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 |
|---|---|---|---|---|---|---|---|
Q9Y5W3 | P78509 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | KLF2 transactivates the reelin promoter in K562 cells. | SIGNOR-266048 |
P17676 | P49675 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.365 | Electrophoretic mobility shift assay demonstrated that this region of the StAR promoter was bound by C/EBPalpha, C/EBPbeta, and CREB. Forced expression of either C/EBPalpha or C/EBPbeta alone was sufficient to up-regulate StAR promoter activity whereas PGE(2) was needed to induce StAR promoter activity in CREB-overexpressed cells. | SIGNOR-254046 |
P17612 | P13861 | 2 | binding | down-regulates activity | 0.876 | Inactive PKA exists as a holoenzyme, comprised of two regulatory (R) subunits and two catalytic subunits . In the presence of cAMP, the holoenzyme becomes active by binding two cAMP molecules cooperatively to each R subunit, resulting in a conformational change in the R subunits, thus releasing the two C subunits to phosphorylate downstream targets | SIGNOR-258752 |
P50876 | P78527 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.568 | We show that RNF144A induces ubiquitination of DNA-PKcs in vitro and in vivo and promotes its degradation. | SIGNOR-272213 |
Q9UJ41 | P20339 | 2 | binding | up-regulates | 0.923 | We have previously shown that rab5, which regulates various steps of transport along the early endocytic pathway, is activated by a complex consisting of rabex-5, a rab5 nucleotide exchange factor, and the effector rabaptin-5. | SIGNOR-109398 |
O00238 | O15198 | 1 | phosphorylation | up-regulates activity | 0.708 | Two types of bmp-induced signaling pathways are known, the smad and p38 mapk pathways. In the former case, bmpr1 phosphorylates smad-1,-5,-8, which forms a complex with smad4 that translocates into the nucleus and regulates gene expression. | SIGNOR-255264 |
Q01726 | P50148 | 2 | binding | up-regulates activity | 0.345 | 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-256956 |
O95155 | P04637 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.396 | We show that ubiquitination factor E4B (UBE4B), an E3 and E4 ubiquitin ligase, physically interacts with p53 and Hdm2 (also known as Mdm2 in mice). UBE4B promotes p53 polyubiquitination and degradation and inhibits p53-dependent transactivation and apoptosis. | SIGNOR-271907 |
P16220 | P10645 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.265 | Recently, binding of specific protein 1 (Sp1) and cAMP response element binding protein (CREB) to a GC-rich element at -92/-62 has been identified as a critical step in gastrin-dependent regulation of the chromogranin A (CgA) gene in gastric epithelial cells. Here we demonstrate that binding of early growth response protein 1 (Egr-1) to the distal part of the -92/-62 site is also required for gastrin-dependent CgA transactivation. | SIGNOR-254276 |
P62987 | Q93009 | 0 | cleavage | up-regulates quantity | 0.735 | Here we provide data suggesting that two of the four mammalian ubiquitin precursors, UBA52 and UBA80, are processed mostly post-translationally whereas the other two, UBB and UBC, probably undergo a combination of co- and post-translational processing. Using an unbiased biochemical approach we found that UCHL3, USP9X, USP7, USP5 and Otulin/Gumby/FAM105b are by far the most active DUBs acting on these precursors. | SIGNOR-270823 |
P35498 | Q92914 | 2 | binding | down-regulates activity | 0.259 | Sodium channel fast inactivation is modulated by alpha subunit interaction with a family of cytoplasmic proteins termed fibroblast growth factor homologous factors (FHFs). In this paper, we report that all A-type FHFs exert rapid onset long-term inactivation on Nav1.6 and other sodium channels. | SIGNOR-253422 |
Q6NT76 | P01579 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | Additionally, by luciferase reporter assay, HMBOX1 displayed suppressive effect on the transcription activity of IFN-γ promoter. | SIGNOR-261625 |
P20827 | P21709 | 2 | binding | up-regulates | 0.83 | The eph family receptors and ligands. | SIGNOR-51932 |
Q00987 | P27695 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.416 | Once the reaction proceeds beyond the monoubiquitination stage, MDM2 polyubiquitinates APE1 for degradation. | SIGNOR-278555 |
P18846 | P51812 | 0 | phosphorylation | up-regulates activity | 0.318 | ATF1 and CREB can be phosphorylated by Rsk2 which is a protein kinase directly activated by Erk MAP kinase. These results suggest a signaling pathway in which Erk MAP kinase activates the c-fos enhancer by direct phosphorylation of p62TCF and by activation of Rsk related kinases that phosphorylate ATF1 and CREB.|ATF1 and CREB can be phosphorylated by Rsk2 which is a protein kinase directly activated by Erk MAP kinases. | SIGNOR-280117 |
Q96EA4 | Q70EL2 | 0 | deubiquitination | up-regulates activity | 0.2 | Spindly is mono-ubiquitylated and this ubiquitin can be removed by active USP45. K48 ubiquitylated complex that interacts with Spindly is also de-ubiquitylated by USP45. In the absence of USP45 catalytic activity, interaction is abolished and cell migration is affected similarly to the phenotype described for lack of Spindly. | SIGNOR-268505 |
A7KAX9 | Q9UQC2 | 0 | relocalization | up-regulates | 0.374 | Gc-gap, a rho family gtpase-activating protein that interacts with signaling adapters gab1 and gab2we propose that gab1 and gab2 in cooperation with other adapter molecules might regulate the cellular localization of gc-gap under specific stimuli. | SIGNOR-102628 |
P42574 | Q13043 | 1 | cleavage | up-regulates activity | 0.617 | In response to apoptotic stimuli, caspase cleavage of mst1 occurs at asp-326 and asp-349, resulting in the separation of its n-terminal kinase domain from the nes-containing c-terminal domain. Thus, caspase cleavage of mst1 serves two purposes: one is activation of mst1 kinase activity and the other is translocation of mst1 into the nucleus. | SIGNOR-109878 |
P34981 | P30679 | 2 | binding | up-regulates activity | 0.487 | Ga16 is phosphorylated in vivo by PMA and by TRH receptor stimulation | SIGNOR-278132 |
Q8WY64 | P10275 | 1 | ubiquitination | down-regulates quantity | 0.2 | MYLIP knockdown increased AR protein levels whereas CNPY2 knockdown increased MYLIP and reduced AR protein expression levels.|These results showed that the E3 ligase MYLIP could ubiquitinate lysine 845 and 847 residues of AR. | SIGNOR-278766 |
P20339 | Q9UJ41 | 2 | binding | up-regulates | 0.923 | We have previously shown that rab5, which regulates various steps of transport along the early endocytic pathway, is activated by a complex consisting of rabex-5, a rab5 nucleotide exchange factor, and the effector rabaptin-5. | SIGNOR-109398 |
Q99835 | Q5GLZ8 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.2 | Our data showed that Herc4 mediated Smo degradation by proteasome and lysosome, but mainly by proteasome.|Using the cell based ubiquitination assay, we found that both Myc-SmoK13R and Myc-SmoK49R exhibited reduced ubiquitination compared with Myc-Smo by Herc4, but Myc-SmoK49R resulted in a more dramatic reduction in Smo ubiquitination (XREF_FIG), suggesting that Smo is ubiquitinated by Herc4 at multiple Lys residues. | SIGNOR-278521 |
O14490 | Q9Y566 | 1 | relocalization | up-regulates activity | 0.857 | SHANK proteins are ‘master’ scaffolding proteins that tether and organize intermediate scaffolding proteins. They are located at excitatory synapses, where they are crucial for proper synaptic development and function. SAPAP proteins subsequently bind to the PDZ domain of members of the SHANK protein family. SHANK proteins then bind to the actin cytoskeleton and to Homer protein, which in turn interacts with mGluRs. Through these extended links, PSD95, SAPAP, SHANK and Homer proteins form a quaternary complex that brings together mGluR and NMDAR complexes in the PSD (FIG. 3). | SIGNOR-264586 |
Q6ZNJ1 | Q96N67 | 2 | binding | up-regulates activity | 0.38 | In summary, from 129 binding partners of Nbeal2 identified by mass spectrometry, we have confirmed the interaction of 3, Dock7, Sec16a, and Vac14, by different biochemical and cellular approaches|Given the significant reduction of Dock7 levels and its altered localization in Nbeal2−/− platelets, we postulated that this canonical signaling pathway may be disrupted and set out to test this using control and Nbeal2−/− platelets. | SIGNOR-261891 |
Q9UKT6 | O15273 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | FBXL21 is a clock-controlled E3 ligase modulating circadian periodicity via subcellular-specific CRYPTOCHROME degradation. How FBXL21 regulates tissue-specific circadian physiology and what mechanism operates upstream is poorly understood. Here we report the sarcomere component TCAP as a cytoplasmic substrate of FBXL21. | SIGNOR-264853 |
P04049 | Q99683 | 2 | binding | down-regulates | 0.395 | Raf-1 interacts with the proapoptotic, stress-activated protein kinase ask1 (apoptosis signal-regulating kinase 1) in vitro and in vivo. | SIGNOR-109023 |
Q03135 | O60260 | 0 | ubiquitination | down-regulates quantity | 0.2 | Parkin induces the degradation of cav-1 through the proteasome dependent pathway.|We also demonstrated that WT parkin ubiquitinates cav-1 for degradation. | SIGNOR-278710 |
P24928 | Q9NYV4 | 0 | phosphorylation | up-regulates activity | 0.784 | Cyck/cdk12 can activate transcription and phosphorylate ser2 in the ctd of rnapii / phosphorylation of serine at position 2 (ser2) is thought to be responsible for productive transcriptional elongation and synthesis of full-length mature mrna | SIGNOR-176805 |
P00533 | P14618 | 1 | phosphorylation | down-regulates activity | 0.449 | EGFR binds to and phosphorylates PKM2 to inhibit its activity. | SIGNOR-277197 |
Q13489 | O43353 | 1 | polyubiquitination | up-regulates activity | 0.787 | CIAP1/2 are direct E3 ligases conjugating diverse types of ubiquitin chains to receptor interacting proteins kinases 1 to 4 (RIP1-4).Together, our results demonstrate that depleting cIAP1/2 inhibits RIP1-4 mediated NF-kB activation without affecting RIP auto-phosphorylation. | SIGNOR-272715 |
P25116 | P24158 | 0 | cleavage | down-regulates activity | 0.42 | PAR1E and PAR2E (10 microM) were incubated in the presence of the different proteases | The enzymes were used at the following concentrations: 0.5 unit/mL thrombin, 2.5 nM trypsin, 20 nM plasmin, 20 nM cathepsin G, 20 nM elastase, 20 nM proteinase 3, and 2 units/mL calpain I and II|Protease-activated receptors (PARs) mediate cell activation after proteolytic cleavage of their extracellular amino terminus.|Protease-activated receptors (PARs) mediate cell activation after proteolytic cleavage of their extracellular amino terminus.|Plasmin, calpain and leukocyte elastase, cathepsin G, and proteinase 3 cleaved at multiple sites and would be expected to disable PAR1 by cleaving COOH-terminal to the activation site. | SIGNOR-263577 |
Q05655 | P06239 | 0 | phosphorylation | up-regulates activity | 0.526 | The tyrosine phosphorylation sites of PKC delta in the H(2)O(2)-treated cells were identified as Tyr-311, Tyr-332, and Tyr-512 by mass spectrometric analysis with the use of the precursor-scan method and by immunoblot analysis with the use of phosphorylation site-specific antibodies. Tyr-311 was the predominant modification site among them. In an in vitro study, phosphorylation at this site by Lck, a non-receptor-type tyrosine kinase, enhanced the basal enzymatic activity and elevated its maximal velocity in the presence of diacylglycerol. phosphorylation at Tyr-311 between the regulatory and catalytic domains is a critical step for generation of the active PKC delta in response to H(2)O(2). | SIGNOR-251386 |
Q99576 | Q04206 | 2 | binding | down-regulates activity | 0.373 | GILZ inhibits NF-kappaB nuclear translocation and DNA binding due to a direct protein-to-protein interaction of GILZ with the NF-kappaB subunits. | SIGNOR-253297 |
P10275 | Q13285 | 2 | binding | up-regulates | 0.409 | Ar suppresses transcription of the lhbeta subunit by interacting with steroidogenic factor-1. | SIGNOR-109996 |
P55212 | P02545 | 1 | cleavage | down-regulates | 0.662 | Lamin a breakdown is largely mediated by caspase-6 during the execution phase of apoptosis. | SIGNOR-83611 |
Q9NTX7 | Q9Y2T1 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.671 | Here, we identify RNF146, a RING-domain E3 ubiquitin ligase, as a positive regulator of Wnt signalling. RNF146 promotes Wnt signalling by mediating tankyrase-dependent degradation of axin. Mechanistically, RNF146 directly interacts with poly(ADP-ribose) through its WWE domain, and promotes degradation of PARsylated proteins. Using proteomics approaches, we have identified BLZF1 and CASC3 as further substrates targeted by tankyrase and RNF146 for degradation. | SIGNOR-263336 |
Q14344 | Q9BPV8 | 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-257299 |
Q9HCS4 | Q9H9S0 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.341 | These experiments showed that Tcf3 is associated with chromatin in the Nanog promoter regions and that the DNA-binding activity of Tcf3 was required for repression. | SIGNOR-266081 |
P67870 | P55010 | 1 | phosphorylation | up-regulates activity | 0.379 | Mass spectrometric analysis of maximally in vitro phosphorylated eIF5 localized the major phosphorylation sites at Ser-387 and Ser-388 near the C-terminus of eIF5. These serine residues are embedded within a cluster of acidic amino acid residues and account for nearly 90% of the total in vitro eIF5 phosphorylation. A minor phosphorylation site at Ser-174 was also observed. | The results suggest that phosphorylation of eIF5 may have a role in stimulating the rate of eIF5-promoted GTP hydrolysis. | SIGNOR-251070 |
O14770 | P12830 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | We show that the Pbx1 and Meis2 homeodomain proteins interact with Klf4 and can be recruited to DNA elements comprising a Klf4 site or G C box, with adjacent Meis and Pbx sites. Meis2d and Pbx1a activate expression of p15(Ink4a) and E-cadherin, dependent on the Meis2d transcriptional activation domain. We suggest a model in which genes with Klf4 sites can be cooperatively activated by Meis2/Pbx1 and Klf4, dependent primarily on recruitment by Klf4. | SIGNOR-267242 |
P50750 | Q9UM73 | 0 | phosphorylation | up-regulates activity | 0.296 | We report that anaplastic lymphoma kinase (ALK) directly phosphorylates CDK9 at tyrosine-19 to promote homologous recombination (HR) repair and PARP inhibitor resistance. Phospho-CDK9-Tyr19 increases its kinase activity and nuclear localization to stabilize positive transcriptional elongation factor b and activate polymerase II-dependent transcription of HR-repair genes. | SIGNOR-277607 |
Q8WY64 | P01130 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.723 | The RING E3 ubiquitin ligase inducible degrader of the LDL receptor (IDOL, also known as MYLIP) promotes ubiquitylation and subsequent lysosomal degradation of the LDL receptor (LDLR), thus acting to limit uptake of lipoprotein-derived cholesterol into cells. | SIGNOR-271485 |
P15863 | P50221 | 2 | binding | up-regulates activity | 0.512 | We show that Mox1 and Mox2 proteins are capable of interacting with Pax1 and Pax3. We propose that the Mox family of homeodomain proteins participates in the molecular signaling network regulating the diverse events of somite development through the physical interaction with the Pax1 and Pax3 members of the Pax family. | SIGNOR-222193 |
P01178-PRO_0000020495 | P16870 | 0 | cleavage | up-regulates activity | 0.2 | First, OT preprohormone is produced, that will be cleaved and matured by successive enzymes. The OT gene encodes for the Pre-Pro-OT-Neurophysin I (pre-pro-hormone), which is cleaved by different enzymes to give rise to different OT intermediate forms and to the Neurophysin I, and finally to the mature amidated form that is released (Figure 2). | SIGNOR-270338 |
P24941 | P25205 | 1 | phosphorylation | up-regulates | 0.796 | In this study, we demonstrate that mcm3 is a substrate of cyclin e/cdk2 and can be phosphorylated by cyclin e/cdk2 at thr-722. | SIGNOR-176656 |
O60674 | Q9P0J1 | 1 | phosphorylation | down-regulates activity | 0.264 | Here we report that phosphorylation at another tyrosine residue, Tyr-94, inhibits PDP1 by reducing the binding ability of PDP1 to lipoic acid, which is covalently attached to the L2 domain of dihydrolipoyl acetyltransferase (E2) to recruit PDP1 to PDC. We found that multiple oncogenic tyrosine kinases directly phosphorylated PDP1 at Tyr-94, and Tyr-94 phosphorylation of PDP1 was common in diverse human cancer cells and primary leukemia cells from patients. | SIGNOR-276642 |
Q12933 | P67775 | 0 | dephosphorylation | down-regulates activity | 0.2 | We show that the Thr117 residue in TRAF2 is phosphorylated following TNFalpha stimulation. This phosphorylation process is modulated by PP2A and is required for TRAF2 functional activity. | SIGNOR-248640 |
P52333 | O14939 | 1 | phosphorylation | up-regulates | 0.407 | We identified three kinases capable of phosphorylating pld2 in vitro-epidermal growth factor receptor (egfr), jak3, and src (with jak3 reported for the first time in this study)-that phosphorylate an inhibitory, an activator, and an ambivalent (one that can yield either effect) site, respectively. Mass spectrometry analyses indicated the target of each of these kinases as y(296) for egfr, y(415) for jak3, and y(511) for src. | SIGNOR-163858 |
O60674 | P48029 | 1 | relocalization | down-regulates activity | 0.2 | Janus-activated kinase-2 (JAK2) participates in the regulation of the Na⁺-coupled glucose transporter SGLT1 and the Na⁺-coupled amino acid transporter SLC6A19. JAK2 is a novel regulator of the creatine transporter SLC6A8, which downregulates the carrier, presumably by interference with carrier protein insertion into the cell membrane. | SIGNOR-265781 |
Q14790 | P07948 | 0 | phosphorylation | down-regulates activity | 0.311 | The non-receptor tyrosine kinase, Lyn, can phosphorylate caspase-8 on Tyr-397 and Tyr-465, rendering it resistant to activational cleavage and inhibiting apoptosis. | SIGNOR-272980 |
Q8NI51 | Q99933 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.28 | DNA methyltransferase 1 and 3B activate BAG-1 expression via recruitment of CTCFL/BORIS and modulation of promoter histone methylation | SIGNOR-254107 |
Q9NZQ7 | Q96J02 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.2 | ITCH Ubiquitinates and Down-Regulates Tumor-Surface PD-L1.|The current study supports a model (Fig. 7) in which the E3 ligase ITCH mediates poly-ubiquitination of PD-L1 and down-regulates tumor cell-surface PD-L1 levels (via ubiquitin-directed lysosomal degradation) in MAPKi-adapted melanoma cells and in potentially other biologic contexts such quasi-mesenchymal tumor cell-states that contribute to therapy resistance and metastatic potential. | SIGNOR-278815 |
P10721 | O96017 | 0 | phosphorylation | up-regulates | 0.286 | In this report, we characterize the binding of sh2(chk) to specific phosphotyrosine sites on the c-kit protein sequence. the sh2(chk) binding to the two sites is direct and not through phosphorylated intermediates such as fyn or shc. this indicates that chk binds to the same site on c-kit to which fyn binds, possibly bringing the two into proximity on associated c-kit subunits and leading to the down-regulation of fyn by chk. | SIGNOR-197281 |
P35222 | Q9NSA3 | 2 | binding | down-regulates | 0.816 | We identify a novel beta-catenin-interacting protein, icat, that was found to inhibit the interaction of beta-catenin with tcf-4 and represses beta-catenin-tcf-4-mediated transactivation. | SIGNOR-79399 |
O14757 | Q9UNS1 | 2 | binding | up-regulates activity | 0.795 | We performed a detailed molecular characterization of TIM interactions with the core clock protein CRY1 and the DNA damage signal transducer CHK1, and found that the N-terminus of TIM is required for association with both proteins, as well as for homodimerization. | SIGNOR-268054 |
Q16832 | Q96P44 | 2 | binding | up-regulates activity | 0.2 | The Discoidin Domain Receptors (DDRs) constitute a unique set of receptor tyrosine kinases that signal in response to collagen.|Consistent with this view128, we showed that ectopic expression of DDR1b or DDR2 in HT1080 cells elicited a potent growth inhibitory effect only when the cells were cultured on 2D or 3D COL1 matrices, in agreement with previous studies in melanoma48, breast cancer76,78, and lung cancer cells74,75. | SIGNOR-272343 |
Q9Y5H8 | P05556 | 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. | SIGNOR-265668 |
Q13237 | Q03393 | 1 | phosphorylation | up-regulates | 0.53 | Upon expression in cos-1 cells, ptps-s19a was stable but not phosphorylated and had a reduced activity of approximately 33% in comparison to wild-type ptps. Addition of cgmp stimulated phosphotransferase activity 2-fold. Extracts from transfected cos-1 cells overexpressing cgkii stimulated ser(19) phosphorylation more than 100-fold.In assays with purified enzymes, wild-type but not ptps-s19a was a specific substrate for the cgmp-dependent protein kinase (cgk) type i and ii. Upon expression in cos-1 cells, ptps-s19a was stable but not phosphorylated and had a reduced activity of approximately 33% in comparison to wild-type ptps | SIGNOR-71751 |
O60260 | O75385 | 0 | phosphorylation | up-regulates activity | 0.2 | Furthermore, the Parkin band shift induced by catalytically active WT ULK1 was diminished by treatment of cell lysates with lambda-phosphatase, as was the mobility of ULK1 itself (XREF_FIG).|Parkin is phosphorylated by ULK1 at Ser 108 in its recently described nine amino acid ACT element at this early time point | SIGNOR-279663 |
P78317 | Q9HBE1 | 2 | binding | down-regulates | 0.511 | In vitro and in vivo interaction between rnf4 and patz was demonstrated / patz acted as a transcriptional repressor, whereas its partner rnf4 behaved as a transcriptional activator./ the association of patz with rnf4 switches activation to repression | SIGNOR-75775 |
O60664 | P35790 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.2 | In addition, as a protein kinase, CHKα2 phosphorylates PLIN2 at Tyrosine 232 and PLIN3 at Tyrosine 251. Phosphorylated PLIN2 and PLIN3 are separated from lipid droplets and degraded by Hsc70-mediated autophagy, thereby promoting lipid droplet lipolysis, fatty acid oxidation and glioblastoma growth | SIGNOR-267650 |
P45984 | P45983 | 0 | phosphorylation | up-regulates | 0.593 | Our studies revealed a novel mechanism in which phosphorylation of jnk2 is mediated by jnk1 before phosphorylation of p53, and then p53 is directly phosphorylated by jnk2 at ser6. | SIGNOR-155205 |
P17612 | Q9UBI6 | 2 | binding | down-regulates | 0.4 | As pka suppresses the activity of gli, smo might use the stimulation of pi3k by galfai and gbetagamma subu- nits to block pka in cells that have high levels of camp. | SIGNOR-152615 |
Q13315 | Q15910 | 1 | phosphorylation | down-regulates quantity | 0.458 | Enhancer of zeste homolog 2 (EZH2), a core catalytic component of polycomb repressive complex 2, is a new ATM kinase target, and ATM-mediated phosphorylation of EZH2 on Ser734 reduces protein stability.|We verified that S734 is the predominant ATM site on EZH2 by performing ATM in vitro kinase assays using GST-EZH2 fusion proteins as substrates (Fig. 2b). The phosphorylation signal was nearly lost when the EZH2-S734A mutant was used as substrate | SIGNOR-279586 |
O43318 | O14920 | 1 | phosphorylation | up-regulates activity | 0.755 | Tak1 become activated and then phosphorylates and activates ikk2 which in turn now phosphorylates ikba, marking it for k48-ubiquitination and proteasomal degradation. tak1 kinase complex phosphorylates and activates ikk in a manner that depends on traf6 and ubc13-uev1a our studies suggests that tak1_ acts as an upstream activating kinase for ikkbeta. | SIGNOR-109490 |
P11309 | P38936 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.481 | Pim-2 phosphorylation of p21(cip1/waf1) enhances its stability and inhibits cell proliferation in hct116 cellshere we demonstrate that like pim-1, pim-2 also phosphorylates the cell cycle inhibitor p21(cip1/waf1) (p21) on thr145 in vitro and in vivo | SIGNOR-164642 |
Q12778 | Q16512 | 0 | phosphorylation | down-regulates | 0.2 | Furthermore, estrogen induced phosphorylation and perinuclear localization of the cell survival forkhead transcription factor fkhr in the cytoplasm in a pak1-dependent manner. In addition, pak1 directly interacted with fkhr and phosphorylated it. The noticed phosphorylation-dependent exclusion of fkhr from the nucleus impaired the ability of fkhr to activate its target fas ligand promoter containing the fkhr binding motif (fre) in cells treated with estrogen or expressing catalytically active pak1. | SIGNOR-97882 |
Q02577 | Q96EB6 | 0 | deacetylation | up-regulates activity | 0.383 | SIRT1 deacetylates the brain-specific helix-loop-helix transcription factor NHLH2 on lysine 49 to increase its activation of the MAO-A promoter | SIGNOR-254830 |
P46459 | Q02156 | 0 | phosphorylation | up-regulates activity | 0.234 | PKCepsilon phosphorylation enhances the ATPase activity of NSF.|These results indicate that PKCepsilon phosphorylates NSF at both S460 and T461 in vitro. | SIGNOR-278300 |
Q9HAZ2 | P37231 | 2 | binding | up-regulates | 0.469 | Prdm16 stimulates brown adipogenesis by binding to ppar-gamma (peroxisome-proliferator-activated receptor-gamma) and activating its transcriptional function | SIGNOR-180298 |
P06213 | P29353 | 2 | binding | up-regulates | 0.71 | The npxy motif around 960-tyr residue of the insulin receptor binds to the n-terminal ptb domain of shc. | SIGNOR-84251 |
Q8NEB9 | Q6ZNE5 | 2 | binding | up-regulates activity | 0.881 | Characterization of the new proteins revealed that atg14l enhances vps34 lipid kinase activity and upregulates autophagy, | SIGNOR-235448 |
Q12772 | O75874 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.277 | IDH1 gene transcription is sterol regulated and activated by SREBP-1a and SREBP-2 in human hepatoma HepG2 cells|evidence that IDH1 may regulate lipogenesis in hepatic cells | SIGNOR-253133 |
Q8WU17 | P36956 | 1 | ubiquitination | down-regulates quantity | 0.298 | Induction of TRC8 destabilized the precursor forms of the transcription factors SREBP-1 and SREBP-2. TRC8 destablizes SREBP precursors in a RING and proteasome-dependent manner | SIGNOR-271957 |
P16104 | Q13535 | 0 | phosphorylation | up-regulates activity | 0.2 | ATR and ATM also phosphorylate histone H2AX at Ser 139 (gammaH2AX) in response to DNA double-strand breaks (DSBs), which spreads along the DNA up to 200-400 kb and helps in the recruitment of proteins involved in DNA damage repair and checkpoint activation . | SIGNOR-279356 |
Q13049 | Q96EV8 | 1 | ubiquitination | down-regulates quantity | 0.537 | TRIM32 is an E3 ubiquitin ligase for dysbindin. TRIM32 targets dysbindin for degradation. | SIGNOR-265658 |
Q8IYT4 | Q9UJT0 | 2 | binding | down-regulates quantity by destabilization | 0.2 | KATNAL2 does not sever microtubules composed of α- and β-tubulin but does interact with δ- and ε-tubulin | SIGNOR-267176 |
Q9UKW4 | P12931 | 0 | phosphorylation | up-regulates | 0.325 | Activation of rac1 and the exchange factor vav3 are involved in npm-alk signaling in anaplastic large cell lymphomas. | SIGNOR-159240 |
P55290 | P35222 | 2 | binding | up-regulates activity | 0.534 | At its C-terminus, cadherin interacts with β-catenin, which dynamically associates with α-catenin, a direct binding partner of filamentous actin | SIGNOR-265853 |
P10071 | Q93074 | 2 | binding | down-regulates | 0.504 | We propose that activated gli3 physically targets med12 in mediator to reverse mediator-dependent suppression of shh target gene (i.e., Gli1 or cyclin d1) transcription. | SIGNOR-149876 |
Q676U5 | O43353 | 2 | binding | down-regulates activity | 0.384 | In human monocyte-derived dendritic cells, NOD2 activation by MDP induced physical interaction between ATG16L1 and RIPK2 and negatively regulated NF-κB activation. It is important to note that ATG16L1 acts synergistically with IRF4 to inhibit RIPK2 polyubiquitination. | SIGNOR-280457 |
P55036 | P46934 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.451 | S5a/Rpn10 is a ubiquitin (Ub)-binding protein that is a subunit of the 26S proteasome but also exists free in the cytosol. It binds poly-Ub chains through its two Ub-interacting motifs (UIMs). We discovered that, unlike typical substrates of Ub ligases (E3s), S5a can be ubiquitinated by all E3s tested including multimeric and monomeric Ring finger E3s (MuRF1, Siah2, Parkin, APC, and SCF(betaTRCP1)), the U-box E3, CHIP, and HECT domain E3s (E6AP and Nedd4) when assayed with UbcH5 or related Ub-conjugating enzymes.The short half-life of S5a presumably is because of the presence of the UIM domain and reflects the ubiquitination of free S5a by many E3s. | SIGNOR-272753 |
P38405 | Q969V1 | 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-256938 |
Q8IZU3 | Q06609 | 2 | binding | up-regulates activity | 0.362 | The eukaryotic RecA homologues RAD51 and DMC1 function in homology recognition and formation of joint-molecule recombination intermediates during yeast meiosis. We also show that mouse RAD51 and DMC1 establish protein-protein interactions with each other and with the chromosome core component COR1(SCP3) in a two-hybrid system and in vitro binding analyses. These results suggest that the formation of a multiprotein recombination complex associated with the meiotic chromosome cores is essential for the development and fulfillment of the meiotic recombination process. | SIGNOR-264205 |
P02788 | Q8WWA0 | 2 | binding | up-regulates activity | 0.362 | Intelectin 1 (IntL) is known as a lectin expressed in intestinal epithelia and also as a receptor for an iron-binding protein, lactoferrin (LF). | SIGNOR-272500 |
Q9NR28 | O15033 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.377 | AREL1 ubiquitinated SMAC, primarily on Lys62 and Lys191 |E701A substitution in the AREL1 HECT domain substantially increased its autopolyubiquitination and SMAC ubiquitination activity, whereas deletion of the last three amino acids at the C terminus completely abrogated AREL1 autoubiquitination and reduced SMAC ubiquitination. | SIGNOR-267672 |
Q8TCW9 | P58294 | 2 | binding | up-regulates | 0.412 | The present study demonstrates that eg-vegf/prokineticin 1 and a peptide closely related to eg-vegf, prokineticin 2, are cognate ligands of two orphan g-protein-coupled receptors designated zaq (=eg-vegf/pk-r1) and i5e (=eg-vegf/pk-r2) | SIGNOR-89084 |
P17612 | P25054 | 1 | phosphorylation | down-regulates activity | 0.307 | Changing a serine residue (Ser(2054)) to aspartic acid mutated the potential protein kinase A site adjacent to NLS2(APC), resulting in both inhibition of the NLS2(APC)-mediated nuclear import of a chimeric beta-galactosidase fusion protein and a reduction of full-length APC nuclear localization. | SIGNOR-250335 |
Q05655 | P13498 | 1 | phosphorylation | up-regulates | 0.2 | Phosphorylation of p22phox on threonine 147 enhances NADPH oxidase activity by promoting p47phox binding. | Threonine 147 of p22phox Is Phosphorylated by PKC-α and PKC-δ in Vitro | SIGNOR-260892 |
Q15796 | Q15796 | 2 | binding | up-regulates activity | 0.2 | Smad2 and Smad3 form homo-oligomers upon phosphorylation by the constitutively active TGF-beta type I receptor, and this oligomerization does not require Smad4 | SIGNOR-232149 |
Q9BTM1 | Q86Y13 | 0 | monoubiquitination | up-regulates activity | 0.2 | 2A-HUB catalyzes monoubiquitination of H2A at lysine 119, functioning as a combinatoric component of the repression machinery required for specific gene regulation programs. Thus, 2A-HUB mediates a selective repression of a specific set of chemokine genes in macrophages, critically modulating migratory responses to TLR activation. H2A monoubiquitination acts to prevent FACT recruitment at the transcriptional promoter region, blocking RNA polymerase II release at the early stage of elongation. | SIGNOR-271763 |
P42224 | Q05655 | 0 | phosphorylation | up-regulates | 0.589 | All stats are phosphorylated on at least one serine residue in their tad specifically, ser727 in stats 1 and 3 and ser721 in stat4. Stat serine kinases have been identified through the use of inhibitors, dominant-negative alleles, and in vitro kinase assays. They include mapk (p38mapk: stats 1, 3, 4;erk: stat3, 5;jnk: stat3), pkc_ (stat1, stat3), mtor (stat3), nlk (stat3 (42)), and camkii and ikk_ (stat1 (39, 40, 43)).STAT Serine phosphorylation regulates transcriptional activity (see below). | SIGNOR-154791 |
P38432 | Q99986 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.361 | The active murine VRK1, but not its kinase-dead mutant (K179E), also phosphorylates coilin in Ser184 ( xref ). | SIGNOR-279772 |
P98172 | P54753 | 2 | binding | up-regulates | 0.762 | The activation of eph receptors by their ligands, which are membrane-anchored molecules, involves a cell-cell recognition event that often causes cell repulsion. | SIGNOR-52517 |
P35318 | P05549 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.267 | These findings suggest that NF-IL6 and AP-2 sites in the promoter region are the functional elements in the transcriptional regulation of human AM gene in vascular endothelial cells. | SIGNOR-254048 |
P27361 | P36507 | 0 | phosphorylation | up-regulates | 0.742 | The primary structure of mek, a protein kinase that phosphorylates the erk gene product | SIGNOR-19244 |
Q07687 | P35548 | 2 | binding | down-regulates activity | 0.392 | We demonstrate that dimerization by Msx and Dlx proteins is mediated through their homeodomains and that the residues required for this interaction correspond to those necessary for DNA binding. Unlike most other known examples of homeoprotein interactions, association of Msx and Dlx proteins does not promote cooperative DNA binding; instead, dimerization and DNA binding are mutually exclusive activities. Msx proteins act as transcriptional repressors and Dlx proteins act as activators, while in combination, Msx and Dlx proteins counteract each other's transcriptional activities. | SIGNOR-240911 |
O95786 | P62136 | 0 | dephosphorylation | up-regulates activity | 0.2 | We identified PP1alpha and PP1gamma as primary phosphatases responsible for MDA5 and RIG-I dephosphorylation, leading to their activation.|endogenous RIG-I and MDA5 that interacted with PP1 exhibited markedly decreased phosphorylation levels at S8 and S88, respectively | SIGNOR-264581 |
O95644 | Q16539 | 0 | phosphorylation | down-regulates | 0.622 | We show that jnk, erk, and p38 physically associate with the nfatc n-terminal regulatory domain and can directly phosphorylate functionally important residues involved in regulating nfatc subcellular localization, namely ser(172) and the conserved nfatc ser-pro repeats. | SIGNOR-74560 |
P04141 | P15509 | 2 | binding | up-regulates | 0.857 | We have determined the nmr structure of a ligand-binding domain of the granulocyte colony-stimulating factor (g-csf) receptor comparisons between the spectra of the 15n-labelled domain with and without g-csf indicate that the major ligand-recognition site is on the fg loop just upstream of the wsxws sequence. | SIGNOR-72458 |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.