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 |
|---|---|---|---|---|---|---|---|
Q5T0T0 | O00220 | 1 | ubiquitination | down-regulates quantity | 0.2 | The collective data indicate that endogenous MARCH-8 ubiquitinates TRAIL-R1 to attenuate its cell surface expression. | SIGNOR-278570 |
P01100 | P63279 | 0 | sumoylation | down-regulates activity | 0.365 | We report here that lysine 265 of c-Fos is conjugated by the peptidic posttranslational modifiers SUMO-1, SUMO-2, and SUMO-3 and that c-Jun can be sumoylated on lysine 257 as well as on the previously described lysine 229. Sumoylation of c-Fos preferentially occurs in the context of c-Jun/c-Fos heterodimers.|Inhibition of c-Fos and c-Jun sumoylation stimulates AP-1-dependent transcription activity. | SIGNOR-263013 |
P49840 | Q8NHW3 | 1 | phosphorylation | up-regulates activity | 0.2 | We also demonstrate that gsk-3 triggers mafa sequential phosphorylation on residues s61, t57, t53, and s49 /we demonstrated that phosphorylation by gsk-3 is conserved among the large maf proteins. It couples ubiquitination/degradation and transcriptional activation and modulates maf biological activity./ Taken together, these results suggest that, in contrast to what can be expected from ubiquitination/degradation, gsk-3-mediated mafa phosphorylation increases its transactivating ability, thereby controlling its biological activity. | SIGNOR-159377 |
P49327 | Q5VWC8 | 0 | chemical activation | up-regulates activity | 0.2 | Very long-chain fatty acids are produced through a four-step cycle. However, the 3-hydroxyacyl-CoA dehydratase catalyzing the third step in mammals has remained unidentified. Mammals have four candidates, HACD1-4, based on sequence similarities to the recently identified yeast Phs1, although HACD3 and HACD4 share relatively weak similarity. We demonstrate that all four of these human proteins are indeed 3-hydroxyacyl-CoA dehydratases, | SIGNOR-267763 |
Q9Y6K9 | Q9H6Z9 | 2 | binding | down-regulates activity | 0.326 | Here we report that EGLN3, but not EGLN1 or -2, interacts with and inhibits K63-linked ubiquitination of IKKγ. The effect appears to be related to inhibition of IKKγ ubiquitination mediated by cIAP1 rather than to stimulation of IKKγ deubiquitination by the deubiquitinases A20 and CYLD (cylindromatosis). EGLN3 does not affect the protein levels of cIAP1 or its E2 ubiquitin-conjugating enzymes UbcH5 and Ubc13. EGLN3 hydroxylase activity is not responsible for its effect on IKKγ ubiquitination and NF-κB signaling. Instead, interaction with IKKγ is required for the ability of EGLN3 to inhibit IKKγ ubiquitination and IKK-NF-κB signaling. | SIGNOR-262005 |
P37173 | Q9HAU4 | 0 | ubiquitination | down-regulates activity | 0.595 | Smurf1 and smurf2 are e3 ubiquitin ligases known to suppress tgf-beta signaling through degradation of smads and receptors for tgf-beta and bmps. | SIGNOR-195681 |
P19484 | O75807 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | We found that the main regulator of the starvation-induced transcriptional program, TFEB, counteracts protein synthesis inhibition by directly activating expression of GADD34, a component of the protein phosphatase 1 complex that dephosphorylates eIF2α. | SIGNOR-276789 |
O14579 | Q96PM5 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.471 | PIRH2 promotes the ubiquitylation of epsilon-COP in vitro and in vivo and consequently promotes the degradation of epsilon-COP. | SIGNOR-272630 |
P31751 | Q92945 | 1 | phosphorylation | down-regulates | 0.343 | AKT phosphorylates the mRNA decay-promoting factor KSRP at a unique serine residue, induces its association with the multifunctional protein 14-3-3, and prevents KSRP interaction with the exoribonucleolytic complex exosome. This impairs KSRPs ability to promote rapid mRNA decay. | SIGNOR-151220 |
P48023 | O95407 | 2 | binding | down-regulates | 0.65 | Tr6 specifically binds fas ligand. Tr6 may play a regulatory role for suppressing in fasl- mediated cell death. | SIGNOR-67434 |
P34981 | P20396 | 2 | binding | up-regulates activity | 0.762 | When TRH reaches the pars distalis of the pituitary, it regulates cells that express TRH receptor-1 (TRH-R1), such as the thyrotrophs. These cell types are subject to a multifactorial regulation that determines the extent and specificity of their response to TRH. | SIGNOR-267200 |
Q16539 | P11362 | 1 | phosphorylation | down-regulates | 0.274 | Fgfr1 translocation requires p38 mapk activation which phosphorylates the c-term tail of fgfr1 on ser777 | SIGNOR-166598 |
P49841 | P20929 | 1 | phosphorylation | down-regulates | 0.306 | Gsk3b is able to phosphorylate nebulin at two ser sites in the c-terminal region of nebulin localized to the z-disk, thus preventing the interaction of nebulin with neuronal wiscott-aldrich syndrome protein (nwasp), a ubiquitously expressed member of the wasp family, which is involved in actin assembly. | SIGNOR-175659 |
P49841 | O75030 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.435 | We also show that the MITF protein was stabilized by Wnt signaling, through the novel C-terminal GSK3 phosphorylations identified here. | SIGNOR-276476 |
P63096 | P34969 | 2 | binding | up-regulates activity | 0.281 | 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-257055 |
Q13489 | Q96FA3 | 0 | ubiquitination | up-regulates quantity by stabilization | 0.455 | Notably, Pellino-1 directly interacted with cIAP2 and stabilized cIAP2 through lysine63-mediated polyubiquitination via its E3 ligase activity. | SIGNOR-259395 |
P10275 | Q6ZRS2 | 2 | binding | up-regulates activity | 0.41 | The SNF2-related CBP activator protein (SRCAP) serves as a coactivator for several nuclear receptors including the androgen receptor (AR). SRCAP is an ATPase that is the core subunit of a large multiprotein complex and was shown to incorporate the histone variant H2A.Z into nucleosomes. In this report, we demonstrate that SRCAP is expressed in the epithelium of normal prostate and in prostate carcinoma cells, and is associated with AR in the nucleus | SIGNOR-255221 |
P53350 | Q13188 | 1 | phosphorylation | down-regulates activity | 0.331 | We conclude that TRIM69A promotes multi-site phosphorylation of MST2.We demonstrate that TRIM69 stimulates formation of an MST2-PLK1 complex and promotes phosphorylation of MST2 at S15, a known PLK1 site. PLK1-mediated MST2 phosphorylation at S15 is necessary for subsequent phosphorylation of NEK2A to dissociate c-NAP1 from daughter centrioles (7). Thus, we provide a new molecular mechanism by which TRIM69 promotes MST2- and PLK1-mediated centrosome disjunction. | SIGNOR-277904 |
P48729 | O43524 | 1 | phosphorylation | down-regulates | 0.2 | Casein kinase (ck) 1 mediates the hierarchical phosphorylation of foxo3a at s318 and s321, which like foxo1 (rena et al., 2002 blue right-pointing triangle, 2004 blue right-pointing triangle), is probably to enhance its rate of nuclear export | SIGNOR-163676 |
Q13163 | P10912 | 0 | phosphorylation | up-regulates activity | 0.2 | The MEK5-dependent activation of ERK5 promotes binding of the transcription factor SP1 to the promoter of the genes encoding the transcription factors Klf2 and Klf4, leading to their increased abundance. Subsequently, Klf2 and Klf4 bind to the Npnt promoter and induce the production of nephronectin during myoblast fusion | SIGNOR-255452 |
P62826 | P53350 | 0 | phosphorylation | up-regulates | 0.264 | Plk1 is capable of phosphorylating co-immunoprecipitated ran in vitro on serine-135 and ran is phosphorylated in vivo at the same site during mitosis when plk1 is normally activated. Deregulation of ran phosphorylation disrupts normal spindle structure and segregation of chromosomes. | SIGNOR-149073 |
Q9UQL6 | P34947 | 0 | phosphorylation | down-regulates activity | 0.356 | GRK5 phosphorylates and promotes the nuclear export of the histone deacetylase, HDAC5. | SIGNOR-279045 |
P28482 | Q15349 | 1 | phosphorylation | up-regulates | 0.717 | Erk-activates the rsk family of serine/threonine kinases,rsk1, rsk2, and rsk3. | SIGNOR-161515 |
Q6IE81 | P98161 | 2 | binding | down-regulates quantity by destabilization | 0.328 | Full-length PC1 bound, stabilized and colocalized with Jade-1 and inhibited Jade-1 ubiquitination. Jade-1 ubiquitination was mediated by Siah-1, an E3 ligase that binds PC1. | SIGNOR-272917 |
Q12955 | O95166 | 2 | binding | up-regulates activity | 0.445 | Importantly, the 480 kDa ankyrin-G isoform has also been shown to stabilize GABAergic synapses on the soma and AIS of excitatory pyramidal neurons by interacting with the GABAA receptor-associated protein (GABARAP) to inhibit GABAA receptor endocytosis | SIGNOR-266709 |
Q15652 | P22415 | 2 | binding | up-regulates activity | 0.2 | We show that, by direct interaction with USF-1, JMJD1C is recruited to lipogenic promoters. We also show that JMJD1C is phosphorylated at T505 by mammalian target of rapamyci (mTOR) to be recruited to lipogenic genes in response to insulin/feeding. | SIGNOR-265167 |
P17612 | P63104 | 1 | phosphorylation | down-regulates activity | 0.566 | Phosphorylation by pka leads to modulation of 14-3-3zeta dimerization and affect its interaction with partner proteins. Substitution of ser58 to ala completely abolished phosphorylation of 14-3-3zeta by pka. | SIGNOR-143373 |
Q02779 | P45985 | 1 | phosphorylation | up-regulates activity | 0.445 | MST/MLK2, a member of the mixed lineage kinase family, directly phosphorylates and activates SEK1, an activator of c-Jun N-terminal kinase/stress-activated protein kinase. | SIGNOR-278954 |
O00327 | P20393 | 0 | 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 |
Q9UNS2 | P58340 | 2 | binding | up-regulates | 0.403 | As downstream elements of mlf1 leading to cell growth arrest due to p53 accumulation, we identified two factors, csn3, the third component of the cop9 signalosome (csn), and cop1, a recently characterized e3 ubiquitin ligase for p53 | SIGNOR-135937 |
P04628 | O75581 | 2 | binding | up-regulates activity | 0.828 | Ligands such as wnt1, wnt3a, and wnt8 couple the seventransmembrane domain receptor frizzled (fzd) and the single-membrane-spanning low-density receptor-related protein 5/6 (lrp5/6) to activate wnt?Beta-catenin signaling. | SIGNOR-169648 |
Q9BYF1 | P59594 | 2 | binding | down-regulates activity | 0.2 | Cell entry of severe acute respiratory syndrome coronavirus (SARS-CoV) is mediated by the viral spike (S) protein. Amino acids 319-510 on the S protein have been mapped as the receptor-binding domain (RBD), which mediates binding to the SARS-CoV receptor angiotensin converting enzyme 2 (ACE2) on SARS-CoV susceptible cells. Here, we demonstrate that the RBD spike protein alone can be internalized together with ACE2. We propose that after binding to ACE2, the RBD spike protein activates the ACE2 mediated cellular endocytosis signal pathway, by which SARS-CoV enters the susceptible cells. | SIGNOR-260283 |
Q13247 | Q13627 | 0 | phosphorylation | up-regulates activity | 0.432 | These results suggest that Dyrk1A enhances SRp55 promoted cTnT exon 5 inclusion.|These results supported the finding that phosphorylation of SRp55 by Dyrk1A promotes cTnT exon 5 inclusion.Alternative splicing of cTnT exon 5 is regulated developmentally. | SIGNOR-279166 |
P32245 | P38405 | 2 | binding | up-regulates activity | 0.27 | 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-256940 |
P15172 | P24941 | 0 | phosphorylation | down-regulates | 0.522 | Cyclin e/cdk2 can phosphorylate myod at serine 200, which causes ubiquitination and degradation of this transcription factor during g1, preventing its accumulation and a commitment to differentiation. | SIGNOR-176509 |
Q13258 | P63092 | 2 | binding | up-regulates activity | 0.593 | 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-256755 |
P40189 | Q9UBD9 | 2 | binding | up-regulates | 0.56 | Some of these biological activities of il-6 are also often exerted by other cytokines, i.e. Il-11, lif, osm, cntf, and ct-6 | SIGNOR-47959 |
Q7Z6M2 | O00303 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | Mediation of eIF3-f polyubiquitination by the SCFMAFbx. The association of MAFbx with the essential Skp1, Roc 1 and Cul1 proteins, specific components of an E3 ubiquitin–protein ligase (SCFMAFbx), was previously described. Here, we present evidence that during muscle atrophy MAFbx targets the eukaryotic initiation factor 3 subunit 5 (eIF3-f) for ubiquitination and degradation by the proteasome. | SIGNOR-271768 |
Q9NPG1 | Q03113 | 2 | binding | up-regulates | 0.244 | Gpcrs signal through four relatively small families of galfa proteins (galfas, galfai/o, galfaq, and galfa12/13), and if fzd receptors are classic gpcrs, they should signal through one of these four galfa families. | SIGNOR-122889 |
Q13185 | Q6KC79 | 2 | binding | up-regulates activity | 0.436 | The heterochromatin protein HP1γ (also known as CBX3) recruits NIPBL to DNA double-strand breaks (DSBs) through the corresponding HP1-binding motif within the N-terminus. | SIGNOR-264524 |
O95433 | P08238 | 2 | binding | up-regulates activity | 0.661 | The N-terminal region of Aha1 interacts with the central domain of Hsp90 and stimulates Hsp90 ATPase activity | SIGNOR-252212 |
P16070 | Q9UQM7 | 0 | phosphorylation | up-regulates activity | 0.2 | In previous studies we have demonstrated that a key control point for this receptor is the phosphorylation of CD44 on a conserved cytoplasmic serine residue, Ser(325). This modification is not required for efficient ligand binding, but is an essential component of CD44-dependent cell migration on a hyaluronan substratum. We demonstrate here that cd44 is phosphorylated to high stoichiometry in resting cells and that ca(2+)/calmodulin-dependent protein kinase ii is a cd44 ser(325) kinase. | SIGNOR-109502 |
Q9BXW9 | Q13535 | 0 | phosphorylation | up-regulates | 0.673 | In the present study, we identify two novel dna damage-inducible phosphorylation sites on fancd2, threonine 691 and serine 717. Atr phosphorylates fancd2 on these two sites, thereby promoting fancd2 monoubiquitination and enhancing cellular resistance to dna cross-linking agents | SIGNOR-149305 |
Q9NUW8 | P78527 | 0 | phosphorylation | up-regulates | 0.537 | Optimal function of the dna repair enzyme tdp1 requires its phosphorylation by atm and/or dna-pk. Here we show that top1-associated dna double-stranded breaks (dsbs) induce the phosphorylation of tdp1 at s81. This phosphorylation is mediated by the protein kinases: ataxia-telangiectasia-mutated (atm) and dna-dependent protein kinase (dna-pk) | SIGNOR-188776 |
O60566 | P53350 | 0 | phosphorylation | up-regulates | 0.84 | We identify s676 as a plk1-specific phosphorylation site on bubr1. These findings describe the first in vivo verified phosphorylation site for human bubr1, identify plk1 as the kinase responsible for causing the characteristic mitotic bubr1 upshift, and attribute a kt-specific function to the hyperphosphorylated form of bubr1 in the stabilization of kt-mt interactions. | SIGNOR-157646 |
Q9NQW1 | Q53G59 | 2 | binding | up-regulates activity | 0.553 | By analyzing mouse embryonic stem cell (mESC) division, we have identified Cul3Klhl12 as a regulator of COPII coat formation. Cul3Klhl12 monoubiquitinates Sec31 and drives assembly of large COPII-coats. As a result, ubiquitination by Cul3Klhl12 is essential for collagen export, a step that is required for integrin-dependent mESC division. | SIGNOR-272014 |
P25963 | Q9UQB9 | 0 | phosphorylation | up-regulates activity | 0.2 | AURKC directly induces IkappaBalpha activation via an interaction between the two proteins, leading to phosphorylation of IkappaBalpha.|AURKC phosphorylates IkappaBalpha on S32 and binds its ankyrin repeat domain. | SIGNOR-278470 |
Q14680 | O15530 | 1 | phosphorylation | down-regulates activity | 0.267 | The results showed that MPK38 interacted with and inhibited PDK1 activity via Thr(354) phosphorylation. | SIGNOR-276414 |
P08709 | P04070 | 0 | cleavage | down-regulates activity | 0.237 | Activated protein C (APC), which cleaves and inactivates both FVIIIa and FVa, thereby shutting down both the tenase and prothrombinase complexes | SIGNOR-263527 |
Q96G30 | Q01718 | 2 | binding | up-regulates activity | 0.536 | We report that MRAP and MRAP2 can interact with all 5 MCRs. This interaction results in MC2R surface expression and signaling.We have previously identified MRAP as an accessory protein for MC2R, required for receptor trafficking to the cell surface and the formation of a functional MC2R. Here we have identified MRAP2 as a homologue of MRAP. Like MRAP, MRAP2 is able to support MC2R cell-surface expression, producing a functional ACTH-responsive receptor. | SIGNOR-252361 |
Q96NI6 | P23468 | 2 | binding | up-regulates activity | 0.277 | SALM5 trans-synaptically interacts with LAR-RPTPs in a splicing-dependent manner to regulate synapse development. we identified LAR-RPTPs as novel ligands of SALM5 that mediates SALM5-dependent presynaptic differentiation in a splicing-dependent manner. Our data indicate that SALM5 interacts with all three known LAR-RPTPs—LAR, PTPδ, and PTPσ (Fig. 1). | SIGNOR-264086 |
P48729 | Q13315 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Mechanistically, CK1α phosphorylates the serine residue S1270 and modulates the protein abundance of ataxia telangiectasia mutated (ATM), a primary initiator of DNA double-strand break (DSB)-response signaling, which is compromised in ENZA-resistant cells and patients. Inhibition of CK1α stabilizes ATM, resulting in the restoration of DSB signaling, and thus increases ENZA-induced cell death and growth arrest. | SIGNOR-277918 |
Q12933 | O75460 | 2 | binding | up-regulates activity | 0.677 | Activated IRE1 has been demonstrated to recruit TRAF2 and ASK1 on the ER membrane and thus to activate ASK1|ASK1 was found to associate with IRE1 only in the presence of TRAF2 and SOD1mut (Fig. 4B), suggesting that SOD1mut induces formation of an IRE1–TRAF2–ASK1 complex on the ER membrane and thus activates ASK1 by triggering ER stress-induced IRE1 activation. | SIGNOR-262790 |
O15105 | O15379 | 2 | binding | up-regulates | 0.342 | We show here that smad7 can form a complex with endogenous histone deacetylase proteins hdac-1 and hdac-3 in nih 3t3 mouse fibroblast cells | SIGNOR-199967 |
Q8N0X7 | Q96J02 | 2 | binding | up-regulates activity | 0.2 | Cytosolic endogenous spartin is mono-ubiquitinated and we demonstrate that it interacts via a PPXY motif with the ubiquitin E3 ligases AIP4 [atrophin-interacting protein 4; ITCH (itchy E3 ubiquitin protein ligase homologue] [corrected] and AIP5 (WWP1). Surprisingly, the PPXY motif, AIP4 and AIP5 are not required for spartin's ubiquitination, and so we propose that spartin acts as an adaptor for these proteins. | SIGNOR-261306 |
Q9HCK8 | P50553 | 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-268914 |
Q00536 | P46527 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.333 | In vitro kinase assays showed PCTAIRE1 phosphorylates p27 at Ser10. PCTAIRE1 silencing modulated Ser10 phosphorylation on p27 and led to its accumulation in cancer cells but not in nontransformed cells.|Together our findings reveal an unexpected role for PCTAIRE1 in regulating p27 stability, mitosis, and tumor growth, suggesting PCTAIRE1 as a candidate cancer therapeutic target. | SIGNOR-273016 |
P49841 | P07384 | 0 | cleavage | up-regulates activity | 0.297 | 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-251586 |
P45983 | P35568 | 1 | phosphorylation | down-regulates activity | 0.771 | Insulin also activates jnk, erk, pkc and mtor, which induce the phosphorylation of irs1 on serine residues 307, 612 and 632 and inhibit its functions. Our results indicate that the insulin-stimulated degradation of irs-1 via the phosphatidylinositol 3-kinase pathway is in part dependent upon the ser(312) phosphorylation of irs-1. | SIGNOR-96948 |
Q14814 | Q13164 | 0 | phosphorylation | up-regulates | 0.705 | Here, we demonstrate that, in addition to mef2c, bmk1 phosphorylates and activates mef2a and mef2d but not mef2b. the sites phosphorylated by activated bmk1 were mapped to ser-355, thr-312, and thr-319 of mef2a and ser-179 of mef2d both in vitro and in vivo. | SIGNOR-236041 |
P01106 | P22626 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.356 | We also demonstrate that the oncogenic transcription factor c-Myc upregulates transcription of PTB, hnRNPA1 and hnRNPA2, | SIGNOR-268691 |
Q9BXM7 | Q9H300 | 0 | cleavage | down-regulates quantity by destabilization | 0.613 | Using an unbiased RNA-mediated interference (RNAi)-based screen, we identified four mitochondrial proteases, mitochondrial processing peptidase (MPP), presenilin-associated rhomboid-like protease (PARL), m-AAA and ClpXP, involved in PINK1 degradation. We find that PINK1 turnover is particularly sensitive to even modest reductions in MPP levels. Moreover, PINK1 cleavage by MPP is coupled to import such that reducing MPP activity induces PINK1 accumulation at the mitochondrial surface, leading to Parkin recruitment and mitophagy. | SIGNOR-261364 |
O00463 | Q15628 | 2 | binding | up-regulates | 0.607 | Upon stimulation of the tumor necrosis factor receptor1 (tnfr1), tnf-receptor-associated death domain (tradd) provides a scaffold for the assembly of complex i at the plasma membrane by binding receptor interacting protein 1 (rip1), tnfreceptor-associated factor 2 ,traf2. | SIGNOR-187058 |
Q92878 | P49959 | 2 | binding | up-regulates | 0.2 | To organize the mrn complex, the mre11 exonuclease directly binds nbs1, dna, and rad50. | SIGNOR-157478 |
P46531 | O00505 | 0 | relocalization | up-regulates | 0.324 | Nicd binds via one of its four potential nuclear localization signals to importins alfa3, alfa4, and alfa7. | SIGNOR-165280 |
Q14847 | P05771 | 0 | 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 |
P20023 | P03200 | 2 | 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 |
Q02078 | Q99623 | 2 | binding | down-regulates | 0.31 | Phb2 interacts with both myod and mef2, and represses both myod- and mef2-dependent gene transcription. Furthermore, binding of phb2 to both myod and mef2 significantly decreases upon myogenic differentiation. | SIGNOR-235840 |
P08069 | P43250 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.306 | GRK2 and GRK6 coimmunoprecipitate with IGF-1R and increase IGF-1R serine phosphorylation, promoting β-arrestin1 association. Using immunoprecipitation, confocal microscopy, and FRET analysis, we demonstrated β-arrestin/IGF-1R association to be transient for GRK2 and stable for GRK6. Using bioinformatic studies we identified serines 1248 and 1291 as the major serine phosphorylation sites of the IGF-1R. Targeted mutation of S1248 recapitulates GRK2 modulation, whereas S1291 mutation resembles GRK6 effects on IGF-1R signaling/degradation | SIGNOR-276412 |
Q9NRF2 | P20273 | 2 | binding | up-regulates activity | 0.2 | SHP-1 is recruited by the phosphorylated ITIM-bearing receptors such as CD22 and it dephosphorylates proximal BCR signaling molecules such as CD79, SYK, BLNK. | SIGNOR-268444 |
Q06609 | P51587 | 2 | binding | up-regulates activity | 0.947 | We suggest that interactions of the BRCA2 C-terminal region with RAD51 may facilitate efficient nucleation of RAD51 multimers on DNA and thereby stimulate recombination-mediated repair. | SIGNOR-259905 |
Q9NQU5 | P05141 | 1 | phosphorylation | up-regulates quantity | 0.2 | In the present study, it was demonstrated that ANT2 was phosphorylated by PAK6 at T107.|Moreover, PAK6 overexpression upregulated the protein expression of ANT2, while PAK6 knockdown led to opposing effects. | SIGNOR-279473 |
Q92481 | P02511 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Aberrant expression of CRYAB has been shown to be associated with several neurological diseases and malignant neoplasms. To identify transcriptional regulators of CRYAB expression, we examined its promoter for binding sites of transcription factors and identified four potential AP-2 binding sites in addition to a p53 binding site reported previously|Taken together, our results indicate that AP-2_ up-regulates the transcription of the CRYAB gene through stabilizing p53 | SIGNOR-253637 |
P31749 | O60343 | 1 | phosphorylation | down-regulates | 0.764 | Recently, we identified a 160-kda protein in adipocytes, designated as160, that is phosphorylated by the insulin-activated kinase akt | SIGNOR-252594 |
Q96CV9 | Q8IYU2 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.401 | Here we report that tumor suppressor HACE1, a ubiquitin ligase, ubiquitylates OPTN and promotes its interaction with p62 and SQSTM1 to form the autophagy receptor complex, thus accelerating autophagic flux.|Ubiquitylation of Autophagy Receptor Optineurin by HACE1 Activates Selective Autophagy for Tumor Suppression.|HACE1 mediated K48 linked poly-Ub chains targets OPTN for autophagic degradation. | SIGNOR-278748 |
P32245 | P50148 | 2 | binding | up-regulates activity | 0.25 | 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-257336 |
P17252 | Q92793 | 1 | phosphorylation | down-regulates | 0.261 | The action of metformin was shown to be mediated through activation of apkc?/?, Which phosphorylates cbp at ser436, and disrupts the transcriptionally active creb-cbp-crtc2 complex, | SIGNOR-166368 |
P54762 | Q92823 | 1 | phosphorylation | up-regulates activity | 0.411 | EphB receptors were found to induce phosphorylation of NrCAM on the tyrosine residue within the FIGQY ankyrin binding motif, inhibiting ankyrin recruitment. Furthermore, NrCAM phospho-FIGQY levels in the SC were decreased in EphB1/3 and EphB1/2/3 null mice and increased in mutant mice overexpressing constitutively active EphB2 kinase. | SIGNOR-262862 |
P07947 | Q9GZV5 | 1 | phosphorylation | up-regulates activity | 0.317 | Yes directly phosphorylates YAP and TAZ, resulting in their increased nuclear localization and transcriptional activity.Analysis by mass spectrometry identified Tyr391 and Tyr407 as the two phosphorylation sites of YAP, whereas Tyr305 was the sole phosphorylated residue of TAZ (Fig. 5F and fig. S4, A to C). | SIGNOR-277654 |
P41250 | P18848 | 0 | 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-269426 |
O95837 | P30968 | 2 | binding | up-regulates activity | 0.478 | 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-257331 |
P01106 | P27361 | 0 | phosphorylation | up-regulates activity | 0.707 | ERK1 phosphorylates MYC Ser62 resulting in MYC stabilization and activation | SIGNOR-236250 |
Q92830 | Q15796 | 2 | binding | up-regulates | 0.337 | Gcn5 functions like pcaf, in that it binds to tgf-beta-specific r-smads, and enhances transcriptional activity induced by tgf-beta. In addition, gcn5, but not pcaf, interacts with r-smads for bone morphogenetic protein (bmp) signalling pathways, and enhances bmp-induced transcriptional activity, suggesting that gcn5 and pcaf have distinct physiological functions in vivo. | SIGNOR-123315 |
P25021 | O95837 | 2 | binding | up-regulates activity | 0.25 | 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-257424 |
P40763 | P51452 | 0 | dephosphorylation | down-regulates activity | 0.2 | DUSP3 interacted with the C-terminal domain of STAT3 and dephosphorylated p-Y705 of STAT3.|In summary, DUSP3 downregulated the transcriptional activity of STAT3 via dephosphorylation at Y705 and also suppressed the migratory activity of cancer cells. | SIGNOR-277070 |
P32239 | P50148 | 2 | binding | up-regulates activity | 0.454 | 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-257305 |
Q13535 | O75717 | 1 | phosphorylation | up-regulates activity | 0.539 | And-1 is phosphorylated at T826 by ATR following replication stress, and this phosphorylation is required for And-1 to accumulate at the damage sites, where And-1 promotes the interaction between Claspin and Chk1, thereby stimulating efficient Chk1 activation by ATR. | SIGNOR-262664 |
Q13315 | Q13362-3 | 1 | phosphorylation | up-regulates activity | 0.378 | In the present study, we demonstrate that ataxia-telangiectasia mutated (ATM) directly phosphorylates and specifically regulates B56γ3, B56γ2 and B56δ, after DNA damage. We further show that phosphorylation of B56γ3 at Ser510 leads to an increase in B56γ3-PP2A complexes, and direction of PP2A phosphatase activity toward the substrate p53, activating its tumor-suppressive functions. we show that Ser510 phosphorylation significantly enhances the ability of B56γ3 to inhibit cell proliferation and anchorage-independent growth. | SIGNOR-276320 |
Q9NS75 | P50148 | 2 | binding | up-regulates activity | 0.517 | 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-257024 |
Q06830 | Q13043 | 0 | phosphorylation | down-regulates activity | 0.2 | Mst1 inactivates Prdx1 by phosphorylating it at Thr-90 and Thr-183, leading to accumulation of hydrogen peroxide in cells.Prdx1 is phosphorylated by Mst1 predominantly at Thr-18, Thr-90, and Thr-183. | SIGNOR-276486 |
O95837 | P32245 | 2 | binding | up-regulates activity | 0.25 | 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-257392 |
Q969R2 | P48729 | 0 | phosphorylation | up-regulates activity | 0.2 | CK1a1, JNK1 and CDK1 had the highest site-specific activity for ORP4L, while CDK1, GSK3a, CK1a1 and GSK3b showed the highest specificity for the site when corrected for background activity with ORP4L-S4A. Because of the complexity of the serine/proline-rich site, we did not determine which serine(s) in ORP4L were phosphorylated by candidate kinases.|We conclude that phosphorylation of a unique serine/proline motif in the ORD induces a conformation change in ORP4L that enhances interaction with vimentin and cholesterol extraction from membranes. | SIGNOR-264877 |
P61586 | Q13829 | 2 | binding | down-regulates quantity | 0.35 | BACURDs form ubiquitin ligase complexes, which selectively ubiquitinate RhoA, with Cul3. Our studies reveal a previously unknown mechanism for controlling RhoA degradation and regulating RhoA function in various biological contexts, which involves a Cul3/BACURD ubiquitin ligase complex. | SIGNOR-264235 |
Q06413 | Q09472 | 2 | binding | up-regulates | 0.742 | Once released from associated repressors, MEF2 is bound by the p300 coactivator, which possesses histone acetyltransferase activity. Thus, the net result of CaMK signaling to MEF2 complexes is increased histone acetylation (Ac), which relaxes chromatin and stimulates MEF2 target gene transcription. | SIGNOR-232159 |
P46734 | Q7L7X3 | 0 | phosphorylation | up-regulates activity | 0.578 | The activation of and binding to MEK3 by TAO1 implicates TAO1 in the regulation of the p38-containing stress-responsive MAP kinase pathway | SIGNOR-60818 |
P03372 | P04626 | 0 | phosphorylation | up-regulates | 0.572 | The results presented here show for the first time that er redistribution to the cytoplasm and its interaction with her2 are important downstream effects of her2 overexpression, that erk1/2 is important for er cytoplasmic localization, and that subcellular localization of er may play a mechanistic role in determining the responsiveness of breast cancer cells to tamoxifen. | SIGNOR-124962 |
P10275 | P50750 | 0 | phosphorylation | up-regulates activity | 0.537 | AR S81 phosphorylation by CDK9 is tightly linked to chromatin binding and transcriptional activation. | SIGNOR-279456 |
P42680 | O75444 | 1 | phosphorylation | up-regulates activity | 0.2 | We subsequently investigated whether Tec phosphorylated c-Maf at Tyr21/92/131.|We found that overexpression of Tec enhanced the binding of c-Maf to the MARE site derived from the IL-4 promoter (XREF_FIG).|As shown in xref , tyrosine phosphorylation of c-Maf was strongly enhanced by Tec and this Tec-induced tyrosine phosphorylation was completely mitigated by Ptpn22. | SIGNOR-279433 |
Q05397 | P23470 | 0 | dephosphorylation | up-regulates activity | 0.243 | 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-254719 |
Q9NXR1 | P28482 | 0 | phosphorylation | up-regulates activity | 0.374 | Moreover, both proteins were phosphorylated by Cdc2 and Erk2 in vitro. In the case of Nudel, the phosphorylation sites were also located in the S/TP motifs. Detailed mutagenesis study indicated that T219, S242, and T245 were phosphorylated by Cdc2, while T219 and T245 were phosphorylated by Erk2.|Phosphorylation of Nudel in M phase appears to positively modulate dynein motor activity. Both phosphorylated and unphosphorylated forms of Nudel were transported by dynein (Fig. 7 and 9 and data not shown), indicating that neither of them inactivated the dynein motor. On the other hand, both phospho-Nudel and Nudelpmt5 bound Lis1 more strongly than Nudel or Nudelmt5 did | SIGNOR-249422 |
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