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 |
|---|---|---|---|---|---|---|---|
Q13555 | Q4G163 | 1 | phosphorylation | down-regulates activity | 0.2 | Activated CaMKII and polo-like kinase simultaneously phosphorylate and inactivate Emi2 [ xref , xref , xref , xref , xref ]). | SIGNOR-280200 |
P17252 | P13498 | 1 | phosphorylation | up-regulates | 0.2 | Phosphorylation of p22phox on threonine 147 enhances NADPH oxidase activity by promoting p47phox binding. | Threonine 147 of p22phox Is Phosphorylated by PKC-α and PKC-δ in Vitro | SIGNOR-260891 |
P06493 | P40337 | 1 | phosphorylation | up-regulates activity | 0.2 | Mechanistically, CDK1 directly phosphorylates pVHL at Ser80, which primes the recognition of pVHL by PIN1.|PIN1 and CDK1 cooperatively modulate the protein turnover of pVHL, thereby conferring tumor growth, chemotherapeutic resistance and metastasis both in vitro and in vivo. | SIGNOR-280207 |
P21127 | O43172 | 1 | phosphorylation | up-regulates activity | 0.2 | Furthermore, hPRP4 interacted directly with Clk1 on its COOH terminus, and the arginine and serine rich domain of hPRP4 was phosphorylated by Clk1 in vitro.|Overexpression of Clk1 caused redistribution of hPRP4, from the speckled to the diffuse pattern in nucleoplasm, whereas inactive mutant of Clk1 caused no change of hPRP4 localization. | SIGNOR-280208 |
P05771 | Q13131 | 1 | phosphorylation | down-regulates activity | 0.2 | Purified PKC and Akt both phosphorylated AMPKα1 Ser487 in vitro with similar efficiency. PKC activation was associated with reduced AMPK activity, as inhibition of PKC increased AMPK activity and phorbol esters inhibited AMPK, an effect lost in cells expressing mutant AMPKα1 Ser487Ala. Consistent with a pathophysiological role for this modification, AMPKα1 Ser487 phosphorylation was inversely correlated with insulin sensitivity in human muscle. | SIGNOR-276460 |
Q14493 | Q8N257 | 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-265388 |
P68400 | Q96PX8 | 1 | phosphorylation | up-regulates activity | 0.2 | In our studies, SICD was phosphorylated by PKA, PKC, and CK2, and association of SLITRK1 with 14-3-3 was regulated by phosphorylation at Ser695. Co-precipitation experiments demonstrated much greater recovery of 14-3-3 in SLITRK1 precipitates when wild-type or S695E was used, as compared with S695A, consistent with the results with purified peptides. | SIGNOR-273633 |
Q9Y572 | P09622 | 1 | phosphorylation | up-regulates activity | 0.2 | Here, we show that RIP3 activates the pyruvate dehydrogenase complex (PDC, also known as PDH), the rate-limiting enzyme linking glycolysis to aerobic respiration, by directly phosphorylating the PDC E3 subunit (PDC-E3) on T135. | SIGNOR-266372 |
Q53ET0 | Q99576 | 1 | transcriptional regulation | up-regulates quantity | 0.2 | CRTC2 knockdown attenuates glucocorticoid-responsive GILZ mRNA expression in HeLa cells | SIGNOR-256109 |
O60684 | P46531 | 1 | relocalization | up-regulates | 0.2 | Nicd binds via one of its four potential nuclear localization signals to importins alfa3, alfa4, and alfa7. importins alpha3, alpha4 (and to a lesser extent, alpha7) mediate nuclear import of nicd and thus are directly involved in notch signaling. | SIGNOR-165343 |
Q9H4A3 | Q15796 | 1 | phosphorylation | up-regulates quantity | 0.2 | In addition, WNK1 and WNK4 can phosphorylate Smad2, and silencing of WNK1 reduces Smad2 protein levels in HeLa cells, suggesting that WNKs have complex effects on TGFbeta signaling, which itself can promote cancer or act in a tumor suppressing manner. | SIGNOR-280164 |
P43403 | Q13433 | 1 | phosphorylation | up-regulates activity | 0.2 | To summarize, upon TCR triggering Zap70 activates Zip6, which is localized to the IS, through phosphorylation of tyrosine residues likely located in the long cytoplasmic loop.|Zip6 Is Phosphorylated by Zap70 in Response to TCR Stimulation. | SIGNOR-280165 |
P00519 | P78337 | 1 | phosphorylation | up-regulates activity | 0.2 | Notably, c-Abl controls augmentation of Pitx1 at the post-transcriptional level.|Overexpression of c-Abl induces tyrosine phosphorylation of Pitx1, either directly or indirectly. | SIGNOR-280171 |
P12931 | Q13263 | 1 | phosphorylation | down-regulates activity | 0.2 | Among SFKs, Src strongly induces tyrosine phosphorylation of KAP1.|Immunostaining and chromatin fractionation show that Src and Lyn decrease the association of KAP1 with heterochromatin in a kinase activity-dependent manner. | SIGNOR-280137 |
Q9Y6E0 | Q7L7X3 | 1 | phosphorylation | up-regulates activity | 0.2 | Thus, MST3 phosphorylates TAO1 and TAO2, enabling their association with Myosin Va. | SIGNOR-280140 |
Q9P289 | P35222 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.2 | In response to Wnt3a stimulation, the kinase MST4 directly phosphorylates \u03b2-catenin at Thr40 to block its Ser33 phosphorylation by GSK3\u03b2. | SIGNOR-280141 |
Q13043 | P10275 | 1 | phosphorylation | down-regulates activity | 0.2 | Here we showed that MST1 is an androgen receptor kinase and phosphorylates androgen receptor at Ser-650 ( ).|Mst1 plays a critical role in the regulation of programmed cell death and it has been implicated in PCa development. Interestingly, MST1 has been detected in AR-chromatin complexes, and forced expression of MST1 reduces AR binding to androgen-responsive elements along the PSA promoter. | SIGNOR-280143 |
Q16539 | Q12948 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.2 | P38 interacts with and phosphorylates the Ser241 and ser272 sites of FOXC1 to maintain its stability by inhibiting ubiquitination and degradation. | SIGNOR-275913 |
P29350 | Q8NER1 | 1 | dephosphorylation | down-regulates activity | 0.2 | Shp-1 dephosphorylates TRPV1 in dorsal root ganglion neurons and alleviates CFA-induced inflammatory pain in rats.|These results suggested that Shp-1 dephosphorylated and inhibited TRPV1 in DRG neurons, contributing to maintain thermal nociceptive thresholds in normal rats, and as a compensatory mechanism, Shp-1 increased in DRGs of rats with CFA-induced inflammatory pain, which was involved in protecting against excessive thermal hyperalgesia. | SIGNOR-277129 |
P33981 | P21589 | 1 | phosphorylation | up-regulates activity | 0.2 | Intermolecular NTE phosphorylation by Mps1 requires a topology in which sites proximal to the NTE interact with the active Mps1 in order to promote phosphorylation. | SIGNOR-280157 |
O00712 | O00712 | 2 | binding | down-regulates activity | 0.2 | Coexpression of NFI-B3 with other isoforms of the NFI-B, -C, and -X family, however, led to a strong reduction of transcriptional activation compared with the expression of these factors alone. NFI-B3 apparently forms heterodimers with other NFI proteins thereby interfering with their function. | SIGNOR-240883 |
Q14012 | Q14012 | 2 | phosphorylation | up-regulates activity | 0.2 | CaM kinase I was autophosphorylated in a Ca2+/CaM-dependent manner at a threonyl residue (Thr-177) which is located at a position equivalent to that of the threonyl residue (Thr-197) autophosphorylated in cAMP-dependent protein kinase. | SIGNOR-250612 |
Q96BR1 | Q66PJ3 | 1 | phosphorylation | down-regulates activity | 0.2 | AIP4 is phosphorylated by CISK in vitro on WW domain residues, which may impact its ability to interact with and ubiquitinate substrate proteins.|Expression of a constitutively active CISK inhibits CXCR4 degradation, possibly by attenuating CXCR4 binding to and ubiquitination by AIP4 and/or modulating the action of AIP4 on a protein involved in CXCR4 endosomal sorting . | SIGNOR-280124 |
Q9H2G2 | P41161 | 1 | phosphorylation | up-regulates activity | 0.2 | Here, we report that the direct activation of the three mammalian ERMs by the Ste20-like kinase (SLK) is crucial for guiding the mitotic spindle toward the expected orientation in two mammalian models of oriented cell division: micropatterned cells and apical progenitors of the mouse neocortex.|SLK directly phosphorylates mammalian ERMs and controls their cortical activation in mitosis. | SIGNOR-280126 |
Q05519 | Q14114 | 1 | post transcriptional regulation | up-regulates quantity by stabilization | 0.2 | We demonstrate that SFRS11 directly binds to the 3' UTR of LRP8 mRNA, as well as to the third exon of apoE mRNA, resulting in stabilization of these mRNAs, eventually deactivating JNK signaling. | SIGNOR-269670 |
Q04759 | P29350 | 1 | phosphorylation | down-regulates activity | 0.2 | SHP-1 phosphorylation is mediated through PKC-θ. Here, we show that phosphorylation of SHP-1 in NK cells on the S591 residue by PKC-θ promotes the inhibited SHP-1 'folded' state. Silencing PKC-θ maintains SHP-1 in the active conformation, reduces NK cell activation and cytotoxicity, and promotes tumor progression in vivo. | SIGNOR-277590 |
O75116 | Q9UBR4 | 1 | phosphorylation | up-regulates activity | 0.2 | Rok-\u03b1 phosphorylates and activates LIM kinase, which in turn phosphorylates and inactivates cofilin. | SIGNOR-280110 |
Q05655 | P09874 | 1 | phosphorylation | down-regulates activity | 0.2 | Interestingly, comparable experiments with the Ca 2+ -independent PKC\u03b4 isoform revealed that PKC\u03b4 phosphorylates ARTD1 at the N-terminus (amino acids 1\u2013214) and phosphorylation of ARTD1 by PKC\u03b4 inhibited DNA-induced PAR formation by ARTD1 in vitro (Supplementary Figure S6A and S6B), suggesting that the observed stimulatory effect of the PKCi on PAR formation might be due to inhibition of ARTD1 by PKC\u03b4. | SIGNOR-280085 |
Q9H3D4 | Q6ZMZ3 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Here we show that in the developing skin, epidermal progenitor cells of mice lacking p63 transcription factor display alterations in the nuclear shape accompanied by a marked decrease in expression of several nuclear envelope-associated components (Lamin B1, Lamin A/C, Sun1, Nesprin-3, Plectin) compared with controls. Furthermore, chromatin immunoprecipitation-quantitative PCR assay showed enrichment of p63 on Sun1, Syne3, and Plec promoters, suggesting them as p63 targets. | SIGNOR-263280 |
Q9UBF6 | P42574 | 1 | ubiquitination | down-regulates activity | 0.2 | SAG (Sensitive to Apoptosis Gene), also known as RBX2 (RING box protein 2), ROC2 (Regulator of Cullins 2), or RNF7 (RING Finger Protein 7), was originally cloned in our laboratory as a redox inducible antioxidant protein and later characterized as the second member of the RBX/ROC RING component of the SCF (SKP1-CUL-F-box Proteins) E3 ubiquitin ligase. by forming a complex with other components of the SCF E3 ligase, SAG promotes ubiquitination and degradation of a number of protein substrates, including c-JUN, DEPTOR, HIF-1α, IκBα, NF1, NOXA, p27, and procaspase-3, thus regulating various signaling pathways and biological processes. | SIGNOR-271448 |
P0DTC2 | Q9BYF1 | 1 | binding | down-regulates activity | 0.2 | SARS-CoV and likely SARS-CoV-2 lead to downregulation of the ACE2 receptor, but not ACE, through binding of the spike protein with ACE2. This leads to viral entry and replication, as well as severe lung injury. | SIGNOR-260742 |
P59594 | Q9BYF1 | 1 | binding | down-regulates activity | 0.2 | Cell entry of severe acute respiratory syndrome coronavirus (SARS-CoV) is mediated by the viral spike (S) protein. Amino acids 319-510 on the S protein have been mapped as the receptor-binding domain (RBD), which mediates binding to the SARS-CoV receptor angiotensin converting enzyme 2 (ACE2) on SARS-CoV susceptible cells. Here, we demonstrate that the RBD spike protein alone can be internalized together with ACE2. We propose that after binding to ACE2, the RBD spike protein activates the ACE2 mediated cellular endocytosis signal pathway, by which SARS-CoV enters the susceptible cells. | SIGNOR-260283 |
P41240 | P41240 | 2 | phosphorylation | up-regulates activity | 0.2 | Taken together these results indicate that Csk can be phosphorylated in vivo at Tyr-184 by an as yet unknown tyrosine kinase, and that autophosphorylation of Tyr-304 occurs only at abnormally high Csk concentrations in vitro. Furthermore, Tyr-304 is required for the maintenance of the structure of the Csk kinase domain. | SIGNOR-250778 |
O96013 | O14713 | 1 | phosphorylation | down-regulates activity | 0.2 | We further demonstrate that p21 activated kinase 4 (PAK4) can phosphorylate ICAP1 at Ser 10 both in vitro and in cultured cells, and that active PAK4 inhibits ICAP1 nuclear accumulation in a Ser-10-dependent manner.|We further demonstrate that p21-activated kinase 4 (PAK4) can phosphorylate ICAP1 at Ser-10 both in vitro and in cultured cells, and that active PAK4 inhibits ICAP1 nuclear accumulation in a Ser-10-dependent manner. | SIGNOR-280056 |
Q9NQU5 | P08134 | 1 | phosphorylation | down-regulates activity | 0.2 | It is possible that Pak6 may directly phosphorylate RhoC to regulate its activity.|Nevertheless, our results clearly show that the kinase activity of Pak6 is required to inhibit RhoC induced cell contraction. | SIGNOR-280059 |
Q9NQU5 | P48431 | 1 | phosphorylation | up-regulates quantity | 0.2 | PAK5 promotes the cell stemness ability by phosphorylating SOX2 in lung squamous cell carcinomas.|The absence of PAK5 abolishes self-renewal ability of LUSC cells by decreasing the expression and phosphorylation of SOX2 in vitro and in vivo. | SIGNOR-280060 |
Q16512 | Q969V6 | 1 | phosphorylation | down-regulates activity | 0.2 | Although RHOA mediated actin polymerization accelerated MRTFA induced gene transcription, PKN1 and PKN2 inhibited the interaction of MRTFA with G-actin by phosphorylating MRTFA, causing increased serum response factor (SRF)-mediated expression of cardiac hypertrophy- and fibrosis associated genes.|Further, we identified MRTFA as a novel substrate of PKN1 and PKN2 and found that MRTFA phosphorylation by PKN was considerably more effective than that by ROCK in vitro . | SIGNOR-280067 |
Q9H4B4 | P16104 | 1 | phosphorylation | up-regulates activity | 0.2 | Phosphorylation of H2AX at serine 139 was catalyzed by hyperosmotic stress-induced activation of Plk3.|Osmotic stress induced phosphorylation of H2AX by polo like kinase 3 affects cell cycle progression in human corneal epithelial cells.|Our results for the first time reveal that hyperosmotic stress-activated Plk3 elicited \u03b3H2AX. | SIGNOR-280073 |
Q9Y4B6 | Q99878 | 1 | phosphorylation | up-regulates activity | 0.2 | Here we report that VprBP possesses an intrinsic protein kinase activity and is capable of phosphorylating histone H2A on threonine 120 (H2AT120p) in a nucleosomal context. Functional studies reveal that H2AT120p by VprBP is sufficient to repress chromatin transcription. | SIGNOR-279884 |
P17612 | P30305 | 1 | phosphorylation | up-regulates activity | 0.2 | Overall, PRKACA may directly phosphorylate CDC25B on Ser321 to control cell cycle progression in mouse-fertilized eggs [ xref ].|PRKACA phosphorylates and activates CDC25B in fertilized eggs of mice [ xref ]. | SIGNOR-280077 |
P17252 | O15511 | 1 | phosphorylation | up-regulates activity | 0.2 | PKC\u03b1 phosphorylates and activates ARPC5, which organizes the actin net dorsolateral of nucleus. | SIGNOR-280078 |
P41743 | P29474 | 1 | phosphorylation | down-regulates activity | 0.2 | The phosphorylation of both S617 and S635 have also been shown to promote increased eNOS-derived NO release (Michell et al., 2002). The phosphorylaiton of S617 can be induced by PKA or Akt activity, and may serve to sensitize eNOS to calmodulin binding and modulate the phosphorylation of other eNOS sites | SIGNOR-251635 |
P42345 | Q9Y6M1 | 1 | phosphorylation | up-regulates activity | 0.2 | IGF2BP2 can be activated by mTOR and promotes its binding to IGF2 mRNA of IGF2 thereby leading to diabetes mellitus [ xref , xref ].|In addition, phosphorylation of IGF2BP2 in the linker region between RRM2 and KH1 by mTOR promotes its binding to the IGF leader 3 mRNA 5\u2032-UTR, enhancing the initiation of IGF2 translation through eIF-4E- and 5\u2032 cap-independent internal ribosomal entry [ xref ]. | SIGNOR-280046 |
Q9H093 | O43561 | 1 | phosphorylation | down-regulates activity | 0.2 | Analysis by an in vitro kinase assay revealed that NUAK2 could phosphorylate immunoprecipitated LATS and that this phosphorylation was lost in the LATS double mutant (DM), T246A/S613A (Fig.\u00a0 xref ).|We showed that phosphorylation of Ser613, located upstream of the KD, adjacent to the MOB binding site and to a lesser extent the N-terminal localized T246, are required for NUAK2 to inhibit LATS. | SIGNOR-280052 |
Q13153 | P23975 | 1 | phosphorylation | down-regulates activity | 0.2 | PAK1 negatively regulates the activity of the Rho exchange factor NET1.|Specifically, PAK1 phosphorylates NET1 on three sites in vitro : serines 152, 153, and 538. | SIGNOR-280054 |
O96013 | P17676 | 1 | phosphorylation | up-regulates activity | 0.2 | Importantly, we found that PAK4 enhanced CEBPB phosphorylation on Thr 235.|In summary, we showed that PAK4 mediated CEBPB activation upregulated CLDN4 expression to promote breast cancer cell migration and invasion. | SIGNOR-280055 |
Q9UK99 | Q13501 | 1 | binding | down-regulates quantity by destabilization | 0.2 | F-box protein Fbxo3 targets Smurf1 ubiquitin ligase for ubiquitination and degradation. Here we show that another F-box protein Fbxo3, belonging to the FBXO type protein family, also interacts with and targets Smurf1 for poly-ubiquitination and proteasomal degradation. The SCF complex is composed of F-box protein, Skp1, Cullin1 (Cul1) and ROC1. Fbxo3, whose substrates are few, forms SCF Fbxo3 ubiquitin ligase and regulates the degradations of Fbxl2, p62, HIPK2 and p300 through the ubiquitin-proteasome pathway. | SIGNOR-272444 |
P49760 | Q9UBK2 | 1 | phosphorylation | down-regulates activity | 0.2 | Clk2 could also repress PGC-1alpha activation of Foxo1 on the IRS response element , as well as repress the Pepck promoter .|Clk2 phosphorylates and represses PGC-1\u03b1. | SIGNOR-278228 |
P17612 | Q9NS28 | 1 | phosphorylation | up-regulates activity | 0.2 | Cyclic AMP- and cyclic GMP-dependent kinases (PKA, PKG) inhibit the interaction of RGS18 and 14-3-3 by phosphorylating S216. | SIGNOR-273786 |
Q9P286 | O43426 | 1 | phosphorylation | up-regulates activity | 0.2 | We identified two novel Pak5 substrates, Pacsin1 and Synaptojanin1, proteins that directly interact with one another to regulate synaptic vesicle endocytosis and recycling. Pacsin1 and Synaptojanin1 were phosphorylated by Pak5 and the other group II Paks in vitro, and Pak5 phosphorylation promoted Pacsin1-Synaptojanin1 binding both in vitro and in vivo. | SIGNOR-263026 |
Q8IXL6 | Q2M3R5 | 1 | phosphorylation | up-regulates activity | 0.2 | Notably, phosphorylation of Stim1 by Fam20C enhances Stim1 activation and store-operated Ca 2+ entry.|We feel that the western blot shows an appropriate range of contrast to support the conclusion that Stim1 can be activated by Fam20C under high calcium conditions. | SIGNOR-280012 |
Q15119 | Q9H300 | 1 | phosphorylation | up-regulates activity | 0.2 | As expected, knocking down PDK2 in HEK293 cells that overexpress PARL resulted in a significant increase in beta cleavage in comparison to the control cells.|Furthermore, we show that PDK2, a key regulator in metabolic plasticity, phosphorylates PARL and regulates \u03b2 cleavage. | SIGNOR-280018 |
Q15759 | P30281 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | P38SAPK2 phosphorylates cyclin D3 at Thr-283 and targets it for proteasomal degradation. | SIGNOR-280023 |
Q00535 | A0A1B0GVQ0 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Cdk5 also phosphorylates PSD-95-interacting protein Spine Associated RapGAP (SPAR), resulting in its degradation ([98], Table 2). | SIGNOR-280219 |
P25098 | O95398 | 1 | phosphorylation | down-regulates activity | 0.2 | The observation that GRK2 co-immunoprecipitates with Epac1 suggests a direct association between GRK2 and Epac1 in DRGs. xref A detailed study of the influence of GRK2 on the Epac1 level found that phosphorylation of ser108 in Epac1 by GRK2 can lead to a reduction of Epac1 activation. xref Downstream consequence of a reduction of GRK2 was explored. xref Low GRK2 expression in GRK2(\u00b1) DRGs was found to facilitate CPT-induced Rap1 activation and increase the phosphorylated ERK1/2 level. | SIGNOR-280001 |
P0DMV9 | Q9HC29 | 1 | binding | up-regulates quantity by stabilization | 0.2 | The molecular chaperone HSP70 binds to and stabilizes NOD2, an important protein involved in Crohn disease. | SIGNOR-252417 |
Q06187 | Q15417 | 1 | phosphorylation | up-regulates quantity | 0.2 | Co-expression of calponin-3 with various kinases in S2 Schneider cells promoted a phosphorylation of calponin-3 by Syk, but also by the Tec family kinase Btk. | SIGNOR-280196 |
P54762 | Q03135 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | EphB1-dependent Y-14 phosphorylation of Cav-1 regulates caveolae endocytosis and endothelial permeability. | SIGNOR-280008 |
Q16549 | P18850 | 1 | phosphorylation | up-regulates | 0.2 | We discovered that azc, an agent that causes the formation of abnormal proteins, stimulates the stress-activated kinase p38 mapk, which phosphorylates atf6 | SIGNOR-89813 |
Q9Y5H9 | Q9Y5G1 | 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-265685 |
P05556 | Q12809 | 2 | binding | up-regulates activity | 0.2 | One such mechanism is operant in colorectal cancer (CRC) cells. On integrin-dependent CRC cell adhesion, the Kv11.1/β1 integrin complex recruits the PI3K p85 subunit, which stimulates AKT phosphorylation and thus regulates autophagy | SIGNOR-277614 |
P36873 | P42575 | 1 | dephosphorylation | up-regulates activity | 0.2 | nutrient-replete oocytes inhibit C2 via S135 phosphorylation catalyzed by calcium/calmodulin-dependent protein kinase II. We now show that C2 phosphorylated at S135 binds 14-3-3zeta, thus preventing C2 dephosphorylation. Moreover, we determined that S135 dephosphorylation is catalyzed by protein phosphatase-1 (PP1), which directly binds C2. | SIGNOR-248503 |
P06241 | Q9ULL1 | 1 | phosphorylation | up-regulates activity | 0.2 | We also show that this activation of PLEKHG1 by FYN requires interaction between these two proteins and FYN-induced tyrosine phosphorylation of PLEKHG1 .|We also show that this activation of PLEKHG1 by FYN requires interaction between these two proteins and FYN-induced tyrosine phosphorylation of PLEKHG1. | SIGNOR-279988 |
Q15835 | O00254 | 1 | phosphorylation | down-regulates activity | 0.2 | For example, RhoK phosphorylates and inhibits TIAM1, STEF, and PAR3; disrupts the polarity complex; and prevents Rac activation ( xref ). | SIGNOR-279993 |
Q15835 | Q13009 | 1 | phosphorylation | down-regulates activity | 0.2 | For example, RhoK phosphorylates and inhibits TIAM1, STEF, and PAR3; disrupts the polarity complex; and prevents Rac activation ( xref ). | SIGNOR-279995 |
Q15818 | Q07812 | 1 | relocalization | up-regulates activity | 0.2 | Immunofluorescence staining and subcellular fractionation analyses revealed increased mitochondrial translocation of Bad and Bax proteins from cytoplasm following OGD (4 h) and simultaneously increased release of Cyt C from mitochondria followed by activation of caspase-3. NP1 protein was immunoprecipitated with Bad and Bax proteins; OGD caused increased interactions of NP1 with Bad and Bax, thereby, facilitating their mitochondrial translocation and dissipation of mitochondrial membrane potential | SIGNOR-261439 |
P25098 | Q13304 | 1 | phosphorylation | down-regulates activity | 0.2 | As depicted in Fig. 8 A and B, GRK2 silencing resulted in up-regulation of GPR17 and down-regulation of the mature markers CNPase and MBP, indicating a shift of cells toward a less differentiated stage.Having established that, in primary cultured OPCs, LTD 4 mediated desensitization of GPR17 through the primary recruitment of GRK2, we then asked whether GRK2 pharmacological inhibition had any effects on cysLT promoted cell maturation.|These data demonstrate that LTD 4 -induced GPR17 phosphorylation is preferentially mediated by GRK2 and only partially by GRK5, whereas UDP-glucose-mediated receptor phosphorylation exclusively requires the GRK5 isoform.We examined the involvement of GRK2 and GRK5 in agonist induced desensitization of GPR17. | SIGNOR-279999 |
Q9Y478 | 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-277609 |
Q9H158 | 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-269032 |
P18031 | Q05655 | 1 | dephosphorylation | down-regulates | 0.2 | Dephosphorylation of tyrosine residues by ptp1b, a protein tyrosine phosphatase, reduced the enhanced pkcdelta activity. | SIGNOR-107754 |
O60341 | P84243 | 1 | demethylation | up-regulates activity | 0.2 | Here, we provide evidence that LSD1 (KIAA0601), a nuclear homolog of amine oxidases, functions as a histone demethylase and transcriptional corepressor. LSD1 specifically demethylates histone H3 lysine 4, which is linked to active transcription. | SIGNOR-264509 |
Q02156 | Q16612 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Site-directed mutagenesis of S59A retarded P311 degradation and induced glioma cell motility. In contrast, S59D mutation resulted in the rapid degradation of P311 and reduced glioma cell migration.Taken together, our results show that the serine phosphorylation of P311 is dependent on the function of both PKCε and PKCz. | SIGNOR-273830 |
Q9UDY6 | P60484 | 1 | ubiquitination | down-regulates quantity | 0.2 | Collectively, these results indicate that TRIM10 may lead to ubiquitination and degradation of PTEN, which could be an underlying reason for AKT signalling inhibition in cardiac hypertrophy processes (Figure\u00a05D).4\n\nDISCUSSION.|In addition, we found that the effect regulated by TRIM10 was mediated by interactions with phosphatase and tensin homolog (PTEN); specifically, TRIM10 promoted PTEN ubiquitination, thus leading to AKT signalling activation.|The results showed that TRIM10 overexpression decreased PTEN expression, and MG132 reversed the reduction in PTEN (Figure\u00a05C). | SIGNOR-278729 |
Q92830 | Q71DI3 | 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-269601 |
P16144 | P48736 | 1 | binding | up-regulates | 0.2 | Stable expression of alpha6beta4 increased carcinoma invasion in a pi3k-dependent manner, and transient expression of a constitutively active pi3k increased invasion in the absence of alpha6beta4. Ligation of alpha6beta4 stimulated significantly more pi3k activity than ligation of beta1 integrins, establishing specificity among integrins for pi3k activation. | SIGNOR-54703 |
P15172 | Q8NG27 | 1 | transcriptional regulation | up-regulates quantity | 0.2 | ... chromatin immunoprecipitation (ChIP) analysis showed MYOD binds to a site upstream the Pja1 promoter preferentially in C2C12 cells induced to differentiate (Fig. 2c). In addition, over-expression of MyoD in human fibroblasts is sufficient to up-regulate Pja1 expression | SIGNOR-255718 |
Q92844 | O95147 | 1 | ubiquitination | up-regulates activity | 0.2 | TRAF2-mediated Lys63-linked ubiquitination of DUSP14/MKP6 is essential for its phosphatase activity. Mass spectrometry and mutational analyses identified that DUSP14 was Lys63-linked ubiquitinated at lysine 103 residue.Here we report that DUSP14 was Lys63-linked ubiquitinated at Lys103 residue by the E3 ligase TRAF2 during TCR signaling. Furthermore, ubiquitination of DUSP14 was essential for its phosphatase activity. | SIGNOR-272811 |
P00533 | Q96FA3 | 2 | phosphorylation | up-regulates activity | 0.2 | EGFR is positively correlated with PELI1 expression in breast cancers, and its activation led to the phosphorylation of PELI1 at Tyr154 and Thr264, which subsequently activated its E3 ubiquitin ligase. | SIGNOR-277874 |
P17252 | P35503 | 1 | phosphorylation | up-regulates activity | 0.2 | Curcumin and calphostin C suppressed the activity and phosphorylation of recombinant UGT1A3 expressed in Sf9 cells. These results indicate that UGT1A3 undergoes phosphorylation, which is required for its catalytic activity. Calphostin C is a highly specific protein kinase C (PKC) inhibitor, so three predicted PKC phosphorylation sites in UGT1A3 were examined. In conclusion, phosphorylation plays an important role in UGT1A3 activity, and the serine at site 43 in UGT1A3 is most likely a phosphorylation site. | SIGNOR-273823 |
Q04759 | Q15052 | 1 | phosphorylation | up-regulates activity | 0.2 | Recently, we have reported that the active form of Rac 1 GTPase binds to the glycogen phosphorylase muscle isoform (PYGM) and modulates its enzymatic activity leading to T cell proliferation.|More specifically, αPIX, a known guanine nucleotide exchange factor for the small GTPases of the Rho family, preferentially Rac 1, mediates PYGM activation in Kit 225 T cells stimulated with IL-2. Using directed mutagenesis, phosphorylation of αPIX Rho-GEF serines 225 and 488 is required for activation of the Rac 1/PYGM pathway. | SIGNOR-272168 |
P59594 | Q9H2X3 | 1 | binding | up-regulates activity | 0.2 | Here we show that DC-SIGN and DC-SIGNR enhance infection mediated by the glycoprotein (GP) of Marburg virus (MARV) and the S protein of severe acute respiratory syndrome coronavirus and might promote viral dissemination. | SIGNOR-260269 |
Q8IXL6 | Q96HE7 | 1 | phosphorylation | up-regulates activity | 0.2 | We further show that ER oxidoreductin 1α (Ero1α), the pivotal sulfhydryl oxidase that catalyzes disulfide formation in the ER, is phosphorylated by Fam20C in the Golgi apparatus and retrograde-transported to the ER mediated by ERp44. The phosphorylation of Ser145 greatly enhances Ero1α oxidase activity and is critical for maintaining ER redox homeostasis and promoting oxidative protein folding. | SIGNOR-277395 |
Q9UNW8 | 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-256945 |
Q13315 | Q8WVD3 | 1 | phosphorylation | up-regulates activity | 0.2 | We further confirm that RNF138 is phosphorylated by ATM at Ser124. | SIGNOR-279505 |
O00398 | 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-257005 |
P78317 | Q13952 | 1 | binding | up-regulates activity | 0.2 | Coactivator RNF4 is involved in the GCH gene expression. Through serial deletion and mutagenesis studies of the GCH promoter, we defined the RNF4-responsive element on GCH proximal promoter as a CCAAT box. RNF4 did not possess specific DNA binding activity toward this CCAAT box, which suggests that RNF4 may be a coactivator of the CCAAT boxbinding protein nuclear factor Y (NF-Y). RNF4 is a coactivator for nuclear factor Y on GTP cyclohydrolase I proximal promoter. | SIGNOR-252231 |
O95819 | Q15797 | 1 | phosphorylation | down-regulates activity | 0.2 | Msn kinases directly phosphorylate α-helix 1 of Smad. we have identified Misshapen (Msn) and the mammalian orthologs TNIK, MINK1, and MAP4K4 as the kinases responsible for α-helix 1 phosphorylation. | SIGNOR-276335 |
Q9H2X6 | Q08050 | 1 | phosphorylation | up-regulates activity | 0.2 | In conclusion, the phosphorylation of FOXM1 by HIPK2 can promote FOXM1 transcription activity and cell proliferation in RCC, thus, indicating a potential mechanism for the treatment of human RCC in the future. | SIGNOR-278944 |
P08174 | P48960 | 1 | binding | up-regulates | 0.2 | This interaction may facilitate cell activation and migration through the blood-brain barrier. In addition, cd97-cd55 interactions in the parenchyma of the brain may contribute to the inflammation. | SIGNOR-95458 |
P53671 | Q99801 | 1 | phosphorylation | down-regulates activity | 0.2 | LIMK2 also downregulates NKX3.1 mRNA levels.|While WT-NKX3.1 was efficiently phosphorylated, the S185A mutant showed no phosphorylation ( xref A), confirming that LIMK2 only phosphorylates the S185 site in NKX3.1. | SIGNOR-278951 |
Q8TDC3 | P20810 | 1 | phosphorylation | up-regulates activity | 0.2 | Here, we show that an AZ cytomatrix protein CAST and an AZ-associated protein kinase SAD-B coordinately regulate STD by controlling reloading of the AZ with release-ready synaptic vesicles. SAD-B phosphorylates the N-terminal serine (S45) of CAST, and S45 phosphorylation increases with higher firing rate. | SIGNOR-263051 |
P53671 | Q15672 | 1 | phosphorylation | up-regulates quantity | 0.2 | LIMK2 directly phosphorylated TWIST1, indicating that LIMK2 also regulates TWIST1 post-translationally (XREF_FIG).|LIMK2 positively regulates TWIST1 protein levels. | SIGNOR-278952 |
Q9Y4C1 | P84243 | 1 | demethylation | up-regulates activity | 0.2 | Using a biochemical assay coupled with chromatography, we have purified a JmjC domain-containing protein, JHDM2A, which specifically demethylates mono- and dimethyl-H3K9. | SIGNOR-276845 |
Q13547 | Q01543 | 1 | deacetylation | up-regulates | 0.2 | Hdac1 interacts with fli1 and mediates its deacetylation / our previous studies have shown that pcaf-dependent acetylation of fli1 at lysine 380 decreases its protein stability / p300 promotes the interaction of fli1 with hdac1 and increases the dna binding ability of fli1 through deacetylation of lysine 380 | SIGNOR-202689 |
O43379 | P45985 | 1 | relocalization | up-regulates activity | 0.2 | In the WT brain, the WDR62 scaffold organizes a protein complex including MEKK3, MKK4/7, and JNK1 to control NPC development during corticogenesis | SIGNOR-271715 |
P15336 | Q9Y6E7 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | Our data suggest that mTORC1 promotes the binding of the E3 ligase, βTrCP, to CREB2 (Figure 4D), promoting CREB2 degradation by the proteasome (Figure 4E). Here, we show that mTORC1 promotes glutamine anaplerosis by activating glutamate dehydrogenase (GDH). This regulation requires transcriptional repression of SIRT4, the mitochondrial-localized sirtuin that inhibits GDH. Mechanistically, mTORC1 represses SIRT4 by promoting the proteasome-mediated destabilization of cAMP-responsive element binding 2 (CREB2). | SIGNOR-267831 |
Q9ULU4 | P16070 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | Our quantitative ChIP experiments confirmed that ZMYND8 and JARID1D were co-localized at Slug, CD44, VEGFA, and EGFR genes (Figures 4F–4I). Our ChIP results also showed that ZMYND8 repressed and occupied other JARID1D target genes, such as the matrix metalloproteinase 1 (MMP1) and MMP3, that we previously reported | SIGNOR-262039 |
Q7Z570 | O43451 | 1 | transcriptional regulation | down-regulates quantity by repression | 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-269466 |
Q96PU5 | Q9NRA0 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | In this study, we found that NEDD4L interacted with SphK2 to ubiquitinate SphK2 protein.|NEDD4L Mediates the Degradation of SphK2 Protein Through the Ubiquitin-Proteasomal Pathway. | SIGNOR-278660 |
Q13625 | Q96A00 | 1 | binding | down-regulates | 0.2 | The phosphorylase phosphatase activity of pp1 was inhibited by p53bp2 at nanomolar concentrations. | SIGNOR-39666 |
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