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 |
|---|---|---|---|---|---|---|---|
P35368 | P38405 | 1 | binding | up-regulates activity | 0.278 | 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-256950 |
P68400 | P13569 | 1 | phosphorylation | down-regulates | 0.278 | Cftr possesses two ck2 phosphorylation sites (s422 and t1471) the t1471 residue, previously described as a site for cftr phosphorylation by ck2 (25), seems to be critical for cftr turnover and processing. | SIGNOR-176627 |
P49841 | Q9NRR4 | 1 | phosphorylation | up-regulates activity | 0.278 | Our findings suggest that phosphorylation of Drosha at multiple sites including S300 promotes its translocation to the cytoplasm. Interestingly, GSK3beta can phosphorylate Drosha at S300 and S302 in vitro. This has been reported to promote the nuclear localization of Drosha under basal condition (Tang et al., 2011). Thus, it appears that phosphorylation of S300 by GSK3beta and p38 MAPK is involved in opposing processes. | SIGNOR-264846 |
P17252 | P24844 | 1 | phosphorylation | down-regulates | 0.278 | Rlc can also be phosphorylated at ser1/ser2/thr9 by protein kinase c (pkc). Biophysical studies show that phosphorylation at these sites leads to an increase in the km of myosin light chain kinase (mlck) for rlc, thereby indirectly inhibiting myosin ii activity | SIGNOR-192792 |
P49841 | Q15208 | 1 | phosphorylation | down-regulates activity | 0.278 | GSK-3β phosphorylated STK38 on residues S6 and T7 in vitro, depending largely on a PKA-mediated priming phosphorylation of STK38 on residues S10 and S11, respectively. Our results indicate that that GSK-3β inhibits STK38's full activation, and suggest that STK38 activation is required to prevent cell death in response to oxidative stress. | SIGNOR-276392 |
Q9H0K1 | Q09472 | 1 | phosphorylation | down-regulates activity | 0.278 | Indeed, overexpression of SIK2 increased p300 phosphorylation at Ser89, while knockdown of SIK2 decreased it (Fig. 4B). | SIGNOR-278368 |
Q99814 | P41229 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.278 | To this end, we confirm that KDM3A, KDM4B, KDM4C, KDM5B, KDM5C, and KDM62 are direct targets of HIF-1a while extent the list of known targets to KDM2A, KDM2B, KDM4D, KDM5A, and KDM6A. The results demonstrated that majority of the KDMs were similarly induced (KDM2A, KDM2B, KDM3A, KDM4B, KDM4C, KDM4D, KDM5A, KDM5B, KDM5C, KDM6B, and KDM7A) or repressed (KDM NO66 and KDM1A) by both HIF-1a and HIF-2a. | SIGNOR-271579 |
P50750 | Q9H0D6 | 1 | phosphorylation | up-regulates activity | 0.278 | Among the RNA processing factors phosphorylated by Cdk9 was the 5'-to-3' "torpedo" exoribonuclease Xrn2, required in transcription termination by Pol II, which we validated as a bona fide P-TEFb substrate in vivo and in vitro. Phosphorylation by Cdk9 or phosphomimetic substitution of its target residue, Thr439, enhanced enzymatic activity of Xrn2 on synthetic substrates in vitro. | SIGNOR-277194 |
O14965 | P06730 | 1 | phosphorylation | up-regulates activity | 0.278 | In this study, we demonstrated for the first time that AURKA can phosphorylate and activate EIF4E. | SIGNOR-279495 |
P16298 | O00429 | 1 | dephosphorylation | up-regulates activity | 0.278 | When mitochondrial depolarization is associated with sustained cytosolic Ca(2+) rise, it activates the cytosolic phosphatase calcineurin that normally interacts with Drp1. Calcineurin-dependent dephosphorylation of Drp1, and in particular of its conserved serine 637, regulates its translocation to mitochondria as substantiated by site directed mutagenesis. | SIGNOR-248361 |
P35348 | P38405 | 1 | binding | up-regulates activity | 0.278 | 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-256955 |
P25100 | P38405 | 1 | binding | up-regulates activity | 0.278 | 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-256951 |
P11308 | P33151 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.278 | Erg overexpression resulted in an approximate 1.8-fold transactivation of VE-cadherin promoter activity. Thus, our data indicate that Erg drives constitutive VE-cadherin expression in human ECs | SIGNOR-261595 |
P07996 | P01138 | 1 | binding | up-regulates | 0.278 | We have identified a mechanism for the activation of latent tgf-beta that involves binding of the secreted and extracellular matrix protein, thrombospondin-1 (tsp-1), to the latent precursor. | SIGNOR-75624 |
Q9NXA8 | P11413 | 1 | catalytic activity | up-regulates activity | 0.278 | Here, we report that SIRT5 desuccinylates and deglutarylates isocitrate dehydrogenase 2 (IDH2) and glucose-6-phosphate dehydrogenase (G6PD), respectively, and thus activates both NADPH-producing enzymes. | SIGNOR-261211 |
Q8TDV5 | P63096 | 1 | binding | up-regulates activity | 0.278 | 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-257040 |
P21917 | P19086 | 1 | binding | up-regulates activity | 0.278 | 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-257098 |
P49683 | P08754 | 1 | binding | up-regulates activity | 0.278 | 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-256837 |
O94986 | P24941 | 1 | relocalization | up-regulates activity | 0.278 | Primary microcephaly (MCPH) associated proteins CDK5RAP2, CEP152, WDR62 and CEP63 colocalize at the centrosome. We found that they interact to promote centriole duplication and form a hierarchy in which each is required to localize another to the centrosome, with CDK5RAP2 at the apex, and CEP152, WDR62 and CEP63 at sequentially lower positions. MCPH proteins interact with distinct centriolar satellite proteins; CDK5RAP2 interacts with SPAG5 and CEP72, CEP152 with CEP131, WDR62 with MOONRAKER, and CEP63 with CEP90 and CCDC14. These satellite proteins localize their cognate MCPH interactors to centrosomes and also promote centriole duplication. Consistent with a role for satellites in microcephaly, homozygous mutations in one satellite gene, CEP90, may cause MCPH. The satellite proteins, with the exception of CCDC14, and MCPH proteins promote centriole duplication by recruiting CDK2 to the centrosome. | SIGNOR-271724 |
P78415 | P17302 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.278 | Irx3 directly represses Cx43 transcription | SIGNOR-266044 |
Q06187 | Q00987 | 1 | phosphorylation | down-regulates activity | 0.278 | Phosphorylation of MDM2 by BTK suppresses its ubiquitination activity. | SIGNOR-278330 |
P27361 | P51168 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.278 | Using a number of different approaches it was demonstrated that the protein kinase acting on betaThr-613 and gammaThr-623 is the extracellular regulated kinase (ERK). It is suggested that an ERK-mediated phosphorylation of betaThr-613 and gammaThr-623 down-regulates the channel by facilitating its interaction with Nedd4. | SIGNOR-249447 |
Q15750 | Q01974 | 1 | phosphorylation | down-regulates | 0.278 | Tak1 (tgf-beta activated kinase 1), a map3k, interacts with ror2 and phosphorylates its intracellular carboxyterminal serine/thronine/proline-rich (stp) domain | SIGNOR-180566 |
O60755 | P09471 | 1 | binding | up-regulates activity | 0.278 | 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-256998 |
P01106 | P11908 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.277 | Analysis of in vivo C-MYC interactions with TS, IMPDH2 and PRPS2 genes confirmed that they are direct C-MYC targets. C-MYC depletion did not significantly affect levels of E2F1 protein reported to regulate expression of many S-phase specific genes, but resulted in the repression of several genes encoding enzymes rate-limiting for dNTP metabolism. These included thymidylate synthase (TS), inosine monophosphate dehydrogenase 2 (IMPDH2) and phosphoribosyl pyrophosphate synthetase 2 (PRPS2). C-MYC depletion also resulted in reduction in the amounts of deoxyribonucleoside triphosphates (dNTPs) and inhibition of proliferation. | SIGNOR-267376 |
P45983 | Q01094 | 1 | phosphorylation | down-regulates activity | 0.277 | JNK1 phosphorylates E2F1 in vitro, and co-transfection of JNK1 reduces the DNA binding activity of E2F1 | SIGNOR-279218 |
P63279 | Q6DJT9 | 1 | sumoylation | down-regulates | 0.277 | Sumoylation decreases the transcriptional activity of plag1 / plag1 is sumoylated at 2 specific lysine residues (lys-244 and lys-263) | SIGNOR-126048 |
Q13153 | Q7L099 | 1 | phosphorylation | up-regulates quantity | 0.277 | (a) PAK1 phosphorylates RUFY3 in vitro.|Taken together, these results indicate that PAK1 can upregulate RUFY3 protein expression. | SIGNOR-279243 |
P29320 | Q13153 | 1 | phosphorylation | up-regulates activity | 0.277 | Etk kinase directly phosphorylates and activates PAK1 in response to estrogen.|We demonstrated that estrogen-activated Etk directly phosphorylated PAK1 on Tyr153. | SIGNOR-278398 |
Q12772 | O75874 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.277 | IDH1 gene transcription is sterol regulated and activated by SREBP-1a and SREBP-2 in human hepatoma HepG2 cells|evidence that IDH1 may regulate lipogenesis in hepatic cells | SIGNOR-253133 |
Q05086 | Q13200 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.277 | Our experiments collectively suggest that UBE3A stimulates Wnt pathway activation by interacting with, ubiquitinating, and reducing the levels of multiple (PSMB1, PSMC2, PSMD2, and PSMD7) proteasome subunits. | SIGNOR-265133 |
Q05513 | Q96A00 | 1 | phosphorylation | up-regulates activity | 0.277 | 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-249261 |
P56945 | P84022 | 1 | binding | down-regulates | 0.277 | In this study, we show that, after tyrosine phosphorylation of p130cas mediated by integrin signaling, the phosphorylated p130cas is able to interact with phosphorylated smad3 and in turn prevent transcriptional activation by smad3 | SIGNOR-161265 |
P27361 | Q9H9Z2 | 1 | phosphorylation | down-regulates activity | 0.277 | Here we show that Lin28a is directly phosphorylated by ERK1/2 kinases at Ser-200. | SIGNOR-277337 |
Q92913 | P35498 | 1 | binding | down-regulates activity | 0.277 | 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-253419 |
P51668 | Q9C040 | 1 | binding | up-regulates activity | 0.277 | Here, we show that TRIM RING finger protein TRIM2, highly expressed in the nervous system, is an UbcH5a-dependent ubiquitin ligase. We further demonstrate that TRIM2 binds to neurofilament light subunit (NF-L) and regulates NF-L ubiquitination. Together, our results indicate that TRIM2 is an ubiquitin ligase that binds to and ubiquitinates NF-L and that TRIM2 deficiency leads to neurodegeneration in mice likely by altering NF-L metabolism with consequent NF-L accumulation in axons and impairment of axonal transport. | SIGNOR-271775 |
P49841 | P06401 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.277 | Here, we have found that glycogen synthase kinase (GSK)-3β phosphorylation of progesterone receptor-A (PR-A) facilitates its ubiquitination. GSK-3β-mediated phosphorylation of serine 390 in PR-A regulates its subsequent ubiquitination and protein stability. | SIGNOR-276498 |
Q12913 | P07949 | 1 | dephosphorylation | down-regulates activity | 0.277 | The receptor-type protein tyrosine phosphatase J antagonizes the biochemical and biological effects of RET-derived oncoproteins.|PTPRJ expression induces dephosphorylation of the RET(C634R) and, probably via an indirect mechanism, RET/PTC1 oncoproteins on two key RET autophosphorylation sites (Tyr1062 and Tyr905). This results in a significant decrease of RET-induced Shc and extracellular signal-regulated kinase 1/2 phosphorylation levels | SIGNOR-248701 |
P46934 | Q13501 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.277 | Depletion of NEDD4 dramatically reduced the LC3 protein level and elevated the SQSTM1 protein level.|Furthermore, SQSTM1 is ubiquitinated by NEDD4 while LC3 functions as an activator of NEDD4 ligase activity. | SIGNOR-278637 |
P20309 | P63096 | 1 | 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-256739 |
P48729 | Q6IE81 | 1 | phosphorylation | down-regulates activity | 0.277 | We demonstrate that the destruction complex component casein kinase 1α (CK1α) phosphorylates Jade-1 at a conserved SLS motif and reduces the ability of Jade-1 to inhibit β-catenin signaling. | SIGNOR-273618 |
P28482 | Q14674 | 1 | phosphorylation | down-regulates | 0.277 | Both cdc2/cyclinb1 and mapk (erk2) efficiently phosphorylate separase at its major inhibitory site in vitro | SIGNOR-113130 |
Q9Y2M5 | Q14457 | 1 | binding | down-regulates quantity by destabilization | 0.277 | 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-272415 |
O96013 | P03372 | 1 | phosphorylation | up-regulates activity | 0.277 | Further, PAK4 phosphorylated ER\u03b1-Ser305, a phosphorylation event needed for the PAK4 activation of ER\u03b1-dependent transcription.|Further, PAK4 phosphorylated ERalpha-Ser305, a phosphorylation event needed for the PAK4 activation of ERalpha dependent transcription. | SIGNOR-279472 |
Q96NI6 | P23468 | 1 | binding | up-regulates activity | 0.277 | SALM5 trans-synaptically interacts with LAR-RPTPs in a splicing-dependent manner to regulate synapse development. we identified LAR-RPTPs as novel ligands of SALM5 that mediates SALM5-dependent presynaptic differentiation in a splicing-dependent manner. Our data indicate that SALM5 interacts with all three known LAR-RPTPs—LAR, PTPδ, and PTPσ (Fig. 1). | SIGNOR-264086 |
O15294 | P17858 | 1 | glycosylation | down-regulates activity | 0.277 | O-GlcNAcylation was induced at serine 529 of phosphofructokinase 1 (PFK1) in response to hypoxia. Glycosylation inhibited PFK1 activity and redirected glucose flux through the pentose phosphate pathway| O-GlcNAc transferase (OGT) catalyzes the transfer of N-acetylglucosamine from uridine diphospho-N-acetylglucosamine (UDP-GlcNAc) to serine or threonine residues | SIGNOR-267585 |
P39687 | P55211 | 1 | binding | up-regulates activity | 0.277 | PHAP proteins promoted caspase-9 activation after apoptosome formation, whereas ProT negatively regulated caspase-9 activation by inhibiting apoptosome formation. | SIGNOR-259082 |
P63104 | P07196 | 1 | binding | down-regulates activity | 0.277 | These results suggest the important role of 14-3-3 in the dynamic regulation of NF-L assembly, and in the capacity to prevent the formation of NF-L aggregates. all seven isoforms specifically interacted with NF-L, but not NF-M or NF-H. specific interaction of 14-3-3 proteins with phosphorylated NF-L subunits also indicated the role of 14-3-3 and NF-L phosphorylation in the disassembly of neurofilaments. What is more, binding of 14-3-3 to phosphorylated NF-L subunits may prevent the dephosphorylation of these subunits by phosphatases, maintaining the hyperphosphorylation state of the subunits, which facilitates the disassembly of neurofilaments. | SIGNOR-252397 |
Q05513 | P46937 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.277 | Yap and β-catenin are direct substrates of PKCζ.We show here that PKCζ suppresses intestinal stem cell function by promoting the downregulation of β-catenin and Yap through direct phosphorylation.Consistent with MS/MS analysis, mutation to alanine of these two sites completely abolished Yap phosphorylation by PKCζ. Interestingly, S109 and T110 sites were highly conserved among species (Figure S3B), which suggested an important role in Yap regulation. | SIGNOR-276877 |
P51149 | P63000 | 1 | binding | up-regulates activity | 0.277 | Rab7-Rac1 interaction may mediate late endosomal transport between microtubules and microfilaments | SIGNOR-261304 |
P28335 | Q03113 | 1 | 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-257405 |
P23470 | Q13224 | 1 | dephosphorylation | up-regulates activity | 0.277 | 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-254702 |
Q9NQS5 | P08754 | 1 | 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 |
Q5TGU0 | P12235 | 1 | binding | up-regulates activity | 0.277 | Our results demonstrate the existence of a VDAC-TSPO2-ANT complex that mediates ATP release from RBCs. We previously demonstrated that the translocase protein TSPO2 together with the voltage-dependent anion channel (VDAC) and adenine nucleotide transporter (ANT) were involved in a membrane transport complex in human red blood cells (RBCs). . The present results show that TSPO ligands induce polymerization of VDAC, coupled to activation of ATP release by a supramolecular complex involving VDAC, TSPO2 and ANT. | SIGNOR-261825 |
O75365 | P15311 | 1 | dephosphorylation | down-regulates activity | 0.277 | Here we report the identification of Ezrin as a specific and direct cellular substrate of PRL-3. In HCT116 colon cancer cell line, Ezrin was identified among the cellular proteins whose phosphorylation level decreased upon ectopic over-expression of wtPRL-3 but not of catalytically inactive PRL-3 mutants. Although PRL-3 over-expression in HCT116 cells appeared to affect Ezrin phosphorylation status at both tyrosine residues and Thr567, suppression of the endogenous protein by RNA interference pointed to Ezrin-Thr567 as the residue primarily affected by PRL-3 action. | SIGNOR-248342 |
P37231 | P20393 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.277 | Mutations of the 5' or 3' half-sites of the response element totally abrogated PPARgamma binding and transcriptional activation, identifying this site as a novel type of functional PPARgamma response element. Finally, ectopic expression of Rev-Erbalpha in 3T3-L1 preadipocytes potentiated adipocyte differentiation induced by the PPARgamma ligand rosiglitazone. These results identify Rev-Erbalpha as a target gene of PPARgamma in adipose tissue and demonstrate a role for this nuclear receptor as a promoter of adipocyte differentiation. | SIGNOR-268022 |
P53355 | P09493 | 1 | phosphorylation | up-regulates activity | 0.277 | We identified, for the first time, death-associated protein kinase 1 (DAP kinase 1) as the kinase that phosphorylates tropomyosin-1 in response to ERK activation by hydrogen peroxide (H(2)O(2)). We also report that the phosphorylation of tropomyosin-1 mediated by DAP kinase occurs on Ser283. Our finding that tropomyosin-1 is phosphorylated downstream of ERK and DAP kinase and that it helps regulate the formation of stress fibers will aid understanding the role of this protein in regulating the endothelial functions associated with cytoskeletal remodeling. | SIGNOR-262845 |
P41595 | P63096 | 1 | 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-256743 |
Q08209 | O00429 | 1 | dephosphorylation | up-regulates activity | 0.277 | When mitochondrial depolarization is associated with sustained cytosolic Ca(2+) rise, it activates the cytosolic phosphatase calcineurin that normally interacts with Drp1. Calcineurin-dependent dephosphorylation of Drp1, and in particular of its conserved serine 637, regulates its translocation to mitochondria as substantiated by site directed mutagenesis. | SIGNOR-248676 |
Q13191 | P04629 | 1 | ubiquitination | down-regulates quantity | 0.276 | Cbl-b modulated TrkA ubiquitination and function in the dorsal root ganglion of mice.|Viral expression of constitutively active Cbl-b in DRGs of osteoarthritic mice effectively repressed TrkA protein level and more importantly, alleviated mechanical allodynia and heat hyperalgesia. | SIGNOR-278690 |
P41143 | O95837 | 1 | binding | up-regulates activity | 0.276 | 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-256962 |
P29317 | P19174 | 1 | phosphorylation | up-regulates activity | 0.276 | EphA2 activates PLC\u03b31 in human lung cancer cells.|The result here showed that only wild-type EphA2, but not K646M\nor Y588F mutants, could phosphorylate PLC\u03b31, demonstrating that\nPLC\u03b31 phosphorylation is dependent on the kinase activity of EphA2. | SIGNOR-279708 |
P24666 | Q05397 | 1 | dephosphorylation | down-regulates activity | 0.276 | Lymphocyte function-associated antigen-1-mediated T cell adhesion is impaired by low molecular weight phosphotyrosine phosphatase-dependent inhibition of FAK activity. 4000254={CellProcess=4107155 CellType=10000184}}|Moreover, in these conditions LMW-PTP causes FAK dephosphorylation, thus preventing the activation of FAK downstream pathways. | SIGNOR-277064 |
P06493 | O14745 | 1 | phosphorylation | down-regulates activity | 0.276 | During the early stages of mitosis in HeLa cells, Cdc2 phosphorylates EBP50 on serine residues 280 and 302.|Phosphorylation by Cdc2 inhibits EBP50's role in forming microvilli in interphase but not mitotic cells. (A) Results from scoring JEG-3 cells for the presence of microvilli; error bars indicate mean \u00b1 SD. (B) Representative images from the microvillar rescue assay. | SIGNOR-278305 |
Q96J02 | O95999 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.276 | The HECT domain ubiquitin ligases NEDD4 and Itch promote ubiquitination and degradation of Bcl10, thus downmodulating NF-kappa B activation. | SIGNOR-271414 |
P01106 | P34896 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.276 | Myc regulates the de novo purine and pyrimidine synthetic genes in multiple biological systems. Intriguingly, MYC was found to directly activate the expression of SHMT1, and SHMT2, which are enzymes involved in single carbon metabolism and are essential for dNTP synthesis | SIGNOR-267379 |
P62258 | P07196 | 1 | binding | down-regulates activity | 0.276 | These results suggest the important role of 14-3-3 in the dynamic regulation of NF-L assembly, and in the capacity to prevent the formation of NF-L aggregates. all seven isoforms specifically interacted with NF-L, but not NF-M or NF-H. specific interaction of 14-3-3 proteins with phosphorylated NF-L subunits also indicated the role of 14-3-3 and NF-L phosphorylation in the disassembly of neurofilaments. What is more, binding of 14-3-3 to phosphorylated NF-L subunits may prevent the dephosphorylation of these subunits by phosphatases, maintaining the hyperphosphorylation state of the subunits, which facilitates the disassembly of neurofilaments. | SIGNOR-252398 |
Q00987 | Q9Y5A7 | 1 | ubiquitination | up-regulates activity | 0.276 | Our results rather suggest that Mdm2 specifically ubiquitinates NUB1 on lysine 159 and that this modification is required for NUB1 functions.|We conclude that Mdm2 acts as a positive regulator of NUB1 function, by modulating NUB1 ubiquitination on lysine 159. | SIGNOR-278556 |
Q14119 | P05305 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.276 | Vascular endothelial zinc finger 1 (Vezf1)/DB1 is a recently identified zinc finger-containing protein that is expressed specifically within endothelial cells during development. In this report, we demonstrate that Vezf1/DB1 is a nuclear localizing protein that potently and specifically activates transcription mediated by the human endothelin-1 promoter, in a Tax-independent manner, in transient transfection assays. Regulation of endothelin-1 promoter activity by Vezf1/DB1 provides a mechanism for endothelin-1 expression in the vascular endothelium during development and to maintain vascular tone | SIGNOR-266884 |
P62714 | P01106 | 1 | dephosphorylation | down-regulates | 0.276 | Phosphorylation at ser-62 by pro-directed kinases (p-k) is a prerequisite for gsk3-dependent phosphorylation of thr-58. This triggers binding of pin1, subsequently protein phosphatase 2a (pp2a)-dependent dephosphorylation of ser-62, and then recruitment of scf-fbw7 to the thr-58-phosphorylated myc. Scf-fbw7 polyubiquitinylates myc (branching through lys-48), leading to its proteasomal degradation. | SIGNOR-149726 |
P62714 | P37840 | 1 | dephosphorylation | down-regulates activity | 0.276 | α-Synuclein (α-Syn) is a key protein that accumulates as hyperphosphorylated aggregates in pathologic hallmark features of Parkinson's disease (PD) and other neurodegenerative disorders. Phosphorylation of this protein at serine 129 is believed to promote its aggregation and neurotoxicity, suggesting that this post-translational modification could be a therapeutic target. Here, we demonstrate that phosphoprotein phosphatase 2A (PP2A) dephosphorylates α-Syn at serine 129 | SIGNOR-248592 |
P27361 | Q9UBS5 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.276 | 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-277854 |
P04201 | P30556 | 1 | binding | down-regulates activity | 0.276 | our findings demonstrate that the protein encoded by the Mas proto-oncogene exhibits direct antagonistic properties on the AT1 receptor in vitro and that this oligomeric interaction may represent a natural state for these receptors in vivo in some tissues. the present findings in native tissues suggest that the Mas receptor can act as an in vivo functional antagonist of the AT1 receptor owing to formation of a hetero-oligomeric complex | SIGNOR-260626 |
Q13164 | O14757 | 1 | phosphorylation | up-regulates activity | 0.276 | Moreover, we demonstrate that ERK5 facilitates Chk1 phosphorylation induced by IR.|Since we have found that ERK5 was able to accelerate the phosphorylation and activation of IR-induced Chk1, therapeutic targeting of Chk1 in NSCLC cells with high ERK5 expression might be an effective strategy for overcoming radioresistance. | SIGNOR-280028 |
P07332 | P16284 | 1 | phosphorylation | up-regulates activity | 0.276 | PECAM-1 Is Phosphorylated by Fer and, To a Lesser Extent, by Fes. These results suggest that Fer not only functions as a tyrosine kinase for PECAM-1 but also that Fer modulates the downstream signaling of PECAM-1 by inducing phosphorylation of SHP-2 and Gab1. | SIGNOR-262868 |
P17706 | P01116 | 1 | dephosphorylation | down-regulates activity | 0.276 | Mechanistically, PTPN2 negatively regulates tyrosine phosphorylation of KRAS, which, in turn, affects the activation KRAS and its downstream signaling. | SIGNOR-277039 |
P17676 | Q99988 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.276 | Promoter analysis and chromatin immunoprecipitation analysis revealed that CEBPB could contribute to K7174-mediated transcriptional activation of GDF15. | SIGNOR-254050 |
Q8IXJ9 | P42772 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.276 | Tumor suppressor ASXL1 is essential for the activation of INK4B expression in response to oncogene activity and anti-proliferative signals | SIGNOR-241759 |
Q13976 | P11831 | 1 | phosphorylation | up-regulates | 0.275 | Myotonic dystrophy protein kinase (DMPK), a muscle- and neuron-restricted kinase, enhanced SRF-mediated promoter activity of the skeletal and cardiac alpha-actin genes in C2C12 myoblasts as well as in nonmyogenic cells. | Threonine 159 in the MADS box alphaI coil was a specific phosphorylation target in vitro as well as in vivo of both DMPK and protein kinase C-alpha. | SIGNOR-188185 |
P42685 | P46937 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.275 | Mechanistically, FRK interacted with and phosphorylated YAP on Tyr391/407/444, which recruited the classical E3 ubiquitin ligase Siah1 to catalyze ubiquitination and eventually degradation of YAP. | SIGNOR-275456 |
P22612 | Q14896 | 1 | phosphorylation | up-regulates | 0.275 | Phosphorylation of cmybp-c by pka speeds actomyosin interactions and contributes to increased cardiac contractility following _-adrenergic stimulation.7, 8 phosphorylation by pka is essential for proper cardiac function /for the human isoform, three pka sites were previously identified (ser275, ser284, and ser304) /our results indicate that pka phosphorylates up to four sites in both the murine and human m-domains including a novel site not previously described for either protein (ser307 for mouse and ser311 for human). | SIGNOR-163788 |
P08069 | O00443 | 1 | phosphorylation | up-regulates | 0.275 | Analysis of the ability of the full-length igfr and its mutant receptors described above to associate with phosphatidylinositol 3 kinase indicated that the association required ptk activity and tyrosine [?] Phosphorylation of the receptors and correlated well with their transforming activities | SIGNOR-32076 |
P08246 | P01019 | 1 | cleavage | up-regulates activity | 0.275 | Cathepsin G, elastase, and proteinase 3 are serine proteinases released by activated neutrophils. Cathepsin G can cleave angiotensinogen to release angiotensin II, but this activity has not been previously reported for elastase or proteinase 3. In this study we show that elastase and proteinase 3 can release angiotensin I from angiotensinogen and release angiotensin II from angiotensin I and angiotensinogen. | SIGNOR-256313 |
Q03431 | P50148 | 1 | binding | up-regulates activity | 0.275 | This calciotropic hormone exerts its actions via binding to the PTH/PTH-related peptide receptor (PTH1R), which couples to multiple heterotrimeric G proteins, including Gs and Gq/11. | SIGNOR-270550 |
O14640 | Q9NQ66 | 1 | null | up-regulates activity | 0.275 | Dsh through PLC activates IP3, which leads to release of intracellular Ca2+, which in turn activates CamK11 and calcineurin | SIGNOR-258978 |
P53355 | P19105 | 1 | phosphorylation | up-regulates activity | 0.275 | DAPK Phosphorylates Myosin II RLC in Vitro and in Vivo. Together these results show that similar to the conventional MLCKs, Ser-19 is the primary RLC residue phosphorylated by DAPK and that phosphorylation of Thr-18 is also possible. | SIGNOR-262842 |
P17612 | Q14896 | 1 | phosphorylation | up-regulates | 0.275 | Phosphorylation of cmybp-c by pka speeds actomyosin interactions and contributes to increased cardiac contractility following _-adrenergic stimulation.7, 8 phosphorylation by pka is essential for proper cardiac function /for the human isoform, three pka sites were previously identified (ser275, ser284, and ser304) /our results indicate that pka phosphorylates up to four sites in both the murine and human m-domains including a novel site not previously described for either protein (ser307 for mouse and ser311 for human). | SIGNOR-163760 |
Q05513 | P35612 | 1 | phosphorylation | down-regulates | 0.275 | We now demonstrate that ptn stimulates the phosphorylation of serines 713 and 726 in the myristoylated alanine-rich protein kinase (pk) c substrate domain of beta-adducin through activation of either pkc alpha or beta. | SIGNOR-139914 |
P49683 | P50148 | 1 | binding | up-regulates activity | 0.275 | 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-257089 |
P49841 | P19793 | 1 | phosphorylation | up-regulates activity | 0.275 | GSK3β-induced RXRα phosphorylation decreased for RXRα-S49A, RXRα-S66A and RXRα-S78A in HEK293 cells compared with RXRα WT by western blot analysis. | SIGNOR-277371 |
P15336 | Q9H6S0 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.275 | Collectively, these data show that YTHDC2 plays an important role in tumor cells growth and activation/recruitment of c-Jun and ATF-2 to the YTHDC2 promoter is necessary for the transcription of YTHDC2, and that HDAC activity is required for the efficient expression of YTHDC2 in both of hepatocyte and HCC cells. | SIGNOR-269001 |
Q12948 | Q06330 | 1 | binding | up-regulates | 0.275 | We demonstrate that physical interactions occur between wt1, foxc1/2 and rbpj, suggestive of the formation of multimeric transcriptional complexes. | SIGNOR-176183 |
P28702 | P24468 | 1 | binding | up-regulates | 0.275 | Arp-1/rxr, coup-tfi/rxr, and arp-1/coup-tfi heterodimers bound the fp330-3' site. | SIGNOR-79452 |
Q96BR1 | Q14524 | 1 | phosphorylation | up-regulates activity | 0.275 | Among the sites identified, only six were previously suggested to be the targets for specific kinases using in silico and/or in vitro analyses: S36 and S525 were attributed to the regulation by PKA; S484 and S664 were assigned to the serum- and glucocorticoid-inducible kinase 3 (SGK3); and S516 and S571 were ascribed to CaMKII (reviewed in Marionneau and Abriel, 2015). In marked contrast, several previously described phosphorylation sites were not detected in the present study, including the PKA-dependent S528, the CaMKII-associated T594, the PKC-dependent S1506, the adenosine monophosphate–activated protein kinase (AMPK)–dependent T101 (Liu et al., 2019), and the six Fyn-dependent tyrosines (Ahern et al., 2005; Iqbal et al., 2018).|The simplest interpretation of these findings is that these three phosphorylation clusters, at positions S457-S460, S483-T486, and S664-S671, are likely involved in regulating the basal and/or gating properties of native cardiac NaV1.5 channels. Conversely, the other phosphorylation sites, with lower stoichiometries, may play spatially or temporally distinct roles in the physiological or more pathophysiological regulation of channel expression or gating. | Remarkably, this MS analysis also revealed that the vast majority of identified phosphorylation sites (at least 26) are clustered, suggesting concomitant phosphorylation and roles in regulating channel expression and/or function. Unexpectedly, however, except for S664, S667, and S671, no apparent effects of phosphomimetic or phosphosilent mutations were observed on heterologously expressed (in HEK-293 cells) NaV1.5 | SIGNOR-275767 |
P07949 | P42224 | 1 | phosphorylation | up-regulates activity | 0.275 | In detail, RET and PTC3 induced STAT1 overexpression and phosphorylation at Ser 727 and Tyr 701. | SIGNOR-279276 |
Q9GZV5 | P15172 | 1 | binding | up-regulates | 0.275 | Taz physically interacts with myod through the ww domain and activates myod-dependent gene transcription. | SIGNOR-165414 |
O14757 | P19838 | 1 | phosphorylation | down-regulates | 0.275 | Taken together, the above findings suggest that chk1 phosphorylates p50 at s329 and further, that this phosphorylation blocks p50 dna binding. | SIGNOR-195208 |
P53350 | Q49MG5 | 1 | phosphorylation | up-regulates | 0.275 | We also demonstrate that asap is a novel substrate of plk1 phosphorylation and have identified serine 289 as the major phosphorylation site by plk1 in vivo. Asap phosphorylated on serine 289 is localized to centrosomes during mitosis, but this phosphorylation is not required for its plk1-dependent localization at the spindle poles. We show that phosphorylated asap on serine 289 contributes to spindle pole stability in a microtubule-dependent manner | SIGNOR-166564 |
P15056 | P00519 | 1 | phosphorylation | up-regulates activity | 0.275 | BRAF V600E activates Abl and Arg.|Rather, BRAF V600E, a serine threonine kinase, induced Abl threonine phosphorylation (XREF_FIG), and tyrosine phosphorylation of kinase-inactive Abl or Arg, which lack the ability to autophosphorylate (XREF_FIG). | SIGNOR-278914 |
Q9H0M0 | Q4VCS5 | 1 | ubiquitination | up-regulates quantity by stabilization | 0.275 | Here low serum and high LATS1 activity are found to enhance the levels of the 130-kDa isoform of angiomotin (Amot130) through phosphorylation by LATS1/2 at serine 175, which then forms a binding site for 14-3-3. Such phosphorylation, in turn, enables the ubiquitin ligase atrophin-1 interacting protein (AIP)4 to bind, ubiquitinate, and stabilize Amot130 | SIGNOR-275847 |
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