IdA stringlengths 6 21 | IdB stringlengths 6 21 | labels int64 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 |
|---|---|---|---|---|---|---|---|
P17861-2 | P18850 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.654 | Apart from ER protein chaperones, ATF6 also induces the expression of CHOP and XBP1, thereby connecting the three UPR branches into an integrated signaling network | SIGNOR-260184 |
P00441 | Q9BUN8 | 2 | binding | down-regulates activity | 0.457 | Various proteins involved in ERAD have been identified recently (Meusser et al. 2005). Among them, components of the retro-translocation machinery including ATPase p97, its cofactors Ufd1 and Npl4, and the ER membrane proteins Derlin-1 and VIMP are of key importance to ERAD function |Here we show that SOD1(mut) specifically interacted with Derlin-1, a component of endoplasmic reticulum (ER)-associated degradation (ERAD) machinery and triggered ER stress through dysfunction of ERAD. | SIGNOR-262785 |
P25103 | P38405 | 2 | 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-256919 |
Q9Y6D6 | P17612 | 0 | phosphorylation | up-regulates activity | 0.2 | Within 20 min after addition of 8-Br-cAMP, BIG1 accumulated in nuclei, and this effect was blocked by protein kinase A (PKA) inhibitors H-89 and PKI, suggesting a dependence on PKA-catalyzed phosphorylation. |Mutant BIG1 (S883A) in which Ala replaced Ser-883, a putative PKA phosphorylation site, did not move to the nucleus with cAMP addition, whereas replacement with Asp (S883D) resulted in nuclear accumulation of BIG1 without or with cAMP exposure, consistent with the mechanistic importance of a negative charge at that site | SIGNOR-272146 |
P05198 | P49770 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.802 | EIF2B converts the protein synthesis initiation factor 2 (eIF2) from an inactive GDP-bound form to an active eIF2-GTP complex owing to its guanine nucleotide exchange factor (GEF) activity. | SIGNOR-269125 |
P29274 | P63096 | 2 | binding | up-regulates activity | 0.273 | 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-257038 |
Q9BXM7 | P61006 | 1 | phosphorylation | down-regulates activity | 0.271 | For Rab8a, it was shown that serine 111 phosphorylation (pS111) is dependent on the protein kinase PINK1 and that mimicking the phosphorylation at S111 by a serine/glutamate substitution (S111E) impaired Rab8a activation by its cognate nucleotide exchange factor (GEF) Rabin8. | SIGNOR-260268 |
P01112 | P49356 | 0 | null | up-regulates activity | 0.46 | 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-242565 |
Q01344 | P05113 | 2 | binding | up-regulates | 0.883 | Single chain and wt il5 also had similar binding affinity for soluble il5 receptor alpha chain, the specificity subunit of the il5 receptor, as measured kinetically with an optical biosensor. | SIGNOR-40039 |
Q9ULB4 | P35222 | 2 | binding | up-regulates activity | 0.586 | At its C-terminus, cadherin interacts with β-catenin, which dynamically associates with α-catenin, a direct binding partner of filamentous actin | SIGNOR-265871 |
Q969H4 | P12931 | 0 | phosphorylation | up-regulates activity | 0.506 | We identified Tyr 26 as a PDGF-induced and, additionally, Tyr 519 and Tyr 665 as SRC-induced tyrosine phosphorylation sites. Phosphomimetic mutants indicate that phosphorylation of Tyr 519 recruits CNK1 to the nucleus and additional phosphorylation of Tyr 26 enables CNK1 to promote SRE-dependent gene expression. | SIGNOR-275918 |
P09874 | Q00535 | 0 | phosphorylation | down-regulates activity | 0.258 | These results would suggest that the phosphorylation of PARP-1 via Cdk5's kinase activity is necessary for its persistence at damage sites.Based on these results and the recruitment data, we hypothesize that the phosphorylation of the PARP-1 protein by Cdk5 on one or more of the serines 782, 785, and 786 results in an attenuation of its ribosylating activity facilitating its persistence at the sites of DNA damage. | SIGNOR-276359 |
Q09472 | Q9UPG8 | 1 | acetylation | up-regulates | 0.2 | Plag1 and plagl2 are also regulated by acetylation. They are acetylated and activated by p300 and deacetylated and repressed by hdac7. | SIGNOR-140947 |
P20393 | O00327 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.671 | In this study, we found that NPAS2, like BMAL1, is a direct target gene of RORα and REV-ERBα. it appears in the context of the NPAS2 promoter RORα functions as a transcriptional activator, but REV-ERBα may only function as an inhibitor of RORα activity by blocking binding. | SIGNOR-267983 |
P07948 | Q01344 | 1 | phosphorylation | up-regulates activity | 0.475 | Lyn activate and expand IL-5RA intracellular signaling through FIP1L1-PDGFRA/JAK2/Lyn/Akt network complex, provoking eosinophils proliferation and exaggerated activation manifested as CEL.|We further delineated that Lyn can induce IL-5RA tyrosine phosphorylation and physically associate with IL-5RA in F/P expressing cells. | SIGNOR-279059 |
Q9Y5A7 | Q00987 | 0 | ubiquitination | up-regulates activity | 0.276 | Our results rather suggest that Mdm2 specifically ubiquitinates NUB1 on lysine 159 and that this modification is required for NUB1 functions.|We conclude that Mdm2 acts as a positive regulator of NUB1 function, by modulating NUB1 ubiquitination on lysine 159. | SIGNOR-278556 |
P00519 | P18031 | 0 | dephosphorylation | down-regulates | 0.612 | These results illustrate selectivity in the effects of ptps in a cellular context and suggest that ptp1b may function as a specific, negative regulator of p210 bcr-abl signalling in vivo. | SIGNOR-56815 |
O15294 | Q9NZJ5 | 0 | phosphorylation | up-regulates activity | 0.2 | Collectively, these results indicate that upon cold and \u03b2-adrenergic stimulation PERK-activated OGT catalyzes the O-GlcNAcylation of CK2\u03b1 and TOM70 which enhances MIC19 import into the mitochondria increasing cristae formation and cell respiration (Figure 7I).|Here, we report that the ER-resident kinase PERK is activated upon cold or \u03b2-adrenergic stimulation and directly phosphorylates OGT. | SIGNOR-279736 |
P22681 | P10721 | 2 | ubiquitination | down-regulates activity | 0.618 | KIT binds to and induces the phosphorylation of Cbl proteins, which in turn act as E3 ligases, mediating the ubiquitination and degradation of KIT and themselves. Tyrosine kinase binding and RING finger domains of Cbl are essential for Cbl-mediated ubiquitination and degradation of KIT. | SIGNOR-260104 |
P25116 | P19086 | 2 | binding | up-regulates activity | 0.447 | 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-257127 |
Q13535 | P23025 | 1 | phosphorylation | up-regulates activity | 0.492 | ATR mediated phosphorylation of XPA on S196 enhances cAMP-mediated optimization of NER, and is promoted by SIRT1-mediated deacetylation of XPA on K63, K67 and K215. | SIGNOR-258985 |
Q9NP97 | P17612 | 0 | 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 |
O43353 | O43353 | 2 | phosphorylation | up-regulates activity | 0.2 | In summary, our results indicate that s176 is a regulatory autophosphorylation site for rip2 and that s176 phosphorylation can be used to monitor the activation state of rip2. | SIGNOR-229701 |
Q13237 | P48764 | 1 | phosphorylation | down-regulates activity | 0.377 | CGMP and cGKII increased NHE3 phosphorylation at three sites (rabbit Ser (554), Ser (607), and Ser (663), equivalent to mouse Ser (552), Ser (605), and Ser (659)), all of which had to be present at the same time for cGMP to inhibit NHE3.|cGMP and cGKII rapidly inhibited NHE3, which was associated with reduced surface NHE3. | SIGNOR-280096 |
Q05655 | Q6NXT1 | 1 | phosphorylation | up-regulates activity | 0.2 | The mechanism by which phosphorylation of Ankrd54 by PKC\u03b4 enhances cytoplasmic accumulation of Ankrd54 and its interaction with Lyn remains to be determined.|This revealed, in agreement with the biochemical analysis, that PKCdelta significantly promotes cytoplasmic accumulation of Ankrd54. | SIGNOR-279259 |
Q01970 | Q13237 | 0 | phosphorylation | down-regulates activity | 0.525 | PKG can directly phosphorylate PLC-beta2 and PLC-beta3 in vitro with purified proteins and in vivo with metabolic labeling. Phosphorylation of PLC-beta leads to the inhibition of G-protein-activated PLC-beta3 activity by 50-70% in COS-7 cell transfection assays. By using phosphopeptide mapping and site-directed mutagenesis, we further identified two key phosphorylation sites for the regulation of PLC-beta3 by PKG (Ser(26) and Ser(1105)). Mutation at these two sites (S26A and S1105A) of PLC-beta3 completely blocked the phosphorylation of PLC-beta3 protein catalyzed by PKG. | SIGNOR-249078 |
Q9UNE7 | Q13950 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.407 | Here, we show that CHIP promotes Runx2 ubiquitination and degradation and thereby negatively regulates osteoblast differentiation. | SIGNOR-278600 |
Q86U44 | P27361 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.271 | Mass spectrometry analysis showed that ERK phosphorylates METTL3 at three highly conserved residues: S43, S50, and S525 (Figures 2D and 2E). Mutational analysis further confirmed these three sites as main ERK phosphorylation sites (Figure 2F). Phosphorylation of METTL3 increases interaction with USP5, decreasing ubiquitination to stabilize the m6 A methyltransferase complex. | SIGNOR-265949 |
Q13651 | O60674 | 1 | phosphorylation | up-regulates activity | 0.432 | IL10R2 recruits cytoplasmic protein Jak1 followed by phosphorylation of tyrosine at position 705 in the STAT3 (705Y-STAT3) molecule. Phosphorylated STAT3 forms a homodimer, which is then translocated to the nucleus to facilitate transcriptional regulation of target genes. | SIGNOR-249545 |
Q15562 | P46937 | 2 | binding | up-regulates | 0.884 | When dephosphorylated, yap/taz enter nuclei and induce gene transcription by interacting with transcription factors tead14. | SIGNOR-201468 |
P49585 | Q02447 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Sp1 and Sp3 function as transcriptional activators of the Ctpct promoter | SIGNOR-266232 |
O00401 | Q07912 | 0 | phosphorylation | up-regulates activity | 0.307 | Because TNK2 phosphorylation of WASL increases its actin nucleation activity ( xref ), we reasoned that it might be possible to complement the TNK2 deficiency by overexpression of WASL.|For NCK1, based on its reported binding to WASL and TNK2, we hypothesized that its function is to recruit WASL to TNK2, which could then activate WASL via phosphorylation ( xref ; xref ). | SIGNOR-280155 |
Q969U6 | O00444 | 0 | phosphorylation | down-regulates activity | 0.543 | The activity of SCF-FBXW5 is in turn negatively regulated by Polo-like kinase 4 (PLK4), which phosphorylates FBXW5 at Ser 151 to suppress its ability to ubiquitylate HsSAS-6. | SIGNOR-275476 |
P48736 | P27986 | 2 | binding | up-regulates activity | 0.723 | Signal transduction pathways triggered by Tie2 have been extensively examined. Tyr-1101of Tie2 directly associates in a phosphotyrosine (pTyr)-dependent manner with the p85 regulatory subunit of phosphatidylinositol (PI) 3-kinase, which in turn activate PI 3-kinase, leading to cell motility and survival | SIGNOR-242646 |
P06493 | Q15910 | 1 | phosphorylation | down-regulates | 0.575 | Cdk1, which phosphorylates ezh2 at threonines 345 and 487.Phosphorylation of thr-345 and thr-487 promotes ezh2 ubiquitination and subsequent degradation by the proteasome | SIGNOR-174058 |
P02452 | Q08345 | 2 | binding | up-regulates activity | 0.335 | The Discoidin Domain Receptors (DDRs) constitute a unique set of receptor tyrosine kinases that signal in response to collagen.|Consistent with this view128, we showed that ectopic expression of DDR1b or DDR2 in HT1080 cells elicited a potent growth inhibitory effect only when the cells were cultured on 2D or 3D COL1 matrices, in agreement with previous studies in melanoma48, breast cancer76,78, and lung cancer cells74,75. | SIGNOR-272340 |
O75487 | P41221 | 2 | binding | up-regulates | 0.373 | Gpc4 bound to wnt3a and wnt5a which activate the beta-catenin-dependent and -independent pathways, respectively, and colocalized with wnts on the cell surface. Expression of gpc4 enhanced the wnt3a-dependent beta-catenin pathway and the wnt5a-dependent beta-catenin-independent pathway, and knockdown of gpc4 suppressed both pathways | SIGNOR-195752 |
P49841 | Q9NRR4 | 1 | phosphorylation | up-regulates activity | 0.278 | Our findings suggest that phosphorylation of Drosha at multiple sites including S300 promotes its translocation to the cytoplasm. Interestingly, GSK3beta can phosphorylate Drosha at S300 and S302 in vitro. This has been reported to promote the nuclear localization of Drosha under basal condition (Tang et al., 2011). Thus, it appears that phosphorylation of S300 by GSK3beta and p38 MAPK is involved in opposing processes. | SIGNOR-264846 |
P31751 | P04049 | 1 | phosphorylation | down-regulates activity | 0.451 | Akt (protein kinase b), a member of a different signaling pathway that also regulates these responses, interacted with raf and phosphorylated this protein at a highly conserved serine residue in its regulatory domain in vivo. This phosphorylation of raf by akt inhibited activation of the raf-mek-erk signaling pathway and shifted the cellular response in a human breast cancer cell line from cell cycle arrest to proliferation. | SIGNOR-235678 |
P08887 | O60674 | 1 | phosphorylation | up-regulates activity | 0.569 | On binding of IL-6 to its receptor IL-6R, JAK2 is phosphorylated, then STAT3 is phosphorylated by JAK2 | SIGNOR-254405 |
Q66PJ3 | Q96BR1 | 0 | phosphorylation | down-regulates activity | 0.2 | AIP4 is phosphorylated by CISK in vitro on WW domain residues, which may impact its ability to interact with and ubiquitinate substrate proteins.|Expression of a constitutively active CISK inhibits CXCR4 degradation, possibly by attenuating CXCR4 binding to and ubiquitination by AIP4 and/or modulating the action of AIP4 on a protein involved in CXCR4 endosomal sorting . | SIGNOR-280124 |
Q68DV7 | P12830 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.267 | To identify the E-cadherin ubiquitination site, we individually mutated three lysines in its cytoplasmic domain, including K816A, K855A, and K871A, of which E-cad K816A failed to restore E-cadherin ubiquitination (Additional file xref : Figure S3D), indicating that RNF43 ubiquitinated E-cadherin at the cytoplasmic lysine 816.|Together , these results suggest that RNF43 potentially downregulates E-cadherin in lung adenocarcinoma in the context of c-Src activation . | SIGNOR-278598 |
Q6ZRV2 | P48729 | 2 | binding | up-regulates quantity | 0.387 | We identified members of the FAM83 family of proteins as partners of CK1 in cells. All eight members of the FAM83 family (FAM83A–H) interacted with the α and α-like isoforms of CK1; FAM83A, -B, -E, and -H also interacted with the δ and ε isoforms of CK1. The intrinsic catalytic activity of CK1 is not affected by or required for the association of CK1 with FAM83 proteins. Our findings imply that the DUF1669 domains of FAM83 proteins anchor CK1 α, α-like, δ, and ε isoforms in specific subcellular compartments and potentially mediate their association with substrates. | SIGNOR-273747 |
Q12778 | Q16828 | 0 | dephosphorylation | up-regulates activity | 0.428 | It has been previously demonstrated that MKP-3 dephosphorylates FOXO1 on Ser256 and promotes nuclear translocation of FOXO1 , which subsequentially binds to the promoters of gluconeogenic genes and turns on the gluconeogenic program.|We also reported that MKP-3 can activate FOXO1 by at least dephosphorylating Ser 256, one of the Akt phosphorylation sites xref . | SIGNOR-276983 |
P39905 | P56159 | 2 | binding | up-regulates | 0.8 | A receptor complex comprised of trnr1 (gdnfr alpha) and ret was recently identified and found to be capable of mediating both gdnf and ntn signaling | SIGNOR-49091 |
Q9ULW0 | O14965 | 0 | phosphorylation | up-regulates activity | 0.965 | Here we show that TPX2, a microtubule-bundling protein and activator of Aurora A, plays an important role. TPX2 was phosphorylated by Aurora A during mitosis. Its phospho-null mutant caused short metaphase spindles coupled with low microtubule flux rate. Interestingly, phosphorylation of TPX2 regulated its interaction with CLASP1 but not Kif2a.|This suggests that TPX2 phosphorylation positively regulates the function of CLASP1.| This is in accord with a phosphoproteomics study that identified S121 and S125 as potential phosphorylation sites for Aurora A in mitotic HeLa cells | SIGNOR-265089 |
Q06945 | Q01344 | 2 | binding | up-regulates activity | 0.417 | Sox4 activation by IL-5R_ appears to be direct, with syntenin functioning as an adaptor molecule. Syntenin mediates IL-5induced Sox4 activation. | SIGNOR-223010 |
P04637 | O14980 | 0 | relocalization | down-regulates activity | 0.549 | We identify the major poly(ADP-ribosyl)ated sites of p53 by PARP-1 and find that PARP-1-mediated poly(ADP-ribosyl)ation blocks the interaction between p53 and the nuclear export receptor Crm1, resulting in nuclear accumulation of p53. These findings molecularly link PARP-1 and p53 in the DNA-damage response, providing the mechanism for how p53 accumulates in the nucleus in response to DNA damage.|PARP-1 is super-activated by binding to damaged DNA, and poly(ADP-ribosyl)ates p53. Poly(ADP-ribosyl)ation probably induces a structural change that mask the NES, and thus Crm1 can no longer target p53 to the nuclear export machinery, resulting in accumulation of p53 in the nucleus. | SIGNOR-260067 |
Q92585 | P49841 | 0 | phosphorylation | down-regulates | 0.2 | We found that gsk3beta inhibits maml1 transcriptional activity by directly targeting the n-terminal domain of maml1 | SIGNOR-187896 |
Q5S007 | P61020 | 1 | phosphorylation | up-regulates activity | 0.599 | Using recombinant proteins, we show here that LRRK2 phosphorylates Rab5b at its Thr6 residue in in vitro kinase assays with mass spectrophotometry analysis. Phosphorylation of Rab5b by LRRK2 on the threonine residue was confirmed by western analysis using cells stably expressing LRRK2 G2019S. The phosphomimetic T6D mutant exhibited stronger GTPase activity than that of the wild-type Rab5b. In addition, phosphorylation of Rab5b by LRRK2 also exhibited GTPase activity stronger than that of the unphosphorylated Rab5b protein. | SIGNOR-276873 |
Q14493 | P20671 | 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-265399 |
Q8IYW5 | Q969R5 | 2 | binding | down-regulates quantity | 0.246 | 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-266788 |
O43524 | Q14164 | 0 | phosphorylation | down-regulates | 0.407 | Ikbke phosphorylation and inhibition of foxo3a: a mechanism of ikbke oncogenic functionhere we report that ikbke regulates foxo3a through phosphorylation of foxo3a-ser644. The phosphorylation of foxo3a resulted in its degradation and nuclear-cytoplasmic translocation. | SIGNOR-202054 |
P42575 | P68400 | 0 | phosphorylation | down-regulates | 0.309 | Here we show that protein kinase (pk) ck2 phosphorylates procaspase-2 directly at serine-157. When intracellular pkck2 activity is low or downregulated by specific inhibitors, procaspase-2 is dephosphorylated, dimerized, and activated in a piddosome-independent manner. | SIGNOR-140836 |
P29122 | P04275 | 1 | cleavage | up-regulates activity | 0.293 | Like PACE,PACE4 was able to process pro-vWF to its mature form, and efficient cleavage required both the P4 arginine and the P2 lysine | SIGNOR-260367 |
P07711 | P02818 | 1 | cleavage | down-regulates quantity by destabilization | 0.2 | This study has been undertaken to compare the degradation of BGP by the cysteine proteinases cathepsins L, B, H, S, and the aspartic proteinase cathepsin D. Cathepsins B, L, H, and S readily cleave BGP at the G7-A8 bond; cathepsin L also cleaves at R43-R44; cathepsin B also cleaves at R44-F45; and cathepsin D cleaves only at A41-Y42. | SIGNOR-256322 |
Q969V5 | P31749 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.475 | The results of the functional studies suggest that the degradation of Akt by MULAN suppresses cell proliferation and viability. | SIGNOR-252437 |
P68431 | Q13185 | 2 | binding | up-regulates activity | 0.2 | A core characteristic of heterochromatin is its association with heterochromatin protein 1 (HP1) proteins, a highly conserved family of chromosomal proteins that bind to di- and trimethylated H3K9 via a conserved N-terminal domain called the chromodomain (CD) HP1 proteins are a highly conserved family of eukaryotic proteins that bind to methylated histone H3 lysine 9 (H3K9) and are required for heterochromatic gene silencing. | SIGNOR-264496 |
P08559 | Q16654 | 0 | phosphorylation | down-regulates | 0.686 | Mammalian pyruvate dehydrogenase (?2_2) (e1) is regulated by phosphorylation-dephosphorylation, catalyzed by the e1-kinase and the phospho-e1-phosphatase. | SIGNOR-33201 |
Q14938 | 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-268910 |
P43405 | P19174 | 1 | phosphorylation | up-regulates activity | 0.775 | Syk isolated from antigen receptor-activated B cells phosphorylated PLC-gamma1 on Tyr-771 and the key regulatory residue Tyr-783 in vitro, whereas Lyn from the same B cells phosphorylated PLC-gamma1 only on Tyr-771. | SIGNOR-246576 |
Q16539 | P42224 | 1 | phosphorylation | up-regulates activity | 0.72 | All stats are phosphorylated on at least one serine residue in their tad specifically, ser727 in stats 1 and 3 and ser721 in stat4. Stat serine kinases have been identified through the use of inhibitors, dominant-negative alleles, and in vitro kinase assays. They include mapk (p38mapk: stats 1, 3, 4;erk: stat3, 5;jnk: stat3), pkc_ (stat1, stat3), mtor (stat3), nlk (stat3 (42)), and camkii and ikk_ (stat1 (39, 40, 43)).STAT Serine phosphorylation regulates transcriptional activity (see below). | SIGNOR-154779 |
P54793 | Q96SB4 | 0 | phosphorylation | up-regulates activity | 0.2 | Phosphorylation by SRPK1 drives ASF from the cytosol to the nucleus.|Phosphorylation of ASF by SR protein kinase 1 (SRPK1) in the cytosol results in ASF relocation to the nucleus, whereas phosphorylation of ASF by Clk and Sty releases ASF from speckles and recruits it into nascent transcripts where ASF regulates alternative splicing. | SIGNOR-279765 |
Q14344 | P28336 | 2 | binding | up-regulates | 0.25 | These neuropeptides, including gastrin-releasing peptide, neuromedin b, neurotensin, gastrin, cholecystokinin and arginine vasopressin bind seven transmembrane-spanning receptors that couple to heterotrimeric g proteins. Studies with human small cell lung cancer (sclc) cells support a requirement for balanced signaling through g(q) and g(12/13) proteins leading to intracellular ca2+ mobilization, pkc activation and regulation of the erk and jnk map kinase pathways. | SIGNOR-107028 |
Q9UPZ9 | P22607 | 0 | phosphorylation | down-regulates activity | 0.2 | FGF signaling partially abolished ICK's kinase activity, through FGFR-mediated ICK phosphorylation at conserved residue Tyr15, which interfered with optimal ATP binding. | SIGNOR-277436 |
P63211 | P19174 | 2 | binding | up-regulates | 0.409 | Furthermore, this work suggested that the gbetagamma subunits released upon gi activation activated phospholipase c-gamma (plc-gamma) to produce inositol 3 phosphate (ip3) which would subsequently increase intracellular ca2+ abundance. | SIGNOR-199144 |
O43524 | P31749 | 0 | phosphorylation | down-regulates activity | 0.91 | Akt-dependent phosphorylation of foxo3a (thr32, ser253, and ser315 for human foxo3) enhances foxo3a/14?3?3 Interaction and promotes foxo3a nuclear export to the cytoplasm, resulting in the repression of foxo3a transcriptional function | SIGNOR-252523 |
Q16620 | P18031 | 0 | dephosphorylation | down-regulates activity | 0.38 | Collectively, these data establish a direct enzyme-substrate interaction between PTP1B and phosphorylated Y705/706 (p-Y705/706) TRKB, the critical autophosphorylation sites that mediate BDNF-induced signaling.| Therefore, the data are consistent with a role of PTP1B as an inhibitor of BDNF/TRKB signaling | SIGNOR-264554 |
Q15042 | P20336 | 1 | gtpase-activating protein | down-regulates activity | 0.439 | Rab3A, a member of the Rab3 small G protein family, regulates Ca(2+)-dependent exocytosis of neurotransmitter. The cyclical activation and inactivation of Rab3A are essential for the Rab3A action in exocytosis. GDP-Rab3A is activated to GTP-Rab3A by Rab3 GDP/GTP exchange protein (Rab3 GEP), and GTP-Rab3A is inactivated to GDP-Rab3A by Rab3 GTPase-activating protein (Rab3 GAP). | SIGNOR-265580 |
O60504 | P00519 | 0 | phosphorylation | up-regulates activity | 0.412 | Abl kinase interacts with and phosphorylates vinexin. | SIGNOR-280172 |
O95835 | Q14872 | 1 | phosphorylation | down-regulates activity | 0.2 | The Hippo pathway kinases LATS1 and LATS2 attenuate cellular responses to heavy metals through phosphorylating MTF1|the Hippo pathway kinase LATS phosphorylates and inhibits MTF1|LATS phosphorylates MTF1 at S152 and disrupts its association with the promoters of heavy metal response genes, resulting in the loss of heavy metal response gene expression | SIGNOR-275473 |
P31749 | Q9UHD2 | 0 | phosphorylation | up-regulates | 0.407 | Upon mitogen stimulation, triggering of the innate immune response, re-exposure to glucose, or oncogene activation, tbk1 is recruited to the exocyst, where it activates akt. Akt is a direct tbk1 substrate that connects tbk1 to prosurvival signaling. | SIGNOR-252608 |
Q9NS23 | Q969H4 | 2 | binding | up-regulates | 0.402 | Cnk1 binds to rassf1a and promotes apoptosis through a pathway that requires rassf1a and mst kinases. | SIGNOR-198432 |
Q9NZR2 | O14641 | 2 | binding | down-regulates activity | 0.385 | In this study, we have shown that LRP1B inhibited the activity of beta-catenin/TCF signaling possibly by interacting with DVL2. The molecular mechanism study revealed that LRP1B interacted with DVL2, inhibited the interaction between DVL2 and Axin, and negatively regulated beta-catenin/TCF signaling. | SIGNOR-259090 |
Q969H0 | P24864 | 2 | binding | down-regulates quantity by destabilization | 0.567 | Cdk2 (S384) and GSK3 (T380) prime cyclin E for destruction. The hyper-phosphorylated T380/S384 degron has high affinity for monomeric Fbw7α, which engages the remainder of the SCF to initiate cyclin E's ubiquitination by an E2 enzyme | SIGNOR-271643 |
Q92831 | Q8IXJ6 | 2 | binding | down-regulates | 0.53 | Sir2 forms a complex with the acetyltransferase pcaf and myod and, when overexpressed, retards muscle differentiation. | SIGNOR-104248 |
O15169 | Q6ZNA4 | 2 | binding | up-regulates | 0.642 | Here, we show that axin activates tgf-beta signaling by forming a multimeric complex consisting of smad7 and ubiquitin e3 ligase arkadia. Axin is a scaffold protein in tgf-beta signaling that promotes degradation of smad7 by arkadia. | SIGNOR-119660 |
Q9Y4P1 | O95166 | 1 | cleavage | up-regulates activity | 0.861 | In vivo and in vitro biochemical analyses have shown that human atg4b is an authentic cysteine protease essential for cleavage of the c terminus of each atg8 homolog to expose the c-terminal gly | SIGNOR-141929 |
P45983 | P42226 | 1 | phosphorylation | down-regulates | 0.353 | Deactivation of stat6 through serine 707 phosphorylation by jnk. | SIGNOR-170153 |
P00740 | P03951 | 0 | cleavage | up-regulates activity | 0.484 | Factor XI (FXI) is the zymogen of an enzyme (FXIa) that contributes to hemostasis by activating factor IX.|The characterization of the apple disk structure, and its relationship to the catalytic domain, have provided new insight into the mechanism of FXI activation, the interaction of FXIa with the substrate factor IX, and the binding of FXI to platelets. | SIGNOR-263537 |
P24666 | P06241 | 0 | phosphorylation | up-regulates activity | 0.382 | We identify Tyr-131 as the major phosphorylation site and Tyr-132 as a minor site and the Src family PTKs Lck and Fyn as enzymes capable of phosphorylating these sites in vivo and in vitro. Both Tyr-131 and Tyr-132 are located next to the catalytic pocket of LMPTP, and especially, Tyr-131 seems to be important for the activity of LMPTP. Phosphorylation of Tyr-131 or Tyr-132, particularly the former, caused an increase in the activity of LMPTP. | SIGNOR-251150 |
O60307 | P60484 | 2 | binding | up-regulates | 0.569 | Pten binds to and is phosphorylated by mast kinases./ Pdz domain-mediated binding to pten facilitates its phosphorylation by mast kinases / pdz domain binding increases pten protein stability. | SIGNOR-138077 |
P41146 | P19086 | 2 | binding | up-regulates activity | 0.252 | 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-257117 |
P40763 | P23468 | 0 | dephosphorylation | down-regulates activity | 0.517 | Transfection of wild-type PTPRD resulted in the specific dephosphorylation of STAT3 at tyrosine 705, a residue that must be phosphorylated for STAT3 to be active | SIGNOR-248442 |
Q14118 | Q9Y4C0 | 2 | binding | up-regulates activity | 0.2 | The DGC is potentially recruited to the postsynaptic membrane though a direct neurexin–dystroglycan interaction and an indirect interaction with NL2 via the synaptic scaffolding protein S-SCAM. | SIGNOR-265463 |
Q5T0F9 | P08908 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.335 | Human Freud-2/CC2D1B: a novel repressor of postsynaptic serotonin-1A receptor expression|Human Freud-2 showed strong repressor activity at the human 5-HT1A or heterologous promoter in human HEK-293 5-HT1A-negative cells and neuronal SK-N-SH cells, a model of postsynaptic 5-HT1A receptor-positive cells. | SIGNOR-268298 |
O95271 | Q9NTX7 | 0 | ubiquitination | down-regulates quantity | 0.723 | 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-260004 |
Q13761 | P12931 | 0 | phosphorylation | down-regulates activity | 0.58 | In this study, we provide evidence that Src phosphorylates RUNX3 at multiple tyrosine residues.|Our finding that Src inactivates RUNX3 by cytoplasmic sequestration in gastric cancer and breast cancer suggests that the inactivation of RUNX3 may be a key function of oncogenic kinases. | SIGNOR-278199 |
Q9BYP7 | Q9H4A3 | 1 | phosphorylation | up-regulates activity | 0.282 | We found that wild-type WNK2 (Figure 8A) or WNK3 (Figure 8B) phosphorylated kinase-inactive WNK1 (1–667, D368A) at Ser382 in vitro. | SIGNOR-260789 |
P05198 | Q13144 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.84 | EIF2B converts the protein synthesis initiation factor 2 (eIF2) from an inactive GDP-bound form to an active eIF2-GTP complex owing to its guanine nucleotide exchange factor (GEF) activity. | SIGNOR-269123 |
Q9Y3E5 | Q15139 | 0 | phosphorylation | up-regulates | 0.3 | Overexpression of constitutively active pkd or pkd activation by treatment with phorbol 12-myristate 13-acetate results in phosphorylation of two serine residues (ser5 and ser87) in a form of bit1 that is confined to the cytoplasm and concomitantly increases the apoptotic activity of cytoplasmic bit1 | SIGNOR-180085 |
O75449 | Q9BVA0 | 2 | binding | up-regulates activity | 0.753 | In its active ATP-bound state, KATNA1 forms hexameric rings capable of binding to and severing microtubule polymers. Typically, KATNA1 binding to KATNB1 enhances severing, likely due to KATNB1 increasing the stability of the KATNA1 hexamer | SIGNOR-267174 |
Q495A1 | P32121 | 2 | binding | up-regulates activity | 0.2 | With TIGIT/PVR engagement, cytoplasmic TIGIT was phosphorylated at Tyr-225 and Tyr-231 residues. Phosphorylated Tyr-225 recruits adaptor protein beta arrestin 2|TIGIT/PVR signaling mediates suppression of IFN- gamma production via the NF-kappaB pathway. We identified a new adaptor β-arrestin 2 that associates with phosphorylated TIGIT and mediates recruitment of inositol phosphatase SHIP1 through the ITT-like motif (Fig. 7). Finally, SHIP1 impairs TRAF6 autoubiquitination to abolish NF-kappaB activation, leading to inhibition of IFN- gamma production in NK cells. | SIGNOR-261482 |
P60953 | Q9NR80 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.739 | We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2). | SIGNOR-260532 |
Q14524 | Q96PU5 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.464 | The control of Nav density at the cell membrane is crucial to ensuring normal neuronal excitability. Navs are subject to posttranslational modifications that may influence their cell membrane availability. Ubiquitylation is a key process that orchestrates the internalization and subsequent degradation or recycling of Navs. This is accomplished by ubiquitin protein ligases, such as NEDD4-2 (neuronal precursor cell expressed developmentally downregulated-4 type 2). | SIGNOR-253456 |
Q09013 | P11831 | 1 | phosphorylation | up-regulates | 0.289 | Myotonic dystrophy protein kinase (DMPK), a muscle- and neuron-restricted kinase, enhanced SRF-mediated promoter activity of the skeletal and cardiac alpha-actin genes in C2C12 myoblasts as well as in nonmyogenic cells. | Threonine 159 in the MADS box alphaI coil was a specific phosphorylation target in vitro as well as in vivo of both DMPK and protein kinase C-alpha. | SIGNOR-236982 |
Q9UBK2 | Q969H0 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.398 | We then examined the effect of necdin on ubiquitin-dependent degradation of PGC-1α using Rnf34, a PGC-1α E3 ubiquitin ligase22. Rnf34 reduced the PGC-1α level, and necdin completely inhibited the reduction (Fig. 4i). In addition, necdin strongly suppressed Rnf34-mediated ubiquitination of PGC-1α (Fig. 4j). Necdin also protected PGC-1α against ubiquitination mediated by Fbxw7, another PGC-1α E3 ubiquitin ligase23 (Fig. 4k). These data indicate that necdin stabilizes PGC-1α by inhibiting its degradation in the ubiquitin-proteasomal system. | SIGNOR-253394 |
Q13404 | P61088 | 2 | binding | up-regulates activity | 0.854 | Ubc13, the partner of rnf8 and rnf168, usually cooperates with an e2-like protein, uev1 (also known as ube2v1) or mms2 (also known as ube2v2), for the synthesis of lys63-linked polyubiquitin chains. | SIGNOR-166177 |
P23528 | O14965 | 0 | phosphorylation | down-regulates activity | 0.316 | However, this study identified that CFL-1 also acts as a direct substrate of Aur-A, which phosphorylates CFL-1 at multiple sites, including S3, S8, and T25, resulting in its inactivation.|In early cell mitotic phases, LIMK1 and Aur-A phosphorylate and inactivate CFL-1, while at the later stages, SSH-1 inactivates LIMK1 and dephosphorylates and activates CFL-1 [33] . | SIGNOR-279798 |
Q96J02 | Q15366 | 2 | binding | up-regulates activity | 0.615 | Only AIP4 associated with PCBP2 and caused MAVS degradation. The interaction between PCBP2 and AIP4 was abrogated when the linker region or WB2 of PCBP2 was deleted, which confirmed our previous data indicating that this region was critical for PCBP2-mediated degradation of MAVS | SIGNOR-260361 |
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