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 |
|---|---|---|---|---|---|---|---|
Q01094 | P80370 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Using luciferase reporter assay, ChIP assay and EMSA, we found that the -211/-194 region of the pref-1 promoter is essential for the binding of E2F1 as well as E2F1-dependent transcriptional activation. | SIGNOR-271684 |
P53779 | P54259 | 1 | phosphorylation | down-regulates activity | 0.2 | Dentatorubral-pallidoluysian atrophy protein is phosphorylated by c-jun nh2-terminal kinase. serine 734 of the drpla protein is a phospho-acceptor site by jnk. The phosphorylation may be coupled to the activation of a protease. The molecular size of drpla protein detected in the rat brain with the specific phosphopeptide antibody was 150_kda, which was slightly smaller than that expected from the sequence and the results with the human protein. The phosphorylated forms of ha-tagged human drpla gradually disappeared after osmotic treatment, | SIGNOR-102394 |
P51398 | Q05655 | 0 | phosphorylation | up-regulates | 0.2 | Dap3 is phosphorylated by protein kinase cdelta on thr237. Dap3 was originally identified as a pro-apoptotic protein. The mutation of the phosphorylation site thr237 to alanine reversed the cell death caused by the wild-type dap3 | SIGNOR-160488 |
P31749 | P10276 | 1 | phosphorylation | down-regulates | 0.602 | We report that akt, which is constitutively activated in nsclc cells, phosphorylates raralpha and inhibits its transactivation. / mutation of ser96 to alanine abrogated the suppressive effect of akt. | SIGNOR-252489 |
P54829 | Q16611 | 1 | dephosphorylation | up-regulates activity | 0.2 | In this study, we report that on apoptotic stimulation Bak undergoes dephosphorylation at tyrosine residue 108 (Y108), a critical event that is necessary but not sufficient for Bak activation, but is required both for early exposure of the occluded N-terminal domain and multimerisation. | SIGNOR-248542 |
Q15691 | P48730 | 0 | phosphorylation | up-regulates activity | 0.505 | We further show that casein kinase 1\u03b4 binds and phosphorylates EB1 and promotes microtubule growth. | SIGNOR-279165 |
P34998 | P50148 | 2 | binding | up-regulates activity | 0.286 | Previous studies have indicated that CRHR could couple to multiple Galpha proteins including Gs, Gi, and Gq/11 and then go on to induce changes in AC activity and activation of PLC-beta3 | SIGNOR-268619 |
P53350 | O95235 | 1 | phosphorylation | up-regulates activity | 0.761 | MKlp2 treated with Plk1 did not form the regular microtubule bundles seen with MKlp2 only; many single microtubules were seen instead, and the bundles that were formed were loose parallel arrays rather than the dense bundles seen with untreated MKlp2.|We propose that phosphorylation of MKlp2 by Plk1 is necessary for the spatial restriction of Plk1 to the central spindle during anaphase and telophase, and the complex of these two proteins is required for cytokinesis. | SIGNOR-278201 |
P12821 | P01019 | 1 | cleavage | up-regulates activity | 0.782 | Angiotensin I-converting enzyme is a zinc metallopeptidase that plays an important role in blood pressure regulation by cleaving the inactive decapeptide angiotensin I to angiotensin II, a potent vasopressor octapeptide. | SIGNOR-253326 |
Q92934 | Q92843 | 2 | binding | down-regulates | 0.538 | Bad, however, bound tightly to bcl-2, bcl2l1, and bcl2l2. | SIGNOR-133805 |
Q16827 | P12931 | 1 | dephosphorylation | down-regulates activity | 0.422 | SRC activation triggered by loss of PTPRO leads to c-CBL degradation.|These data corroborate that PTPRO directly dephosphorylates SRC at Y416. | SIGNOR-277004 |
P58753 | P30622 | 2 | binding | down-regulates activity | 0.2 | CLIP170 promotes ubiquitination and degradation of TIRAP | SIGNOR-280460 |
P07948 | P41240 | 0 | phosphorylation | down-regulates | 0.538 | Lyn tyr507 kinase, csk, is recruited by pag, which targets lipid rafts by palmitoylation.Thus, our data suggest that il-6 treatment induces the translocation of cd45 to lipid rafts sequentially, followed by the association of cd45 with lyn and pag;dephosphorylation of lyn tyr507 and pag tyr314;lyn activation;and csk release from lipid rafts | SIGNOR-132912 |
P54259 | P45983 | 0 | phosphorylation | down-regulates activity | 0.376 | Dentatorubral-pallidoluysian atrophy protein is phosphorylated by c-jun nh2-terminal kinase. serine 734 of the drpla protein is a phospho-acceptor site by jnk. The phosphorylation may be coupled to the activation of a protease. The molecular size of drpla protein detected in the rat brain with the specific phosphopeptide antibody was 150_kda, which was slightly smaller than that expected from the sequence and the results with the human protein. The phosphorylated forms of ha-tagged human drpla gradually disappeared after osmotic treatment, | SIGNOR-102398 |
P08559 | Q15120 | 0 | phosphorylation | down-regulates activity | 0.871 | Activity of the mammalian pyruvate dehydrogenase complex is regulated by phosphorylation-dephosphorylation of the alpha subunit of the pyruvate dehydrogenase (e1) component. Phosphorylation is carried out by four pyruvate dehydrogenase kinase (pdk) isoenzymes. | SIGNOR-109647 |
P78352 | Q8N0W4 | 0 | relocalization | up-regulates activity | 0.754 | Like NRXNs, NLGNs bind to intracellular PDZ-domain proteins, but in contrast to NRXNs, NLGNs bind to class I PDZ domains such as those contained in PSD95, a postsynaptic MAGUK protein65. PSD95 and its homologues are centrally involved in recruiting glutamate receptors at postsynaptic sites66. Similarly to CASK, PSD95 binds to intracellular adaptor proteins, and especially to GKAP (a protein that binds to the guanylate-kinase domain of PSD95), which, in turn, binds to SHANK proteins (Fig. 1b). A possible role of these interactions is to recruit postsynaptic adaptor proteins to the site of synaptic junctions. | SIGNOR-264192 |
P01116 | Q8WWW0 | 2 | binding | up-regulates activity | 0.69 | NORE1A can bind K-Ras.GTP through its RA domain and regulate the proapoptotic activity of MST1/2 kinases | SIGNOR-249586 |
Q969H0 | Q00653 | 2 | binding | down-regulates quantity by destabilization | 0.396 | Fbxw7α is a member of the F-box family of proteins, which function as the substrate-targeting subunits of SCF (Skp1/Cul1/F-box protein) ubiquitin ligase complexes. Using differential purifications and mass spectrometry, we identified p100, an inhibitor of NF-κB signalling, as an interactor of Fbxw7α. p100 is constitutively targeted in the nucleus for proteasomal degradation by Fbxw7α | SIGNOR-272907 |
P31749 | Q6PIY7 | 1 | phosphorylation | down-regulates activity | 0.2 | We found that Gld2 activity is regulated by site-specific phosphorylation in its disordered N-terminal domain. We identified two phosphorylation sites (S62, S110) where phosphomimetic substitutions increased Gld2 activity and one site (S116) that markedly reduced activity. Using mass spectrometry, we confirmed that HEK 293 cells readily phosphorylate the N-terminus of Gld2. We identified protein kinase A (PKA) and protein kinase B (Akt1) as the kinases that site-specifically phosphorylate Gld2 at S116, abolishing Gld2-mediated nucleotide addition. | SIGNOR-259405 |
P46108 | P16234 | 2 | binding | up-regulates | 0.647 | Crk could bind to both pdgf alpha- and beta-receptors in vivo. | SIGNOR-75881 |
P38398 | O95714 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.561 | HERC2 ubiquitinates BRCA1; this reaction depends on Cys(4762) of HERC2, the catalytic ubiquitin binding site, and the degron of BRCA1.|Significantly, HERC2 depletion antagonizes the effects of BARD1 depletion by restoring BRCA1 expression and G(2)-M checkpoint activity. | SIGNOR-278813 |
P36871 | Q13153 | 0 | phosphorylation | up-regulates | 0.343 | The signaling kinase p21-activated kinase 1 (pak1) binds to, phosphorylates and enhances the enzymatic activity of phosphoglucomutase 1 (pgm), | SIGNOR-127135 |
O60674 | P40189 | 0 | phosphorylation | up-regulates activity | 0.639 | All IL-6-type cytokines recruit gp130to their receptot complexes They either signal via gp130 alone [8] or in combination with LIFR [9] or the recently cloned OSMR [10], which are all able to activate Jaks proteins. Two tyrosine residues at the corresponding positions of Jak2 (tyrosine-1007 and tyrosine-1008) were found to be phosphorylated, and a single mutation of tyrosine-1007 eliminated essentially all tyrosine kinase activity [59]. | SIGNOR-238634 |
Q13490 | Q86VP3 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.303 | Under basal conditions, PACS-2 underwent K48-linked poly-ubiquitination, resulting in PACS-2 proteasomal degradation. Biochemical assays showed cIAP-1 and cIAP-2 interacted with PACS-2 in vitro and co-immunoprecipitation studies demonstrated that the two cIAPs bound PACS-2 in vivo. More importantly, both cIAP-1 and cIAP-2 directly mediated PACS-2 ubiquitination in a cell-free assay. | SIGNOR-272851 |
P63092 | P34969 | 2 | binding | up-regulates activity | 0.521 | 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-256783 |
P59768 | P42336 | 2 | binding | up-regulates | 0.477 | Gbetagamma subunits released from gi can activate pi3k (phosphoinositide 3-kinase), and can be therefore implicated in smo-dependent activation of akt. | SIGNOR-145122 |
P42345 | Q15382 | 2 | binding | up-regulates activity | 0.95 | Rheb stimulates the phosphorylation of mtor and plays an essential role in regulation of s6k and 4ebp1 in response to nutrients and cellular energy status. | SIGNOR-162006 |
P31749 | P09651 | 1 | phosphorylation | down-regulates | 0.412 | Our data also suggest that akt negatively regulates hnrnp a1-mediated ires activity via phosphorylation at ser199. | SIGNOR-252519 |
P17612 | Q92934 | 1 | phosphorylation | down-regulates | 0.542 | Ser-155 is the major phosphoacceptor site for pka on bad, but that pka also phosphorylates ser-112 and ser-136. Phosphorylated bad appears to be the inactive moiety. These results implicate pkac as the candidate kinase for s112 phosphorylation in vivo. | SIGNOR-67387 |
Q8N5S9 | P0DP25 | 2 | binding | up-regulates | 0.608 | The binding of Ca2+/CaM to CaM-KK is absolutely required for its activation and efficient phosphorylation of target protein kinases | SIGNOR-266344 |
O14965 | Q13526 | 1 | phosphorylation | down-regulates activity | 0.254 | Here, we found that aurora a can interact with and phosphorylate pin1 at ser16, which suppresses the g2/m function of pin1 by disrupting its binding ability and mitotic entry. | SIGNOR-202487 |
O75439 | Q9BXM7 | 1 | cleavage | down-regulates quantity by destabilization | 0.339 | 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-261363 |
P04049 | P62136 | 0 | dephosphorylation | up-regulates activity | 0.271 | We have identified a complex comprised of Shoc2/Sur-8 and the catalytic subunit of protein phosphatase 1 (PP1c) as a highly specific M-Ras effector. M-Ras targets Shoc2-PP1c to stimulate Raf activity by dephosphorylating the S259 inhibitory site of Raf proteins | SIGNOR-251649 |
Q9Y6H5 | P37840 | 2 | binding | up-regulates activity | 0.8 | Synphilin-1 interacts in vivo with α-synuclein, and their coexpression promotes the formation of Lewy body-like inclusions | SIGNOR-272597 |
Q969H0 | Q9UBK2 | 1 | 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 |
P17676 | Q99988 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.276 | Promoter analysis and chromatin immunoprecipitation analysis revealed that CEBPB could contribute to K7174-mediated transcriptional activation of GDF15. | SIGNOR-254050 |
O14965 | P57073 | 1 | phosphorylation | up-regulates activity | 0.2 | Therefore, Aurora-A not only directly phosphorylates SOX8 but also promotes SOX8 transcription indirectly by regulating c-Myc protein. | SIGNOR-280189 |
P27361 | Q15796 | 1 | phosphorylation | down-regulates | 0.748 | These results suggest that oncogenic ras, acting through mek1 and erk kinases, induces the phosphorylation of smad2 and smad3 | SIGNOR-66778 |
P17252 | Q5JVS0 | 1 | phosphorylation | down-regulates activity | 0.29 | We found a strong phosphorylation of Ki-1/57 by PKCalphabeta, PKCdelta, PKClambda/zeta, and especially by PKCsigma, however not by PKCmi. These data show that Ki-1/57 can serve in principal as a substrate for a wide variety of different PKC isoforms but also that its phosphorylation is strongest with PKCsigma. | This suggests that the two threonine residues present in this fragment (Thr354 and Thr375) might be the main target residues for phosphorylation by PKC in vitro. | Ki-1/57 Exits the Nucleus upon PMA Activation | SIGNOR-249246 |
Q9UHF5 | Q9NRM6 | 2 | binding | up-regulates | 0.748 | Here we report on the discovery of a novel il-17 homolog (il-17b), together with the identification of a novel cell surface receptor that specifically binds to it. We detail the molecular cloning, tissue distribution, and expression of both il-17b and il-17br, describe thein vivo activity of il-17b, and demonstrate binding to il-17br. | SIGNOR-76544 |
Q13485 | Q96JC1 | 0 | relocalization | down-regulates activity | 0.318 | The data demonstrating binding of TLP to TGF-β and activin type II receptors and selective inhibition of Smad3/Smad4 complex formation by deregulated TLP suggest that TLP is involved in localizing these receptors and Smad4 to specific intracellular compartments, where it regulates formation of Smad3/Smad4 but not Smad2/Smad4 complexes. | SIGNOR-261377 |
P35222 | O75309 | 2 | binding | up-regulates activity | 0.366 | At its C-terminus, cadherin interacts with β-catenin, which dynamically associates with α-catenin, a direct binding partner of filamentous actin | SIGNOR-265855 |
Q9HAU4 | O15105 | 2 | polyubiquitination | down-regulates quantity by destabilization | 0.87 | Smad7 Recruits Smurf2 to the TGFβ Receptor Complex. Here, we identify Smurf2, a C2-WW-HECT domain ubiquitin ligase and show that Smurf2 associates constitutively with Smad7. Smurf2 is nuclear, but binding to Smad7 induces export and recruitment to the activated TGF beta receptor, where it causes degradation of receptors and Smad7 via proteasomal and lysosomal pathways. | SIGNOR-272940 |
P18754 | Q13188 | 0 | phosphorylation | up-regulates | 0.2 | MST2 Phosphorylates RCC1 In Vitro and In Vivo. Using an antibody generated against phospho-S2/11 in RCC1 [18], we found that these two residues were also efficiently phosphorylated by MST1 and MST2 (Figure 2D), further supporting that S2 and/or S11 are genuine MST2 phosphorylation targets. | SIGNOR-263146 |
P30304 | Q9Y297 | 0 | ubiquitination | up-regulates | 0.494 | Scfb-trcp has recently been shown to degrade phosphorylated cdc25a in the s and g2 phases. | SIGNOR-128436 |
P42858 | P17612 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Moreover, phosphorylation of C-HEAT Ser2550 by cAMP-dependent protein kinase (PKA), the top hit in kinase activity screens, was found to hasten huntingtin degradation, such that levels of the catalytic subunit (PRKACA) were inversely related to huntingtin levels. | SIGNOR-277625 |
O95271 | Q9H2G9 | 1 | ADP-ribosylation | down-regulates quantity by destabilization | 0.351 | Here, we identify RNF146, a RING-domain E3 ubiquitin ligase, as a positive regulator of Wnt signalling. RNF146 promotes Wnt signalling by mediating tankyrase-dependent degradation of axin. Mechanistically, RNF146 directly interacts with poly(ADP-ribose) through its WWE domain, and promotes degradation of PARsylated proteins. Using proteomics approaches, we have identified BLZF1 and CASC3 as further substrates targeted by tankyrase and RNF146 for degradation. | SIGNOR-263385 |
O95622 | P38405 | 2 | binding | up-regulates activity | 0.615 | D1-class dopamine receptors (D1 and D5) activate the G s/olf family of G proteins to stimulate cAMP produc tion by AC and are found exclusively postsynaptically on dopamine-receptive cells, such as GABA-ergic medium spiny neurons (MSNs) in the striatum. | SIGNOR-264997 |
Q9NSD9 | Q2TAL8 | 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-269404 |
Q14814 | P12882 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.34 | Myocyte enhancer factor-2 and serum response factor binding elements regulate fast Myosin heavy chain transcription in vivo. We show that the upstream promoter region of the gene most abundantly expressed in mouse skeletal muscles, IIb MyHC, retains binding activity and transcriptional activation for three positive transcription factors, the serum response factor, Oct-1, and myocyte enhancer factor-2, whereas the other two genes (IIa and IId/x) have nucleotide substitutions in these sites that reduce binding and transcriptional activation | SIGNOR-238751 |
P19838 | O14920 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.853 | Ikkbeta phosphorylates p105 resulting in its degradation, which releases tpl2 resulting in activation of the pro-proliferative map kinase- pathway. | SIGNOR-70473 |
O15146 | Q9UPQ7 | 0 | ubiquitination | down-regulates quantity | 0.543 | We have identified a PDZ domain containing RING finger 3 (PDZRN3) as a synapse-associated E3 ubiquitin ligase and have demonstrated that it regulates the surface expression of muscle-specific receptor tyrosine kinase (MuSK), the key organizer of postsynaptic development at the mammalian neuromuscular junction. PDZRN3 binds to MuSK and promotes its ubiquitination. Together, these data demonstrate that PDZRN3 is a catalytically active RING-type E3 ubiquitin ligase | SIGNOR-271664 |
P42226 | O15524 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.638 | We found that IL-4, like IFN-gamma, induces rapid de novo expression of SOCS-1 in primary macrophages. Induction of SOCS-1 gene expression by IL-4 is STAT6-dependent. | SIGNOR-249570 |
P48740 | Q15485 | 2 | binding | up-regulates activity | 0.788 | H-ficolin binds to PSA, a polysaccharide produced by Aerococcus viridans. C4 was activated by H-ficolin preparations bound to PSA which had been coated on ELISA plates. These results indicate that H-ficolin is a second ficolin which is associated with MASPs and sMAP, and which activates the lectin pathway|Proteolytic activation of complement components by H-ficolin-MASP. | SIGNOR-263411 |
P12956 | Q13315 | 0 | phosphorylation | up-regulates activity | 0.713 | Ku70 phosphorylation occurs within minutes of genotoxic stress and involves DNA-PKcs and/or ATM kinase activities.By using specific vectors enabling the simultaneous shRNA-mediated inhibition of endogenous Ku70 and the expression of exogenous Ku70 resistant to shRNA (i.e. S27-S33-Ku70 and A27-A33-Ku70 expressing cells), we showed that phospho-Ku70 contributes to faster but error-prone DNA repair resulting in higher levels of chromosomal breaks. | SIGNOR-274020 |
Q13188 | Q7L9L4 | 1 | phosphorylation | up-regulates | 0.817 | Mob1, when phosphorylated by MST1/2, binds to the autoinhibitory motif in Lats1/2, which in turn leads to the phosphorylation of the Lats activation loop (Lats1 S909 and Lats2 S872) and thereby an increase of their kinase activity | SIGNOR-201290 |
P06213 | P10586 | 0 | dephosphorylation | down-regulates | 0.577 | Lar ptpase shows strong preference for dephosphorylation first at py5 (at tri-, di-, and monophosphotyrosyl levels). Initially this regioselectivity gives the y5(py9)(py10) diphospho regioisomer, followed by equal dephosphorylation at py9 or py10 to give the corresponding monophosphoryl species on the way to fully dephosphorylated product. | SIGNOR-76005 |
P51608 | Q14353 | 1 | post transcriptional regulation | up-regulates quantity by expression | 0.279 | MeCP2 binds to the promoter region of six target genes. ChIP with anti-MeCP2 antibody shows that MeCP2 binds to the promoter regions of activated targets Sst, Oprk1, Gamt, and Gprin1, and repressed targets Mef2c and A2bp1. | SIGNOR-264678 |
P49841 | Q92908 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.308 | We identified the AKT-repressed signal as glycogen synthase kinase 3 (GSK3)-catalyzed phosphorylation of Ser(37) on the long form of the transcription factor GATA6. Phosphorylation of GATA6 on Ser(37) promoted its degradation, thereby preventing GATA6 from repressing transcripts that are induced by TNF and attenuated by insulin. | SIGNOR-277241 |
P19525 | Q9NYA1 | 1 | phosphorylation | up-regulates activity | 0.2 | This suggests that PKR is critical in the phosphorylation of SPHK1 at Ser225.|We confirmed that phosphorylated PKR activates SPHK1 kinase activity, but it remained necessary to determine whether there has mutual correlation or any reciprocal effect between these two kinases in stressed cells. | SIGNOR-278514 |
P16104 | P45984 | 0 | phosphorylation | up-regulates | 0.2 | H2ax interacts with numerous proteins required for dna damage signaling and repair when phosphorylated on ser-140. Phosphorylation of ser-140 (h2ax139ph) in response to ionizing radiation is mediated by both atm and prkdc. Our data showed that h2ax is phosphorylated by uva-activated jnk. | SIGNOR-160210 |
Q14790 | Q15628 | 2 | binding | up-regulates activity | 0.909 | Tradd recruits caspase-8 | SIGNOR-118591 |
P01189-PRO_0000024969 | P29120 | 0 | cleavage | up-regulates quantity | 0.2 | POMC is post-translationally cleaved by prohormone convertase enzymes 1 and 2 (PC1, PC2) into ACTH, an N-terminal glycopeptide | SIGNOR-268724 |
P61073 | Q86V86 | 0 | phosphorylation | up-regulates quantity | 0.263 | Pim-1 and Pim-3 enhance phosphorylation and cell surface expression of CXCR4.|The intracellular tail of CXCR4 can be phosphorylated in vitro at Ser339 by Pim-1 kinase and by Pim-3, as shown here, but not by Pim-2. | SIGNOR-279092 |
P49715 | P49715 | 2 | transcriptional regulation | up-regulates quantity | 0.2 | Here, we demonstrate that C/EBPα indeed activates its promoter in transient transfection assays in myeloid cells. | SIGNOR-255673 |
Q05655 | Q16820 | 1 | phosphorylation | down-regulates quantity | 0.307 | These findings suggest that activation of a protein kinase, presumably PKC, mediates PMA-induced hmeprinβ shedding. By labeling COS-1 cells transfected with mutant constructs lacking the potential phosphorylation sites, we identified Ser687 as the main 32P-acceptor. These data provide evidence that the cytoplasmic domain of hmeprinβ can function as a PKC substrate. | SIGNOR-263171 |
Q05513 | Q05513 | 2 | phosphorylation | up-regulates | 0.2 | Our findings suggest that insulin, via pip(3), provokes increases in pkc-zeta enzyme activity through (a) pdk-1-dependent t410 loop phosphorylation, (b) t560 autophosphorylation | SIGNOR-85505 |
Q9Y4K3 | Q9C0C7 | 2 | binding | up-regulates activity | 0.588 | In this condition, AMBRA1, interacting with the E3-ligase TRAF6, supports ULK1 ubiquitylation by LYS-63-linked chains, and its subsequent stabilization, self-association and function. | SIGNOR-272963 |
Q8WUI4 | Q5H9F3 | 2 | binding | up-regulates activity | 0.48 | BCoR-L1 interacts with Class II HDACs, HDAC4, HDAC5, and HDAC7, suggesting that they are involved in its function as transcriptional corepressor. | SIGNOR-259114 |
P49336 | Q9UHV7 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.901 | Here, cyclin C-Cdk8 phosphorylation of Med13 most likely primes the phosphodegron for destruction. | SIGNOR-279687 |
Q13315 | Q9NQS1 | 2 | phosphorylation | up-regulates activity | 0.381 | Aven is also a substrate of the ATM kinase. Mutation of ATM-mediated phosphorylation sites on Aven reduced its ability to activate ATM, suggesting that Aven activation of ATM after DNA damage is enhanced by ATM-mediated Aven phosphorylation. We found that mutating S135 and S308 sites to Alanine largely dampened Aven’s phosphorylation by ATM (though some phosphorylation remained, due to either a contaminating kinase or an unidentified ATM phosphorylation site). | SIGNOR-262636 |
O60506 | P11362 | 0 | phosphorylation | down-regulates | 0.2 | Novel in vivo tyrosine phosphorylation sites were found in the fgfr-1, phospholipase cgamma, p90 ribosomal s6 kinase, cortactin, and ns-1-associated protein-1. Syncrip, was very recently found to be phosphorylated in response to insulin treatment of 3t3-l1 adipocytes (32). Phosphorylation of syncrip was accommodated by the insulin receptor tyrosine kinase in vitro but was inhibited upon binding of rna. Tyrosine phosphorylation at tyr-373 in the third rna recognition motif domain of nsap1/syncrip can possibly influence its rna binding properties and thus link fgfr-1 signaling to mrna metabolism. | SIGNOR-98704 |
P08709 | P05981 | 0 | cleavage | up-regulates activity | 0.347 | Hepsin, a putative membrane-associated serine protease, activates human factor VII and initiates a pathway of blood coagulation on the cell surface leading to thrombin formation|In contrast, an activation cleavage site factor VII mutant, R152E factor VII, was not cleaved by hepsin-transfected cells, suggesting that factor VII and S344A factor VII were activated on these cells by cleavage of the Arg152-Ile153 peptide bond. I | SIGNOR-263638 |
P15923 | O60682 | 2 | binding | down-regulates activity | 0.463 | ABF-1 contains a transcriptional repression domain and is capable of inhibiting the transactivation capability of E47 in mammalian cells. | SIGNOR-241315 |
O43508 | P11055 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | TWEAK induces ubiquitination of MyHCf and expression of atrogin-1 and MuRF1 in myotubes. our data show that TWEAK rapidly increases the conjugation of ubiquitin to MyHCf (Fig. 3A) and ubiquitination preceded the degradation of MyHCf (Fig. 2C and Fig. 3A). | SIGNOR-272628 |
O75326 | O60486 | 2 | binding | up-regulates | 0.913 | Plexin-c1 is a receptor for the gpi-anchored semaphorin sema7a. The cytoplasmic domain of plexins associates with a tyrosine kinase activity. Plexins may also act as ligands mediating repulsion in epithelial cells in vitro. | SIGNOR-71260 |
O00410 | Q8TD84 | 1 | relocalization | up-regulates activity | 0.2 | DSCAM and DSCAML1 specifically interacted with the importin beta IPO5, whereas deletion of the identified NLSs abolished this specific interaction and suppressed nuclear translocation of the DSCAM/L1 ICDs in cell lines and cultured neurons. This suggests a direct role of IPO5 in the nuclear import of the DSCAM/L1 ICDs. | SIGNOR-264274 |
Q6U7Q0 | Q969H0 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.2 | CK1delta and GSK3beta kinases sequentially phosphorylate ZNF322A at serine-396 and then serine-391. Moreover, the doubly phosphorylated ZNF322A protein creates a destruction motif for the ubiquitin ligase FBXW7alpha leading to ZNF322A protein destruction. | SIGNOR-264898 |
P51812 | P07101 | 1 | phosphorylation | up-regulates | 0.267 | Mitogen-activated protein-kinase (map) kinase-activated protein kinases 1 and 2 (mapkap kinase-1, mapkap kinase-2), were found to phosphorylate bacterially expressed human tyrosine hydroxylaserecombinant human tyrosine hydroxylase (hth1) was found to be phosphorylated by mitogen and stress-activated protein kinase 1 (msk1) at ser40 and by p38 regulated/activated kinase (prak) on ser19. Phosphorylation by msk1 induced an increase in vmax | SIGNOR-34682 |
Q13535 | Q8IUH4 | 1 | phosphorylation | up-regulates activity | 0.2 | Collectively these results suggest that ZDHHC13 phosphorylation by ATR following UVB irradiation promotes its interaction with MC1R to stimulate MC1R palmitoylation. | SIGNOR-273517 |
Q7Z2E3 | P05129 | 0 | phosphorylation | up-regulates | 0.32 | We show the novel molecular consequences of increased kinase activities of mutants: aprataxin (aptx), a dna repair protein causative for autosomal recessive ataxia, was found to be a preferential substrate of mutant pkc gamma, and phosphorylation inhibited its nuclear entry. ollectively, phosphorylation occurred at thr111, reducing nuclear aptx. | SIGNOR-186409 |
Q9C0F0 | Q92560 | 2 | binding | up-regulates activity | 0.53 | We report a critical link between BAP1 complex and BRD4, which is bridged by the physical interaction between ASXL3 and BRD4 in an SCLC subtype (SCLC-A), which expresses a high level of ASCL1. We further showed that ASXL3 functions as an adaptor protein, which directly interacts with BRD4's extra-terminal (ET) domain via a novel BRD4 binding motif (BBM), and maintains chromatin occupancy of BRD4 to active enhancers. | SIGNOR-266761 |
P08754 | O43614 | 2 | binding | up-regulates activity | 0.264 | 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-256872 |
O14640 | P46937 | 2 | binding | down-regulates | 0.333 | Yap restricts elevated wnt independently of the axinapcgsk-3beta complex partly by limiting the activity of dishevelled (dvl). | SIGNOR-199806 |
Q8NEB9 | P06493 | 0 | phosphorylation | down-regulates | 0.42 | We show that vps34 is phosphorylated on thr159 by cdk1, thr159 phosphorylation negatively regulates the ptdins3 kinase activity of vps34 and autophagy | SIGNOR-165768 |
Q04721 | Q4G148 | 2 | binding | up-regulates | 0.336 | We have previously identified two human genes, gxylt1 and gxylt2, encoding glucoside xylosyltransferases responsible for the transfer of xylose to o-linked glucose. The identity of the enzyme further elongating the glycan to generate the final trisaccharide xylose-xylose-glucose, however, remained unknown. Here, we describe that the human gene c3orf21 encodes a udp-xylose:alfa-xyloside alfa1,3-xylosyltransferase, acting on xylose-alfa1,3-glucosebeta1-containing acceptor structures. We have, therefore, renamed it xxylt1 (xyloside xylosyltransferase 1). Xxylt1 cannot act on a synthetic acceptor containing an alfa-linked xylose alone, but requires the presence of the underlying glucose. Activity on notch egf repeats was proven by in vitro xylosylation of a mouse notch1 fragment recombinantly produced in sf9 insect cells, a bacterially expressed egf repeat from mouse notch2 modified in vitro by rumi and gxylt2 and in vivo by co-expression of the enzyme with the notch1 fragment. The enzyme was shown to be a typical type ii membrane-bound glycosyltransferase localized in the endoplasmic reticulum. | SIGNOR-177694 |
P31749 | Q16763 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.437 | Mechanistically, Akt1 physically interacted with and phosphorylated UBE2S at Thr 152, enhancing its stability by inhibiting proteasomal degradation. | SIGNOR-265078 |
O00566 | P46782 | 2 | binding | up-regulates activity | 0.626 | Mpp10 is able to bind the ribosome biogenesis factor Utp3/Sas10 through two conserved motifs in its N-terminal region. In addition, Mpp10 interacts with the ribosomal protein S5/uS7 using a short stretch within an acidic loop region. Thus, our findings reveal that Mpp10 provides a platform for the simultaneous interaction with multiple proteins in the 90S pre-ribosome. | SIGNOR-261175 |
P51608 | O15111 | 0 | phosphorylation | up-regulates activity | 0.2 | Representative confocal micrographs of 4th day differentiating cultures are shown. (C) IKK\u03b1 promotes MeCP2-dependent BDNF expression.|The characterization of IKK\u03b1-mediated phosphorylation of MeCP2 at Ser421 and other residues and their effects on the activity of MeCP2 is a topic of current work in our laboratory. | SIGNOR-279459 |
P35611 | Q13464 | 0 | phosphorylation | up-regulates | 0.376 | Rho-associated kinase (rho- kinase), which is activated by the small guanosine triphosphatase rho, phosphorylates alpha-adducin and thereby enhances the f-actin-binding activity of alpha-adducin in vitro. Here we identified the sites of phosphorylation of alpha-adducin by rho-kinase as thr445 and thr480 | SIGNOR-66996 |
P08123 | P03956 | 0 | cleavage | down-regulates quantity by destabilization | 0.401 | In vitro, MMP1 initiates degradation of native fibrillar collagens, crucial components of vertebrate extracellular matrix (ECM), by cleaving the peptide bond between Gly775–Ile776 or Gly775–Lys776 in native type I, II or III collagen molecules3,4. | SIGNOR-272337 |
P22694 | Q92934 | 1 | phosphorylation | down-regulates | 0.429 | Ser-155 is the major phosphoacceptor site for pka on bad, but that pka also phosphorylates ser-112 and ser-136. | SIGNOR-81141 |
P19438 | Q15628 | 2 | binding | up-regulates activity | 0.805 | We have identified a novel 34 kda protein, designated tradd, that specifically interacts with an intracellular domain of tnfr1 tradd interacts with the death domain of tnfrsf1a to initiate distinct signaling cascades for two of the most important biological activities of tnf, nf-kb activation and programmed cell death tradd, a novel protein that specifically interacts with the death domain of tnfr1 and activates signaling pathways for both of these activities when overexpressed. | SIGNOR-32739 |
P24394 | O60674 | 1 | phosphorylation | up-regulates activity | 0.624 | Downstream intracellular signaling from the IL-4IL-4Rc complex involves activation of the Jak1 and Jak3 kinases, phosphorylation of the Stat6 transcription factor, and activation of the insulin receptor substrate (IRS)-2 and Dok2-signaling intermediates. IL-13 initially binds to IL-13R1 with intermediate affinity, and then heterodimerizes with IL-4R. The IL-13IL-13R1IL-4R complex activates the Tyk2, Jak2, and Jak1 kinases and Stat6. | SIGNOR-249530 |
Q07812 | Q07820 | 2 | binding | down-regulates | 0.736 | Which of the multiple pro-survival proteins that can bind Bax (fig. S15A) can functionally restrain it? Mcl-1 must, because neutralizing Mcl-1 by enforced Noxa expression rendered MEFs containing only Bax (Bak KO cells) sensitive to the Bad BH3 mimetic ABT-737 (Fig. 4A), which inactivates Bcl-2, Bcl-xL, and Bcl-w | SIGNOR-151787 |
P12931 | Q9UK53 | 1 | phosphorylation | down-regulates activity | 0.367 | Src Decreases the Stability and Level of ING1.|This study, as well as a previous report identifying Ser-126 of ING1 as a kinase target, confirm that ING1 stability is also regulated by phosphorylation. However, the mechanism may be complex since phosphorylation of Ser-126 stabilizes the protein while phosphorylation by Src reduces ING1 stability and causes a relocalization of ING1 from the nucleus to the cytoplasm. | SIGNOR-279760 |
Q13188 | Q13188 | 2 | phosphorylation | up-regulates | 0.2 | Consistent with previous studies, sts alone induces mst2 cleavage and autophosphorylation of thr180, an indicator of mst2 activation, as well as apoptosis. | SIGNOR-164310 |
P43405 | P29350 | 0 | dephosphorylation | down-regulates | 0.737 | We propose that shp1 can dephosphorylate sites in zap-70 and syk that are involved in coupling these kinases to downstream signaling cascades, including erk2 and elements of the il-2 gene. | SIGNOR-70234 |
P06493 | Q8IXJ6 | 1 | phosphorylation | down-regulates | 0.412 | Here, we demonstrate that sirt2 is phosphorylated both in vitro and in vivo on serine 368 by the cell-cycle regulator, cyclin-dependent kinase 1. Overexpression of sirt2 mediates a delay in cellular proliferation that is dependent on serine 368 phosphorylation. | SIGNOR-154681 |
P60709 | P12277 | 0 | relocalization | up-regulates quantity | 0.292 | In summary, data presented here strongly suggest that locally generated ATP is an important regulator for actin-based cytoskeletal dynamics involved in cell extension and motility and that CK-B is a controlling enzyme in the compartmentalization of ATP availability. CK-B co-localizes with cortical actin and facilitates spreading of astrocytes | SIGNOR-265791 |
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