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 |
|---|---|---|---|---|---|---|---|
Q96J02 | P00533 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.48 | In summary, we have shown that CBLC and AIP4 can interact and that these two E3 ligases could contribute to down-regulate EGFR signaling by ubiquitination. | SIGNOR-272604 |
P00519 | P12532 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.2 | Here, we show that oncogenic HER2 tyrosine kinase signaling induces phosphorylation of mitochondrial creatine kinase 1 (MtCK1) on tyrosine 153 (Y153) in an ABL-dependent manner in breast cancer cells. Y153 phosphorylation, which is commonly upregulated in HER2+ breast cancers, stabilizes MtCK1 to increase the phosphocreatine energy shuttle and promote proliferation. | SIGNOR-277406 |
P48730 | P56645 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.719 | We show here that mPer proteins, negative limbs of the autoregulatory loop, are specific substrates for CKIepsilon and CKIdelta. The CKI phosphorylation of mPer1 and mPer3 proteins results in their rapid degradation, which is dependent on the ubiquitin-proteasome pathway. | SIGNOR-267998 |
O00444 | Q96RT7 | 1 | phosphorylation | up-regulates activity | 0.701 | Plk4 interacts with and phosphorylates GCP6. we show that GCP6 is an integral component of the centriole and required for centriole duplication. Moreover, we find that GCP6 interacts in vitro and in vivo with Plk4. We show that phosphorylation of GCP6 by Plk4 is required for Plk4-induced centriole overduplication. | SIGNOR-262902 |
O95831 | Q9NQU5 | 0 | phosphorylation | down-regulates activity | 0.2 | Furthermore, PAK5 phosphorylates AIF at Thr281 site to inhibit the formation of AIF/importin \u03b13 complex, leading to decrease AIF nuclear translocation.|These results suggested that PAK5 can inhibit AIF from entering the nucleus and prevent caspase- independent apoptosis. | SIGNOR-278969 |
O15350 | P62913 | 2 | binding | up-regulates | 0.359 | We report that rpl5 and rpl11 can also enhance the transcriptional activity of a p53 homolog tap73 | SIGNOR-205514 |
O14965 | Q9UPY8 | 1 | phosphorylation | up-regulates | 0.442 | Aurora-a and aurora-b phosphorylate eb3 at ser-176 in a spatial and cell cycle-specific manner, respectively during mitosis two kinases, aurora-a and aurora-b, phosphorylate eb3 at ser-176, and the resulting phosphorylation disrupts the eb3-siah-1 complex. Indeed, eb3 is stabilized during mitosis and facilitates cell cycle progression. | SIGNOR-187657 |
P09471 | Q15722 | 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-256970 |
P53041 | Q9UPZ9 | 1 | dephosphorylation | down-regulates activity | 0.2 | MAK and MRK require dual phosphorylation in a TDY motif catalyzed by an unidentified human threonine kinase and tyrosine autophosphorylation.| Protein phosphatase 5 (PP5) interacts with MRK in a complex and dephosphorylates MRK at T157 in vitro and in situ. | SIGNOR-248541 |
O43614 | O43612 | 2 | binding | up-regulates | 0.776 | Identification and initial biological characterization of two orexins as well as their two receptors | SIGNOR-55848 |
Q9Y618 | Q9C0J9 | 2 | binding | up-regulates | 0.2 | The spen protein, sharp (smrt/hdac1-associated repressor protein), was identified as a component of transcriptional repression complexes in both nuclear receptor and notch/rbp-jkappa signaling pathways. | SIGNOR-104489 |
O00418 | P54646 | 0 | phosphorylation | up-regulates activity | 0.498 | Stimulation of the AMP-activated Protein Kinase Leads to Activation of Eukaryotic Elongation Factor 2 Kinase and to Its Phosphorylation at a Novel Site, Serine 398. phosphorylation of eEF2 kinase at Ser-398 leads to an increase in its activity. | SIGNOR-250158 |
P28482 | Q96LC9 | 1 | phosphorylation | up-regulates | 0.253 | Phosphomimetic mutation of this site (s74d) moderately enhanced bmf apoptotic activity in vivo.22 here, we demonstrate a previously unrecognized mode of regulation of bmf. We show that b-raf-mek-erk2 signaling regulates bmf phosphorylation at serine 74 and serine 77. Phosphorylation of serine 77 downregulates the pro-apoptotic activity of bmf. | SIGNOR-195475 |
Q92793 | Q16566 | 0 | phosphorylation | up-regulates activity | 0.635 | Ser301 of CBP was identified as a major target of CaMKIV phosphorylation in vitro and in vivo. CaM kinase inhibitors attenuated phosphorylation at Ser301 and blocked CBP-dependent transcription. Additionally, mutation of Ser301 impaired NMDA- and CaMKIV-stimulated transcription. These findings demonstrate that activity-induced CaMKIV signaling contributes to CREB/CBP-dependent transcription by phosphorylating CBP at Ser301. | SIGNOR-250710 |
Q9Y5H1 | Q9Y5I2 | 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-265713 |
Q13177 | P63000 | 2 | binding | up-regulates activity | 0.75 | A new brain serine/threonine protein kinase may be a target for the p21ras-related proteins Cdc42 and Rac1. The kinase sequence is related to that of the yeast protein STE20, implicated in pheromone-response pathways. | SIGNOR-248250 |
P23769 | Q03112 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.359 | Evi1 directly binds to the promoter region of GATA-2 and thus enhances the GATA-2 transcription. | SIGNOR-266062 |
Q06330 | Q96JK9 | 2 | binding | up-regulates | 0.877 | When bound to the active intracellular domain of notch (nicd), rbpj recruits a coactivator complex, including a mastermind homologue (maml1-3 in mammals), and drives a complex transcriptional program with pervasive phenotypic effects. | SIGNOR-176200 |
O95997 | Q9UQM7 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.309 | CaMKII phosphorylates securin at PP2A substrate site(s).Securin is destabilized by phosphorylation and stabilized by PP2A-dependent dephosphorylation on separase | SIGNOR-276381 |
P0C0S8 | Q86Y13 | 0 | monoubiquitination | up-regulates activity | 0.2 | 2A-HUB catalyzes monoubiquitination of H2A at lysine 119, functioning as a combinatoric component of the repression machinery required for specific gene regulation programs. Thus, 2A-HUB mediates a selective repression of a specific set of chemokine genes in macrophages, critically modulating migratory responses to TLR activation. H2A monoubiquitination acts to prevent FACT recruitment at the transcriptional promoter region, blocking RNA polymerase II release at the early stage of elongation. | SIGNOR-271749 |
P03951 | P00740 | 1 | cleavage | up-regulates activity | 0.484 | Factor XI (FXI) is the zymogen of an enzyme (FXIa) that contributes to hemostasis by activating factor IX.|The characterization of the apple disk structure, and its relationship to the catalytic domain, have provided new insight into the mechanism of FXI activation, the interaction of FXIa with the substrate factor IX, and the binding of FXI to platelets. | SIGNOR-263537 |
P35503 | P17252 | 0 | phosphorylation | up-regulates activity | 0.2 | Curcumin and calphostin C suppressed the activity and phosphorylation of recombinant UGT1A3 expressed in Sf9 cells. These results indicate that UGT1A3 undergoes phosphorylation, which is required for its catalytic activity. Calphostin C is a highly specific protein kinase C (PKC) inhibitor, so three predicted PKC phosphorylation sites in UGT1A3 were examined. In conclusion, phosphorylation plays an important role in UGT1A3 activity, and the serine at site 43 in UGT1A3 is most likely a phosphorylation site. | SIGNOR-273823 |
P25098 | Q96A54 | 1 | phosphorylation | down-regulates activity | 0.2 | AdipoR1 is Directly Phosphorylated by GRK2.|In summary, our study demonstrates for the first time that cardiometabolic-regulatory, anti-inflammatory, and cardioprotective functions of APN are significantly impaired by GRK2 mediated AdipoR1 phosphorylative desensitization during a critical period of post-MI HF development. | SIGNOR-279463 |
O15530 | O00141 | 1 | phosphorylation | up-regulates activity | 0.65 | PDK1 activates SGK in vitro by phosphorylating Thr256. | SIGNOR-250275 |
O96013 | P28698 | 1 | phosphorylation | up-regulates activity | 0.2 | Here, we link ErbB2 activation to invasion via ErbB2-induced, SUMO-directed phosphorylation of a single serine residue, S27, of the transcription factor myeloid zinc finger-1 (MZF1). Phosphorylation of MZF1-S27 is an early response to ErbB2 activation and results in increased transcriptional activity of MZF1.The phosphorylation of MZF1-S27 is preceded by poly-SUMOylation of K23, which can make S27 accessible to efficient phosphorylation by PAK4. | SIGNOR-277422 |
P35638 | P18848 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.816 | ATF4 also induces another bZIP protein C/EBP-homologous protein (CHOP), which is responsible for triggering apoptosis in cells under prolonged ER stress. ATF4 and CHOP further induce growth arrest and DNA damage–inducible protein 34 (GADD34),a regulatory subunit of protein phosphatase 1 (PP1) that dephosphorylates eIF2α. This negative feedback mechanism enables protein synthesis to resume after resolution of ER stress. | SIGNOR-260170 |
P53350 | O14920 | 1 | phosphorylation | down-regulates | 0.343 | Plk1 phosphorylates serines 733, 740, and 750 in the gammabd of ikkbeta in vitro. Phosphorylating gammabd with plk1 decreased its affinity for ikkgamma | SIGNOR-181802 |
P12036 | P49840 | 0 | phosphorylation | down-regulates activity | 0.254 | Our results demonstrate that whereas GSK-3 alpha, GSK-3 beta, and cdk-5 will all phosphorylate NF-H, they generate different antibody reactivity profiles. | SIGNOR-279783 |
Q02086 | P49585 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | Sp3 is an activator, and Sp2 a repressor, of the Ctpct promoter in SL2 cells. | SIGNOR-266230 |
P37088 | O95180 | 2 | binding | up-regulates activity | 0.2 | This study describes the functional interaction between Cav3.2 calcium channels and the Epithelial Sodium Channel (ENaC). β- and γ-ENaC subunits could be co-immunoprecipitated with Cav3.2 calcium channels from brain lysates, dorsal horn and lumbar dorsal root ganglia. Αβγ-ENaC channels enhanced Cav3.2 calcium channel trafficking to the plasma membrane in tsA-201 cells. This effect was reciprocal such that Cav3.2 channel expression also enhanced β-ENaC trafficking to the cell surface. these findings reveal ENaC as an interactor and potential regulator of Cav3.2 calcium channels expressed in neuronal tissues. | SIGNOR-269272 |
P68400 | Q00613 | 1 | phosphorylation | up-regulates activity | 0.37 | Transcriptional activity and DNA binding of heat shock factor-1 involve phosphorylation on threonine 142 by CK2. | SIGNOR-250898 |
Q13950 | Q9UQL6 | 0 | deacetylation | down-regulates | 0.458 | Hdac4 and hdac5 deacetylate runx2 and lead to a smurf-mediated degradation | SIGNOR-145983 |
P17612 | Q9Y6Q9 | 1 | phosphorylation | up-regulates | 0.364 | Herein, we report the successful identification of six functional in vivo src-3 phosphorylation sites. | SIGNOR-129349 |
O43464 | O15033 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.406 | Furthermore, the ubiquitination and degradation of SMAC, HtrA2, and ARTS were significantly enhanced in AREL1-expressing cells following apoptotic stimulation, indicating that AREL1 binds to and ubiquitinates cytosolic but not mitochondria-associated forms of IAP antagonists | SIGNOR-267669 |
P02788 | O60260 | 0 | ubiquitination | down-regulates activity | 0.2 | We propose that Parkin ubiquitylation of LTF at K649 perturbs LTF\u2019s ability to accumulate intracellular iron levels and that depletion of Parkin, or substitution of K649 on LTF, allows LTF to accumulate intracellular iron levels.|Parkin dependent ubiquitylation of LTF occurred most often on lysines (K) 182 and 649. | SIGNOR-278641 |
P12931 | O75581 | 1 | 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 |
P49427 | P68400 | 0 | phosphorylation | down-regulates activity | 0.395 | The ubiquitin-conjugating enzyme, cdc34, has been implicated in the ubiquitination of a number of vertebrate substrates, including p27(kip1), ikappabalpha, wee1, and myod. We show that mammalian cdc34 is a phosphoprotein that is phosphorylated in proliferating cells. Phosphorylation of cdc34 by the associated kinase maps predominantly to residues 203 and 222. Mutation of cdc34 at ck2-targeted residues, ser-203, ser-222, ser-231, thr-233, and ser-236, abolishes the phosphorylation of cdc34 observed in vivo and markedly shifts nuclearly localized cdc34 to the cytoplasm. | SIGNOR-110399 |
Q96FA3 | P32754 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | Decreased expression of 4-hydroxyphenylpyruvic acid dioxygenase (HPD), a key enzyme for tyrosine metabolism, is a cause of human tyrosinemia. However, the regulation of HPD expression remains largely unknown. Here, we demonstrate that molecular chaperone TTC36, which is highly expressed in liver, is associated with HPD and reduces the binding of protein kinase STK33 to HPD, thereby inhibiting STK33-mediated HPD T382 phosphorylation. The reduction of HPD T382 phosphorylation results in impaired recruitment of FHA domain-containing PELI1 and PELI1-mediated HPD polyubiquitylation and degradation. | SIGNOR-272959 |
P09471 | P24530 | 2 | binding | up-regulates activity | 0.456 | 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-257254 |
Q03113 | Q12802 | 2 | binding | up-regulates activity | 0.524 | These data suggest that G12 is an upstream activator of AKAP-Lbc in the Rho signaling pathway. | SIGNOR-278882 |
P63092 | P25101 | 2 | binding | up-regulates activity | 0.477 | 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-256780 |
P52564 | P45984 | 1 | phosphorylation | up-regulates | 0.473 | A map kinase kinase kinase (mapkkk), termed ask1, was identified that activated two different subs of map kinase kinases (mapkk), sek1 (or mkk4) and mkk3/mapkk6 (or mkk6), which in turn activated stress-activated protein kinase (sapk, also known as jnk;c-jun amino-terminal kinase) | SIGNOR-45369 |
P01033 | P14780 | 2 | binding | down-regulates activity | 0.807 | Tissue inhibitor of metalloproteinase (TIMP-1) is an inhibitor of MMP-9 that binds to MMP-9 precursors and to the active form. | SIGNOR-278116 |
Q5JXC2 | Q04206 | 2 | binding | up-regulates activity | 0.2 | Here, we show that EGF stimulation induces PKCε-dependent phosphorylation of migration and invasion inhibitory protein (MIIP) at Ser303; this phosphorylation promotes the interaction between MIIP and RelA in the nucleus, by which MIIP prevents histone deacetylase 6 (HDAC6)-mediated RelA deacetylation, and thus enhances transcriptional activity of RelA and facilitates tumor metastasis. | SIGNOR-273829 |
Q2TAL8 | Q5ST30 | 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-269409 |
O00418 | Q9UKB1 | 0 | ubiquitination | down-regulates | 0.436 | Eef2k was degraded by the ubiquitin-proteasome system through the ubiquitin ligase scf(__trcp) (skp1-cul1-f-box protein, __-transducin repeat-containing protein) to enable rapid resumption of translation elongation. This event required autophosphorylation of eef2k on a canonical __trcp-binding domain | SIGNOR-197730 |
P32245 | Q03113 | 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-257440 |
Q05397 | P06241 | 0 | phosphorylation | up-regulates activity | 0.602 | Because Fyn deletion prevented FAK phosphorylation at tyrosine residues 397 and 576 (XREF_FIG), we generated a phosphorylation mimicking mutant of FAK to test whether restoring FAK phosphorylation in the fyn -/- mouse lung could restore lung vascular permeability responses to PAR1 agonist to the level seen in WT mice.|Our findings that interaction of activated FAK with p120-catenins subsequent to Fyn activation of FAK facilitates reannealing of AJ leading to reestablishment of the basal endothelial barrier suggest that the Fyn-FAK pathway plays a critical role in restoring endothelial barrier function. | SIGNOR-278441 |
P27361 | P10415 | 1 | phosphorylation | up-regulates | 0.56 | Erk1 and erk2 directly phosphorylate bcl2 exclusively at ser-70 p44mapk/extracellular signal-regulated kinase 1 (erk1) and p42 mapk/erk2 are activated by il-3, colocalize with mitochondrial bcl2, and can directly phosphorylate bcl2 on ser-70 in a stauro-resistant manner both in vitro and in vivo molecular association. | SIGNOR-74935 |
Q53EL6 | P31749 | 0 | phosphorylation | down-regulates | 0.435 | Both akt and p70(s6k) phosphorylate pdcd4, allowing for binding of the e3-ubiquitin ligase beta-trcp and consequently ubiquitylation. | SIGNOR-252505 |
Q14344 | Q99500 | 2 | binding | up-regulates | 0.529 | Edg-3 and edg-5 couple not only to gibut also to gqand g13. | SIGNOR-70710 |
P11487 | P21802 | 2 | binding | up-regulates | 0.767 | Using fgf 1 as an internal standard we have determined the relative activity of all the other members of the fgf family. These data should serve as a biochemical foundation for determining developmental, physiological, and pathophysiological processes that involve fgf signaling pathways | SIGNOR-42374 |
Q13332 | P00533 | 1 | dephosphorylation | down-regulates activity | 0.43 | Similarly, Pestana et al. (89) have reported that overexpression of RPTPsigma in human A431 carcinoma cells partially inhibits EGFR activation, whereas antisense mediated suppression of RPTPsigma expression enhances EGFR activation, substrate phosphorylation, and signalling.|These data indicate that LAR and RPTPsigma may have a significant role in GPCR induced EGFR signalling.Whereas in A431 cells LAR and RPTPsigma may act to suppress the EGFR in response to GPCR activation, it is possible that the converse may also be true in other cell types. | SIGNOR-277145 |
P04150 | O43524 | 1 | transcriptional regulation | up-regulates quantity | 0.415 | We show that FOXO3 is an immediate early glucocorticoid receptor (GR) target, whose transcription is even further enhanced by conditions that mimic metabolic stress. | SIGNOR-255759 |
Q15642 | Q68EM7 | 2 | binding | down-regulates activity | 0.501 | Screening for potential mediators of this effect resulted in the identification of the Rac1-specific GTPase-activating protein ARHGAP17 and the guanine nucleotide exchange factor ARHGEF6 as new PKA and PKG substrates in platelets. We mapped the PKA/PKG phosphorylation sites to serine 702 on ARHGAP17 using Phos-tag gels and to serine 684 on ARHGEF6. |ARHGAP17 is a Rho GTPase-activating protein of Rac1 and is bound to the SH3 domain of CIP4 via its SH3 binding region in resting platelets. Endothelial PGI2 stimulates the activation of PKA and leads to the phosphorylation of Ser-702 in ARHGAP17, which results in the dissociation of the ARHGAP17-CIP4 complex. | SIGNOR-272158 |
Q9UP38 | P56704 | 2 | binding | up-regulates activity | 0.796 | Ligands such as wnt1, wnt3a, and wnt8 couple the seventransmembrane domain receptor frizzled (fzd) and the single-membrane-spanning low-density receptor-related protein 5/6 (lrp5/6) to activate wnt?Beta-catenin signaling.All the frizzled genes studied have a complex and partially overlapping pattern of expression in different regions of the embryo, and many of them (fz1, 3, 7, 8 and 9) have specific expression in the epithelial somites as well as in the newly formed myotomes. | SIGNOR-169651 |
P07101 | P17612 | 0 | phosphorylation | up-regulates activity | 0.368 | HTH1 was phosphorylated at Ser40 by PKA. Tyrosine hydroxylase (TH) has been reported to require binding of 14-3-3 proteins for optimal activation by phosphorylation. phosphorylationof hTH1‚4 at Ser40, to a stoichiometry of up to 1.0 molphosphate per mol TH subunit, dramatically increases their binding to 14-3-3 proteins. | SIGNOR-250061 |
P12931 | Q07666 | 1 | phosphorylation | up-regulates activity | 0.825 | 26 In particular, Sam68 was shown to play a scaffold role in Src kinase activated pathways, 16,27 and tyrosine phosphorylation of Sam68 by Src kinases triggers the release of bound RNA and might allow translational activation. | SIGNOR-279121 |
P23470 | P49023 | 1 | dephosphorylation | up-regulates activity | 0.26 | PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity. | SIGNOR-254721 |
P84022 | Q13950 | 2 | binding | down-regulates activity | 0.738 | Tgf-beta inhibited the expression of the cbfa1 and osteocalcin genes, whose expression is controlled by cbfa1 in osteoblast-like cell lines. This inhibition was mediated by smad3, which interacts physically with cbfa1 and represses its transcriptional activity at the cbfa1-binding ose2 promoter sequence. | SIGNOR-235902 |
P01213 | P35372 | 1 | chemical activation | up-regulates activity | 0.674 | Accordingly, for the OTDP, the binding affinity and activity of a large number of opiate compounds have been tested at μ-, δ-, and κ-opiate receptors. Binding studies were originally conducted in guinea pig brain membranes, and subsequent studies have been carried out in CHO cells transfected with human receptors. Table 7 shows a biochemical method for determining activity and potency of opioid compounds, stimulation of [35S]GTPγS binding in membranes from cells transfected with human μ, δ, or κ receptors. | SIGNOR-258414 |
O75534 | P01100 | 1 | post transcriptional regulation | down-regulates quantity | 0.295 | By testing different classes of mammalian poly(A) nucleases, we identified CCR4 as a poly(A) nuclease involved in the mCRD-mediated rapid deadenylation in viv | SIGNOR-261145 |
P05412 | Q9H4B4 | 0 | phosphorylation | up-regulates | 0.369 | Stress-induced c-jun activation mediated by polo-like kinase 3 in corneal epithelial cells. Hypoxia/reoxygenation activated plk3 in hce cells to directly phosphorylate c-jun proteins at phosphorylation sites ser-63 and ser-73, and to increase dna binding activity of c-jun. | SIGNOR-157721 |
Q08881 | Q06124 | 0 | dephosphorylation | down-regulates activity | 0.324 | Using genetic and pharmacological approaches, we discovered that SHP2 dephosphorylates ITK specifically downstream of PD-1 and that this event was associated with PD-1 inhibitory cellular functions. | SIGNOR-277174 |
P27361 | P27361 | 2 | phosphorylation | up-regulates activity | 0.2 | Microtubule-associated protein 2 kinases, ERK1 and ERK2, undergo autophosphorylation on both tyrosine and threonine residues: implications for their mechanism of activation.| | SIGNOR-249471 |
P17612 | P09341 | 2 | binding | down-regulates | 0.2 | As pka suppresses the activity of gli, smo might use the stimulation of pi3k by galfai and gbetagamma subu- nits to block pka in cells that have high levels of camp. | SIGNOR-152594 |
P11940 | P06730 | 2 | binding | up-regulates activity | 0.805 | The binding of PABP to mRNA poly(A) tails is followed by interactions with eukaryotic initiation factor (eIF4G) and other translation factors, including eIF4E, to constitute a translation initiation complex, which mediates cellular mRNA circularization and enhances cap-dependent translation by facilitating ribosome recycling | SIGNOR-260968 |
Q13207 | P15173 | 2 | binding | down-regulates activity | 0.249 | We have found that TBX2 is highly up regulated in both ERMS and ARMS subtypes of RMS and demonstrate that TBX2 is a repressor of myogenesis by binding to MyoD and myogenin and inhibiting their activity. | SIGNOR-251561 |
P51955 | Q13257 | 1 | phosphorylation | down-regulates activity | 0.845 | We demonstrated that overexpression of Nek2 can enhance the ability of Mad2 to cause delays in cell division.|We have demonstrated that Nek2 can bind and phosphorylate Mad2 and Cdc20. | SIGNOR-278446 |
P28845 | P17676 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.284 | In conclusion, C/EBPalpha and C/EBPbeta control basal transcription, and TNF-alpha upregulates 11beta-HSD1, most likely by p38 MAPK-mediated increased binding of C/EBPbeta to the human HSD11B1 promoter. | SIGNOR-268972 |
P08581 | Q04206 | 0 | transcriptional regulation | up-regulates quantity | 0.25 | Together, these results indicate that the Met gene is a direct target of NFkappaB and that Met participates in NFkappaB-mediated cell survival. | SIGNOR-241929 |
P04637 | Q9BXM7 | 0 | phosphorylation | up-regulates activity | 0.321 | Our studies thus indicated that mitophagy\npositively regulated hepatic CSCs by suppressing p53, which otherwise would be activated by\nPINK1 to suppress the expression of NANOG and hepatic CSCs.|These results indicated that the phosphorylation of p53 at S392 by\nPINK1 likely took place on mitochondria. | SIGNOR-278418 |
Q9Y6Q9 | P49840 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.2 | GSK3 Phosphorylates SRC-3 on S505.In this report, we identified GSK3 as a kinase that phosphorylates SRC-3 on S505 and demonstrated that this phosphorylation modulates SRC-3 transcriptional function and turnover. | SIGNOR-276067 |
Q16539 | O75928 | 1 | phosphorylation | up-regulates activity | 0.316 | The switch between the coactivating and inhibitory actions of PIASxα is controlled, at least in part, through PIASxα phosphorylation. PIASxα is itself phosphorylated by p38 in vitro and in vivo in response to the activation of stress signaling pathways (Figure 2, Figure 3, Figure 4). We identify Ser113 and Ser 116 as two residues that are phosphorylated by p38 and have important functional roles | SIGNOR-262949 |
P49116 | O43541 | 2 | binding | down-regulates | 0.2 | Smad6 interacts with tak1 and tab1, and smad7 with tab1 | SIGNOR-112636 |
P19086 | Q9UBY5 | 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-257229 |
Q13131 | Q14694 | 1 | phosphorylation | up-regulates activity | 0.309 | Under energy stress, USP10 activity in turn is enhanced through AMPK-mediated phosphorylation of Ser76 of USP10. | SIGNOR-277207 |
P53350 | Q8N137 | 1 | phosphorylation | up-regulates activity | 0.324 | However, unlike NEK2, PLK1 phosphorylation enhances the microtubule stabilizing activity of centrobin [22].|PLK1 phosphorylation of centrobin is critical for bipolar spindle formation. | SIGNOR-279551 |
P49137 | Q14457 | 1 | phosphorylation | up-regulates activity | 0.432 | Beclin 1 S90 is phosphorylated by MAPKAPK2 (MK2) and MAPKAPK3 (MK3). | SIGNOR-278342 |
P46937 | P35221 | 2 | binding | down-regulates | 0.353 | The trimeric complex of alfa-catenin, 14-3-3, and yap sequesters yap at ajs and prevents yap dephosphorylation/activation. | SIGNOR-201173 |
P42338 | P01116 | 2 | binding | up-regulates | 0.714 | Grb2 binds and activates sos, which then activates ras, and this activates p110 independently of p85./it was also described that ras interacts with pi3k in a direct manner./lysine residue 227 is essential for the interaction of ras with pi3k. | SIGNOR-175207 |
P61328 | P35498 | 2 | binding | down-regulates activity | 0.386 | Sodium channel fast inactivation is modulated by alpha subunit interaction with a family of cytoplasmic proteins termed fibroblast growth factor homologous factors (FHFs). In this paper, we report that all A-type FHFs exert rapid onset long-term inactivation on Nav1.6 and other sodium channels. | SIGNOR-253420 |
Q96GG9 | P46934 | 0 | monoubiquitination | up-regulates quantity | 0.368 | Here we revealed a previously unknown mechanism that regulates hDCNL1. In cultured mammalian cells ectopically expressed hDCNL1 was mono-ubiquitinated predominantly at K143, K149, and K171. Using a classical chromatographic purification strategy, we identified Nedd4-1 as an E3 ligase that can catalyze mono-ubiquitination of hDCNL1 in a reconstituted ubiquitination system.Taken together, these results suggest a mono-ubiquitination-mediated mechanism that governs nuclear-cytoplasmic trafficking of hDCNL1, | SIGNOR-272719 |
O43524 | Q06418 | 0 | phosphorylation | down-regulates activity | 0.2 | However, the present study in tPA and NMDA treated neurons establishes the link between PS mediated activation of Tyro3 and FKHRL1 phosphorylation which inactivates pro apoptotic FKHRL1 and mediates PS 's beneficial effects.|We also show that inhibition of the extrinsic apoptotic cascade by PS requires Tyro3 mediated phosphorylation of FKHRL1 which in turn inhibits FasL production and FasL dependent caspase-8 activation in the extrinsic pathway. | SIGNOR-279669 |
P48431 | P00533 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.48 | These data indicate that EGFR\u2010induced SOX2 Tyr277 phosphorylation prevents the autophagic degradation of SOX2 and enhances its stability. | SIGNOR-279036 |
Q13616 | P01106 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.483 | Furthermore, c-myc activation can also promote the degradation of p27kip1 protein by directly activating the cul1 gene, which encodes a critical component of the ubiquitin ligase scfskp2 | SIGNOR-102749 |
Q8NEB9 | Q9Y2M5 | 2 | binding | down-regulates quantity by destabilization | 0.295 | Cul3-KLHL20 Ubiquitin Ligase Governs the Turnover of ULK1 and VPS34 Complexes to Control Autophagy Termination. KLHL20 promotes ubiquitination of phagophore-residing VPS34 and Beclin-1 | SIGNOR-272414 |
Q15465 | P00450 | 2 | binding | down-regulates | 0.2 | Binding of sonic hedgehog (shh) to patched (ptc) relieves the latter's tonic smoothened (smo), a receptor that spans the cell membrane seven times. Ptch exists in vertebrates as two isoforms, ptch1 and ptch2, which seem to be equivalent in terms of binding the three hh isoforms. | SIGNOR-132672 |
Q15078 | Q00535 | 2 | binding | up-regulates activity | 0.943 | Cyclin-dependent kinase 5 (Cdk5) is required for proper development of the mammalian central nervous system. To be activated, Cdk5 has to associate with its regulatory subunit, p35. We have found that p25, a truncated form of p35, accumulates in neurons in the brains of patients with Alzheimer's disease. This accumulation correlates with an increase in Cdk5 kinase activity. Unlike p35, p25 is not readily degraded, and binding of p25 to Cdk5 constitutively activates Cdk5, changes its cellular location and alters its substrate specificity. | SIGNOR-268153 |
P68400 | Q14005 | 1 | phosphorylation | up-regulates activity | 0.326 | We now show that N-terminal to the NLS domain of pro-IL-16 are protein kinase CK2 substrate and cdc2 kinase substrate sites which, along with the NLS, constitute a dual phosphorylation-regulated CcN motif which regulates nuclear localization of pro-IL-16. In addition, we demonstrate that mutation of either site is associated with impairment of the N-terminal domain's ability to induce G(0)/G(1) cell cycle arrest. | Thus, we confirm that the N-terminal (42SLNEE46) sequence of pro-IL-16 is in fact a site for protein kinase CK2 phosphorylation. | SIGNOR-250905 |
P13056 | P28482 | 0 | phosphorylation | down-regulates activity | 0.2 | We also reported that ERK2-phosphorylated TR2 is recruited to PML nuclear bodies (PML NBs) for its subsequent small ubiquitin-like modification (SUMOylation) and function as a potent transcriptional repressor xref , xref . | SIGNOR-278957 |
P63151 | P31749 | 2 | binding | down-regulates activity | 0.484 | Regulation of phosphorylation of Thr-308 of Akt, cell proliferation, and survival by the B55alpha regulatory subunit targeting of the protein phosphatase 2A holoenzyme to Akt.|Phosphorylation of Akt at regulatory residues Thr-308 and Ser-473 leads to its full activation. The protein phosphatase 2A (PP2A) has long been known to negatively regulate Akt activity. The PP2A holoenzyme consists of the structural |Here we report the identification of the specific B regulatory subunit that targets the PP2A holoenzyme to Akt. We found endogenous association of PP2A AB55C holoenzymes with Akt by co-immunoprecipitation analyses in pro-lymphoid FL5.12 cells.subunit (A), catalytic subunit (C), and a variable regulatory subunit (B). | SIGNOR-252637 |
Q86UY5 | Q8N752 | 2 | 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-273756 |
P43146 | Q6ZN44 | 2 | binding | down-regulates activity | 0.661 | In the presence of netrin-1, UNC5 co-immuno-precipitates with DCC, suggesting the formation of a ternary complex of netrin-1 with ecto-domains of DCC and UNC5. DCC binding to netrin-1 alone leads to axon attraction. Importantly, DCC has the ability to switch the netrin-1-mediated responses from attraction to repulsion when another receptor UNC5 co-exists. DCC binding to netrin-1 alone leads to axon attraction. Importantly, DCC has the ability to switch the netrin-1-mediated responses from attraction to repulsion when another receptor UNC5 co-exists. | SIGNOR-268164 |
P36639 | Q13309 | 2 | binding | down-regulates quantity by destabilization | 0.253 | Here, we report that MTH1 is regulated by polyubiquitination mediated by the E3 ligase Skp2. In melanoma cells, MTH1 was upregulated commonly mainly due to its improved stability caused by K63-linked polyubiquitination. Although Skp2 along with other components of the Skp1-Cullin-F-box (SCF) ubiquitin ligase complex was physically associated with MTH1, blocking the SCF function ablated MTH1 ubiquitination and expression. Conversely, overexpressing Skp2-elevated levels of MTH1 associated with an increase in its K63-linked ubiquitination. | SIGNOR-272790 |
P25105 | P38405 | 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-256932 |
P07948 | P07948 | 2 | phosphorylation | up-regulates activity | 0.2 | Lyn is a member of the Src family of protein-tyrosine kinases that can readily undergo autophosphorylation in vitro. The site of autophosphorylation is Tyr397. Autophosphorylation results in a 17-fold increase in protein-tyrosine kinase activity. | SIGNOR-251402 |
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 |
P11309 | P36888 | 1 | phosphorylation | up-regulates quantity | 0.42 | Pim-1 Kinase Phosphorylates and Stabilizes 130 kDa FLT3 and Promotes Aberrant STAT5 Signaling in Acute Myeloid Leukemia with FLT3 Internal Tandem Duplication[...]Pim-1 inhibition also decreased phosphorylation of FLT3 at tyrosine 591 and of STAT5, and expression of Pim-1 itself, consistent with inhibition of the FLT3-ITD-STAT5 signaling pathway. | SIGNOR-259927 |
P11215 | P05362 | 2 | binding | up-regulates | 0.773 | Before leaving the vessel lumen, neutrophils crawl on the endothelium, primarily using cell surface Mac-1 integrins binding to endothelial ICAM-1. | SIGNOR-255041 |
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