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 |
|---|---|---|---|---|---|---|---|
P17706 | P08581 | 1 | dephosphorylation | down-regulates | 0.501 | We have identified ptp1b and tcptp as negative regulators of the hepatocyte growth factor receptor, the met receptor-tyrosine kinase. In vivo, loss of ptp1b or tcptp enhances hepatocyte growth factor-mediated phosphorylation of met. | SIGNOR-181331 |
O94806 | Q8WUI4 | 1 | phosphorylation | up-regulates activity | 0.2 | Histone deacetylase (HDAC) 5 and 7, two members of the class II of classical HDAC [62], are in vivo substrates of PKD3 and PKD [63]. In response to a variety of signals, including phorbol esters, T cell receptor engagement, vascular endothelial growth factor and angiotensin stimulation, the activity of HDAC5 and 7 are regulated by a mechanism that involves PKD3 and PKD-mediated phosphorylation of the highly conserved Ser259 and Ser498 residues that are located in N-terminus of class II HDACs [63–67]. | SIGNOR-275934 |
O95997 | P06493 | 0 | phosphorylation | up-regulates | 0.598 | Hpttg is phosphorylated by cdc2 at ser165 these results suggest that hpttg is induced by, and may have a role in, regulatory pathways involved in the control of cell proliferation. | SIGNOR-74619 |
Q9UKY1 | P63279 | 0 | sumoylation | up-regulates quantity by stabilization | 0.452 | Here, we report that the SUMO-E2 conjugating enzyme Ubc9 was identified to interact with ZHX1 by an interaction screen using a yeast two-hybrid system. This interaction was confirmed by co-immunoprecipitation and co-localization assays. Further study showed that ZHX1 is SUMOylated by Ubc9 with SUMO1 at the sites K159, K454, and K626. Furthermore, we demonstrated that the SUMOylation of ZHX1 regulated the stability, ubiquitination and transcriptional activity of ZHX1. The sumoylation of zinc‐fingers and homeoboxes 1 (ZHX1) by ubc9 regulates its stability and transcriptional repression activity. However, in the current work, we demonstrated that ZHX1 was only SUMOylated by SUMO1. | SIGNOR-263901 |
P15172 | P08047 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.373 | These data suggest a regulatory model in which MyoD activation during myogenesis causes the down-regulation of Sp1, which contributes to the repression of GLUT1 gene transcription and, therefore, leads to the reduction in GLUT1 expression and glucose transport. | SIGNOR-241765 |
Q15633 | P31749 | 0 | phosphorylation | up-regulates activity | 0.2 | We demonstrate that S6 kinases can phosphorylate the extended C-terminal domain of TRBP and interact with TRBP in situ in primary cells. TRBP serines 283/286 are essential for S6K-mediated TRBP phosphorylation, optimal expression of TRBP, and the S6K-TRBP interaction in human primary cells. | SIGNOR-274067 |
Q8NEB9 | P31749 | 1 | relocalization | up-regulates | 0.434 | One of the best characterized targets of pi3k lipid products is the protein kinase akt or protein kinase b (pkb). In quiescent cells, pkb resides in the cytosol in a low-activity conformation. Upon cellular stimulation, pkb is activated through recruitment to cellular membranes by pi3k lipid products and phosphorylation by 3h-phosphoinositide-dependent kinase-1 (pdk1). | SIGNOR-252632 |
P00519 | P23759 | 1 | phosphorylation | up-regulates activity | 0.272 | Furthermore, we show that c-Abl interacts with and phosphorylates Pax7 protein.|Indeed, reporter gene assays indicate that c-Abl inhibition decreases Pax7 dependent activation of the 6xPRS9-luc reporter. | SIGNOR-279773 |
Q9H2X6 | Q13363 | 1 | phosphorylation | down-regulates | 0.47 | Homeodomain-interacting protein kinase-2 mediates ctbp phosphorylation and degradation in uv-triggered apoptosishipk2 phosphorylates ctbp at ser-422 | SIGNOR-134040 |
P12830 | Q68DV7 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.267 | To identify the E-cadherin ubiquitination site, we individually mutated three lysines in its cytoplasmic domain, including K816A, K855A, and K871A, of which E-cad K816A failed to restore E-cadherin ubiquitination (Additional file xref : Figure S3D), indicating that RNF43 ubiquitinated E-cadherin at the cytoplasmic lysine 816.|Together , these results suggest that RNF43 potentially downregulates E-cadherin in lung adenocarcinoma in the context of c-Src activation . | SIGNOR-278598 |
P50148 | O15552 | 2 | binding | up-regulates activity | 0.492 | 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-257188 |
Q00526 | P05412 | 1 | phosphorylation | up-regulates | 0.443 | Egf-induced cdk3 activation caused c-jun phosphorylation at ser63 and ser73, resulting in increased ap-1 transactivation. | SIGNOR-183013 |
Q05655 | P61978 | 1 | phosphorylation | down-regulates | 0.344 | Ser302 is a major k protein site phosphorylated by pkcdelta in vitrothe ability of pkc_ to inducibly bind and phosphorylate k protein may serve not only to alter the activity of k protein itself, but k protein may also provide an avenue for pkc_ to engage in a cross-talk with other k protein molecular partners in response to specific changes in the extracellular environment | SIGNOR-67515 |
P17612 | P19174 | 1 | phosphorylation | down-regulates | 0.2 | The observation that pka also phosphorylates plc-yl on serine 1248 suggests that phosphorylation of this residue may be a common mechanism by which pkc and pka inhibit plc-yl. | SIGNOR-17901 |
P09917 | P49137 | 0 | phosphorylation | up-regulates activity | 0.546 | Arachidonic acid promotes phosphorylation of 5-lipoxygenase at Ser-271 by MAPK-activated protein kinase 2 (MK2). when stimulated with only exogenous arachidonic acid, activity for the S271A mutant was significantly lower as compared with wild type 5-LO. | SIGNOR-250143 |
Q6UXI9 | Q5H8C1 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.366 | The loss of QBRICK significantly diminished the expression of nephronectin, an integrin α8β1 ligand necessary for renal development. In vivo, nephronectin associated with QBRICK and localized at the sublamina densa region, where QBRICK was also located. Collectively, these findings indicate that QBRICK facilitates the integrin α8β1-dependent interactions of cells with basement membranes by regulating the basement membrane assembly of nephronectin and explain why renal defects occur in Fraser syndrome. | SIGNOR-253308 |
Q14814 | P11802 | 2 | binding | down-regulates | 0.28 | In contrast to cdk2, cyclin d/cdk4 blocks myod activity through an as yet unclear mechanism that may involve direct binding. Cyclin d/cdk4 can also block the activity of myogenin and all mef2 isoforms. | SIGNOR-176524 |
Q14190 | P27540 | 2 | binding | up-regulates activity | 0.497 | We demonstrate that both SIM1 and SIM2 can heterodimerize via their helix-loop-helix·PAS regions with ARNT, but not with AHR, and that they do not form homodimers. Furthermore, SIM1 may have a dual role, both negatively affecting AHR·ARNT binding to the XRE and also acting in concert with ARNT as a novel DNA-binding heterodimer. | SIGNOR-240808 |
P29353 | P36897 | 0 | phosphorylation | up-regulates | 0.548 | We now report that upon TGF-_ stimulation, T_RI phosphorylates ShcA on serine and, to a lesser degree, on tyrosine to activate Erk MAP kinases. | SIGNOR-227503 |
P06241 | P14923 | 1 | phosphorylation | up-regulates activity | 0.561 | Phosphorylation of plakoglobin by Fer and Fyn kinases decreases plakoglobin-desmoplakin interaction and increases plakoglobin-α-catenin association. Fyn mainly phosphorylated Tyr549 and that it phosphorylated Tyr133 with a much lower activity | SIGNOR-251176 |
O95837 | P25101 | 2 | binding | up-regulates activity | 0.471 | 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-257427 |
P52657 | P20226 | 2 | binding | up-regulates activity | 0.9 | The general transcription factor IIA (TFIIA) binds to the TATA binding protein (TBP) and mediates transcriptional activation by distinct classes of activators. |Our results show that different activators utilize the general factor TFIIA in unique ways and that TFIIA contributes transcription activation functions in addition to the facilitation of TBP-DNA binding. | SIGNOR-262591 |
Q13469 | P45984 | 0 | phosphorylation | down-regulates | 0.541 | Jnks directly phosphorylate nuclear factor of activated t-cell (nfat) transcription factors, thus antagonizing the effects of calcium-regulated signaling through the protein phosphatase calcineurin | SIGNOR-118223 |
Q8WUF5 | P06493 | 0 | phosphorylation | up-regulates activity | 0.505 | Cyclin B/cyclin-dependent kinase 1 (CDK1) phosphorylates inhibitor of apoptosis stimulating protein of P53 (iASPP) to promote iASPP nucleus localization and its inhibitory effect on p53. | SIGNOR-273585 |
O60381 | P14598 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.265 | Together, these results indicate that HBP1 may contribute to the regulation of NADPH oxidase-dependent superoxide production through transcriptional repression of the p47phox gene. | SIGNOR-261614 |
Q8NFZ3 | Q9P2S2 | 2 | binding | up-regulates activity | 0.2 | Pre- and postsynaptic plasma membranes are always precisely aligned, and are separated by a synaptic cleft of ~20 nm. The cleft contains an undefined proteinaceous material in the middle, and is presumably bridged by synaptic cell-adhesion molecules such as Nrxns and Nlgns that align the pre- and postsynaptic elements and mediate trans-synaptic signaling.|Nlgns bind to both alpha- and beta-Nrxns with nanomolar affinities; binding involves the sixth LNS-domain of alpha-Nrxns which corresponds to the only LNS-domain of beta-Nrxns52. The binding affinities differ characteristically between various pairs of Nlgns and Nrxns, and are controlled by alternative splicing of both Nrxns and Nlgns (Figure 1c) | SIGNOR-264153 |
P17252 | Q13188 | 0 | phosphorylation | up-regulates activity | 0.2 | Thus, the phosphorylation of PKCα at Ser226 and Thr228 by Mst1 and Mst2 is required for the optimal activation of PKCα. | SIGNOR-277176 |
Q8N122 | Q9HB90 | 2 | binding | up-regulates | 0.941 | Active rag and gtr heterodimers are able to bind and activate torc1, through direct interactions with raptor. | SIGNOR-162054 |
Q14653 | Q14164 | 0 | phosphorylation | up-regulates activity | 0.741 | Virus-induced phosphoactivation of irf-3, thought to be mediated directly or indirectly by ikk? And/or tbk1 occurs in the c-terminal region of irf-3 at seven ser/thr residues, 385sslentvdlhisnshplslts405 (fig. 1a).Within This region, irf-3 has two phosphorylation sites: site 1 includes ser385 and ser386, whereas site 2 includes ser396, ser398, ser402, ser405, and thr404. | SIGNOR-178379 |
Q9Y6K1 | P53350 | 0 | phosphorylation | down-regulates activity | 0.269 | 2.11 Plk1 Directly Phosphorylates DNMT3a at S393.|Elevated Plk1 further inhibited DNMT3a via phosphorylation at S393 in mitosis in accord with its mitotic role during cell cycle. | SIGNOR-279552 |
Q15717 | P06493 | 0 | phosphorylation | down-regulates activity | 0.407 | Cdk1 inhibition promoted a cytoplasmic accumulation of HuR, while a predominately nuclear localization of HuR was observed under conditions of high Cdk1 activity.|Kim et al. further showed that Cdk1-dependent Ser-202 phosphorylation of HuR was essential for 14-3-3\u03b8 binding to HuR. | SIGNOR-279014 |
Q15139 | P35222 | 1 | phosphorylation | up-regulates | 0.388 | This study provides evidence that pkd1 interacts with and phosphorylates beta-catenin at thr(112) and thr(120) we postulate that pkd1 phosphorylation is required to maintain _-catenin transcription activity. | SIGNOR-183384 |
P29371 | Q14344 | 2 | binding | up-regulates activity | 0.283 | 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-257438 |
Q15208 | P53350 | 0 | phosphorylation | down-regulates activity | 0.316 | Here, we identified a conserved signaling axis in which NDR1 kinase activity is regulated by PLK1 in mitosis. PLK1 phosphorylates NDR1 at three putative threonine residues (T7, T183 and T407) at mitotic entry, which elicits PLK1-dependent suppression of NDR1 activity and ensures correct spindle orientation in mitosis. | SIGNOR-276914 |
P17600 | Q13131 | 0 | phosphorylation | down-regulates activity | 0.2 | It has been reported that site 1 of syn i can be phosphorylated by pka. Pka-mediated synapsin i ser9 phosphorylation occurs in response to cgs 21680 treatment. Results show that the adenosine a2a receptor agonist, cgs 21680, increases neurotransmitter release, in particular, glutamate and noradrenaline and such response is mediated by protein kinase a activation, which in turn increased synapsin i phosphorylation | SIGNOR-78891 |
P68431 | Q96GD4 | 0 | phosphorylation | down-regulates activity | 0.2 | Histone code pathway involving h3 s28 phosphorylation and k27 acetylation activates transcription and antagonizes polycomb silencingaurora-b phosphorylates histone h3 at serine28 with regard to the mitotic chromosome condensation | SIGNOR-171717 |
Q5JR12 | P45983 | 0 | phosphorylation | down-regulates | 0.344 | Specific phosphorylation of pp2czeta at ser (92) by stress-activated jnk attenuates its phosphatase activity in cells. | SIGNOR-178930 |
Q86YJ5 | Q13291 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | MARCH9, a member of the RING-CH family of transmembrane E3 ubiquitin ligases, down-regulates CD4, major histocompatibility complex-I (MHC), and ICAM-1 in lymphoid cells. To identify novel MARCH9 substrates, we used high throughput flow cytometry and quantitative mass spectrometry by stable isotope labeling by amino acids in cell culture (SILAC) to determine the differential expression of plasma membrane proteins in a MARCH9-expressing B cell line. This combined approach identified 13 potential new MARCH9 targets. | SIGNOR-271537 |
Q8IXQ9 | P38117 | 1 | methylation | down-regulates activity | 0.2 | Accordingly, we found that METTL20-mediated methylation of ETFβ in vitro reduced its ability to receive electrons from the medium chain acyl-CoA dehydrogenase and the glutaryl-CoA dehydrogenase. In conclusion, the present study establishes METTL20 as the first human KMT localized to mitochondria and suggests that it may regulate cellular metabolism through modulating the interaction between its substrate ETFβ and dehydrogenases. | SIGNOR-269450 |
P06241 | Q15438 | 1 | phosphorylation | up-regulates activity | 0.394 | Fyn directly binds, phosphorylates, and activates cytohesin-1. | SIGNOR-280015 |
Q9UBK2 | P49760 | 0 | phosphorylation | down-regulates activity | 0.2 | Clk2 could also repress PGC-1alpha activation of Foxo1 on the IRS response element , as well as repress the Pepck promoter .|Clk2 phosphorylates and represses PGC-1\u03b1. | SIGNOR-278228 |
P00533 | P48050 | 1 | phosphorylation | up-regulates activity | 0.2 | These results demonstrate that the EGF receptor tyrosine kinase up-regulates the K(IR) 2.3 channel via phosphorylation of the Y234 residue of the WT protein. | SIGNOR-276322 |
P25874 | Q7LBC6 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | We show that Jhdm2a expression is induced by beta-adrenergic stimulation, and that Jhdm2a directly regulates peroxisome proliferator-activated receptor alpha (Ppara) and Ucp1 expression. | SIGNOR-266638 |
O43255 | P12931 | 0 | phosphorylation | up-regulates activity | 0.334 | In human breast cancer cell lines, the protein kinase Src has been shown to activate Siah2 by phosphorylation of tyrosines 86, 140, and 263.|This function is promoted by Src phosphorylation of Siah2, which increases C/EBPdelta binding, ubiquitination, and degradation. | SIGNOR-279555 |
P10071 | Q2M1P5 | 2 | binding | up-regulates quantity by stabilization | 0.577 | These results suggest a role for Kif7 in coordinating Hh signal transduction at the tip of cilia and preventing Gli3 cleavage into a repressor form in the presence of Hh. | SIGNOR-209614 |
P11802 | P38398 | 1 | phosphorylation | down-regulates | 0.665 | In particular, we have identified ser 632 of brca1 as a cyclin d1/cdk4 phosphorylation site in vitro. Using chromatin immunoprecipitation assays, we observed that the inhibition of cyclin d1/cdk4 activity resulted in increased brca1 dna binding at particular promoters in vivo. | SIGNOR-153450 |
Q9UJT1 | Q14980 | 2 | binding | up-regulates | 0.2 | Direct binding of numa to tubulin is mediated by a novel sequence motif in the tail domain that bundles and stabilizes microtubules. | SIGNOR-117159 |
Q7KZI7 | Q92974 | 1 | phosphorylation | down-regulates | 0.503 | We also show that par1b-induced serine 885/serine 959 phosphorylation inhibits rhoa-specific gef activity of gef-h1. As a consequence, gef-h1 phosphorylated on both of the serine residues loses the ability to stimulate rhoa and thereby fails to induce rhoa-dependent stress fiber formation | SIGNOR-177100 |
Q16878 | Q15465 | 2 | binding | up-regulates | 0.2 | Cdo and boc bind shh through a high-affinity interaction with a specific fibronectin repeat that is essential for activity. We propose a model where cdo and boc enhance shh signaling within its target field. | SIGNOR-146461 |
Q08499 | P28482 | 0 | phosphorylation | down-regulates | 0.353 | Long pde4d forms are inhibited by erk2 phosphorylation | SIGNOR-77574 |
P12882 | Q06413 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.383 | 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-238754 |
P23470 | P35968 | 1 | dephosphorylation | down-regulates activity | 0.253 | PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity. | SIGNOR-254707 |
Q09472 | P17861-2 | 1 | acetylation | up-regulates quantity by stabilization | 0.285 | P300 increases the acetylation and protein stability of XBP1s, and enhances its transcriptional activity, whereas SIRT1 deacetylates XBP1s and inhibits its transcriptional activity.. The mRNA encoding the active spliced form of XBP1 (XBP1s) is generated from the unspliced form by IRE1 (inositol-requiring enzyme 1) during the UPR. | SIGNOR-260429 |
Q96PU5 | Q15858 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.334 | The control of Nav density at the cell membrane is crucial to ensuring normal neuronal excitability. Navs are subject to posttranslational modifications that may influence their cell membrane availability. Ubiquitylation is a key process that orchestrates the internalization and subsequent degradation or recycling of Navs. This is accomplished by ubiquitin protein ligases, such as NEDD4-2 (neuronal precursor cell expressed developmentally downregulated-4 type 2). | SIGNOR-253458 |
P19784 | Q712K3 | 1 | phosphorylation | up-regulates activity | 0.449 | UBC3B is specifically phosphorylated by CK2 in vitro and in vivo. We mapped by deletions and site directed mutagenesis the phosphorylation site to a serine residue within the C-terminal domain in position 233 of UBC3B and in the corresponding serine residue of UBC3. | Following CK2-dependent phosphorylation both UBC3B and UBC3 bind to the F-box protein beta-TrCP, the substrate recognition subunit of an SCF (Skp1, Cul1, F-box) ubiquitin ligase. Furthermore, we observed that co-transfection of CK2alpha' together with UBC3B, but not with UBC3DeltaC, enhances the degradation of beta-catenin. | SIGNOR-251047 |
P12830 | O00192 | 2 | binding | up-regulates quantity by stabilization | 0.422 | To clarify the role of p120 in mammalian cells, we have knocked down p120 with siRNA in cells expressing epithelial (E-), placental (P-), neuronal (N-), and vascular endothelial (VE-) cadherins. We report that each of these cadherins, as well as α- and β-catenins, were rapidly degraded in the absence of p120, resulting in loss of cell–cell adhesion. The effect was clearly dose dependent, indicating that p120 expression levels may directly determine cadherin levels. Degradation of p120-uncoupled cadherin occurred after its arrival at the surface, indicating that p120 regulates cadherin turnover at the level of internalization or recycling. p120 homologues ARVCF and δ-catenin could substitute for p120, so at least one family member is likely required to maintain adhesion. Thus, cadherin complexes are rapidly turned over and degraded in mammalian cells in the absence of direct interaction with p120 or a p120 family member. | SIGNOR-252133 |
Q14457 | O60674 | 0 | phosphorylation | up-regulates activity | 0.297 | Mechanistically, IL-6 triggers the interaction between JAK2 and BECN1, where JAK2 phosphorylates BECN1 at Y333. We demonstrate that BECN1 Y333 phosphorylation is crucial for BECN1 activation and IL-6-induced autophagy by regulating PI3KC3 complex formation. | SIGNOR-277567 |
Q9UJU2 | Q9H161 | 2 | binding | up-regulates quantity by expression | 0.445 | Alx4 Stably Interacts with LEF-1. LEF-1 enhances Alx4 binding to DNA, suggesting that both interaction with LEF-1 and DNA binding are required to mediate its effects on the N-CAM promoter. | SIGNOR-254547 |
P06493 | P52926 | 1 | phosphorylation | down-regulates | 0.374 | Architecture of high mobility group protein i-c dna complex and its perturbation upon phosphorylation by cdc2 kinase. Phosphorylation by cdc2 reduces binding strength of the mammalian and insect hmgi proteins to dna. After phosphorylation of the protein at ser-43 and ser-58 by cdc2 kinase multiple contacts of dbds, especially with the bases, are impaired and the protein binds to dna in a different way, extending the contacts to the sugar-phosphate backbone. | SIGNOR-74098 |
Q96LB1 | P08754 | 2 | binding | up-regulates activity | 0.2 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-257172 |
P49137 | Q7L5N7 | 1 | phosphorylation | up-regulates activity | 0.2 | Mass spectrometry and mutagenesis analyses identified Ser34 of LPCAT2 as the phosphorylation site to enhance the catalytic activities. The experiments using inhibitors and siRNA against MAPK cascades demonstrated that LPCAT2 phosphorylation through LPS-TLR4 signaling may directly depend on MAPK-activated protein kinase 2 (MAPKAP kinase 2 or MK2). | SIGNOR-263077 |
P10721 | P42224 | 1 | phosphorylation | up-regulates activity | 0.725 | KIT is responsible for the permanent phosphorylation of all three STAT proteins. STAT1, -3, and -5 were phosphorylated on their activation-specific Tyr701, Tyr704, and Tyr694, respectively, following KIT stimulation. | SIGNOR-251365 |
P17252 | P32004 | 1 | phosphorylation | down-regulates activity | 0.2 | CKII phosphorylates T1172 of the L1 CD and phosphorylation of T1172 is responsible for loss of 2C2 signal. | SIGNOR-276283 |
Q15637 | Q01844 | 2 | binding | down-regulates | 0.418 | Here we report that zfm1 also interacts withews / overexpression of zfm1 in hepg2 cells represses the transactivation of reporter gene expression driven by gal4-ews-ntd fusion protein and this repression correlates with zfm1 binding to ews. | SIGNOR-58928 |
P40763 | Q13627 | 0 | phosphorylation | up-regulates activity | 0.265 | DYRK1A overexpression promotes STAT3 activity by phosphorylating STAT3 at Ser727 and contributes to reduced neuronal production and increased astroglial generation in DS. | SIGNOR-279992 |
O15169 | Q13233 | 2 | binding | up-regulates | 0.515 | We found that in contrast to axin, dvl2 activation of jnk does not require mekk1. | SIGNOR-77591 |
P16220 | Q9UQM7 | 0 | phosphorylation | down-regulates | 0.594 | Phosphorylation of creb1 at ser142 and ser143 is selectively activated by ca(2+) influx;phosphorylation of ser142 and ser143, disrupts the interaction of creb with its cofactor cbp. Phosphorylation of serine 142 in creb by camkii leads to dissociation of the creb dimer. | SIGNOR-82501 |
Q53ET0 | Q99576 | 1 | transcriptional regulation | up-regulates quantity | 0.2 | CRTC2 knockdown attenuates glucocorticoid-responsive GILZ mRNA expression in HeLa cells | SIGNOR-256109 |
P53671 | P23528 | 1 | phosphorylation | down-regulates activity | 0.766 | We report here that limk1 and limk2 phosphorylate both cofilin and actin-depolymerizing factor (adf) specifically at ser-3 and exhibit partially distinct substrate specificity when tested using site-directed cofilin mutants as substrates | SIGNOR-105098 |
O15111 | Q9NQC7 | 1 | phosphorylation | up-regulates activity | 0.544 | The phosphorylation of cyld was completely abolished by the combined mutations of the entire serine cluster (m4, lane 5). Similar results were obtained with the ikk holoenzyme (fig. 4c, panel 1), recombinant ikk_ (panel 2), and recombinant ikk_cyld phosphorylation may serve as a mechanism to inactivate its traf2 deubiquitination activity. | SIGNOR-204692 |
P63096 | Q9HBW0 | 2 | binding | up-regulates | 0.625 | Lysophosphatidic acid (lpa), a major g protein coupled receptor (gpcr)-activating ligand present in serum, elicits growth factor like responses by stimulating specific gpcrs coupled to heterotrimeric g proteins such as g(i), g(q), and g12/13. lpa2 also can couple to the gi/o, g12/13, and gqfamilies. | SIGNOR-84559 |
P46531 | P49757 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.798 | Mammalian numb proteins promote notch1 receptor ubiquitination and degradation of the notch1 intracellular domain | SIGNOR-99762 |
Q9P1Y6 | P09874 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | Furthermore, PHRF1 mediates PARP1 polyubiquitination for proteasomal degradation. | SIGNOR-278774 |
Q01973 | P41221 | 2 | binding | up-regulates | 0.747 | Ror1 and ror2 bind wnt5a. | SIGNOR-196133 |
P12830 | Q9UHD2 | 0 | phosphorylation | down-regulates activity | 0.272 | Inhibition of TBK1 increases association of Cdh1 with APC1.|It was found that TBK1 phosphorylates both Cdc20 as well as Cdh1 (Figure 2F). | SIGNOR-278996 |
P04637 | P62136 | 0 | dephosphorylation | down-regulates activity | 0.314 | Protein serine/threonine phosphatase-1 dephosphorylates p53 at Ser-15 and Ser-37 to modulate its transcriptional and apoptotic activities|In addition, our results reveal that one of the molecular mechanisms by which PP-1 promotes cell survival is to dephosphorylate p53, and thus negatively regulate p53-dependent death pathway. | SIGNOR-248557 |
Q6UB99 | P23560 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Neurite growth-related genes such as Trkb, Bdnf, Gap43, Coronin 1B, and Rab13 are downregulated in ANKRD11-deficient neurons. | SIGNOR-266732 |
P00519 | Q06124 | 1 | phosphorylation | up-regulates activity | 0.374 | Direct phosphorylation of SHP-2 by Abl kinases (Y580) promotes sustained activation of SHP-2 signaling and proliferation, and c-Abl/Abl-Related Gene-dependent activation of tyrosine kinase X further potentiates SHP-2 signaling by phosphorylating SHP-2 on Y63.|Endogenous Abl kinases phosphorylate SHP-2 on Y580 and induce sustained ERK phosphorylation in response to PDGF. | SIGNOR-278217 |
Q07866 | P27361 | 0 | phosphorylation | down-regulates | 0.264 | Phosphorylation of kinesin light chain 1 at serine 460 modulates binding and trafficking of calsyntenin-1mutation of klc1ser460 to an alanine residue, to preclude phosphorylation, increased the binding of calsyntenin-1, whereas mutation to an aspartate residueklc1ser460 is a predicted mitogen-activated protein kinase (mapk) target site, and we show that extracellular-signal-regulated kinase (erk) phosphorylates this residue in vitro. | SIGNOR-172642 |
P00533 | Q14457 | 1 | phosphorylation | down-regulates activity | 0.521 | The mechanism by which EGFR suppresses Beclin 1 function involves EGFR interaction with two domains (BH3 and ECD) of Beclin 1; EGFR mediated multisite tyrosine phosphorylation of Beclin 1 on residues Y229, Y233 and Y352; and EGFR mediated alterations in the Beclin 1 interactome (increased binding to the negative regulators, Bcl-2 and Rubicon, and decreased binding to the VPS34 lipid kinase).|Thus, EGFR signaling suppresses autophagy via its interaction with Beclin 1 during normal mitogenic signaling as well as during aberrant cell proliferation in cancer cells. | SIGNOR-278357 |
P15336 | P53778 | 0 | phosphorylation | up-regulates | 0.542 | Our results indicate that atf-2 not only directly binds to smad3/4 hetero-oligomers but also that atf-2 is phosphorylated by tgf-beta signaling via tak1 and p38. The two pathways, smad and tak1, synergistically enhance the activity of atf-2 which acts as their common nuclear target | SIGNOR-65589 |
Q05397 | P09769 | 0 | phosphorylation | up-regulates | 0.552 | Phosphorylated on tyrosine residues upon activation. Phosphorylation at tyr-925 is important for interaction with grb2 and depends on the complex formation between fak and the src-kinase fgr. | SIGNOR-94405 |
Q15750 | O95147 | 0 | dephosphorylation | down-regulates activity | 0.298 | DUSP14 directly interacted with TGF-beta-activated kinase 1 (TAK1)-binding protein 1 (TAB1) and dephosphorylated TAB1 at Ser (438), leading to TAB1 and TAK1 complex inactivation in T cells. | SIGNOR-277147 |
P46108 | Q92918 | 2 | binding | up-regulates | 0.686 | We found that hpk1 interacted with crk and crkl adaptor proteins in vitro and in vivo and that the proline-rich motifs within hpk1 were involved in the differential interaction of hpk1 with the crk proteins and grb2. Crk and crkl not only activated hpk1 but also synergized with hpk1 in the activation of jnk. | SIGNOR-63988 |
Q9NWT8 | O14965 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.681 | AIP is phosphorylated on Serine 70 by Aurora‐A but not Aurora‐B and expression of phosphorylation mimic mutant of AIP results in prolonged protein stability compared to unphosphorylatable mutant. Phosphorylation of AIP Prolongs its Protein Stability | SIGNOR-262648 |
Q9H0M0 | Q13887 | 1 | ubiquitination | up-regulates activity | 0.459 | WWP1 and Smurf2 were adopted to induce ubiquitination of endogenous KLF5 protein in cells.|WWP1 or Smurf2 degrades KLF5 by ubiquitination to repress fracture healing. | SIGNOR-278683 |
Q9UEW8 | Q9Y6R1 | 1 | phosphorylation | down-regulates activity | 0.348 | SPAK phosphorylates the transporters to reduce their surface expression and thus their activity and consequently inhibits ductal secretion to stabilize the resting state. PP1 reverses the effect of SPAK. Molecular analysis revealed that the WNK kinases acted as scaffolds to recruit SPAK, which phosphorylated CFTR and NBCe1-B, reducing their cell surface expression. | SIGNOR-263133 |
Q18PE1 | P46108 | 2 | binding | up-regulates activity | 0.357 | Here, we identify two tyrosine residues in Dok-7 that are phosphorylated by Agrin stimulation, and show that two proteins, Crk and Crk-L, are recruited to these phosphorylation sites in Dok-7. | SIGNOR-273847 |
P56159 | P07949 | 2 | binding | up-regulates | 0.754 | Gdnfr-alpha-ligand complex, together with the tyrosine kinase receptor (cret) forms a functional receptor that activates downstream signal transduction pathways | SIGNOR-77587 |
Q9UPT6 | P45984 | 2 | binding | up-regulates | 0.663 | The c-jun nh2-terminal kinase (jnk)-interacting protein (jip) group of scaffold proteins (jip1, jip2, and jip3) can interact with components of the jnk signaling pathway and potently activate jnk. | SIGNOR-134561 |
Q9BYU1 | P55075 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | Our results in ES cells suggest that Engrailed inhibits Fgf8 expression in the absence of Pbx1. We identified single Engrailed- and Pbx-binding sites in the Fgf8 intron that inhibit expression of Fgf8 in mouse ES cells, but that together can allow full Fgf8 expression. Our data support the model that Engrailed heterodimerized with Pbx might activate transcription, while Engrailed or Pbx proteins alone might repress transcription | SIGNOR-265806 |
Q9BUL8 | Q12923 | 0 | dephosphorylation | down-regulates activity | 0.567 | In addition, our yeast two-hybrid analysis revealed that CCM3 also binds to the 270-kDa nonreceptor protein tyrosine phos- phatase FAP-1 in a region predicted to contain the C- terminal phosphatase domain [23]. We have shown that this catalytic domain is capable to dephosphorylate CCM3. By dephosphorylation, FAP-1 might therefore negatively reg- ulate CCM3 activity and downstream signaling. | SIGNOR-248714 |
P05129 | Q05586 | 1 | phosphorylation | up-regulates activity | 0.351 | Serines 890 and 896 of the NMDA receptor subunit NR1 are differentially phosphorylated by protein kinase C isoforms. The results show that PKC alpha phosphorylates preferentially S896 and PKC gamma preferentially S890. | SIGNOR-263176 |
P33032 | P42127 | 2 | binding | down-regulates activity | 0.5 | The melanocortin (MC) receptor family consists of five Gs-coupled receptors that control various physiological functions in response to four distinct agonists, adrenocorticotropic hormone (ACTH, also known as corticotrophin) and alpha, beta, and gamma melanocyte-stimulating hormone (MSH), which are derived from the proopiomelanocortin precursor protein, and two inverse agonists, agouti and agouti-related proteins | SIGNOR-268713 |
Q96GD0 | P23528 | 1 | dephosphorylation | down-regulates activity | 0.447 | Chronophin, a novel HAD-type serine protein phosphatase, regulates cofilin-dependent actin dynamics|Cofilin is a key regulator of actin cytoskeletal dynamics whose activity is controlled by phosphorylation of a single serine residue. We report the biochemical isolation of chronophin (CIN), a unique cofilin-activating phosphatase of the haloacid dehalogenase (HAD) superfamily. | SIGNOR-248764 |
Q86WV6 | Q7Z434 | 2 | binding | up-regulates activity | 0.2 | MAVS also interacts with STING that locates at the ER (endoplasmic reticulum), and induces the ubiquitination and dimerization of STING. The activated STING recruits TBK1 and IRF3 and contributes to the phosphorylation of IRF3 mediated by TBK1. | SIGNOR-260152 |
Q6NYC1 | Q7L2J0 | 1 | cleavage | down-regulates activity | 0.268 | JMJD6 cleaves MePCE. we propose that JMJD6 is the cognate protease of MePCE and cleaves at the R171 site within MePCE. Experiments using purified JMJD6 showed that it could make a cut in an enzyme called MePCE, which belongs to the group of proteins that hold P-TEFb in its inactive form. The levels of activated Pol II were lower in cells without JMJD6 and higher in those without MePCE. Together, the results suggest that JMJD6 cuts MePCE to release P-TEFb, which then activates Pol II. | SIGNOR-261037 |
P63151 | P04049 | 2 | binding | up-regulates activity | 0.464 | ... the PP2A holoenzymes ABC and ABC act downstream of Ras and upstream of MEK1 to promote activation of this MAPK signaling cascade. Furthermore both PP2A holoenzymes were found to associate with Raf1 and catalyze dephosphorylation of inhibitory phospho-Ser-259. | SIGNOR-243417 |
O43541 | Q15797 | 2 | binding | down-regulates | 0.579 | Smad6 also inhibits bmp signaling by forming a complex with smad1 and by interfering with complex formation between smad1 and smad4 | SIGNOR-103621 |
Q9UKV0 | Q9Y463 | 0 | phosphorylation | down-regulates | 0.2 | Mirk activated mef2 not through direct phosphorylation of mef2 but by phosphorylation of its inhibitors, the class ii histone deacetylases (hdacs). Mef2 is sequestered by class ii hdacs such as hdac5 and mef2-interacting transcriptional repressor (mitr). Mirk antagonized the inhibition of mef2c by mitr, whereas kinase-inactive mirk was ineffective. Mirk phosphorylates class ii hdacs at a conserved site within the nuclear localization region, reducing their nuclear accumulation in a dose-dependent and kinase-dependent manner | SIGNOR-235813 |
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