylation, and open reading frame 6 (ORF6) binds importin Karyopherin α 2 (KPNA2) to inhibit IRF3 nuclear translocation. the results indicate that (1) nsp6 binds to TBK1 without affecting TBK1 phosphorylation, but the nsp6/TBK1 interaction decreases IRF3 phosphorylation, which leads to reduced IFN-β production; and (2) nsp13 binds and inhibits TBK1 phosphorylation, resulting in decreased IRF3 activation and IFN-β production (Figure 2F). | SIGNOR-262512 |
P25098 | Q8IXH6 | 1 | phosphorylation | down-regulates activity | 0.2 | In conclusion, experimental results demonstrate that GRK2 chronically downregulates DOR functional competence at the PM in peripheral sensory neurons, as well as peripheral DOR anti-nociception in vivo.|These data demonstrate that BK does not affect GRK2 mediated phosphorylation of DOR at its primary desensitization site. | SIGNOR-279739 |
P17252 | P48048 | 1 | phosphorylation | down-regulates activity | 0.2 | The giant patch clamp together with site direct mutagenesis revealed that Thr-193 is the phosphorylation site on PKC that regulates the pH(i) sensitivity of ROMK1 channels. Mutation of PKC-induced phosphorylation sites (T193A) decreases the pH(i) sensitivity and increases the interaction of channel-PIP(2). | SIGNOR-276389 |
Q92914 | Q9NY46 | 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-253446 |
P49959 | Q9NWS0 | 1 | binding | up-regulates activity | 0.2 | Here we show that MRE11 directly interacts with PIH1D1, a subunit of heat-shock protein 90 cochaperone R2TP complex, which is required for the assembly of large protein complexes, such as RNA polymerase II, small nucleolar ribonucleoproteins and mammalian target of rapamycin complex 1. The MRE11-PIH1D1 interaction is dependent on casein kinase 2 (CK2) phosphorylation of two acidic sequences within the MRE11 C terminus containing serines 558/561 and 688/689. | SIGNOR-265898 |
O00410 | O60469 | 1 | relocalization | up-regulates activity | 0.2 | DSCAM and DSCAML1 specifically interacted with the importin beta IPO5, whereas deletion of the identified NLSs abolished this specific interaction and suppressed nuclear translocation of the DSCAM/L1 ICDs in cell lines and cultured neurons. This suggests a direct role of IPO5 in the nuclear import of the DSCAM/L1 ICDs. | SIGNOR-264273 |
Q8N6F7 | P62993 | 1 | binding | down-regulates activity | 0.2 | Herein, we demonstrate that the adaptor protein HGAL, specifically expressed in GC lymphocytes and GC-derived lymphomas, directly binds to Grb2 upon BCR activation and negates the inhibitory effects of Grb2 on the BCR-induced biochemical signaling cascade. | SIGNOR-273608 |
Q5T447 | P55211 | 1 | polyubiquitination | down-regulates activity | 0.2 | HECTD3 binds and ubiquitinates caspase-9.HECTD3 inhibits caspase-9 oligomerization and association with Apaf-1. HECTD3 suppressing caspase-9 activation is dependent on T157 phosphorylation by ERK. | SIGNOR-272329 |
P25098 | P09619 | 2 | phosphorylation | down-regulates activity | 0.2 | In 293 cells, GRK2 overexpression reduced PDGFRbeta/NHERF association by 60%. | SIGNOR-278379 |
P01189-PRO_0000024969 | P41968 | 1 | binding | up-regulates activity | 0.2 | The melanocortin (MC) receptor family consists of five Gs-coupled receptors that control various physiological functions in response to four distinct agonists, adrenocorticotropic hormone (ACTH, also known as corticotrophin) and alpha, beta, and gamma melanocyte-stimulating hormone (MSH), which are derived from the proopiomelanocortin precursor protein, and two inverse agonists, agouti and agouti-related proteins | SIGNOR-268706 |
Q7Z589 | Q15326 | 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-263916 |
Q9Y2H1 | P21333 | 1 | phosphorylation | up-regulates activity | 0.2 | Activated Ndr2 Promotes FLNa Release From LFA-1.|Taken together the data depicted in Figures xref and xref indicate that Ndr2 phosphorylates FLNa at S2152 both in vitro and in vivo . | SIGNOR-278501 |
Q9UK22 | O00459 | 1 | binding | down-regulates quantity by destabilization | 0.2 | FBXL2 interacts with the pool of p85β that is free of p110 PI(3)K catalytic subunits and targets this pool for ubiquitylation and subsequent proteasomal degradation. | SIGNOR-271936 |
P01137 | P01222 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | TGF-β inhibits thyroid-stimulated hormone (TSH)-induced NIS mRNA and protein levels in a dose-dependent manner. This effect takes place at the transcriptional level, as TGF-β inhibits TSH-induced transcription | SIGNOR-251991 |
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