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 |
|---|---|---|---|---|---|---|---|
P12931 | P53396 | 1 | phosphorylation | up-regulates activity | 0.265 | We demonstrate the binding of PIP2 to the CoA-binding domain of ACLY and identify the six tyrosine residues of ACLY that are phosphorylated by Lyn. Three of them (Y682, Y252, Y227) can be also phosphorylated by Src and they are located in catalytic, citrate binding and ATP binding domains, respectively. PI3K and Lyn inhibitors reduce the ACLY enzyme activity, ACLY-mediated Acetyl-CoA synthesis, phospholipid synthesis, histone acetylation and cell growth. Thus, PIP2/PIP3 binding and Src tyrosine kinases-mediated stimulation of ACLY links oncogenic pathways to Acetyl-CoA-dependent pro-growth and survival metabolic pathways in cancer cells. | SIGNOR-274107 |
P07948 | P46527 | 1 | phosphorylation | down-regulates | 0.553 | We previously reported that y88 phosphorylation of p27(kip1) by oncogenic tyrosine kinases impairs p27(kip1)-mediated cdk inhibition, and initiates its ubiquitin-dependent proteasomal degradation. | SIGNOR-172904 |
P84022 | Q9Y6X2 | 2 | binding | up-regulates activity | 0.597 | We have further shown that PIAS3, Smad3, and p300 can form a ternary complex, which is significantly increased by TGF-_ treatment. Taken together, these results suggest that PIAS3 stimulates Smad transcriptional activity through formation of a complex with Smad proteins and p300/CBP. | SIGNOR-217725 |
Q8N2H9 | Q15306 | 1 | ubiquitination | down-regulates activity | 0.2 | Peli3 induces the degradation of IRF4 through K48‐mediated ubiquitination |To detect the direct interaction of Peli3 and IRF4, Peli3 and IRF4 DNA constructs were transfected into HEK293 cells. | SIGNOR-280453 |
Q15139 | O96013 | 1 | phosphorylation | up-regulates activity | 0.252 | When PKD3 was knocked-down using isoform-specific shRNA (PKD3-shRNA), PAK4 activity (judged by its phosphorylation status at the activation loop using the pS474-PAK4 antibody) was decreased | SIGNOR-275930 |
Q9C037 | O75298 | 1 | ubiquitination | down-regulates quantity | 0.2 | 2: TRIM4 ubiquitinates and degrades the NSP2 protein.|Mechanistic studies showed that TRIM4 ubiquitinated modified NSP2 and down-regulated NSP2 expression. | SIGNOR-278793 |
P36896 | Q13705 | 0 | phosphorylation | up-regulates activity | 0.691 | Activin binds directly to ActR-IIB, and this complex associates with ActR-IB, which does not bind ligand on its own. In the resulting complex, ActR-IB becomes hyperphosphorylated, and this requires the kinase activity of ActR-IIB. | SIGNOR-235146 |
P49137 | P35900 | 1 | phosphorylation | up-regulates activity | 0.2 | P38 phosphorylates the type II keratin, K8 at Ser73, whereas MK2 phosphorylates the binding partners K18 at Ser52 and K20 at Ser13. | SIGNOR-263071 |
Q13882 | P78357 | 1 | phosphorylation | up-regulates activity | 0.2 | As a consequence, Brk stimulates p190 and attenuates p120 functions, leading to RhoA inactivation and Ras activation, respectively.|Brk phosphorylates p190 at the Y (1105) residue both in vitro and in vivo, thereby promoting the association of p190 with p120RasGAP (p120). | SIGNOR-279274 |
P08648 | P31249 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.25 | The homeobox transcription factor Hox D3 promotes integrin alpha5beta1 expression and function during angiogenesis. | SIGNOR-261649 |
P11717 | Q8IWJ2 | 0 | relocalization | up-regulates activity | 0.529 | Rab9-dependent transport from late endosomes to the Golgi requires the Rab9 effectors p40 (Diaz et al., 1997) and TIP47 (Diaz and Pfeffer, 1998), a protein that recognizes the cytoplasmic domains of the two types of MPRs and packages them into nascent transport vesicles (Carroll et al., 2001). MPR recycling also utilizes a TGN-localized coiled-coil protein named GCC185 that is also a Rab9 effector | SIGNOR-253085 |
Q05513 | Q16612 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Site-directed mutagenesis of S59A retarded P311 degradation and induced glioma cell motility. In contrast, S59D mutation resulted in the rapid degradation of P311 and reduced glioma cell migration.Taken together, our results show that the serine phosphorylation of P311 is dependent on the function of both PKCε and PKCz. | SIGNOR-273831 |
P61586 | Q9P2N2 | 0 | gtpase-activating protein | down-regulates activity | 0.504 | 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-260483 |
P28749 | P11802 | 0 | phosphorylation | up-regulates activity | 0.807 | Here we assessed the effects of alanine substitution at the individual or combined Cdk4(6)-specific sites in p130, compared with homologous sites in p107 (Thr(369)/Ser(650)/Ser(964)). In U-2-OS cells, the triple p107(DeltaCdk4)* mutant strongly inhibited E2F-4 activity and imposed a G(1) arrest resistant to cyclin D1 coexpression. | SIGNOR-250764 |
P08754 | P08912 | 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-256873 |
P15407 | P22415 | 2 | binding | down-regulates activity | 0.465 | USF specifically interacts with Fra1. USF was repressing this modest Fra1 transactivation | SIGNOR-240975 |
O95886 | P78352 | 2 | binding | up-regulates activity | 0.758 | SAPAPs are specifically expressed in neuronal cells and enriched in the PSD fraction. SAPAPs induce the enrichment of PSD-95/SAP90 to the plasma membrane in transfected cells. Thus, SAPAPs may have a potential activity to maintain the structure of PSD by concentrating its components to the membrane area. | SIGNOR-264211 |
Q9H4E7 | P62834 | 2 | binding | up-regulates activity | 0.257 | Mechanistic studies revealed that SLAT interacts, through its PH domain, with a key component of inside-out signaling, namely the active form of the small GTPase Rap1 (which has two isoforms, Rap1A and Rap1B). This interaction has been further shown to facilitate the interdependent recruitment of Rap1 and SLAT to the T cell immunological synapse upon TCR engagement. Furthermore, a SLAT mutant lacking its PH domain drastically inhibited LFA-1 activation and CD4(+) T cell adhesion. | SIGNOR-253365 |
P17481 | Q01995 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | Results from these experiments demonstrated that in 10T1/2 cells Hoxa10-1 increased the activity of the telokin promoter 3-fold without affecting the activity of the other promoters analyzed (Fig. 2A). Similar results were also observed in A10 SMC (data not shown). In contrast, Hoxb8 significantly repressed the activity of the telokin, smooth muscle α-actin, and SM22α promoters by 70, 50, and 70%, respectively | SIGNOR-261642 |
O60674 | P42226 | 1 | phosphorylation | up-regulates activity | 0.67 | Downstream intracellular signaling from the IL-4IL-4Rc complex involves activation of the Jak1 and Jak3 kinases, phosphorylation of the Stat6 transcription factor, and activation of the insulin receptor substrate (IRS)-2 and Dok2-signaling intermediates. IL-13 initially binds to IL-13R1 with intermediate affinity, and then heterodimerizes with IL-4R. The IL-13IL-13R1IL-4R complex activates the Tyk2, Jak2, and Jak1 kinases and Stat6. | SIGNOR-249532 |
P54646 | P08559 | 1 | phosphorylation | up-regulates activity | 0.2 | AMPKα phosphorylates PDHA subunit on Ser295 and Ser314 to activate PDH complex | SIGNOR-276838 |
Q9Y3Q4 | P12931 | 0 | phosphorylation | up-regulates | 0.371 | These results demonstrate that src tyrosine kinase enhances hcn4 currents by shifting their activation to more positive potentials and increasing the whole cell channel conductance as well as speeding the channel kinetics. The tyrosine residue that mediates most of src s actions on hcn4 channels is tyr531. | SIGNOR-158707 |
P33032 | P01189 | 2 | binding | up-regulates activity | 0.766 | 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-268715 |
P49683 | P50148 | 2 | binding | up-regulates activity | 0.275 | 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-257089 |
P49840 | Q04206 | 1 | phosphorylation | up-regulates activity | 0.2 | Redundant functions of GSK-3_ and GSK-3_ through phosphorylation of RelA at Thr-254 play a crucial role in early stages of chondrocyte differentiation | SIGNOR-255827 |
O00418 | P17612 | 0 | phosphorylation | up-regulates activity | 0.305 | EEF-2K can be phosphorylated in vitro by cAMP-dependent protein kinase (PKA) and that this induces significant Ca(2+)/calmodulin (CaM)-independent eEF-2K activity. sites of phosphorylation were Ser-365 and Ser-499 | SIGNOR-250354 |
P50458 | Q86U70 | 2 | binding | up-regulates activity | 0.538 | Cofactor CLIM2 promotes the repressive action of LIM homeodomain transcription factor Lhx2 in the expression of porcine pituitary glycoprotein hormone alpha subunit gene. | SIGNOR-223962 |
Q7Z2G1 | Q14493 | 0 | translation regulation | up-regulates quantity by expression | 0.2 | Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control. | SIGNOR-265387 |
Q15746 | Q13153 | 0 | phosphorylation | down-regulates activity | 0.556 | P21-activated kinase 1 (PAK1) phosphorylates MLCK, resulting in decreased MLCK activity. | SIGNOR-250317 |
Q16537 | Q9P2K6 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | PPP2R5ϵ is a KLHL42 substrate and affects TGF-β signaling in SSc. Lys-84 is a candidate ubiquitin acceptor site within PPP2R5ϵ. | SIGNOR-272205 |
P68431 | Q9UKI8 | 0 | phosphorylation | up-regulates activity | 0.2 | Purified tlk1b phosphorylated histone h3 at s(10) with high specificity both in a mix of core histones and in isolated chromatin, suggesting that histone h3 is a physiological substrate for tlk1b. Phosphorylation of H3 has been linked to the activation of the immediate-early genes upon mitogenic stimulation, and to chromatin condensation during mitotic/meiotic events. | SIGNOR-107037 |
Q9Y3I1 | Q15398 | 2 | binding | down-regulates quantity by destabilization | 0.45 | We show here that Fbx7, an F-box protein without WD repeats and leucine-rich repeats, is required for the proteasome-mediated proteolysis of the hepatoma up-regulated protein (HURP).Thus, Fbx7 is a functional adaptor of the SCF complex with a proline-rich region as the substrate-binding module. Depletion of Fbx7 by small interfering RNA leads to depression of HURP ubiquitination and accumulation of HURP abundance. In the SCFFbx7 complex, Fbx7 recruits HURP through its C-terminal proline-rich region in a Cdk1-cyclin B-phosphorylation dependent manner. | SIGNOR-271506 |
P27361 | P67775 | 0 | dephosphorylation | down-regulates | 0.647 | P-erk1/2 proteins were efficiently dephosphorylated in vitro by protein phosphatases 1 and 2a (pp1/2a) and mapk phosphatase 3 (mkp3). | SIGNOR-103162 |
Q9Y618 | P10275 | 1 | acetylation | down-regulates | 0.562 | In this study we assessed the effect of smrt and dax-1 on ar and pr activity in the presence of both agonists and partial antagonists. We show that smrt and dax-1 repress agonist-dependent activity of both receptors, and the mechanism of repression includes disruption of the receptor dimer interactions rather than recruitment of histone deacetylases. | SIGNOR-101286 |
P30304 | P20248 | 1 | dephosphorylation | up-regulates activity | 0.692 | Cdc25A dephosphorylates and activates CyclinE\u2013Cdk2, CyclinA\u2013Cdk2 and CyclinB\u2013Cdk1, whereas Cdc25B and Cdc25C primarily target CyclinB\u2013Cdk1 [4,5] . | SIGNOR-277136 |
Q05513 | P31946 | 1 | phosphorylation | down-regulates activity | 0.368 | Our results with the 14-3-3 mutants indirectly imply a new phosphorylation site, 130Ser (and to a lesser extent 141Thr), in 14-3-3b that regulates the association}dissociation of 14-3-3b and PKC-f. | SIGNOR-249035 |
P49736 | Q9H211 | 2 | binding | up-regulates activity | 0.813 | Chromosomal DNA replication requires the recruitment of the six-subunit minichromosome maintenance (Mcm) complex to chromatin through the action of Cdc6 and Cdt1. | SIGNOR-261681 |
Q06413 | Q32MK0 | 0 | phosphorylation | up-regulates activity | 0.269 | Here, we show that phosphorylation of MEF2C on T(80) by skeletal myosin light chain kinase (skMLCK) enhances skeletal and not cardiac myogenesis.|Here, we show that skMLCK directly phosphorylates MEF2C, leading to p300/PCAF recruitment, increased acetylation of skeletal muscle-specific genes, and enhanced skeletal myogenesis | SIGNOR-264565 |
P08588 | P63092 | 2 | binding | up-regulates activity | 0.527 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ‚â• -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ‚â• -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ‚â• -1.0. | SIGNOR-256758 |
Q96PX8 | P68400 | 0 | phosphorylation | up-regulates activity | 0.2 | In our studies, SICD was phosphorylated by PKA, PKC, and CK2, and association of SLITRK1 with 14-3-3 was regulated by phosphorylation at Ser695. Co-precipitation experiments demonstrated much greater recovery of 14-3-3 in SLITRK1 precipitates when wild-type or S695E was used, as compared with S695A, consistent with the results with purified peptides. | SIGNOR-273633 |
P41143 | P01189 | 0 | chemical activation | up-regulates activity | 0.65 | Accordingly, for the OTDP, the binding affinity and activity of a large number of opiate compounds have been tested at μ-, δ-, and κ-opiate receptors. Binding studies were originally conducted in guinea pig brain membranes, and subsequent studies have been carried out in CHO cells transfected with human receptors. Table 7 shows a biochemical method for determining activity and potency of opioid compounds, stimulation of [35S]GTPγS binding in membranes from cells transfected with human μ, δ, or κ receptors. | SIGNOR-258409 |
O60285 | Q15831 | 0 | phosphorylation | up-regulates | 0.546 | A total of 12 human kinases (nuak1, nuak2, brsk1, brsk2, qik, qsk, sik, mark1, mark2, mark3, mark4 and melk) are related to ampk. Here we demonstrate that lkb1 can phosphorylate the t-loop of all the members of this subfamily, apart from melk, increasing their activity >50-fold. | SIGNOR-122686 |
Q92945 | Q92997 | 2 | binding | down-regulates | 0.2 | Ksrp was shown to interact with the c-terminus of dvl3. We show that ksrp negatively regulates wnt/beta-catenin signaling at the level of post-transcriptional ctnnb1 (beta-catenin) mrna stability. | SIGNOR-23800 |
Q92585 | P24863 | 1 | relocalization | up-regulates | 0.447 | Cycc:cdk8 and cyct1:cdk9/p-tefb are recruited with notch and associated coactivators (mam, skip) to the hes1 promoter in signaling cells. | SIGNOR-130709 |
P27986 | P15391 | 2 | binding | up-regulates activity | 0.585 | CD19 has an extracellular region containing two C2-type Ig-like domains and a cytoplasmic region of ~240 amino acids with 9 conserved tyrosine residues24. Lyn, a Src-family protein tyrosine kinase member, is the dominant kinase that phosphorylates CD19 upon stimulation. Once tyrosyl-phosphorylated, CD19 serves as a membrane-bound adaptor protein for Src homology 2-containing signaling molecules such as Lyn, Vav, and phosphatidylinositol 3-kinase, which further mediate downstream activation cascades. | SIGNOR-242900 |
Q02790 | P10275 | 2 | binding | up-regulates activity | 0.72 | We noted that FK506 altered nuclear localization of the GR and inhibited expression of GR-responsive genes. Furthermore, si-RNA knockdown of FKBP4 gene, coding for the immunophilin FKBP52, inhibited cortisol-activated GR nuclear translocation | SIGNOR-252034 |
P03956 | P02458 | 1 | cleavage | down-regulates quantity by destabilization | 0.445 | MMP-1 cleaves type II collagen at the peptide bond Gly906-Leu907 Proteolysis of triple-helical collagen is an important step in the progression toward irreversible tissue damage in osteoarthritis. Earlier work on the expression of enzymes in cartilage suggested that collagenase-1 (MMP-1) contributes to the process. | SIGNOR-256341 |
Q05397 | O14965 | 0 | phosphorylation | up-regulates activity | 0.255 | A schematic of regulation between these three kinases is shown in XREF_FIG, suggesting that Src was the upstream kinase regulating both FAK and AURA, whereas FAK might be downstream of AURA (as AURA phosphorylation of FAK yielded more incorporation of [32 P] gammaATP compared to FAK phosphorylation of AURA).|The effect of AURA on cell migration is augmented in the presence of Src and, in return, AURA also activates FAK. | SIGNOR-280188 |
Q16659 | Q8IW41 | 1 | phosphorylation | up-regulates activity | 0.69 | ERK3, ERK4 and p38 MAPK can all phosphorylate MK5 at Thr 182 , , , - ], but it is not known whether these enzymes also can phosphorylate Ser 115 and whether this modification contributes to ERK3-, ERK4-, or p38 MAPK -regulated subcellular localization of MK5. | SIGNOR-279073 |
P17612 | O43164 | 1 | phosphorylation | up-regulates activity | 0.2 | In vitro kinase assays demonstrated that purified PKAc directly phosphorylates wild-type Flag–praja2, but not the Flag–praja2S342A,T389A mutant, confirming these residues as the main PKA phosphorylation sites (Fig. 5h). | SIGNOR-276316 |
Q92985 | Q14164 | 0 | phosphorylation | up-regulates | 0.687 | In response to a viral infection, phosphorylated on ser-477 and ser-479 by tbk1 and ikbke1. Phosphorylation, and subsequent activation is inhibited by vaccinia virus protein e3. | SIGNOR-79139 |
Q9NZM5 | Q13315 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.2 | PICT-1 S233 and T289 were identified as the key phosphorylation sites in this pathway, as mutating both to alanine abolished UVB-induced increase of PICT-1 phosporylation. Inhibition of PIKKs or ATM (with wortmannin and KU55933, respectively) prevented the agglomeration and degradation of PICT-1, suggesting that ATM is a key regulator of PICT-1. | SIGNOR-273506 |
P49841 | Q15797 | 1 | phosphorylation | down-regulates | 0.504 | Phosphorylation at the gsk3 sites represses the transcriptional activity of smad1 by enhancing proteasomal degradation of psmad1cter | SIGNOR-159484 |
P04637 | Q99986 | 0 | phosphorylation | up-regulates | 0.523 | Vrk1 phosphorylates murine p53 in threonine 18. This threonine is within the p53 hydrophobic loop (residues 13-23) required for the interaction of p53 with the cleft of its inhibitor mdm-2. | SIGNOR-81222 |
Q04724 | O95343 | 2 | binding | up-regulates activity | 0.4 | Biochemical and mutational analysis shows that the Six domain of both SIX3 and SIX6 strongly interact with the QD domain of TLE1 and AES. TLE1 over-expression induces an enlargement of the eye field and reinforcesSIX3/SIX6 capability of initiating retina formation | SIGNOR-234595 |
P04637 | Q9NRC8 | 0 | deacetylation | down-regulates | 0.498 | We found that sirt7 interacts with p53 and efficiently deacetylates p53 in vitro, which corresponds to hyperacetylation of p53 in vivo. | SIGNOR-160539 |
Q99836 | O60603 | 2 | binding | up-regulates activity | 0.673 | 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-266740 |
P36897 | Q15796 | 1 | phosphorylation | up-regulates activity | 0.825 | Recently, it was demonstrated that Smad2 interacts transiently with and is a direct substrate of the transforming growth factor-beta (TGF-beta) type I receptor, TbetaRI. Phosphorylation sites on Smad2 were localized to a carboxyl-terminal fragment containing three serine residues at positions 464, 465, and 467. These results indicate that receptor-dependent phosphorylation of Smad2 on serines 465 and 467 is required in mammalian cells to permit association with Smad4 and to propagate TGF-_ signals. | SIGNOR-235995 |
P17481 | P40424 | 2 | binding | up-regulates activity | 0.499 | the ability of HoxB8 to heterodimerizes with endogenous Pbx proteins on DNA alters gene transcription in a manner that prevents progression through an intrinsic genetic differentiation program. In conjunction with Pbx, HoxB8 could alter transcription of Pbx target genes by direct or indirect mechanisms. | SIGNOR-223153 |
O75475 | O00311 | 0 | phosphorylation | up-regulates | 0.334 | We now report identification of the cdc7-activator of s-phase kinase (ask) heterodimer as a novel interactor of ledgf. the kinase phosphorylated ledgf in vitro, with ser-206 being the major target, and ledgf phosphorylated at this residue could be detected during s phase of the cell cycle. Ledgf potently stimulated the enzymatic activity of cdc7-ask, increasing phosphorylation of mcm2 in vitro by more than 10-fold. | SIGNOR-25763 |
Q9H6R7 | O00139 | 2 | binding | up-regulates activity | 0.2 | PLK1 Phosphorylates MMAP to Promote Its Interaction with KIF2A and MRE11. | SIGNOR-273732 |
P01106 | P28482 | 0 | phosphorylation | up-regulates activity | 0.735 | Transactivation of gene expression by myc is inhibited by mutation at the phosphorylation sites thr-58 and ser-62. | SIGNOR-235700 |
P06681 | O00187 | 0 | cleavage | up-regulates activity | 0.436 | The MASPs in the preparations had proteolytic activities against C4, C2, and C3 in the fluid phase | SIGNOR-263416 |
Q12968 | P05231 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.283 | The calcineurin/nuclear factor of activated T cells (NFAT) signaling pathway has been found to play a role in regulating growth and differentiation in several cell types. However, the functional significance of NFAT in the vasculature is largely unclear. Here we show that NFATc1, NFATc3, and NFATc4 are expressed in human myometrial arteries. |Chronic inhibition of NFAT significantly reduced IL-6 production in intact myometrial arteries and inhibited cell proliferation in vascular smooth muscle cells cultured from explants from the same arteries. | SIGNOR-251732 |
Q504Q3 | Q13315 | 0 | phosphorylation | up-regulates activity | 0.2 | Here, we identify that USP52 directly interacts with and deubiquitinates CtIP, thereby promoting DNA end resection and HR. Mechanistically, USP52 removes the ubiquitination of CtIP to facilitate the phosphorylation and activation of CtIP at Thr-847. In addition, USP52 is phosphorylated by ATM at Ser-1003 after DNA damage, which enhances the catalytic activity of USP52. | SIGNOR-273508 |
P00533 | Q9UQM7 | 0 | phosphorylation | down-regulates activity | 0.371 | We show that serines 1046/1047 are sites for CaM kinase II phosphorylation, although there is a preference for serine 1047, which resides within the consensus -R-X-X-S-. In addition, we have identified major phosphorylation sites at serine 1142 and serine 1057, which lie within a novel -S-X-D- consensus. Mutation of serines 1046/1047 in full-length EGFR enhanced both fibroblast transformation and tyrosine autokinase activity that was significantly potentiated by additional mutation of serines 1057 and 1142. A single CaM kinase II site was also identified at serine 744 within sub-kinase domain III, and autokinase activity was significantly affected by mutation of this serine to an aspartic acid making this site appear constitutively phosphorylated. We have addressed the mechanism by which CaM kinase II phosphorylation of the EGFR might regulate receptor autokinase activity and show that this modification can hinder association of the cytoplasmic tail with the kinase domain to prevent an enzyme-substrate interaction. | SIGNOR-250621 |
P11308 | P33151 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.278 | Erg overexpression resulted in an approximate 1.8-fold transactivation of VE-cadherin promoter activity. Thus, our data indicate that Erg drives constitutive VE-cadherin expression in human ECs | SIGNOR-261595 |
P61586 | Q96PE2 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.549 | 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-260542 |
Q9H2K2 | Q13148 | 2 | binding | up-regulates quantity by stabilization | 0.2 | Upon investigating the functional effect, we find that interaction with Tnks-1/2 inhibits the ubiquitination and proteasomal turnover of TDP-43, leading to its stabilization. We further show that proteasomal turnover of TDP-43 occurs preferentially in the nucleus; our data indicate that Tnks-1/2 stabilizes TDP-43 by promoting cytoplasmic accumulation, which sequesters the protein from nuclear proteasome degradation. | SIGNOR-262116 |
P17612 | P17600 | 1 | phosphorylation | down-regulates activity | 0.338 | 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-250058 |
P33032 | P38405 | 2 | binding | up-regulates activity | 0.292 | 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-256941 |
Q9UL68 | Q14469 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | ChIP–seq experiments showed that 80% of Myt1l targets, including the transcription factor Hes1, were co-bound by the repressive Sin3b–HDAC1 complex early during reprogramming | SIGNOR-266775 |
P12931 | Q99836 | 1 | phosphorylation | up-regulates activity | 0.445 | Because MyD88 was phosphorylated at the tyrosine 58 residue in hemi-ITAM by LPS ( xref ), whether Src phosphorylates MyD88 at the tyrosine 58 residue was examined further, and MyD88 was phosphorylated by Src at Y58 ( xref ).|Src activates MyD88 by phosphorylation at Y58 via the Src kinase domain. | SIGNOR-279655 |
P62258 | P07196 | 2 | binding | down-regulates activity | 0.276 | These results suggest the important role of 14-3-3 in the dynamic regulation of NF-L assembly, and in the capacity to prevent the formation of NF-L aggregates. all seven isoforms specifically interacted with NF-L, but not NF-M or NF-H. specific interaction of 14-3-3 proteins with phosphorylated NF-L subunits also indicated the role of 14-3-3 and NF-L phosphorylation in the disassembly of neurofilaments. What is more, binding of 14-3-3 to phosphorylated NF-L subunits may prevent the dephosphorylation of these subunits by phosphatases, maintaining the hyperphosphorylation state of the subunits, which facilitates the disassembly of neurofilaments. | SIGNOR-252398 |
Q15075 | P51148 | 2 | binding | up-regulates activity | 0.829 | The Rab5 effector early endosome antigen 1 (EEA1) is a parallel coiled coil homodimer with an N-terminal C(2)H(2) Zn(2+) finger and a C-terminal FYVE domain. Rab5 binds to independent sites at the N and C terminus of EEA1.|The results demonstrate that the C(2)H(2) Zn(2+) finger is both essential and sufficient for the N-terminal interaction with Rab5. | SIGNOR-261266 |
P26045 | P10912 | 1 | dephosphorylation | down-regulates activity | 0.43 | PTPH1 only bound Tyr534, whereas PTP1B and TC-PTP bound multiple phosphopeptides. Earlier work suggests that Tyr332, Tyr487, Tyr534, Tyr566, and Tyr627 are all phosphorylated after GH stimulation (21). Apart from Tyr627, all of these also appear good PTP substrates | SIGNOR-248459 |
Q15418 | O75030 | 1 | phosphorylation | down-regulates | 0.41 | The current study reveals that c-kit signaling triggers two phosphorylation events on mi, which up-regulate transactivation potential yet simultaneously target mi for ubiquitin-dependent proteolysis. The specific activation/degradation signals derive from mapk/erk targeting of serine 73, whereas serine 409 serves as a substrate for p90 rsk-1. An unphosphorylatable double mutant at these two residues is at once profoundly stable and transcriptionally inert. | SIGNOR-174760 |
Q9NPB9 | Q99731 | 2 | binding | up-regulates activity | 0.664 | In the present study, however, we demonstrate for the first time the concentration-dependent recruitment of β-arrestins to the atypical chemokine receptor CCX-CKR upon stimulation with CCL19, CCL21, or CCL25 using three different methodologies in various transfected cell lines. | SIGNOR-268416 |
Q9C0H9 | P12931 | 0 | phosphorylation | up-regulates activity | 0.496 | Phosphorylation of multiple tyrosine-containing motifs found on Sin correlated with c-Crk and cellular phosphoprotein binding to Sin as well as increased c-Src activity. These data suggest that (1) SH2 and SH3 ligand sites on Sin cooperatively activate the signaling potential of c-Src, (2) Sin acts as both an activator and a substrate for c-Src, and (3) phosphorylated Sin may serve as a signaling effector molecule for Src by binding to multiple cellular proteins. | SIGNOR-263196 |
Q7Z6M1 | P51151 | 0 | null | up-regulates activity | 0.581 | P40 is a very potent transport factor in that the pure, recombinant protein can stimulate, significantly, an in vitro transport assay that measures transport of mannose 6-phosphate receptors from endosomes to the trans-Golgi network. The functional importance of p40 is confirmed by the finding that anti-p40 antibodies inhibit in vitro transport. Finally, p40 shows synergy with Rab9 in terms of its ability to stimulate mannose 6-phosphate receptor transport. These data are consistent with a model in which p40 and Rab9 act together to drive the process of transport vesicle docking. | SIGNOR-253088 |
P09471 | P48039 | 2 | binding | up-regulates activity | 0.25 | 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-256985 |
Q6P1J9 | Q13882 | 0 | phosphorylation | down-regulates activity | 0.368 | PTK6 impairs the coactivator function of parafibromin.|To study the functional consequence of parafibromin phosphorylation by PTK6, we examined the effect of PTK6 inhibition on Wnt signal activation. | SIGNOR-279273 |
P04628 | P11308 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Interestingly, our data showed that ERG drastically induced Wnt ligand gene expression. | SIGNOR-261597 |
Q13164 | O14757 | 1 | phosphorylation | up-regulates activity | 0.276 | Moreover, we demonstrate that ERK5 facilitates Chk1 phosphorylation induced by IR.|Since we have found that ERK5 was able to accelerate the phosphorylation and activation of IR-induced Chk1, therapeutic targeting of Chk1 in NSCLC cells with high ERK5 expression might be an effective strategy for overcoming radioresistance. | SIGNOR-280028 |
P63096 | Q9H244 | 2 | binding | up-regulates activity | 0.404 | 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-256712 |
P35222 | P67870 | 0 | phosphorylation | up-regulates activity | 0.601 | We show that CKII phosphorylates the N-terminal region of beta-catenin and we identified Ser29, Thr102, and Thr112 as substrates for the enzyme. We provide evidence that CKII regulates the cytoplasmic stability of beta-catenin and acts synergistically with GSK-3beta in the multi-protein complex that controls the degradation of beta-catenin | SIGNOR-251067 |
Q14774 | P19419 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | In this study, we have identified cell cycle regulatory genes as downstream targets of the homeobox gene HLX in cultured trophoblast cells, namely RB1, MYC, EGR1, CDKN1C, ELK1, CCNB1, and JUN. RB1 and MYC mRNA expression was increased with HLX inactivation, whereas EGR1, CDKN1C, ELK1, CCNB1, and JUN mRNA expression was decreased compared with mock-transfected control cells. | SIGNOR-261622 |
P24941 | Q01167 | 1 | phosphorylation | up-regulates | 0.369 | We have mapped two cdk phosphorylation sites, serines 368 and 423, which play a role in defining foxk2 function through regulating its stability and its activity as a transcriptional repressor protein. These two cdk sites appear vital for foxk2 function because expression of a mutant lacking these sites cannot be tolerated and causes apoptosis. | SIGNOR-167834 |
P48382 | P33076 | 2 | binding | up-regulates activity | 0.759 | RFX5 can activate transcription only in cooperation with CIITA. RFX5 and CIITA associate to form a complex capable of activating transcription from class II major histocompatibility complex promoters. In this complex, promoter specificity is determined by the DNA binding domain of RFX5 and the general transcription apparatus is recruited by the acidic activation domain of CIITA. | SIGNOR-240980 |
Q07343-2 | P28482 | 0 | phosphorylation | up-regulates activity | 0.268 | The short-form PDE4B2 isoenzyme was activated by Erk2 phosphorylation. These functional changes in PDE activity were mimicked by mutation of the target serine for Erk2 phosphorylation to the negatively charged amino acid, aspartic acid. | SIGNOR-275971 |
P49841 | O75581 | 1 | phosphorylation | up-regulates activity | 0.794 | Glycogen synthase kinase 3 (gsk3), which is known for its inhibitory role in wnt through the promotion of beta-catenin phosphorylation and degradation, mediates the phosphorylation and activation of lrp6. We show that wnt induces sequential phosphorylation of lrp6 by gsk3 and casein kinase 1, and this dual phosphorylation promotes the engagement of lrp6 with the scaffolding protein axin. | SIGNOR-143041 |
P23352 | O00712 | 0 | transcriptional regulation | down-regulates quantity | 0.2 | By integrating transcriptomic profiling (RNA-seq) of Nfia- and Nfix-deficient GNPs with epigenomic profiling (ChIP-seq against NFIA, NFIB and NFIX, and DNase I hypersensitivity assays), we reveal that these transcription factors share a large set of potential transcriptional targets, suggestive of complementary roles for these NFI family members in promoting neural development | SIGNOR-268878 |
O15105 | Q09472 | 0 | acetylation | up-regulates | 0.464 | Here we present evidence that smad7 interacts with the transcriptional coactivator p300, resulting in acetylation of smad7 on two lysine residues in its n terminus. Acetylation or mutation of these lysine residues stabilizes smad7 and protects it from tgfbeta-induced degradation. we have recently shown that smad7 is acetylated on lysine residues 64 and 70 by p300 | SIGNOR-95169 |
P57737 | P12931 | 0 | phosphorylation | up-regulates activity | 0.339 | We establish that Src activity is indispensable for the interaction of Crn7 with Golgi membranes. Crn7 binds Src in vivo and can be phosphorylated by recombinant Src in vitro. We demonstrate that tyrosine-758 is the major Src phosphorylation site. | SIGNOR-274005 |
Q9Y4P1 | Q9GZQ8 | 1 | cleavage | up-regulates | 0.803 | Human atg4 homologues cleave the carboxyl termini of the three human atg8 homologues, microtubule-associated protein light chain 3 (lc3), gabarap, and gate-16. | SIGNOR-125449 |
P29460 | P42701 | 2 | binding | up-regulates | 0.676 | Characterization of the p40 proteins for binding and bioactivity showed that both the p40 monomer and dimer inhibited 125i-labeled il-12 binding to il-12r, but the 80-kda species, having a 50% inhibitory concentration (ic50) of 20 to 70 ng/ml, was at least 20-fold more effective than the monomer. The results suggest that the il-12 p40 subunit contains the essential epitopes for receptor binding. | SIGNOR-27690 |
P12931 | Q5TCZ1 | 1 | phosphorylation | up-regulates activity | 0.64 | First, we observed that the co-expression of both activated Src and wild-type Tks5 stimulated gelatin degradation beyond that of Tks5 overexpression alone ( ).|In melanoma cells Src dependent phosphorylation of Tks5 at tyrosine 557 is important for binding to Nck, for Nck recruitment to invadopodia, and for invadopodia associated matrix degradation activity . | SIGNOR-280134 |
P23443 | Q05195 | 1 | phosphorylation | down-regulates | 0.304 | Both rsk and s6k phosphorylate serine 145 of mad1 upon serum or insulin stimulation. Ser-145 phosphorylation of mad1 accelerates the ubiquitination and degradation of mad1 through the 26s proteasome pathway, which in turn promotes the transcriptional activity of myc. | SIGNOR-178590 |
P01106 | P30304 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.627 | Expression of Cdc25A is transcriptionally regulated by Myc and E2F-1 , both of which are expressed in MCF-7 cells in response to estrogen | SIGNOR-245465 |
P05771 | Q6ZVD8 | 0 | dephosphorylation | down-regulates quantity | 0.328 | Here we show that the two PHLPP isoforms, PHLPP1 and PHLPP2, also dephosphorylate the hydrophobic motif on PKC betaII, an event that shunts PKC to the detergent-insoluble fraction, effectively terminating its life cycle | SIGNOR-237039 |
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