IdA stringlengths 6 21 | IdB stringlengths 6 21 | labels float64 0 2 | mechanism stringclasses 40 values | effect stringclasses 10 values | score float64 0.1 0.99 ⌀ | sentence stringlengths 10 1.63k ⌀ | signor_id stringlengths 12 14 |
|---|---|---|---|---|---|---|---|
P31751 | Q13418 | 0 | phosphorylation | up-regulates activity | 0.615 | ILK mediated activation of Akt2 is required for Tbeta4 inducible expression of MMP-2 and EC motility.|Our experiments suggest that ILK phosphorylates Akt2 at Ser474, that Akt2 is a better substrate than Akt1, and that a post-translational modification to ILK is required for its activity. | SIGNOR-279055 |
Q96J02 | Q15366 | 0 | 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 |
Q07889 | P16333 | 0 | binding | up-regulates | 0.615 | We also found that nck binds directly to the guanine nucleotide exchange factor sos. / by binding to sos, nckmay bring sos to cell membrane where the ras protein is located. | SIGNOR-236321 |
P20936 | P12931 | 0 | phosphorylation | down-regulates | 0.615 | The phosphorylation of p120-gap by p60c-src inhibited its ability to stimulate the ha-ras-gtpase activity | SIGNOR-86008 |
P63000 | P12931 | 0 | phosphorylation | up-regulates activity | 0.615 | In addition, Rac1 is phosphorylated at Y64 by FAK and Src kinases ( xref ); Y64 phosphorylation targets Rac1 to focal adhesions. | SIGNOR-280132 |
O60674 | P26951 | 0 | binding | up-regulates | 0.615 | Indeed, only upon fibronectin adhesion is janus kinase 2 (jak2) recruited to the beta1 integrin-il-3r complex and triggers il-3r beta common phosphorylation, leading to the formation of docking sites for activated stat5a. | SIGNOR-134859 |
P37173 | Q9HCE7 | 0 | ubiquitination | down-regulates activity | 0.615 | 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-195672 |
Q08334 | Q8IU54 | 0 | binding | up-regulates | 0.615 | Il-28 and il-29 interacted with a heterodimeric class ii cytokine receptor that consisted of il-10 receptor beta (il-10rbeta) and an orphan class ii receptor chain, designated il-28ralpha. | SIGNOR-96177 |
Q96J02 | P49757 | 0 | binding | up-regulates | 0.615 | Numb activates the catalytic activity of itch, releasing it from an inhibitory intramolecular interaction between its homologous to e6-ap c-terminus and ww domains. | SIGNOR-167844 |
P48551 | P01562 | 0 | binding | up-regulates activity | 0.614 | Ifn-alpha, ifn-beta, and ifn-omega, induce somewhat different cellular effects but act through a common receptor complex, ifnar, composed of subunits ifnar-1 and ifnar-2. | SIGNOR-219298 |
Q13469 | P16298 | 0 | dephosphorylation | up-regulates | 0.614 | Calcineurin dephosphorylates members of the nuclear factor of activated T cells (NFAT)2 transcription factor family, allowing NFAT to translocate to the nucleus where it cooperates with other transcription factors to induce transcription of target genes. | SIGNOR-233438 |
P50148 | P35368 | 0 | binding | up-regulates activity | 0.614 | 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-257079 |
O15519 | Q96J02 | 0 | ubiquitination | down-regulates quantity | 0.614 | Depends on JNK-mediated phosphorylation and activation of the E3 ubiquitin ligase Itch, which specifically ubiquitinates c-FLIP and induces its proteasomal degradation. | SIGNOR-245307 |
P00519 | P22681 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.614 | We found that while c-cbl e3 ligase induced ubiquitin-dependent degradation of mature and phosphorylated bcr-abl proteins | SIGNOR-167194 |
Q04206 | Q9UHD2 | 0 | phosphorylation | up-regulates | 0.614 | Chromatographic fractionation of cell extracts allowed the identification of two distinct enzymatic activities phosphorylating ser-536. Peak 1 represents an unknown kinase, whereas peak 2 contained ikkalpha, ikkbeta, ikkepsilon, and tbk1. collectively, our results provide evidence for at least five kinases that converge on ser-536 of p65 and a novel function for this phosphorylation site in the recruitment of components of the basal transcriptional machinery to the interleukin-8 promoter. | SIGNOR-129951 |
P53667 | Q13153 | 0 | phosphorylation | up-regulates activity | 0.614 | Activation of lim-kinase by pak1 couplesp21-activated kinase (pak1) phosphorylates lim-kinase at threonine residue 508 within lim-kinase's activation loop | SIGNOR-72142 |
P35968 | P12931 | 0 | phosphorylation | up-regulates activity | 0.614 | In contrast, our analysis showed that over-expression of c-Src significantly enhances the ability of VEGFR-2 to stimulate proliferation of PAE cells and over-expression of dominant negative Src (Src kinase-dead) inhibits the VEGFR-2 driven proliferation of PAE cells (XREF_FIG).|Taken together, the data demonstrate that Src kinases upon activation by VEGFR-2 phosphorylate Y1173 of VEGFR-2 (XREF_FIG). | SIGNOR-279120 |
P25054 | P49674 | 0 | phosphorylation | up-regulates activity | 0.614 | Apc can be phosphorylated by ck1epsilon at ser1279 and ser1392. Mutation of conserved serine residues in the beta-catenin regulatory motifs of APC interfered with both axin-dependent phosphorylation and phosphorylation by CKIepsilon and impaired the ability of APC to regulate beta-catenin. | SIGNOR-109664 |
Q53EL6 | P23443 | 0 | phosphorylation | down-regulates | 0.614 | Both akt and p70(s6k) phosphorylate pdcd4, allowing for binding of the e3-ubiquitin ligase beta-trcp and consequently ubiquitylation. | SIGNOR-150144 |
O60353 | Q9ULT6 | 0 | ubiquitination | down-regulates quantity | 0.614 | Here we show that the cell-surface transmembrane E3 ubiquitin ligase zinc and ring finger 3 (ZNRF3) and its homologue ring finger 43 (RNF43) are negative feedback regulators of Wnt signalling. ZNRF3 is associated with the Wnt receptor complex, and inhibits Wnt signalling by promoting the turnover of frizzled and LRP6. | SIGNOR-260114 |
O75553 | P06241 | 0 | phosphorylation | down-regulates activity | 0.614 | Tyrosine phosphorylation of Dab1 by Fyn inhibits its interaction with APP, while increasing its interaction with Fyn. | SIGNOR-278476 |
Q9H2K2 | Q9NTX7 | 0 | ubiquitination | down-regulates quantity | 0.614 | 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-260005 |
Q9Y4P1 | O75385 | 0 | phosphorylation | down-regulates activity | 0.614 | Here we find that ULK1, a protein kinase activated at the autophagosome formation site, phosphorylates human ATG4B on serine 316.|Thus ULK1 is able to inhibit LC3 processing by a direct effect on ATG4B, possibly by phosphorylation of a serine residue of ATG4B.Fig. 1ULK1 inhibits ATG4B-mediated LC3 cleavage. a Average ATG4B activity in Actin-LC3-DelN Luciferase HEK293T obtained by measuring the secreted luciferase activity 48 h after transfection with the indicated constructs (n = 3, average \u00b1 s.d.) and representative immunoblot from one experiment showing expression of the different constructs. b GST-LC3 assay to measure in vitro activity of recombinant ATG4B after incubation with active recombinant ULK1. | SIGNOR-279434 |
Q99704 | P07949 | 0 | binding | up-regulates | 0.614 | Dok proteins directly associate with tyrosine 1062 of ret and could be its substrates. Phosphorylation of dok1 is necessary for interaction with ras-gap in vitro and in vivo. Dok1 is a negative regulator for the ras/erk signaling pathway activated by ret. | SIGNOR-90158 |
O60674 | P10721 | 0 | binding | up-regulates activity | 0.614 | C-Kit stimulates rapid and transient tyrosine phosphorylation of JAK2. JAK2 was found to be constitutively associated with c-Kit, with increased association after ligand stimulation of c-Kit | SIGNOR-254954 |
Q12778 | Q9UBE8 | 0 | phosphorylation | down-regulates activity | 0.613 | Here, we report that the transforming growth factor-beta-activated kinase (TAK1)-Nemo-like kinase (NLK) pathway negatively regulates FOXO1. We show that NLK binds and phosphorylates FOXO1 at Pro-directed Ser/Thr residues in the transactivation domain. The phosphorylation by TAK1-NLK pathway inhibits the transcriptional activity of FOXO1 and excludes FOXO1 from the nucleus, which is independent of phosphatidylinositol 3-kinase/Akt pathway. | SIGNOR-273907 |
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 |
Q969V1 | P20382 | 0 | binding | up-regulates | 0.613 | Upon several purification steps, followed by mass spectrometric analysis and peptide sequencing, the ligand was identified as melanin concentrating hormone (mch), revealing that the orphan slc-1 is the mch receptor. | SIGNOR-70520 |
P05106 | P31749 | 0 | phosphorylation | down-regulates activity | 0.613 | A survey of several protein kinases revealed that Thr-753 was avidly phosphorylated by PDK1 and Akt/PKB in vitro. These observations suggest that activation of PDK1 and/or Akt/PKB in platelets may modulate the binding activity and/or specificity of beta(3) for signaling molecules. | SIGNOR-252552 |
P14653 | P55347 | 0 | binding | up-regulates activity | 0.613 | we observe the formation of a ternary Prep1-Pbx1-HOXB1 complex on a HOXB1-responsive target in vitro. Interaction with Prep1 enhances the ability of the HOXB1-Pbx1 complex to activate transcription in a cooperative fashion from the same target. | SIGNOR-241215 |
P46531 | Q969H0 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.613 | Purified recombinant cycc:cdk8 phosphorylates the notch icd within the tad and pest domains, and expression of cycc:cdk8 strongly enhances notch icd hyperphosphorylation and pest-dependent degradation by the fbw7/sel10 ubiquitin ligase in vivo. | SIGNOR-130706 |
P84022 | O15105 | 0 | transcriptional regulation | down-regulates quantity | 0.613 | The downstream molecules including mad2, smad3, smad4 and smad7 are involved in TGF-β1-induced EMT,while Smad7 blocks the smad3 expression | SIGNOR-260437 |
P52564 | Q99683 | 0 | phosphorylation | up-regulates activity | 0.613 | A MAP kinase kinase kinase (MAPKKK), termed ASK1, was identified that activated two different subgroups of MAP kinase kinases (MAPKK), SEK1 (or MKK4) and MKK3/MAPKK6 (or MKK6), which in turn activated stress-activated protein kinase (SAPK, also known as JNK; c-Jun amino-terminal kinase) and p38 subgroups of MAP kinases, respectively. | SIGNOR-45353 |
P07225 | P38435 | 0 | carboxylation | up-regulates activity | 0.613 | Gamma-carboxylation is essential in the activation and proper functioning of multiple VK-dependent proteins (VKDP), the most well-known of which are involved in blood clotting, including coagulation factors (FII, FVII, FIX and FX) and natural anti-clotting agents (protein C, protein S (ProS; OMIM*176880) and protein Z | SIGNOR-265924 |
P98177 | P45983 | 0 | phosphorylation | up-regulates | 0.612 | Upon treatment of cells with h2o2, the small gtpase ral is activated and this results in a jnk-dependent phosphorylation of foxo4 on threonine 447 and threonine 451. This ral-mediated, jnk-dependent phosphorylation is involved in the nuclear translocation and transcriptional activation of foxo4 after h2o2 treatment. | SIGNOR-130385 |
P45985 | Q9Y2U5 | 0 | phosphorylation | up-regulates activity | 0.612 | Both mekk2 and mekk3 are able to activate the jun kinase pathway in vivo. However, following routine immunoprecipitation in triton x-100, mekk2 but not mekk3 is able to effectively phosphorylate both sek-1 and mek-1 and to undergo autophosphorylation | SIGNOR-107695 |
Q14814 | Q16539 | 0 | phosphorylation | up-regulates activity | 0.612 | Targeting of ash2l to specific genes is mediated by the transcriptional regulator mef2d. Furthermore, this interaction is modulated during differentiation through activation of the p38 mapk signaling pathway via phosphorylation of mef2d. | SIGNOR-159331 |
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 |
Q12931 | Q9BXM7 | 0 | phosphorylation | up-regulates activity | 0.612 | This would mean that PINK1 knockdown should reduce TRAP1 activity, thereby potentiating BAY induced cell death.|PINK1 can phosphorylate TRAP1 to prevent apoptosis induced by oxidative stress. | SIGNOR-278186 |
P10301 | P29323 | 0 | phosphorylation | down-regulates activity | 0.612 | Tyrosine 66 of R-Ras is phosphorylated by EphB2|. R-Ras, a small intracellular GTPase, regulates the binding of integrins to their ligands outside the cell. |Cells in which EphB2 is activated become poorly adherent to substrates coated with integrin ligands, and a tyrosine residue in the R-Ras effector domain is phosphorylated. | SIGNOR-251125 |
P50549 | P49137 | 0 | phosphorylation | up-regulates | 0.612 | Neverthless, some transcription factors, such as e47, er81, srf and creb are also phosphorylated by mk2 | SIGNOR-166625 |
Q05586 | Q14957 | 0 | binding | up-regulates activity | 0.612 | Here, we demonstrate that PKB/Akt directly phosphorylates NR2C on serine 1096 (S1096). In addition, we identify 14-3-3epsilon as an NR2C interactor, whose binding is dependent on S1096 phosphorylation. These data are all consistent with a model in which NR1 and NR2C oligomerize, PKB phosphorylates S1096, and 14-3-3ε binds to phosphorylated NR2C thereby promoting NR2C-containing NMDA receptor surface expression in cerebellar granule cells. | SIGNOR-262621 |
P40763 | P19525 | 0 | phosphorylation | up-regulates activity | 0.612 | Silencing PKR gene expression in HepG2 cells with siRNA reduced STAT3 phosphorylation at Tyr705 and Ser727 (XREF_FIG).|The results also revealed that PKR activates STAT3, a transcription factor associated with primary liver tumors, which is suggested to promote tumor cell proliferation. | SIGNOR-279613 |
O60462 | Q13275 | 0 | binding | up-regulates | 0.612 | In the nervous system, neuropilins mediate axon retraction and guidance by binding class iii semaphorins. We found that sema3f could compete with metabolically labeled vegf-c for the binding to np1-ig and np2-ig fusion proteins. | SIGNOR-147608 |
P00533 | O60674 | 0 | phosphorylation | up-regulates activity | 0.612 | Tyrosine at residue 1,068 of the EGFR is proposed to be one of the principal phosphorylation sites and Grb2-binding sites stimulated by growth hormone via Jak2. Our results indicate that the role of EGFR in signalling by growth hormone is to be phosphorylated by Jak2, thereby providing docking sites for Grb2 and activating MAP kinases and gene expression, independently of the intrinsic tyrosine kinase activity of EGFR.  | SIGNOR-251347 |
Q9UER7 | Q86Z02 | 0 | phosphorylation | down-regulates activity | 0.611 | HIPK1 phosphorylates Daxx on Ser 669, and phosphorylation of this site is important in modulating the ability of Daxx to function as a transcriptional repressor. | Therefore, phosphorylation at Ser 669 by HIPK1 diminishes the ability of Daxx to repress transcription. | SIGNOR-260842 |
P52565 | Q13153 | 0 | phosphorylation | down-regulates | 0.611 | Pak1 binds and phosphorylates rhogdi both in vitro and in vivo at ser101 and ser174. This resulted in dissociation of rac1-rhogdi, but not rhoa-rhogdi, complexes, as determined by in vitro assays of complexation and in vivo by coimmunoprecipitation analysis. We observed that cdc42-induced rac1 activation is inhibited by expression of pak1 autoinhibitory domain. The dissociation of rac1 from rhogdi and its subsequent activation stimulated by pdgf or egf is also attenuated by pak1 autoinhibitory domain, and this is dependent on the ability of rhogdi to be phosphorylated at ser101/174. | SIGNOR-126654 |
P55085 | P00734 | 0 | binding | up-regulates | 0.611 | Other major aspects of par-2 are highlighted, in particular the ability of several serine protease enzymes, in addition to trypsin, to function as activators of par-2. | SIGNOR-108183 |
P30291 | O14757 | 0 | phosphorylation | up-regulates | 0.611 | Chk1 also phosphorylates and stabilizes wee1. | SIGNOR-163164 |
P53350 | P06493 | 0 | binding | up-regulates activity | 0.611 | Moreover, CDK1 phosphorylates RSF1 at Ser1375, and this phosphorylation is necessary for PLK1 recruitment. Subsequently, PLK1 phosphorylates RSF1 at Ser1359, stabilizing PLK1 deposition. | SIGNOR-273589 |
P04637 | Q15759 | 0 | phosphorylation | up-regulates | 0.611 | We show that prak activates p53 by direct phosphorylation. | SIGNOR-152843 |
O75582 | Q16539 | 0 | phosphorylation | up-regulates activity | 0.611 | In the present study, we show that, in addition to being phosphorylated on Thr-581 and Ser-360 by ERK1/2 or p38, MSK1 can autophosphorylate on at least six sites: Ser-212, Ser-376, Ser-381, Ser-750, Ser-752 and Ser-758. Of these sites, the N-terminal T-loop residue Ser-212 and the 'hydrophobic motif' Ser-376 are phosphorylated by the C-terminal kinase domain of MSK1, and their phosphorylation is essential for the catalytic activity of the N-terminal kinase domain of MSK1 | SIGNOR-249199 |
Q8TD19 | P53350 | 0 | phosphorylation | up-regulates activity | 0.611 | We now identify Plk1 as Nek9 direct activator and propose a two-step activation mechanism that involves Nek9 sequential phosphorylation by CDK1 and Plk1. while CDK1 activity is necessary for Nek9 phosphorylation in mitosis and the resulting change in electrophoretical mobility, Nek9 Thr210 phosphorylation and mitotic activation requires both CDK1 and Plk1. | SIGNOR-273888 |
Q12888 | Q9NS91 | 0 | ubiquitination | up-regulates activity | 0.611 | RAD18 associates with 53BP1 and is recruited to DSB sites in a 53BP1 dependent manner specifically during G1-phase, RAD18 monoubiquitinates KBD domain of 53BP1 at lysine 1268 in vitro.|These results suggest that RAD18 directed modification at Lysine 1268 of 53BP1 promotes the retention of 53BP1 at DSBs. | SIGNOR-278593 |
P62987 | Q93008 | 0 | cleavage | up-regulates quantity | 0.611 | Here we provide data suggesting that two of the four mammalian ubiquitin precursors, UBA52 and UBA80, are processed mostly post-translationally whereas the other two, UBB and UBC, probably undergo a combination of co- and post-translational processing. Using an unbiased biochemical approach we found that UCHL3, USP9X, USP7, USP5 and Otulin/Gumby/FAM105b are by far the most active DUBs acting on these precursors. | SIGNOR-270825 |
P04637 | Q13362 | 0 | dephosphorylation | up-regulates quantity by stabilization | 0.611 | Ablation of the B56gamma protein by RNAi, which abolishes the Thr55 dephosphorylation in response to DNA damage, reduces p53 stabilization, Bax expression and cell apoptosis. To investigate the molecular mechanisms, we have shown that the endogenous B56gamma protein level and association with p53 increase after DNA damage. Finally, we demonstrate that Thr55 dephosphorylation is required for B56gamma3-mediated inhibition of cell proliferation and cell transformation. | SIGNOR-268154 |
P36894 | Q13253 | 0 | binding | down-regulates activity | 0.611 | Noggin binds the domain that is re-quired for bmp-7 to interact with bmp type i and type ii receptors (PMID 22298955).Noggin Inhibits bmp by blocking the molecular interfaces of the binding epitopes for both type i and type ii receptors. | SIGNOR-219221 |
P62837 | P28328 | 0 | binding | up-regulates activity | 0.611 | Here we report on the identification of the protein-ubiquitin ligases that are responsible for the ubiquitination of the peroxisomal protein import receptor Pex5. It is demonstrated that each of the three RING peroxins Pex2, Pex10, and Pex12 exhibits ubiquitin-protein isopeptide ligase activity. Our results show that Pex2 mediates the Ubc4-dependent polyubiquitination whereas Pex12 facilitates the Pex4-dependent monoubiquitination of Pex5.While polyubiquitinated Pex5 is degraded by the proteasome, monoubiquitinated Pex5 is destined for a new round of the receptor cycle. | SIGNOR-253025 |
P98077 | P00533 | 0 | binding | up-regulates | 0.611 | Shc exists in three different isoforms, p46shc, p52shc and p66shc which are tyrosine phosphorylated upon egf stimulation and bind to the activated egfr and grb2. Interestingly, while the 46 and 52 kda isoforms increase mitogenic signalling after egf stimulation and are able to transform nih3t3 cells (pelicci et al. 1992), p66shc has no transforming potential and negatively influences egf-induced c-fos transcription | SIGNOR-107750 |
Q09472 | Q9H2X6 | 0 | phosphorylation | up-regulates activity | 0.611 | Furthermore, HIPK2 forms a complex with the coactivator p300 and AML1, phosphorylates p300 at multiple Serine/Threonine sites and activates p300 HAT activity and coactivator function. | SIGNOR-278943 |
O75197 | P09544 | 0 | binding | up-regulates | 0.611 | Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation. | SIGNOR-131727 |
P07585 | P09237 | 0 | cleavage | down-regulates quantity by destabilization | 0.61 | Degradation of decorin by matrix metalloproteinases. These data indicate proteolytic degradation of DCN by MMP-2, MMP-3 and MMP-7, and suggest the possibility that, under pathophysiological conditions, the digestion by the MMPs may induce tissue reactions mediated by TGF-beta1 released from DCN in the connective tissues. | SIGNOR-256352 |
P40692 | P04637 | 0 | transcriptional regulation | up-regulates quantity | 0.61 | .... numerous potentially novel targets, including the DNA mismatch repair genes MLH1 and PMS2. Both of these genes were determined to be responsive to DNA damage and p53 activation in normal human fibroblasts, and have p53-response elements within their first intron. | SIGNOR-257605 |
P04637 | Q9Y4K3 | 0 | ubiquitination | up-regulates activity | 0.61 | Here, we show that TRAF6 E3 ligase is a crucial factor to restrict mitochondrial translocation of p53 and spontaneous apoptosis by promoting K63-linked ubiquitination of p53 at K24 in cytosol, and such ubiquitination limits the interaction between p53 and MCL-1/BAK.|We mutated every conserved lysine (K) residue on p53 and found that TRAF6 preferentially ubiquitinates p53 at K24 in the in vivo ubiquitination assay (XREF_FIG, XREF_SUPPLEMENTARY, XREF_SUPPLEMENTARY and XREF_SUPPLEMENTARY). | SIGNOR-278728 |
P31785 | Q9HBE4 | 0 | binding | up-regulates | 0.61 | The common gamma-chain (gamma(c)) is an indispensable subunit of the functional receptor complexes for il-4, il-7, il-9, and il-15 as well as il-2. Here we show that the gamma(c) is also shared with the il-21r complex | SIGNOR-108858 |
P26038 | P61586 | 0 | phosphorylation | up-regulates activity | 0.61 | Rev-erbα interacted with OPHN-1, promoted RhoA activity and phosphorylation of ERM. etection of phosphorylated ezrin (Thr567)/radixin (Thr564)/moesin (Thr558)(p-ERM) in Rev-erbαfl/flCre− and Rev-erbαfl/flPF4Cre+ platelets using phospho-specific antibodies. | SIGNOR-268431 |
Q15691 | Q7Z460 | 0 | binding | up-regulates activity | 0.61 | CLIP-associating protein (CLASP) 1 and CLASP2 are mammalian microtubule (MT) plus-end binding proteins, which associate with CLIP-170 and CLIP-115.|We demonstrate that the middle part of CLASPs binds directly to EB1 and to MTs. | Both EB1- and cortex-binding domains of CLASP are required to promote MT stability. | SIGNOR-265094 |
P11441 | Q92995 | 0 | deubiquitination | up-regulates activity | 0.61 | USP13 and gp78 control ubiquitination of Ubl4A.These data suggest that USP13 and gp78 play antagonizing roles in regulation of Ubl4A ubiquitination: While gp78 assembles ubiquitin chains on Ubl4A, USP13 antagonizes this activity to limit Ubl4A ubiquitination.Ubiquitination of Ubl4A preferentially occurs on Lys48. We identify the Bag6 cofactor Ubl4A as a shared substrate of gp78 and USP13. USP13 depletion is associated with hyper-ubiquitination of Ubl4A and altered interaction between the Bag6 complex and its co-chaperone SGTA. Because the interaction of Ubl4A with SGTA is mediated by positively-charged residues in Ubl4A including Lys48 (Chartron et al., 2012; Xu et al., 2012), which happens to be the major ubiquitination site, the simplest model to explain reduced Bag6-SGTA interaction in USP13 knockdown cells is that ubiquitin conjugates on Ubl4A sterically hinder SGTA binding. | SIGNOR-272857 |
P43405 | P07948 | 0 | phosphorylation | up-regulates activity | 0.61 | Lyn phosphorylates and activates Syk and LAT. | SIGNOR-279415 |
Q9Y3F4 | O15105 | 0 | binding | up-regulates | 0.61 | Strap recruits smad7 to the activated type i receptor and forms a complex | SIGNOR-76771 |
P35638 | Q16539 | 0 | phosphorylation | up-regulates activity | 0.61 | CHOP, a member of the C/EBP family of transcription factors, mediates effects of cellular stress on growth and differentiation. It accumulates under conditions of stress and undergoes inducible phosphorylation on two adjacent serine residues (78 and 81). In vitro, CHOP is phosphorylated on these residues by p38 mitogen-activated protein kinase (MAP kinase). | SIGNOR-250096 |
O43586 | Q05209 | 0 | dephosphorylation | down-regulates activity | 0.61 | We also demonstrate that PTP-PEST dephosphorylates PSTPIP at tyrosine 344. Importantly, we identified tyrosine 344 as the main phosphorylation site of PSTPIP by performing tryptic phosphopeptide maps. |The biological functions of the complexes formed between PSTPIP and SH2 domain-containing tyrosine kinases may be to transmit the signals from activated EGF and PDGF receptor.|Furthermore, we show that PSTPIP is phosphorylated downstream of the activated PDGF and EGF receptors. This phosphorylation of PSTPIP is most likely mediated by c-Abl | SIGNOR-248656 |
P52735 | O60716 | 0 | binding | up-regulates | 0.61 | We demonstrate that p120-catenin participates in the stimulation of rac1 activity, binding directly to this protein. In addition we show that vav2 also binds to p120-catenin and is required for rac1 activation and for beta-catenin translocation to the nucleus.Vav2 And rac1 association with p120-catenin was modulated by phosphorylation of this protein, which was stimulated upon serine/threonine phosphorylation by ck1 and inhibited by tyrosine phosphorylation by src or fyn | SIGNOR-198941 |
Q6ZN44 | Q9HB63 | 0 | binding | up-regulates | 0.61 | The unc5hs are axon guidance receptors that mediate netrin-1-dependent chemorepulsion, and dependence receptors that mediate netrin-1-independent apoptosis. | SIGNOR-98483 |
P42336 | Q15303 | 0 | binding | up-regulates | 0.609 | Pi3k is the sole binding partner to six tyrosines of erbb3 and one in erbb4. | SIGNOR-146879 |
Q9NRM7 | Q13188 | 0 | phosphorylation | up-regulates | 0.609 | Activation of mst1/2 leads to phosphorylation and activation of their direct substrates, lats1/2. | SIGNOR-175801 |
P46108 | P09619 | 0 | binding | up-regulates | 0.609 | Crk could bind to both pdgf alpha- and beta-receptors in vivo | SIGNOR-75884 |
Q9UBS0 | O15530 | 0 | phosphorylation | up-regulates activity | 0.609 | Mutational analysis revealed that the phosphorylation of Thr241 and Thr401 in p70beta1 was indispensable for the kinase activity. In contrast, a p70beta1 mutant in which Ser383 was substituted with Gly (S383G) still retained nearly the half maximal activity. Sequential phosphorylation of wild-type and S383G mutant of p70beta1 with mTOR and 3-phosphoinositide-dependent protein kinase 1 (PDK1) in vitro synergistically activated their kinase activities. | SIGNOR-250272 |
Q99728 | P24941 | 0 | phosphorylation | down-regulates activity | 0.609 | CDK2-cyclin A1/E1 and CDK1-cyclin B1 phosphorylate BARD1 on its NH(2) terminus in vivo and in vitro. 44999999="E1" 45999998="terminus"}|Here we show that the ubiquitin ligase activity of BRCA1-BARD1 is down-regulated by CDK2. | SIGNOR-280211 |
O43424 | A4D2P6 | 0 | binding | up-regulates quantity | 0.609 | We identified a novel GluRdelta2-interacting protein, named Delphilin, that contains a single PDZ domain and formin homology (FH) domains FH1 and FH2 plus coiled-coil structure. Delphilin is selectively localized at the postsynaptic junction site of the parallel fiber-Purkinje cell synapse and colocalized with GluRdelta2. Thus, Delphilin is a postsynaptic scaffolding protein at the parallel fiber-Purkinje cell synapse, where it may serve to link GluRdelta2 with actin cytoskeleton and various signaling molecules. | SIGNOR-264475 |
P33176 | Q86UP2 | 0 | binding | up-regulates | 0.609 | This study demonstrated the effect of kinectin-kinesin interaction on lysosome dynamics and observed that the kinesin-binding domain of kinectin can significantly enhance the mt-stimulated atpase activity of kinesin. | SIGNOR-128092 |
O75581 | O00744 | 0 | binding | up-regulates activity | 0.609 | Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation. | SIGNOR-131631 |
P63000 | Q70Z35 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.609 | 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-260571 |
P12694 | O14874 | 0 | phosphorylation | down-regulates | 0.609 | Phosphorylation sites and inactivation of branched-chain alpha-ketoacid dehydrogenase isolated from rat heart, bovine kidney, and rabbit liver, kidney, heart, brain, and skeletal muscle. | SIGNOR-25084 |
P00533 | P17252 | 0 | phosphorylation | down-regulates activity | 0.609 | Biochemical and morphological analyses indicate that threonine-phosphorylated EGFR molecules undergo normal internalization, but instead of sorting to lysosomal degradation, they recycle back to the cell surfaceThe inhibitory effects of pkc are mediated by a single threonine residue (threonine 654) of egfr | SIGNOR-77421 |
Q99496 | Q8NHM5 | 0 | binding | up-regulates activity | 0.609 | BcoR and Fbxl10/Jhdm1B are among the most abundant Ring1B/Rnf2 interactors identified with the highest confidence, and their association has been validated by coimmunoprecipitation studies; hence we call this the Fbxl10-BcoR complex. The assembly of Fbxl10-BcoR complex(es), the associations among its various subunits, and its functional significance remain to be characterized but are presently under investigation. | SIGNOR-252242 |
Q15303 | Q96JA1 | 0 | ubiquitination | down-regulates | 0.608 | We report upregulation of lrig1 transcript and protein upon egf stimulation, and physical association of the encoded protein with the four egfr orthologs of mammals. Upregulation of lrig1 is followed by enhanced ubiquitylation and degradation of egfr. The underlying mechanism involves recruitment of c-cbl, an e3 ubiquitin ligase that simultaneously ubiquitylates egfr and lrig1 and sorts them for degradation. | SIGNOR-139954 |
P08581 | Q12913 | 0 | dephosphorylation | down-regulates activity | 0.608 | When co-expressed in 293 cells, the full-length substrate-trapping mutant form of DEP-1 formed a stable complex with the chimeric receptor colony stimulating factor 1 (CSF)-Met and wild type DEP-1 dephosphorylated CSF-Met. Furthermore, we observed that DEP-1 preferentially dephosphorylated a Gab1 binding site (Tyr(1349)) and a COOH-terminal tyrosine implicated in morphogenesis (Tyr(1365)), | SIGNOR-248702 |
Q8N5S9 | P0DP25 | 0 | 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 |
Q15797 | P28482 | 0 | phosphorylation | down-regulates | 0.608 | Phosphorylation of the linker region of smads mediated by erk2, gsk3?, And cdk2/4 negatively regulates smad activity by preventing their relocation to the nucleus, by inhibiting their interactions with coactivators, or by accelerating their degradation;in contrast, erk2 phosphorylated all four smad1 residues almost evenly, while showing a preference for s204 over s208 and s213 in smad3 | SIGNOR-161597 |
Q8TEP8 | P53350 | 0 | phosphorylation | up-regulates activity | 0.608 | In the presence of AurA binding, Plk1 preferentially phosphorylates and interacts with the T44 motif of Cep192 through the “self-priming and binding” mechanism | SIGNOR-266405 |
O00187 | Q15485 | 0 | binding | up-regulates activity | 0.608 | In the lectin pathway, mannose-binding lectin (MBL) and ficolins bind to pathogens and activate MBL-associated serine protease-2 (MASP-2) | SIGNOR-263413 |
P63279 | P35227 | 0 | binding | down-regulates activity | 0.608 | Based on this finding of interaction between MEL-18 and UBC9, we envisioned a mechanism in which MEL-18 bound to HSF2 inhibits its sumoylation by binding to and inhibiting the activity of UBC9 enzymes that approach HSF2. | SIGNOR-226248 |
P17302 | P28482 | 0 | phosphorylation | down-regulates activity | 0.608 | These studies confirm that connexin-43 is a MAP kinase substrate in vivo and that phosphorylation on Ser255, Ser279, and/or Ser282 initiates the down-regulation of gap junctional communication. Studies with connexin-43 mutants suggest that MAP kinase phosphorylation at one or more of the tandem Ser279/Ser282 sites is sufficient to disrupt gap junctional intercellular communication. | SIGNOR-249401 |
Q92888 | Q14344 | 0 | binding | up-regulates activity | 0.608 | It turned out that RGS domain of p115RhoGEF is specific for Gα12 and Gα13, and does not bind Gαi, Gαs and Gαq (Kozasa et al., 1998). The binding of Gα13 but not Gα12 stimulated GEF activity for Rho | SIGNOR-256521 |
P50148 | P28223 | 0 | binding | up-regulates activity | 0.608 | 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-257137 |
P12318 | P07948 | 0 | phosphorylation | up-regulates activity | 0.608 | Phosphorylation of FcgammaRIIa/c by Lyn is clearly dependent on the presence of Y-298, since all mutants lacking this residue are not phosphorylated by this PTK. This result suggests that Y-298 might be the only tyrosine residue of FcgammaRIIa/c phos- phorylated by Lyn. | SIGNOR-249379 |
P04637 | Q66K89 | 0 | ubiquitination | up-regulates activity | 0.608 | E4F1 Has an Intrinsic Ubiquitin E3 Ligase Activity that Drives K48-type Ubiquitylation of p53. These data demonstrate that E4F1 stimulates the ubiquitylation of p53 on the lysine cluster K319–K321, i.e., at sites distinct from those targeted by Hdm2. p53 forms Ubiquitylated by E4F1 Are Localized on Chromatin. In striking contrast with Ub-p53 forms stimulated by Hdm2, which are mainly cytosoluble and targeted to the proteasome, we found that E4F1-stimulated Ub-p53 forms are tightly associated with chromatin, suggesting that they could be involved in transcription. | SIGNOR-271394 |
Q00535 | P06241 | 0 | phosphorylation | up-regulates activity | 0.608 | Constitutively active Fyn phosphorylated Tyr15 of Cdk5. Fyn Facilitates Kinase Activity of Cdk5 Via Tyr15 Phosphorylation | SIGNOR-251156 |
Q8N6U8 | O75386 | 0 | relocalization | up-regulates activity | 0.608 | Upon knockdown of Tulp3 using siRNA in IMCD3 cells, ciliary localization of Gpr161 was severely reduced | SIGNOR-259938 |
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