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 |
|---|---|---|---|---|---|---|---|
P43268 | Q15831 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.622 | LKB1 phosphorylated PEA3 and promoted its degradation through a proteasome-mediated mechanism. | SIGNOR-279293 |
Q9Y5N1 | P08754 | 2 | binding | up-regulates activity | 0.437 | 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-256832 |
Q9HB90 | Q8N122 | 2 | binding | up-regulates | 0.941 | Active rag and gtr heterodimers are able to bind and activate torc1, through direct interactions with raptor. | SIGNOR-162054 |
P45983 | Q05639 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.374 | Ribosome-associated JNK phosphorylates the eukaryotic translation elongation factor 1A isoform 2 (eEF1A2) on serines 205 and 358 to promote degradation of NSPs by the proteasome. | SIGNOR-276492 |
P0DMV9 | O15217 | 1 | relocalization | up-regulates activity | 0.2 | Model showing Ser189/Thr193 protein kinase dependent phosphorylation of GST A4‐4 has increased affinity for chaperone Hsp70 which activates mitochondrial competent import signals for GSTA4‐4. |Protein kinase A mediated phosphorylation of serine residues of CYPs increases the affinity of proteins for binding to cytoplasmic chaperones such as heat shock proteins (Hsp), Hsp70/Hsp90, resulting in increased mitochondrial translocation | SIGNOR-264800 |
Q13207 | P38936 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.345 | TBX2 and TBX3 function as transcriptional repressors and both have been shown to inhibit myogenesis (Carlson et al, 2002; Zhu et al, 2014). Abnormal expression of TBX2 has been reported in several cancers including breast, pancreas, and melanoma, where it has been shown to drive proliferation (reviewed in Abrahams et al (2010)). As has been previously shown in other cell types, TBX2 was found to induce a downregulation of p14/19ARF and function as a direct repressor of p21 in RMS | SIGNOR-249593 |
P24941 | Q12959 | 1 | phosphorylation | up-regulates | 0.282 | We also show that dlg1 is phosphorylated by both cdk1 and cdk2 on ser158 and ser442. These phosphorylated sites together affect the nuclear localisation of the protein, and implicate the role of phosphorylation on ser158 and ser442 in its putative nuclear functions as a tumour suppressor. phosphorylation on ser158 and ser442 enhances nuclear expression of dlg1 | SIGNOR-182765 |
P35716 | Q9HCK8 | 0 | transcriptional regulation | down-regulates quantity | 0.2 | Many of the most significantly up-regulated genes in Chd8+/− and Chd8−/− NPCs are involved in later stages of neuronal development, including Ascl1 [a central driver of neural reprogramming (29)], Dcx, Map2, Nefm, Neurod4, and Neurog1 (Fig. 2 E and F). Additionally, we found that Sox3 is derepressed in both Chd8+/− and Chd8−/− NPCs, and several other Sox TF members (Sox2, Sox7, and Sox11) became derepressed in the Chd8−/− cells | SIGNOR-268923 |
Q14164 | Q9UHD2 | 2 | binding | up-regulates activity | 0.646 | STING recruits TBK1 and IKKε and forms the TBK1-IKKε complex via the association with TRAF3. The TBK1 complex induces the phosphorylation, dimerization, and nuclear translocation of IRF3. | SIGNOR-260155 |
P29992 | P35348 | 2 | binding | up-regulates activity | 0.573 | In this report, we demonstrate that in transfected cos-7 cells Gal4 and Ga16, like Gaq and Ga11, can activate PIPLC j3l and that all three al-ARs, alA, alB and alC, can activate endogenous PI-PLC by coupling to Gaq or Ga11. | SIGNOR-278121 |
Q96KB5 | P81274 | 1 | phosphorylation | up-regulates | 0.27 | We found that the 450th threonine (thr450) of lgn/gpsm2 was phosphorylated by the serine/threonine kinase pbk/topk during mitosis. Western blot analysis indicated the highest expression and the phosphorylated form of lgn/gpsm2 protein in g2/m phase. | SIGNOR-166461 |
Q99835 | P11488 | 2 | binding | up-regulates | 0.262 | Consistent with its predicted topology, smo couples to a specific family of inhibitory g protein (gis) to regulate hh signaling. | SIGNOR-148496 |
Q9NTG7 | P05108 | 1 | deacetylation | up-regulates quantity by stabilization | 0.2 | Resveratrol stimulates cortisol biosynthesis by activating SIRT-dependent deacetylation of P450scc.|Stable overexpression of SIRT3 abrogates the cellular content of acetylated P450scc, concomitant with an increase in P450scc protein expression and cortisol secretion. Mutation of K148 and K149 to alanine stabilizes the expression of P450scc and results in a 1.5-fold increase in pregnenolone biosynthesis. | SIGNOR-268718 |
O75197 | Q93097 | 2 | binding | up-regulates | 0.588 | Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors andinitiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation. | SIGNOR-131780 |
P22681 | P12931 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.738 | Cbl-b also targets active Src for degradation in cells, and Nedd4 similarly reverses Cbl mediated Src degradation.|Cbl-b also targets active Src for degradation in cells, and Nedd4 similarly reverses Cbl-mediated Src degradation | SIGNOR-278539 |
P23760 | P11802 | 0 | phosphorylation | up-regulates activity | 0.296 | In summary, our study showed that Cdk4 phosphorylates and activates PAX3-FOXO1, thereby promoting its oncogenic function.|These findings suggest that Cdk4 phosphorylates the Ser 430 residue of PAX3-FOXO1 in vitro . | SIGNOR-278512 |
P19086 | P41595 | 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-257022 |
Q02156 | P41594 | 1 | phosphorylation | up-regulates activity | 0.396 | Thus, we showed that it is phosphorylation of Ser-839, not Thr-840, that is absolutely required for the unique Ca2+ oscillations produced by mGluR5 activation. The Thr-840 residue is important only in that it is permissive for the PKC-dependent phosphorylation of Ser-839. | SIGNOR-249288 |
P46934 | Q2KJY2 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.316 | Nedd4 polyubiquitinates Kif26b and thus targets it for degradation via the ubiquitin-proteasome pathway. | SIGNOR-278767 |
Q07812 | Q9NY61 | 0 | transcriptional regulation | down-regulates quantity | 0.2 | We identify the transcriptional regulator apoptosis-antagonizing transcription factor (AATF)/Che-1 as a critical regulator of the cellular outcome of the p53 response. Upon genotoxic stress, AATF is phosphorylated by the checkpoint kinase MK2. Phosphorylation results in the release of AATF from cytoplasmic MRLC3 and subsequent nuclear translocation where AATF binds to the PUMA, BAX and BAK promoter regions to repress p53-driven expression of these pro-apoptotic genes. | SIGNOR-259916 |
P14618 | P00533 | 0 | phosphorylation | down-regulates activity | 0.449 | EGFR binds to and phosphorylates PKM2 to inhibit its activity. | SIGNOR-277197 |
P78337 | P18031 | 0 | dephosphorylation | down-regulates quantity by destabilization | 0.354 | PTP1B dephosphorylates PITX-1 at Y160, 175 and Y179.|Through directly dephosphorylating PITX-1 at Y160, Y175 and Y179, PTP1B promoted proteasomal degradation of PITX-1, thus leaded in downregulating p120RasGAP and CRC cell survival. | SIGNOR-276973 |
Q13164 | Q13163 | 2 | phosphorylation | up-regulates | 0.703 | Phosphorylation and activation of extracellular-signal-regulated protein kinase 5 (erk5) by mitogen-activated protein kinase kinase 5 (mkk5)activated erk5 also phosphorylated mitogen-activated protein kinase kinase 5 (mkk5) extensively at ser(129), ser(137), ser(142) and ser(149) | SIGNOR-99127 |
P33151 | P35222 | 2 | binding | up-regulates activity | 0.76 | At its C-terminus, cadherin interacts with β-catenin, which dynamically associates with α-catenin, a direct binding partner of filamentous actin | SIGNOR-265867 |
Q14232 | P20042 | 1 | guanine nucleotide exchange factor | up-regulates activity | 0.78 | 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-269129 |
P41161 | Q12857 | 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-268874 |
O75581 | P12931 | 0 | phosphorylation | down-regulates activity | 0.396 | Both Src and Fer associate with LRP6 and phosphorylate LRP6 directly.|Wnt3a treatment of cells enhances tyrosine phosphorylation of endogenous LRP6 and, mechanistically, Src reduces cell surface LRP6 levels and disrupts LRP6 signalosome formation. | SIGNOR-279289 |
P17252 | P15311 | 1 | phosphorylation | up-regulates | 0.547 | Phosphorylation of ezrin is required for both conformational activation and for signaling to downstream events. The activating c-terminal threonine phosphorylation on t567 was first described to be downstream of the rho pathway (matsui et al., 1998). Additional studies have implicated protein kinase c (pkc) in the phosphorylation of ezrin t567. | SIGNOR-133223 |
Q9UNH5 | Q16659 | 1 | dephosphorylation | down-regulates | 0.641 | Using ms analysis, we identified four novel phosphorylation sites, ser684, ser688, thr698 and ser705, located at the extreme c-terminus of erk3.alanine substitution of the four c-terminal phosphorylation sites markedly decreased the half-life of erk3 in mitosis, thereby linking phosphorylation to the stabilization of the kinase.we found that the phosphatases cdc14a and cdc14b (cdc is cell-division cycle) bind to erk3 and reverse its c-terminal phosphorylation in mitosis. | SIGNOR-164412 |
Q16539 | Q9UBK2 | 1 | phosphorylation | up-regulates | 0.586 | Cytokine stimulation of energy expenditure through p38 map kinase activation of ppargamma coactivator-1we show here that many cytokines activate the transcriptional ppar gamma coactivator-1 (pgc-1) through phosphorylation by p38 kinase, resulting in stabilization and activation of pgc-1 proteinp38 mapk directly phosphorylates pgc-1 on residues threonine 262, serine 265, and threonine 298 | SIGNOR-112774 |
P25105 | P08754 | 2 | binding | up-regulates activity | 0.2 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-257174 |
P53355 | P46821 | 2 | binding | up-regulates | 0.262 | Dapk-1 interacts with the microtubule-associated protein map1b, in particular in conditions of amino-acid starvation. | SIGNOR-181305 |
P17252 | P09651 | 1 | phosphorylation | down-regulates | 0.2 | A survey of seven protein kinases showed that a1 was heavily phosphorylated by protein kinase c (pkc) and also was phosphorylated by casein kinase iiamino acid sequencing revealed that these sites were ser95, ser192, and ser199;phosphorylation at ser192 was more abundant than at ser95 and ser199. Phosphorylation by pkc inhibited the strand annealing activity of a1. | SIGNOR-32291 |
Q9GZQ4 | Q5H8A3 | 2 | binding | up-regulates | 0.631 | Here we identify a novel neuropeptide of 36 amino-acid residues in rat brain as an endogenous ligand for the orphan g protein-coupled receptor fm-4/tgr-1, which was identified to date as the neuromedin u (nmu) receptor, and designate this peptide 'neuromedin s (nms)' because it is specifically expressed in the suprachiasmatic nuclei (scn) of the hypothalamus. | SIGNOR-133131 |
P16157 | O94856 | 0 | relocalization | up-regulates quantity | 0.685 | Neurofascin, L1, NrCAM, NgCAM, and neuroglian are membrane-spanning cell adhesion molecules with conserved cytoplasmic domains that are believed to play important roles in development of the nervous system. This report presents biochemical evidence that the cytoplasmic domains of these molecules associate directly with ankyrins, a family of spectrin-binding proteins located on the cytoplasmic surface of specialized plasma membrane domains. | SIGNOR-266718 |
Q2TAL8 | Q9UGM6 | 1 | 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-269411 |
O00230 | P31391 | 2 | binding | up-regulates | 0.65 | Cortistatin is known to bind all five cloned somatostatin receptors and share many pharmacological and functional properties with somatostatin including the depression of neuronal activity. | SIGNOR-82493 |
O95786 | Q7Z434 | 2 | binding | up-regulates activity | 0.937 | Initially, RIG-I and MDA5 sense dsRNA in the cytoplasm, produced as a by-product of RNA virus replication.Once one or both of these sensors are activated, they interact with a mitochondrial membrane protein called MAVS (mitochondrial antiviral) (also called IPS1, Cardif, and VISA). They signal to the mitochondrial membrane protein MAVS, which in turn activates the kinases TBK1 and IKKɛ. | SIGNOR-260139 |
Q92831 | Q71DI3 | 1 | acetylation | down-regulates activity | 0.2 | The HAT module within the SAGA and ADA complexes acetylates histone H3, mainly on residues K9 and K14. | SIGNOR-269626 |
P06493 | Q07820 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.461 | Mcl-1 is phosphorylated at two sites in mitosis, ser64 and thr92. Phosphorylation of thr92 by cyclin-dependent kinase 1 (cdk1)-cyclin b1 initiates degradation of mcl-1 in cells arrested in mitosis by microtubule poisons. | SIGNOR-165867 |
Q99250 | Q8NEV1 | 0 | phosphorylation | up-regulates activity | 0.2 | We found that the ankyrin-binding motif of Na(v)1.2 that determines channel concentration at the AIS depends on a glutamate residue (E1111), but also on several serine residues (S1112, S1124, and S1126). We showed that phosphorylation of these residues by protein kinase CK2 (CK2) regulates Na(v) channel interaction with ankyrins. | inhibition of CK2 activity reduced sodium channel accumulation at the AIS of neurons. In conclusion, CK2 contributes to sodium channel organization by regulating their interaction with ankyrin G. | SIGNOR-275755 |
Q00613 | Q92630 | 0 | phosphorylation | up-regulates activity | 0.318 | To test whether in a similar way DYRK2 phosphorylates and activates HSF1 in human cancer cells, we overexpressed DYRK2 and, by use of phosphospecific antibodies, we observed that the levels of endogenous HSF1 phosphorylated at S326 and S320 (two main phosphorylation events linked to HSF1 activation) were increased (Fig.\u00a0 xref ).|Together, these results show that DYRK2 phosphorylates HSF1 in cells and in vitro at S320 and also at S326, which is critical for HSF1 activation.Next, to test whether endogenous DYRK2 plays a role in HSF1 activation by proteotoxic stress, we used the prototypical HSF1 inducer heat shock (HS), in the absence or in the presence of harmine, observing that the inhibitor clearly impaired the phosphorylation of HSF1 upon HS (Fig S1F). | SIGNOR-278355 |
P0C0S8 | 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-265403 |
Q9ULU4 | P25440 | 0 | relocalization | up-regulates activity | 0.287 | ZMYND8 and BRD2 therefore work together to protect H4Ac domains from HDAC activity.|Further, when BRD2 was depleted, ZMYND8 accumulation was lost (Fig. 2e), indicating that either BRD2, or the underlying H4Ac, is required for ZMYND8 loading. | SIGNOR-262036 |
Q96T58 | P35548 | 2 | binding | up-regulates | 0.481 | Furthermore, in addition to msx2, both tlx1 and nkx2-5 proteins interacted with notch-pathway repressors, spen/mint/sharp and tle1/grg1, representing a potential mechanism for (de)regulation. | SIGNOR-188572 |
Q8IY84 | P30291 | 1 | phosphorylation | down-regulates activity | 0.48 | Furthermore, purified bacterially produced Nim1 kinase directly phosphorylates and inactivates Wee1 in vitro.|Phosphorylation and inactivation of the mitotic inhibitor Wee1 by the nim1 and cdr1 kinase. | SIGNOR-279238 |
Q9UQC2 | A7KAX9 | 1 | 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 |
Q5VT25 | Q9BZL4 | 1 | phosphorylation | down-regulates activity | 0.558 | Identification of the Phosphorylation Site of p85 on Threonine 560 by MRCKα-CAT | Wild-type p85 but not the mutant p85AA, when phosphorylated in vitro with MRCKα-CAT, showed significant reduction in the rate of MLC2 dephosphorylation. These results confirm a similar observation with MBS130 where phosphorylation of a conserved threonine 695 within a highly conserved motif was essential for the inhibition of phosphatase catalytic activity | SIGNOR-250724 |
P00519 | P78352 | 1 | phosphorylation | up-regulates activity | 0.441 | Moreover, c-Abl phosphorylates PSD-95 at tyrosine 533.|c-Abl modulates the synaptic contact number and PSD-95 clustering. | SIGNOR-278391 |
Q15208 | P17612 | 0 | phosphorylation | down-regulates activity | 0.295 | GSK-3β phosphorylated STK38 on residues S6 and T7 in vitro, depending largely on a PKA-mediated priming phosphorylation of STK38 on residues S10 and S11, respectively. Our results indicate that that GSK-3β inhibits STK38's full activation, and suggest that STK38 activation is required to prevent cell death in response to oxidative stress. | SIGNOR-276390 |
P49841 | P19838 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.388 | GSK-3 beta forms an in vivo complex with and specifically phosphorylates NF-kappa B1/p105 at Ser-903 and Ser-907 in vitro. GSK-3 beta has a dual effect on p105: it stabilizes p105 under resting conditions and primes p105 for degradation upon tumor necrosis factor (TNF)-alpha treatment. Indeed, constitutive processing of p105 to p50 occurs at a higher rate in cells lacking GSK-3 beta with respect to wild-type cells and can be reduced upon reintroduction of GSK-3 beta by transfection. S903A and S907A point mutations impair p105 proteolysis in response to TNF-α. | SIGNOR-251251 |
Q9UHD2 | P0DTD1-PRO_0000449624 | 2 | binding | down-regulates activity | 0.2 | We use unbiased screening to identify SARS-CoV-2 proteins that antagonize type I interferon (IFN-I) response. We found three proteins that antagonize IFN-I production via distinct mechanisms: nonstructural protein 6 (nsp6) binds TANK binding kinase 1 (TBK1) to suppress interferon regulatory factor 3 (IRF3) phosphorylation, nsp13 binds and blocks TBK1 phosphorylation, and open reading frame 6 (ORF6) binds importin Karyopherin α 2 (KPNA2) to inhibit IRF3 nuclear translocation. the results indicate that (1) nsp6 binds to TBK1 without affecting TBK1 phosphorylation, but the nsp6/TBK1 interaction decreases IRF3 phosphorylation, which leads to reduced IFN-β production; and (2) nsp13 binds and inhibits TBK1 phosphorylation, resulting in decreased IRF3 activation and IFN-β production (Figure 2F). | SIGNOR-262510 |
P37840 | Q9H4B4 | 0 | phosphorylation | down-regulates activity | 0.319 | Polo-like kinase (plk) family (plk1, plk2, and plk3) phosphorylate alpha-syn and beta-syn specifically at ser-129 and ser-118, respectively. Polo-like kinase 2 (plk2) phosphorylates alpha-synuclein at serine 129 in central nervous system. The membrane association of pd-linked mutant alpha -synuclein, but not wild-type -synuclein, was increased by serine 129 phosphorylation. | SIGNOR-189053 |
Q12968 | P45984 | 0 | relocalization | down-regulates | 0.711 | Jnks directly phosphorylate nuclear factor of activated t-cell (nfat) transcription factors, thus antagonizing the effects of calcium-regulated signaling through the protein phosphatase calcineurin. | SIGNOR-103360 |
Q12888 | Q99986 | 0 | phosphorylation | up-regulates | 0.399 | The kinase vrk1 is activated by dna double strand breaks induced by ionizing radiation (ir) and specifically phosphorylates 53bp1 in serum-starved cells./ Vrk1 knockdown resulted in the defective formation of 53bp1 foci in response to ir both in number and size | SIGNOR-197625 |
P33981 | P10636 | 1 | phosphorylation | up-regulates activity | 0.2 | Fig. 6C-1 shows that the GST-TTK fusion protein phosphorylated both tau and tubulin, but the phosphorylating activity on tau was much higher than that on tubulin. | SIGNOR-279132 |
P12931 | P51812 | 1 | phosphorylation | up-regulates | 0.355 | Together, our findings suggest that src-dependent phosphorylation at tyr-529 facilitates inactive erk binding to rsk2, which might be a general requirement for rsk2 activation by egf through the mek/erk pathway. | SIGNOR-160052 |
Q9H2X3 | P59594 | 2 | binding | up-regulates activity | 0.2 | Here we show that DC-SIGN and DC-SIGNR enhance infection mediated by the glycoprotein (GP) of Marburg virus (MARV) and the S protein of severe acute respiratory syndrome coronavirus and might promote viral dissemination. | SIGNOR-260269 |
P28482 | Q8IZP0 | 1 | phosphorylation | up-regulates | 0.445 | Our mass spectrometry also identified abi1 s183 and s225 on abi1 (numbering corresponds to abi1 isoform 1) as sites phosphorylated on endogenous protein and in the wildtype erk-dependent in vitro phosphorylated sample. these data indicate erk phosphorylation of abi1 is required for basal and egf-induced wrc interaction with the wrp2/3 complex. | SIGNOR-172873 |
Q8IVS8 | P27361 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.2 | Mechanistically, glucose deprivation-activated ERK1 phosphorylates GLYCTK2 at serine 220 directly, which prevents STUB1 (ubiquitin E3 ligase) binding, thereby abrogating the ubiquitination and degradation of GLYCTK2. ERK1 phosphorylates GLYCTK2 at S220 to promotes its stability | SIGNOR-280257 |
P24941 | P05067 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.267 | These include a significant increase in APP phosphorylation at Thr 668 by cdk2, cdk4, and cdk5, which increases its beta-amyloid production and APP proteolysis by the activated caspases during cell cycle ( xref ; xref ; xref ; xref ). | SIGNOR-280210 |
Q9Y5I2 | Q9Y5H0 | 2 | binding | up-regulates activity | 0.2 | The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion. They also form oligomers with Pcdh-gamma proteins at the same membrane sites. | SIGNOR-265699 |
Q13043 | Q15424 | 1 | phosphorylation | down-regulates activity | 0.2 | In the present study, we demonstrate that the chromatin scaffold protein SAFB1 interacts with and is phosphorylated by MST1 and is a novel regulator of AR capable of integrating signaling between the AR and MST1 networks. | SIGNOR-279296 |
Q9NZJ5 | Q15382 | 2 | binding | down-regulates activity | 0.2 | Rheb GTPase directly binds and activates PERK in vitro | SIGNOR-260873 |
Q86YJ5 | Q9BV40 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | MARCH9, a member of the RING-CH family of transmembrane E3 ubiquitin ligases, down-regulates CD4, major histocompatibility complex-I (MHC), and ICAM-1 in lymphoid cells. To identify novel MARCH9 substrates, we used high throughput flow cytometry and quantitative mass spectrometry by stable isotope labeling by amino acids in cell culture (SILAC) to determine the differential expression of plasma membrane proteins in a MARCH9-expressing B cell line. This combined approach identified 13 potential new MARCH9 targets. | SIGNOR-271531 |
P18031 | P08581 | 1 | dephosphorylation | down-regulates activity | 0.637 | It has been reported that the protein tyrosine phosphatase PTP1B could inactivate MET by direct dephosphorylation of Tyr 1234 and 1235 in its activation loop, and that this dephosphorylation takes place in peri-nuclear region of the cell [ xref ]. | SIGNOR-277001 |
Q9H1Y0 | P49411 | 2 | binding | down-regulates activity | 0.423 | PINK1 interacts with the autophagy effector TUFm and phosphorylates TUFm at Ser222. These results indicated that p222-hTUFm sequestered more monomer Atg5 and reduced the conjugated Atg5-Atg12 complex to subdue mitophagy. | SIGNOR-266383 |
P63096 | P29275 | 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-257039 |
O95837 | P34995 | 2 | binding | up-regulates activity | 0.435 | 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-257194 |
Q15391 | P09471 | 2 | binding | up-regulates activity | 0.248 | 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-257002 |
P15311 | P12931 | 0 | phosphorylation | up-regulates | 0.648 | Src phosphorylates ezrin at tyrosine 477 and induces a phosphospecific association between ezrin and a kelch-repeat protein family member | SIGNOR-132907 |
P63092 | P48546 | 2 | binding | up-regulates activity | 0.444 | The GPCRs are allocated in five families where the GLP-1R and GIPR are found within the secretin family, also classified as class B [31,32]. Upon stimulation by an extracellular stimuli (ligand), GPCRs undergo conformational changes, and triggers downstream intracellular signals by coupling with G proteins (or other intracellular proteins such as arrestins), causing a wide range of both physiological and pathological processes.To stimulate insulin secretion, and in the presence of elevated blood glucose concentrations, GLP-1R activation in pancreatic beta cells promote recruitment and activation of Gαs protein leading to adenylate cyclase-mediated cAMP production, elevation of Ca2+, and ERK1/2 phosphorylation (Fig. 3) | SIGNOR-278138 |
P49841 | P20393 | 1 | phosphorylation | up-regulates | 0.282 | We show here that gsk3beta phosphorylates and stabilizes the orphan nuclear receptor rev-erbalpha, a negative component of the circadian clock. | SIGNOR-144570 |
P07197 | Q00535 | 0 | phosphorylation | down-regulates quantity | 0.42 | Converse to the effect of PKA overexpression, overexpression of CDK5 and its activator, p35, decreased the association between spinophilin and NF-M as well as the expression of NF-M.|Moreover, CDK5 phosphorylates NF-M [ xref ], and this was also apparent in our data, given a dramatic molecular weight shift in the NF-M band following CDK5 overexpression. | SIGNOR-279683 |
P19793 | P45983 | 0 | phosphorylation | down-regulates activity | 0.464 | Under stress conditions, hyperphosphorylated by activated jnk on ser-56, ser-70, thr-82 and ser-260. These findings indicate that inflammation-mediated cell signaling leads to rapid and profound reductions in nuclear rxralpha levels, via a multistep, jnk-dependent mechanism involving ser260, nuclear export, and proteasomal degradation. | SIGNOR-145297 |
O43164 | P17612 | 0 | 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 |
P31751 | Q13835 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.267 | Akt2 phosphorylates PKP1 in vitro. Phosphorylated PKP1 is more resistant to degradation. PKP1 phosphorylation sites identified by peptide microarray analyses and mass spectrometry. | SIGNOR-273494 |
Q9UPP1 | Q12834 | 2 | binding | down-regulates quantity by destabilization | 0.339 | We showed that PHF8 interacts with the CDC20-containing APC (APC(cdc20)) primarily during mitosis. we demonstrate that mutations of the LXPKXLF motif abrogate polyubiquitylation of PHF8 by the APC. APC substrates are typically cell cycle regulators, and consistent with this, the loss of PHF8 leads to prolonged G2 phase and defective mitosis. | SIGNOR-272879 |
Q9UER7 | O43791 | 0 | ubiquitination | down-regulates quantity | 0.483 | These results suggest that SPOP/Cul3-ubiquitin ligase plays an essential role in the control of Daxx level and, thus, in the regulation of Daxx-mediated cellular processes, including transcriptional regulation and apoptosis. | SIGNOR-268858 |
Q13772 | P10275 | 2 | binding | up-regulates | 0.86 | We demonstrated that ara70 and ar physically interact and that ara70 can function as an androgen-dependent coactivator for ar. | SIGNOR-67684 |
P10636 | Q9UQM7 | 0 | phosphorylation | down-regulates activity | 0.596 | We found that when tau was first phosphorylated by A-kinase, C-kinase, cdk5, or CaM kinase II and then by GSK-3, its binding to microtubules was inhibited by 45, 61, 78, and 79%, respectively. Further, the kinase combinations cdk5/GSK-3 and CaM kinase II/GSK-3 rapidly phosphorylated the sites Thr 231 and Ser 235. When these sites were individually replaced by Ala and the phosphorylation experiments repeated, tau binding to microtubules was inhibited by 54 and 71%, respectively. By comparison, when Ser 262 was replaced by Ala, tau binding to microtubules was inhibited by only 8% after phosphorylation by CaM kinase II. | SIGNOR-249315 |
Q9UI47 | P14923 | 1 | relocalization | up-regulates quantity | 0.484 | Overexpression of CTNNA3 in a CTNNA1 negative colon carcinoma cell line resulted in the reassembly of the adherens and tight junctions through the recruitment of CTNNA3 interacting partners such as E-cadherin, β-catenin, plakoglobin, and ZO-14 | SIGNOR-265494 |
O43521 | P53779 | 0 | phosphorylation | up-regulates activity | 0.689 | JNKs specifically phosphorylate BIMEL at Ser55, 65, and/or 73. several observations demonstrate that the phosphorylation of BIMEL is a physiologically important mechanism for enhancing its proapoptotic activity. | SIGNOR-250130 |
O00141 | Q9UN36 | 1 | phosphorylation | up-regulates | 0.395 | Sgk1 phosphorylated ndrg2 at thr330, ser332 and thr348 in vitro. for example, the phosphorylation of thr330 or ser332 by sgk1 may prime ndrg2 for phosphorylation by gsk3 at ser326 and ser328 respectively, for example, the phosphorylation of thr330 or ser332 by sgk1 may prime ndrg2 for phosphorylation by gsk3 at ser326 and ser328 respectively, the phosphorylation of thr348 by sgk1 may prime for phosphorylation at ser344 | SIGNOR-129676 |
O14640 | Q9ULV1 | 2 | binding | up-regulates activity | 0.598 | Through study of FZD4 and its associated ligand Norrin, we report that a minimum of three residues distal to the KTXXXW motif in the C-terminal tail of Frizzled-4 are essential for DVL recruitment and robust Lef/Tcf-dependent transcriptional activation in response to Norrin. | SIGNOR-258955 |
Q8IWI9 | P61244 | 2 | binding | up-regulates activity | 0.57 | the role MAX plays in transcription is thought to be primarily as a cofactor for DNA binding. In this capacity, however, it appears to be essential for most, if not all, the known biological activities of MYC. MAX also functions as a cofactor for DNA binding for a group of bHLHZip proteins related to MYC, including MNT, MXD1-4 (formerly Mad1, Mxi1, Mad3 and Mad4), and MGA. Like MYC, these proteins do not homodimerize and appear to be incapable of binding DNA on their own, but when bound to MAX, they recognize E-box sequences. | SIGNOR-240261 |
P54274 | P53350 | 0 | phosphorylation | up-regulates | 0.373 | Plk1 phosphorylation of trf1 is essential for its binding to telomeres | SIGNOR-179461 |
Q12906 | P05771 | 0 | phosphorylation | up-regulates activity | 0.2 | Upon T cell activation, NF90 translocates from the nucleus into the cytoplasm, where it binds to the AU-rich element-containing 3' untranslated regions of IL-2 mRNA and stabilizes it.|Our results support a model in which PMA stimulation activates PKCβI to phosphorylate NF90-Ser647, and this phosphorylation triggers NF90 relocation to the cytoplasm and stabilize IL-2 mRNA. | SIGNOR-168173 |
P12931 | Q13905 | 1 | phosphorylation | up-regulates | 0.671 | C3g is activated upon phosphorylation at tyrosine 504 c3g is phosphorylated in vivo on y504 upon coexpression with src or hck, two members of the src family tyrosine kinases. | SIGNOR-128273 |
P17612 | P29474 | 1 | phosphorylation | up-regulates | 0.399 | Recently many investigators have shown that protein phosphorylation of enos by several serine/threonine kinases is a critical control step for no production by endothelial cells. Phosphorylation by amp kinase, akt (or protein kinase b), or protein kinase aon serine 1179 (bovine) or serine 1177 (human) of enos leads to enhanced activity of the enzyme and, thus, augmented production of no. | SIGNOR-112371 |
P19447 | Q96ME1 | 2 | binding | down-regulates quantity by destabilization | 0.2 | These results led us to propose a model that spironolactone may trigger the phosphorylation of XPB at Ser90 by CDK7, which promotes the recognition and polyubiquitination of XPB by SCFFBXL18 for proteasomal degradation. | SIGNOR-277434 |
P50148 | P47901 | 2 | binding | up-regulates activity | 0.435 | 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-257264 |
P03372 | P23443 | 0 | phosphorylation | up-regulates | 0.595 | Serine 167 is the major phosphorylation site on the human estrogen receptor. Phosphorylation is mediated by casein kinase ii. | SIGNOR-34117 |
Q92949 | Q5JVL4 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.356 | FOXJ1 expression in basal cells induced the expression of a panel of cilia-associated genes, including centrin 2 (CETN2); dynein, axonemal, heavy chain 11 (DNAH11); dynein, axonemal, intermediate chain 1 (DNAI1); dynein, axonemal, light intermediate chain 1 (DNALI1); EF-hand domain, C-terminal, containing 1 (EFHC1); sperm associated antigen 6 (SPAG6); tektin 1 (TEKT1), TEKT2 and tubulin, alpha 1a (TUBA1A; Figure 3C and Additional file 2: Table S1). | SIGNOR-266934 |
Q9Y4K3 | Q92985 | 1 | ubiquitination | up-regulates activity | 0.732 | We have shown that TRAF6 E3 ligase promotes IRF7 K63-linked ubiquitination that is required for EBV LMP1 activation of IRF7 [ xref ]; however, A20, a member with both E3 ligase and deubiquitinase activities in the OTU family, inhibits LMP1-stimulated IRF7 activity by acting as a deubiquitinase [ xref ]. | SIGNOR-278788 |
Q9UKL3 | P19838 | 2 | binding | up-regulates | 0.246 | In addition, both cleavage products of c-flip turned out to be inducers of nf-kb activity by binding to the ikk complex. | SIGNOR-177104 |
P98161 | Q8IUQ4 | 2 | binding | up-regulates activity | 0.333 | Full-length PC1 bound, stabilized and colocalized with Jade-1 and inhibited Jade-1 ubiquitination. Jade-1 ubiquitination was mediated by Siah-1, an E3 ligase that binds PC1. | SIGNOR-272916 |
Q9Y2I2 | Q9HCJ2 | 2 | binding | up-regulates activity | 0.772 | The NGL (netrin-G ligand; LRRC4) family of synaptic cell adhesion molecules belongs to the superfamily of leucine-rich repeat (LRR) proteins. The three known members of the NGL family, NGL-1, NGL-2, and NGL-3, are mainly localized to the postsynaptic side of excitatory synapses, and interact with the presynaptic ligands, netrin-G1, netrin-G2, and LAR, respectively. | SIGNOR-264047 |
Q93008 | P19544 | 1 | deubiquitination | up-regulates quantity by stabilization | 0.2 | Here, we find that CDC14B antagonizes CDK1-mediated activating mitotic phosphorylation of the deubiquitinase USP9X at serine residue 2563, which we show to be essential for USP9X to mediate mitotic survival. Starting from an unbiased proteome-wide screening approach, we specify Wilms' tumor protein 1 (WT1) as the relevant substrate that becomes deubiquitylated and stabilized by serine 2563-phosphorylated USP9X in mitosis. | SIGNOR-275614 |
P04637 | Q9H0F5 | 0 | ubiquitination | down-regulates activity | 0.363 | Here we demonstrate that RNF38 is a functional ubiquitin protein ligase (E3). We show that RNF38 isoform 1 is localized to the nucleus by a bipartite nuclear localization sequence (NLS). We confirm that RNF38 is a binding partner of p53 and demonstrate that RNF38 can ubiquitinate p53 in vitro and in vivo. Finally, we show that overexpression of RNF38 in HEK293T cells results in relocalization of p53 to discrete foci associated with PML nuclear bodies. | SIGNOR-272130 |
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