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 |
|---|---|---|---|---|---|---|---|
Q13322 | P06241 | 0 | phosphorylation | down-regulates | 0.38 | Grb10 tyrosine phosphorylation was stimulated by expression of constitutively active src or fyn in cells and by incubation with purified src or fyn in vitro. The insulin stimulated or src/fyn-mediated tyrosine phosphorylation in vivo was significantly reduced when grb10 tyrosine 67 was changed to glycine. This mutant form of grb10 bound with higher affinity to the ir in cells than that of the wild-type protein, suggesting that tyrosine phosphorylation of grb10 may normally negatively regulate its binding to the ir. | SIGNOR-78702 |
P55072 | Q9BUN8 | 2 | binding | up-regulates activity | 0.884 | VIMP mediates p97 binding to hDerlin-1. these data suggest that Derlin-1 and VIMP form a membrane protein complex that serves as a receptor for p97. | SIGNOR-261372 |
P28221 | P19086 | 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-257116 |
Q92878 | Q6NUQ1 | 2 | binding | up-regulates activity | 0.471 | We propose that p130, forming a complex with Rad50 through RINT-1, blocks telomerase-independent telomere lengthening in normal cells. | SIGNOR-265030 |
P27361 | P14598 | 1 | phosphorylation | up-regulates | 0.42 | Upon activation, several serine residues on the cytosolic oxidase subunit p47phox become phosphorylated. Mitogen-activated protein kinase phophorylated only the peptide containing ser345/348. | SIGNOR-40821 |
O43776 | P18848 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress. | SIGNOR-269422 |
Q9Y4P1 | P31749 | 0 | phosphorylation | up-regulates activity | 0.31 | In this study, we identified a novel phosphorylation site at Ser34 of ATG4B induced by AKT in HCC cells.| In brief, our results demonstrate for the first time that the phosphorylation of ATG4B at Ser34 participates in the metabolic reprogramming of HCC cells via repressing mitochondrial function, which possibly results from the Ser34 phosphorylation-induced mitochondrial enrichment of ATG4B and the subsequent inhibition of F1Fo-ATP synthase activity. | SIGNOR-275834 |
Q96QU1 | P11362 | 0 | phosphorylation | up-regulates activity | 0.2 | FGFR1 mediated protocadherin-15 loading mediates cargo specificity during intraflagellar transport in inner ear hair-cell kinocilia.|We find that on activation, FGFR1 binds and phosphorylates Pcdh15. | SIGNOR-280014 |
P08238 | P10275 | 2 | binding | up-regulates activity | 0.704 | The unliganded AR resides predominately in the cytoplasm as a heteromeric complex with hsp90 and other chaperone proteins. These chaperone proteins maintain AR in a form that is receptive to ligand binding. Regulation of gene expression by androgen-activated AR occurs through receptor nuclear translocation, dimerization, and binding to androgen response elements (AREs) in the DNA of target genes. | SIGNOR-251535 |
Q9UHD2 | P36406 | 2 | binding | up-regulates activity | 0.519 | TRIM23 interacts with TBK1 and p62. TRIM23 GTPase activates TBK1 to phosphorylate p62. Biochemical characterization showed that TRIM23 binds with its C-terminal ARF domain to the N-terminal KD of TBK1, and that GTP hydrolysis activity of the ARF stimulates TBK1-mediated phosphorylation of p62 at S403 in its ubiquitin-associated (UBA) domain, which was shown to promote cargo recruitment and autophagic flux | SIGNOR-266654 |
P02751 | P05154 | 2 | binding | down-regulates activity | 0.312 | SERPINA5 inhibits HCC cell migration by directly interacting with fibronectin. SERPINA5 disrupts the fibronectin–integrin β1 signaling pathway. | SIGNOR-265881 |
Q13526 | O14965 | 0 | phosphorylation | down-regulates activity | 0.254 | Here, we found that aurora a can interact with and phosphorylate pin1 at ser16, which suppresses the g2/m function of pin1 by disrupting its binding ability and mitotic entry. | SIGNOR-202487 |
P15289 | P68871 | 1 | acetylation | up-regulates activity | 0.2 | ASA acetylates hemoglobin. Purified acetylated hemoglobin had a slightly increased oxygen affinity and decreased heme-heme interaction. | SIGNOR-251772 |
Q13490 | P42575 | 2 | binding | down-regulates | 0.498 | However, among hiap1, hiap2 and xiap, only hiap2 binds and inhibits caspase-2. | SIGNOR-146738 |
P21127 | O43172 | 1 | phosphorylation | up-regulates activity | 0.2 | Furthermore, hPRP4 interacted directly with Clk1 on its COOH terminus, and the arginine and serine rich domain of hPRP4 was phosphorylated by Clk1 in vitro.|Overexpression of Clk1 caused redistribution of hPRP4, from the speckled to the diffuse pattern in nucleoplasm, whereas inactive mutant of Clk1 caused no change of hPRP4 localization. | SIGNOR-280208 |
P48546 | P09681 | 2 | binding | up-regulates activity | 0.876 | GLP-1 and GIP exert their physiological actions via stimulation of the two G protein-coupled receptors (GPCRs): the GLP-1 receptor (GLP-1R) and the GIP receptor (GIPR), respectively. | SIGNOR-278134 |
Q96GD4 | Q96CF2 | 1 | phosphorylation | up-regulates | 0.469 | Moreover, we find that the cpc's catalytic subunit, aurora b kinase, phosphorylates one of the three human snf7 paralogues-chmp4c-in its c-terminal tail, a region known to regulate its ability to form polymers and associate with membranes. Phosphorylation at these sites appears essential for chmp4c function because their mutation leads to cytokinesis defects. The introduction of the s214a and s215a mutations together with s210a almost completely abolished aurora b phosphorylation | SIGNOR-197967 |
P15172 | P15692 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.391 | We further demonstrate that the myogenic transcription factor, MyoD, and its heterodimeric binding proteins E12 and E47, up-regulate the expression of endogenous VEGF through direct interaction with the VEGF promoter. | SIGNOR-257598 |
O15111 | Q8IUD2 | 2 | binding | up-regulates | 0.59 | Elks likely functions by recruiting ikappabalpha to the ikk complex and thus serves a regulatory function for ikk activation. | SIGNOR-126430 |
P31749 | O43521 | 1 | phosphorylation | down-regulates activity | 0.567 | Recombinant Akt could directly phosphorylate a GST-Bim(EL) fusion protein and identified the Akt phosphorylation site in the Bim(EL) domain as Ser(87). Further, we demonstrated that cytokine stimulation promotes Bim(EL) binding to 14-3-3 proteins. Finally, we show that mutation of Ser(87) dramatically increases the apoptotic potency of Bim(EL). | SIGNOR-252487 |
Q0VAM2 | P01111 | 2 | binding | up-regulates | 0.299 | Gefs catalyse the transition from gdp-bound, inactive ras to gtp-bound, active ras. | SIGNOR-161481 |
P49841 | Q02750 | 0 | phosphorylation | up-regulates activity | 0.343 | In vitro kinase assay was carried out using a recombinant human active mek1 and we found that gsk-3beta was phosphorylated on tyr(216) by this kinase in a dose- and time-dependent manner. Further, the pretreatment of fibroblasts with u0126 inhibited serum-induced nuclear translocation of gsk-3beta. These results suggested that mek1/2 induces tyrosine phosphorylation of gsk-3beta and this cellular event might induce nuclear translocation of gsk-3beta. | SIGNOR-236622 |
P68400 | Q04206 | 1 | phosphorylation | up-regulates activity | 0.443 | We demonstrate that casein kinase II (CKII) interacts with p65 in vivo and can phosphorylate p65 at serine 529 in vitro. A CKII inhibitor (PD144795) inhibited TNFalpha-induced p65 phosphorylation in vivo. Furthermore, our results indicate that the association between IkappaBalpha and p65 inhibits p65 phosphorylation by CKII and that degradation of IkappaBalpha allows CKII to phosphorylate p65 to increase NF-kappaB transactivation potential. | SIGNOR-250942 |
Q8IYK4 | P02452 | 1 | glycosylation | up-regulates activity | 0.442 | Recombinant GLT25D1 and GLT25D2 enzymes showed a strong galactosyltransferase activity toward various types of collagen and toward the serum mannose-binding lectin MBL, which contains a collagen domain. Amino acid analysis of the products of GLT25D1 and GLT25D2 reactions confirmed the transfer of galactose to hydroxylysine residues. | SIGNOR-261156 |
P25116 | P08754 | 2 | binding | up-regulates activity | 0.401 | 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-256875 |
Q9UHD2 | Q13568 | 1 | phosphorylation | up-regulates | 0.541 | Activation of interferon regulatory factor 5 by site specific phosphorylation. Although the gene induction by irf5 in the presence of tbk-1 was modest, phosphorylation by tbk-1 produced a significant shift in the mobility of irf5 in sds-page. For this reason we identified the residues that are phosphorylated on irf5 by tbk-1 with mass spectrometry. Ser-158 and ser-309 were found to be phosphorylated | SIGNOR-196528 |
O14763 | Q96D59 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | RNF183 mediated K63-linked ubiquitination and lysosomal degradation of DR5. | SIGNOR-272212 |
Q16763 | Q9UM11 | 2 | binding | up-regulates activity | 0.761 | Ube2S depends on the cell cycle-dependent association with the APC/C activators Cdc20 and Cdh1 for its activity | SIGNOR-265081 |
Q05655 | P08575 | 0 | dephosphorylation | down-regulates activity | 0.297 | Taken together, these data indicate that CD45 inhibits PMA dependent PKCdelta activation by impeding PMA dependent PKCdelta tyrosine phosphorylation.|reduction in CD45 expression caused the duration of peak PMA-induced MEK and extracellular signal-regulated kinase (ERK) 1/2 activity to increase from 5 min to 30 min while leading to a 4-fold increase in PMA-dependent PKCdelta activation. | SIGNOR-277028 |
Q9H9Q4 | P31749 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.358 | Akt1 phosphorylates XLF at T181 Here, we report that Akt phosphorylates XLF at Thr181 to trigger its dissociation from the DNA ligase IV/XRCC4 complex, and promotes its interaction with 14-3-3β leading to XLF cytoplasmic retention, where cytosolic XLF is subsequently degraded by SCF(β-TRCP) in a CKI-dependent manner. | SIGNOR-276881 |
Q00536 | P17612 | 0 | phosphorylation | down-regulates | 0.314 | Here, we report that cdk16 is activated by membrane-associated cyclin y (ccny). Treatment of transfected human cells with the protein kinase a (pka) activator forskolin blocked, while kinase inhibition promoted, ccny-dependent targeting of cdk16-green fluorescent protein (gfp) to the cell membrane. Ccny binding to cdk16 required a region upstream of the kinase domain and was found to be inhibited by phosphorylation of serine 153, a potential pka phosphorylation site. | SIGNOR-191623 |
Q9UI47 | Q06413 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.241 | GATA-4 and MEF2C are known to bind to the GATA box 2 in the major promoter of CTNNA3 and this element is essential in directly regulating expression of CTNNA3 in cardiac muscle cells. The co-transfection of GATA-4 with MEF2C leads to a synergistic activation of the CTNNA3 promoter | SIGNOR-265491 |
P61457 | P35680 | 2 | binding | up-regulates activity | 0.581 | Overexpression in a human kidney cell line showed that wild-type PCBD1 binds HNF1B to costimulate the FXYD2 promoter, the activity of which is instrumental in Mg(2+) reabsorption in the DCT. | SIGNOR-254910 |
P13497 | P20908 | 1 | cleavage | up-regulates activity | 0.623 | 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.NH2-terminal sequencing of an ∼35-kDa band in the BMP-1-treated material (N-α1(V), Fig. 3 B,lanes 2 and 3) showed it to correspond to the NH2-terminal portion of the pro-α1(V) N-propeptide previously shown to be cleaved in pro-α1(V)3 homotrimers by BMP-1 (39), whereas NH2-terminal sequencing of an ∼38-kDa band (C-α1(V)BMP-1, Fig. 3 B,lanes 2 and 3) showed it to correspond to pro-α1(V) C-propeptides cleaved between Asp-1594 and Asp-1595. | SIGNOR-256344 |
P63096 | Q13304 | 2 | binding | up-regulates activity | 0.411 | 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-256692 |
Q5TCX8 | Q02750 | 1 | phosphorylation | up-regulates activity | 0.2 | These experiments showed that MEK1 is phosphorylated by MLK4 on Ser217/221 | SIGNOR-260767 |
Q99750 | P15172 | 2 | binding | down-regulates activity | 0.497 | We demonstrate that I-mf inhibits the transactivation activity of the MyoD family and represses myogenesis. I-mf associates with MyoD family members and retains them in the cytoplasm by masking their nuclear localization signals. | SIGNOR-240436 |
P55017 | O95747 | 0 | phosphorylation | up-regulates | 0.388 | We demonstrate that the spak and osr1 kinases that are activated by wnk1 phosphorylate human ncc at three conserved residues (thr46, thr55 and thr60) / our results also indicate that phosphorylation of thr60 plays the most crucial role in triggering the activation of ncc in hek293 cells and its mutation also inhibits phosphorylation of the adjacent thr46 and thr55 sites. | SIGNOR-160833 |
P06241 | Q9C0B5 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.388 | Our study demonstrates that under basal conditions, PSD-95 and Fyn cooperatively stabilize DHHC5 at the synaptic membrane through Fyn-mediated phosphorylation of DHHC5 at tyrosine residue 533 and the subsequent inhibition of DHHC5 association with endocytic proteins (Fig. 10). | SIGNOR-279738 |
Q04759 | P22681 | 1 | phosphorylation | up-regulates activity | 0.355 | PKC-θ-mediated phosphorylation of serine and tyrosine residues of c-Cbl prevents its inhibitory effect. Phosphorylation of c-Cbl by PKC-θ inhibits the recruitment of Sh2-containing proteins and subsequent association of cbl E3 ubiquitin ligase with its target proteins | SIGNOR-274144 |
O60563 | Q92585 | 0 | relocalization | up-regulates | 0.2 | Cycc:cdk8 and cyct1:cdk9/p-tefb are recruited with notch and associated coactivators (mam, skip) to the hes1 promoter in signaling cells. | SIGNOR-130712 |
Q9Y4K3 | Q99836 | 2 | binding | up-regulates activity | 0.922 | In innate immunity, nearly all Toll-like receptors (TLRs), as well as the receptors of the interleukin 1 (IL-1) family of cytokines, initiate signaling by recruiting the adaptor protein MyD88. This is followed by the interaction of IL-1-receptor (IL-R)-associated kinase 4 (IRAK4) with MyD88 and then the interaction of other IRAK family members with IRAK4, to form an oligomeric complex, termed the Myddosome (8, 9). IRAK1 and IRAK2 can then interact with TRAF6 (10, 11) and induce TRAF6 dimerization (12), which triggers the activation of its E3 ligase activity | SIGNOR-260160 |
O00308 | Q9P2A4 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | The AIP2 E3 ligase acts as a novel negative regulator of ABA signaling by promoting ABI3 degradation. Here, we show that ABI3 is an unstable protein and that an ABI3-interacting protein (AIP2), which contains a RING motif, can polyubiquitinate ABI3 in vitro. | SIGNOR-272656 |
Q8WYL5 | Q15139 | 0 | phosphorylation | down-regulates | 0.479 | Pkd-mediated phosphorylation of serines 937 and 978 regulates ssh1l subcellular localization by binding of 14-3-3 proteins 14-3-3 proteins associate with ssh1l when phosphorylated at serines 937 and 978, thereby sequestering ssh1l in the cytoplasm and preventing translocation of the phosphatase to f-actin_rich membrane protrusions | SIGNOR-186471 |
Q99986 | O75531 | 1 | phosphorylation | down-regulates | 0.877 | We demonstrate that phosphorylation of ser4 and/or thr2/thr3 abrogates the interaction of baf with dna and reduces its interaction with the lem domain. Coexpression of vrk1 and gfp-baf greatly diminishes the association of baf with the nuclear chromatin/matrix and leads to its dispersal throughout the cell | SIGNOR-144783 |
P62993 | P10721 | 2 | binding | up-regulates activity | 0.65 | We furthermore demonstrate that the adapter protein Grb2 is a specific binding partner for both phosphorylated Tyr-703 and phosphorylated Tyr-936, whereas the adapter protein Grb7 binds selectively to phosphorylated Tyr-936. | SIGNOR-248283 |
P24941 | P24941 | 2 | phosphorylation | up-regulates | 0.2 | Our results demonstrate that cdk2 is capable of autophosphorylation at thr160. | SIGNOR-153636 |
P49790 | O94901 | 2 | binding | up-regulates activity | 0.43 | The NXF1:NXT1 complex and NUP153 interact with the amino terminus of SUN1 |In analogy to a proposal made by Chang et al.4, Nesprins could help anchoring SUN1 near the NPC to enable it to fulfill its task in mRNA export. | SIGNOR-263294 |
O95243 | P50613 | 0 | phosphorylation | down-regulates activity | 0.2 | The mechanistic basis for the phase-separation of MED1 is not well understood, and we hypothesize that this may be due to the phosphorylation of MED1 by CDK7 in response to growth stimuli or nuclear translocation of steroid hormone receptors, such as AR.|Together, we demonstrate that CDK7 inhibition selectively targets MED1 mediated, AR dependent oncogenic transcriptional amplification, thus representing a potential new approach for the treatment of CRPC. | SIGNOR-279686 |
P68431 | Q9NRC8 | 0 | deacetylation | up-regulates activity | 0.2 | SIRT7 links H3K18 deacetylation to maintenance of oncogenic transformation.|Genome-wide binding studies reveal that SIRT7 binds to promoters of a specific set of gene targets, where it deacetylates H3K18Ac and promotes transcriptional repression. | SIGNOR-275874 |
A7KAX9 | Q13480 | 0 | relocalization | up-regulates | 0.314 | Gc-gap, a rho family gtpase-activating protein that interacts with signaling adapters gab1 and gab2. | SIGNOR-102586 |
O75925 | P49137 | 0 | phosphorylation | up-regulates | 0.2 | T he mitogen-activated protein kinase (mapk)-activated protein kinase-2 is a proinflammatory kinase and phosphorylates pias1 at the ser522 residue. Activation of mapk-activated protein kinase-2 enhances p53-sumoylation, but a pias1 phosphorylation mutant, pias1-s522a, abolished this p53-sumoylation, suggesting a critical role for pias1-s522 phosphorylation in its sumo ligase activity. | SIGNOR-199944 |
Q5VU43 | P13861 | 2 | binding | up-regulates | 0.454 | Mmgl acts as a dual-specific akap by anchoring pka regulatory isoforms r1a and r2a. | SIGNOR-173831 |
P16220 | P60484 | 0 | 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 |
P17612 | Q5S007 | 1 | phosphorylation | down-regulates activity | 0.406 | Furthermore, our work establishes S1444 as a PKA-regulated 14-3-3 docking site.Strikingly, 14-3-3 binding to phospho-S1444 decreased LRRK2 kinase activity in vitro. | SIGNOR-237444 |
Q9GZV5 | P84022 | 2 | binding | up-regulates | 0.555 | Taz has been shown to interact with smad2 and smad3 through its coiled-coil region, and to be important in maintaining the nuclear localization of smad2 and smad3 as well as the expression of their target genes in response to tgf-b signaling and, thus, in the maintenance of human esc self-renewal. | SIGNOR-169841 |
P05230 | P21802 | 2 | binding | up-regulates | 0.909 | We have crystallized a complex between human FGF1 and a two-domain extracellular fragment of human FGFR2. | SIGNOR-73811 |
O75582 | Q04206 | 1 | phosphorylation | up-regulates | 0.718 | Transcriptional activation of the nf-kappab p65 subunit by mitogen- and stress-activated protein kinase-1 (msk1)mutational analysis of p65 revealed ser276 as a target for phosphorylation and transactivation in response to tnf. Moreover, we identified msk1 as a nuclear kinase for p65, since msk1 associates with p65 in a stimulus-dependent way and phosphorylates p65 at ser276. | SIGNOR-99210 |
Q13568 | Q9UHD2 | 0 | phosphorylation | up-regulates | 0.541 | Activation of interferon regulatory factor 5 by site specific phosphorylation. Although the gene induction by irf5 in the presence of tbk-1 was modest, phosphorylation by tbk-1 produced a significant shift in the mobility of irf5 in sds-page. For this reason we identified the residues that are phosphorylated on irf5 by tbk-1 with mass spectrometry. Ser-158 and ser-309 were found to be phosphorylated | SIGNOR-196528 |
Q99683 | P51812 | 0 | phosphorylation | down-regulates activity | 0.2 | We provide evidence to show that RSK2 inhibits ASK1 by phosphorylating S83, T1109, and T1326 through a novel mechanism in which phospho-T1109/T1326 inhibits ATP binding to ASK1, while phospho-S83 attenuates ASK1 substrate MKK6 binding. | SIGNOR-276463 |
Q9C0C9 | O43541 | 1 | ubiquitination | down-regulates | 0.464 | We showed that ube2o functions as an e2-e3 hybrid to monoubiquitinate smad6 at lysine 174 | SIGNOR-192255 |
P09471 | Q13304 | 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-256971 |
P07900 | P36897 | 2 | binding | up-regulates | 0.415 | The data in fig. 5 suggest that hsp90 specifically interacts with t?RI And t?RII In vitro and in vivo. Coupled with our data showing that loss of hsp90 function decreases t?R Levels and blocks tgf?-Induced smad2/3 activation and transcription, this result suggests that hsp90 controls tgf? Signaling as an essential component for stabilizing t?Rs. | SIGNOR-179268 |
Q5VWQ8 | Q13546 | 0 | phosphorylation | up-regulates activity | 0.426 | We further show that RIP1 (the Ser/Thr protein kinase receptor-interacting protein) associates with the GAP domain of AIP1 and mediates TNF-induced AIP1 phosphorylation at Ser-604 and JNK/p38 activation as demonstrated by both overexpression and small interfering RNA knockdown of RIP1 in EC. | SIGNOR-259976 |
Q9H1B7 | P01148 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.416 | EAP1 encoded a nuclear protein expressed in neurons involved in the inhibitory and facilitatory control of reproduction. EAP1 transactivated genes required for reproductive function, such as GNRH1, and repressed inhibitory genes, such as preproenkephalin. It contained a RING finger domain of the C3HC4 subclass required for this dual transcriptional activity.These results suggest that EAP1 is a transcriptional regulator that, acting within the neuroendocrine brain, contributes to controlling female reproductive function. | SIGNOR-267154 |
P38405 | Q9HBW0 | 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-256927 |
P24941 | P33991 | 1 | phosphorylation | down-regulates activity | 0.767 | We reported that the dna helicase activity of the human and mouse mcm4-6-7 complex, a sub-complex of the mcm2-7 heterohexamer, is inhibited by the phosphorylation by cdk2-cyclin a we identified six sites, including ser-32, ser-53, and thr-109, in the amino-terminal region of mouse mcm4 that are required for the phosphorylation with cdk2-cyclin a. | SIGNOR-100881 |
Q6UXL0 | Q9UHD0 | 2 | binding | up-regulates | 0.719 | Il-19 signals only through the type i il-20r complex. | SIGNOR-151820 |
P62993 | P00519 | 2 | binding | up-regulates | 0.58 | We demonstrate that bcr-abl exists in a complex with grb-2 in vivo. Binding of grb-2 to bcr-abl is mediated by the direct interaction of the grb-2 sh2 domain with a phosphorylated tyrosine, y177, within the bcr first exon. | SIGNOR-39049 |
P06401 | P03372 | 2 | binding | up-regulates | 0.624 | Here we identify two domains of prb, erid-i and -ii, mediating a direct interaction with the ligand-binding domain of eralpha. | SIGNOR-98807 |
P17252 | Q92934 | 1 | phosphorylation | down-regulates activity | 0.2 | Phosphorylation of BAD at ser112 and ser136 in the setting of lapatinib treatment was fully restored by PRKACA expression in BT474, SKBr3, and ZR-75-30 cells (XREF_FIG).|We found that neither PRKACA nor PIM1 restored MAPK or PI3K activation after lapatinib or trastuzumab treatment, but rather inactivated the pro apoptotic protein BAD, thereby permitting survival signaling through BCL-XL. | SIGNOR-280080 |
Q13315 | Q4G0J3 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Altogether, the results suggest that ATM-mediated T440 phosphorylation enhances LARP7-BARD1 interaction and facilitates BRCA1/BARD1-mediated LARP7 ubiquitination and degradation. | SIGNOR-275580 |
Q8NHM5 | Q99814 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | To this end, we confirm that KDM3A, KDM4B, KDM4C, KDM5B, KDM5C, and KDM62 are direct targets of HIF-1a while extent the list of known targets to KDM2A, KDM2B, KDM4D, KDM5A, and KDM6A. The results demonstrated that majority of the KDMs were similarly induced (KDM2A, KDM2B, KDM3A, KDM4B, KDM4C, KDM4D, KDM5A, KDM5B, KDM5C, KDM6B, and KDM7A) or repressed (KDM NO66 and KDM1A) by both HIF-1a and HIF-2a. | SIGNOR-271582 |
Q8WVD3 | P24941 | 0 | phosphorylation | up-regulates activity | 0.2 | Altogether, our results suggest RNF138 is phosphorylated at position T27 in a CDK1- and CDK2-dependent manner.Altogether, our results suggest RNF138 is phosphorylated at position T27 in a CDK1- and CDK2-dependent manner. | SIGNOR-277831 |
Q6N021 | O15294 | 2 | binding | up-regulates | 0.444 | Tet2 and tet3 associate with the o_glcnac transferase ogt / tet2 and tet3 promote ogt_mediated glcnacylation | SIGNOR-200695 |
Q9UM73 | P21246 | 2 | binding | up-regulates | 0.547 | We conclude from this series of experiments that ptn specifically binds to the alk orphan receptor as a high affinity ligand at least in part via the putative ligand binding domain described above. | SIGNOR-106411 |
P08047 | Q92820 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Overexpression of Sp1 led to enhanced GGH promoter activity and GGH mRNA expression in allele-specific manners. These findings suggested that Sp1 acted as a positive regulator of human GGH transcription through the rs3758149 polymorphism in CEM/C1 cells. | SIGNOR-261350 |
P06493 | Q9Y6X9 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Mechanically, PTX and VCR activate cyclin-dependent kinase 1, which in turn induces MORC2 phosphorylation at threonine 717 (T717) and T733. Phosphorylated MORC2 enhances its interation with HSPA8 and LAMP2A, two essential components of the chaperone-mediated autophagy (CMA) mechinery, resulting in its autophagic degradation. | SIGNOR-277837 |
P11802 | Q92879 | 1 | phosphorylation | up-regulates activity | 0.398 | These studies showed that both the increased levels of CUGBP1 and cdk4-mediated hyper-phosphorylation of CUGBP1 are involved in the age-associated induction of the CUGBP1-eIF2 complex. The CUGBP1-eIF2 complex is bound to C/EBPbeta mRNA in the liver of old animals, and this binding correlates with the increased amounts of liver-enriched activator protein and liver-enriched inhibitory protein. | SIGNOR-262735 |
P04049 | Q13188 | 2 | binding | down-regulates | 0.36 | Raf-1 prevents dimerization and phosphorylation of the activation loop of mst2 independently of its protein kinase activity.Raf-1 counteracts apoptosis by suppressing the activation of mammalian sterile 20-like kinase (mst2) | SIGNOR-132824 |
Q04912 | P00533 | 0 | phosphorylation | up-regulates activity | 0.334 | This showed that EGFR activation transphosphorylated Ron.|Together, these data suggested that (1) Ron activation transphosphorylated EGFR and vice versa and (2) activated Ron biochemically interacted with EGFR. | SIGNOR-280000 |
P28702 | P10828 | 2 | binding | up-regulates | 0.636 | Like many receptors belonging to the superfamily of steroid/thyroid nuclear receptors, thyroid hormone receptors (trs) bind to specific th-dna responsive elements (tre) upstream of target gene in heterodimeric complex with the 9-cis retinoid acid receptor (rxr | SIGNOR-81455 |
P17275 | Q96J02 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.408 | Itch promotes Ub conjugation to JunB Molecularly, Itch associated with and induced ubiquitination of JunB, a transcription factor that is involved in TH2 differentiation. However, in Itch−/− T cells under the same conditions, degradation of JunB was markedly delayed. | SIGNOR-272619 |
Q96SB3 | Q92974 | 2 | binding | up-regulates activity | 0.396 | The Rho Family GEF Lfc Interacts with Neurabin and Spinophilin. Neurabin and spinophilin are homologous protein phosphatase 1 and actin binding proteins that regulate dendritic spine function. The results obtained in the present study suggest a mechanism by which neurabin or spinophilin contributes to the organization of the F-actin cytoskeleton in dendritic spines, and in turn to the regulation of spine morphology, via the activity-dependent recruitment of the Rho-specific GEF Lfc | SIGNOR-269176 |
P12931 | P51809 | 1 | phosphorylation | up-regulates activity | 0.286 | We found that TI-VAMP is phosphorylated in vitro by c-Src kinase on tyrosine 45 of the Longin domain.Mimicking tyrosine 45 phosphorylation activates both t-SNARE binding and exocytosis of TI-VAMP. | SIGNOR-273819 |
Q7KZI7 | Q15831 | 0 | phosphorylation | up-regulates activity | 0.588 | MARK family kinases can be activated by phosphorylation of a conserved threonine (Thr-208 in MARK2), and inactivated by phosphorylation of a serine (Ser-212), both in the activation loop of the catalytic domain. Activation is achieved by the kinases MARKK/TAO1 or LKB1, although the inactivating kinase was unknown. We show here that GSK3beta serves the role of the inhibitory kinase. | SIGNOR-276165 |
P00519 | Q13233 | 1 | phosphorylation | up-regulates activity | 0.258 | Moreover, c-Abl activates MEKK-1 in vitro and in response to DNA damage.|The results demonstrate that the nuclear c-Abl binds to MEKK-1 and that c-Abl phosphorylates MEKK-1 in vitro and in vivo. | SIGNOR-279672 |
Q9NR50 | P41091 | 1 | guanine nucleotide exchange factor | up-regulates activity | 0.735 | EIF2B converts the protein synthesis initiation factor 2 (eIF2) from an inactive GDP-bound form to an active eIF2-GTP complex owing to its guanine nucleotide exchange factor (GEF) activity. | SIGNOR-269136 |
Q01844 | P17252 | 0 | phosphorylation | down-regulates activity | 0.331 | Here we report thatews, a nuclearrna-bindingprooncoprotein, contains an iq domain, is phosphorylated byproteinkinase c, and interacts with calmodulin. Interestingly, pkc phosphorylation of ews inhibits its binding to rna homopolymers, and conversely,rna binding to ews interferes with pkc phosphorylation./ these data indicate that ews contains an iq domain with ser266 acting as the primary site for pkc phosphorylation. | SIGNOR-52850 |
Q9UHC6 | Q12860 | 1 | relocalization | up-regulates activity | 0.477 | These results suggest that the targeting of contactin to different axonal domains may be determined, in part, via its association with Caspr. | SIGNOR-269074 |
Q96QV1 | Q14623 | 2 | binding | down-regulates activity | 0.713 | Hip encodes a membrane glycoprotein that binds to all three mammalian hedgehog proteins with an affinity comparable to that of ptc-1. our findings support a model in which hip attenuates hedgehog signalling as a result of binding to hedgehog proteins: a negative regulatory feedback loop established in this way could thus modulate the responses to any hedgehog signal. | SIGNOR-65075 |
P28482 | P49715 | 1 | phosphorylation | down-regulates | 0.352 | Ccaat/enhancer-binding protein alpha (c/ebpalpha) is one of the key transcription factors that mediate lineage specification and differentiation of multipotent myeloid progenitors into mature granulocytes.Here we report that inducers of monocyte differentiation inhibit the alternate cell fate choice, that of granulopoiesis, through inhibition of c/ebpalpha. This inhibition is mediated by extracellular signal-regulated kinases 1 and/or 2 (erk1/2), which interact with c/ebpalpha through an fxfp docking site and phosphorylate serine 21. | SIGNOR-120566 |
Q8WYQ5 | Q8IYW5 | 2 | binding | up-regulates activity | 0.2 | Specifically, radiation-induced ATM-dependent phosphorylation of DGCR8 at serine 677 facilitates USP51 to bind, deubiquitinate, and stabilize DGCR8, which leads to the recruitment of DGCR8 and DGCR8's binding partner RNF168 to MDC1 and RNF8 at DSBs. | SIGNOR-277309 |
P49336 | Q92585 | 2 | binding | up-regulates | 0.597 | Mastermind recruits cycc:cdk8 to phosphorylate the notch icd and coordinate activation with turnover | SIGNOR-130715 |
P04626 | P51452 | 0 | dephosphorylation | down-regulates activity | 0.268 | Expression of VHR inhibited the activation of phospholipase Cγ and protein kinase C, both downstream effectors of Tyr-992 phosphorylation of EGFR. | We found that VHR decreased ErbB2 phosphorylation in vitro and in a cellular context, and the dephosphorylation of ErbB2 was more evident at Tyr-877 and Tyr-1221 than those at Tyr-1139 and Tyr-1248 (supplemental Fig. S1). Our data indicated that VHR was a cellular PTP against EGFR and ErbB2. | SIGNOR-248533 |
Q9Y566 | Q9Y2H0 | 0 | relocalization | up-regulates activity | 0.696 | 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-264595 |
Q58EX7 | P60953 | 1 | guanine nucleotide exchange factor | up-regulates activity | 0.36 | 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-260564 |
Q07869 | Q15466 | 2 | binding | up-regulates | 0.533 | Surprisingly, shp potentiated transcription by pparalpha/rxralpha heterodimers from the hd-ppre. This is the first demonstration of positive transcriptional activity attributable to shp. Together, these results suggest that shp can modulate pparalpha/rxralpha-mediated transcription in a response element-specific manner. | SIGNOR-108252 |
P41968 | P09471 | 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-257026 |
P52655 | P68400 | 0 | phosphorylation | up-regulates activity | 0.379 | We now show that human TFIIA is phosphorylated in vivo on serine residues that are partially conserved between yeast and human TFIIA large subunits. Alanine substitution mutation of serine residues 316 and 321 in TFIIA alphabeta reduced TFIIA phosphorylation significantly in vivo. Additional alanine substitutions at serines 280 and 281 reduced phosphorylation to undetectable levels. Mutation of all four serine residues reduced the ability of TFIIA to stimulate transcription in transient transfection assays with various activators and promoters, indicating that TFIIA phosphorylation is required globally for optimal function. | SIGNOR-250877 |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.