IdA stringlengths 6 21 | IdB stringlengths 6 21 | labels float64 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 |
|---|---|---|---|---|---|---|---|
Q9NY61 | Q07812 | 1 | 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 |
P47900 | Q03113 | 1 | 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-257394 |
P20339 | Q9GZQ3 | 1 | binding | up-regulates activity | 0.2 | The N terminus of COMMD5 binds to the endosomal Rab5, and its C terminus, including the COMMD domain, binds to the cytoskeletal scaffolding. | SIGNOR-261691 |
P17612 | Q9NRD9 | 1 | phosphorylation | up-regulates | 0.2 | We analyzed the duox1 phosphorylation state with an anti-rxx(ps/pt) antibody that could potentially recognize phosphorylation on ser955 and ser1217 but not on thr1007. duox1 but not duox2 activity is stimulated by forskolin (ec50 = 0.1 _m) via protein kinase a-mediated duox1 phosphorylation on serine 955. duox1 is positively regulated by the camp-dependent protein kinase a (pka)6 cascade | SIGNOR-183449 |
Q8IZL9 | Q15910 | 1 | phosphorylation | up-regulates activity | 0.2 | In addition to the transcriptional feedback loop, we also identified a feed-forward loop in which CCRK induces EZH2 phosphorylation, thereby promoting p-EZH2 Ser21 -AR physical interaction for CCRK promoter co-occupancy and transcriptional activation. | SIGNOR-279017 |
Q96GD4 | P68431 | 1 | phosphorylation | down-regulates activity | 0.2 | Histone code pathway involving h3 s28 phosphorylation and k27 acetylation activates transcription and antagonizes polycomb silencingaurora-b phosphorylates histone h3 at serine28 with regard to the mitotic chromosome condensation | SIGNOR-171717 |
P22612 | Q6PIY7 | 1 | phosphorylation | down-regulates activity | 0.2 | We found that Gld2 activity is regulated by site-specific phosphorylation in its disordered N-terminal domain. We identified two phosphorylation sites (S62, S110) where phosphomimetic substitutions increased Gld2 activity and one site (S116) that markedly reduced activity. Using mass spectrometry, we confirmed that HEK 293 cells readily phosphorylate the N-terminus of Gld2. We identified protein kinase A (PKA) and protein kinase B (Akt1) as the kinases that site-specifically phosphorylate Gld2 at S116, abolishing Gld2-mediated nucleotide addition. | SIGNOR-259404 |
O14965 | P68431 | 1 | phosphorylation | up-regulates activity | 0.2 | Phosphorylation at ser-11 (h3s10ph) by aurkb is crucial for chromosome condensation and cell-cycle progression during mitosis and meiosis. Phosphorylation at ser-11 (h3s10ph) by aurkb is crucial for chromosome condensation and cell-cycle progression during mitosis and meiosis. | SIGNOR-98289 |
Q13434 | Q8IVH8 | 1 | ubiquitination | down-regulates quantity | 0.2 | MKRN4 ubiquitinated GLK at Lys650 residue.|Remarkably, MKRN4 overexpression induced GLK protein degradation in HEK293T cells and Jurkat T cells (figure 5A and B). | SIGNOR-278658 |
P01178-PRO_0000020496 | P01178-PRO_0000020495 | 1 | binding | up-regulates quantity | 0.2 | Neurophysins I and II (NPI and NPII) serve in the neurosecretory granules of the posterior pituitary as carrier proteins for the neurophyseal hormones oxytocin (OT) and vasopressin (VP), respectively, until the latter are released into blood. | SIGNOR-270351 |
Q02156 | O60716 | 1 | phosphorylation | down-regulates | 0.2 | We find that ctnnd1/p120ctn phosphorylation at serine 268 (p-s268) occurs in a strictly pkc_-dependent manner,serine/threonine phosphorylation of p120-ctn has been reported to affect the integrity of ajs [12], [24] and [25]. Xia et al. (2003) reported that several residues (ser122, ser252, ser268, ser288, thr310, ser312, ser873, and thr910) in p120ctn can be either phosphorylated or dephosphorylated upon pkc activation | SIGNOR-201600 |
Q96QT6 | Q04727 | 1 | binding | up-regulates activity | 0.2 | We have cloned and characterized a new member of the PHD zinc finger family called Pf1 that interacts with two global transcription corepressors: mSin3A and TLE. Pf1 interacts with TLE. The Groucho/TLE proteins are members of an abundant corepressor family, and we hypothesized that Pf1 might interact with TLE family members. Together, these data suggest that in the absence of interactions with mSin3A, Gal4-Pf1 (102–273 L212P/A216P)-dependent repression can be attributed to interaction with endogenous TLE. | SIGNOR-266989 |
P17252 | Q96AX2 | 1 | phosphorylation | down-regulates activity | 0.2 | We also show that Rab37 is phosphorylated by protein kinase Cα (PKCα) at threonine 172 (T172), leading to attenuation of its GTP-bound state, and impairment of the Rab37-mediated exocytosis of TIMP1, and thus reduces its suppression activity on lung cancer cell motility. | SIGNOR-273803 |
Q96QB1 | P35579 | 1 | binding | down-regulates activity | 0.2 | Our study has shown that Dlc1 interacts with non-muscle myosin heavy chain II-A (Myh9), plectin and spectrin proteins in different multiprotein complexes. Overexpression of Dlc1 led to increased phosphorylation of Myh9 protein and activation of Rac1 GTPase. Dlc1 interacts with phosphorylated Myh9 (Ser-1943). This association of Dlc1 with S1943 phosphorylated Myh9, suggests that Dlc1 may be involved in reduced Myh9 filament stability. | SIGNOR-269283 |
P62714 | Q13153 | 1 | dephosphorylation | down-regulates activity | 0.2 | Both sites were dephosphorylated with the same kinetics; the anti-Ser(P)198 antibody was subsequently used as it exhibited lower background staining. Direct comparison of PP2Cα with purified PP1 and PP2A lead us to conclude that at the same molar ratio PP2Cα was the most efficient in dephosphorylating PAK1 (Fig. 1D). In this case we monitored two autophosphorylation sites in the Pak1 N-terminal regulatory region (Ser57 and Ser198/203) using phosphospecific antibodies: both sites showed the same kinetics of inactivation. | SIGNOR-248600 |
P39900 | P02671 | 1 | cleavage | down-regulates quantity by destabilization | 0.2 | Matrix metalloproteinases collagenase-2, macrophage elastase, collagenase-3, and membrane type 1-matrix metalloproteinase impair clotting by degradation of fibrinogen and factor XII| We have now investigated the role of collagenase-2 (MMP-8), macrophage elastase (MMP-12), collagenase-3 (MMP-13), and membrane type 1-matrix metalloproteinase (MT1-MMP, MMP-14) in the degradation of fibrinogen and Factor XII of the plasma clotting system. |Fibrinogen was subjected to MMP-cleavage, and the resulting fragments were isolated. The amino acid sequences were determined by automated Edman degradation.|MMP-12 20ADSGEGD a-chain| 540FVSETESRG a-chain|433LVTSKGDK a-chain | SIGNOR-263622 |
Q13418 | Q13418 | 2 | phosphorylation | up-regulates activity | 0.2 | Although ilk has been shown to autophosphorylate serine 343 (s343) is in the hydrophobic motif fsf within the activation loop of the kinase domain and has previously been suggested to be the target of autophosphorylation (9). Mutation of serine 343 to alanine (s343a) resulted in the inability of ilk to stimulate phosphorylation of pkb/akt in cos cells (9). | SIGNOR-106838 |
O60502 | P17858 | 1 | deglycosylation | up-regulates activity | 0.2 | Our previous investigation on O-GlcNAcylation of PFK1 has demonstrated that O-GlcNAcylation inhibits PFK1 enzyme activity|In cells, a single set of antagonistic enzymes-O-GlcNAc transferase (OGT) and O-GlcNAc hydrolase are responsible for the addition and removal of GlcNAc moiety, respectively. | SIGNOR-267608 |
O14965 | O14965 | 2 | phosphorylation | up-regulates | 0.2 | The upstream pak1 kinase can phosphorylate aurora a at t288, autophosphorylation appears to be the essential mode of activation. Our experiments suggest that phosphorylation of t288 is important for regulation of the aurora2 kinase both for its activity and its stability | SIGNOR-205106 |
Q9HBM1 | Q9BRS2 | 1 | binding | up-regulates activity | 0.2 | This study demonstrates that SPC25 acts as a molecular scaffold, mediating SPC25/RIOK1/MYH9 complex formation and triggering the RIOK1‐mediated phosphorylation of MYH9 at Ser1943.Taken together, these results suggested that SPC25 increases MYH9 phosphorylation at Ser1943, enhancing the nuclear accumulation of MYH9 and consequently modulating the transcription of CTNNB1. | SIGNOR-278893 |
Q9HBM1 | P35579 | 1 | binding | up-regulates activity | 0.2 | This study demonstrates that SPC25 acts as a molecular scaffold, mediating SPC25/RIOK1/MYH9 complex formation and triggering the RIOK1‐mediated phosphorylation of MYH9 at Ser1943.Taken together, these results suggested that SPC25 increases MYH9 phosphorylation at Ser1943, enhancing the nuclear accumulation of MYH9 and consequently modulating the transcription of CTNNB1. | SIGNOR-278894 |
Q16584 | Q16584 | 2 | phosphorylation | up-regulates | 0.2 | These residues within the activation loop are critical for mlk-3 autophosphorylation and activation. In addition, when the thr277 and ser281 residues were mutated to negatively charged glutamic acid to mimic phosphorylated serine/threonine residues, the resulting mutants were fully functional, implying that these two residues may serve as the autophosphorylation sites. | SIGNOR-83407 |
P16104 | O60934 | 1 | binding | up-regulates | 0.2 | Nbs1 physically interacts with ?-H2ax to form nuclear foci at dna damage sites. The inhibition of this interaction by introduction of anti-?-H2ax antibody into cells abolishes nbs1 foci formation in response to dna damage. | SIGNOR-133020 |
O15550 | Q01543 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | Our findings reveal a dual role for UTX in suppressing acute myeloid leukaemia via repression of oncogenic ETS and upregulation of tumor suppressive GATA programs. several ETS transcription factors, including Elf4, Etv6, Erg, Fli1, Ets2, Spi1 and Elk3 were upregulated immediately after Utx loss in the preleukaemic phase | SIGNOR-260034 |
Q13554 | Q9UBS5 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | ERK1/2 and CaMKIIβ mediated phosphorylation of GABAB1 at serine 867 (S867) and threonine 872 (T872). We found that, in addition to CaMKIIβ, also ERK1/2 is involved in the degradation pathway of GABAB receptors under physiological and ischemic conditions. In contrast to our previous view, CaMKIIβ does not appear to directly phosphorylate S867. Instead, the data support a mechanism in which CaMKIIβ activates ERK1/2, which then phosphorylates S867 and T872 in GABAB1. | SIGNOR-277851 |
Q05655 | Q9UQ13 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | PKCalpha/delta phosphorylate Sur8 at Thr-71 and Ser-297, respectively. This phosphorylation is essential for polyubiquitin-dependent degradation of Sur8. | SIGNOR-275565 |
O14843 | P08754 | 1 | 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-256821 |
P62140 | Q00987 | 1 | dephosphorylation | up-regulates quantity by stabilization | 0.2 | Three phosphorylation sites identified are Ser342, Ser367, and Ser403. In the present study, we identify protein phosphatase 1 (PP1) as a negative regulator in the p53 signaling pathway. PP1 directly interacts with Mdmx and specifically dephosphorylates Mdmx at Ser367. The dephosphorylation of Mdmx increases its stability and thereby inhibits p53 activity. | SIGNOR-248577 |
P05771 | P16949 | 1 | phosphorylation | down-regulates | 0.2 | Op18 is multisite phosphorylated on four ser residues during mitosis;two of these ser residues, ser-25 and ser-38, are targets for cyclin-dependent protein kinases. our findings suggest that stathmin phosphorylation in reh6 cells could be in part mediated by pkc activation. | SIGNOR-50598 |
O60216 | P11308 | 1 | relocalization | down-regulates activity | 0.2 | Large-scale AML genome re-sequencing efforts have identified novel recurrently mutated genes, including the members of the cohesin complex (RAD21, SMC3, SMC1A, and STAG2), implicated in the pathogenesis of this disease.Using ATAC-seq, we determined that mutant cohesin lead to a state of elevated chromatin accessibility and higher predicted binding at transcription factor binding sites for ERG, GATA2, and RUNX1. Moreover, using ChIP-Seq, we formally demonstrated increased binding of GATA2 and RUNX1 to these sites. Finally, we demonstrated that knockdown of these three TFs in human HSPC can revert the differentiation block induced by mutant cohesin. These results support a model in which mutant cohesin impairs hematopoietic differentiation and enforces stem cell programs through the modulation of ERG, GATA2, and RUNX1 chromatin accessibility, expression, and activity. | SIGNOR-261515 |
P68400 | Q99808 | 1 | phosphorylation | up-regulates activity | 0.2 | These data suggest that inhibition of CK2-mediated phosphorylation at Ser254 had the same effect on transporter function as the actual loss of Ser254 in mENT1a, implying that this site is constitutively phosphorylated by CK2. | SIGNOR-276063 |
P36897 | Q96JC1 | 1 | binding | up-regulates activity | 0.2 | TLP interacts with TGF-β and activin receptors in vivo. Endogenous TLP associates with both active and kinase-deficient TGF-beta and activin type II receptors, but interacts with the common-mediator Smad4 only in the presence of TGF-beta/activin signaling. | SIGNOR-261375 |
P09619 | P34947 | 1 | phosphorylation | up-regulates activity | 0.2 | Purified GRK5 was tyrosine-phosphorylated by the wild-type PDGFRbeta to a stoichiometry of 0.8 mol phosphate/mol GRK5, an extent approximately 5 times greater than observed with a Y857F PDGFRbeta mutant that fails to phosphorylate exogenous substrates but autophosphorylates and activates Src normally.|We conclude that GRK5 tyrosyl phosphorylation is required for the activation of GRK5 by the PDGFRbeta, but not by the beta(2)-adrenergic receptor, and that by activating GRK5, the PDGFRbeta triggers its own desensitization. | SIGNOR-279642 |
Q96PU5 | Q9C0H2 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | Our data indicate that Nedd4-2 binds to two family members, TTYH2 and TTYH3, which contain consensus PY ((L/P)PXY) binding sites for HECT type E3 ubiquitin ligases, but not to TTYH1, which lacks this motif. Consistently, Nedd4-2 ubiquitinates both TTYH2 and TTYH3. Importantly, we have shown that endogenous TTYH2 and Nedd4-2 are binding partners and demonstrated that the TTYH2 PY motif is essential for these interactions. We have also shown that Nedd4-2-mediated ubiquitination of TTYH2 is a critical regulator of cell surface and total cellular levels of this protein. | SIGNOR-272633 |
Q8NFZ3 | P78352 | 1 | relocalization | up-regulates activity | 0.2 | Like NRXNs, NLGNs bind to intracellular PDZ-domain proteins, but in contrast to NRXNs, NLGNs bind to class I PDZ domains such as those contained in PSD95, a postsynaptic MAGUK protein65. PSD95 and its homologues are centrally involved in recruiting glutamate receptors at postsynaptic sites66. Similarly to CASK, PSD95 binds to intracellular adaptor proteins, and especially to GKAP (a protein that binds to the guanylate-kinase domain of PSD95), which, in turn, binds to SHANK proteins (Fig. 1b). A possible role of these interactions is to recruit postsynaptic adaptor proteins to the site of synaptic junctions. | SIGNOR-264190 |
Q13131 | P60891 | 1 | phosphorylation | down-regulates activity | 0.2 | We demonstrate here that glucose deprivation or hypoxia results in the AMPK-mediated phosphorylation of phosphoribosyl pyrophosphate synthetase 1 (PRPS1) S180 and PRPS2 S183, leading to conversion of PRPS hexamers to monomers and thereby inhibiting PRPS1/2 activity, nucleotide synthesis, and nicotinamide adenine dinucleotide (NAD) production. | SIGNOR-265729 |
O00410 | Q8TD84 | 1 | relocalization | up-regulates activity | 0.2 | DSCAM and DSCAML1 specifically interacted with the importin beta IPO5, whereas deletion of the identified NLSs abolished this specific interaction and suppressed nuclear translocation of the DSCAM/L1 ICDs in cell lines and cultured neurons. This suggests a direct role of IPO5 in the nuclear import of the DSCAM/L1 ICDs. | SIGNOR-264274 |
P0C6X7-PRO_0000037312 | O75348 | 1 | cleavage | down-regulates activity | 0.2 | Cleavage of the V-ATPase G1 fusion protein by SARS-CoV 3CLpro was found in this study (Fig. 3), implying that 3CLpro potentially cleaves the cellular V-ATPase G1, and affects the function of vacuolar H(+)-ATPase. Meanwhile, a significant intracellular acidification has been demonstrated in the 3CLpro-expressing cells (Fig. 4D). The result correlated well with previous reports in that V-ATPase-specific inhibitors cause acidic pHi [28], [29], and influences cell apoptosis | SIGNOR-260264 |
P32121 | Q92835 | 1 | binding | up-regulates activity | 0.2 | We identified a new adaptor beta-arrestin 2 that associates with phosphorylated TIGIT and mediates recruitment of inositol phosphatase SHIP1 through the ITT-like motif (Fig. 7). Finally, SHIP1 impairs TRAF6 autoubiquitination to abolish NF-kappaB activation, leading to inhibition of IFN- gamma production in NK cells. | SIGNOR-261428 |
Q86YJ5 | P15151 | 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-271530 |
Q96G91 | P63096 | 1 | 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-257060 |
Q96RU2 | P12830 | 1 | deubiquitination | up-regulates quantity by stabilization | 0.2 | Usp28 deubiquitylates and consequently stabilizes Claspin in response to DNA damage | SIGNOR-274057 |
P17612 | Q9GZU1 | 1 | phosphorylation | down-regulates | 0.2 | The stimulatory effect of h89 on mcoln1 function was not observed when ser(557) and ser(559) were mutated to alanine residues, indicating that these two residues are essential for pka-mediated negative regulation of mcoln1. | SIGNOR-158946 |
P68400 | Q06265 | 1 | phosphorylation | up-regulates | 0.2 | Indeed recombinant pmscl1 undergoes ck2-mediated phosphorylation in vitro at various serine residues, including serines 409 and 411, which reside within the phosphosim region. the exchange of hydrophobic core residues or serines 409 and 411 to alanine attenuates binding of sumo to the phosphosim-containing fragment of pmscl1 in a yeast two-hybrid assay | SIGNOR-184031 |
Q8IWT3 | Q9BQL6 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | M-phase-specific CDK1–cyclin B1 complex directly binds KIND1 and KIND2 and phosphorylates a conserved proline-directed CDK1 consensus motif in the flexible and intrinsically disordered loop of the F1 domain. This then results in the recruitment of the CUL9–FBXL10 complex, modification with K48-linked polyubiquitin chains and proteasomal degradation of KIND1 and KIND2. | SIGNOR-276718 |
Q9Y6X9 | Q9H0A0 | 1 | binding | up-regulates activity | 0.2 | MORC2 directly interacts with PARP1. MORC2 mediates the interaction between PARP1 and NAT10 and thereby promotes NAT10-mediated PARP1 acetylation at K949, which blocks CHFR-mediated ubiquitination and degradation of PARP1. | SIGNOR-273716 |
P04201 | P21333 | 1 | binding | up-regulates activity | 0.2 | We further determined that GPCRs, AT1R, and MAS directly recruited FLNa and promoted its phosphorylation by cellular S/T kinases in an agonist-dependent manner. Our studies thus provide a structural framework for filamin in GPCR signaling, potentially regulating a variety of cellular responses. MAS likely binds filamin constitutively and hence leads to constitutive filamin phosphorylation. These results emphasize that it is the active receptor that mediates filamin phosphorylation by PKA or other cellular S/T kinases | SIGNOR-260627 |
Q8TD08 | Q8TD08 | 2 | phosphorylation | up-regulates | 0.2 | Erk8 (extracellular-signal-regulated protein kinase 8) expressed in escherichia coli or insect cells was catalytically active and phosphorylated at both residues of the thr-glu-tyr motif.Our results suggest that the activity of erk8 in transfected hek-293 cells depends on the relative rates of erk8 autophosphorylation | SIGNOR-142969 |
Q14934 | Q9Y625 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | NFAT transcriptionally regulates GPC6 induction in breast cancer cells and binds to three regulatory elements in the GPC6 proximal promoter. Expression of GPC6 in response to NFAT signalling promotes invasive migration, whereas GPC6 silencing with shRNA (small-hairpin RNA) potently blocks this phenotype. | SIGNOR-264023 |
O15393 | P14210 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | we identified pro-hepatocyte growth factor (HGF) as a TMPRSS2 substrate and confirmed that HGF and it’s cognate receptor c-Met are activated in prostate cancers expressing TMPRSS2, a finding that also associated with the acquisition of a pro-invasive mesenchymal gene expression program. | SIGNOR-263657 |
Q05513 | O43315 | 1 | phosphorylation | up-regulates | 0.2 | Wt-pkc_-mediated phosphorylation of wt aqp9 in vitro. In the experiments, substitution of ser11 to ala markedly inhibited phosphorylation. the s11a mutation in fibroblasts caused a smoother cell periphery with fewer aqp9-induced filopodia | SIGNOR-176278 |
O15297 | P16104 | 1 | dephosphorylation | down-regulates | 0.2 | Wild-type p53-induced phosphatase 1 dephosphorylates histone variant gamma-h2ax and suppresses dna double strand break repair. Here, we demonstrate that the wild-type p53-induced phosphatase 1 (wip1) also dephosphorylates gamma-h2ax at serine 139 in vitro and in vivo. | SIGNOR-163693 |
Q9UPC5 | P09471 | 1 | 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-256967 |
Q15751 | P62195 | 1 | ubiquitination | down-regulates quantity | 0.2 | HERC1 interacts with and ubiquitinates nascent PSMC5.|PSMC5 produced in the absence of PAAF1 is presumably misfolded (consistent with its aggregation in the PURE system), triggering PSMC5 degradation by a HERC1-independent pathway. | SIGNOR-278812 |
Q8N4C8 | Q15797 | 1 | phosphorylation | down-regulates activity | 0.2 | Msn kinases directly phosphorylate α-helix 1 of Smad. we have identified Misshapen (Msn) and the mammalian orthologs TNIK, MINK1, and MAP4K4 as the kinases responsible for α-helix 1 phosphorylation. | SIGNOR-276336 |
P43405 | O14986 | 1 | phosphorylation | down-regulates activity | 0.2 | We identified spleen tyrosine kinase (Syk), which is activated by oxidants, as a candidate PIP5Kbeta kinase in this pathway, and mapped the oxidant-sensitive tyrosine phosphorylation site to residue 105. The PIP5KbetaY105E phosphomimetic is catalytically inactive and cytosolic, whereas the Y105F non-phosphorylatable mutant has higher intrinsic lipid kinase activity and is much more membrane associated than wild type PIP5Kbeta. | SIGNOR-276227 |
P00519 | Q04760 | 1 | phosphorylation | up-regulates activity | 0.2 | We show that Glo1 activity is promoted by phosphorylation on Tyrosine 136 via multiple kinases. Glo1 Y136 is phosphorylated by multiple different kinases including all members of the Src family. Depletion of multiple different kinases led to a partial reduction in Glo1(Y136) phosphorylation. These included members of the Src family (Src, Yes1, FGR, and the related Abl1), and of the FAK, EPHA, FGFR, and VEGFR families (Figure 2B), suggesting phosphorylation of Glo1 on Y136 by multiple different kinases. In vitro kinase assays revealed that all the members of the Src family, as well as Epha5 and VEGFR3, can efficiently phosphorylate recombinant Glo1 on Y136 (Figure 2C–D). | SIGNOR-276187 |
P42684 | P42684 | 2 | phosphorylation | up-regulates quantity by stabilization | 0.2 | The results show that Arg is stabilized in response to 0.1 mM H2O2 by autophosphorylation of Y-261, consistent with involvement of the Arg kinase function in regulating Arg levels. The results further demonstrate that c-Abl-mediated phosphorylation of Arg on Y-261 similarly confers Arg stabilization.. These findings indicate that abrogation of the Arg kinase function by the Y261F mutation is dependent on phosphorylation of the Y-439 site. | SIGNOR-276033 |
P51608 | P18031 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | In this study, we have demonstrated that the PTPN1 gene, which encodes PTP1B, was a direct target of MECP2 and that PTP1B protein levels were dramatically increased in Mecp2-mutant mice and in fibroblasts derived from patients with RTT. | SIGNOR-264546 |
P17612 | O75899 | 1 | phosphorylation | down-regulates activity | 0.2 | Here we show that the functional coupling of GABA(B)R1/GABA(B)R2 receptors to inwardly rectifying K(+) channels rapidly desensitizes. This effect is alleviated after direct phosphorylation of a single serine residue (Ser892) in the cytoplasmic tail of GABA(B)R2 by cyclic AMP (cAMP)-dependent protein kinase (PKA). | SIGNOR-263150 |
Q9Y2H1 | Q9Y2H1 | 2 | phosphorylation | up-regulates | 0.2 | Ndr1/ndr2 protein kinase is activated by phosphorylation on the activation loop phosphorylation site ser281/ser282 and the hydrophobic motif phosphorylation site thr444/thr442. Autophosphorylation of ndr is responsible for phosphorylation on ser281/ser282, whereas thr444/thr442 is targeted by an upstream kinase. Here we show that mst3, a mammalian ste20-like protein kinase, is able to phosphorylate ndr protein kinase at thr444/thr442. In vitro, mst3 selectively phosphorylated thr442 of ndr2, resulting in a 10-fold stimulation of ndr activity. | SIGNOR-142518 |
P48730 | P43629 | 1 | phosphorylation | up-regulates | 0.2 | In this study, we have mapped constitutive phosphorylation sites for casein kinases, protein kinase c, and an unidentified kinase on the kir cytoplasmic domain. Three of these phosphorylation sites are highly conserved in human inhibitory kir. Functional studies of the wild-type receptor and serine/threonine mutants indicated that phosphorylation of ser(394) by protein kinase c slightly suppresses kir3dl1 inhibitory function, and reduces receptor internalization and turnover. | SIGNOR-158125 |
Q9BXC1 | P38405 | 1 | 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-256900 |
P53779 | P54259 | 1 | phosphorylation | down-regulates activity | 0.2 | Dentatorubral-pallidoluysian atrophy protein is phosphorylated by c-jun nh2-terminal kinase. serine 734 of the drpla protein is a phospho-acceptor site by jnk. The phosphorylation may be coupled to the activation of a protease. The molecular size of drpla protein detected in the rat brain with the specific phosphopeptide antibody was 150_kda, which was slightly smaller than that expected from the sequence and the results with the human protein. The phosphorylated forms of ha-tagged human drpla gradually disappeared after osmotic treatment, | SIGNOR-102394 |
Q9Y463 | Q9Y463 | 2 | phosphorylation | up-regulates | 0.2 | Mirk kinase is activated by autophosphorylation on tyrosine at the y271/y273 site | SIGNOR-79810 |
P43146 | O00555 | 1 | null | up-regulates activity | 0.2 | DCC activation by a netrin-1 gradient creates a high-level [Ca2+]i gradient by triggering LCC activity and by stimulating the cAMP–PKA pathway, which further activates LCC in the plasma membrane (PM) and Ca2+ channels in the ER. | SIGNOR-268293 |
Q86UY5 | P49674 | 1 | binding | up-regulates quantity | 0.2 | We identified members of the FAM83 family of proteins as partners of CK1 in cells. All eight members of the FAM83 family (FAM83A–H) interacted with the α and α-like isoforms of CK1; FAM83A, -B, -E, and -H also interacted with the δ and ε isoforms of CK1. The intrinsic catalytic activity of CK1 is not affected by or required for the association of CK1 with FAM83 proteins. Our findings imply that the DUF1669 domains of FAM83 proteins anchor CK1 α, α-like, δ, and ε isoforms in specific subcellular compartments and potentially mediate their association with substrates. | SIGNOR-273761 |
P30153 | P10636 | 1 | dephosphorylation | down-regulates | 0.2 | Galpha12 directly interacts with pp2a: evidence for galpha12-stimulated pp2a phosphatase activity and dephosphorylation of microtubule-associated protein, tau. | SIGNOR-130136 |
Q13043 | P42336 | 1 | phosphorylation | down-regulates activity | 0.2 | MST1/2 and HGK inhibit catalytic activity of p110α through phosphorylation at T1061 | SIGNOR-277920 |
O43791 | Q27J81 | 1 | binding | down-regulates activity | 0.2 | SPOP acts as an adaptor protein of the CUL3-RBX1 E3 ubiquitin ligase complex that generally recruits substrates for ubiquitination and subsequent degradation. Here, we revealed that SPOP recognizes a Ser/Thr (S/T)-rich motif in the C-terminal region of INF2 and triggers atypical polyubiquitination of INF2. These ubiquitination modifications do not lead to INF2 instability, but rather reduces INF2 localization in ER and mitochondrially associated DRP1 puncta formation, therefore abrogates its ability to facilitate mitochondrial fission. It revealed that INF2 was ubiquitinated at least at 7 lysine residues (Fig 2I). Interestingly, 5 of 7 ubiquitin attachment sites are localized in a short stretch of sequence (amino acids 612–682) within the FH2 domain of INF2 (Fig 2J). | SIGNOR-272798 |
P42345 | O95163 | 1 | phosphorylation | up-regulates activity | 0.2 | Human ELP1 S1174 phosphorylation was triggered by insulin treatment, as shown by the specific phosphorylated (p)ELP1 (S1174) antibody, and addition of a phosphorylation-mutant variant of the ELP1 protein (ELP1(S1174A)) to ELP1-depleted BRAFV600E melanoma cells failed to rescue cell survival |In line with these findings, mTORC2 activity, but not mTORC1, was required for the insulin-induced phosphorylation of Elp1 S1174 | SIGNOR-275541 |
Q99986 | P16104 | 1 | phosphorylation | up-regulates activity | 0.2 | In response to DNA damage induced by ionizing radiation, histone H2AX is phosphorylated in Ser139 by VRK1. | SIGNOR-278370 |
O15552 | Q03113 | 1 | 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-257342 |
Q92831 | P84243 | 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-269620 |
P04629 | P04629 | 2 | phosphorylation | up-regulates | 0.2 | In vitro studies indicate that trka autophosphorylates at tyrosines 490, 670, 674, 675, and 785 | SIGNOR-47171 |
Q8IZL9 | Q9UPZ9 | 1 | phosphorylation | up-regulates | 0.2 | Recombinant cak1p phosphorylates thr-157 in the tdy motif of recombinant ick and activates its activity in vitro. | SIGNOR-138420 |
O43638 | P48023 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | As we expected, Fkhl18 suppressed, dose-dependently,human and mouseFasLpromoter in bovine vascularsmooth muscle cells | SIGNOR-261612 |
Q99683 | O14548 | 1 | phosphorylation | up-regulates activity | 0.2 | Phosphorylation of EB1 by ASK1 promotes the binding of EB1 to CLIP-170 and p150 glued. | SIGNOR-278341 |
P31751 | P55265 | 1 | phosphorylation | down-regulates activity | 0.2 | AKT-dependent phosphorylation of the adenosine deaminases ADAR-1 and -2 inhibits deaminase activity. Coimmunoprecipitation studies and in vitro kinase assays revealed that AKT-1, -2, and -3 interact with both ADAR1p110 and ADAR2 and phosphorylate these RNA editases. Using site-directed mutagenesis of suspected AKT phosphorylation sites, AKT was found to primarily phosphorylate ADAR1p110 and ADAR2 on T738 and T553, respectively | SIGNOR-276192 |
P19525 | Q9H3R0 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | In the absence of Wnt3a, protein kinase R phosphorylated KDM4C at Ser918, inducing KDM4C ubiquitination and degradation. | SIGNOR-277497 |
P49841 | O00159 | 1 | phosphorylation | up-regulates activity | 0.2 | Here, we report that at early G1 the glycogen synthase kinase 3\u03b2 phosphorylates and stabilizes Nuclear myosin 1c, allowing for Nuclear myosin 1c association with the chromatin. | SIGNOR-279184 |
P13674 | Q01581 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | In this study, we found that the prolyl 4-hydroxylase (P4H) subunit P4HA1 protects NPC cells from erastin-induced ferroptosis by activating HMGCS1, a key enzyme in the mevalonate pathway. Our results show that HMGCS1 and HMGCR are regulated by P4HA subunits at the transcriptional level (Fig. S4). | SIGNOR-279853 |
Q92520 | P42702 | 1 | binding | up-regulates activity | 0.2 | Interleukin-like EMT inducer (ILEI) a cytokine from the FAM3 family, also functions as a ligand for LIFR-gp130 heterodimer and mediates intracellular signal through STAT activation. | SIGNOR-277986 |
P16234 | P16234 | 2 | phosphorylation | up-regulates activity | 0.2 | We have identified two autophosphorylation sites, Tyr-988 and Tyr-1018, in the platelet-derived growth factor (PDGF) alpha-receptor carboxyl-terminal tail, which are involved in binding of phospholipase C-gamma (PLC-gamma). We conclude that phosphorylated Tyr-988 and Tyr-1018 in the PDGF α-receptor carboxyl-terminal tail bind PLC-γ, but this association leads to only a relatively low level of tyrosine phosphorylation and activation of PLC-γ. | SIGNOR-250252 |
Q04759 | P15407 | 1 | phosphorylation | up-regulates activity | 0.2 | PKCθ-induced phosphorylations, in part at T217 and T227 residues, strongly and specifically increased Fra-1 transcriptional activity through the stimulation of Fra-1 transactivation domain, without affecting JUN factors. | SIGNOR-260879 |
Q96QT6 | Q04724 | 1 | binding | up-regulates activity | 0.2 | We have cloned and characterized a new member of the PHD zinc finger family called Pf1 that interacts with two global transcription corepressors: mSin3A and TLE. Pf1 interacts with TLE. The Groucho/TLE proteins are members of an abundant corepressor family, and we hypothesized that Pf1 might interact with TLE family members. Together, these data suggest that in the absence of interactions with mSin3A, Gal4-Pf1 (102–273 L212P/A216P)-dependent repression can be attributed to interaction with endogenous TLE. | SIGNOR-266994 |
Q9NR19 | Q14457 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | As expected, we found that glucose deprivation induced the binding of TFEB (Figure S4C) and ACSS2 (Figure S4D) to the promoter regions of MAP1LC3B, ATG3, and WIPI-1 as well as mRNA (Figure 3H) and protein (Figure 3I) expression of these genes; | SIGNOR-276561 |
P55286 | Q14653 | 1 | transcriptional regulation | up-regulates quantity | 0.2 | CHD8 binds to histone H3 di- and trimethylated on lysine 4. It resides on the human U6 promoter as well as the mRNA IRF3 promoter in vivo and contributes to efficient transcription from both these promoters | SIGNOR-266898 |
P47710 | Q04206 | 1 | phosphorylation | up-regulates | 0.2 | Phosphorylation of serine 529 of p65 is mediated by casein kinase ii, but is prevented in nonstimulated cells by the interaction with ikba | SIGNOR-171222 |
P49840 | Q07869 | 1 | phosphorylation | up-regulates activity | 0.2 | GSK-3alpha phosphorylates PPARalpha at Ser280, located in the ligand binding domain.|These results suggest that GSK-3alpha positively regulates PPARalpha activity through Ser280 phosphorylation. | SIGNOR-278515 |
P51812 | O60825 | 1 | phosphorylation | up-regulates activity | 0.2 | Heart 6-phosphofructo-2-kinase activation by insulin results from ser-466 and ser-483 phosphorylation and requires 3-phosphoinositide-dependent kinase-1, but not protein kinase b. | SIGNOR-23753 |
P30411 | Q14344 | 1 | 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-257399 |
Q9C0A6 | P68431 | 1 | methylation | up-regulates activity | 0.2 | SETD5 Exhibits Intrinsic Methyltransferase Activity on H3K36. This assay showed that SETD5 has specific histone methyltransferase activity toward K36 but not for other residues such as K4 and K27 (Figure 8B). we revealed that SETD5 is endowed with H3K36 methyltransferase, which is necessary for RNA elongation and processing and, ultimately, correct gene transcription. | SIGNOR-264620 |
Q86UY5 | P48729 | 1 | binding | up-regulates quantity | 0.2 | We identified members of the FAM83 family of proteins as partners of CK1 in cells. All eight members of the FAM83 family (FAM83A–H) interacted with the α and α-like isoforms of CK1; FAM83A, -B, -E, and -H also interacted with the δ and ε isoforms of CK1. The intrinsic catalytic activity of CK1 is not affected by or required for the association of CK1 with FAM83 proteins. Our findings imply that the DUF1669 domains of FAM83 proteins anchor CK1 α, α-like, δ, and ε isoforms in specific subcellular compartments and potentially mediate their association with substrates. | SIGNOR-273748 |
P27361 | Q8NET8 | 1 | phosphorylation | up-regulates activity | 0.2 | We observed that ERK-mediated phosphorylation of TRPV3 alters its responsiveness to repeated chemical stimuli. Among several putative ERK phosphorylation sites, we identified threonine 264 in the N-terminal ankyrin repeat domain as the most critical site for the ERK-dependent modulation of TRPV3 channel activity. Of note, Thr264 is in close vicinity to a structurally and functionally important TRPV3 region comprising an atypical finger 3 and oxygen-dependent hydroxylation site. In summary, our findings indicate that Thr264 in TRPV3 is a key ERK phosphorylation site mediating EGFR-induced sensitization of the channel to stimulate signaling pathways involved in regulating skin homeostasis. | SIGNOR-273672 |
P55085 | P63096 | 1 | 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-256895 |
P68400 | P49321 | 1 | phosphorylation | down-regulates activity | 0.2 | Here, we show that somatic nuclear autoantigenic sperm protein (sNASP) binds to TRAF6 to prevent TRAF6 autoubiquitination in unstimulated macrophages. Following LPS stimulation, a complex consisting of sNASP, TRAF6, IRAK4, and casein kinase 2 (CK2) is formed. CK2 phosphorylates sNASP at serine 158, allowing sNASP to dissociate from TRAF6. Free TRAF6 is then autoubiquitinated, followed by activation of downstream signaling pathways. | SIGNOR-273627 |
Q9UEW8 | O95863 | 1 | phosphorylation | up-regulates activity | 0.2 | In this study, we found that STK39 also enhances SNAI1 stability by its phosphorylation at T203.|STK39 interacts with SNAI1 and phosphorylates SNAI1 on T203. | SIGNOR-279128 |
Q14004 | Q86VE9 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | In addition, CDK13-KD disrupted Nef downregulation of SERINC5 from the cell surface, whereas CDK12-KD did not (Figures 2D and 2E).|Thus, S360 phosphorylation increases interactions between Nef and SERINC5 and initiates the destruction of SERINC5 by the endocytic machinery.|Thus, we conclude that CycK/CDK13 phosphorylates the S360 residue of SERINC5. | SIGNOR-278918 |
Q9UIK4 | Q9UIK4 | 2 | phosphorylation | down-regulates activity | 0.2 | Autophosphorylation restrains the apoptotic activity of DRP-1 kinase by controlling dimerization and calmodulin binding. | It comprises a single autophosphorylation event mapped to Ser308 within the CaM regulatory domain. | SIGNOR-251084 |
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