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 |
|---|---|---|---|---|---|---|---|
P20823 | Q63ZE4 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Luciferase reporter gene constructs containing the OAT5 (SLC22A10) and OAT7 (SLC22A9) promoter regions were transactivated by HNF-1 in HepG2 cells. | SIGNOR-268983 |
P00533 | Q15645 | 2 | phosphorylation | up-regulates quantity | 0.2 | Reciprocally, TRIP13 was phosphorylated at tyrosine(Y) 56 by EGFRvIII and EGF-activated EGFR. Abrogating TRIP13 Y56 phosphorylation dramatically attenuated TRIP13 expression-enhanced EGFR signaling and GBM cell growth. | SIGNOR-265083 |
Q6T4R5 | Q9NYB9 | 1 | binding | up-regulates activity | 0.2 | NHS may preferentially bind one or more Abi's in vivo, and it is also likely that specificity is governed by spatiotemporal expression of both proteins. Abi2 is highly expressed in the lens and plays a pivotal role in the development of the anterior and posterior sutures. This suggests that an NHS–Abi2 interaction may be physiologically important for lens development and that null mutations in the NHS gene could cause congenital cataract by disruption of this interaction and the actin cytoskeleton. | SIGNOR-253579 |
Q13557 | P51787 | 1 | phosphorylation | down-regulates activity | 0.2 | CaMKII regulates KCNQ1 at S484 during sustained β-AR stimulation to inhibit IKs. The ability of CaMKII to inhibit IKs may contribute to arrhythmogenicity during HF. | SIGNOR-275479 |
P36956 | Q7KZF4 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | These findings reveal that SREBP-2 and SREBP-1 bind to specific sites in SND1 promoter and regulate SND1 transcription in opposite ways; it is induced by SREBP-2 activating conditions and repressed by SREBP-1 overexpression. | SIGNOR-259137 |
Q13976 | Q9UH03 | 1 | phosphorylation | up-regulates activity | 0.2 | Mutation of Ser-91 to Ala in recombinant Sept3 also abolished PKG phosphorylation, confirming that Ser-91 is the major site in vitro. Therefore Sept3 is phosphorylated on Ser-91 in nerve terminals and its phosphorylation may contribute to the regulation of its subcellular localization in neurons. | SIGNOR-263183 |
P17861 | P17861 | 2 | binding | up-regulates activity | 0.2 | E4BP4, ATF-6, OASIS, and XBP-1 all formed strong homodimeric associations on the array Transcription factor dimerization can increase the selectivity of protein-DNA interactions and generate a large amount of DNA binding diversity from a relatively small number of proteins | SIGNOR-224199 |
Q13330 | Q8NHY2 | 2 | binding | down-regulates quantity by destabilization | 0.2 | MTA1 destabilizes COP1 by promoting its autoubiquitination. in addition to polyubiquitination of its substrates, COP1 also catalyzes its autoubiquitination for degradation as a part of an autoregulatory mechanism | SIGNOR-271892 |
P35367 | P63096 | 1 | binding | up-regulates activity | 0.2 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-257050 |
Q9UN73 | 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-265666 |
O43561 | O00459 | 1 | binding | up-regulates activity | 0.2 | By substituting these tyrosine residues in LAT with phenylalanine and by utilizing phosphorylated peptides derived from these sites, we mapped the tyrosine residues in LAT required for the direct interaction and activation of Vav, p85/p110alpha and phospholipase Cgamma1 (PLCgamma1). Our results indicate that Tyr(226) and Tyr(191) are required for Vav binding, whereas Tyr(171) and Tyr(132) are necessary for association and activation of phosphoinositide 3-kinase activity and PLCgamma1 respectively. | SIGNOR-246055 |
Q14493 | Q96KK5 | 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-265402 |
P00533 | P00367 | 1 | phosphorylation | up-regulates activity | 0.2 | EGFR phosphorylates GDH1 at Y135 and contributes to GDH1 activation.|Mechanistically, GDH1 is activated by EGFR through phosphorylation at tyrosine 135 and, together with RSK2, enhances the cAMP response element-binding protein (CREB) activity via CaMKIV signaling, thereby promoting metastasis. | SIGNOR-279706 |
O96006 | P62753 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | HDRE-like sequences act as positive regulatory elements for RP gene promoter activities in vivo. | Cotransfection of a plasmid expressing hDREF increased luciferase expression directed by each RP gene promoter more than 30% compared with the values obtained without the hDREF-expressing plasmid. | SIGNOR-266082 |
P22455 | Q13043 | 1 | phosphorylation | down-regulates activity | 0.2 | FGFR4 phosphorylates MST1 to confer breast cancer cells resistance to MST1/2 dependent apoptosis.|We provide evidence suggesting that by Y433-MST1 phosphorylation , FGFR4 inhibits MST1 / 2 activation . | SIGNOR-279714 |
P17612 | Q9UQL6 | 1 | phosphorylation | up-regulates activity | 0.2 | PKA/Cdk5-mediated phosphorylation of HDAC5 at Ser279 within the NLS promotes nuclear localization of HDAC5 and interaction with the nuclear corepressor complex | SIGNOR-198658 |
K9N643 | Q9UHD2 | 1 | binding | down-regulates activity | 0.2 | Previous studies have shown that MERS-CoV ORF4b antagonizes the early antiviral alpha/beta interferon (IFN-α/β) response, which may significantly contribute to MERS-CoV pathogenesis; however, the underlying mechanism is poorly understood. Here, we found that ORF4b in the cytoplasm could specifically bind to TANK binding kinase 1 (TBK1) and IκB kinase epsilon (IKKε), suppress the molecular interaction between mitochondrial antiviral signaling protein (MAVS) and IKKε, and inhibit IFN regulatory factor 3 (IRF3) phosphorylation and subsequent IFN-β production. these results indicate that MERS-CoV ORF4b inhibits the induction of type I IFN through a direct interaction with IKKε/TBK1 in the cytoplasm | SIGNOR-260593 |
Q2TAL8 | P41250 | 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-269405 |
Q5VWQ8 | P15976 | 1 | binding | up-regulates activity | 0.2 | DAB2IP suppresses transcription of stem cell factor receptor CD117, by interacting with GATA-1 on a silencer element on its gene | SIGNOR-254770 |
O96013 | P28698 | 1 | phosphorylation | up-regulates activity | 0.2 | Here, we link ErbB2 activation to invasion via ErbB2-induced, SUMO-directed phosphorylation of a single serine residue, S27, of the transcription factor myeloid zinc finger-1 (MZF1). Phosphorylation of MZF1-S27 is an early response to ErbB2 activation and results in increased transcriptional activity of MZF1.The phosphorylation of MZF1-S27 is preceded by poly-SUMOylation of K23, which can make S27 accessible to efficient phosphorylation by PAK4. | SIGNOR-277422 |
Q00535 | O60260 | 1 | phosphorylation | down-regulates | 0.2 | Phosphorylation by cdk5 decreased the auto-ubiquitylation of parkin both in vitro and in vivo. | SIGNOR-153445 |
P06493 | Q92934 | 1 | phosphorylation | up-regulates activity | 0.2 | CDK1-mediated Bcl-2 serine 70 phosphorylation enhances its pro-apoptotic function, whereas CDK1-mediated Bad serine 128 phosphorylation promotes apoptosis. | SIGNOR-267921 |
Q9UPW6 | P01871 | 1 | transcriptional regulation | up-regulates quantity | 0.2 | The SATB2 protein was shown to bind MAR sequences flanking the enhancer of the endogenous immunoglobulin μ heavy chain (IgH) gene in vivo, and this binding was found to correlate with an increase in the expression of a transfected rearranged μ wild-type gene | SIGNOR-268933 |
Q14938 | O75093 | 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-268906 |
O95835 | P11908 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Recruitment of TRAF2 to PRPS1/2 requires phosphorylation of PRPS1 S285 or PRPS2 T285, which is mediated by low stiffness-activated large tumor suppressor (LATS)1/2 kinases.LATS1/2-dependent S/T285 phosphorylation is required for PRPS1/2 ubiquitination and degradation at low stiffness. | SIGNOR-276506 |
Q13131 | Q9Y297 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Glucose deprivation activates AMPK kinase to phosphorylate β-TrCP1 and promotes the subsequent ubiquitination and degradation of β-TrCP1 by β-TrCP2, but does not promote β-TrCP2 degradation by β-TrCP1. | SIGNOR-277475 |
Q9BZL6 | Q9UBF8 | 1 | phosphorylation | up-regulates | 0.2 | Binding of 14-3-3 proteins to pi4kiiibeta involved the pkd phosphorylation site ser294, evident from reduced 14-3-3 binding to a s294a pi4kiiibeta mutant. Phospho-specific binding of 14-3-3 proteins to phosphatidylinositol 4-kinase iii beta protects from dephosphorylation and stabilizes lipid kinase activity. | SIGNOR-148880 |
Q9UQM7 | Q05469 | 1 | phosphorylation | down-regulates | 0.2 | Phosphorylation of bovine hormone-sensitive lipase by the amp-activated protein kinase. | SIGNOR-58251 |
Q99677 | 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-257325 |
Q16539 | Q9NQU5 | 1 | phosphorylation | up-regulates | 0.2 | The activation of pak6 by both p38 map kinase and mkk6 suggests that pak6 plays a role in the cellular response to stress-related signals. | SIGNOR-130979 |
P29371 | 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-256794 |
P49841 | P57059 | 1 | phosphorylation | up-regulates activity | 0.2 | Glycogen synthase kinase-3beta (GSK-3beta) phosphorylates Ser/Thr residues located at the fourth position ahead of the pre-phosphorylated Ser/Thr residues, and inhibitors of GSK-3beta reduce the phosphorylation at Thr182. The results of an in vitro reconstitution assay also indicate that GSK-3beta could be the SIK1 kinase. However, overexpression and knockdown of GSK-3beta in LKB1-defective HeLa cells suggests that GSK-3beta alone may not be able to phosphorylate or activate SIK1, indicating that LKB1 may play a crucial role by phosphorylating SIK1 at Thr182, possibly as an initiator of the autophosphorylation cascade, and GSK-3beta may phosphorylate SIK1 at Thr182 by recognizing the priming-autophosphorylation at Ser186 in cultured cells. | SIGNOR-279742 |
Q96J02 | Q8N0X7 | 2 | binding | up-regulates activity | 0.2 | SPG20 Protein Spartin Is Recruited to Midbodies by ESCRT-III Protein Ist1 and Participates in Cytokinesis. Spartin colocalizes with Ist1 at the midbody, and depletion of Ist1 in cells significantly decreases the number of cells where spartin is present at midbodies. | SIGNOR-261308 |
Q86YJ5 | P31994 | 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-271541 |
O14757 | O14974 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | MYPT1 is phosphorylated by CDK1, thus recruiting protein phosphatase 1β (PP1cβ) to dephosphorylate and inactivate Plk1. Here we identified that Chk1 directly interacts with MYPT1 and preferentially phosphorylates MYPT1 at Ser20, which is essential for MYPT1-PP1cβ interaction and subsequent Plk1 dephosphorylation. | SIGNOR-277870 |
P63244 | Q92615 | 1 | binding | up-regulates activity | 0.2 | Here we show that LARP4B is a cytoplasmic protein that co-sediments with polysomes and accumulates upon stress induction in stress granules. Biochemical studies further show that the protein interacts with two key factors of the translational machinery, namely, the cytoplasmic poly(A) binding protein (PABPC1) and the receptor for activated C Kinase (RACK1). The biochemical and functional data of LARP4B presented in this study suggest a possible mode of action of LARP4B in translation. Assuming that LARP4B interacts with mRNA-associated PABPC1 and RACK1 simultaneously, it may form a bridge between the 3′ end of mRNAs and the initiating ribosome. This process would lead to mRNA circularization, possibly in an analogous way as it has been described for PABPC1 and eIF4G, the scaffold protein of the cap-binding complex. | SIGNOR-260941 |
Q99942 | O43511 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | E3 ubiquitin ligase Rma1 is involved in Pendrin degradation | SIGNOR-271497 |
P23470 | Q05655 | 1 | dephosphorylation | up-regulates activity | 0.2 | PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity. | SIGNOR-254716 |
O43318 | Q9Y572 | 1 | phosphorylation | up-regulates activity | 0.2 | Collectively, TAK1 activates RIPK3, RIPK3 activates TAK1, and RIPK1 activates RIPK3 and facilitates interaction between TAK1 and RIPK3.|We found that prolonged and hyperactivation of TAK1 induced phosphorylation and activation of RIPK3, leading to necrosis without caspase activation. | SIGNOR-279634 |
Q13131 | O95863 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.2 | Serines 11 and 92 participate in the control of snail1 stability and positively regulate snail1 repressive function and its interaction with msin3a corepressor. Furthermore, serines 11 and 92 are required for snail1-mediated emt and cell viability, respectively. Pka and ck2 have been characterized as the main kinases responsible for in vitro snail1 phosphorylation at serine 11 and 92, respectively. | SIGNOR-161779 |
O14842 | 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-256799 |
Q02156 | P21802 | 1 | phosphorylation | up-regulates | 0.2 | Phosphorylation of serine 779 in fibroblast growth factor receptor 1 and 2 by protein kinase c(epsilon) regulates ras/mitogen-activated protein kinase signaling and neuronal differentiation | SIGNOR-201675 |
Q9NY61 | P07288 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Chromatin immunoprecipitation in combination with siRNA-mediated knockdown revealed that recruitment of AATF and ZIPK to the PSA enhancer was dependent on AR, whereas recruitment of TSG101 was dependent on AATF. | SIGNOR-253669 |
Q9UIF8 | P84243 | 1 | binding | down-regulates activity | 0.2 | The BAZ2B bromodomain has been shown to bind to acetylated H3K14 (H3K14ac), whose presence at promoter regions is generally associated with gene activation. This suggests a potential role for BAZ2B in transcriptional activation. | SIGNOR-266619 |
Q9Y243 | P78563 | 1 | phosphorylation | down-regulates activity | 0.2 | AKT-dependent phosphorylation of the adenosine deaminases ADAR-1 and -2 inhibits deaminase activity. Coimmunoprecipitation studies and in vitro kinase assays revealed that AKT-1, -2, and -3 interact with both ADAR1p110 and ADAR2 and phosphorylate these RNA editases. Using site-directed mutagenesis of suspected AKT phosphorylation sites, AKT was found to primarily phosphorylate ADAR1p110 and ADAR2 on T738 and T553, respectively | SIGNOR-276195 |
Q96CW1 | Q9UI40 | 1 | binding | down-regulates quantity | 0.2 | we report that the first tyrosine motif of NCKX2 interacts with AP2M1 and that the interaction is required for endocytosis of NCKX2 from the dendritic surface. Furthermore, we show that a Src family kinase (SFK) modulates the endocytosis of NCKX2 by tyrosine-phosphorylation of the AP-2 recognition motif in NCKX2. | SIGNOR-264388 |
Q9HC56 | 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-269035 |
Q9UIF8 | Q6NXT2 | 1 | binding | down-regulates activity | 0.2 | The BAZ2B bromodomain has been shown to bind to acetylated H3K14 (H3K14ac), whose presence at promoter regions is generally associated with gene activation. This suggests a potential role for BAZ2B in transcriptional activation. | SIGNOR-266621 |
P17252 | O60500 | 1 | phosphorylation | up-regulates activity | 0.2 | Binding of _-arrestin2 to the nephrin intracellular domain depended on phosphorylation of nephrin threonine residues 1120 and 1125 by pkc_. | SIGNOR-172056 |
Q96JA1 | Q9ULV8 | 2 | binding | up-regulates | 0.2 | Upregulation of lrig1 is followed by enhanced ubiquitylation and degradation of egfr. The underlying mechanism involves recruitment of c-cbl, an e3 ubiquitin ligase that simultaneously ubiquitylates egfr and lrig1 and sorts them for degradation | SIGNOR-127301 |
Q9Y653 | P61586 | 1 | binding | up-regulates activity | 0.2 | Like many other adhesion GPCRs, GPR56 is cleaved via a GPCR autoproteolysis-inducing (GAIN) domain into N- and C-terminal fragments (GPR56N and GPR56C); | We demonstrate that ligand binding releases GPR56N from the membrane-bound GPR56C and triggers the association of GPR56C with lipid rafts and RhoA activation. | SIGNOR-253981 |
Q15077 | Q03113 | 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-257343 |
P10828 | 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-267256 |
P17612 | Q9NR82 | 1 | phosphorylation | up-regulates activity | 0.2 | We conclude that phosphorylation of S53 on the amino terminus of Kv7.5 is essential for PKA-dependent enhancement of channel activity in response to βAR activation in vascular and airway smooth muscle cells. | SIGNOR-265980 |
P17509 | P69891 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | HOXB6 protein represses globin transcript levels in stably transfected K562 cells in a DNA-binding dependent fashion. | SIGNOR-261638 |
P41231 | 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-264307 |
P41743 | P08670 | 1 | phosphorylation | up-regulates activity | 0.2 | Results suggest that aPKCs target multiple activation sites (Ser33/39/56) on Vimentin and therefore is essential for VIF dynamics regulation during the metastasis of prostate cancer cells. | SIGNOR-277623 |
Q9Y5I1 | 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-265670 |
Q99704 | P26012 | 1 | binding | down-regulates activity | 0.2 | Integrins also bind to many PTBdomain-containing proteins (Calderwood et al., 2003) – including Dok1 and integrincytoplasmic-domain-associated protein 1 (ICAP1) – and these can compete with talin for binding to integrin and so can impair activation | SIGNOR-257698 |
Q7Z6Z7 | Q86YD1 | 1 | ubiquitination | down-regulates quantity | 0.2 | Our data suggest that HUWE1 can ubiquitinate PTOV1 in vitro and depletion of HUWE1 in cells increases the stability of PTOV1 S36A protein in the nucleus.|Our data suggest that depletion of HUWE1 elevates PTOV1 protein levels, which, in turn, promote the expression of cJun, a pro-growth translational target of PTOV1 (18)\n In our model, we propose that HUWE1 mediates the degradation of PTOV1 in the nucleus. | SIGNOR-278755 |
Q96HN2 | Q9NRJ5 | 1 | binding | down-regulates activity | 0.2 | Inositol 1,4,5-triphosphate receptor-binding protein released with inositol 1,4,5-triphosphate (IRBIT) associates with components of the mRNA 3' processing machinery in a phosphorylation-dependent manner and inhibits polyadenylation|In addition to CPSF, IRBIT interacted in vitro with poly(A) polymerase (PAP), which is the enzyme recruited by CPSF to elongate the poly(A) tail, and inhibited PAP activity in a phosphorylation-dependent manner. | SIGNOR-268332 |
O14920 | Q9H765 | 2 | phosphorylation | up-regulates activity | 0.2 | We found that ASB8 was phosphorylated at the N-terminal Ser-31 by host IkappaB kinase beta (IKKbeta). In turn, ASB8 facilitated K48-linked ubiquitination and degradation of IKKbeta via the ubiquitin-proteasome pathway, resulting in remarkable inhibition of I-kappa-B-alpha (IkappaBalpha) and of p65 phosphorylation, consequently suppressing NF-kappaB activity. | SIGNOR-272242 |
Q9NX47 | Q13794 | 1 | ubiquitination | down-regulates quantity | 0.2 | MARCH5 promotes ubiquitination of MCL1 and NOXA.|Of note, MARCH5 depletion led to the accumulation of MCL1 and NOXA in asynchronous as well as G2 cells, suggesting that MARCH5 controls NOXA/MCL1 levels throughout the cell cycle. | SIGNOR-278758 |
Q9UHD2 | P60891 | 1 | phosphorylation | up-regulates activity | 0.2 | Here, we show that ionizing radiation results in TBK1-mediated phosphorylation of phosphoribosyl pyrophosphate synthetase (PRPS)1/2 at T228, thereby enhancing PRPS1/2 catalytic activity and promoting deoxyribonucleotide synthesis. | SIGNOR-277316 |
Q9Y5H9 | Q9Y5G7 | 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-265694 |
Q13239 | P10721 | 2 | ubiquitination | down-regulates quantity by destabilization | 0.2 | In this report, we show that SLAP associates with both wild-type and oncogenic c-Kit (c-Kit-D816V). The association involves the SLAP SH2 domain and receptor phosphotyrosine residues different from those mediating Src interaction. Association of SLAP triggers c-Kit ubiquitylation which, in turn, is followed by receptor degradation | SIGNOR-263143 |
P00797 | P01019-PRO_0000032457 | 1 | cleavage | up-regulates quantity | 0.2 | Renin is an aspartic protease that enzymatically cleaves its substrate angiotensinogen, which is produced by the liver, to form an inactive peptide: angiotensin (Ang)I or Ang (1–10). | SIGNOR-260225 |
Q13043 | Q15424 | 1 | phosphorylation | down-regulates activity | 0.2 | In the present study, we demonstrate that the chromatin scaffold protein SAFB1 interacts with and is phosphorylated by MST1 and is a novel regulator of AR capable of integrating signaling between the AR and MST1 networks. | SIGNOR-279296 |
O43781 | Q9Y6Q9 | 1 | phosphorylation | down-regulates activity | 0.2 | Mechanistically, Dyrk3 directly phosphorylated NCOA3 at Ser-1330, disrupting its binding to ATF4 and thereby causing the inhibition of ATF4 transcriptional activity. | SIGNOR-275451 |
P05129 | P49768 | 1 | phosphorylation | up-regulates activity | 0.2 | A phosphorylation site at serine residue 346 was identified that is selectively phosphorylated by PKC but not by PKA. This site is localized within a recognition motif for caspases, and phosphorylation strongly inhibits proteolytic processing of PS1 by caspase activity during apoptosis. | SIGNOR-249238 |
Q13315 | Q4G0J3 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Altogether, the results suggest that ATM-mediated T440 phosphorylation enhances LARP7-BARD1 interaction and facilitates BRCA1/BARD1-mediated LARP7 ubiquitination and degradation. | SIGNOR-275580 |
Q96G91 | P08754 | 1 | binding | up-regulates activity | 0.2 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-257173 |
P17252 | P13726 | 1 | phosphorylation | up-regulates | 0.2 | We previously showed that the phosphorylation of ser253 within the cytoplasmic domain of human tissue factor (tf) initiates the incorporation and release of this protein into cell-derived microparticles. Furthermore, subsequent phosphorylation of ser258 terminates this process. The phosphorylation of ser253 is known to be mediated by protein kinase c_ | SIGNOR-199872 |
P48729 | O14503 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | CK1α-mediated phosphorylation of DEC1 on a conserved degron is required for DEC1 degradation. | SIGNOR-276851 |
P49841 | Q9BYG3 | 1 | phosphorylation | up-regulates activity | 0.2 | The forkhead-associated (FHA) domain of human Ki67 interacts with the human nucleolar protein hNIFK, recognizing a 44-residue fragment, hNIFK226-269, phosphorylated at Thr234. Here we show that high-affinity binding requires sequential phosphorylation by two kinases, CDK1 and GSK3, yielding pThr238, pThr234 and pSer230. phosphorylation of Thr234 by GSK3 proceeds only after Thr238 is already phosphorylated by CDK1. | SIGNOR-262698 |
P00519 | P29474 | 1 | phosphorylation | up-regulates activity | 0.2 | Two kinases, i.e. abelson-tyrosine protein kinase (ABL)1 and Src were identified as eNOS Tyr81 kinases as their inhibition and down-regulation significantly reduced the basal and Yoda1-induced tyrosine phosphorylation and activity of eNOS. | SIGNOR-277519 |
Q16236 | Q92626 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | PXDN expression in response to H2O2 and the Nrf2-specific inducers, tert-butylhydroquinone (tBHQ) and sulforaphane (SFN), was determined by western blotting and immunofluorescence microscopy, in HeLa and HEK293 cells.We found that Nrf2 binds to and increases luciferase reporter gene expression from the PXDN promoter via a putative Nrf2-binding site. In summary, we show that PXDN is a novel target of the redox sensitive transcription factor Nrf2. | SIGNOR-265248 |
P31751 | Q92900 | 1 | phosphorylation | up-regulates activity | 0.2 | AKT-Mediated UPF1 Phosphorylation at T151 Promotes UPF1 Helicase Activity | SIGNOR-277595 |
P06493 | P12272 | 1 | phosphorylation | down-regulates | 0.2 | Phosphorylation at the cyclin-dependent kinases site (thr85) of parathyroid hormone-related protein negatively regulates its nuclear localization | SIGNOR-68544 |
Q9NYL2 | P52566 | 1 | phosphorylation | down-regulates activity | 0.2 | In the present study, we provide evidence that ZAK serves as a RhoGDIbeta kinase, and demonstrate the phosphorylation of RhoGDIbeta by ZAK in vitro, as well as the physical association between ZAK and RhoGDIbeta.|These two proteins could negatively regulate one another such that ZAK suppresses RhoGDIbeta functions through phosphorylation and RhoGDIbeta counteracts the effects of ZAK by physical interaction. | SIGNOR-279633 |
O60260 | P27695 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | Based on these results, we conclude that Parkin directly ubiquitinates APE1.|These results indicated that degradation of APE1 by Parkin was limited compared to the transiently expressed APE1, suggesting that a large portion of APE1 is not in contact with the Parkin and PINK1 without induction of stresses such as oxidative stress. | SIGNOR-278531 |
P15056 | Q96TA1 | 1 | phosphorylation | down-regulates activity | 0.2 | Overall, this indicates that BRAF-dependent phosphorylation of FAM129B controls its cellular localization and thus its ability to bind to KEAP1 to block NRF2 degradation. | SIGNOR-279595 |
P78317 | P41229 | 1 | sumoylation | up-regulates activity | 0.2 | Hendriks and coworkers showed that, in response to alkylation damage by methyl methanesulfonate (MMS), SUMOylated JARID1B (KDM5B) is ubiquitylated by the SUMOtargeted ubiquitin ligase RNF4 and degraded by the proteasome, whereas JARID1C (KDM5C) is SUMOylated and recruited to the chromatin to demethylate histone H3K4 (Hendriks et al., 2015). | SIGNOR-271576 |
A7MCY6 | Q9BWT7 | 1 | relocalization | up-regulates activity | 0.2 | TBKBP1 recruits TBK1 to protein kinase C-theta (PKCθ) through a scaffold protein, CARD10. This enables PKCθ to phosphorylate TBK1 at Ser 716, a crucial step for TBK1 activation | SIGNOR-272470 |
P14859 | P35580 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Myocyte enhancer factor-2 and serum response factor binding elements regulate fast Myosin heavy chain transcription in vivo. We show that the upstream promoter region of the gene most abundantly expressed in mouse skeletal muscles, IIb MyHC, retains binding activity and transcriptional activation for three positive transcription factors, the serum response factor, Oct-1, and myocyte enhancer factor-2, whereas the other two genes (IIa and IId/x) have nucleotide substitutions in these sites that reduce binding and transcriptional activation | SIGNOR-238772 |
Q14938 | A8MYZ6 | 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-268887 |
Q6VVB1 | P43004 | 1 | ubiquitination | up-regulates activity | 0.2 | On the contrary, overexpression of the laforin/malin complex promotes the retention of GLT-1 at the plasma membrane.|This is due to a direct ubiquitination of GLT-1 by laforin and malin and/or to changes in the dynamics of its Nedd4.2-mediated endocytosis, which is assisted by specific adaptors (\u03b1- and \u03b2-arrestins). | SIGNOR-278586 |
Q02156 | P59047 | 1 | phosphorylation | up-regulates activity | 0.2 | MATER protein as substrate of PKCepsilon in human cumulus cells. we performed coimmunoprecipitation experiments using HEK293T cells expressing human MATER; a similar approach was then followed in human cumulus/follicular cells. In MATER(+)HEK293T cells, we observed that this protein acts as a phosphorylation substrate of PKCepsilon. Since PKCepsilon is known to collaborate with antiapoptotic signalling pathways, this suggests a novel mechanism for the function of MATER in follicular maturation. | SIGNOR-263175 |
Q14493 | O60814 | 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-265383 |
P16519 | P01178-PRO_0000020496 | 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-270337 |
Q9H2T7 | P15923 | 1 | binding | up-regulates | 0.2 | Yeast two-hybrid, mammalian two-hybrid, and co-immunoprecipitation analyses demonstrate specific interaction of e12 with ranbp17, a novel member of the importin-beta superfamily;this interaction maps to the crm1 homology region of ranbp17. Ectopic expression of ranbp17 leads to a approximately 3-fold increase in e2a/myod mediated transactivation of an e-box regulated luciferase reporter gene. | SIGNOR-165655 |
P17481 | P62736 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | Results from these experiments demonstrated that in 10T1/2 cells Hoxa10-1 increased the activity of the telokin promoter 3-fold without affecting the activity of the other promoters analyzed (Fig. 2A). Similar results were also observed in A10 SMC (data not shown). In contrast, Hoxb8 significantly repressed the activity of the telokin, smooth muscle α-actin, and SM22α promoters by 70, 50, and 70%, respectively | SIGNOR-261641 |
Q4ZG55 | Q15796 | 1 | binding | down-regulates activity | 0.2 | GREB1 is localized to the nucleus where it binds Smad2/3 in a competitive manner with p300 and inhibits TGFβ signaling, thereby promoting HepG2 HB cell proliferation. Binding of GREB1 to Smad2/3 inhibits transcription | SIGNOR-265884 |
P30622 | P58753 | 1 | binding | down-regulates activity | 0.2 | CLIP170 promotes ubiquitination and degradation of TIRAP | SIGNOR-280460 |
P06239 | Q06830 | 1 | phosphorylation | down-regulates activity | 0.2 | Inactivation of peroxiredoxin I by phosphorylation allows localized H(2)O(2) accumulation for cell signaling. To determine whether Prxs are phosphorylated, we subjected recombinant human PrxI and II to an in vitro kinase assay with two nonreceptor PTKs, Lck and Abl, in the presence of [γ-32P]ATP. Both PTKs phosphorylated PrxI and PrxII. Phosphorylation of the wild-type protein was detected, whereas that of the Y194F mutant was not (Figure 1B), indicating that Tyr194 is the only site of tyrosine phosphorylation. | SIGNOR-276277 |
Q9UNH5 | Q9NQR1 | 1 | dephosphorylation | down-regulates quantity by destabilization | 0.2 | The dephosphorylation of S29 during late mitosis by the Cdc14 phosphatases was required for APC(cdh1)-mediated ubiquitination of PR-Set7 and subsequent proteolysis. | SIGNOR-248835 |
Q969R5 | Q14676 | 1 | binding | up-regulates activity | 0.2 | L3MBTL2 links RNF8 and RNF168 in the DNA double strand break response. The protein kinase ATM phosphorylates L3MBTL2, which recruits it to the DNA lesion by promoting the interaction between MDC1 and L3MBTL2. L3MBTL2 is subsequently ubiquitinated by RNF8, which acts as a docking site for RNF168, thereby recruiting the ubiquitin ligase to the damage site. RNF168, in turn, ubiquitinates H2A-type histones to amplify the DNA damage response and recruit downstream DNA repair proteins for proper DSB signaling. | SIGNOR-266786 |
P67775 | P32519 | 1 | dephosphorylation | down-regulates activity | 0.2 | Elf-1 enhances the expression of CD3zeta, whereas it suppresses the expression of FcRgamma gene and lupus T cells have decreased amounts of DNA-binding 98 kDa form of Elf-1. We show that the aberrantly increased PP2A in lupus T cells dephosphorylates Elf-1 at Thr-231. Dephosphorylation results in limited expression and binding of the 98 kDa Elf-1 form to the CD3zeta and FcRgamma promoters. Suppression of the expression of the PP2A leads to increased expression of CD3zeta and decreased expression of FcRgamma genes and correction of the early signaling response | SIGNOR-248634 |
Q12851 | Q13200 | 1 | phosphorylation | up-regulates activity | 0.2 | Seven of these kinases (PIM1/2/3, MAP4K1/2, PKA, and NEK6) directly and robustly phosphorylated recombinant GST-Rpn1 at S361 in vitro (Fig. 3D and SI Appendix, Fig. S3 A and B). | SIGNOR-273900 |
Q9H3D4 | Q15149 | 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-263279 |
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