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 |
|---|---|---|---|---|---|---|---|
P17252 | P35222 | 1 | phosphorylation | down-regulates | 0.413 | As shown in Fig. 1 B, PKCalpha readily phosphorylated Ser33 and Ser37 / Thr41 on full-length beta-catenin (beta-catenin 1 - 781) and CTD deletion mutant (beta-catenin 1-682).|To examine the effect of the armadillo repeats 1-5 on PKCalpha mediated beta-catenin degradation, DNA constructs expressing beta-catenin 1 - 781 and beta-catenin deletion mutants (beta-catenin 1-422 and beta-catenin 1-138) were transfected into HEK293 cells, followed by treatment with increasing concentrations of A23187 and CGK062, which are known activators of PKCalpha. | SIGNOR-278492 |
Q9P275 | Q9H6R0 | 1 | deubiquitination | up-regulates quantity by stabilization | 0.508 | Loss of the deubiquitinase USP36 destabilizes the RNA helicase DHX33 and causes preimplantation lethality in mice. | SIGNOR-272289 |
P55957 | Q96J02 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.352 | The ubiquitin ligase Itch mediates the antiapoptotic activity of epidermal growth factor by promoting the ubiquitylation and degradation of the truncated C-terminal portion of Bid | SIGNOR-271415 |
Q9UMS4 | O43395 | 1 | polyubiquitination | up-regulates activity | 0.754 | Here, we report that the spliceosomal Prp19 complex modifies Prp3, a component of the U4 snRNP, with nonproteolytic K63-linked ubiquitin chains. The K63-linked chains increase the affinity of Prp3 for the U5 snRNP component Prp8, thereby allowing for the stabilization of the U4/U6.U5 snRNP. | SIGNOR-271966 |
P27361 | P40763 | 1 | phosphorylation | up-regulates | 0.72 | The activation of stat-3 is regulated by phosphorylation of tyrosine 705 by receptor and nonreceptor protein tyrosine kinases these include epidermal growth factor receptor (egfr) kinase,92 src,5 janus-activated kinases (jak), and extracellular signal-regulated kinase (erk)a constitutively active galpha16 mutant, galpha16ql, stimulated stat3-dependent luciferase activity as well as the phosphorylation of stat3 at both tyr705 and ser727. Galpha16ql-induced stat3 activation was enhanced by overexpression of extracellular signal-regulated kinase 1 (erk1 | SIGNOR-118596 |
P06493 | P33991 | 1 | phosphorylation | down-regulates activity | 0.592 | We report here that human mcm4, a subunit of the putative dna replicative helicase, is extensively phosphorylated in hela cells when they are incubated in the presence of inhibitors of dna synthesis or are exposed to uv irradiation. The data presented here indicate that the consecutive actions of atr-chk1 and cdk2 kinases are involved in this phosphorylation in the presence of hydroxyurea. Phosphorylation of t19 correlates with lowered level of dna helicase activity of the purified mcm4,6,7 complex. | SIGNOR-100877 |
P12755 | P31749 | 0 | phosphorylation | down-regulates | 0.337 | The phosphorylation of ski at threonine 458 is induced by akt pathway activators including insulin, insulin-like growth factor-1, and hepatocyte growth factor. The phosphorylation of ski causes its destabilization and reduces ski-mediated inhibition of expression of another negative regulator of tgf-beta, smad7 | SIGNOR-252527 |
P11362 | P27361 | 0 | phosphorylation | down-regulates | 0.32 | Erk-mediated phosphorylation of fibroblast growth factor receptor 1 on ser777 inhibits signaling | SIGNOR-200884 |
P31749 | Q13418 | 0 | phosphorylation | up-regulates | 0.779 | Ilk can phosphorylate pkb-akt on serine-473, whereas kinase-deficient ilk severely inhibits endogenous phosphorylation of pkb-akt on serine-473, demonstrating that ilk is involved in agonist stimulated, pi(3)k-dependent, pkb-akt activation. | SIGNOR-252597 |
P14866 | Q16566 | 0 | phosphorylation | up-regulates | 0.379 | Here we show that the regulation of the stress axis-regulated exon of the slo1 potassium channel transcripts by membrane depolarization requires a highly conserved camkiv target serine (ser-513) of the heterogeneous ribonucleoprotein l. Ser-513 phosphorylation within the rna recognition motif 4 enhanced heterogeneous ribonucleoprotein l interaction with the camkiv-responsive rna element 1 of stress axis-regulated exon and inhibited binding of the large subunit of the u2 auxiliary factor u2af65. | SIGNOR-197367 |
P00352 | O14965 | 0 | phosphorylation | up-regulates activity | 0.372 | AURKA phosphorylates ALDH1A1 at three critical residues which exert a multifaceted regulation over its level, enzymatic activity, and quaternary structure. While all three phosphorylation sites contribute to its increased stability, T267 phosphorylation primarily regulates ALDH1A1 activity. AURKA-mediated phosphorylation rapidly dissociates tetrameric ALDH1A1 into a highly active monomeric species. | SIGNOR-276748 |
Q9BV73 | Q96CN5 | 2 | binding | up-regulates activity | 0.408 | Here, we show that LRRC45 is a centrosome linker that localizes at the proximal ends of the centrioles and forms fiber-like structures between them. Depletion of LRRC45 results in centrosome splitting during interphase. LRRC45 interacts with C-Nap1 and rootletin | SIGNOR-273703 |
P18031 | P00533 | 2 | dephosphorylation | down-regulates activity | 0.76 | We have shown previously that amino acid residues flanking the phosphotyrosine are important for efficient PTP1 catalysis (Table 1 and Refs. 9, 10, and 17). For example, the kcat/Km value for the undecapeptide, EGFR988-989 (epidermal growth factor autophosphorylation site Tyr992, residues 988-998) (Asp-Ala-Asp-Glu-pTyr-Leu-Ile-Pro-Gln-Gln-Gly) is 3220-fold higher than that of phosphotyrosine (Table 1). We further demonstrated that a minimum of six amino acid residues are required for the most efficient PTP1 binding and catalysis. | SIGNOR-248407 |
O60260 | Q9Y6H5 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | Here we show that parkin interacts with and ubiquitinates the alpha-synuclein-interacting protein, synphilin-1. | SIGNOR-278550 |
Q99558 | Q9UHD2 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.37 | TBK1 induces NIK phosphorylation and degradation. | SIGNOR-279767 |
P15407 | P15408 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.403 | Members of the AP1 family distinctly regulated the fra-1 promoter. In particular, coexpression of c-Jun, Jun-D, and Fra-2 up-regulated fra-1 transcription. | SIGNOR-261602 |
P06493 | O94782 | 1 | phosphorylation | up-regulates activity | 0.371 | In this study, we show that Ser313 phosphorylation in USP1 is required for its interaction with UAF1 and for the stimulation of USP1's activity. We further demonstrated that CDK1 is responsible for Ser313 phosphorylation, and protein phosphatase treatment of USP1 can lead to inactivation of USP1/UAF1. | SIGNOR-276423 |
P17600 | P20336 | 2 | binding | up-regulates activity | 0.616 | Synapsins, a family of neuron-specific phosphoproteins, have been demonstrated to regulate the availability of synaptic vesicles for exocytosis by binding to both synaptic vesicles and the actin cytoskeleton in a phosphorylation-dependent manner. The interaction between synapsin I and Rab3A was confirmed by photoaffinity labeling experiments on purified synaptic vesicles and by the formation of a chemically cross-linked complex between synapsin I and Rab3A in intact nerve terminals. The data indicate that synapsin I is a novel Rab3 interactor on synaptic vesicles and suggest that the synapsin-Rab3 interaction may participate in the regulation of synaptic vesicle trafficking within the nerve terminals. | SIGNOR-269181 |
P26927 | P17252 | 1 | 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-277179 |
O14904 | O75197 | 2 | binding | up-regulates | 0.658 | 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-132073 |
Q16555 | P49841 | 0 | phosphorylation | down-regulates activity | 0.724 | Here, we showed that glycogen synthase kinase-3beta (gsk-3beta) phosphorylated crmp-2 at thr-514 and inactivated it | SIGNOR-133255 |
P41240 | P08575 | 1 | phosphorylation | up-regulates | 0.469 | Tyrosine phosphorylation of cd45 phosphotyrosine phosphatase by p50csk kinase creates a binding site for p56lck tyrosine kinase and activates the phosphatase. | SIGNOR-26785 |
P45983 | P40763 | 1 | phosphorylation | up-regulates activity | 0.567 | Transfection of the cells with sirna specific for jnk1 revealed that jnk silencing reduced serine727 phosphorylation of stat3, | SIGNOR-235704 |
P05067 | P07339 | 0 | cleavage | down-regulates quantity by destabilization | 0.489 | The precise cathepsin D cleavage sites within these recombinant betaAPP substrates were identified using this technique. Both recombinant substrates were cleaved at the following sites: Leu49-Val50, Asp68-Ala69, Phe93-Phe94. | two additional cleavage sites near the amino terminus of betaA4, Glu-3-Val-2 and Glu3-Phe4, were observed, indicating that cathepsin D cleavage of betaAPP is influenced by the structural integrity of the substrate. Taken together, these results indicate that in vitro, cathepsin D is unlikely to function as gamma-secretase; however, the ability of this enzyme to efficiently cleave betaAPP substrates at nonamyloidogenic sites within the molecule may reflect a role in betaAPP catabolism. | SIGNOR-261767 |
P68400 | P20810 | 1 | phosphorylation | up-regulates activity | 0.2 | We also showed that casein kinase 2, a pro-survival kinase overexpressed in many cancer types, phosphorylated calpastatin at Ser-633. Our results indicate that calpastatin phosphorylation promotes radiation resistance in GBM cells by increasing the activity of calpain proteases, which are known to promote survival and invasion in cancer. | SIGNOR-277388 |
O15530 | P08069 | 0 | phosphorylation | up-regulates | 0.341 | Previous studies indicate that optimal activation of PDK1 requires phosphorylation of Tyr373/376 (11, 12, 14, 17), and growth factor receptor activation leads to PDK1 recruitment to the plasma membrane, followed by sequential phosphorylation of Tyr9 and then Tyr373/376 | SIGNOR-166710 |
P04150 | Q9UNS1 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.252 | GR directly regulates transcription of circadian clock components in mouse and human primary MSCs. Per2, E4bp4, Per1, and Timeless rapidly respond to glucocorticoid stimulation. Primary glucocorticoid receptor (GR) target genes are those at which GR occupies a nearby genomic glucocorticoid response element (GRE) and regulates target gene transcription | SIGNOR-268052 |
Q01196 | P24941 | 0 | phosphorylation | up-regulates activity | 0.2 | We have identified four phosphorylation sites on aml1c that are necessary for transcriptional activity of aml1c in k562 and 293t cells (27).4 mutation of these four sites (serine 276, serine 293, serine 303, and threonine 300) to alanine abolishes transcriptional activation, whereas mutation of these sites to aspartic acid (which mimics phosphorylation) results in a hyperactive protein. | SIGNOR-138932 |
P10242 | O75444 | 2 | binding | down-regulates | 0.66 | Full-length c-maf binds to the c-myb and ets-1. / c-maf inhibits c-myb and ets-1 transcriptional activity. | SIGNOR-56811 |
P35367 | P09471 | 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-257251 |
P10071 | Q13635 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.709 | GLI activators bind to GACCACCCA motif to regulate transcription of GLI1, PTCH1, PTCH2, HHIP1, MYCN, CCND1, CCND2, BCL2, CFLAR, FOXF1, FOXL1, PRDM1 (BLIMP1), JAG2, GREM1, and Follistatin | SIGNOR-188884 |
Q13608 | Q7Z412 | 2 | binding | up-regulates activity | 0.78 | Pex26 recruits Pex6–Pex1 complexes to peroxisomes. Pex26 anchors Pex6 and Pex1 through Pex26–Pex6 and Pex6–Pex1 interactions. | SIGNOR-253614 |
Q04206 | Q92793 | 2 | binding | up-regulates | 0.879 | Both p53 and rela(p65) interact with the transcriptional coactivator proteins p300 and creb-binding protein (cbp), and we demonstrate that these results are consistent with competition for a limiting pool of p300/cbp complexes in vivo. | SIGNOR-66953 |
Q9P1W9 | Q13200 | 1 | phosphorylation | up-regulates activity | 0.2 | Seven of these kinases (PIM1/2/3, MAP4K1/2, PKA, and NEK6) directly and robustly phosphorylated recombinant GST-Rpn1 at S361 in vitro (Fig. 3D and SI Appendix, Fig. S3 A and B). | SIGNOR-273896 |
Q14974 | P52294 | 2 | binding | up-regulates activity | 0.86 | Although ORF6 causes a relocalization of KPNA2 from the cytosol to the ER/Golgi membrane, KPNA2 is not directly involved in the translocation of the STAT1:STAT2:IRF9 (ISGF3) complex into the nucleus; rather, KPNA1 interacts with KPNB1 to initiate ISGF3's nuclear localization. | SIGNOR-260273 |
P10451 | P09237 | 0 | cleavage | up-regulates activity | 0.706 | In this study, we found a novel motif, LRSKSRSFQVSDEQY, in the C-terminal fragment of MMP-3/7-cleaved mouse OPN binds to α9β1 integrin. Importantly, this novel motif is involved in the development of anti-type II collagen antibody-induced arthritis (CAIA). This study provides the first in vitro and in vivo evidence that OPN cleavage by MMP-3/7 is an important regulatory mechanism for CAIA. | SIGNOR-253321 |
Q9H0H5 | P63000 | 1 | gtpase-activating protein | down-regulates activity | 0.586 | 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-260512 |
O14965 | P07195 | 1 | phosphorylation | up-regulates activity | 0.2 | Aurora-A-mediated phosphorylation of LDHB serine 162 significantly increases its activity in reducing pyruvate to lactate, which efficiently promotes NAD+ regeneration, glycolytic flux, lactate production and bio-synthesis with glycolytic intermediates. | SIGNOR-277493 |
O43541 | O95947 | 2 | binding | down-regulates quantity by destabilization | 0.327 | Smad6 mediates Tbx6 ubiquitination and proteasomal degradation. Tbx6 forms a ternary complex with Smad6 and Smurf1. Here, we report that Tbx6 interacts directly with Smad6, an inhibitory Smad that antagonizes the BMP signal. This interaction is mediated through the Mad homology 2 (MH2) domain of Smad6 and residues 90-180 of Tbx6. We demonstrate that Smad6 facilitates the degradation of Tbx6 protein through recruitment of Smurf1, a ubiquitin E3 ligase. | SIGNOR-272785 |
Q9UQD0 | Q96PU5 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.325 | 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-253461 |
P31749 | Q9BRS8 | 1 | phosphorylation | up-regulates activity | 0.353 | Akt dependent phosphorylation of LARP6. We provide the first description that LARP6 is phosphorylated at multiple sites and that phosphorylation of S451 is critical to activate the protein in type I collagen biosynthesis. | SIGNOR-277213 |
P60484 | P16220 | 1 | dephosphorylation | down-regulates activity | 0.436 | Our study demonstrates that PTEN can dephosphorylate CREB at Ser133 and that PTEN protein phosphatase activity is required for CREB dephosphoryation.|Moreover, we use both in vitro and in vivo experiments to show PTEN can dephosphorylate CREB in a phosphatase-dependent manner, suggesting that CREB is a substrate of PTEN nuclear phosphatase. Loss of Pten results in an elevated RNA level of multiple CREB transcriptional targets and increased cell proliferation, which can be reversed by a nonphosphorylatable CREB mutant or knockdown of CREB. These data reveal a mechanism for PTEN modulation of CREB-mediated gene transcription and cell growth. | SIGNOR-248543 |
P15408 | P15407 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.403 | Members of the AP1 family distinctly regulated the fra-1 promoter. In particular, coexpression of c-Jun, Jun-D, and Fra-2 up-regulated fra-1 transcription. | SIGNOR-261602 |
P31751 | Q05513 | 0 | phosphorylation | up-regulates activity | 0.498 | The activation of PKBbeta and PKBgamma by PDK1 was accompanied by the phosphorylation of the residues equivalent to Thr308 in PKBalpha, namely Thr309 (PKBbeta) and Thr305 (PKBgamma). PKBgamma which had been activated by PDK1 possessed a substrate specificity identical with that of PKBalpha and PKBbeta towards a range of peptides. The activation of PKBgamma and its phosphorylation at Thr305 was triggered by insulin-like growth factor-1 in 293 cells. | SIGNOR-248997 |
P51003 | O43865 | 2 | binding | down-regulates activity | 0.246 | Inositol 1,4,5-triphosphate receptor-binding protein released with inositol 1,4,5-triphosphate (IRBIT) associates with components of the mRNA 3' processing machinery in a phosphorylation-dependent manner and inhibits polyadenylation|In addition to CPSF, IRBIT interacted in vitro with poly(A) polymerase (PAP), which is the enzyme recruited by CPSF to elongate the poly(A) tail, and inhibited PAP activity in a phosphorylation-dependent manner. | SIGNOR-268329 |
P52945 | P78527 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.307 | The interaction of PDX-1 with Ku subunits and its phosphorylation on threonine 11 by the DNA-PK appear to be implicated in its degradation by the proteosome. | SIGNOR-225542 |
O15392 | Q9UJT9 | 2 | binding | down-regulates quantity by destabilization | 0.307 | Fbxl7 targets survivin for polyubiquitylation and proteasomal degradation.these data suggest that the Skp1·Cul1·F-box protein complex subunit Fbxl7 modulates mitochondrial function by controlling the cellular abundance of survivin. These results suggest that both Lys-90 and Lys-91 are critical for Fbxl7-mediated polyubiquitylation. | SIGNOR-272436 |
Q9BUR4 | Q13315 | 0 | phosphorylation | up-regulates activity | 0.337 | Here, we show that in response to various types of DNA damage, including IR and UV, WRAP53β is phosphorylated on serine residue 64 by ATM with a time-course that parallels its accumulation at DNA lesions. Interestingly, recruitment of phosphorylated WRAP53β (pWRAP53βS64) to sites of such DNA damage promotes its interaction with γH2AX at these locations. | SIGNOR-273511 |
P40189 | P29353 | 2 | binding | up-regulates | 0.345 | Shc mediates IL-6 signaling by interacting with gp130 and Jak2 kinase. | SIGNOR-250574 |
Q8WW38 | P43694 | 2 | binding | down-regulates activity | 0.782 | FOG-2 associates physically with the N-terminal zinc finger of GATA-4 both in vitro and in vivo. This interaction appears to modulate specifically the transcriptional activity of GATA-4 because overexpression of FOG-2 in both NIH 3T3 cells and primary rat cardiomyocytes represses GATA-4-dependent transcription from multiple cardiac-restricted promoters. | SIGNOR-236959 |
P40763 | P22607 | 0 | phosphorylation | up-regulates activity | 0.631 | Activation of Stat1 and Stat3 by FGFR derivatives. Lysates of 293T cells transfected as indicated were analysed by Western blotting using Phospho-Stat1 (Y701) antisera (top) or Stat1 antisera (bottom). (b) The same lysates in (a) were re-examined for phosphorylated Stat3 by Western blotting with Phospho-Stat3 (Y705) (top). all three FGFR family members examined here are able to lead to Stat activation. Expression of the 'TDII-like' derivatives of FGFR1, FGFR3, and FGFR4, as well as myrR1-WT, led to phosphorylation of both Stat1 and Stat3. | SIGNOR-251139 |
P08754 | P34969 | 2 | binding | up-regulates activity | 0.281 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-257168 |
O15033 | O75431 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | Therefore, these results implied that AREL1 ubiquitinates and promotes the degradation of MTX2. | SIGNOR-267674 |
P51812 | P12931 | 0 | phosphorylation | up-regulates | 0.355 | Together, our findings suggest that src-dependent phosphorylation at tyr-529 facilitates inactive erk binding to rsk2, which might be a general requirement for rsk2 activation by egf through the mek/erk pathway. | SIGNOR-160052 |
P06213 | P0DP24 | 1 | phosphorylation | down-regulates | 0.352 | The in vitro phosphorylation of calmodulin by the insulin receptor tyrosine kinase. Phosphorylated calmodulin does not exhibit the characteristic ca2+ shift normally observed with calmodulin in electrophoretic gels, an observation that is consistent with this modification affecting the biological activity of the molecule. | SIGNOR-266320 |
P17252 | P29972 | 1 | phosphorylation | up-regulates | 0.2 | Activation of protein kinase c (pkc) by 1-oleoyl-2-acetyl-sn-glycerol (oag) induced a marked increase of aqp1-dependent water permeability. This regulation was abolished in mutated aqp1 channels lacking both consensus pkc phosphorylation sites thr(157) and thr(239) (termed aqp1 deltapkc). | SIGNOR-155106 |
P67775 | Q9UIC8 | 0 | methylation | up-regulates activity | 0.908 | Methylation of the carboxy-terminal Leu309 in a conserved TPDYFL309 motif of the C subunit has been shown to enhance the affinity of the PP2A core enzyme for some, but not all, regulatory subunits |The PP2A core enzyme was methylated by a PP2A-specific leucine carboxyl methyltransferase (LCMT1) | SIGNOR-265749 |
P49682 | Q07325 | 2 | binding | up-regulates activity | 0.782 | The chemokines CXCL9, 10, and 11 exert their action via CXC chemokine receptor-3 (CXCR3), a receptor highly expressed on activated T cells. | SIGNOR-260970 |
P15172 | P00519 | 0 | phosphorylation | down-regulates activity | 0.286 | We have found that c-Abl can phosphorylate MyoD at a conserved N-terminal tyrosine (Tyr30) that is located within the transactivation domain. Mutation of Tyr30 to Phe does not interfere with the function of MyoD, but theTyr30Phe mutant becomes resistant to the inhibitory effect of DNA damage. | SIGNOR-253055 |
P05771 | P11388 | 1 | phosphorylation | up-regulates activity | 0.359 | Here, we have shown that the enzymatic activity of topoisomerase II alpha protein purified from HeLa cell nuclei was strongly enhanced following phosphorylation by protein kinase C. | Site-directed mutagenesis studies indicated that phosphorylation of serine 29 generated both of these phosphopeptides. | SIGNOR-249195 |
Q5JVS0 | Q05655 | 0 | phosphorylation | down-regulates activity | 0.29 | We found a strong phosphorylation of Ki-1/57 by PKCalphabeta, PKCdelta, PKClambda/zeta, and especially by PKCsigma, however not by PKCmi. These data show that Ki-1/57 can serve in principal as a substrate for a wide variety of different PKC isoforms but also that its phosphorylation is strongest with PKCsigma. | This suggests that the two threonine residues present in this fragment (Thr354 and Thr375) might be the main target residues for phosphorylation by PKC in vitro. | Ki-1/57 Exits the Nucleus upon PMA Activation | SIGNOR-249254 |
O00206 | Q8IUC6 | 2 | binding | up-regulates activity | 0.85 | To initiate the innate immune response, Toll-like receptors (TLRs) associate with cytoplasmic adaptor proteins through TIR (Toll/interleukin-1 receptor) domain interactions. The four principal signaling adaptor proteins include MyD88, MAL, TRIF and TRAM, and the fifth protein SARM, involved in negative regulation of TLR pathways, is usually considered a part of the TIR domain-containing adaptor protein group | SIGNOR-252067 |
P07585 | P08253 | 0 | cleavage | down-regulates quantity by destabilization | 0.695 | 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-256350 |
Q9UBN7 | O43791 | 0 | ubiquitination | down-regulates quantity | 0.2 | Cullin3 SPOP ubiquitin E3 ligase promotes the poly-ubiquitination and degradation of HDAC6 | SIGNOR-268862 |
P84022 | Q92831 | 2 | binding | up-regulates | 0.676 | P/caf was found to interact directly with smad3 in vitro. Moreover, smad2 and smad3 interacted with p/caf upon tgf-beta type i receptor activation in cultured mammalian cells. these results demonstrate the co-activator function of p/caf for smad2 and smad3. | SIGNOR-83607 |
P55211 | Q07817 | 2 | binding | down-regulates activity | 0.681 | Bcl2l1 associates with casp9 and apaf-1 in mammalian cells.Bcl-XL interacts with Apaf-1 and inhibits Apaf-1-dependent caspase-9 activation | SIGNOR-56402 |
P29353 | P35968 | 0 | relocalization | up-regulates activity | 0.711 | In a similar fashion, KDR associates with Grb2 and Nck in a ligand-dependent fashion, suggesting Shc, Grb2, and Nck as potential candidates involved in the regulation of endothelial function. | SIGNOR-261949 |
Q15637 | Q13976 | 0 | phosphorylation | down-regulates activity | 0.438 | PKG phosphorylates SF1 at Ser20, which inhibits the SF1-U2AF65 interaction leading to a block of pre-spliceosome assembly. Mutation of Ser20 to Ala or Thr also inhibits the interaction with U2AF65, indicating that Ser20 is essential for binding. | SIGNOR-249018 |
P13497 | P05997 | 1 | cleavage | up-regulates activity | 0.607 | BMP-1 Can Efficiently Cleave Pro-α1(V) N-propeptides and Pro-α2(V) C-propeptides and Less Efficiently Cleave Pro-α1(V) C-propeptides in Vitro. BMP-1 efficiently cleaves pro-α2(V) C-propeptides at a single site between residues 1250 (Glu) and 1251 (Asp). | SIGNOR-256343 |
O00712 | Q13562 | 1 | transcriptional regulation | up-regulates quantity | 0.282 | For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8) | SIGNOR-268897 |
Q92830 | P19174 | 1 | acetylation | down-regulates activity | 0.2 | The histone acetyltransferase GCN5 (general control non-repressed protein 5) acetylates PGC-1alpha and suppresses its transcriptional activity, whereas sirtuin 1 deacetylates and activates PGC-1alpha. | SIGNOR-275498 |
O15350 | Q15067 | 2 | binding | down-regulates quantity by destabilization | 0.2 | Downregulation of ACOX1 increased p73, but not p53, expression. p73 expression was critical for apoptosis induction induced by ACOX1 downregulation. ACOX1 reduced p73 expression by destabilizing p73 protein. We also found that ACOX1 interacted with p73 protein | SIGNOR-261056 |
P42574 | P55212 | 1 | cleavage | up-regulates | 0.619 | Caspase-3 is required for the activation of caspases 6 | SIGNOR-64179 |
P00519 | Q13588 | 2 | binding | up-regulates | 0.267 | We show that the grb2-related adapter protein, gads, also associates with bcr-abl, specifically through y177 and demonstrate that bcr-abl-driven lymphoid disease requires gads | SIGNOR-200871 |
P05771 | P49840 | 1 | phosphorylation | down-regulates | 0.327 | Convergence of multiple signaling cascades at glycogen synthase kinase 3: edg receptor-mediated phosphorylation and inactivation by lysophosphatidic acid through a protein kinase c-dependent intracellular pathway. | SIGNOR-115718 |
Q96GD4 | Q8IX90 | 1 | phosphorylation | up-regulates activity | 0.455 | Aurora B directly phosphorylated Ska1 and Ska3 in vitro, and expression of phosphomimetic mutants of Ska1 and Ska3 impaired Ska KT recruitment and formation of stable KT-MT fibers (K-fibers), disrupting mitotic progression. We propose that Aurora B phosphorylation antagonizes the interaction between the Ska complex and the KMN network, thereby controlling Ska recruitment to KTs and stabilization of KT-MT attachments. | SIGNOR-262661 |
P40763 | Q15256 | 0 | dephosphorylation | down-regulates activity | 0.2 | Here, we report identification of signal transducer and activator of transcription 3 (STAT3) as a substrate of PTPRT. Phosphorylation of a tyrosine at amino acid Y705 is essential for the function of STAT3, and PTPRT specifically dephosphorylated STAT3 at this position. | SIGNOR-248719 |
P11413 | P04637 | 2 | binding | down-regulates activity | 0.583 | The p53 protein binds to glucose-6-phosphate dehydrogenase (G6PD), the first and rate-limiting enzyme of the PPP, and prevents the formation of the active dimer. | SIGNOR-267468 |
P51449 | O00327 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.502 | As RORs function as transcriptional activators and their expression correlates with histone acetylation and chromatin accessibility, RORs are thought to function as positive regulators of Bmal1 expression at its peak levels, whereas REV-ERBs block ROR and negatively regulate Bmal1 at the trough of its expression. | SIGNOR-268004 |
P07947 | P40189 | 0 | phosphorylation | up-regulates activity | 0.2 | Binding of LIF to the LIFR-gp130 receptor complex has been previously shown to activate YES and YAP/TAZ-TEAD -dependent transcription, which is required to maintain self-renewal in embryonic stem cells | SIGNOR-278033 |
P11802 | Q08050 | 1 | phosphorylation | up-regulates | 0.624 | We identified the forkhead box m1 (foxm1) transcription factor as a common critical phosphorylation target. Cdk4/6 stabilize and activate foxm1, thereby maintain expression of g1/s phase genes, suppress the levels of reactive oxygen species (ros), and protect cancer cells from senescence. | SIGNOR-177266 |
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 |
P15172 | P15173 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.46 | We conclude that MyoD is the major MRF that binds to the E-box from the myogenin promoter during differentiation. | SIGNOR-255640 |
Q03468 | P27695 | 2 | binding | down-regulates activity | 0.418 | CSB stimulates the AP site incision activity of APE1 on normal (i.e. fully paired) and bubble AP-DNA substrates, with the latter being more pronounced (up to 6-fold). This activation is ATP-independent, and specific for the human CSB and full-length APE1 protein. CSB and APE1 were also found in a common protein complex in human cell extracts, and recombinant CSB, when added back to CSB-deficient whole cell extracts, resulted in increased total AP site incision capacity. | SIGNOR-251932 |
P10912 | P54764 | 0 | phosphorylation | up-regulates activity | 0.2 | EphA4 binds to growth hormone receptor at both its extracellular and intracellular domains and phosphorylates growth hormone receptor when stimulated with a ligand.|These findings suggest that EphA4 activates not only GHR, as shown above, but also JAK2 by direct phosphorylation. | SIGNOR-279461 |
Q9UFD9 | Q9UJD0 | 2 | binding | down-regulates activity | 0.285 | SH3 domains of RBPs interact with RIMs. The enhancement of depolarization-induced secretion in PC12 cells by fusion proteins that suppress the associations of RBPs with RIMs and α1 suggests that RBPs may repress RIMs, either directly or through associated proteins. | SIGNOR-264370 |
Q6ZVD8 | P23443 | 1 | dephosphorylation | down-regulates activity | 0.49 | We show that PHLPP preferentially dephosphorylates the hydrophobic motif T389 site in S6K1 in vitro | SIGNOR-248247 |
P48729 | Q9H4H8 | 2 | binding | up-regulates quantity | 0.384 | We identified members of the FAM83 family of proteins as partners of CK1 in cells. All eight members of the FAM83 family (FAM83A–H) interacted with the α and α-like isoforms of CK1; FAM83A, -B, -E, and -H also interacted with the δ and ε isoforms of CK1. The intrinsic catalytic activity of CK1 is not affected by or required for the association of CK1 with FAM83 proteins. Our findings imply that the DUF1669 domains of FAM83 proteins anchor CK1 α, α-like, δ, and ε isoforms in specific subcellular compartments and potentially mediate their association with substrates. | SIGNOR-273749 |
Q99801 | P19784 | 0 | phosphorylation | up-regulates | 0.315 | In vitro kinase assays followed by mass spectrometric analyses demonstrated that ck2 phosphorylated recombinant nkx3.1 on thr89 and thr93. We have also determined that nkx3.1 is degraded primarily through a proteasomal pathway, suggesting that phosphorylation by ck2 protects nkx3.1 from degradation. | SIGNOR-145501 |
P23470 | Q14247 | 1 | dephosphorylation | down-regulates activity | 0.2 | 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-254696 |
P08670 | Q5JTV8 | 2 | binding | up-regulates activity | 0.2 | Co-immune precipitation studies revealed association between vimentin and torsinA in a complex. these studies suggest that mutant torsinA interferes with cytoskeletal events involving vimentin, possibly by restricting movement of these particles/filaments, and hence may affect development of neuronal pathways in the brain. | SIGNOR-261313 |
P63151 | P36897 | 2 | binding | up-regulates | 0.536 | In this report, we show that another WD-40 repeat protein, the B_ subunit of protein phosphatase 2A, associates with the cytoplasmic domain of type I TGF-_ receptors. [...] We therefore conclude that B_ specifically and directly associates with the type I receptor cytoplasmic domain in vitro. | SIGNOR-227517 |
Q9Y3R0 | Q06413 | 2 | binding | up-regulates | 0.403 | The cofactors grip-1, cbp/p300 and pcaf have hat activity and function as co-activators for mef-2c during myogenesis. | SIGNOR-83883 |
P26441 | P42702 | 2 | binding | up-regulates | 0.742 | Ciliary neurotrophic factor (cntf) is a cytokine supporting the differentiation and survival of various cell types in the peripheral and central nervous systems. Its receptor complex consists of a non-signaling alpha chain, cntfr, and two signaling beta chains, gp130 and the leukemia inhibitory factor receptor (lifr) | SIGNOR-81382 |
Q16204 | Q13315 | 0 | phosphorylation | up-regulates | 0.274 | Phosphorylation of ccdc6 at thr434 by atm during dna damage response prevents fbxw7-mediated ccdc6 degradation. | SIGNOR-199276 |
Q9Y5I2 | Q9Y5G3 | 2 | binding | up-regulates activity | 0.2 | The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion. They also form oligomers with Pcdh-gamma proteins at the same membrane sites. | SIGNOR-265703 |
P62877 | P19838 | 1 | ubiquitination | up-regulates | 0.451 | The scf-betatrcp complex is responsible for the ubiquitination of p100 and p105 following their phosphorylation by ikk. | SIGNOR-106781 |
P49815 | Q9NX09 | 2 | binding | up-regulates activity | 0.639 | Redd1 is a negative regulator of mTOR, mediating dissociation of 14-3-3 from tuberous sclerosis complex (TSC)2, which allows formation of a TSC-TSC2 complex. | SIGNOR-277469 |
P51168 | P27361 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.278 | Using a number of different approaches it was demonstrated that the protein kinase acting on betaThr-613 and gammaThr-623 is the extracellular regulated kinase (ERK). It is suggested that an ERK-mediated phosphorylation of betaThr-613 and gammaThr-623 down-regulates the channel by facilitating its interaction with Nedd4. | SIGNOR-249447 |
P04626 | Q96PG8 | 1 | phosphorylation | down-regulates activity | 0.281 | These results show for the first time that PUMA can be phosphorylated at tyrosine residues directly by HER2.|Together, our results demonstrate, for the first time, that PUMA can be tyrosine phosphorylated and that HER2-mediated phosphorylation destabilizes PUMA protein. | SIGNOR-278224 |
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