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 |
|---|---|---|---|---|---|---|---|
P17612 | P41161 | 1 | phosphorylation | up-regulates activity | 0.2 | We further show that the increase in erm transcriptional activity after pka phosphorylation is closely correlated with a drastic reduction in the dna binding of the transcription factor. These results indicate that the phosphorylation of erm by pka is involved in erm-mediated transcription and suggest that the activation of erm is probably related to conformational changes. | SIGNOR-111239 |
Q8N752 | O94916 | 1 | phosphorylation | up-regulates activity | 0.2 | However, the siRNA knockdown of CK1α1L significantly reduced the nuclear export of OREBP/TonEBP under hypotonic conditions (Fig. 5F). Taken together, these data suggest that CK1α1L is the kinase that phosphorylates Ser-158 in the regulation of OREBP/TonEBP export. | SIGNOR-274111 |
Q9Y2T6 | Q14344 | 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-256670 |
P31751 | P78563 | 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-276196 |
O15530 | P53350 | 1 | phosphorylation | up-regulates activity | 0.2 | Here, we report that PDK1 directly induces phosphorylation of Polo-like kinase 1 (PLK1), which in turn induces MYC phosphorylation and protein accumulation. We show that PDK1-PLK1-MYC signaling is critical for cancer cell growth and survival, and small-molecule inhibition of PDK1/PLK1 provides an effective approach for therapeutic targeting of MYC dependency | SIGNOR-243519 |
O43318 | P53805 | 1 | phosphorylation | up-regulates activity | 0.2 | Here we showed that TAK1 directly phosphorylated RCAN1 at two novel sites (serine 94 and -136), resulting in activation of calcineurin-NFAT signaling.|Indeed, low doses of RCAN1 facilitated calcineurin-nuclear factor of activated T cells signaling in the presence of TGF-\u03b2-activated kinase 1+TAB1 ( ), suggesting that TGF-\u03b2-activated kinase 1 augments calcineurin-nuclear factor of activated T cells signaling through RCAN1. | SIGNOR-279535 |
P18848 | Q9Y2Z4 | 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-269432 |
P12931 | P63244 | 1 | phosphorylation | up-regulates | 0.2 | We found that rack1 is a src substrate. Moreover, src activity is necessary for both the tyrosine phosphorylation of rack1 and the binding of rack1 to src's sh2 domain that occur following pkc activation. To identify the tyrosine(s) on rack1 that is phosphorylated by src, we generated and tested a series of rack1 mutants. We found that src phosphorylates rack1 on tyr 228 and/or tyr 246 | SIGNOR-94800 |
P06241 | P84243 | 1 | phosphorylation | down-regulates activity | 0.2 | Here we provide evidence that fyn kinase, a member of the src kinase family, is involved in the uvb-induced phosphorylation of histone h3 at serine 10 | SIGNOR-130274 |
P17252 | Q9UQ13 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | PKCalpha/delta phosphorylate Sur8 at Thr-71 and Ser-297, respectively. This phosphorylation is essential for polyubiquitin-dependent degradation of Sur8. | SIGNOR-275568 |
P01137 | Q06710 | 1 | binding | down-regulates activity | 0.2 | DNA Binding Activity of Pax8 to the NIS Promoter Is Reduced by Smad3. TGF-β decreases Pax8 DNA binding to the NIS promoter and also found a physical interaction between Pax8 and Smad3. | SIGNOR-251993 |
Q9UIQ6 | P01178-PRO_0000020495 | 1 | cleavage | down-regulates quantity by destabilization | 0.2 | It has been shown that the steady state of the mature OT form can be controlled by an oxytocinase (P-LAP) that is produced in periphery and centrally by the OT-magnocellular neurons. Noticeably, P-LAP is also expressed in parvocellular OT neurons and in other brain structures| The OT intermediate forms are produced from E16.5 (see above) but the mature amidated OT form is detected only from birth. The released mature form is then degraded by an oxytocinase (PLAP) | SIGNOR-268552 |
P24941 | P25098 | 1 | phosphorylation | down-regulates | 0.2 | We report that grk2 protein levels are transiently down-regulated during the g2/m transition by a mechanism involving cdk2-mediated phosphorylation of grk2 at serine670, which triggers binding to the prolyl-isomerase pin1 and subsequent degradation. | SIGNOR-163279 |
Q9NQU5 | P05141 | 1 | phosphorylation | up-regulates quantity | 0.2 | In the present study, it was demonstrated that ANT2 was phosphorylated by PAK6 at T107.|Moreover, PAK6 overexpression upregulated the protein expression of ANT2, while PAK6 knockdown led to opposing effects. | SIGNOR-279473 |
Q99717 | O95257 | 1 | transcriptional regulation | up-regulates quantity | 0.2 | Chromatin immunoprecipitation (ChIP) revealed a subset of the BIG (BMP4 induced genes) signature, including Satb2, Smad6, Hand1, Gadd45γ and Gata3, that was bound by Smad1/5 in the developing mandible, revealing direct Smad-mediated regulation | SIGNOR-268942 |
P51955 | Q9UMX1 | 1 | phosphorylation | up-regulates activity | 0.2 | Intriguingly, Nek2A is found to stabilize SuFu at least partly depending on its kinase activity, thereby triggering phosphorylation of the SuFu protein.|Nek2A phosphorylates and stabilizes SuFu: A new strategy of Gli2/Hedgehog signaling regulatory mechanism. | SIGNOR-279235 |
Q00341 | Q06609 | 1 | binding | up-regulates activity | 0.2 | We show that vigilin interacts with the DNA damage response (DDR) proteins RAD51 and BRCA1, and vigilin depletion impairs their recruitment to DSB sites. | SIGNOR-266697 |
Q05655 | P07108 | 1 | phosphorylation | up-regulates | 0.2 | Acyl coenzyme a-binding protein (acbp) is phosphorylated following protein kinase c activation. | SIGNOR-160393 |
Q8WXH5 | O75553 | 1 | binding | down-regulates quantity by destabilization | 0.2 | SOCS7 promotes Dab1 polyubiquitylation and degradation. SOCS7-CRL5 complexes stimulate the ubiquitylation and turnover of Dab1. SOCS7, a CRL5 substrate adaptor protein, is also required for neocortical layering. SOCS7-CRL5 complexes stimulate the ubiquitylation and turnover of Dab1. | SIGNOR-272139 |
P48729 | Q9UGI0 | 1 | phosphorylation | up-regulates activity | 0.2 | Interestingly, ZRANB1 is phosphorylated at Thr35, and Ser209 residues by CSNK1A1, and this phosphorylation activates its deubiquitinating activity. | SIGNOR-273621 |
P62805 | P25440 | 1 | relocalization | up-regulates activity | 0.2 | Thus, the TIP60 HAT complex is recruited to MYC-target genes and, probably with other other HATs, contributes to histone acetylation in response to mitogenic signals. | SIGNOR-262062 |
Q7Z434 | Q86WV6 | 1 | binding | up-regulates activity | 0.2 | MAVS also interacts with STING that locates at the ER (endoplasmic reticulum), and induces the ubiquitination and dimerization of STING. The activated STING recruits TBK1 and IRF3 and contributes to the phosphorylation of IRF3 mediated by TBK1. | SIGNOR-260152 |
Q9UIG0 | P16104 | 1 | phosphorylation | up-regulates | 0.2 | We show that wstf phosphorylates tyr 142 of h2a.x, and that wstf activity has an important role in regulating several events that are critical for the dna damage response | SIGNOR-182831 |
P29350 | P14618 | 1 | dephosphorylation | down-regulates activity | 0.2 | SHP-1 dephosphorylates PKM2 at Y105 to inhibit nuclear function of PKM2 and determines the efficacy of targeted drugs.|SHP-1 directly dephosphorylated PKM2 at Y105 and further decreased the proliferative activity of PKM2; similar effects were found in sorafenib-treated hepatocellular carcinoma cells.|SHP-1 dephosphorylates p-PKM2Y105 and further affects the nucleus-related cell proliferation. | SIGNOR-276997 |
P31749 | P54198 | 1 | phosphorylation | up-regulates activity | 0.2 | Consistently, HIRA phosphorylation was effectively decreased by Akt1 knockdown and was completely eliminated by the depletion of both Akt1 and Akt2, suggesting that HIRA is phosphorylated primarily by Akt1 and that Akt2 seemed to contribute to HIRA phosphorylation as a supplementary kinase in myoblasts (XREF_FIG).|In this study, HIRA was more efficiently targeted by Akt1 in myoblasts. | SIGNOR-279584 |
P22681 | O15519 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | We therefore conclude that c-cbl is a e3 ubiquitin ligase for flips and that the interaction of flips with c-cbl requires phosphorylation of both ser4 and tyr211 of flips.This interaction triggered proteasomal degradation of FLIP(S), which promoted activation of caspase-8 and apoptosis. | SIGNOR-186998 |
Q13153 | Q96P20 | 1 | phosphorylation | up-regulates activity | 0.2 | Pak1 phosphorylates NLRP3 to promote inflammasome activation. | SIGNOR-277547 |
P49841 | P17812 | 1 | phosphorylation | down-regulates activity | 0.2 | We found that low serum conditions increased phosphorylation of endogenous CTPS1 and this phosphorylation was inhibited by the glycogen synthase kinase 3 (GSK3) inhibitor indirubin-3'-monoxime and GSK3beta short interfering RNAs, demonstrating the involvement of GSK3 in phosphorylation of endogenous human CTPS1. Separating tryptic peptides from [(32)P]orthophosphate-labeled cells and analyzing the phosphopeptides by mass spectrometry identified Ser-574 and Ser-575 as phosphorylated residues. Incubation with an alkaline phosphatase increased CTPS1 activity in a time-dependent manner, demonstrating that phosphorylation inhibits CTPS1 activity. | SIGNOR-276069 |
O60674 | Q9Y4C1 | 1 | phosphorylation | up-regulates activity | 0.2 | KDM3A is tyrosine-phosphorylated by JAK2 in the nucleus and functions as a STAT3-dependent transcriptional coactivator. JAK2 phosphorylates KDM3A at tyrosine 1101 residue. | SIGNOR-277884 |
P17612 | Q68EM7 | 1 | phosphorylation | down-regulates activity | 0.2 | Screening for potential mediators of this effect resulted in the identification of the Rac1-specific GTPase-activating protein ARHGAP17 and the guanine nucleotide exchange factor ARHGEF6 as new PKA and PKG substrates in platelets. We mapped the PKA/PKG phosphorylation sites to serine 702 on ARHGAP17 using Phos-tag gels and to serine 684 on ARHGEF6. |ARHGAP17 is a Rho GTPase-activating protein of Rac1 and is bound to the SH3 domain of CIP4 via its SH3 binding region in resting platelets. Endothelial PGI2 stimulates the activation of PKA and leads to the phosphorylation of Ser-702 in ARHGAP17, which results in the dissociation of the ARHGAP17-CIP4 complex. | SIGNOR-272155 |
P17612 | P55211 | 1 | phosphorylation | down-regulates | 0.2 | We show that protein kinase a inhibits activation of caspase-9 and caspase-3 downstream of cytochrome c in xenopus egg extracts and in a human cell-free system. Protein kinase a directly phosphorylates human caspase-9 at serines 99, 183, and 195. | SIGNOR-133884 |
P17252 | Q9UQL6 | 1 | phosphorylation | down-regulates activity | 0.2 | We also demonstrate that protein kinase D (PKD), a downstream effector of PKC, directly phosphorylates HDAC5 and stimulates its nuclear export. | Finally, we assessed the ability of PKD to phosphorylate HDAC5 in cells by employing an antibody that specifically recognizes HDAC5 that has been phosphorylated at serine 259. HDAC5 was basally phosphorylated at serine 259, and phosphorylation at this site was dramatically increased by coexpression of constitutively active PKD S/E | SIGNOR-249269 |
O15355 | P63162 | 1 | dephosphorylation | up-regulates quantity by stabilization | 0.2 | Dephosphorylation of survival motor neurons (SMN) by PPM1G and PP2Cgamma governs Cajal body localization and stability of the SMN complex.|This indicates that the catalytic activity of PPM1G promotes accumulation of the SMN complex in CBs and suggests that PPM1G is a major determinant of the SMN-complex localization in the nucleus. | SIGNOR-277021 |
Q96ME1 | P19447 | 1 | binding | down-regulates quantity by destabilization | 0.2 | These results led us to propose a model that spironolactone may trigger the phosphorylation of XPB at Ser90 by CDK7, which promotes the recognition and polyubiquitination of XPB by SCFFBXL18 for proteasomal degradation. | SIGNOR-277434 |
Q8TCQ1 | P06213 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | MARCH1 ubiquitinates INSR to decrease cell surface INSR levels, but unlike other INSR ubiquitin ligases, MARCH1 acts in the basal state rather than after insulin stimulation. | SIGNOR-278819 |
P68400 | Q03112 | 1 | phosphorylation | up-regulates activity | 0.2 | We also identified EVI1 phosphorylation sites by MS analysis and showed that Ser538 and Ser858 can be phosphorylated and dephosphorylated by two EVI1 interactome proteins, casein kinase II and protein phosphatase-1α. Finally, mutations that impair EVI1 phosphorylation at these sites reduced EVI1 DNA binding through its C-terminal zinc finger domain and induced cancer cell proliferation. | SIGNOR-273427 |
Q05655 | Q9H6E5 | 1 | phosphorylation | up-regulates activity | 0.2 | PKCdelta associates with and directly phosphorylates Star-PAP. | SIGNOR-279385 |
Q16539 | O43255 | 1 | phosphorylation | up-regulates | 0.2 | We show that siah2 is subject to phosphorylation by p38 mapk, which increases siah2-mediated degradation of phd3. | SIGNOR-149890 |
Q96LB1 | P09471 | 1 | binding | up-regulates activity | 0.2 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-257260 |
O96013 | O96013 | 2 | phosphorylation | up-regulates | 0.2 | Intracellular localization;enzymatic activity, induced;cell growth, altered; | SIGNOR-168301 |
Q9NRW1 | Q7Z7G8 | 1 | binding | up-regulates activity | 0.2 | Cohen syndrome-associated protein COH1 physically and functionally interacts with the small GTPase RAB6 at the Golgi complex and directs neurite outgrowth. We show that COH1 forms a physical and functional complex with RAB6. Our results point to a role of COH1 as a RAB6 effector protein. Depletion of COH1 leads to decreased neurite outgrowth in cultured primary hippocampal neurons. These results establish a critical role for RAB6-dependent function of COH1 in neuritogenesis by regulating Golgi complex organization. | SIGNOR-266870 |
Q8TAB3 | P34903 | 1 | binding | up-regulates quantity by stabilization | 0.2 | Here, we found that PCDH19 binds the alpha subunits of GABAAR and regulates its surface availability and currents in cultured hippocampal neurons. The PCDH19 gene (Xp22.1) encodes the cell-adhesion protein protocadherin-19 (PCDH19) and is responsible for a neurodevelopmental pathology characterized by female-limited epilepsy, cognitive impairment and autistic features, the pathogenic mechanisms of which remain to be elucidated. Here, we identified a new interaction between PCDH19 and GABAA receptor (GABAAR) alpha subunits in the rat brain. PCDH19 shRNA-mediated downregulation reduces GABAAR surface expression and affects the frequency and kinetics of miniature inhibitory postsynaptic currents (mIPSCs) in cultured hippocampal neurons. | SIGNOR-267222 |
Q14493 | P16104 | 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-265405 |
Q5JU85 | P42262 | 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-264913 |
Q9Y4B6 | P35240 | 1 | binding | down-regulates quantity by destabilization | 0.2 | VprBP targets Merlin to the Roc1-Cul4A-DDB1 E3 ligase complex for degradation. In this study, we provide evidence to show that Merlin is regulated in a Roc1-Cullin4A-DDB1-dependent manner. Following serum stimulation, Merlin is recruited to the E3 ligase complex through a direct interaction with the WD40-containing adaptor protein VprBP. Loading of Merlin to the E3 ubiquitin ligase complex resulted in its polyubiquitination, and consequently its proteasome-mediated degradation. | SIGNOR-271673 |
P45973 | P84243 | 1 | binding | up-regulates activity | 0.2 | A core characteristic of heterochromatin is its association with heterochromatin protein 1 (HP1) proteins, a highly conserved family of chromosomal proteins that bind to di- and trimethylated H3K9 via a conserved N-terminal domain called the chromodomain (CD) HP1 proteins are a highly conserved family of eukaryotic proteins that bind to methylated histone H3 lysine 9 (H3K9) and are required for heterochromatic gene silencing. | SIGNOR-264488 |
P07437 | Q15796 | 1 | binding | down-regulates | 0.2 | Smad2/3 also binds to _-tubulin, which provides a negative regulatory mechanism controlling tgf-_ activity. the results showed that the mh2 domain of smad2 binds to _-tubulin with almost the same efficiency as the full-length (wild-type) smad2. Similar results were obtained for the smad3 binding to _-tubulin. | SIGNOR-154316 |
P63244 | P67775 | 1 | binding | up-regulates activity | 0.2 | RACK1 Mediates the Formation of the IRF3-RACK1-PP2A Complex and Promotes the Dephosphorylation of IRF3.Here we report that IRF3 is deactivated via dephosphorylation mediated by the serine and threonine phosphatase PP2A and its adaptor protein RACK1. The PP2A-RACK1 complex negatively regulated the IRF3 pathway after LPS or poly(I:C) stimulation or Sendai virus (SeV) infection. | SIGNOR-260945 |
Q9Y5I2 | Q9Y5G3 | 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-265703 |
P06730 | Q9UDX5 | 1 | translation regulation | up-regulates activity | 0.2 | In this study, we demonstrate that mTORC1 stimulates mitochondrial fission via 4E-BP-mediated translational regulation of the mitochondrial fission factor MTFP1. Suppression of mTORC1 activity by pharmacological or genetic means causes mitochondrial hyperfusion, branching, and circularization. This is a consequence of downregulation of MTFP1 levels via the mTORC1/4E-BP pathway, thereby eliciting changes in phosphorylation and localization of the mitochondrial fission factor DRP1 | SIGNOR-275429 |
Q8NHY2 | Q13330 | 2 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | Here we report that MTA1 is an ubiquitinated protein and targeted by the RING-finger E3 ubiquitin-protein ligase constitutive photomorphogenesis protein 1 (COP1) for degradation via the ubiquitin-proteasome pathway. | SIGNOR-271891 |
P23470 | O60496 | 1 | dephosphorylation | up-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-254698 |
P17612 | O43164 | 1 | phosphorylation | up-regulates activity | 0.2 | In vitro kinase assays demonstrated that purified PKAc directly phosphorylates wild-type Flag–praja2, but not the Flag–praja2S342A,T389A mutant, confirming these residues as the main PKA phosphorylation sites (Fig. 5h). | SIGNOR-276316 |
P01106 | P49761 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | C-Myc enhances transcriptional activation of CLK3 promoter in CCA cells. | SIGNOR-274123 |
Q96G91 | 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-256931 |
Q96FF9 | Q7Z5K2 | 1 | binding | down-regulates activity | 0.2 | We show that DNA replication and cohesin acetylation promote binding of Sororin to cohesin, and that Sororin displaces Wapl from its binding partner Pds5. | SIGNOR-265266 |
P25098 | P30559 | 1 | phosphorylation | down-regulates activity | 0.2 | Recent experiments in COS-7 cells transfected with OTR have demonstrated that a rapid GRK2-mediated phosphorylation of the agonist-occupied OTR is a key first step leading to its desensitization, and that it precedes and is required for β-arrestin-dependent internalization | SIGNOR-270329 |
Q9P2K8 | P56192 | 1 | phosphorylation | down-regulates | 0.2 | Here we demonstrate that aimp3 is released from mrs by uv irradiation-induced stress. Dissociation was induced by phosphorylation of mrs at ser662 by general control nonrepressed-2 (gcn2) following uv irradiation. Substitution of ser662 to asp (s662d) induced a conformational change in mrs and significantly reduced its interaction with aimp3. This mutant possessed significantly reduced mrs catalytic activity because of loss of trna(met) binding, resulting in down-regulation of global translation. | SIGNOR-177648 |
Q13555 | Q9Y618 | 1 | phosphorylation | down-regulates | 0.2 | The kinase activity of camkii was essential for the activation of notch signaling. We also determined that camkii could enhance the association between notch1-ic and rbp-jk. Furthermore, the physical association between rbp-jk and smrt was substantially suppressed by camkii. We demonstrated that camkii directly bound and phosphorylated smrt at ser-1407, thereby facilitating smrt translocation from the nucleus to the cytoplasm and proteasome-dependent degradation. | SIGNOR-191777 |
Q9Y222 | P15514 | 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-261582 |
Q8WZ74 | Q9BYB0 | 1 | binding | up-regulates activity | 0.2 | Synaptopathy, a key feature of autism spectrum disorders (ASD), is likely relevant to the impaired phase separation and/or transition of ASD-linked synaptic proteins. Here, we report that LLPS and zinc-induced liquid-to-gel phase transition regulate the synaptic distribution and protein-protein interaction of cortactin-binding protein 2 (CTTNBP2), an ASD-linked protein. CTTNBP2 forms self-assembled condensates through its C-terminal intrinsically disordered region and facilitates SHANK3 co-condensation at dendritic spines. | SIGNOR-269702 |
Q9H2K2 | Q13148 | 1 | binding | up-regulates quantity by stabilization | 0.2 | Upon investigating the functional effect, we find that interaction with Tnks-1/2 inhibits the ubiquitination and proteasomal turnover of TDP-43, leading to its stabilization. We further show that proteasomal turnover of TDP-43 occurs preferentially in the nucleus; our data indicate that Tnks-1/2 stabilizes TDP-43 by promoting cytoplasmic accumulation, which sequesters the protein from nuclear proteasome degradation. | SIGNOR-262116 |
P24941 | P78317 | 1 | phosphorylation | up-regulates activity | 0.2 | Here we reported that CDK2 could phosphorylate RNF4 on T26 and T112 and enhance RNF4 E3 ligase activity, which is important for MDC1 degradation and proper HR repair during S phase. | SIGNOR-276900 |
Q75N03 | P07355 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | By immunoprecipitation, we present evidence that Hakai interacts with Hsp90 chaperone complex in several epithelial cells and demonstrate that is a novel Hsp90 client protein. Interestingly, by overexpressing and knocking-down experiments with Hakai, we identified Annexin A2 as a Hakai-regulated protein. Interestingly, geldanamycin-induced Hakai degradation is accompanied by an increased expression of E-cadherin and Annexin A2. | SIGNOR-271473 |
Q14493 | P84243 | 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-265418 |
P17612 | Q13185 | 1 | phosphorylation | up-regulates | 0.2 | We demonstrate that p-ser 83-hp1gamma has an exclusively euchromatic localization, interacts with ku70 (a regulatory protein involved in multiple nuclear procesess), has impaired silencing activity and serves as a marker for transcription elongation. | SIGNOR-145109 |
P21802 | P21802 | 2 | phosphorylation | up-regulates activity | 0.2 | Our data also show that tyrosine 769 is not involved in the regulation of the endocytic process of KGFR.Following ligand binding, KGFR is rapidly autophosphorylated on specific tyrosine residues | SIGNOR-276026 |
Q16539 | P78356 | 1 | phosphorylation | down-regulates | 0.2 | Inhibition of pip4kbeta activity occurs through the direct phosphorylation of pip4kbeta at ser326 by the p38 stress-activated protein kinase. | SIGNOR-149359 |
P51813 | P25116 | 1 | phosphorylation | down-regulates activity | 0.2 | As shown in xref \u2013 xref , BMX overexpression increased PAR1-WT phosphorylation but had no effect on PAR1 Y 381 FY 383 F mutant, indicating that BMX phosphorylated PAR1 at Y 381 and Y 383 .|Mechanically , BMX represses PAR1 signaling in ECs by promoting PAR1 phosphorylation and internalization . | SIGNOR-279593 |
Q96T68 | P68431 | 1 | methylation | up-regulates activity | 0.2 | Here, we have characterized a previously undescribed member of the histone H3K9 methyltransferase family named CLLD8 (or SETDB2 or KMT1F). This protein contributes to the trimethylation of both interspersed repetitive elements and centromere-associated repeats and participates in the recruitment of heterochromatin protein 1 to centromeres. Methylation of histone H3 at lysine 9 (H3K9) has emerged as an important player in the formation of heterochromatin, chromatin condensation, and transcriptional repression. | SIGNOR-263896 |
P35626 | 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-251462 |
Q9P2E7 | P05556 | 1 | binding | up-regulates activity | 0.2 | The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion. | SIGNOR-269034 |
P35367 | 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-257318 |
P18848 | P49589 | 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-269416 |
O14874 | P53396 | 1 | phosphorylation | up-regulates activity | 0.2 | BCKDK can activate ACLY and promote the cleavage of citric acid into acetyl-CoA, and oxaloacetate.|BCKDK can phosphorylate BCKDHA and ATP citrate lyase (ACLY), exerting opposing effects on both. | SIGNOR-280194 |
Q14493 | P68431 | 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-265413 |
Q14469 | P04150 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | HES1 binding to the promoter of the NC3C1 gene inhibits its expression and results in insufficient production of the encoded glucocorticoid receptor- rendering these cells resistant to treatment with dexamethasone | SIGNOR-251674 |
Q9HCI7 | Q16778 | 1 | monoubiquitination | down-regulates activity | 0.2 | MSL1/2 ubiquitylates histone H2B on K 34. Importantly, only mono-ubiquitylation of H2B by MSL1/2 was detected in cells (data not shown), suggesting that MSL1/2, like RNF20/RNF40, was mainly a mono-ubiquitylase under physiological conditions.the MOF-MSL complex functions to promote both H4 K16ac and H2B K34ub. H2B K34ub, in turn, promotes H2B K120ub, H3 K4me3 and K79me2 to facilitate transcription elongation. | SIGNOR-271976 |
O60260 | Q13002 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | Parkin interacts with and ubiquitinates the GluK2 KAR subunit and regulates GluK2 levels and KAR currents.|The loss of parkin function increases surface and total GluK2 levels, and consistently increases KAR currents. | SIGNOR-278541 |
Q9Y2K2 | O15055 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | In the current study, we found that SIK3 promotes phosphorylation of PER2 and regulates the abundance of the protein by accelerating its degradation. | SIGNOR-279570 |
Q96G91 | P09471 | 1 | binding | up-regulates activity | 0.2 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-257261 |
Q16549 | P49715 | 1 | phosphorylation | down-regulates | 0.2 | Addition of active p38a induced phosphorylation of wild-type c/ebp_? (c/ebp_?WT) on serine 21 | SIGNOR-186202 |
Q2M2I3 | P48729 | 1 | binding | up-regulates quantity | 0.2 | We identified members of the FAM83 family of proteins as partners of CK1 in cells. All eight members of the FAM83 family (FAM83A–H) interacted with the α and α-like isoforms of CK1; FAM83A, -B, -E, and -H also interacted with the δ and ε isoforms of CK1. The intrinsic catalytic activity of CK1 is not affected by or required for the association of CK1 with FAM83 proteins. Our findings imply that the DUF1669 domains of FAM83 proteins anchor CK1 α, α-like, δ, and ε isoforms in specific subcellular compartments and potentially mediate their association with substrates. | SIGNOR-273750 |
P17252 | P23528 | 1 | phosphorylation | down-regulates | 0.2 | Pkc_ phosphorylates cofilin at ser-23 and/or ser-24 during degranulationthese results indicate that a novel pkc_-mediated phosphorylation event regulates cofilin by inhibiting its ability to depolymerize f-actin and bind to 14-3-3_, thereby promoting f-actin polymerization | SIGNOR-198478 |
P06493 | Q8N884 | 1 | phosphorylation | down-regulates activity | 0.2 | The major mitotic kinase CDK1-cyclin B complex phosphorylates human cGAS at S305 or mouse cGAS at S291, which inhibits its ability to synthesize cGAMP upon mitotic entry. | SIGNOR-276526 |
P41279 | P53350 | 1 | phosphorylation | up-regulates | 0.2 | Xplkk1 phosphorylates and activates mammalian plk / xplkk1 phosphorylates thr-210 | SIGNOR-92274 |
P24941 | Q5TZA2 | 1 | phosphorylation | down-regulates | 0.2 | Finally, phosphorylation of tax1bp2 at serine-763 by cyclin-dependent kinase (cdk)2 abolished the tax1bp2-mediated p38 activation and tumor-suppressive activity, indicating that tax1bp2 can adapt cdk2 signaling to the p38/p53/p21 pathway. | SIGNOR-197593 |
P00441 | Q15046 | 1 | binding | down-regulates quantity by destabilization | 0.2 | In the presence of mutant SOD1, mitoKARS displays a high propensity to misfold and aggregate prior to its import into mitochondria, becoming a target for proteasome degradation. | SIGNOR-262800 |
Q9NRM7 | Q14872 | 1 | phosphorylation | down-regulates activity | 0.2 | The Hippo pathway kinases LATS1 and LATS2 attenuate cellular responses to heavy metals through phosphorylating MTF1|the Hippo pathway kinase LATS phosphorylates and inhibits MTF1|LATS phosphorylates MTF1 at S152 and disrupts its association with the promoters of heavy metal response genes, resulting in the loss of heavy metal response gene expression | SIGNOR-275475 |
Q16512 | Q12778 | 1 | phosphorylation | down-regulates | 0.2 | Furthermore, estrogen induced phosphorylation and perinuclear localization of the cell survival forkhead transcription factor fkhr in the cytoplasm in a pak1-dependent manner. In addition, pak1 directly interacted with fkhr and phosphorylated it. The noticed phosphorylation-dependent exclusion of fkhr from the nucleus impaired the ability of fkhr to activate its target fas ligand promoter containing the fkhr binding motif (fre) in cells treated with estrogen or expressing catalytically active pak1. | SIGNOR-97882 |
Q2TAL8 | P54577 | 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-269412 |
Q92831 | Q6NXT2 | 1 | acetylation | down-regulates activity | 0.2 | The HAT module within the SAGA and ADA complexes acetylates histone H3, mainly on residues K9 and K14. | SIGNOR-269617 |
Q9P1Y6 | P09874 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | Furthermore, PHRF1 mediates PARP1 polyubiquitination for proteasomal degradation. | SIGNOR-278774 |
P27361 | P25098 | 1 | phosphorylation | down-regulates | 0.2 | Erk1 phosphorylates grk2 at ser(670). Inhibition of erk activity in hek293 cells potentiates grk2 activity, whereas, conversely, erk activation inhibits grk2 activity. | SIGNOR-72582 |
Q96P44 | Q16832 | 1 | binding | up-regulates activity | 0.2 | The Discoidin Domain Receptors (DDRs) constitute a unique set of receptor tyrosine kinases that signal in response to collagen.|Consistent with this view128, we showed that ectopic expression of DDR1b or DDR2 in HT1080 cells elicited a potent growth inhibitory effect only when the cells were cultured on 2D or 3D COL1 matrices, in agreement with previous studies in melanoma48, breast cancer76,78, and lung cancer cells74,75. | SIGNOR-272343 |
O96017 | P10636 | 1 | phosphorylation | down-regulates | 0.2 | Tau pseudophosphorylation at specific sites such as s262, s293, s324 and s356 was reported to induce tau conformational change and attenuate tau binding to microtubules (fischer et al., 2009). Then, newly soluble tau proteins are targeted by post-translational modifications that directly or indirectly alter tau conformation, promoting tau dimerization in an anti-parallel manner. Stable tau dimers form tau oligomers, which continue in the aggregation process | SIGNOR-171026 |
P68400 | Q9H2G2 | 1 | phosphorylation | down-regulates | 0.2 | Slk down-regulation by v-src is indirect and is accompanied by slk hyperphosphorylation on serine residues. Deletion analysis revealed that casein kinase ii (ck2) sites at position 347/348 are critical for v-src-dependent modulation of slk activity. | SIGNOR-147879 |
Q96QT6 | Q04725 | 1 | binding | up-regulates activity | 0.2 | We have cloned and characterized a new member of the PHD zinc finger family called Pf1 that interacts with two global transcription corepressors: mSin3A and TLE. Pf1 interacts with TLE. The Groucho/TLE proteins are members of an abundant corepressor family, and we hypothesized that Pf1 might interact with TLE family members. Together, these data suggest that in the absence of interactions with mSin3A, Gal4-Pf1 (102–273 L212P/A216P)-dependent repression can be attributed to interaction with endogenous TLE. | SIGNOR-266992 |
Q05655 | Q05655 | 2 | phosphorylation | up-regulates | 0.2 | This study identifies novel in vitro pkcdelta autophosphorylation sites at thr(141) adjacent to the pseudosubstrate domain, thr(218) in the c1a-c1b interdomain, ser(295), ser(302), and ser(304) in the hinge region, and ser(503) adjacent to thr(505) in the activation loop. studies reported herein show that a t505a substitution reduces pkcdelta-thr(295) autophosphorylation | SIGNOR-185287 |
P19784 | O95786 | 1 | phosphorylation | down-regulates activity | 0.2 | Phosphorylation of RIG-I by casein kinase II inhibits its antiviral response.Threonine at amino acid (aa) 770 and serine at aa 854 to 855 of RIG-I are phosphorylated by casein kinase II (CK2) in the resting state of the cell and dephosphorylated when cells are infected by RNA virus. | SIGNOR-276285 |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.