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 |
|---|---|---|---|---|---|---|---|
P27361 | Q15046 | 1 | phosphorylation | up-regulates | 0.2 | Lysrs serves as a key signaling molecule in the immune response by regulating gene expression. Lysrs was phosphorylated on serine 207 in a mapk-dependent manner, released from the multisynthetase complex, and translocated into the nucleus. | SIGNOR-186125 |
Q9Y3A5 | Q7Z2Z2 | 1 | binding | up-regulates | 0.2 | Sbds stimulates 60s-dependent gtp hydrolysis by efl1 | SIGNOR-173533 |
O60678 | P00352 | 1 | binding | down-regulates activity | 0.2 | We identified the specific residues in the catalytic domain of PRMT3 that facilitate interaction with the C-terminal region of ALDH1A1. PRMT3 inhibits the enzymatic activity of ALDH1A1 and negatively regulates the expression of retinoic acid responsive genes in a methyltransferase activity independent manner. | SIGNOR-276751 |
P17612 | P19174 | 1 | phosphorylation | down-regulates | 0.2 | The observation that pka also phosphorylates plc-yl on serine 1248 suggests that phosphorylation of this residue may be a common mechanism by which pkc and pka inhibit plc-yl. | SIGNOR-17901 |
P53779 | P31947 | 1 | phosphorylation | down-regulates | 0.2 | Here we demonstrate that activated jnk promotes bax translocation to mitochondria through phosphorylation of 14-3-3, a cytoplasmic anchor of bax. Phosphorylation of 14-3-3 led to dissociation of bax from this protein.Jnk phosphorylates 14-3-3zeta_ at ser-184 and 14-3-3sigma_ at ser-191 | SIGNOR-124005 |
Q9C0C7 | P62714 | 1 | binding | up-regulates activity | 0.2 | We found that AMBRA1 favours the interaction between c-Myc and its phosphatase PP2A and that, when mTOR is inhibited, it enhances PP2A activity on this specific target, thereby reducing the cell division rate. As expected, such a de-regulation of c-Myc correlates with increased tumorigenesis in AMBRA1-defective systems, thus supporting a role for AMBRA1 as a haploinsufficient tumour suppressor gene. | SIGNOR-272964 |
Q13554 | Q9H6L5 | 1 | phosphorylation | up-regulates activity | 0.2 | Under ER-stress conditions, activated CAMK2B phosphorylates the reticulon-homology domain of FAM134B, which enhances FAM134B oligomerization and activity in membrane fragmentation to accommodate high demand for ER-phagy. | SIGNOR-273554 |
Q05655 | P12830 | 1 | phosphorylation | down-regulates activity | 0.2 | Phosphorylation of E-cadherin at threonine 790 by protein kinase Cδ reduces β-catenin binding and suppresses the function of E-cadherin. | SIGNOR-260893 |
P05129 | 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-251633 |
Q99814 | O94953 | 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-271584 |
Q15139 | O95251 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.2 | We show that PKD1 directly interacts and phosphorylates KAT7 at Thr97 and Thr331 in vitro and in vivo. PKD1-mediated phosphorylation of KAT7 enhances its expression levels and stability by reducing its ubiquitination-mediated degradation. | SIGNOR-277828 |
Q13315 | Q15797 | 1 | phosphorylation | up-regulates | 0.2 | On genotoxic stress, atm phosphorylates bmps-activated smad1 in the nucleus on s239, which disrupts smad1 interaction with protein phosphatase ppm1a, leading to enhanced activation and upregulation of smad1. | SIGNOR-197533 |
Q13309 | Q8WWM9 | 1 | binding | down-regulates quantity by destabilization | 0.2 | Skp2 induces ubiquitin-dependent degradation of Cygb. To this end, we performed an in vivo ubiquitination assay in HEK293T cells by transfecting relevant plasmids as indicated. The V5-Skp2DN was generated by deleting the N-terminal residues from 1 to 153 containing the F-box domain, which is involved in recruiting Skp2 to the SCF complex. | SIGNOR-272792 |
Q16549 | P67775 | 1 | phosphorylation | up-regulates | 0.2 | This together with the rapid kinetics of pp1-pp2a activation following p38 activation suggests that pp1 and/or pp2a complexes are direct targets for p38-mediated phosphorylation | SIGNOR-105783 |
O95155 | O95997 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | We further demonstrate that Ufd2 directly and efficiently ubiquitylates securin in vitro and is required for securin polyubiquitylation in vivo. This is the first description of a physiologic substrate for Ufd2, establishing this E4 enzyme as an important regulator of chromosome condensation and separation during mitosis in human cells. | SIGNOR-271523 |
Q6IN85 | P60510 | 1 | binding | up-regulates | 0.2 | Our data demonstrate that pp4r4 forms a novel cytosolic complex with pp4c, independent from the complexes containing pp4r1, pp4r2.PP4R3, and alpha4, and that the regulatory subunits of pp4c have evolved different modes of interaction with the catalytic subunit. | SIGNOR-180244 |
Q96NR3 | Q96QK1 | 1 | binding | up-regulates quantity | 0.2 | Using Western blotting, we validated our MS approach confirming the binding of Dgl4 (also known as PSD95) and VPS35 to the recombinant Ptchd1 C terminus. Endogenous DLG4 and VPS35 from membrane and soluble mouse brain fractions were recovered specifically on the GST fusion proteins containing the cytoplasmic but not the extracellular, negative control sequences of Ptchd1 (Fig. 5E). Binding of DLG4 was dependent on the PDZ-binding motif in Ptchd1, whereas VPS35 binding was not (Fig. 5E). These results demonstrate a biochemical interaction of Ptchd1 with postsynaptic trafficking proteins in the mouse brain. Together, these data suggest that loss of Ptchd1 results in severe alterations in synaptic function in the dentate gyrus | SIGNOR-266653 |
Q9NTX7 | Q9NTX7 | 2 | ubiquitination | down-regulates quantity | 0.2 | We show that RNF146, tankyrase, and Axin form a protein complex, and that RNF146 mediates ubiquitylation of all three proteins to target them for proteasomal degradation. | SIGNOR-260006 |
P16298 | P21333 | 1 | dephosphorylation | down-regulates quantity by destabilization | 0.2 | Filamin is a phosphoprotein that organizes actin filaments into networks. We report that a purified C-terminal recombinant region of filamin is a suitable substrate for calcineurin |Mutagenesis analysis showed that a dephosphorylation step occurred in Ser 2152, which was previously shown to provide resistance to calpain cleavage when endogenous PKA is activated. In contrast, phosphorylation of Ser 2152 was recently reported to be necessary for membrane dynamic changes. In this regard, we found that CsA protects filamin in platelets from calpain degradation. | SIGNOR-248362 |
P17612 | Q9NP97 | 1 | phosphorylation | up-regulates | 0.2 | Our results show that km23-1 is required for camp-responsive element (cre) transcriptional activation by tgf_, with s73-km23-1 being required for the cre-dependent tgf_ stimulation of fibronectin (fn) transcription. | SIGNOR-200456 |
Q08345 | Q08345 | 2 | phosphorylation | up-regulates activity | 0.2 | The discoidin domain receptor tyrosine kinases are activated by collagen | Here, we present evidence that stimulating DDR1- and DDR2-expressing cells with various types of collagen induces receptor autophosphorylation. | SIGNOR-251086 |
Q14493 | Q96A08 | 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-265393 |
Q9HC97 | 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-257112 |
Q96T68 | P84243 | 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-263894 |
Q13153 | Q99523 | 1 | phosphorylation | down-regulates activity | 0.2 | PAKs specifically phosphorylate Ser15 of the sortilin-cd and alter its trafficking. It can be concluded that PAK1-3 may indeed instigate the phosphorylation of sortilin and that they target a single serine residue (Ser15) located in the kinase domain-binding site of the sortilin-cd. Full-length sortilins with the serine at position 793 (residue 15 in the cytoplasmic domain) (for the sequence, see Fig. 2). Phosphorylation (Ser15) downregulates the sortilin–AP-1 interaction. | SIGNOR-273718 |
P42680 | O75444 | 1 | phosphorylation | up-regulates activity | 0.2 | We subsequently investigated whether Tec phosphorylated c-Maf at Tyr21/92/131.|We found that overexpression of Tec enhanced the binding of c-Maf to the MARE site derived from the IL-4 promoter (XREF_FIG).|As shown in xref , tyrosine phosphorylation of c-Maf was strongly enhanced by Tec and this Tec-induced tyrosine phosphorylation was completely mitigated by Ptpn22. | SIGNOR-279433 |
Q13315 | Q9H981 | 1 | phosphorylation | down-regulates activity | 0.2 | These findings indicate that ATM dependent phosphorylation on ARP8-S412 reduces ARP8 INO80 interaction.|These findings raised the possibility that ATM negatively regulates the interaction of ARP8 with INO80 after etoposide treatment. | SIGNOR-279437 |
P37088 | O95180 | 1 | binding | up-regulates activity | 0.2 | This study describes the functional interaction between Cav3.2 calcium channels and the Epithelial Sodium Channel (ENaC). β- and γ-ENaC subunits could be co-immunoprecipitated with Cav3.2 calcium channels from brain lysates, dorsal horn and lumbar dorsal root ganglia. Αβγ-ENaC channels enhanced Cav3.2 calcium channel trafficking to the plasma membrane in tsA-201 cells. This effect was reciprocal such that Cav3.2 channel expression also enhanced β-ENaC trafficking to the cell surface. these findings reveal ENaC as an interactor and potential regulator of Cav3.2 calcium channels expressed in neuronal tissues. | SIGNOR-269272 |
P17676 | P21291 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | We conclude that c-Rel regulates CRP expression without the requirement of binding to a kappaB site, and binds directly to C/EBPbeta to facilitate the binding of C/EBPbeta to the CRP promoter | SIGNOR-254049 |
P06241 | O15117 | 1 | phosphorylation | up-regulates activity | 0.2 | two tyrosines, Tyr595 and Tyr651, of FYB are major sites of phosphorylation by FYN-T and mediate binding to SLP-76 in Jurkat T cells. We further demonstrate that the loss of SLP-76 binding by mutation of these sites markedly reduced the ability of FYN-T-FYB-SLP-76 to up-regulate IL-2 transcription. | SIGNOR-251163 |
Q15797 | 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-268937 |
P03186 | Q9Y4K3 | 1 | deubiquitination | down-regulates activity | 0.2 | EBV-encoded BPLF1 interacts with and deubiquitinates TRAF6 to inhibit NF-κB signaling during lytic infection. Once lytic replication is induced, BPLF1 then deubiquitinates and inactivates TRAF6 to further block NF-κB signaling, promoting efficient viral genome replication. | SIGNOR-266739 |
Q8TCQ1 | P01903 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | Two E3 ligases, MARCH I and MARCH VIII, have been shown to polyubiquitinate lysine residue 225 in the cytoplasmic tail of I-Abeta and HLA-DRbeta. We show that lysine residue 219 in the cytoplasmic tail of DRalpha is also subject to polyubiquitination. | SIGNOR-271412 |
P0CG48 | O60260 | 1 | binding | up-regulates activity | 0.2 | Mechanism of phospho-ubiquitin-induced PARKIN activation|PhosphoUb binding leads to straightening of a helix in the RING1 domain, and the resulting conformational changes release the Ubl domain from the PARKIN core; this activates PARKIN|Our results show that PINK1-dependent phosphorylation of both parkin and ubiquitin is sufficient for full activation of parkin E3 activity. These findings demonstrate that phosphorylated ubiquitin is a parkin activator. | SIGNOR-249692 |
P31751 | Q9Y2T7 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.2 | In this context, YBX2 is a dual substrate for both AMPK and Akt2. The phosphorylation at Thr115 by AMPK or at Ser137 by Akt2 facilitates YBX2 accumulation in brown adipocytes by decreasing ubiquitination-mediated degradation. | SIGNOR-277869 |
Q86YJ5 | P01920 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | MARCH9, a member of the RING-CH family of transmembrane E3 ubiquitin ligases, down-regulates CD4, major histocompatibility complex-I (MHC), and ICAM-1 in lymphoid cells. To identify novel MARCH9 substrates, we used high throughput flow cytometry and quantitative mass spectrometry by stable isotope labeling by amino acids in cell culture (SILAC) to determine the differential expression of plasma membrane proteins in a MARCH9-expressing B cell line. This combined approach identified 13 potential new MARCH9 targets. | SIGNOR-271539 |
Q86U44 | Q9GZV5 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Here we find that METTL3 promotes translation of certain mRNAs including epidermal growth factor receptor (EGFR) and the Hippo pathway effector TAZ in human cancer cells. | SIGNOR-265955 |
Q5T0T0 | P12830 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | Inhibiting proteasome activity with MG132 prevented CDH1 and beta2M degradation, indicating that MARCH8 might be targeting CDH1 and beta2M for proteasomal degradation.|We demonstrated that MARCH8 interacts with and ubiquitinates CDH1 and beta2M. | SIGNOR-278820 |
P61296 | P61296 | 2 | binding | up-regulates activity | 0.2 | The basic helix-loop-helix factor, HAND2, functions as a transcriptional activator by binding to E-boxes as a heterodimer | SIGNOR-223476 |
P17612 | Q8N5S9 | 1 | phosphorylation | down-regulates activity | 0.2 | In vitro, CaMKK is phosphorylated by PKA and this is associated with inhibition of enzyme activity. The major site of phosphorylation is threonine 108, although additional sites are phosphorylated with lower efficiency. | SIGNOR-256115 |
P20265 | P20265 | 2 | binding | up-regulates activity | 0.2 | These experiments lead to the conclusion that the full-length Brn-2 protein can interact with full-length Brn-2. Assay of homodimerization properties of Brn-2 protein on the b2s1 dimer recognition sequence also demonstrated cooperativity, indicating that protein-protein contacts would be important for synergistic interactions between the Brn-2 subunits. | SIGNOR-221824 |
P06493 | Q9NZI6 | 1 | phosphorylation | up-regulates activity | 0.2 | In addition, overexpression of TFCP2L1 and CDK1 in T24 cells increased clonogenic activity in a clonogenic limiting dilution assay (Fig\u00a05H), confirming the importance of CDK1\u2010TFCP2L1 pathways for the stemness features of BC cells.High levels of co\u2010expression of p\u2010TFCP2L1 and CDK1 were associated with distant metastasis in our cohort of BC patients (Table\u00a01).|Tfcp2l1 Thr177 phosphorylation by CDK1 is essential for proliferation and cell cycle progression of ESCs.|Tfcp2l1 is phosphorylated at Thr177 by CDK1. | SIGNOR-278472 |
Q92519 | P14618 | 1 | phosphorylation | up-regulates activity | 0.2 | This study demonstrated that TRIB2, not a "pseudokinase", has the kinase activity to directly phosphorylate PKM2 at serine 37 in cancer cells. | SIGNOR-275431 |
P42685 | P38398 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.2 | Herein, we demonstrate that Fyn-related kinase (Frk)/Rak plays an important role in maintaining genomic stability, possibly in part through positively regulating BRCA1 protein stability and function via tyrosine phosphorylation on BRCA1 Tyr1552. Rak-mediated tyrosine phosphorylation of BRCA1 is essential for its stability and function | SIGNOR-275454 |
Q2T9J0 | Q2T9J0 | 2 | cleavage | down-regulates activity | 0.2 | Self-cleavage of Tysnd1 in the active oligomer most likely inactivates its protease activity. Subsequently, the cleaved products are degraded by PsLon and removed from the Tysnd1 oligomer. | SIGNOR-261053 |
Q14493 | A0A2R8Y619 | 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-265380 |
P49841 | P11308 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Here, we demonstrate that DNA damage induces proteasomal degradation of wild-type ERG and TMPRSS2-ERG oncoprotein through ERG threonine-187 and tyrosine-190 phosphorylation mediated by GSK3β and WEE1, respectively. | SIGNOR-277528 |
P51956 | P51956 | 2 | phosphorylation | down-regulates activity | 0.2 | Autophosphorylation at Thr-165 is required for NEK3 kinase activity in vitro. | SIGNOR-260919 |
Q96ST3 | P07288 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | Chromatin immunoprecipitation (ChIP) and DNA affinity precipitation analysis demonstrated that Ebp1 and Sin3A associate at the PSA and E2F1 promoters. Functionally, Sin3A enhanced the ability of Ebp1 to repress transcription of androgen receptor (AR) and E2F1 regulated genes. | SIGNOR-253663 |
Q16549 | Q92945 | 1 | phosphorylation | down-regulates | 0.2 | Ksrp phosphorylated by p38 displays compromised binding to are-containing transcripts and fails to promote their rapid decay,although it retains the ability to interact with the mrna degradation machinery. | SIGNOR-143167 |
P06493 | Q5FBB7 | 1 | phosphorylation | up-regulates activity | 0.2 | The complex between shugoshin and protein phosphatase 2A (Sgo1-PP2A) localizes to centromeres in mitosis, binds to cohesin in a reaction requiring Cdk-dependent phosphorylation of Sgo1, dephosphorylates cohesin-bound sororin, and protects a centromeric pool of cohesin from mitotic kinases and the cohesin inhibitor Wapl. | SIGNOR-265263 |
O15357 | Q9ULV8 | 1 | binding | down-regulates | 0.2 | This association between ship2 and cbl could sequester cbl from the egfr, thereby regulating the kinetics of egfr-cbl association and subsequent internalization and degradation of the receptor. | SIGNOR-133388 |
Q969U6 | Q15437 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | SCFFBXW5 interacts with SEC23B and targets it for ubiquitylation and proteasome-mediated degradation. | SIGNOR-265286 |
Q9UJV9 | Q86WV6 | 1 | binding | up-regulates activity | 0.2 | The kinase and SH3/SH2 interaction domains of BTK bind, respectively, the DEAD-box domain of DDX41 and transmembrane region of STING. BTK phosphorylates DDX41, and its kinase activities are critical for STING-mediated IFN-β production. We show that Tyr364 and Tyr414 of DDX41 are critical for its recognition of AT-rich DNA and binding to STING, and tandem mass spectrometry identifies Tyr414 as the BTK phosphorylation site. | SIGNOR-266403 |
Q7KZF4 | Q99685 | 1 | binding | down-regulates quantity by destabilization | 0.2 | Interaction of SND1 with MGLL resulted in ubiquitination and proteosomal degradation of MGLL. We demonstrate that interaction of SND1 with MGLL results in increased ubiquitination and subsequent proteosomal degradation of MGLL. This down-regulation of MGLL is required for SND1 to exert its pro-tumorigenic activity because forced overexpression of MGLL markedly abrogates cell proliferation. | SIGNOR-259138 |
P28482 | Q14686 | 1 | phosphorylation | up-regulates activity | 0.2 | In vitro phosphorylation studies with His-tagged TRBP (795–931) suggested that S884 can be phosphorylated by MAPK (ERK2) in vitro (Fig. 10A).Analysis of in vitro and in vivo receptor interactions with TRBP suggested that S884 allowed selective interactions for ERβ, TR, and RXR vs. ERα. | SIGNOR-265882 |
Q8WXX7 | Q14185 | 1 | binding | up-regulates activity | 0.2 | Mutations in the Autism susceptibility candidate 2 gene (AUTS2), whose protein is believed to act in neuronal cell nuclei, have been associated with multiple psychiatric illnesses, including autism spectrum disorders, intellectual disability, and schizophrenia. Here we show that cytoplasmic AUTS2 is involved in the regulation of the cytoskeleton and neural development. AUTS2 activates Rac1 to induce lamellipodia but downregulates Cdc42 to suppress filopodia. Our loss-of-function and rescue experiments show that a cytoplasmic AUTS2-Rac1 pathway is involved in cortical neuronal migration and neuritogenesis in the developing brain. These results suggest that FL-AUTS2 can activate Rac1 via interaction with P-Rex1 and the Elmo2/Dock180 complex to regulate actin dynamics in N1E-115 cells. | SIGNOR-266820 |
P0C6X7-PRO_0000037317 | P03901 | 1 | binding | down-regulates activity | 0.2 | This result suggests that the nsp10 protein could affect the activities of NADH and cytochrome oxidase II via a direct interaction while being involved in viral replication. | SIGNOR-260253 |
P0DTD1-PRO_0000449619 | P23396 | 1 | binding | down-regulates activity | 0.2 | Nsp1 Locks the 40S in a Conformation Incompatible with mRNA Loading and Disrupts Initiation Factor Binding. Molecular interactions between C-Nsp1 and 40S ribosome components, including uS3, h18, and uS5. | SIGNOR-262507 |
Q14493 | P0DPK2 | 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-265419 |
Q9ULU4 | P03956 | 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-262042 |
Q15084 | Q9NZJ5 | 1 | null | down-regulates activity | 0.2 | Protein disulfide isomerase A6 (PDIA6) interacts with protein kinase RNA-like endoplasmic reticulum kinase (PERK) and inositol requiring enzyme (IRE)-1 and inhibits their unfolded protein response signaling. | SIGNOR-256537 |
P18848 | Q9P2J5 | 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-269420 |
P25098 | P15311 | 1 | phosphorylation | up-regulates | 0.2 | Grk2 phosphorylates glutathione s-transferase (gst)-ezrin, but not an ezrin fusion protein lacking threonine 567 (t567), in vitro. These results suggest that t567, the regulatory phosphorylation site responsible for maintaining ezrin in its active conformation, represents the principle site of grk2-mediated phosphorylation. | SIGNOR-135622 |
P60510 | O75531 | 1 | dephosphorylation | up-regulates | 0.2 | Herein, we demonstrate we demonstrate that phosphorylation of ser4 and/or thr2/thr3 abrogates the interaction of baf with dna and reduces its interaction with the lem domain. We have identified the major phosphatase responsible for dephosphorylation of ser-4 to be protein phosphatase 4 catalytic subunit. | SIGNOR-203281 |
P03186 | Q9Y6K9 | 1 | deubiquitination | down-regulates activity | 0.2 | In the current study, we have found that BPLF1 interferes with innate immune activation by targeting multiple intermediates along the TLR signal transduction pathway, including TRAF6, NEMO, and IκBα. BPLF1 can remove ubiquitin tags from proteins in the TLR signaling cascade. This inhibits TLR signaling and decreases the expression of immune response genes. | SIGNOR-266743 |
Q2TAL8 | Q5ST30 | 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-269409 |
Q9Y222 | P18146 | 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-261584 |
P78368 | P07948 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.2 | Although there have been more than 40 reports of mass spectrometric studies on phosphorylation at Lyn-S13, the kinase responsible remained unclear. We succeeded in identifying casein kinase 1γ (CK1γ) as the kinase responsible for phosphorylation of Lyn-S13. In HEK293 cells co-expressing Lyn and CK1γ, the phosphorylation level of Lyn-S13 increased significantly. we concluded that S-palmitoylated CK1γ encounters N-myristoylated Lyn and specifically phosphorylates the Ser-13 residue at the Golgi during intracellular protein traffic, as shown schematically in Fig. 8. Phosphorylated dual-lipid-modified Lyn and S-palmitoylated CK1γ are then transported from the Golgi to the plasma membrane. | SIGNOR-275397 |
Q8WYQ5 | Q8IYW5 | 1 | binding | up-regulates activity | 0.2 | Specifically, radiation-induced ATM-dependent phosphorylation of DGCR8 at serine 677 facilitates USP51 to bind, deubiquitinate, and stabilize DGCR8, which leads to the recruitment of DGCR8 and DGCR8's binding partner RNF168 to MDC1 and RNF8 at DSBs. | SIGNOR-277309 |
P54652 | Q99683 | 1 | binding | down-regulates | 0.2 | Coimmunoprecipitation analysis revealed a physical interaction between endogenous hsp72 and ask1 in nih 3t3 cells exposed to mild heat shock. Hsp72 blocked both the homo-oligomerization of ask1 and ask1-dependent apoptosis. | SIGNOR-94565 |
Q53GL7 | Q13283 | 1 | post translational modification | up-regulates activity | 0.2 | Further, we pinpoint the core SG component, G3BP1, as a PARP10 substrate and find that PARP10 regulates SG assembly driven by both G3BP1 and its modeled mechanism. Intriguingly, while PARP10 only adds a single ADP-ribose unit to proteins, G3BP1 is PARylated, suggesting its potential role as a scaffold for protein recruitment. PARP10 knockdown alters the SG core composition, notably decreasing translation factor presence. | SIGNOR-273727 |
P29372 | P67775 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | Here we report that MID1 catalyzes the in vitro ubiquitination of the catalytic subunit of PP2A (PP2Ac) in the absence of alpha4. In the presence of alpha4, the level of PP2Ac ubiquitination is reduced.The high molecular weight smear pattern was not as obvious, suggesting that domains within the C-terminal half of MID1 may contribute to the polyubiquitination of PP2Ac. | SIGNOR-271930 |
Q15678 | Q03135 | 1 | dephosphorylation | down-regulates activity | 0.2 | Finally, PTPN14 overexpression in B16F10 cells reduced the ability of CAV1 to induce metastasis in vivo.|Moreover, the CAV1 (Y14F) mutant protein was shown to co-immunoprecipitate with PTPN14 even in the absence of E-cadherin, and overexpression of PTPN14 reduced CAV1 phosphorylation on tyrosine 14, as well as suppressed CAV1 enhanced cell migration, invasion and Rac-1 activation in B16F10, metastatic colon [HT29 (US)] and breast cancer (MDA-MB-231) cell lines. | SIGNOR-277054 |
Q02156 | O94925 | 1 | phosphorylation | up-regulates activity | 0.2 | PKCε is the kinase that phosphorylates GAC at Ser314. | SIGNOR-277387 |
Q8N431 | P01116 | 1 | binding | up-regulates | 0.2 | Gefs catalyse the transition from gdp-bound, inactive ras to gtp-bound, active ras. | SIGNOR-161508 |
O00712 | P29322 | 1 | transcriptional regulation | up-regulates quantity | 0.2 | For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8) | SIGNOR-268903 |
P01019-PRO_0000032457 | Q9BYF1 | 2 | binding | up-regulates activity | 0.2 | At first, ACE2 has been demonstrated to induce conversion of Ang I into Ang (1–7) by means of intermediate production of Ang (1–9), a fragment with unknown function. | SIGNOR-260226 |
Q6R6M4 | O14503 | 1 | deubiquitination | up-regulates quantity by stabilization | 0.2 | Upon DNA damage, DEC1 is rapidly induced in an ATM/ATR-dependent manner. DEC1 induction results from protein stabilization via a mechanism that requires the USP17 ubiquitin protease. USP17 binds and deubiquitylates DEC1, markedly extending its half-life. | SIGNOR-276852 |
P98170 | O43236 | 2 | ubiquitination | down-regulates quantity | 0.2 | Fig. 1 D revealed that co-transfection of ARTS and full length XIAP strongly reduces the levels of ARTS, while co-transfection of ARTS and XIAPdelRING does not change ARTS protein levels.|In this study we show that XIAP also promotes the ubiquitination and degradation of its antagonist ARTS. | SIGNOR-278801 |
Q8N3F0 | Q9UHD2 | 1 | binding | down-regulates activity | 0.2 | Here we report that viral infection induced upregulation of INKIT, an inhibitor for NF-κB and IRF3 that restricted innate antiviral responses by blocking phosphorylation of p65 and IRF3. Viral infection induced IKK-mediated phosphorylation of INKIT at Ser58, resulting in its dissociation from the IKKs. INKIT is associated with IKKα/β and TBK1/IKKɛ and inhibits the recruitment and phosphorylation of p65 and IRF3, respectively. IKKα and TBK1 phosphorylate INKIT at Ser58, which results in disassociation of INKIT from IKKα or TBK1 and thereby allows for the subsequent recruitment and phosphorylation of p65 and IRF3 | SIGNOR-273664 |
P49354 | O14807 | 1 | null | up-regulates activity | 0.2 | Major investments have been made to target Ras through indirect routes. Inhibition of farnesyl transferase to block Ras maturation has failed in large clinical trials. | SIGNOR-242553 |
Q13535 | Q8IUH4 | 1 | phosphorylation | up-regulates activity | 0.2 | Collectively these results suggest that ZDHHC13 phosphorylation by ATR following UVB irradiation promotes its interaction with MC1R to stimulate MC1R palmitoylation. | SIGNOR-273517 |
P49840 | O60936 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | The present study provided evidence that GSK3alpha and beta directly phosphorylates Arc, resulting in its subsequent degradation. | SIGNOR-279179 |
Q15077 | 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-257398 |
P62136 | Q03112 | 1 | dephosphorylation | down-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-273430 |
P19525 | Q9NYA1 | 1 | phosphorylation | up-regulates activity | 0.2 | This suggests that PKR is critical in the phosphorylation of SPHK1 at Ser225.|We confirmed that phosphorylated PKR activates SPHK1 kinase activity, but it remained necessary to determine whether there has mutual correlation or any reciprocal effect between these two kinases in stressed cells. | SIGNOR-278514 |
Q13315 | Q8NHY2 | 1 | phosphorylation | down-regulates | 0.2 | Atm engages autodegradation of the e3 ubiquitin ligase cop1 after dna damage. We observed that in response to dna damage, atm phosphorylated cop1 on ser(387) and stimulated a rapid autodegradation mechanism | SIGNOR-149082 |
P51965 | P29372 | 1 | binding | up-regulates activity | 0.2 | Here we report that MID1 catalyzes the in vitro ubiquitination of the catalytic subunit of PP2A (PP2Ac) in the absence of alpha4. In the presence of alpha4, the level of PP2Ac ubiquitination is reduced.The high molecular weight smear pattern was not as obvious, suggesting that domains within the C-terminal half of MID1 may contribute to the polyubiquitination of PP2Ac. We observed that PP2Ac was ubiquitinated in the presence of UbcH5a-c and UbcH6, similar to results obtained with MID1-catalyzed ubiquitination of alpha4 (Figure 2E) | SIGNOR-271929 |
Q9Y4K3 | Q9Y4K3 | 2 | ubiquitination | up-regulates activity | 0.2 | Here we report that the ubiquitin ligase (e3) traf6 interacts with a consensus motif present in tbetari. The tbetari-traf6 interaction is required for tgf-beta-induced autoubiquitylation of traf6 and subsequent activation of the tak1-p38/jnk pathway, which leads to apoptosis. | SIGNOR-180562 |
P38398 | O96028 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | Proteomic data analysis revealed interaction between NSD2 and BRCA1 and further study revealed that BRCA1 ubiquitinates NSD2 at K292 residue.|These results suggested that BRCA1 interacts with and promotes degradation of NSD2 via polyubiquitination . | SIGNOR-278745 |
P10827 | P23769 | 1 | binding | down-regulates activity | 0.2 | We found that the T3-bound TR inhibits this reporter construct driven by GATA2 alone, indicating that the target of T3-bound TR repression is GATA2. | SIGNOR-267257 |
P07900 | Q75N03 | 1 | binding | up-regulates quantity | 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. Hsp90 participates in the correct folding of its client proteins, allowing them to maintain their stability and activity. | SIGNOR-271474 |
P68400 | O43889 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Here, we found that human CREB3 is phosphorylated within its transcription activation domain on serine 46 by protein kinase CK2. However, phosphorylation at serine 46 reduced the stability of CREB3. | SIGNOR-277501 |
Q92824 | P01178-PRO_0000020495 | 1 | cleavage | up-regulates quantity | 0.2 | Oxytocin-extended form is further cleaved by enzymatic activity to yield the nine-amino-acid active peptide, OT. The proteolysis may involve several pro-hormone convertases, convertase 2 (PC2) (20p11-1-11.2) and convertase 5 (PC5) (9q21.3) (Gabreels et al 1998). Both enzymes are found in OT neurosecretory vesicles and are a part of a family of subtilisen/kexinlike convertases (Seidah et al 1994). It is a product of the OT gene located at human gene locus 20p13 (Rao et al 1992). The processing cascade results in the production of neurophysin I and OT extended form (OT-X), which is OT with a C-terminal, three-amino-acid extension. | SIGNOR-270334 |
P49841 | P10415 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | A previous study has demonstrated that GSK3B triggers the degradation of BCL2 by inducing phosphorylation of BCL2 at Ser70, which induced autophagy by interrupting the interaction between BECN1 and BCL2 [32]. | SIGNOR-279784 |
Q00535 | O95817 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | CDK5-mediated phosphorylation on S297 promotes BAG3 degradation. | SIGNOR-277502 |
P63244 | Q9P126 | 1 | binding | down-regulates quantity by destabilization | 0.2 | In this study, we reported that RACK1, the receptor for activated C-kinase 1, associated with the cytoplasmic tail of CLEC-2. Moreover, overexpression of RACK1 decreased the stability of CLEC-2 through promoting its ubiquitin-proteasome degradation, without impairing surface expression and downstream signaling of CLEC-2. Taken together, these results suggest RACK1 as a novel modulator of CLEC-2 expression.Previous reports indicated that RACK1 mediated ubiquitin–proteasome degradation of HIF-1a and BimEL by recruiting Elongin-C/B ubiquitin ligase complex | SIGNOR-272781 |
Q13976 | Q9UI08 | 1 | phosphorylation | down-regulates activity | 0.2 | Vertebrate Ena/VASP proteins are phosphorylated by PKA, as well as PKG, and the phosphorylation is required for full function in a number of cellular contexts | SIGNOR-268290 |
Q9BYB0 | P12814 | 1 | relocalization | up-regulates activity | 0.2 | SHANK proteins are ‘master’ scaffolding proteins that tether and organize intermediate scaffolding proteins. They are located at excitatory synapses, where they are crucial for proper synaptic development and function. SAPAP proteins subsequently bind to the PDZ domain of members of the SHANK protein family. SHANK proteins then bind to the actin cytoskeleton and to Homer protein, which in turn interacts with mGluRs. Through these extended links, PSD95, SAPAP, SHANK and Homer proteins form a quaternary complex that brings together mGluR and NMDAR complexes in the PSD (FIG. 3). | SIGNOR-264585 |
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