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 |
|---|---|---|---|---|---|---|---|
Q9Y6C9 | P55957 | 1 | relocalization | up-regulates | 0.303 | Mtch2/mimp (mitochondrial carrier homologue 2/met-induced mitochondrial protein), a novel truncated bid (tbid)-interacting protein, is a surface-exposed outer mitochondrial membrane protein that facilitates the recruitment of tbid to mitochondria | SIGNOR-165081 |
Q8IW41 | Q9UKI8 | 0 | phosphorylation | up-regulates activity | 0.2 | We established that TLK1 phosphorylates MK5 on three residues (S160, S354 and S386), resulting in MK5 activation, and additionally, mobility shifts of MK5 also supported its phosphorylation by TLK1 in transfected HEK 293 cells. | SIGNOR-276747 |
Q13164 | Q00535 | 0 | phosphorylation | up-regulates activity | 0.2 | CDK5 directly phosphorylated ERK5 at Thr732 and modulated the ERK5\u2013AP-1 signaling axis. | SIGNOR-279364 |
Q15075 | Q9H8W4 | 2 | binding | up-regulates activity | 0.248 | In yeast two-hybrid analysis we identified Phafin2 as a novel interactor of the endosomal-tethering protein EEA1, and Phafin2 colocalized strongly with EEA1 in microdomains of the endosome membrane. Our results suggest that Phafin2 controls receptor trafficking and fluid-phase transport through early endosomes by facilitating endosome fusion in concert with EEA1. | SIGNOR-261276 |
P35226 | Q9Y243 | 0 | phosphorylation | up-regulates activity | 0.258 | the polycomb group silencing protein Bmi1 can be phosphorylated by AKT, which enhances its oncogenic potential in PCa. Overexpression of Bmi1 can act in combination with PTEN haploinsufficiency to induce invasive carcinogenic formation in the prostate | SIGNOR-249583 |
P29122 | P06213 | 1 | cleavage | up-regulates activity | 0.2 | Here we demonstrate that the two IR isoforms are similarly cleaved by furin, but when this furin-dependent maturation is inefficient, IR proforms move to the cell surface where the proprotein convertase PACE4 selectively supports IRB maturation. | SIGNOR-260366 |
P34903 | Q8TAB3 | 2 | binding | up-regulates quantity by stabilization | 0.2 | Here, we found that PCDH19 binds the alpha subunits of GABAAR and regulates its surface availability and currents in cultured hippocampal neurons. The PCDH19 gene (Xp22.1) encodes the cell-adhesion protein protocadherin-19 (PCDH19) and is responsible for a neurodevelopmental pathology characterized by female-limited epilepsy, cognitive impairment and autistic features, the pathogenic mechanisms of which remain to be elucidated. Here, we identified a new interaction between PCDH19 and GABAA receptor (GABAAR) alpha subunits in the rat brain. PCDH19 shRNA-mediated downregulation reduces GABAAR surface expression and affects the frequency and kinetics of miniature inhibitory postsynaptic currents (mIPSCs) in cultured hippocampal neurons. | SIGNOR-267222 |
P15036 | Q9UQM7 | 0 | phosphorylation | down-regulates | 0.2 | Camkii caused ets-2 phosphorylation.Serine 246, 310, and 313 were the targets. Camkii to phosphorylates ets-2, thus altering ets-2 binding to its downstream promoters | SIGNOR-183596 |
Q9HD67 | P43146 | 2 | relocalization | up-regulates quantity | 0.686 | Here, we provide evidence for the involvement of the unconventional myosin X (Myo X) in netrin-1 function. We find that Myo X interacts with the netrin receptor deleted in colorectal cancer (DCC) and neogenin, a DCC-related protein. Expression of Myo X redistributes DCC to the cell periphery or to the tips of neurites, whereas its silencing prevents DCC distribution in neurites. Moreover, expression of DCC, but not neogenin, stimulates Myo X-mediated formation and elongation of filopodia, suggesting that Myo X function may be differentially regulated by DCC and neogenin. | SIGNOR-268282 |
Q13233 | Q13158 | 1 | phosphorylation | down-regulates activity | 0.503 | The results clearly show that fadd phosphorylation at ser194 affects functions both upstream and downstream of the mekk1/mkk7/jnk1 pathway and is closely associated with chemosensitivity in prostate cancer cells | SIGNOR-123168 |
O60934 | Q14676 | 2 | binding | up-regulates | 0.834 | Mdc1 also undergoes phosphorylation by ck2 after dna damage to generate a phospho-motif on mdc1, which binds directly to nbs1. | SIGNOR-184141 |
P20339 | Q99698 | 2 | binding | down-regulates activity | 0.266 | Mauve interacts with Rab5, Msps, and gamma-tubulin|Mauve/LYST opposes Rab5, which promotes vesicle fusion affecting PCM recruitment | SIGNOR-266001 |
P20929 | O00401 | 2 | binding | up-regulates | 0.352 | Igf1-akt signaling, by inhibiting gsk3b, allows the interaction of n-wasp with the unphosphorylated nebulin;the consequent recruitment of n-wasp to the z-disk promotes actin nucleation and elongation of actin filaments. | SIGNOR-175671 |
P35790 | Q92993 | 0 | acetylation | up-regulates activity | 0.2 | Glucose deprivation induces the binding of choline kinase α2 (CHKα2) to lipid droplets, followed by a continuous PTMs to promote lipolysis of lipid droplets, which are in turn mediated by AMPK-dependent CHKα2 Serine 279 phosphorylation and KAT5-dependent CHKα2 Lysine 247 acetylation. | SIGNOR-267648 |
Q05655 | Q01543 | 1 | phosphorylation | down-regulates | 0.346 | We have previously demonstrated that in response to transforming growth factor _ (tgf_), fli-1 activity is repressed through a series of sequential posttranslational modifications, consisting of protein kinase c_ (pkc_)-induced thr312 phosphorylation, acetylation by p300/creb binding protein-associated factor, and detachment from the collagen promoter. | SIGNOR-172113 |
P35555 | O95967 | 2 | binding | down-regulates activity | 0.393 | Fibulin-4 and -5 are extracellular glycoproteins with essential non-compensatory roles in elastic fiber assembly. Both fibulins differentially bound N-terminal fibrillin-1, which strongly inhibited their binding to lysyl oxidase and tropoelastin. | SIGNOR-251860 |
P00519 | Q05086 | 1 | phosphorylation | down-regulates activity | 0.273 | Our results suggest that c-Abl protects p53 from HPV-E6-E6AP complex-mediated degradation by phosphorylating E6AP and impairing its E3 ligase activity | SIGNOR-260930 |
Q03113 | P31391 | 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-256959 |
P00533 | P0DP24 | 1 | phosphorylation | down-regulates | 0.345 | Phosphorylation of calmodulin by the epidermal-growth-factor-receptor tyrosine kinase. Phosphorylated calmodulin does not exhibit the characteristic ca2+ shift normally observed with calmodulin in electrophoretic gels, an observation that is consistent with this modification affecting the biological activity of the molecule. | SIGNOR-266319 |
Q01094 | P06400 | 2 | binding | down-regulates activity | 0.921 | E2f binds rb. E2f activation domain is the target for rb-induced repression. Rb can silence the 57 residue e2f activation domain. Rb can mask e2f residues involved in the activation process, possibly by mimicking a component of the transcriptional machinery | SIGNOR-37305 |
Q14209 | P06400 | 2 | binding | down-regulates | 0.914 | Cyclin-dependent kinase (cdk) phosphorylation of the retinoblastoma protein (rb) drives cell proliferation through rb complexes with e2f transcription factors and other regulatory proteins. | SIGNOR-197328 |
P84243 | O14647 | 0 | relocalization | up-regulates quantity | 0.2 | Non-homologous end-joining (NHEJ) is the dominant DSB repair pathway in human cells, but our understanding of how it operates in chromatin is limited. Here, we define a mechanism that plays a crucial role in regulating NHEJ in chromatin. This mechanism is initiated by DNA damage-associated poly(ADP-ribose) polymerase 1 (PARP1), which recruits the chromatin remodeler CHD2 through a poly(ADP-ribose)-binding domain. CHD2 in turn triggers rapid chromatin expansion and the deposition of histone variant H3.3 at sites of DNA damage. | SIGNOR-264527 |
P40763 | P42224 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.615 | In summary, we report in this study that STAT1 expression is upregulated by nuclear EGFR, EGFRvIII and HER2, and that STAT3 synergizes with the three receptors to further enhance STAT1 expression. These novel findings establish a novel link between the mitogenic ErbB signaling pathway and the inflammatory pathway mediated by STAT1. The oncogenic transcription factor STAT3 binds to the STAT1 promoter and synergizes with nuclear EGFR to significantly enhance STAT1 gene expression. | SIGNOR-263650 |
P08238 | O14727 | 2 | binding | down-regulates | 0.388 | The present studies demonstrate that heat shock protein 90 (hsp90) forms a cytosolic complex with apaf-1 and thereby inhibits the formation of the active complex. | SIGNOR-81043 |
P19235 | O60674 | 0 | phosphorylation | up-regulates activity | 0.812 | JAK2 in turn phosphorylates several tyrosine residues on the EpoR-cytosolic domain and probably on JAK2 itself that serve as docking sites for SH2 or protein tyrosine binding domains of downstream signal transduction proteins such as STAT5, phosphatidylinositol 3-kinase, Shc, and tyrosine phosphatases SHP1 and SHP2 | SIGNOR-251351 |
Q96LB2 | P19086 | 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-257326 |
Q5VWQ8 | P49841 | 2 | binding | up-regulates activity | 0.311 | DAB2IP activates GSK-3β and antagonizes Wnt-mediated EMT. GSK-3β appears to directly associate with DAB2IP. Because DAB2IP is not a phosphatase, the mechanism of GSK-3β activation by DAB2IP is likely mediated by a separate phosphatase associated within this complex. PP2A is critical for DAB2IP-mediated GSK-3β activation and MET responses. | SIGNOR-254752 |
Q9GZQ8 | Q96A56 | 2 | binding | up-regulates | 0.297 | Tp53inp1-lc3 interaction occurs via a functional lc3-interacting region (lir) | SIGNOR-196673 |
P19367 | P31749 | 2 | binding | up-regulates | 0.445 | The glucose dependence of the antiapoptotic effects of growth factors and akt plus a strong correlation between akt-regulated mitochondrial hexokinase association and apoptotic susceptibility suggest a major role for hexokinases in these effects. | SIGNOR-252495 |
Q14332 | Q9ULT6 | 0 | ubiquitination | down-regulates | 0.292 | Znrf3 is associated with the wnt receptor complex, and inhibits wntby promoting the turnover of frizzled and lrp6. | SIGNOR-197417 |
Q9Y6K9 | Q9BVN2 | 0 | null | up-regulates quantity by stabilization | 0.308 | NESCA interacts with the IKK complex by the N-terminal region of NEMO. This experiment revealed that the overexpression of NESCA completely abolished the TRAF6-mediated polyubiquitination of NEMO, as it appears by using either anti-HA (Fig. 5A) or anti-NEMO (Fig. 5B) antibodies on immunoprecipitated extracts. | SIGNOR-272775 |
P63092 | P21918 | 2 | binding | up-regulates activity | 0.482 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ‚â• -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ‚â• -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ‚â• -1.0. | SIGNOR-256771 |
P00441 | Q9NX47 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.2 | Mitochondrial ubiquitin ligase MITOL ubiquitinates mutant SOD1 and attenuates mutant SOD1-induced reactive oxygen species generation | SIGNOR-272982 |
P50148 | Q9H2D6 | 2 | binding | up-regulates activity | 0.2 | We show that the C-terminal Rho-specific DH-PH cassette of Trio is similarly activated by Galpha(q) | SIGNOR-256494 |
P47712 | Q16539 | 0 | phosphorylation | up-regulates activity | 0.668 | These results provide the first direct evidence that p38 kinase is responsible for cpla2 phosphorylation in sfllrn-stimulated platelets and is involved in the early phosphorylation of cpla2 in thrombin-stimulated platelets | SIGNOR-44673 |
Q08881 | P42680 | 1 | phosphorylation | up-regulates | 0.407 | Tec family protein tyrosine kinases (tfks) play a central role in hematopoietic cellular signaling. Initial activation takes place through specific tyrosine phosphorylation situated in the activation loop. Further activation occurs within the sh3 domain via a transphosphorylation mechanism. Here, we could confirm that y223 is the only site in the btk-sh3 domain being detectably phosphorylated | SIGNOR-98090 |
Q96SB3 | Q00535 | 0 | phosphorylation | down-regulates quantity | 0.396 | CDK5 decreased the expression of both spinophilin (30%) and neurabin (64%).|This suggests that CDK5 phosphorylation of spinophilin at Ser17 is not responsible for the CDK5 dependent increase in the spinophilin and PP1 association. | SIGNOR-279453 |
Q86UR5 | Q9UQM7 | 0 | phosphorylation | up-regulates | 0.347 | Two serine residues in rim1 (ser-241 and ser-287) and one serine residue in rim2 (ser-335) were required for 14-3-3 binding. Incubation with ca2+/calmodulin-dependent protein kinase ii greatly stimulated the interaction of recombinant n-terminal rim but not the s241/287a mutant with 14-3-3, | SIGNOR-103890 |
Q16566 | P16949 | 1 | phosphorylation | down-regulates | 0.49 | Serine 16 of oncoprotein 18 is a major cytosolic target for the ca2+/calmodulin-dependent kinase-gr. | SIGNOR-34743 |
P46531 | P24863 | 0 | phosphorylation | down-regulates | 0.48 | Purified recombinant cycc:cdk8 phosphorylates the notch icd within the tad and pest domains, and expression of cycc:cdk8 strongly enhances notch icd hyperphosphorylation and pest-dependent degradation by the fbw7/sel10 ubiquitin ligase in vivo. | SIGNOR-130592 |
P14635 | P38936 | 2 | binding | down-regulates | 0.829 | P21-mediated degradation of cyclin b1 in response to dna damage is necessary for the maintenance of g2 cell cycle arrest. | SIGNOR-183498 |
P10163 | Q96L73 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.342 | We here demonstrate that NSD1 could bind to the promoter regions of PRB4 and activate promoter activity by reducing the binding of H3K27me2 and increasing the binding of H3K36me2 on PRB4 promoter. | SIGNOR-268459 |
Q86X55 | Q01196 | 1 | methylation | down-regulates activity | 0.282 | We have found that PRMT4 is highly expressed in HSPCs, where it functions as an inhibitor of myeloid differentiation (Figure 7G). In these cells, PRMT4 methylates RUNX1 at R223, promoting the assembly of a DPF2-containing transcriptional co-repressive complex, and repressing transcription at the miR-223 locus. | SIGNOR-261967 |
P09651 | Q13148 | 0 | post transcriptional regulation | up-regulates | 0.406 | TDP-43 regulates the alternative splicing of hnRNP A1 to yield an aggregation-prone variant in amyotrophic lateral sclerosis | SIGNOR-262824 |
P12931 | Q13224 | 1 | phosphorylation | up-regulates activity | 0.559 | We have investigated the tyrosine phosphorylation of NMDA receptor subunits NR2A and NR2B by exogenous Src Phosphorylation-site specific antibodies identified NR2B Tyr1472 as a phosphorylation site for intrinsic PSD tyrosine kinases | SIGNOR-247180 |
Q9UPW6 | Q15797 | 0 | transcriptional regulation | up-regulates quantity | 0.2 | Chromatin immunoprecipitation (ChIP) revealed a subset of the BIG (BMP4 induced genes) signature, including Satb2, Smad6, Hand1, Gadd45γ and Gata3, that was bound by Smad1/5 in the developing mandible, revealing direct Smad-mediated regulation | SIGNOR-268934 |
Q15746 | Q05682 | 1 | phosphorylation | down-regulates | 0.641 | Phosphorylation of caldesmon by myosin light chain kinase increases its binding affinity for phosphorylated myosin filaments. | SIGNOR-166049 |
P10070 | Q6PHR2 | 0 | phosphorylation | up-regulates activity | 0.621 | We show that ULK3 is able to phosphorylate three mammalian GLI proteins in vitro | SIGNOR-260798 |
O00548 | P51608 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.2 | As the first step to reveal how MeCP2 phosphorylation may regulate Notch signaling, we conducted chromatin immunoprecipitation (ChIP) experiment to determine whether the phosphor-mutant MeCP2 protein has altered promoter occupancy at the promoters of Dll1 and Notch1. We found increased binding of the phosphor-mutant protein at the promoters of both Dll1 and Notch1 | SIGNOR-264674 |
Q96J02 | Q9UBN4 | 1 | ubiquitination | down-regulates activity | 0.35 | Ubiquitination of TRPV4 is dramatically increased by the HECT (homologous to E6-AP carboxyl terminus)-family ubiquitin ligase AIP4 without inducing degradation of this channel. Instead, AIP4 promotes the endocytosis of TRPV4 and decreases its amount at the plasma membrane. | SIGNOR-272624 |
Q9H6E5 | Q05655 | 0 | phosphorylation | up-regulates activity | 0.2 | PKCdelta associates with and directly phosphorylates Star-PAP. | SIGNOR-279385 |
Q01484 | P11532 | 1 | relocalization | up-regulates quantity | 0.53 | We present evidence for an ankyrin-based mechanism for sarcolemmal localization of dystrophin and beta-DG. Ankyrin-B thus is an adaptor required for sarcolemmal localization of dystrophin, as well as dynactin-4. | SIGNOR-266712 |
P50613 | P21127 | 1 | phosphorylation | up-regulates activity | 0.335 | We conclude that CDK7 phsphorylates Cdk11, dependent on the conserved Thr219 residue in the CDK11 T loop, and it is therefore likely to be a genuine Cdk11 activating kinase | SIGNOR-245871 |
Q15759 | P05787 | 1 | phosphorylation | up-regulates | 0.427 | Keratin 8 (k8) serine 73 occurs within a relatively conserved type ii keratin motif . Here we show that ser-73 is exclusively phosphorylated in vitro by p38 mitogen-activated protein kinase. The ser-73 --> ala-associated filament reorganization defect is rescued by a ser-73 --> asp mutation. Also, disease-causing keratin mutations can modulate keratin phosphorylation and organization, which may affect disease pathogenesis. | SIGNOR-114063 |
P06493 | Q96JH7 | 1 | phosphorylation | down-regulates activity | 0.537 | We clarified that VCIP135, an essential factor in both p97 membrane fusion pathways, is phosphorylated on Threonine-760 and Serine-767 by Cdc2 at mitosis and that this phosphorylated VCIP135 does not bind to p97. | SIGNOR-265038 |
P08922 | P18031 | 0 | dephosphorylation | down-regulates | 0.374 | In an approach to gain insight into the sequence-dependent dephosphorylation of multiple phosphotyrosyl-containing peptides by the phosphatases shp-1 and ptp1b, we applied a chromatographic technique for the analysis of the dephosphorylation products. | SIGNOR-154199 |
P15172 | P06400 | 2 | transcriptional regulation | up-regulates quantity by expression | 0.394 | Here we report that, at the onset of differentiation, activation by MyoD of the Rb, p21, and cyclin D3 genes occurs in the absence of new protein synthesis and with the requirement of the p300 transcriptional coactivator. | SIGNOR-238532 |
P35222 | P25054 | 2 | binding | down-regulates quantity | 0.921 | Apc binds to both b-catenin and axin, and could shuttle b-catenin from the plasma membrane and nucleus to the cytoplasmic axin complex. APC cooperates with Axin to promote the phosphorylation of _-catenin by GSK3 [which requires priming phosphorylation by casein kinase 1, _-isoform (CK1_)]. | SIGNOR-177230 |
Q9NZ72 | P49840 | 0 | phosphorylation | up-regulates activity | 0.252 | Altogether, these results indicate that CDK5 phosphorylates similarly serines 68 and 73, whereas ERK2 targets mostly serine 68 and GSK-3beta mostly serine 60.|This observation may support the hypothesis of a specific localization of stathmin 3 depending on its phosphorylation by GSK-3beta | SIGNOR-264883 |
Q13153 | Q15831 | 0 | phosphorylation | down-regulates | 0.247 | Lkb1 suppresses p21-activated kinase-1 (pak1) by phosphorylation of thr109 in the p21-binding domain. | SIGNOR-164814 |
Q13526 | P46531 | 2 | binding | up-regulates | 0.384 | Prolyl-isomerase pin1 interacts with notch1 and affects notch1 activation. Pin1 potentiates notch1 cleavage by gamma-secretase, leading to an increased release of the active intracellular domain and ultimately enhancing notch1. pin1 potentiates notch1 cleavage by gamma-secretase | SIGNOR-183461 |
P01112 | P49354 | 0 | null | up-regulates activity | 0.413 | Major investments have been made to target Ras through indirect routes. Inhibition of farnesyl transferase to block Ras maturation has failed in large clinical trials. | SIGNOR-242568 |
Q15637 | P35637 | 2 | binding | down-regulates | 0.561 | We speculate that zfm1 may inhibit transcription driven by the ntds of tls | SIGNOR-58967 |
Q13557 | P51787 | 1 | phosphorylation | down-regulates activity | 0.2 | CaMKII regulates KCNQ1 at S484 during sustained β-AR stimulation to inhibit IKs. The ability of CaMKII to inhibit IKs may contribute to arrhythmogenicity during HF. | SIGNOR-275479 |
Q8IZL2 | Q99466 | 2 | binding | up-regulates | 0.86 | We show here identification of two new members of human mam family (human mastermind-2 (hmam-2) and human mastermind-3 (hmam-3)), which retain characteristics similar to human mastermind-1 (hmam-1) and drosophila mastermind. Both hmam-2 and hmam-3 stabilize and participate in the dna-binding complex rbp-j/cbf-1 protein and the notch intracellular domains that serve as intermediates of the signaling. Both hmam-2 and hmam-3 enhanced the activation of transcription from a target promoter by notch signaling. However, we also show evidence that the activation of the target promoter by notch3 and notch4 is more efficiently potentiated by hmam-2 than by hmam-1 or -3. | SIGNOR-94279 |
Q96A56 | Q9GZQ8 | 2 | binding | up-regulates | 0.297 | Tp53inp1-lc3 interaction occurs via a functional lc3-interacting region (lir) | SIGNOR-196673 |
Q92949 | O75602 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.447 | 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-266935 |
P21860 | Q96JA1 | 0 | ubiquitination | down-regulates | 0.434 | We report upregulation of lrig1 transcript and protein upon egf stimulation, and physical association of the encoded protein with the four egfr orthologs of mammals. Upregulation of lrig1 is followed by enhanced ubiquitylation and degradation of egfr. The underlying mechanism involves recruitment of c-cbl, an e3 ubiquitin ligase that simultaneously ubiquitylates egfr and lrig1 and sorts them for degradation. | SIGNOR-139951 |
Q13485 | O15198 | 0 | phosphorylation | up-regulates | 0.685 | Whereas alk5 signalling is mediated by phosphorylation of smad2 and smad3 proteins, alk1 signalling is mediated by smad1, smad5, and smad8. Activated smads form a complex with the common smad (co-smad; smad4 in mammals) and shuttle into the nucleus. | SIGNOR-168740 |
P17302 | P78415 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.278 | Irx3 directly represses Cx43 transcription | SIGNOR-266044 |
Q8WXD0 | P04090 | 2 | binding | up-regulates | 0.708 | Lgr7 and lgr8, are capable of mediating the action of relaxin through an adenosine 3',5'-monophosphate (camp)-dependent pathway. | SIGNOR-114585 |
Q00535 | Q8NER1 | 1 | phosphorylation | up-regulates activity | 0.2 | TNF-alpha overexpression increased Cdk5-mediated phosphorylation of TRPV1 at T407.|These results suggest that the activation of Cdk5 by p35 enhances the response of TRPV1 to capsaicin, probably by phosphorylation of the channel [34]. | SIGNOR-278437 |
Q06418 | Q13191 | 2 | phosphorylation | up-regulates activity | 0.35 | To test whether phosphorylation of Cbl-b at Tyr133 and/or Tyr363 by Tyro3 is important for its ubiquitin ligase function, we examined the ubiquitination of the Cbl-b mutants and Tyro3. | SIGNOR-279577 |
P27361 | P49715 | 1 | phosphorylation | down-regulates | 0.371 | 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-120570 |
P37840 | P53355 | 0 | phosphorylation | up-regulates quantity | 0.27 | We demonstrated that DAPK1 directly phosphorylates \u03b1-synuclein at Ser129, and induces the formation of insoluble \u03b1-synuclein aggregates. | SIGNOR-278440 |
P30307 | P53350 | 0 | phosphorylation | up-regulates | 0.804 | The nuclear accumulation of active m-phase promoting factor (mpf) during prophase is thought to be essential for coordinating m-phase events in vertebrate cells. The protein phosphatase cdc25c, an activator of mpf, enters the nucleus to keep mpf active in the nucleus during prophase. these results suggest that plk1 phosphorylates cdc25c on ser198 and regulates nuclear translocation of cdc25c during prophase. | SIGNOR-115993 |
O43293 | P40429 | 1 | phosphorylation | up-regulates | 0.402 | Zipk phosphorylates l13a in vitro / l13a is phosphorylated on ser77 in vitro | SIGNOR-182117 |
P06493 | Q14CS0 | 1 | phosphorylation | down-regulates activity | 0.2 | At mitosis, Cdc2 kinase phosphorylates p47 on Serine-140 and p37 on Serine-56 and Threonine-59, respectively. The phosphorylated p47 and p37 are unable to bind to Golgi membranes, resulting in mitotic inhibition of the p97/p47 and the p97/p37 pathways, respectively. | SIGNOR-265041 |
P11171 | Q12959 | 1 | relocalization | up-regulates activity | 0.472 | Together, our results demonstrate that in addition to the N-terminal targeting domain, the alternatively spliced I3 insertion plays a critical role in recruiting hDlg to the lateral membrane in epithelial cells via its interaction with protein 4.1R. | SIGNOR-266011 |
Q8TEB1 | Q17RS7 | 2 | binding | down-regulates quantity by destabilization | 0.2 | (WDR23) isoforms differentially ubiquitinate (GEN1). In the presence of the necessary components for a successful ubiquitination reaction (CUL4A-DDB1-WDR23 complex, UBE1, UBE2D1, ubiquitin, and ATP) GEN1 receives the addition of ubiquitin in a time dependent manner. | SIGNOR-272258 |
Q99626 | Q9HAW8 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.257 | Using gel shift and functional assays, HNF1alpha was demonstrated to bind to and activate the UGT1A8, -1A9, and -1A10 promoters. In contrast, Cdx2 bound to and activated the UGT1A8 and -1A10 promoters but could not activate the UGT1A9 promoter. | SIGNOR-253968 |
P08754 | P41595 | 2 | binding | up-regulates activity | 0.265 | 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-256886 |
Q04206 | Q9Y2K7 | 0 | demethylation | down-regulates | 0.459 | Fbxl11 and nsd1 have opposite effects on nf-kb; both bind to p65 subunit after activation of nf-kb. / nsd1 activates nf-kb and reverses the inhibitory effect of fbxl11 / these data confirm that fbxl11 and nsd1 constitute an enzyme pair that methylates and demethylates p65 on k218 and 221 in response to cytokine stimulation. | SIGNOR-163384 |
Q9Y6R4 | P46734 | 1 | phosphorylation | up-regulates activity | 0.639 | These results, therefore, suggest that mtk1 directly phosphorylates and activates mkk3, mkk6 and sek1. | SIGNOR-50891 |
O43768 | Q96GX5 | 0 | phosphorylation | up-regulates activity | 0.732 | We identified cyclic adenosine monophosphateregulated phosphoprotein 19 (Arpp19) and -Endosulfine as two substrates of Gwl that, when phosphorylated by this kinase, associate with and inhibit PP2A, thus promoting mitotic entry. | SIGNOR-243690 |
Q07352 | Q15418 | 0 | phosphorylation | down-regulates activity | 0.2 | These results indicate that RSK1 directly phosphorylates the C-terminus of ZFP36L1 downstream of ERK, and inhibits the Messenger RNA destabilization activity of ZFP36L1.|These results indicate that RSK1 directly phosphorylates the C-terminus of ZFP36L1 downstream of ERK, and inhibits the mRNA destabilization activity of ZFP36L1. | SIGNOR-279280 |
Q9NXA8 | P54868 | 1 | post translational modification | up-regulates activity | 0.343 | We demonstrate that SIRT5 regu-lates succinylation of the rate-limiting ketogenicenzyme 3-hydroxy-3-methylglutaryl-CoA synthase 2(HMGCS2) both in vivo and in vitro.|Succinylation of Lysine Residues within the SubstrateBinding Pocket Inhibits HMGCS2 Activity|Here, we use a label-freequantitative proteomic approach to characterizethe lysine succinylome in liver mitochondria and itsregulation by the desuccinylase SIRT5 | SIGNOR-267641 |
Q09472 | Q10571 | 2 | binding | up-regulates | 0.342 | Our results indicate that mn1 is a transcription coactivator rather than a sequence-specific transcription factor, and that it may stimulate rar/rxr-mediated transcription through interaction with p160 and p300. | SIGNOR-97899 |
P02649 | Q99523 | 2 | binding | up-regulates quantity | 0.427 | Here, we identified the pro-neurotrophin receptor sortilin as major endocytic pathway for clearance of APOE/Aβ complexes in neurons. Sortilin binds APOE with high affinity. Lack of receptor expression in mice results in accumulation of APOE and of Aβ in the brain and in aggravated plaque burden. Sortilin interacts with all human APOE isoforms. | SIGNOR-273721 |
P08754 | Q9NQS5 | 2 | binding | up-regulates activity | 0.277 | 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-256847 |
Q96EB6 | Q9Y618 | 1 | null | up-regulates | 0.494 | In differentiated adipocyte cell lines, SIRT1 inhibits adipogenesis and enhances fat mobilization through lipolysis by suppressing the activity of PPARγ. SIRT1 achieves this by promoting the assembly of a corepressor complex, involving NCoR1 and SMRT, on the promoters of PPARγ target genes to repress their transcription. | SIGNOR-253506 |
O14578 | Q96GD4 | 0 | phosphorylation | down-regulates activity | 0.283 | Finally, Aurora B phosphorylates CIT-K to control its localization and interaction with central spindle partners.|Together these findings indicate that CIT-K is an Aurora B substrate and that Aurora B phosphorylation at S699 dampens the association of CIT-K with KIF23 and the chromosomal passenger complex in order to reduce CIT-K accumulation at the spindle midzone in early cytokinesis. | SIGNOR-279140 |
Q02156 | Q96A00 | 1 | phosphorylation | up-regulates activity | 0.261 | A major kinase for GPCR‐induced CPI‐17 phosphorylation is PKC which is activated by the PLCbeta‐produced signaling messenger diacylglycerol (DAG). It phosphorylates CPI‐17 at Thr38 residue that directly docks at the active site of MLCP, thereby inhibiting its activity and promoting an increase of phosphorylation of myosin and of other MLCP. | SIGNOR-249258 |
P19838 | P12644 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | The effect of TNF-alpha on the Bmp4 promoter is mediated through NF-kB. | SIGNOR-266086 |
P23246 | P07101 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | It has been reported that DJ-1 is a neuroprotective transcriptional co-activator that sequesters a transcriptional co-repressor polypyrimidine tract-binding protein-associated splicing factor (PSF) from the TH gene promoter. | SIGNOR-271697 |
P18075 | Q13253 | 2 | binding | down-regulates activity | 0.852 | We report the crystal structure of the antagonist Noggin bound to BMP-7, which shows that Noggin inhibits BMP signalling by blocking the molecular interfaces of the binding epitopes for both type I and type II receptors. | SIGNOR-256484 |
P84022 | P15172 | 2 | binding | down-regulates activity | 0.731 | We show that the TGF-beta intracellular effector Smad3, but not Smad2, mediates the inhibition of myogenic differentiation in MyoD-expressing C3H10T1/2 cells and C2C12 myoblasts by repressing the activity of the MyoD family of transcriptional factors. | SIGNOR-252071 |
Q96D59 | Q07817 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.385 | As an E3 ligase, RNF183 ubiquitinates Bcl-xL, causing its degradation and subsequent apoptosis. | SIGNOR-278595 |
Q13950 | P56524 | 0 | deacetylation | down-regulates activity | 0.524 | HDAC4 and HDAC5 deacetylate Runx2, allowing the protein to undergo Smurf-mediated degradation | SIGNOR-227547 |
Q8N8S7 | Q70E73 | 2 | binding | up-regulates activity | 0.544 | Here we show that Lpd is a substrate of Abl kinases and binds to the Abl SH2 domain. Phosphorylation of Lpd positively regulates the interaction between Lpd and Ena/VASP proteins. | SIGNOR-268425 |
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