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 |
|---|---|---|---|---|---|---|---|
P11308 | O00501 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.224 | ETS-related gene (ERG) controls endothelial cell permeability via transcriptional regulation of the claudin 5 (CLDN5) gene. | SIGNOR-261596 |
Q00535 | P54646 | 1 | phosphorylation | down-regulates activity | 0.216 | In vitro, the results show that murine wild-type AMPK-alpha2 was phosphorylated by Cdk5 at a (S/T) PX (K/H/R) phosphorylation consensus sequence, which was associated with decreased AMPK-alpha2 activity.|Inactivated AMPK-alpha2 promotes the progression of diabetic brain damage by Cdk5 phosphorylation at Thr485 site. | SIGNOR-280218 |
P21127 | Q96I25 | 1 | phosphorylation | up-regulates activity | 0.207 | However, Clk1 enhanced SPF45 protein expression, but not mRNA expression, whereas inhibition of Clk1 increased SPF45 degradation through a proteasome dependent pathway.|In the present work, we show that Clk1 phosphorylates SPF45 in vitro on eight serine residues, all of which are N-terminal to the RRM domain required for splicing. | SIGNOR-279510 |
P68400 | Q9NYV6 | 1 | phosphorylation | down-regulates | 0.206 | Here we show that ck2 phosphorylates the transcription initiation factor tif-ia at serines 170 and 172 (ser170/172), and this phosphorylation triggers the release of tif-ia from pol i after transcription initiation. | SIGNOR-178943 |
P21127 | Q9Y2W1 | 1 | phosphorylation | up-regulates activity | 0.206 | In addition, genetic knockout of CLK1 or chemical inhibition in mice ameliorated diet-induced obesity and insulin resistance at 22\u00b0C. Through proteomics, we uncovered thyroid hormone receptor-associated protein 3 (THRAP3) as an interacting partner of CLK1, further confirmed by co-immunoprecipitation assays.|We further demonstrated that CLK1 phosphorylates THRAP3 at Ser243, which is required for its regulatory interaction with phosphorylated peroxisome proliferator-activated receptor gamma (PPAR\u03b3), resulting in impaired adipose tissue browning and insulin sensitivity. | SIGNOR-280209 |
Q9H2P0 | P49711 | 1 | relocalization | down-regulates activity | 0.206 | These results argue against the simultaneous binding of CTCF and ADNP to the same genomic loci. Instead, they support a model in which ADNP counteracts stable association of CTCF with DNA at over 15,000 binding sites in the mouse genome. | SIGNOR-266755 |
Q14938 | Q14393 | 1 | transcriptional regulation | down-regulates quantity | 0.205 | 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-268888 |
P10600 | P10600 | 2 | binding | up-regulates | 0.2 | The active form of tgf-b is a dimer stabilized by hydrophobic interactions and usually further strengthened by an intersubunit disulfide bridge | SIGNOR-148611 |
Q9Y5H7 | 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-265669 |
P35367 | 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-256778 |
Q9P286 | P17844 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.2 | PAK5 promotes RNA helicase DDX5 sumoylation and miRNA-10b processing in a kinase-dependent manner in breast cancer|The increased expression levels of PAK5 and phospho-DDX5 threonine 69 are associated with metastasis and poor clinical outcomes of patients. PAK5 facilitates the phosphorylation-dependent sumoylation of DDX5 to stabilize DDX5. Both the phosphorylation and sumoylation of DDX5 enhance the formation of a DDX5/Drosha/DGCR8 complex, thus promoting microRNA-10b processing. | SIGNOR-275658 |
O60260 | Q9NX09 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | In conclusion, our work in cellular and animal models and in human samples strongly indicates that RTP801 is a substrate of parkin and that RTP801 elevation due to parkin loss of function in both AR-JP and sporadic Parkinson's disease may contribute to neurodegeneration.|We showed that parkin poly-ubiquitinates RTP801, both in vitro and in vivo. | SIGNOR-278560 |
Q70EL2 | Q96EA4 | 1 | deubiquitination | up-regulates activity | 0.2 | Spindly is mono-ubiquitylated and this ubiquitin can be removed by active USP45. K48 ubiquitylated complex that interacts with Spindly is also de-ubiquitylated by USP45. In the absence of USP45 catalytic activity, interaction is abolished and cell migration is affected similarly to the phenotype described for lack of Spindly. | SIGNOR-268505 |
Q99814 | Q9H3R0 | 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-271585 |
P03200 | P20023 | 1 | binding | up-regulates activity | 0.2 | The binding of the Epstein-Barr virus glycoprotein gp350 by complement receptor type 2 (CR2) is critical for viral attachment to B lymphocytes. | SIGNOR-266624 |
Q8NEZ4 | Q9NZQ7 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | MLL3 enhances the transcription of PD-L1 and regulates anti-tumor immunity. We found that MLL3 bound to the enhancer of PD-L1. | SIGNOR-260040 |
P61812 | P61812 | 2 | binding | up-regulates | 0.2 | The active form of tgf-b is a dimer stabilized by hydrophobic interactions and usually further strengthened by an intersubunit disulfide bridge | SIGNOR-148608 |
Q9ULU4 | P15692 | 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-262041 |
O94844 | O76074 | 1 | binding | down-regulates quantity by destabilization | 0.2 | RhoBTB1 augmented the cGMP response to nitric oxide by restraining the activity of phosphodiesterase 5 (PDE5) by acting as a substrate adaptor delivering PDE5 to the Cullin-3 E3 Ring ubiquitin ligase complex for ubiquitination inhibiting PDE5. | SIGNOR-272312 |
O60341 | Q16695 | 1 | demethylation | up-regulates activity | 0.2 | Here, we provide evidence that LSD1 (KIAA0601), a nuclear homolog of amine oxidases, functions as a histone demethylase and transcriptional corepressor. LSD1 specifically demethylates histone H3 lysine 4, which is linked to active transcription. | SIGNOR-264508 |
Q00987 | P25098 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | Our findings show that the signals enabling activity of the GRK2/MST2/Nek2A axis for separation also switches on Mdm2 degradation of GRK2 to ensure accurate centrosome dynamics and proper mitotic spindle functionality.|Our results show now that EGF-induced phosphorylation of GRK2 on S670 is a key event in initiating centrosome separation and also a relevant clue for limiting centrosome separation, as this event simultaneously triggers the Mdm2-dependent ubiquitination and degradation of GRK2 ( xref ). | SIGNOR-278629 |
P51955 | P51955 | 2 | phosphorylation | up-regulates | 0.2 | Enzymatic activity, induced; | SIGNOR-151763 |
P17612 | Q16790 | 1 | phosphorylation | up-regulates | 0.2 | Here, we report that thr443 phosphorylation at the intracellular domain of ca ix by protein kinase a (pka) is critical for its activation in hypoxic cells, with the fullest activity of ca ix also requiring dephosphorylation of ser448. | SIGNOR-176973 |
P13385 | P01137 | 1 | binding | down-regulates activity | 0.2 | Ere, we provide evidence supporting a novel mechanism in which Cripto inhibits the tumor suppressor function of TGF-beta. Cripto bound TGF-beta and reduced the association of TGF-beta with its type I receptor, TbetaRI. | SIGNOR-150006 |
Q00535 | Q15833 | 1 | phosphorylation | down-regulates | 0.2 | It was shown that munc18 inhibition of neuronal syntaxin 1 can be overcome by cdk5 phosphorylation, indicating that structural change disrupts the syntaxin-munc18 interaction. | SIGNOR-157528 |
P17612 | P35367 | 1 | phosphorylation | down-regulates | 0.2 | Two amino acid residues (ser396, ser398) on hr1 were determined to be pkc phosphorylation sites by in vitro phosphorylation studies.Site-directed mutagenesis studies suggests that the ser398 residue was primarily involved in pkc-mediated desensitization. Possibly, phosphorylation of the residues is required for receptor transport from endosomes to lysosomes. | SIGNOR-128411 |
P11362 | P0C6X7-PRO_0000037310 | 1 | chemical inhibition | down-regulates activity | 0.2 | Pyrimidine 13 showed good potency against all the human VEGFR receptors with an IC50 of 10, 30, and 47 nM for VEGFR-1, -2, and -3, respectively. Significant activity was also seen against the closely related tyrosine receptor kinases PDGFRβ, c-Kit, FGF-R1, and c-fms with IC50’s of 84, 74, 140, and 146 nM, respectively. | SIGNOR-260150 |
Q15759 | Q15672 | 1 | phosphorylation | up-regulates | 0.2 | Phosphorylation of serine 68 of twist1 by mapks stabilizes twist1 protein and promotes breast cancer cell invasiveness. this ser 68 is phosphorylated by p38, c-jun n-terminal kinases (jnk), and extracellular signal-regulated kinases1/2 in vitro | SIGNOR-173405 |
P56945 | Q6P5Z2 | 1 | binding | up-regulates activity | 0.2 | Taken together, the data suggest that p130Cas expression induces PKN3 activation and this activation is independent of p130Cas–PKN3 interaction. | SIGNOR-264573 |
Q8NG31 | O43683 | 1 | binding | up-regulates | 0.2 | Association of the amino and middle domain of blinkin with the tpr domains in the amino termini of bubr1 and bub1 is essential for bubr1 and bub1 to execute their distinct mitotic functions | SIGNOR-158378 |
P67775 | Q9UPZ9 | 1 | dephosphorylation | down-regulates | 0.2 | In addition, mass spectrometry showed that pp2a treatment completely abolished the dually phosphorylated form, leaving only the singly phosphorylated form (data not shown). We conclude that a portion of ick in unstimulated and asynchronized hek293t cells is dually phosphorylated on the tdy motif. | SIGNOR-138432 |
Q9H4B4 | P15336 | 1 | phosphorylation | up-regulates | 0.2 | Phosphorylation of thr-69 by mapk14 and mapk11, and at thr-71 by mapk1/erk2, mapk3/erk1, mapk11, mapk12 and mapk14 in response to external stimulus like insulin causes increased transcriptional activity. | SIGNOR-163274 |
Q14774 | P05412 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | In this study, we have identified cell cycle regulatory genes as downstream targets of the homeobox gene HLX in cultured trophoblast cells, namely RB1, MYC, EGR1, CDKN1C, ELK1, CCNB1, and JUN. RB1 and MYC mRNA expression was increased with HLX inactivation, whereas EGR1, CDKN1C, ELK1, CCNB1, and JUN mRNA expression was decreased compared with mock-transfected control cells. | SIGNOR-261623 |
Q02763 | Q02763 | 2 | phosphorylation | down-regulates activity | 0.2 | The Tie2 nucleotide binding loop is in an inhibitory conformation, which is not seen in other kinase structures, while its activation loop adopts an activated-like conformation in the absence of phosphorylation. Tyr-897, located in the N-terminal domain, may negatively regulate the activity of Tie2 by preventing dimerization of the kinase domains or by recruiting phosphatases when it is phosphorylated. | SIGNOR-246662 |
Q99720 | Q9NZQ7 | 1 | stabilization | up-regulates quantity by stabilization | 0.2 | We propose that Sigma1 is a ligand-operated scaffolding protein that promotes the stability, processing, assembly, and trafficking of specific proteins in the secretory pathway of cancer cells. In support of this hypothesis, we found that siRNA-mediated knockdown of Sigma1 resulted in a significant decrease in PD-L1 protein levels in triple-negative MDA-MB-231 breast cancer and androgen-independent PC3 prostate cancer cells | SIGNOR-274974 |
Q9UNW8 | 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-257275 |
Q12857 | P54756 | 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-268895 |
Q14344 | O95835 | 1 | phosphorylation | down-regulates activity | 0.2 | These findings suggest that Galpha13 induced phosphorilation of LATS1 at S909 recruits ITCH to trigger LATS1 degradation, leading to EMT-related phenotypes | SIGNOR-278051 |
P05771 | Q14847 | 1 | phosphorylation | down-regulates activity | 0.2 | Actin binding of human lim and sh3 protein is regulated by cgmp- and camp-dependent protein kinase phosphorylation on serine 146. Phosphorylation of lasp at ser-146 leads to a redistribution of the actin-bound protein from the tips of the cell membrane to the cytosol, accompanied with a reduced cell migration | SIGNOR-97942 |
Q9H0K1 | O75581 | 1 | phosphorylation | up-regulates activity | 0.2 | Mechanistically, SIK2, phosphorylated by CK1α, directly phosphorylated LRP6 in a SIK2 kinase activity-dependent manner, leading to Wnt/β-catenin signaling pathway activation. | SIGNOR-275399 |
Q16539 | Q9H1K0 | 1 | phosphorylation | up-regulates | 0.2 | We found that p38alpha can phosphorylate the rab5 effectors eea1 and rabenosyn-5 on thr-1392 and ser-215, respectively, and these phosphorylation events regulate the recruitment of eea1 and rabenosyn-5 to membranes | SIGNOR-140143 |
P04899 | O95379 | 1 | binding | up-regulates activity | 0.2 | TNFAIP8: a new effector for Galpha(i) coupling to reduce cell death and induce cell transformation | SIGNOR-256492 |
P09619 | P09619 | 2 | phosphorylation | up-regulates activity | 0.2 | We used two platelet-derived growth factor beta-receptor (beta-PDGFR) mutants to identify events that are required for full engagement (autophosphorylation and activation of the kinase activity) of the beta-PDGFR kinase. The F79/81 receptor (Tyr to Phe substitution at 579 and 581 in the juxtamembrane domain of the receptor) was capable of only very modest ligand-dependent autophosphorylation and also failed to associate with numerous SH2 domain-containing proteins. | SIGNOR-250254 |
Q86TM6 | Q16236 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | NRF2 is negatively regulated by three E3 ubiquitin ligase complexes: the KEAP1-CUL3-RBX1 complex, the β-TrCP-SKP1-CUL1-RBX1 complex, and HRD1. | SIGNOR-267360 |
Q13177 | Q13177 | 2 | phosphorylation | up-regulates activity | 0.2 | Eight autophosphorylation sites were identified in Cdc42-activated gamma-PAK, six of which are in common with those previously reported in alpha-PAK, while Ser-19 and Ser-165 appear to be uniquely phosphorylated in the gamma-form. Further, the phosphorylation of Ser-141, Ser-165, and Thr-402 was found to correlate with gamma-PAK activation. Autophosphorylation of γ-PAK with MgATP alone takes place at Ser-19, Ser-20, Ser-55, Ser-192, and Ser-197. | SIGNOR-250227 |
Q00535 | Q96RR4 | 1 | phosphorylation | down-regulates | 0.2 | Cdk5 and gsk3 phosphorylate ser-129, ser-133, and ser-137. Mutation of ser-129, ser-133, and ser-137 increases autonomous activity with little change in ca2 /cam-dependent activity. | SIGNOR-198111 |
Q05655 | P23396 | 1 | phosphorylation | up-regulates activity | 0.2 | Here we show that PKCδ phosphorylates rpS3 resulting in its mobilization in the nucleus to repair damaged DNA | SIGNOR-260895 |
P54753 | P54753 | 2 | phosphorylation | up-regulates activity | 0.2 | Tyrosine-614, the major autophosphorylation site of the receptor tyrosine kinase HEK2, functions as multi-docking site for SH2-domain mediated interactions. a single amino acid substitution (Y614F) clearly reduces the phosphotyrosine content of HEK2 and abrogates its ability to bind rasGAP, Crk and Fyn indicating that this residue functions as major phosphorylation and multi-docking site. | SIGNOR-251126 |
O95684 | Q15691 | 1 | relocalization | up-regulates | 0.2 | Fop also binds to eb1 and is required for localizing eb1 to the centrosome | SIGNOR-142400 |
Q9H2X6 | O15379 | 1 | phosphorylation | down-regulates activity | 0.2 | Mechanistically, HIPK2 bound and phosphorylated histone deacetylase 3 (HDAC3) at serine 374 to inhibit its enzymatic activity, thus reducing the deacetylation of p65 at lysine 218 to suppress NF-κB activation. | SIGNOR-277568 |
O15530 | O15530 | 2 | phosphorylation | down-regulates quantity by destabilization | 0.2 | PDK1 kinase activity is negatively regulated by binding to 14-3-3 through the PDK1 autophosphorylation site Ser-241. PDK1 binds to 14-3-3 in vivo and in vitro through the residues surrounding the autophosphorylation site Ser-241 and that the association is achieved only when Ser-241 has been phosphorylated | SIGNOR-250077 |
Q14689 | Q14247 | 1 | acetylation | up-regulates activity | 0.2 | DIP2A binds to cortactin and modulates cortactin acetylation. Autism candidate gene disconnected-interacting protein homolog 2 A (DIP2A) is known to be involved in acetylated coenzyme A (Ac-CoA) synthesis and is primarily expressed in the brain regions with abundant pyramidal neurons. We further identified that DIP2A interacted with cortactin, an activity-dependent spine remodeling protein. The binding activity of DIP2A-PXXP motifs (P, proline; X, any residue) with the cortactin-Src homology 3 (SH3) domain was critical for maintaining the level of acetylated cortactin. | SIGNOR-266589 |
Q02156 | Q02156 | 2 | phosphorylation | down-regulates | 0.2 | Protein kinase-inactive mutants of pkcepsilon were not phosphorylated at ser(729) in cells, and phosphorylation of this site leads to dephosphorylation of the activation-loop thr(566) | SIGNOR-117324 |
P27361 | O14994 | 1 | phosphorylation | up-regulates | 0.2 | A rare, missense polymorphism, s470n, was identified in the synapsin iii gene and appeared more frequently in individuals with schizophrenia than in controls. Ser470, was determined to be a substrate for mitogen-activated protein kinase, a downstream effector of neurotrophin action. | SIGNOR-121402 |
P41279 | Q01970 | 1 | phosphorylation | up-regulates activity | 0.2 | Additionally, we found that PAR1-induced Ca2+ signals are transduced through Tpl2, which activates phospholipase C\u03b23 by phosphorylation at Ser537.|These findings raised the question whether Tpl2, which phosphorylates PLCbeta 3 at Ser537 (this report) regulates Ca 2+ signaling in thrombin stimulated cells through phosphorylation of PLCbeta 3 at this site. | SIGNOR-278519 |
Q03112 | Q15389 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | We finally observed that the forced expression of Evi1 induced GATA-2 expression in a hematopoietic cell line, EML C1, along with GATA-1, Ang-1, Ang-2 and Tie2 | SIGNOR-266059 |
Q9BV73 | Q68D86 | 1 | relocalization | up-regulates activity | 0.2 | CCDC102B is recruited to the centrosome by C-Nap1 (also known as CEP250) and interacts with the centrosome linker components rootletin and LRRC45. CCDC102B decorates and facilitates the formation of rootletin filaments. Furthermore, CCDC102B is phosphorylated by Nek2A (an isoform encoded by NEK2) and is disassociated from the centrosome at the onset of mitosis. | SIGNOR-275625 |
Q9UQM7 | Q05682 | 1 | phosphorylation | down-regulates | 0.2 | Smooth muscle caldesmon was phosphorylated by smooth muscle calmodulin-dependent protein kinase. Ii | SIGNOR-22635 |
O14920 | O14920 | 2 | phosphorylation | down-regulates activity | 0.2 | Once activated, IKKbeta autophosphorylated at a carboxyl-terminal serine cluster. Such phosphorylation decreased IKK activity and may prevent prolonged activation of the inflammatory response. | SIGNOR-251278 |
P0DTD1-PRO_0000449619 | P15880 | 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-262508 |
P68400 | Q14940 | 1 | phosphorylation | down-regulates activity | 0.2 | CK2 phosphorylation of an acidic Ser/Thr di-isoleucine motif in the Na+/H+ exchanger NHE5 isoform promotes association with beta-arrestin2 and endocytosis | SIGNOR-276250 |
Q99677 | 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-257057 |
Q9HCK8 | P41225 | 1 | transcriptional regulation | down-regulates quantity | 0.2 | Many of the most significantly up-regulated genes in Chd8+/− and Chd8−/− NPCs are involved in later stages of neuronal development, including Ascl1 [a central driver of neural reprogramming (29)], Dcx, Map2, Nefm, Neurod4, and Neurog1 (Fig. 2 E and F). Additionally, we found that Sox3 is derepressed in both Chd8+/− and Chd8−/− NPCs, and several other Sox TF members (Sox2, Sox7, and Sox11) became derepressed in the Chd8−/− cells | SIGNOR-268920 |
Q9NR48 | P68431 | 1 | trimethylation | up-regulates activity | 0.2 | We show that human ASH1L specifically methylates histone H3 Lys-36. Our data implicate that there may be a regulatory mechanism of ASH1L histone methyltransferases | SIGNOR-269055 |
Q96GD4 | Q8TF76 | 1 | phosphorylation | up-regulates activity | 0.2 | Phosphorylation by Aurora B is required for full Haspin activity toward H3T3 in mitosis | SIGNOR-262657 |
P53779 | P63104 | 1 | phosphorylation | down-regulates | 0.2 | Jnk phosphorylates 14-3-3zetaat ser-184 and 14-3-3sigmaat ser-190 | SIGNOR-124009 |
Q3MIX3 | P48436 | 1 | phosphorylation | up-regulates activity | 0.2 | Here we investigated the mechanism of ADCK5 involved in regulating invasion and migration of lung cancer cells, and showed that ADCK5 might regulate the expression of tumor oncogene human pituitary tumor transforming gene-1 (PTTG1) by phosphorylating transcription factor SOX9|Mutagenesis of potential serine phosphorylation sites on SOX9 indicated that serine 181 might be required to maintain transcription activation of SOX9 as well as increase PTTG1 levels. | SIGNOR-264567 |
P27361 | C9JLW8 | 1 | phosphorylation | down-regulates activity | 0.2 | When phosphorylated by ERK, MCRIP1 dissociates from CtBP, allowing CtBP to interact with ZEB1. In this manner, the CtBP co-repressor complex is recruited to, and silences, the E-cadherin promoter by inducing chromatin modifications.| While substitution of S4 or S18 with Ala did not affect the phosphorylation of MCRIP1 by ERK, substitution of either S21 or T30 significantly reduced MCRIP1 phosphorylation | SIGNOR-264772 |
P29350 | P63261 | 1 | dephosphorylation | down-regulates | 0.2 | Our data suggest that shp-1 plays a pivotal role in reorganization of cytoskeletal architecture inducing actin dephosphorylation. These results clearly demonstrate the direct interaction of shp-1 with actin | SIGNOR-99565 |
Q01974 | Q01974 | 2 | binding | up-regulates | 0.2 | Wnt5a induces homodimerization and activation of ror2 receptor tyrosine kinase | SIGNOR-199588 |
P49758 | P05106 | 1 | binding | down-regulates | 0.2 | Numb binds to integrin-betas and localizes to clathrin-coated structures | SIGNOR-156762 |
O43318 | P62820 | 1 | phosphorylation | up-regulates activity | 0.2 | TAK1 preferentially phosphorylates the inactive (GDP-bound) state of Rab1. Phosphorylation of Rab1 disrupts interaction with GDP dissociation inhibitor 1 (GDI1), but not guanine exchange factor (GEF) or GTPase-activating protein (GAP) enzymes, and is exclusive to membrane-localized Rab1, suggesting phosphorylation may stimulate Rab1 membrane association. Furthermore, we found phosphorylation of Rab1 at T75 to be essential for Rab1 function. | SIGNOR-277270 |
Q92585 | O60563 | 1 | relocalization | up-regulates | 0.2 | Cycc:cdk8 and cyct1:cdk9/p-tefb are recruited with notch and associated coactivators (mam, skip) to the hes1 promoter in signaling cells. | SIGNOR-130712 |
P29597 | P29597 | 2 | phosphorylation | up-regulates activity | 0.2 | These results indicate that tyk2 is activated by phosphorylation on tyr-1054 and/or tyr-1055The K930R mutant, bearing a mutation in the ATP binding site, is catalytically inactive (Fig. 3B, lanes 5 and 6). This protein is not basally phosphorylated, while the wt and the Y1054F/Y1055F proteins are (Fig. 3A), suggesting that autophosphorylation is responsible for the basal level of phosphorylation. | SIGNOR-43092 |
P49116 | P22888 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Functional analysis showed that EAR2 and EAR3/COUP-TFI repressed the hLHR promoter activity, whereas TR4 activated hLHR gene transcription. | SIGNOR-266217 |
Q13153 | Q13352 | 1 | phosphorylation | up-regulates | 0.2 | Serine 28 phosphorylation of nrif3 confers its co-activator function for estrogen receptor-alpha transactivation. p21-activated protein kinase 1 (pak1) phosphorylates eralpha at ser305 and this modification is important in eralpha transactivation function. | SIGNOR-178795 |
Q969V6 | P11831 | 1 | binding | up-regulates | 0.2 | Similarly, the myocd-related transcription factor (mrtf) family of proteins, mrtf-a and mrtf-b, are also involved in the transcriptional regulation of contractile gene markers as coactivators of srf. | SIGNOR-174264 |
O60674 | Q92915 | 1 | phosphorylation | up-regulates activity | 0.2 | JAK2 regulates Nav1.6 channel function via FGF14Y158 phosphorylation|Patch-clamp electrophysiology revealed that through Y158, JAK2 controls FGF14-dependent modulation of Nav1.6 channels. In hippocampal CA1 pyramidal neurons, the JAK2 inhibitor Fedratinib reduced firing by a mechanism that is dependent upon expression of FGF14. | SIGNOR-275747 |
P59595 | P16220 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | The transcription factors c-Fos, FosB, CREB-1, and ATF2 were all activated by the addition of SARS-CoV N protein to the sample well | SIGNOR-260729 |
P16066 | P02763 | 1 | phosphorylation | up-regulates activity | 0.2 | On TORC1 inhibition by rapamycin treatment or nutrient limitation, Npr1 phosphorylates and activates Orm1 and Orm2, which in turn promotes synthesis of complex sphingolipids downstream of SPT.|Thus Npr1 directly phosphorylates Orm1 and Orm2 downstream of TORC1. | SIGNOR-278966 |
P17252 | Q6ZN44 | 1 | phosphorylation | down-regulates quantity | 0.2 | We show that protein interacting with C-kinase 1 (PICK1) recruits activated protein kinase Cα (PKCα) to MycUNC5A at the plasma membrane, stimulating its endocytosis. We identify two PKCα phosphorylation sites at serines 408 and 587, as well as dileucine internalization motifs, which are required for this endocytosis. | SIGNOR-268180 |
Q2TAL8 | Q9Y2Z4 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress. | SIGNOR-269413 |
P17252 | O14986 | 1 | phosphorylation | down-regulates | 0.2 | Collaboration of ampk and pkc to induce phosphorylation of ser413 on pip5k1b resulting in decreased kinase activity and reduced ptdins(4,5)p2 synthesis in response to oxidative stress and energy restriction. we demonstrate that pkc can directly phosphorylate ser413 in vitro | SIGNOR-194820 |
Q9UQM7 | Q9P0L9 | 1 | phosphorylation | down-regulates activity | 0.2 | CaM inhibits the function of TRPP3 through promoting CaMK2's phosphorylation towards T591 on TRPP3. | SIGNOR-277812 |
Q92918 | Q92918 | 2 | phosphorylation | up-regulates | 0.2 | Activation of hematopoietic progenitor kinase 1 involves relocation, autophosphorylation, and transphosphorylation by protein kinase d1. | SIGNOR-134490 |
Q9H992 | Q15051 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | MARCH7 induces K48 ubiquitination of NPHP5 and protein degradation, while BBS11 triggers K63 ubiquitination and protein delocalization.|Unlike the catalytically inactive mutant , wild type MARCH7 was able to trigger NPHP5 ubiquitination (XREF_FIG). | SIGNOR-278585 |
Q9Y5H9 | Q9Y5G8 | 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-265695 |
P17252 | Q8NFA2 | 1 | phosphorylation | up-regulates | 0.2 | Phosphorylation of thr341 allows noxo1 to sufficiently interact with noxa1, an interaction that participates in nox1 activation. | SIGNOR-202482 |
P17655 | P49840 | 1 | cleavage | up-regulates activity | 0.2 | Thus, it has been shown that calpain cleaves the inhibitory domain of GSK3 generating two fragments of 40 and 30 kDa. This cleavage enhanced activity of the kinase | SIGNOR-251612 |
Q02156 | Q16625 | 1 | phosphorylation | up-regulates | 0.2 | Thr403, thr404, thr424 and thr438 in the occludin c-terminal domain are the predominant sites of pkc_-dependent phosphorylation . The present study demonstrates that pkc_ phosphorylates occludin on specific threonine residues and promotes assembly of epithelial tight junctions. | SIGNOR-173643 |
P36873 | P50750 | 1 | dephosphorylation | up-regulates | 0.2 | Pp1 is an activator of cdk9. Pp1 dephosphorylates cdk9 thr186. | SIGNOR-173454 |
P07333 | P07333 | 2 | phosphorylation | down-regulates | 0.2 | Csf-1-mediated wild-type (wt)-csf-1r phosphorylation was not markedly affected by sfk inhibition, indicating that lack of sfk binding is not responsible for diminished y559f phosphorylation. Unexpectedly, cells expressing y559f were hyperproliferative in response to csf-1. Hyperproliferation correlated with prolonged activation of akt, erk, and stat5 in the y559f mutant. Consistent with a defect in receptor negative regulation, c-cbl tyrosine phosphorylation and csf-1r/c-cbl co-association were almost undetectable in the y559f mutant. Furthermore, y559f underwent reduced multiubiquitination and delayed receptor internalization and degradation. In conclusion, we propose that tyr559 is a switch residue that functions in kinase regulation, signal transduction and, indirectly, receptor down-regulation. | SIGNOR-127622 |
P48730 | O75581 | 1 | phosphorylation | up-regulates activity | 0.2 | Central to WNT signalosome formation is phosphorylation of LRP6 at multiple sites, with GSK3β phosphorylating LRP6 at S1490 and CK1 family members phosphorylating LRP6 at T1479 and T1493 | SIGNOR-275402 |
Q86V86 | 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-273897 |
P78527 | P54619 | 1 | phosphorylation | up-regulates activity | 0.2 | PRKDC interacted with the AMPK complex and phosphorylated its nucleotide-sensing γ1 subunit PRKAG1/AMPKγ1 at Ser192 and Thr284, both events being significantly reduced upon the activation of the AMPK complex. Alanine substitutions of PRKDC phosphorylation sites in PRKAG1 reduced AMPK complex activation without affecting its nucleotide sensing capacity. | SIGNOR-277503 |
P59595 | P15336 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | The transcription factors c-Fos, FosB, CREB-1, and ATF2 were all activated by the addition of SARS-CoV N protein to the sample well | SIGNOR-260727 |
P49336 | P84243 | 1 | phosphorylation | down-regulates activity | 0.2 | However, within T/G-Mediator, cdk8 phosphorylates serine-10 on histone H3, which in turn stimulates H3K14 acetylation by GCN5L within the complex. Tandem phosphoacetylation of H3 correlates with transcriptional activation, and ChIP assays demonstrate co-occupancy of T/G-Mediator components at several activated genes in vivo. | SIGNOR-273173 |
Q01813 | Q9Y4P1 | 1 | phosphorylation | up-regulates activity | 0.2 | In vitro kinase assay validated that PFKP functioning as a protein kinase phosphorylated ATG4B at S34. This phosphorylation could enhance ATG4B activity and p62 degradation. In addition, PFKP S386 phosphorylation was important to ATG4B S34 phosphorylation and autophagy in HEK293T cells. | SIGNOR-275832 |
P67775 | P84022 | 1 | dephosphorylation | down-regulates | 0.2 | Accordingly, smad3-associated pp2a activity was found under hypoxic conditions. Hypoxia attenuated the nuclear accumulation of tgf-beta-induced smad3 but did not affect smad2. Moreover, the influence of tgf-beta on a set of smad3-activated genes was attenuated by hypoxia, and this was reversed by chemical pp2a inhibition. Our data demonstrate the existence of a smad3-specific phosphatase and identify a novel role for pp2a. | SIGNOR-167480 |
Q05513 | P27448 | 1 | phosphorylation | down-regulates | 0.2 | Hpar-1a, t564, is phosphorylated in vivo and by apkc in vitro.This study establishes a novel functional link between two central determinants of cellular polarity, apkc and par-1, and suggests a model by which apkc may regulate par-1 in polarized cells | SIGNOR-124221 |
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