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 |
|---|---|---|---|---|---|---|---|
P06401 | P27361 | 0 | phosphorylation | down-regulates | 0.561 | Specifically, down-regulation of mature prs occurs by a mechanism in which ligand binding activates pr phosphorylation by mapks at a unique serine residue, which then targets the receptors for degradation. | SIGNOR-74716 |
O95967 | P28300 | 0 | binding | up-regulates activity | 0.561 | Fibulin-4 directly binds LOX, and this interaction enhances fibulin-4 binding to tropoelastin, thus forming a ternary complex that may be critical for elastin cross-linking. | SIGNOR-252135 |
P42768 | P06241 | 0 | phosphorylation | up-regulates activity | 0.561 | As shown in XREF_FIG F, Fyn immunoprecipitates from activated T cells induced the tyrosine phosphorylation of WASp, but neither WASpDeltaPro nor WASpY291F mutant proteins were phosphorylated in this assay. | SIGNOR-279333 |
P35637 | Q15637 | 0 | binding | down-regulates | 0.561 | We speculate that zfm1 may inhibit transcription driven by the ntds of tls | SIGNOR-58967 |
P63096 | P61073 | 0 | binding | up-regulates activity | 0.561 | Using this model, we have reported that CXCL12 activates Gi1, Gi2, or Gi3 heterotrimeric G proteins in a concentration-dependent manner | SIGNOR-278102 |
P19105 | Q13464 | 0 | phosphorylation | up-regulates activity | 0.561 | Phosphorylation of myosin II regulatory light chain (MRLC) is important for cell motility and cytokinesis in nonmuscle cells. Although the regulation of monophosphorylated MRLC at serine 19 throughout the cell cycle was examined in detail, MRLC diphosphorylation at both threonine 18 and serine 19 is still unclear. Here we found that Rho-kinase has an activity for MRLC diphosphorylation in nonmuscle cells using sequential column chromatographies. | SIGNOR-263074 |
P42224 | Q8N2W9 | 0 | binding | down-regulates | 0.561 | First, piasy interacts with stat1 both in vitro and in vivo. The in vivo piasy__stat1 interaction is dependent on cytokine stimulation. Second, piasy can inhibit stat1-mediated gene activation without blocking the dna binding activity of stat1. | SIGNOR-105723 |
P17612 | P24588 | 0 | relocalization | up-regulates activity | 0.561 | In this report, we demonstrate that glutamate receptors and PKA are recruited into a macromolecular signaling complex through direct interaction between the MAGUK proteins, PSD-95 and SAP97, and AKAP79/150 | SIGNOR-261292 |
Q9H492 | Q9BQS8 | 0 | binding | up-regulates activity | 0.561 | The preferential binding to LC3A and -B was confirmed in vivo by co-immunoprecipitation experiments of Myc-tagged FYCO1 and GFP fusions of human ATG8 family pro-teins expressed in HEK293 cells (Fig. 2B). GFP-LC3A and GFP-LC3B were efficiently co-precipitated with Myc-FYCO1,whereas GFP-LC3C, GFP-GABARAP, GFP-GABARAPL1 and-L2 were not. The effects we see on late steps of basal autophagy on mutation of the FYCO1 LIR motif correlate with a role of FYCO1 in regulating kinesin-mediated transport of LC3-positive autophagic structures. | SIGNOR-260598 |
P50148 | P16473 | 0 | binding | up-regulates activity | 0.561 | Activation of TSHR and the linked signaling cascades through binding of circulating TSH plays a pivotal role in controlling thyrocyte growth and in regulating thyroid hormone production/secretion. This is executed through switching on different subtypes of G proteins and signaling pathways. Among them, the Gαs- and Gαq-induced cascades are of the greatest importance, as they have been tightly linked to specific intracellular signal transductions downstream of TSHR in response to stimulations | SIGNOR-267138 |
Q13469 | P49841 | 0 | phosphorylation | down-regulates | 0.561 | Gsk3 was previously shown to directly phosphorylate the n-terminal regulatory domain of nfatc1, thus antagonizing the action of calcineurin and inhibiting nuclear shuttling of nfat. | SIGNOR-179784 |
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 |
Q9NYA1 | P28482 | 0 | phosphorylation | up-regulates | 0.561 | Activation of sphingosine kinase 1 by erk1/2-mediated phosphorylation. | SIGNOR-118546 |
P17600 | Q14012 | 0 | phosphorylation | down-regulates activity | 0.561 | Synapsin phosphorylation in the A domain, at the only phosphorylation site shared by all synapsins, dissociates synapsins from synaptic vesicles.This site is located in the N-terminal A domain and is a substrate for both PKA and CaM Kinase I | SIGNOR-250615 |
P31751 | O95988 | 0 | binding | up-regulates | 0.56 | In vivo, tcl1 forms trimers, which associate with akt. Tcl1 facilitates the oligomerization and activation of akt. Our data show that tcl1 is a novel akt kinase coactivator, which promotes akt-induced cell survival and proliferation. | SIGNOR-81716 |
Q13873 | Q9HCE7 | 0 | ubiquitination | down-regulates | 0.56 | 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-153402 |
Q00987 | P31751 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.56 | Mitogen-induced activation of phosphatidylinositol 3-kinase (pi3-kinase) and its downstream target, the akt/pkb serine-threonine kinase, results in phosphorylation of mdm2 on serine 166 and serine 186. Phosphorylation on these sites is necessary for translocation of mdm2 from the cytoplasm into the nucleus.. Both akt expression and serum treatment induced phosphorylation of mdm2 at ser186. | SIGNOR-109732 |
O75469 | Q15466 | 0 | binding | down-regulates | 0.56 | Our results suggest that shp is a negative regulator of pxr transcriptional activity. This conclusion derives from_ in vitro, cell culture, and_ in vivo_ experiments. | SIGNOR-101924 |
P40189 | Q9UBD9 | 0 | 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 |
P16220-1 | P17676 | 0 | binding | up-regulates activity | 0.56 | We conclude that C/EBP-β can directly bind to the N-terminal Q1 domain of CREB in addition to binding to the leucine zipper domain. The transactivation potential of full-length CREB fused to the DNA-binding domain of Gal4 was increased synergistically by calcium and cGMP, and overexpression of C/EBP-β enhanced the effect, while a dominant negative C/EBP inhibited it | SIGNOR-263654 |
Q9NX95 | P33176 | 0 | relocalization | up-regulates activity | 0.56 | Conventional kinesin I heavy chain binds to syntabulin and associates with syntabulin-linked syntaxin vesicles in vivo. These findings suggest that syntabulin functions as a linker molecule that attaches syntaxin-cargo vesicles to kinesin I, enabling the transport of syntaxin-1 to neuronal processes. | SIGNOR-264811 |
P04637 | O43474 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.56 | Previous work has shown that the Kruppel-like factor 4 (KLF4) transcription factor represses p53 transcription by binding to the PE21 element. | SIGNOR-270544 |
Q9HCE7-2 | Q9H469 | 0 | binding | down-regulates quantity by destabilization | 0.56 | Here, we report that F-box and LRR domain-containing protein 15 (FBXL15), an F-box protein of the FBXL family, forms an Skp1-Cullin1-F-box protein-Roc1 (SCF)(FBXL15) ubiquitin ligase complex and targets Smurf1 for ubiquitination and proteasomal degradation. FBXL15, through its leucine-rich repeat domain, specifically recognizes the large subdomain within the N-lobe of the Smurf1 HECT domain and promotes the ubiquitination of Smurf1 on K355 and K357 within the WW-HECT linker region. In this way, FBXL15 positively regulates BMP signalling in mammalian cells. | SIGNOR-271909 |
P09693 | P06239 | 0 | phosphorylation | up-regulates activity | 0.56 | Last, we demonstrate directly that members of the CD3 complex, including the gamma, delta, and epsilon chains, as well as a putative zeta subunit, can be phosphorylated at tyrosine residues by the CD4/CD8.p56lck complex. | SIGNOR-259931 |
P35573 | Q6VVB1 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.56 | The E3 ubiquitin ligase Malin interacts with and promotes the ubiquitination of AGL. | SIGNOR-271669 |
P10415 | P27361 | 0 | phosphorylation | up-regulates | 0.56 | Erk1 and erk2 directly phosphorylate bcl2 exclusively at ser-70 p44mapk/extracellular signal-regulated kinase 1 (erk1) and p42 mapk/erk2 are activated by il-3, colocalize with mitochondrial bcl2, and can directly phosphorylate bcl2 on ser-70 in a stauro-resistant manner both in vitro and in vivo molecular association. | SIGNOR-74935 |
P06730 | Q9HBH9 | 0 | phosphorylation | up-regulates | 0.56 | Inhibition of mammalian target of rapamycin induces phosphatidylinositol 3-kinase-dependent and mnk-mediated eukaryotic translation initiation factor 4e phosphorylation.Therefore, eif4e is considered a survival protein involved in cell cycle progression, cell transformation, and apoptotic resistance. Phosphorylation of eif4e (usually at ser209) increases its binding affinity for the cap of mrna and may also favor its entry into initiation complexes. | SIGNOR-157537 |
Q9H1J5 | Q9Y5W5 | 0 | binding | down-regulates | 0.56 | Here we describe wnt-inhibitory factor-1 (wif-1), a secreted protein that binds to wnt proteins and inhibits their activities. | SIGNOR-66892 |
P30305 | Q9UNH5 | 0 | dephosphorylation | down-regulates activity | 0.56 | Cdc14A inhibits Cdc25A and Cdc25B activity, the latter through direct binding and dephosphorylation ( ).|Together, these data indicate that Cdc14A dephosphorylates Cdc25B, inhibiting its catalytic activity. | SIGNOR-276968 |
P63000 | Q7Z6B7 | 0 | gtpase-activating protein | down-regulates activity | 0.56 | 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-260515 |
O75581 | Q9GZT5 | 0 | binding | up-regulates | 0.56 | 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-131622 |
P98164 | P10909 | 0 | binding | up-regulates quantity | 0.56 | Our results demonstrate that circulating ApoJ is retained in muscle via LRP2 and that LRP2 signaling could play a role in the maintenance of ApoJ homeostasis in circulation, at least in part. | SIGNOR-265256 |
P15172 | Q969P5 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.56 | Here we present evidence that mafbx targets myod for degradation in several models of skeletal muscle atrophy. | SIGNOR-184861 |
P29597 | Q8IU57 | 0 | binding | up-regulates | 0.559 | Despite signaling through distinct receptor complexes, type i ifns and ifn-_s activate similar signaling events and biological activities, consistent with their common ability to mediate an antiviral state in cells (fig. 6). In both cases, receptor engagement leads via the activation of the jak kinases jak1 and tyk2 | SIGNOR-124483 |
P45985 | P41279 | 0 | phosphorylation | up-regulates | 0.559 | Furthermore, we found that immunoprecipitated tpl-2 could directly phosphorylate and activate both mek-1 and mkk4 (also known as sek-1) | SIGNOR-196744 |
Q99558 | P41279 | 0 | phosphorylation | up-regulates activity | 0.559 | In studies of NIK, we found that Thr-559 located within the activation loop of its kinase domain regulates NIK action. Alanine substitution of Thr-559 but not other serine or threonine residues within the activation loop abolishes its activity and its ability to phosphorylate and activate IKKalpha | SIGNOR-249387 |
Q9H492 | Q14596 | 0 | binding | up-regulates | 0.559 | We performed glutathione s-transferase (gst) pull-down assays using extracts from hek293 cells overexpressing an ha-tagged nbr1(d50r) mutant, which lacks the ability to bind p62 (lamark et al., 2003) and gst fusions of six human atg8 homologs: gabarap, gabarapl1, gabarapl2, lc3a, lc3b, and lc3c. Indeed, nbr1 interacted with all these members of the mammalian atg8 protein family. | SIGNOR-184270 |
Q13224 | P12931 | 0 | phosphorylation | up-regulates activity | 0.559 | We have investigated the tyrosine phosphorylation of NMDA receptor subunits NR2A and NR2B by exogenous Src Phosphorylation-site specific antibodies identified NR2B Tyr1472 as a phosphorylation site for intrinsic PSD tyrosine kinases | SIGNOR-247180 |
P14598 | P31749 | 0 | phosphorylation | up-regulates | 0.559 | Akt phosphorylates p47phox and mediates respiratory burst activity in human neutrophils. A direct interaction between p47(phox) and akt was shown. Active recombinant akt phosphorylated recombinant p47(phox) in vitro. Mutation analysis indicated that 2 aa residues, ser(304) and ser(328), were phosphorylated by akt. Inhibition of akt activity also inhibited fmlp-stimulated neutrophil chemotaxis. | SIGNOR-252586 |
Q02750 | P67775 | 0 | dephosphorylation | down-regulates | 0.559 | In particular, p38 mapk activity stimulates the physical association between ppa2 and mkk1/2- erk1/2 complex, leading to mkk1/2 dephosphorilation by pp2a. | SIGNOR-166649 |
Q04912 | P31749 | 0 | phosphorylation | up-regulates | 0.559 | Akt/pkb phosphorylates ron ser-1394, thus providing a docking site for 14-3-3based on these results, we propose a mechanism based on msp-ron-dependent phosphorylation and 14-3-3 association, whereby the function of alpha6beta4 switches from a mechanical adhesive device into a signaling component, and might be critically involved in human epidermal wound healing | SIGNOR-252471 |
P04637 | P09874 | 0 | relocalization | up-regulates activity | 0.559 | We identify the major poly(ADP-ribosyl)ated sites of p53 by PARP-1 and find that PARP-1-mediated poly(ADP-ribosyl)ation blocks the interaction between p53 and the nuclear export receptor Crm1, resulting in nuclear accumulation of p53. These findings molecularly link PARP-1 and p53 in the DNA-damage response, providing the mechanism for how p53 accumulates in the nucleus in response to DNA damage.|PARP-1 is super-activated by binding to damaged DNA, and poly(ADP-ribosyl)ates p53. Poly(ADP-ribosyl)ation probably induces a structural change that mask the NES, and thus Crm1 can no longer target p53 to the nuclear export machinery, resulting in accumulation of p53 in the nucleus. | SIGNOR-261321 |
P49768 | Q9Y4K3 | 0 | ubiquitination | up-regulates quantity by stabilization | 0.559 | We have also observed that ubiquitination of PS1 by TRAF6 increases the stability of PS1 holoprotein, and TRAF6-deficiency coincides with reduced endogenous PS1 and PS2 levels. | SIGNOR-278601 |
P42224 | P12931 | 0 | phosphorylation | up-regulates activity | 0.559 | The tyr701 phosphorylation of signal transducer and activator of transcription 1 (stat1) induced by interferon-gamma (ifn-gamma) and 12-o-tetradecanoylphorbol 13-acetate (tpa) was inhibited by the protein kinase c (pkc) inhibitor staurosporine, the tyrosine kinase inhibitor herbimycin, or the src kinase inhibitor pp2. An association between c-src and stat1 was increased by ifn-gamma and tpa, indicating the direct phosphorylation of stat1 by pkc-dependent c-src activation. | SIGNOR-235696 |
P46734 | Q99759 | 0 | phosphorylation | up-regulates activity | 0.558 | These data indicate that mkk3 is preferentially activated by mekk3, whereas mkk4 is activated both by mekk2 and mekk3. | SIGNOR-48625 |
P04637 | O15297 | 0 | dephosphorylation | down-regulates activity | 0.558 | PPM1D binds Chk1 and dephosphorylates the ATR-targeted phospho-Ser 345, leading to decreased Chk1 kinase activity. PPM1D also dephosphorylates p53 at phospho-Ser 15. PPM1D dephosphorylations are correlated with reduced cellular intra-S and G2/M checkpoint activity in response to DNA damage induced by ultraviolet and ionizing radiation. Thus, a primary function of PPM1D may be to reverse the p53 and Chk1-induced DNA damage and cell cycle checkpoint responses and return the cell to a homeostatic state following completion of DNA repair. | SIGNOR-248319 |
P04637 | P53355 | 0 | phosphorylation | up-regulates | 0.558 | Dna damage-activated protein kinases like chk1/2 modify the box-i domain of p53 at thr18 and ser20 (46) by an allosteric mechanism (10). | SIGNOR-153491 |
Q96E17 | Q9UQ26 | 0 | relocalization | up-regulates activity | 0.558 | N-terminal interactions of RIMs with RAB3 and MUNC13 regulate DCV fusion. Through N-terminal interactions, RIMs position MUNC13 and recruit DCVs via RAB3, which is located on the vesicle | SIGNOR-264378 |
Q9BZL4 | Q5VT25 | 0 | phosphorylation | down-regulates activity | 0.558 | Identification of the Phosphorylation Site of p85 on Threonine 560 by MRCKα-CAT | Wild-type p85 but not the mutant p85AA, when phosphorylated in vitro with MRCKα-CAT, showed significant reduction in the rate of MLC2 dephosphorylation. These results confirm a similar observation with MBS130 where phosphorylation of a conserved threonine 695 within a highly conserved motif was essential for the inhibition of phosphatase catalytic activity | SIGNOR-250724 |
P52333 | Q9HBE5 | 0 | binding | up-regulates | 0.558 | Retroviral-mediated transduction of wild-type gamma c into xscid jt cells restored function to the il-21r, as shown by il-21-induced tyrosine phosphorylation of jak1 and jak3, and downstream activation of stat5 | SIGNOR-90269 |
P29475 | Q13424 | 0 | relocalization | up-regulates | 0.558 | biochemical studies showed that the N-terminal PDZ domain of nNOS binds to a similar PDZ domain of syntrophin (Fig. 1), a dystrophin-associated protein | SIGNOR-236916 |
Q16539 | Q15256 | 0 | dephosphorylation | down-regulates | 0.558 | As shown, gst-ptp-sl dephosphorylated efficiently both erk2 and p38 wild typetogether, these results indicate that the defective association of the tyrosine phosphatase ptp-sl with erk2 d319n and p38 d316n mutations impairs the retention and inactivation in the cytosol of these map kinases by ptp-sl. | SIGNOR-111762 |
P35222 | P29350 | 0 | dephosphorylation | down-regulates quantity by destabilization | 0.558 | Because SHP-1 can dephosphorylate residues Y86 and Y654 on the \u03b2-catenin protein, these residues were therefore mutated into phenylalanine and the transcriptional activity of the subsequent \u03b2-catenin mutants analyzed: \u03b2-catenin/Y86F, \u03b2-catenin/Y654F and \u03b2-catenin/Y86F/Y654F. As shown in Fig.\u00a03 B, the mutants \u03b2-catenin/Y86F, \u03b2-catenin/Y654F and \u03b2-catenin/Y86F/Y654F had a significantly reduced transcriptional activity in comparison to wild-type \u03b2-catenin.|SHP-1 inhibits \u03b2-catenin function by inducing its degradation and interfering with its association with TATA-binding protein. | SIGNOR-277014 |
P04049 | P17252 | 0 | phosphorylation | down-regulates | 0.558 | Pka can inhibit raf-1 function directly via phosphorylation of the raf-1 kinase domain | SIGNOR-34761 |
Q13233 | O95819 | 0 | phosphorylation | up-regulates | 0.558 | Hpk1 binds and phosphorylates mekk1 directly | SIGNOR-44040 |
O43707 | Q05397 | 0 | phosphorylation | down-regulates | 0.558 | Phosphorylation at y12 by fak reduces _-actinin1's affinity for actin [25] and [27]. _-actinin4 is phosphorylated at y4, y31, and y265. Phosphorylation at y4 or y31 decreases its binding to actin [28] while phosphorylation of y265 increases its affinity for actin | SIGNOR-192195 |
P67809 | P31749 | 0 | phosphorylation | up-regulates | 0.558 | Phosphorylation of yb-1 at the serine 102 residue is required for transcriptional activation of growth-enhancing genes, such as egfr. Herein, we illustrate that activated akt binds to and phosphorylates the yb-1 cold shock domain at ser102 | SIGNOR-252521 |
P12830 | P49841 | 0 | phosphorylation | up-regulates activity | 0.558 | Phosphorylation of the E-cadherin Cytoplasmic Domain by CKII and GSK-3β Increases the Binding to β-catenin. pre-phosphorylation by CKII at Ser-855 and/or Ser-853 of E-cadherin is required before GSK-3β can phosphorylate at Ser-849. | SIGNOR-251225 |
P48736 | Q9Y4H2 | 0 | binding | up-regulates | 0.558 | There was a high level of irs-2 expression and insulin-stimulated tyrosyl phosphorylation as early as embryonic day 15 with robust pi3k binding and activation | SIGNOR-103174 |
P98170 | Q6GPH4 | 0 | binding | down-regulates | 0.558 | Immunoprecipitation studies indicate that xaf1 binds to xiap,birc2,birc3. | SIGNOR-155637 |
P61586 | Q03113 | 0 | binding | up-regulates | 0.558 | Ga12/13 recruitment of rho-gefs causes rhoa activation and f-actin assembly, which promotes lats1/lat2 inactivation by an unknown, but myosin-independent mechanism. | SIGNOR-192108 |
P29353 | P14784 | 0 | binding | up-regulates | 0.558 | The signaling mechanism utilizes an adaptor protein, shc, which binds to a phosphotyrosine residue on the il-2/15r?, Resulting in activation of grb2 and onto akt via the shc-grb2-gab2-pi3k-akt signaling pathway to increase cell proliferation and/or survival | SIGNOR-204975 |
P41279 | P31749 | 0 | phosphorylation | up-regulates activity | 0.558 | Akt-dependent phosphorylation of Cot occurs exclusively on serines 400 and 413. Akt to phosphorylate Cot at two sites in the carboxy-terminal domain, at least one of which may promote binding of substrates or coactivators to Cot, or alternatively may relieve binding of a negative regulator. | SIGNOR-252572 |
P52954 | P84550 | 0 | binding | down-regulates activity | 0.558 | Furthermore, Corl1 interacted with Lbx1 and cooperatively repressed transcription, suggesting that it acts as a transcriptional corepressor for Lbx1 in regulating cell fate determination in the dorsal spinal cord. | SIGNOR-238004 |
Q92630 | Q13315 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.558 | ATM augments nuclear stabilization of DYRK2 by inhibiting MDM2 in the apoptotic response to DNA damage|Upon exposure to genotoxic stress, ATM phosphorylates DYRK2 at Thr-33 and Ser-369, which enables DYRK2 to escape from degradation by dissociation from MDM2 and to induce the kinase activity toward p53 at Ser-46 in the nucleus. | SIGNOR-275577 |
P16885 | P06239 | 0 | phosphorylation | up-regulates | 0.558 | In vitro phosphorylation experiments with recombinant plcgamma2 and recombinant lck, fyn, and lyn tyrosine kinases showed that phosphorylation of plcgamma2 led to activation of the recombinant enzyme. | SIGNOR-91477 |
Q13485 | Q8N2W9 | 0 | binding | down-regulates | 0.558 | Piasy binds most strongly with smad3 and also associates with other receptor-regulated smads and smad4. smad3, smad4, and piasy can form a ternary complex. Piasy does not inhibit smad complex binding to dna, but it represses smad transcriptional activity. | SIGNOR-104541 |
P50539 | P61244 | 0 | binding | up-regulates activity | 0.558 | The role MAX plays in transcription is thought to be primarily as a cofactor for DNA binding. In this capacity, however, it appears to be essential for most, if not all, the known biological activities of MYC. MAX also functions as a cofactor for DNA binding for a group of bHLHZip proteins related to MYC, including MNT, MXD1-4 (formerly Mad1, Mxi1, Mad3 and Mad4), and MGA. Like MYC, these proteins do not homodimerize and appear to be incapable of binding DNA on their own, but when bound to MAX, they recognize E-box sequences. | SIGNOR-240314 |
O95863 | P49841 | 0 | phosphorylation | down-regulates | 0.557 | Snail is a well-known zn-finger transcription factor that promotes emt by repressing e-cadherin expression. It is known that snail is phosphorylated by gsk3beta and degraded by beta-trcp-mediated ubiquitination. A variant of snail (snail-6sa), which abolishes these phosphorylations, is much more stable and resides exclusively in the nucleus to induce emt | SIGNOR-129402 |
P08754 | P14416 | 0 | binding | up-regulates activity | 0.557 | 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-256844 |
Q00613 | P49841 | 0 | phosphorylation | down-regulates activity | 0.557 | Ser-303 is phosphorylated by glycogen synthase kinase 3 (GSK3) through a mechanism dependent on primary phosphorylation of Ser-307 by MAPK. Secondary phosphorylation of Ser-303 by GSK3 may thus repress the activity of HSF-1, and its requirement for priming by MAPK phosphorylation of Ser-307 provides a potential link between the MAPK cascade and HSF-1. | SIGNOR-251216 |
Q05655 | P07948 | 0 | phosphorylation | down-regulates activity | 0.557 | Src, Fyn, or Lyn are the essential kinases that tyrosine phosphorylate and inactivate PKC δ. Lyn phosphorylates tyrosine residue 565 in vitro | SIGNOR-251407 |
P00533 | P27361 | 0 | phosphorylation | down-regulates | 0.557 | It is likely that the map2 and ert kinases account for the phosphorylation of the egf receptor at thr669 (egf receptor (krel veplt669psgeapnqallr)) observed in cultured cells.Phosphorylation at ser-695 is partial and occurs only if thr-693 is phosphorylated. Phosphorylation at thr-678 and thr-693 by prkd1 inhibits egf-induced mapk8/jnk1 activation. | SIGNOR-20549 |
P50570 | P12931 | 0 | phosphorylation | down-regulates activity | 0.557 | We used cSrc-transformed NIH 3T3 fibroblasts to examine the effect of mutant Dyn2Y597. Similar to its effect in myotubes, Dyn2Y597F presented reduced enrichment at podosomes, whereas Dyn2Y597E clearly targeted podosome rosettes (Figures S9B and S9C). Moreover, Dyn2Y597F significantly reduced the podosome area, ECM degradation ability, and lifespan of the podosome in cSrc-transformed NIH 3T3 fibroblasts, whereas Dyn2Y597E displayed contradictory effects (Figures S9D–S9G). | SIGNOR-277539 |
P16885 | P51451 | 0 | phosphorylation | up-regulates activity | 0.557 | Lyn, Syk, Btk, and Blk can also phosphorylate and enhance the activation of phospholipase C gamma 2 (PLCgamma2), which hydrolyzes PI (4,5) P2 to create inositol 3,4,5-trisphosphate (IP3) and diacylglycerol (DAG), stimulating Ca 2+ mobilization and protein kinase C (PKC), respectively. | SIGNOR-280195 |
O14746 | Q96AP0 | 0 | binding | up-regulates | 0.557 | We find that tpp1 and pot1 form a complex with telomeric dna that increases the activity and processivity of the human telomerase core enzyme. | SIGNOR-152321 |
P49840 | P31751 | 0 | phosphorylation | down-regulates | 0.557 | Activated pi3k/akt pathway results in inhibitory phosphorylation of gsk3 | SIGNOR-138179 |
Q14344 | P25101 | 0 | binding | up-regulates | 0.557 | We studied the ability of et receptors to activate galfa13 using an assay for g protein alfa-chain activation that is based on the fact that an activated (gtp-bound) alfa-chain is resistant to trypsinization compared with an inactive (gdp-bound) alfa-chain. | SIGNOR-66856 |
P19174 | Q9Y2X7 | 0 | binding | up-regulates | 0.557 | Git1 interaction with plcgamma is required for plcgamma activation based on inhibition of tyrosine phosphorylation | SIGNOR-118454 |
Q96S59 | P08581 | 0 | binding | up-regulates | 0.557 | Our data suggest that ranbpm, functioning as an adaptor protein for the met tyrosine kinase domain, can augment the hgf-met signaling pathway. | SIGNOR-91028 |
Q8NHV4 | O14965 | 0 | phosphorylation | up-regulates activity | 0.557 | Microtubule nucleation during central spindle assembly requires NEDD1 phosphorylation on serine 405 by Aurora A| In the absence of Aurora A, the HURP (also known as DLGAP5) and NEDD1 proteins that are involved in nucleation of microtubules fail to concentrate in the midzone. | SIGNOR-272965 |
P15336 | Q8WYK2 | 0 | binding | down-regulates activity | 0.557 | JDP2 dimerizes with other AP-1 proteins such as activating transcription factor-2 (ATF2) and Jun to repress transcription from promoters that contain a cyclic AMP-responsive element (CRE). | SIGNOR-226395 |
P15502 | O95967 | 0 | binding | up-regulates activity | 0.557 | Fibulin-4 directly binds LOX, and this interaction enhances fibulin-4 binding to tropoelastin, thus forming a ternary complex that may be critical for elastin cross-linking. | SIGNOR-252136 |
Q92793 | Q9UBE8 | 0 | phosphorylation | up-regulates activity | 0.557 | In vitro kinase assay showed that NLK could phosphorylate the C-terminal domain of CBP. | SIGNOR-280048 |
Q14596 | Q9GZQ8 | 0 | binding | down-regulates | 0.557 | We performed glutathione s-transferase (gst) pull-down assays using extracts from hek293 cells overexpressing an ha-tagged nbr1(d50r) mutant, which lacks the ability to bind p62 (lamark et al., 2003) (figures s1a and s1b, available online), and gst fusions of six human atg8 homologs: gabarap, gabarapl1, gabarapl2, lc3a, lc3b, and lc3c. Indeed, nbr1 interacted with all these members of the mammalian atg8 protein family. downregulation of either lc3 or gabarap (or both) family members leads to stabilization and p62-dependent aggregation of nbr1. | SIGNOR-184252 |
P49841 | P17612 | 0 | phosphorylation | down-regulates activity | 0.557 | Gsk3 is different from most kinases in that it is constitutively partially active and the most common regulatory mechanism is inhibition by phosphorylation of ser21 in gsk3alpha or ser9 in gsk3beta. This inhibitory phosphorylation can be mediated by several kinases, such as akt/protein kinase b (pkb), protein kinase c (pkc) and protein kinase a (pka). | SIGNOR-188577 |
P61586 | Q92502 | 0 | gtpase-activating protein | down-regulates activity | 0.557 | 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-260519 |
P52630 | Q92793 | 0 | acetylation | up-regulates activity | 0.557 | STAT2 is another important component of ISGF3 complex, and its acetylation was similar to IFNaR2 and IRF9 acetylation in many respects: CBP downregulation largely abolished STAT2 acetylation induction by IFNa (Figure 6A), and CBP was more potent than transferases tested in catalyzing STAT2 acetylation (Figure 6B). [...] Figure 6 (I) STAT2-K390R substitution has reduced activity in ISGF3 complex formation. | SIGNOR-217891 |
P35222 | Q13153 | 0 | phosphorylation | up-regulates | 0.557 | Pak1 directly phosphorylates _-catenin proteins at ser675 site and this leads to more stable and transcriptional active _-catenin | SIGNOR-175944 |
O14733 | Q12852 | 0 | phosphorylation | up-regulates activity | 0.556 | Collectively, these data suggest the hypothesis that ApoE activates DLK by increasing its levels | SIGNOR-279630 |
O95149 | Q6ZN04 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.556 | HOTAIR associates with E3 ubiquitin ligases bearing RNA-binding domains, Dzip3 and Mex3b, as well as with their respective ubiquitination substrates, Ataxin-1 and Snurportin-1. In this manner, HOTAIR facilitates the ubiquitination of Ataxin-1 by Dzip3 and Snurportin-1 by Mex3b in cells and in vitro, and accelerates their degradation. | SIGNOR-272079 |
P35222 | P68400 | 0 | phosphorylation | up-regulates activity | 0.556 | The major CK2 phosphorylation site in this domain is Thr393, a solvent-accessible residue in a key hinge region of the molecule. Mutation of this single amino acid reduces beta-catenin phosphorylation, cotranscriptional activity, and stability. | SIGNOR-250849 |
P60953 | O94989 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.556 | 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-260541 |
Q14643 | P17612 | 0 | phosphorylation | down-regulates activity | 0.556 | IP(3)R-I was phosphorylated by PKA and PKG in vitro and exclusively by PKG in vivo. Sequential phosphorylation by PKA and by PKG-Ialpha in vitro showed that PKA phosphorylated the same site as PKG (presumably S(1755)) and an additional PKA-specific site (S(1589)). Phosphorylation of IP(3)R-I in microsomes by PKG, PKA, or a combination of PKG and PKA inhibited IP(3)-induced Ca(2+) release to the same extent, implying that inhibition was mediated by phosphorylation of the PKG-specific site. | SIGNOR-249996 |
P04049 | O75914 | 0 | phosphorylation | up-regulates | 0.556 | The protein kinase pak3 positively regulates raf-1 activity through phosphorylation of serine 338. | SIGNOR-62043 |
Q13501 | Q99759 | 0 | phosphorylation | up-regulates activity | 0.556 | MEKK3 overexpression, but not that of a kinase dead mutant, was able to induce the phosphorylation of p62 at T269 and S272 (XREF_FIG), which correlated with mTORC1 activation (XREF_FIG), suggesting that MEKK3 could be a bona fide regulator of p62 phosphorylation and mTORC1 activity. | SIGNOR-279532 |
P01106 | P45983 | 0 | phosphorylation | up-regulates activity | 0.556 | The jnk pathway is selectively involved in the c-myc-mediated apoptosis and that the apoptotic function of c-myc is directly regulated by jnk pathway through phosphorylation at ser-62 and ser-71. | SIGNOR-236018 |
Q15746 | Q13153 | 0 | phosphorylation | down-regulates activity | 0.556 | P21-activated kinase 1 (PAK1) phosphorylates MLCK, resulting in decreased MLCK activity. | SIGNOR-250317 |
P63096 | P08913 | 0 | binding | up-regulates activity | 0.556 | 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-256698 |
O15409 | Q16650 | 0 | binding | up-regulates activity | 0.556 | We show that TBR1 homodimerizes, that it interacts with FOXP2, a transcription factor implicated in speech/language disorders, and that this interaction is disrupted by pathogenic mutations affecting either protein. | SIGNOR-266831 |
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