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 |
|---|---|---|---|---|---|---|---|
Q9Y653 | Q14344 | 1 | binding | up-regulates activity | 0.2 | Binding of collagen III to ADGRG1 provides a canonical example of adhesion GPCR interactions with ECM proteins (Luo et al., 2011). Identified by an in vitro biotinylation/proteomics approach, extracellular interactions with collagen III were subsequently proven capable of activating ADGRG1-mediated signaling via Gα12/13 followed by RhoA activation to regulate corticogenesis | SIGNOR-272345 |
P48729 | A8MYZ6 | 1 | phosphorylation | down-regulates | 0.2 | Additionally, ck1, dyrk1a, and cdk2 also phosphorylate foxos at various sites to inhibit foxos activity. | SIGNOR-183667 |
Q9UJZ1 | P06239 | 1 | binding | up-regulates activity | 0.2 | In these studies, we also found that SLP-2 interacted with Lck, ZAP70, LAT, and PLC-gamma1 during the 30-min period following stimulation in vitro|The SLP-2-associated pool of these molecules became phosphorylated/activated in a sequential manner, a profile compatible with their temporal involvement in early TCR signalling. | SIGNOR-260376 |
P16144 | P42338 | 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-54615 |
Q92831 | P68431 | 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-269611 |
P18848 | P23381 | 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-269429 |
Q13188 | Q13188 | 2 | phosphorylation | up-regulates | 0.2 | Consistent with previous studies, sts alone induces mst2 cleavage and autophosphorylation of thr180, an indicator of mst2 activation, as well as apoptosis. | SIGNOR-164310 |
Q03135 | P43003 | 1 | binding | down-regulates activity | 0.2 | EAAT3 has previously been shown to form complexes with caveolin-1, a major component of caveolae, which participate in the regulation of transport proteins. The present study explored the impact of caveolin-1 on electrogenic transport by excitatory amino acid transporter isoforms EAAT1-4. caveolin-1 is a powerful negative regulator of the excitatory glutamate transporters EAAT1, EAAT2, EAAT3, and EAAT4. Caveolin-1 has been shown to form complexes with the excitatory amino acid transporter EAAT3 (EAAC1) (Gonzalez et al. 2007) and may thus modify the EAAT isoforms by direct interaction with the carriers. | SIGNOR-264808 |
P45983 | Q969R2 | 1 | phosphorylation | up-regulates activity | 0.2 | CK1a1, JNK1 and CDK1 had the highest site-specific activity for ORP4L, while CDK1, GSK3a, CK1a1 and GSK3b showed the highest specificity for the site when corrected for background activity with ORP4L-S4A. Because of the complexity of the serine/proline-rich site, we did not determine which serine(s) in ORP4L were phosphorylated by candidate kinases.|We conclude that phosphorylation of a unique serine/proline motif in the ORD induces a conformation change in ORP4L that enhances interaction with vimentin and cholesterol extraction from membranes. | SIGNOR-264876 |
P11309 | O60381 | 1 | phosphorylation | up-regulates activity | 0.2 | Pim-1 binds to and phosphorylates the transcription factor high mobility group box transcription factor 1 (HBP1), activating it. | SIGNOR-277346 |
Q6PJ69 | Q9NRY4 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | Ubiquitin ligase TRIM65 promotes colorectal cancer metastasis by targeting ARHGAP35 for protein degradation | SIGNOR-272256 |
Q14004 | Q13541 | 1 | phosphorylation | up-regulates activity | 0.2 | CDK13 directly phosphorylates 4E-BP1 at Thr46 and eIF4B at Ser422; genetically or pharmacologically inhibiting CDK13 disrupts mRNA translation. | SIGNOR-273113 |
Q9NRC8 | Q6NXT2 | 1 | deacetylation | up-regulates activity | 0.2 | Besides confirming the previously reported histone H3K18 deacylation activity, our results revealed that SIRT7 has an astonishingly high activity to catalyze deacylation of H3K36 and is also catalytically active to deacylate H3K37. | SIGNOR-275879 |
Q9H3R0 | P84243 | 1 | demethylation | down-regulates activity | 0.2 | As one member of the Jumonji-C histone demethylase family, JMJD2C has the ability to demethylate tri- or di-methylated histone 3 and 2 in either K9 (lysine residue 9) or K36 (lysine residue 36) sites by an oxidative reaction, thereby affecting heterochromatin formation, genomic imprinting, X-chromosome inactivation, and transcriptional regulation of genes.JMJD2C has been proved to be a demethylase for H3K9 methylation, in the manner of catalyzing the demethylation of H3K9me3/me2 (the known repressive markers of gene regulation), a histone mark found in heterochromatin associated with euchromatic transcriptional silencing and heterochromatin formation | SIGNOR-263869 |
P20393 | O60890 | 1 | binding | up-regulates activity | 0.2 | Rev-erbα regulates OPHN-1-mediated RhoA/ERM signalling in platelets., The results of the co-immunoprecipitation revealed that Rev-erbα coimmunoprecipitated with OPHN-1 in both mouse and human platelets and this interaction significantly increased upon stimulation with agonist U46619. | SIGNOR-268428 |
O43318 | Q6P589 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | TAK1 phosphorylated the Ser3 in the noncanonical degron motif of TIPE2 to trigger its interaction with β-TrCP for subsequent ubiquitination and degradation. | SIGNOR-273668 |
Q96SW2 | Q9H3D4 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | CRBN functions as a substrate receptor of the E3 ubiquitin ligase CRL4, whose substrate specificity is modulated by thalidomide and its analogs.When thalidomide binds to CRBN, substrate specificity of CRL4CRBN is altered and CRBN neomorphically binds to ∆Np63, TAp63 and other neosubstrates and ubiquitinates them for proteasomal degradation. | SIGNOR-272214 |
P13861 | P13861 | 2 | phosphorylation | up-regulates activity | 0.2 | RII subunit containing the 'autophosphorylation' site (Ser-95) | SIGNOR-250073 |
O75129 | O14525 | 1 | binding | down-regulates quantity | 0.2 | Biochemical and flow cytometry experiments show that ASTN2 forms a complex with ASTN1 and regulates surface expression of ASTN1. Coexpression with ASTN2 reduces the cell surface localization of ASTN1. | SIGNOR-269813 |
Q9BY66 | P84243 | 1 | demethylation | up-regulates activity | 0.2 | KDM5 subfamily is capable of removing tri‐ and di‐ methyl marks from lysine 4 on histone H3 (H3K4). Depending on the methylation site, its effect on transcription can be either activating or repressing. | SIGNOR-264310 |
P11309 | Q16665 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.2 | PIM1 kinase directly phosphorylates HIF-1α at threonine 455, a previously uncharacterized site within its oxygen-dependent degradation domain. This phosphorylation event disrupts the ability of prolyl hydroxylases to bind and hydroxylate HIF-1α, interrupting its canonical degradation pathway and promoting constitutive transcription of HIF-1 target genes. | SIGNOR-277311 |
P05129 | P25098 | 1 | phosphorylation | up-regulates | 0.2 | Phosphorylation of grk2 by protein kinase c abolishes its inhibition by calmodulinin vitro, grk2 was preferentially phosphorylated by pkc isoforms alpha, gamma, and delta | SIGNOR-83231 |
Q14493 | Q93079 | 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-265391 |
P0C6X7-PRO_0000037311 | Q14653 | 1 | deubiquitination | down-regulates activity | 0.2 | Here we show that PLpro also inhibits IRF3 activation at a step after phosphorylation and that this inhibition is dependent on the de-ubiquitination (DUB) activity of PLpro. We found that PLpro is able to block the type I IFN induction of a constitutively active IRF3, but does not inhibit IRF3 dimerization, nuclear localization or DNA binding. However, inhibition of PLpro’s DUB activity by mutagenesis blocked the IRF3 inhibition activity of PLpro, suggesting a role for IRF3 ubiquitination in induction of a type I IFN innate immune response. | SIGNOR-260249 |
Q6ZRV2 | Q8N752 | 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-273755 |
Q96EB6 | P19174 | 1 | deacetylation | up-regulates activity | 0.2 | The histone acetyltransferase GCN5 (general control non-repressed protein 5) acetylates PGC-1alpha and suppresses its transcriptional activity, whereas sirtuin 1 deacetylates and activates PGC-1alpha. | SIGNOR-275499 |
P17252 | Q96PH1 | 1 | phosphorylation | up-regulates | 0.2 | A constitutively active form of pkc? Robustly increased basal and pma-stimulated nox5 activity and promoted the phosphorylation of nox5 on ser490, thr494, and ser498. | SIGNOR-204550 |
P51955 | Q5FBB7 | 1 | phosphorylation | up-regulates | 0.2 | Here we show that nek2a phosphorylates human sgo1 and such phosphorylation is essential for faithful chromosome congression in mitosis. phosphorylation sites were mapped to ser(14) and ser(507) | SIGNOR-156882 |
Q9BYF1 | P01019-PRO_0000032457 | 2 | cleavage | up-regulates activity | 0.2 | The ACE2 hydrolytic activity is dependent on the C terminus sequence of the substrate, which is evident from the data with the angiotensin peptides. After 2 h, ACE2 hydrolyzes Ang I partially and Ang II completely, although there is no hydrolysis of angiotensin 1–9, angiotensin 1–7, and angiotensin 1–5, which possess the same N terminus. | SIGNOR-260222 |
P27361 | P27361 | 2 | phosphorylation | up-regulates activity | 0.2 | Microtubule-associated protein 2 kinases, ERK1 and ERK2, undergo autophosphorylation on both tyrosine and threonine residues: implications for their mechanism of activation.| | SIGNOR-249471 |
O15169 | O15169 | 2 | binding | up-regulates activity | 0.2 | The axin dix domain has a novel structural fold largely composed of beta-strands that engage in head-to-tail self-interaction to form filaments in the crystal | SIGNOR-155218 |
Q6P5Z2 | Q8N392 | 1 | phosphorylation | up-regulates activity | 0.2 | We present strong evidence that PKN3-ARHGAP18 interaction is increased upon ARHGAP18 phosphorylation and that the phosphorylation of ARHGAP18 by PKN3 enhances its GAP domain activity and contributes to negative regulation of active RhoA.|These results support our data from phosphoproteomic screen and suggest that ARHGAP18 can be phosphorylated by PKN3 on Thr154, Ser156 and Thr158. | SIGNOR-264572 |
Q9NX47 | Q8IWA4 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | MARCH5, a mitochondrial E3 ubiquitin ligase, has been identified as a molecule that binds mitochondrial fission 1 protein (hFis1), dynamin-related protein 1 (Drp1) and mitofusin 2 (Mfn2), key proteins in the control of mitochondrial fission and fusion.|Notably, a significant increase in Mfn1 level, but not Mfn2, Drp1 or hFis1 levels, was observed in MARCH5-depleted cells, indicating that Mfn1 is a major ubiquitylation substrate. | SIGNOR-274133 |
O43318 | O43318 | 2 | phosphorylation | up-regulates activity | 0.2 | Analyses of phosphorylation site mutants of the activation segment indicate that autophosphorylation of Ser-192 precedes TAB1 phosphorylation and is followed by sequential phosphorylation of Thr-178, Thr-187, and finally Thr-184. Finally, we present a model for the chronological order of events governing TAB1-induced TAK1 autoactivation. | SIGNOR-227544 |
Q8NFZ3 | Q9Y4C0 | 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-264163 |
Q9H244 | 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-256991 |
Q05655 | P68431 | 1 | phosphorylation | up-regulates activity | 0.2 | We identify protein kinase c-delta as the kinase responsible for h3t45ph in vitro and in vivo. Given the nucleosomal position of h3t45, we postulate that h3t45ph induces structural change within the nucleosome to facilitate dna nicking and/or fragmentation. | SIGNOR-185144 |
O15111 | Q9C0C7 | 1 | phosphorylation | up-regulates activity | 0.2 | Furthermore, we show that mitophagy function of AMBRA1 is post-translationally controlled, upon HUWE1 activity, by a positive phosphorylation on its serine 1014. This modification is mediated by the IKKα kinase and induces structural changes in AMBRA1, thus promoting its interaction with LC3/GABARAP (mATG8) proteins and its mitophagic activity. | SIGNOR-272974 |
P12931 | Q16595 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | We found that frataxin can be phosphorylated by Src. Phosphorylation occurs primarily on Y118 and promotes frataxin ubiquitination, a signal for degradation. | SIGNOR-275585 |
P51608 | O75398 | 1 | binding | up-regulates activity | 0.2 | We show that MeCP2 enhances Deaf1 binding to its HTR1A site and co-immunoprecipitates with Deaf1 in cells and brain tissue.To address the role of MeCP2 in HTR1A regulation in vivo, mice with conditional knockout of MeCP2 in adult 5-HT neurons (MeCP2 cKO) were generated. These mice exhibited increased 5-HT1A autoreceptor levels and function, consistent with MeCP2 enhancement of Deaf1 repression in 5-HT neurons. | SIGNOR-269063 |
Q99814 | Q9Y2K7 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | To this end, we confirm that KDM3A, KDM4B, KDM4C, KDM5B, KDM5C, and KDM62 are direct targets of HIF-1a while extent the list of known targets to KDM2A, KDM2B, KDM4D, KDM5A, and KDM6A. The results demonstrated that majority of the KDMs were similarly induced (KDM2A, KDM2B, KDM3A, KDM4B, KDM4C, KDM4D, KDM5A, KDM5B, KDM5C, KDM6B, and KDM7A) or repressed (KDM NO66 and KDM1A) by both HIF-1a and HIF-2a. | SIGNOR-271581 |
Q8TF76 | P53350 | 2 | binding | 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-275420 |
Q00535 | P00352 | 1 | phosphorylation | up-regulates quantity | 0.2 | Cdk5 Phosphorylates ALDH1A1 at S75 and S274.|These results demonstrate that Cdk5 increases ALDH1A1 levels in neurotoxin exposed neuronal cells both at transcriptional level and by direct phosphorylation at S75 and S274 sites. | SIGNOR-279399 |
Q16236 | Q9NP58 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins. This complex binds to AREs to mediate the transcription of genes involved in iron metabolism, GSH metabolism, and ROS detoxification.Two critical enzymes in this pathway, ATP binding cassette subfamily B member 6 (ABCB6) and ferrochelatase (FECH), are regulated by the transcription factor NFE2L2 and play significant roles in inhibiting ferroptosis when upregulated. | SIGNOR-279864 |
P53778 | P37198 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | We further show that imidazole propionate impairs insulin signaling at the level of insulin receptor substrate through the activation of p38γ MAPK, which promotes p62 phosphorylation and, subsequently, activation of mechanistic target of rapamycin complex 1 (mTORC1). | SIGNOR-277416 |
P11362 | P11362 | 2 | phosphorylation | up-regulates | 0.2 | Fgfr signaling is under the control of tyrosine phosphorylation to elicit activation of cellular signaling cascades. Ligand binding induces receptor dimerization and transphosphorylation. Fgfr1 contains eleven tyrosine residues (tyr154, tyr280, tyr307, tyr463, tyr585, tyr605, tyr653, tyr654, tyr730 and tyr766), some of which are directly involved regulating the activity of the receptor and others bind to activate substrates leading to the activation of various transduction pathways. | SIGNOR-98626 |
P06493 | Q9Y6X9 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Mechanically, PTX and VCR activate cyclin-dependent kinase 1, which in turn induces MORC2 phosphorylation at threonine 717 (T717) and T733. Phosphorylated MORC2 enhances its interation with HSPA8 and LAMP2A, two essential components of the chaperone-mediated autophagy (CMA) mechinery, resulting in its autophagic degradation. | SIGNOR-277837 |
P08047 | P24821 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Sp1 and Ets1 are potent transactivators of the TN-C promoter. | SIGNOR-261600 |
Q12857 | Q14393 | 1 | transcriptional regulation | down-regulates quantity | 0.2 | By integrating transcriptomic profiling (RNA-seq) of Nfia- and Nfix-deficient GNPs with epigenomic profiling (ChIP-seq against NFIA, NFIB and NFIX, and DNase I hypersensitivity assays), we reveal that these transcription factors share a large set of potential transcriptional targets, suggestive of complementary roles for these NFI family members in promoting neural development | SIGNOR-268876 |
P38398 | Q15424 | 1 | ubiquitination | up-regulates quantity by stabilization | 0.2 | These results suggest that the BRCA1 and BARD1 heterodimer ubiquitinates SAFB and increases SAFB protein levels. | SIGNOR-278624 |
Q9Y4X5 | Q9NZQ7 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | We find EGFR inhibitors promote PD-L1 ubiquitination and proteasomal degradation following GSK3α-mediated phosphorylation of Ser279/Ser283. We identify ARIH1 as the E3 ubiquitin ligase responsible for targeting PD-L1 to degradation. | SIGNOR-277553 |
Q9H0A0 | P09874 | 1 | acetylation | up-regulates quantity by stabilization | 0.2 | MORC2 directly interacts with PARP1. MORC2 mediates the interaction between PARP1 and NAT10 and thereby promotes NAT10-mediated PARP1 acetylation at K949, which blocks CHFR-mediated ubiquitination and degradation of PARP1. | SIGNOR-273715 |
Q8NBJ5 | Q15848 | 1 | palmitoylation | up-regulates activity | 0.2 | We conclude that GLT25D1 regulates HMW adiponectin secretion and lipid accumulation, consistent with changes in mice after high-fat feeding. These results suggest a novel function of GLT25D1 leading to decreased HMW adiponectin secretion in early obesity. | SIGNOR-261149 |
P67775 | Q12933 | 1 | dephosphorylation | down-regulates activity | 0.2 | We show that the Thr117 residue in TRAF2 is phosphorylated following TNFalpha stimulation. This phosphorylation process is modulated by PP2A and is required for TRAF2 functional activity. | SIGNOR-248640 |
P08047 | P08243 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Sp1 and Sp3 Activate Transcription Driven by the AS Promoter | SIGNOR-268019 |
P17252 | P09758 | 1 | phosphorylation | down-regulates activity | 0.2 | Analyses using HCT116 cells expressing WT Trop-2 (HCT116/WT) or Trop-2 alanine-substituted at Ser-303 (HCT116/S303A) or Ser-322 (HCT116/S322A) revealed that Trop-2 is phosphorylated at Ser-322. sing protein kinase C (PKC) inhibitors and PKC-specific siRNAs, we found that PKCα and PKCδ are responsible for Trop-2 phosphorylation. | SIGNOR-273821 |
Q9UKE5 | 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-276334 |
P17948 | Q04760 | 1 | phosphorylation | up-regulates activity | 0.2 | We show that Glo1 activity is promoted by phosphorylation on Tyrosine 136 via multiple kinases. Glo1 Y136 is phosphorylated by multiple different kinases including all members of the Src family. Depletion of multiple different kinases led to a partial reduction in Glo1(Y136) phosphorylation. These included members of the Src family (Src, Yes1, FGR, and the related Abl1), and of the FAK, EPHA, FGFR, and VEGFR families (Figure 2B), suggesting phosphorylation of Glo1 on Y136 by multiple different kinases. In vitro kinase assays revealed that all the members of the Src family, as well as Epha5 and VEGFR3, can efficiently phosphorylate recombinant Glo1 on Y136 (Figure 2C–D). | SIGNOR-276190 |
P20701 | Q99996 | 1 | binding | up-regulates activity | 0.2 | However, association of CG-NAP/AKAP450 was signifi-cantly enhanced at 37°C in LFA-1-activated cells triggered toundergo motility. Taken together, our findings provide the first definitiveevidence that the protein CG-NAP/AKAP450 is a key scaffoldingcomponent of the multimolecular complex assembled in T cellsupon LFA cross-linking and is functionally indispensable for cellpolarity and migration induced by this integrin. | SIGNOR-260304 |
Q9Y5S2 | P26038 | 1 | phosphorylation | up-regulates activity | 0.2 | In this study, we have shown that MRCKb phosphorylated moesin at Thr-558 | We have shown that the phosphorylation is important to the formation of ®lopodia, and that MRCK may regulate this formation through the phosphorylation of ERM proteins at the tip of ®lopodia. | SIGNOR-260802 |
P11308 | P56704 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Interestingly, our data showed that ERG drastically induced Wnt ligand gene expression. | SIGNOR-261598 |
Q99683 | Q99683 | 2 | phosphorylation | up-regulates activity | 0.2 | Reporter gene assays showed that all three identified in vitro autophosphorylation sites (thr813, thr838, thr842) regulate ask1 signalingmutation of thr838 drastically reduced reporter gene activity when compared to unstimulated control levels. Interestingly, mutation of the other two sites also provided a significant reduction in ask1 function (figure 6a), suggesting that autophosphorylation at the residues thr842 and thr813 regulates ask1 signaling. | SIGNOR-158431 |
Q9NP71 | P25445 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | The present study provides evidence for a direct and dominant role of ChREBP in the glucose regulation of two key liver lipogenic enzymes, acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) | SIGNOR-267947 |
O15550 | P41970 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | Our findings reveal a dual role for UTX in suppressing acute myeloid leukaemia via repression of oncogenic ETS and upregulation of tumor suppressive GATA programs. several ETS transcription factors, including Elf4, Etv6, Erg, Fli1, Ets2, Spi1 and Elk3 were upregulated immediately after Utx loss in the preleukaemic phase | SIGNOR-260037 |
Q9H4E7 | P61224 | 1 | binding | up-regulates activity | 0.2 | Mechanistic studies revealed that SLAT interacts, through its PH domain, with a key component of inside-out signaling, namely the active form of the small GTPase Rap1 (which has two isoforms, Rap1A and Rap1B). This interaction has been further shown to facilitate the interdependent recruitment of Rap1 and SLAT to the T cell immunological synapse upon TCR engagement. Furthermore, a SLAT mutant lacking its PH domain drastically inhibited LFA-1 activation and CD4(+) T cell adhesion. | SIGNOR-253366 |
Q96LB2 | P63092 | 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 ‚â• -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 ‚â• -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ‚â• -1.0. | SIGNOR-256786 |
O60502 | Q01813 | 1 | deglycosylation | up-regulates activity | 0.2 | Our previous investigation on O-GlcNAcylation of PFK1 has demonstrated that O-GlcNAcylation inhibits PFK1 enzyme activity|In cells, a single set of antagonistic enzymes-O-GlcNAc transferase (OGT) and O-GlcNAc hydrolase are responsible for the addition and removal of GlcNAc moiety, respectively. | SIGNOR-267606 |
P17612 | O15554 | 1 | phosphorylation | down-regulates activity | 0.2 | Mutating the single PKA site (S334A) in human KCa3.1 abolished the PKA-dependent regulation. CaM-affinity chromatography showed that CaM binding to KCa3.1 was decreased by PKA-dependent phosphorylation of S334, and this regulation was absent in the S334A mutant.The results above indicate that PKA activation led to a phosphorylation event that inhibited KCa3.1 channel activity | SIGNOR-276855 |
Q9C0B5 | P21453 | 1 | palmitoylation | up-regulates activity | 0.2 | We propose that DHHC5-mediated palmitoylation of S1P1R determines Gi coupling and its signalling in a spatio/temporal manner. | SIGNOR-261140 |
Q9P286 | P15976 | 1 | phosphorylation | up-regulates activity | 0.2 | In addition, we defined GATA1 Ser161, Ser187 were the main phosphorylation sites by PAK5. | SIGNOR-278297 |
P24941 | Q01196 | 1 | phosphorylation | up-regulates activity | 0.2 | We have identified four phosphorylation sites on aml1c that are necessary for transcriptional activity of aml1c in k562 and 293t cells (27).4 mutation of these four sites (serine 276, serine 293, serine 303, and threonine 300) to alanine abolishes transcriptional activation, whereas mutation of these sites to aspartic acid (which mimics phosphorylation) results in a hyperactive protein. | SIGNOR-138932 |
P26045 | P03372 | 1 | dephosphorylation | up-regulates activity | 0.2 | Our recent studies further demonstrated that PTPH1 dephosphorylates estrogen receptor at Y537, increases estrogen receptor stability and nuclear accumulation, and enhances breast cancer sensitivity to anti-estrogens [ ]. | SIGNOR-277127 |
P27361 | Q8IVS8 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.2 | Mechanistically, glucose deprivation-activated ERK1 phosphorylates GLYCTK2 at serine 220 directly, which prevents STUB1 (ubiquitin E3 ligase) binding, thereby abrogating the ubiquitination and degradation of GLYCTK2. ERK1 phosphorylates GLYCTK2 at S220 to promotes its stability | SIGNOR-280257 |
Q99835 | P09341 | 1 | binding | up-regulates | 0.2 | We found that smo, by virtue of what appears to be constitutive activity, activates all members of the g(i) family but does not activate members of the g(s), g(q), and g(12) families. | SIGNOR-148484 |
Q13153 | P15259 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | The ability of Pak1 to phosphorylate wild-type PGAM2 was increased after exposure of the cells to etoposide (XREF_FIG).|Bar, 20 \u00b5m. (E) Primary mouse embryonic fibroblasts at early passages were treated with 20 \u00b5M etoposide in the presence of 20 \u00b5M MG132, and cell lysates were immunoblotted with antibodies against Pak1 and phospho-Ser118 in phosphoglycerate mutase as indicated. (F) Pak1 kinase phosphorylates PGAM2 at Ser118 in vitro. | SIGNOR-280237 |
Q9NX47 | Q9Y3D6 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | MITOL associates with and ubiquitinates mitochondrial fission protein hFis1. (A) Ubiquitination of hFis1 by MITOL. Thus, MITOL may control the protein expression level of hFis1 through the ubiquitin–proteasome pathway. | SIGNOR-274141 |
P23246 | P07101 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | It has been reported that DJ-1 is a neuroprotective transcriptional co-activator that sequesters a transcriptional co-repressor polypyrimidine tract-binding protein-associated splicing factor (PSF) from the TH gene promoter. | SIGNOR-271697 |
P01106 | Q06203 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | PPAT, catalyzing the first step of purine synthesis, and DHODH, an enzyme generating uridine in the middle of the pyrimidine synthesis pathway, were validated as direct c-MYC target genes by all criteria. | SIGNOR-267381 |
P07948 | P25490 | 1 | phosphorylation | down-regulates activity | 0.2 | In the case of Lyn overexpression, single mutations at either tyrosine 8, 254, or 383 severely reduced Lyn-mediated YY1 phosphorylation, suggesting that these three sites may be targets of Lyn in vivo (Fig. 3, A and B). | SIGNOR-276930 |
Q86YB8 | Q9BS26 | 1 | binding | up-regulates quantity by stabilization | 0.2 | Here, we report the functional characterization of a novel UPR-induced ER resident protein (ERp44) that forms mixed disulfides with both hEROs, as well as with partially unfolded Ig subunits. | SIGNOR-261048 |
Q05655 | Q99808 | 1 | phosphorylation | up-regulates activity | 0.2 | Phosphorylation of hENT1 by PKC has effects on both the function and subcellular trafficking of hENT1 | SIGNOR-260888 |
P27361 | Q9BR01 | 1 | phosphorylation | down-regulates | 0.2 | The phosphorylation of sult4a1 allows interaction with pin1, which then promotes degradation of the sulfotransferase. | SIGNOR-168248 |
Q09472 | P84243 | 1 | acetylation | down-regulates activity | 0.2 | These results highlight the substrate and site specificities of hats in cells, demonstrate the distinct roles of gcn5/pcaf- and cbp/p300-mediated histone acetylations in gene activation, and suggest an important role of cbp/p300-mediated h3k18/27ac in nr-dependent transcription. | SIGNOR-170266 |
P06850 | P02533 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | CRH stimulated the expression of cytokeratin 1 and involucrin, and inhibited cytokeratin 14 on both mRNA and protein levels. | SIGNOR-251899 |
P68400 | Q9Y4R8 | 1 | phosphorylation | down-regulates | 0.2 | Here we report that tel2 and tti1 are targeted for degradation within mtorc1 by the scffbxo9 ubiquitin ligase to adjust mtor signalling to growth factor availability. This process is primed by ck2, which translocates to the cytoplasm to mediate mtorc1-specific phosphorylation of tel2/tti1. ere, we show that tel2 is constitutively phosphorylated on conserved serines 487 and 491 by casein kinase 2 (ck2) | SIGNOR-200202 |
Q9UNE7 | O00257 | 1 | ubiquitination | 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-277513 |
P17252 | Q96PY5 | 1 | phosphorylation | up-regulates activity | 0.2 | PKCα associates with and phosphorylates FMNL2 at S1072 within its Diaphanous autoregulatory region, leading to the release of formin autoinhibition. | SIGNOR-273796 |
Q9UNW8 | 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-257187 |
P08631 | P08631 | 2 | phosphorylation | up-regulates activity | 0.2 | Hck transiently expressed in human embryonic kidney 293T cells was found to be phosphorylated at Tyr-29 and Tyr-388, proving that Hck can also undergo autophosphorylation at both sites in vivo. autophosphorylation of Tyr-29 contributes significantly to the activation of Hck. | SIGNOR-251266 |
O15530 | O43865 | 1 | phosphorylation | down-regulates activity | 0.2 | Residue 68 resides in a consensus phosphorylation site for PKD (Figure 1A) [22,23]. Interestingly, phosphorylation of Ser68 could allow for subsequent phosphorylation of Ser71, Ser74, Ser77 and Ser80 by CK1, for which the consensus phosphorylation site is pS/T-X-X-S/T| We found that phosphorylation of Ser71 and Ser74 were sufficient to enable inhibition of IP3 binding to the IP3R | SIGNOR-249174 |
P61289 | Q9NRC8 | 1 | binding | down-regulates quantity by destabilization | 0.2 | Here, the authors show that energy stress induces an AMPK-dependent phosphorylation of Sirt7, which promotes its ubiquitin-independent degradation by REGγ, resulting in the down-regulation of rRNA transcription and cell survival.|These results strongly suggest that the phosphorylation status of SirT7 at T153 plays a crucial role in determining its subcellular distribution, degradation and binding to REGγ. | SIGNOR-275866 |
P17252 | P35367 | 1 | phosphorylation | down-regulates | 0.2 | In this study, we demonstrated that ser396 and ser398 are phosphorylated by pkc and, that phosphorylation of ser398 is particularly involved in pmainduced desensitization of the h1r. | SIGNOR-66015 |
Q7Z570 | P52630 | 1 | binding | up-regulates activity | 0.2 | Together these results indicate the formation of ZNF804A:STAT2 protein complex and its translocation from the cytoplasm into the nucleus upon IFN stimulation, suggesting that it may function as a signal transducer that activates IFN-mediated gene expression programs. | SIGNOR-269460 |
P35626 | P21731-2 | 1 | phosphorylation | down-regulates activity | 0.2 | These data suggest a model whereby agonist-induced PKC phosphorylation of Ser(145) partially impairs TPbeta signalling while GRK2/3 phosphorylation at both Ser(239) and Ser(357) within its IC(3) and C-tail domains, respectively, sterically inhibits G-protein coupling, profoundly desensitizing signalling, and promotes beta-arrestin association and, in turn, facilitates TPbeta internalization. | SIGNOR-274091 |
O00311 | Q13148 | 1 | phosphorylation | up-regulates activity | 0.2 | Among these, CDC7 directly phosphorylates TDP-43 on serines 409 and 410 both in vitro and in vivo . | SIGNOR-278256 |
Q9H992 | P10636 | 1 | ubiquitination | down-regulates activity | 0.2 | We have identified and characterized axotrophin, a protein that binds and preferentially mono-ubiquitinates tau protein. | SIGNOR-278655 |
Q9Y5I2 | Q9UN70 | 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-265696 |
Q9BQ87 | Q13363 | 1 | binding | down-regulates quantity by destabilization | 0.2 | TBL1 interacts in vivo with CtBP and promote its proteasomal degradation | SIGNOR-260902 |
P05771 | Q03721 | 1 | phosphorylation | down-regulates | 0.2 | We found that pkc specifically eliminates rapid inactivation of a cloned human a-type k+ channel (hkv3.4), converting this channel from a rapidly inactivating a type to a noninactivating delayed rectifier type. | SIGNOR-35626 |
Q96QT6 | Q9H808 | 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-266991 |
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