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 |
|---|---|---|---|---|---|---|---|
Q96GD4 | Q8NG31 | 1 | phosphorylation | down-regulates | 0.2 | To determine whether the combinatorial regulation of the kmn network by aurora b observed in vitro is critical to controlling kinetochore-microtubule attachments in vivo, we next investigated the effect of the phosphomimetic (to aspartate) and nonphosphorylatable (to alanine) mutants of dsn1, knl1, and ndc80 in vertebrate cells. We predicted that both types of mutations in critical phosphorylation sites would affect chromosome segregation, since preventing the inactivation of inappropriately attached kinetochores by aurora b (in the nonphosphorylatable mutant) or constitutively inactivating this attachment (in the phosphomimetic mutant). | SIGNOR-165502 |
Q9UK32 | Q9UK32 | 2 | phosphorylation | up-regulates activity | 0.2 | These mutants had minimal kinase activity and showed profoundly decreased phosphorylation at Ser232 compared with wild-type RSK4 (Fig 10B), suggesting that RSK4 can autophosphorylate at Ser232. | SIGNOR-275797 |
O14867 | P52789 | 1 | transcriptional regulation | up-regulates quantity | 0.2 | BACH1 activates transcription of Hexokinase 2 and Gapdh and increases glucose uptake, glycolysis rates, and lactate secretion, thereby stimulating glycolysis-dependent metastasis of mouse and human lung cancer cells. | SIGNOR-259338 |
Q9UKB1 | Q9GZX7 | 1 | binding | down-regulates quantity by destabilization | 0.2 | Further analysis indicated that CUL7 mediated AID ubiquitination by forming a complex with FBXW11. In a CUL7 fl/fl CD19 cre+ mouse model, we demonstrated that CUL7 knockout significantly enhanced AID protein levels in B cells in the germinal center and increased both the IgG1 and IgA class switching. Collectively, our results reveal a subtle regulation mechanism for tightly controlling AID protein levels. F-box proteins are components of SCF ubiquitin-ligase complexes that contain Skp1, CUL1, or CUL7, and an F-box protein | SIGNOR-272024 |
P17481 | Q15746 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | Results from these experiments demonstrated that in 10T1/2 cells Hoxa10-1 increased the activity of the telokin promoter 3-fold without affecting the activity of the other promoters analyzed (Fig. 2A). Similar results were also observed in A10 SMC (data not shown). In contrast, Hoxb8 significantly repressed the activity of the telokin, smooth muscle α-actin, and SM22α promoters by 70, 50, and 70%, respectively | SIGNOR-261640 |
Q14774 | P14635 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | In this study, we have identified cell cycle regulatory genes as downstream targets of the homeobox gene HLX in cultured trophoblast cells, namely RB1, MYC, EGR1, CDKN1C, ELK1, CCNB1, and JUN. RB1 and MYC mRNA expression was increased with HLX inactivation, whereas EGR1, CDKN1C, ELK1, CCNB1, and JUN mRNA expression was decreased compared with mock-transfected control cells. | SIGNOR-261619 |
P17252 | Q38SD2 | 1 | phosphorylation | up-regulates activity | 0.2 | PKCα unexpectedly does not activate LRRK1 by phosphorylating the kinase domain, but instead phosphorylates a cluster of conserved residues (Ser1064, Ser1074 and Thr1075) located within a region of the CORB domain of the GTPase domain. we postulate that phosphorylation of Ser1064, Ser1074 and Thr1075 activates LRRK1 by promoting interaction and stabilization of the αC-helix on the kinase domain. | SIGNOR-276865 |
P17252 | Q8IZQ8 | 1 | phosphorylation | down-regulates activity | 0.2 | PKCalpha directly promoted the basal phosphorylation of endogenous myocardin at serine and threonine residues. | SIGNOR-279099 |
P06493 | Q96PY5 | 1 | phosphorylation | up-regulates activity | 0.2 | In this study we have identified the formin FMNL2 as a novel substrate for CDK1 that plays a role in maintaining adhesion complexes and facilitates cell cycle–dependent changes in adhesion complexes. Knockdown of FMNL2 or expression of a nonphosphorylatable S1016A mutant resulted in the loss of adhesion complexes and stress fibers within the cell body, with peripheral structures being maintained. | SIGNOR-273555 |
P63244 | Q13308 | 1 | binding | up-regulates | 0.2 | Here, we identify rack1 as a novel interaction partner of ptk7. Mechanistically, rack1 is necessary for the ptk7-mediated membrane localization of dishevelled (dsh). Rack1 facilitates the ptk7-dsh interaction by recruiting pkcdelta1, a known effector of dsh membrane translocation. | SIGNOR-172322 |
O15552 | Q14344 | 1 | binding | up-regulates activity | 0.2 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-257397 |
Q9BPV8 | P50148 | 1 | binding | up-regulates activity | 0.2 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-256892 |
P45985 | P19793 | 1 | phosphorylation | down-regulates | 0.2 | Phosphorylation by mkk4/sek1 had profound effects on the biochemical properties of rxr, inhibiting the expression of genes activated by rxr-retinoic acid receptor complexes. Tyr-249 in the rxr de region was required for the inhibitory effect of mkk4/sek1. | SIGNOR-80619 |
P26378 | O14672 | 1 | post transcriptional regulation | up-regulates quantity | 0.2 | Neuronal ELAV (nELAV) proteins are RNA-binding proteins which play a physiological role in controlling gene expression in memory formation, and their alteration may contribute to cognitive impairment associated with neurodegenerative pathologies such as Alzheimer's disease (AD). The experiments show for the first time that ADAM10mRNA represents a nELAV target and that these RNA-binding proteins can play a role in the post-transcriptional regulation of ADAM10 expression. nELAV proteins specifically bind the ADAM10 mRNA and this binding is disrupted following Aβ exposure | SIGNOR-266865 |
P38398 | O75367 | 1 | ubiquitination | up-regulates activity | 0.2 | BRCA1 Ubiquitinates K123 of mH2A1 in a Ligase-Activity-Dependent Manner. | SIGNOR-278752 |
O43318 | Q8IVT5 | 1 | phosphorylation | down-regulates | 0.2 | C-tak1 constitutively associates with mammalian ksr1 and phosphorylates serine 392 to confer 14-3-3 binding and cytoplasmic sequestration of ksr1 in unstimulated cells. In response to signal activation, the phosphorylation state of s392 is reduced, allowing the ksr1 complex to colocalize with activated ras and raf-1 at the plasma membrane | SIGNOR-112779 |
P25105 | P63092 | 1 | binding | up-regulates activity | 0.2 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ‚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-256789 |
P35626 | P35372 | 1 | phosphorylation | down-regulates activity | 0.2 | These results demonstrate that the T180A mutation probably blocks GRK3- and arr3-mediated desensitization of MOR by preventing a critical agonist-dependent receptor phosphorylation and suggest a novel GRK3 site of regulation not yet described for other G-protein-coupled receptors | SIGNOR-247915 |
O15111 | Q07666 | 1 | phosphorylation | up-regulates activity | 0.2 | Sam68 is phosphorylated by IKK\u03b1 in the nucleus. | SIGNOR-278439 |
Q9NRD1 | Q96HE7 | 1 | binding | down-regulates quantity by destabilization | 0.2 | Ero1L is a ubiquitination substrate of FBXO6. FBXO6 mediates the degradation of Ero1L through a ubiquitylation-dependent pathway. Overexpression of FBXO6 increased the polyubiquitination and decreased the stability of Ero1L, whereas inhibition of FBXO6 prolonged the half-life of Ero1L. FBXO6 is the substrate recognition component of a Skp1-Cullin1-F-box protein (SCF) ubiquitin E3 ligase complex | SIGNOR-272326 |
Q8TD19 | Q92974 | 1 | phosphorylation | up-regulates activity | 0.2 | The phosphorylation of ARHGEF2 by NEK9 is the key step of this process. | SIGNOR-279638 |
Q9BPV8 | P30679 | 1 | binding | up-regulates activity | 0.2 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-257143 |
O43896 | Q9NRW1 | 1 | relocalization | up-regulates quantity | 0.2 | Here, we identify Bicaudal-D-related protein 1 (BICDR-1) as an effector of the small GTPase Rab6 and key component of the molecular machinery that controls secretory vesicle transport in developing neurons. BICDR-1 interacts with kinesin motor Kif1C, the dynein/dynactin retrograde motor complex, regulates the pericentrosomal localization of Rab6-positive secretory vesicles and is required for neural development in zebrafish. In young neurons, BICDR-1 accumulates Rab6 secretory vesicles around the centrosome, restricts anterograde secretory transport and inhibits neuritogenesis. Later during development, BICDR-1 expression is strongly reduced, which permits anterograde secretory transport required for neurite outgrowth. These results indicate an important role for BICDR-1 as temporal regulator of secretory trafficking during the early phase of neuronal differentiation. | SIGNOR-266878 |
Q7L576 | Q6T4R5 | 1 | binding | up-regulates activity | 0.2 | We show that the WHD of NHS interacts with the Abi family of proteins, HSPC300, Nap1 and Sra1, and is important for the localization of NHS to the leading edge. | SIGNOR-253575 |
O43583 | O60674 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | DENR directly regulates JAK2 expression. | SIGNOR-269675 |
P52564 | Q9ULV5 | 1 | phosphorylation | up-regulates activity | 0.2 | Regulation of Hsf4b nuclear translocation and transcription activity by phosphorylation at threonine 472| At the upstream, MEK6 was found to interact with Hsf4b and enhance Hsf4b's nuclear translocation and transcription activity, probably by phosphorylation at sites such as T472. Taken together, our results suggest that phosphotylation of Hsf4b at T472 by protein kinases such as MEI | SIGNOR-275493 |
P45984 | P63104 | 1 | phosphorylation | down-regulates | 0.2 | Jnk phosphorylates 14-3-3zetaat ser-184 and 14-3-3sigmaat ser-188 | SIGNOR-124031 |
P0DMV9 | P22413 | 1 | post transcriptional regulation | up-regulates quantity | 0.2 | We demonstrated the binding of heat shock protein 70 (HSP70) to ENPP1-3'UTR. Through this binding, HSP70 stabilizes ENPP1 mRNA and increases ENPP1 transcript and protein levels. This positive modulation of ENPP1 expression is paralleled by a reduced insulin-induced IR and IRS-1 phosphorylation. | SIGNOR-252198 |
P14921 | Q99102 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Through promoter screening, overexpressing methods and luciferase reporter studies, we found that transcription factors CREB, Ets-1, Elk-1 and STAT1 can positively regulate MUC4 expression at the promoter and mRNA level. | SIGNOR-254098 |
O94992 | Q9UGL1 | 1 | relocalization | up-regulates activity | 0.2 | We previously reported that the tumor suppressor HEXIM1 is a mediator of KDM5B recruitment to its target genes, and HEXIM1 is required for the inhibition of nuclear hormone receptor activity by KDM5B. | SIGNOR-273439 |
Q13131 | P49116 | 1 | phosphorylation | down-regulates | 0.2 | Tr4 transactivation is inhibited via phosphorylation bymetformin-induced amp-activated protein kinase (ampk) at the amino acid serine 351, which results in the suppression of scd1 gene expression | SIGNOR-173118 |
P09630 | P04271 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | HOXC6 and HOXC11 increase transcription of S100beta gene in BrdU-induced in vitro differentiation of GOTO neuroblastoma cells into Schwannian cells. | SIGNOR-261646 |
Q6ZNA4 | Q96CW1 | 1 | ubiquitination | up-regulates | 0.2 | Arkadia ubiquitylated the _?2 Subunit at lys130. In addition, arkadia interacted with the ap2 complex, and modified endocytosis of epidermal growth factor receptor (egfr) induced by egf. Arkadia thus appears to regulate egf signalling by modulating endocytosis of egfr through interaction with ap2 complex. | SIGNOR-168931 |
Q8IW41 | P07101 | 1 | phosphorylation | up-regulates | 0.2 | Recombinant human tyrosine hydroxylase (hth1) was found to be phosphorylated by mitogen and stress-activated protein kinase 1 (msk1) at ser40 and by p38 regulated/activated kinase (prak) on ser19. Phosphorylation of both ser40 and ser19 induced a high-affinity binding of 14-3-3 proteins, but only the interaction of 14-3-3 with ser19 increased the hth1 activity. | SIGNOR-95479 |
P30291 | P11308 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Here, we demonstrate that DNA damage induces proteasomal degradation of wild-type ERG and TMPRSS2-ERG oncoprotein through ERG threonine-187 and tyrosine-190 phosphorylation mediated by GSK3β and WEE1, respectively. | SIGNOR-277529 |
Q9Y2H0 | Q9BYB0 | 1 | relocalization | up-regulates activity | 0.2 | SHANK proteins are ‘master’ scaffolding proteins that tether and organize intermediate scaffolding proteins. They are located at excitatory synapses, where they are crucial for proper synaptic development and function. SAPAP proteins subsequently bind to the PDZ domain of members of the SHANK protein family. SHANK proteins then bind to the actin cytoskeleton and to Homer protein, which in turn interacts with mGluRs. Through these extended links, PSD95, SAPAP, SHANK and Homer proteins form a quaternary complex that brings together mGluR and NMDAR complexes in the PSD (FIG. 3). | SIGNOR-264597 |
Q8TD94 | Q9NYA1 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | KLF14 Is a Transcriptional Activator of SK1 Gene Expression in Endothelial Cells | SIGNOR-266047 |
P28324 | Q9Y5U4 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Under these conditions, a significant reduction in INSIG2 expression was only observed when SAP1a siRNA was used. These observations provide supporting evidence that SAP1a may be one of the transactivators of the human INSIG2 promoter. | SIGNOR-261592 |
P33981 | P38646 | 1 | phosphorylation | up-regulates | 0.2 | Mortalin binds to mps1, and is phosphorylated by mps1 on thr62 and ser65. The phosphorylated mortalin then super-activates mps1 in a feedback manner. Mps1-associated acceleration of centrosome duplication depends on the presence of mortalin and super-activation by the thr62/ser65 phosphorylated mortalin | SIGNOR-156185 |
P17252 | Q15080 | 1 | phosphorylation | up-regulates activity | 0.2 | In murine and guinea pig neutrophils, PKCδ is required for the phosphorylation of p40phox, a subunit of the NADPH oxidase complex (Li et al., 2016; Someya et al., 1999). In particular, it mediates phosphorylation of the threonine 154 (T154) residue of p40phox, a key regulatory step in the activation of the NADPH oxidase complex in peripheral neutrophils and B cells, in both mice and humans. In conclusion, the EBV-B cells of patients with PKCδ deficiency have impaired ROS production, associated with lower levels of phosphorylation of the cytosolic NADPH oxidase subunit p40phox by PKCδ. | SIGNOR-277628 |
O75084 | P63092 | 1 | binding | up-regulates activity | 0.2 | Wnt7a binding to fzd7 activates pi3k through a g protein alpha s- dependent mechanism. | SIGNOR-198831 |
Q05901 | P25054 | 1 | binding | up-regulates activity | 0.2 | Treatment of muscle cells with neural agrin causes tyrosine phosphorylation of the AChR β subunit and induces AChR clustering by promoting anchoring of the receptor protein to postsynaptic cytoskeleton. Regulation of acetylcholine receptor clustering by the tumor suppressor APC. By showing a direct requirement for APC in AChR clustering, our present study suggests that the Wnt/β-catenin pathway may crosstalk with the agrin signaling cascade during the formation of mammalian neuromuscular junction. | SIGNOR-264261 |
Q03135 | P48664 | 1 | binding | down-regulates activity | 0.2 | EAAT3 has previously been shown to form complexes with caveolin-1, a major component of caveolae, which participate in the regulation of transport proteins. The present study explored the impact of caveolin-1 on electrogenic transport by excitatory amino acid transporter isoforms EAAT1-4. caveolin-1 is a powerful negative regulator of the excitatory glutamate transporters EAAT1, EAAT2, EAAT3, and EAAT4. Caveolin-1 has been shown to form complexes with the excitatory amino acid transporter EAAT3 (EAAC1) (Gonzalez et al. 2007) and may thus modify the EAAT isoforms by direct interaction with the carriers. | SIGNOR-264810 |
P19838 | P07288 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | NF-kappa B activates prostate-specific antigen expression and is upregulated in androgen-independent prostate cancer. | SIGNOR-253668 |
Q92830 | P0DPK2 | 1 | acetylation | down-regulates activity | 0.2 | The HAT module within the SAGA and ADA complexes acetylates histone H3, mainly on residues K9 and K14. | SIGNOR-269597 |
P11309 | P68431 | 1 | phosphorylation | down-regulates activity | 0.2 | Pim1-dependent phosphorylation of histone h3 at serine 10 is required for myc-dependent transcriptional activation and oncogenic transformation. | SIGNOR-156946 |
Q12857 | Q02535 | 1 | transcriptional regulation | down-regulates quantity | 0.2 | By integrating transcriptomic profiling (RNA-seq) of Nfia- and Nfix-deficient GNPs with epigenomic profiling (ChIP-seq against NFIA, NFIB and NFIX, and DNase I hypersensitivity assays), we reveal that these transcription factors share a large set of potential transcriptional targets, suggestive of complementary roles for these NFI family members in promoting neural development | SIGNOR-268873 |
Q14980 | Q9NY65 | 1 | binding | up-regulates | 0.2 | Direct binding of numa to tubulin is mediated by a novel sequence motif in the tail domain that bundles and stabilizes microtubules. | SIGNOR-116826 |
P17252 | P48730 | 1 | phosphorylation | up-regulates activity | 0.2 | In the present study we analyzed the CK1δ kinase domain for phosphorylation sites targeted by PKCα. Several phosphorylation sites were identified in vitro by initially using GST-CK1δ wild type and phosphorylation-site mutant protein fragments originating from the CK1δ kinase domain. Residues S53, T176, and S181 could finally be confirmed as targets for PKCα. Determination of kinetic parameters of full-length wild type and mutant GST-CK1δ-mediated substrate phosphorylation revealed that integrity of residue T176 is crucial for maintaining CK1δ kinase activity. | SIGNOR-277452 |
K9N643 | Q14164 | 1 | binding | down-regulates activity | 0.2 | Previous studies have shown that MERS-CoV ORF4b antagonizes the early antiviral alpha/beta interferon (IFN-α/β) response, which may significantly contribute to MERS-CoV pathogenesis; however, the underlying mechanism is poorly understood. Here, we found that ORF4b in the cytoplasm could specifically bind to TANK binding kinase 1 (TBK1) and IκB kinase epsilon (IKKε), suppress the molecular interaction between mitochondrial antiviral signaling protein (MAVS) and IKKε, and inhibit IFN regulatory factor 3 (IRF3) phosphorylation and subsequent IFN-β production. these results indicate that MERS-CoV ORF4b inhibits the induction of type I IFN through a direct interaction with IKKε/TBK1 in the cytoplasm | SIGNOR-260592 |
Q12857 | P41161 | 1 | transcriptional regulation | down-regulates quantity | 0.2 | By integrating transcriptomic profiling (RNA-seq) of Nfia- and Nfix-deficient GNPs with epigenomic profiling (ChIP-seq against NFIA, NFIB and NFIX, and DNase I hypersensitivity assays), we reveal that these transcription factors share a large set of potential transcriptional targets, suggestive of complementary roles for these NFI family members in promoting neural development | SIGNOR-268874 |
P53350 | P08670 | 1 | phosphorylation | up-regulates | 0.2 | We observed that plk1 phosphorylates vimentin on ser82, which in turn regulates cell surface levels of 1 integrin. | SIGNOR-159386 |
Q9Y6M4 | P07948 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.2 | Although there have been more than 40 reports of mass spectrometric studies on phosphorylation at Lyn-S13, the kinase responsible remained unclear. We succeeded in identifying casein kinase 1γ (CK1γ) as the kinase responsible for phosphorylation of Lyn-S13. In HEK293 cells co-expressing Lyn and CK1γ, the phosphorylation level of Lyn-S13 increased significantly. we concluded that S-palmitoylated CK1γ encounters N-myristoylated Lyn and specifically phosphorylates the Ser-13 residue at the Golgi during intracellular protein traffic, as shown schematically in Fig. 8. Phosphorylated dual-lipid-modified Lyn and S-palmitoylated CK1γ are then transported from the Golgi to the plasma membrane. | SIGNOR-275395 |
Q9NR19 | O15297 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | As expected, we found that glucose deprivation induced the binding of TFEB (Figure S4C) and ACSS2 (Figure S4D) to the promoter regions of MAP1LC3B, ATG3, and WIPI-1 as well as mRNA (Figure 3H) and protein (Figure 3I) expression of these genes; | SIGNOR-276560 |
P67775 | Q96HP0 | 1 | phosphorylation | down-regulates activity | 0.2 | Akt and PP2A reciprocally regulate the guanine nucleotide exchange factor Dock6 to control axon growth of sensory neurons|At later developmental stages, the abundance of the kinase Akt increased, resulting in the binding of Akt to Dock6 and the phosphorylation of Dock6 at Ser(1194). | In dorsal root ganglion neurons from mice lacking Dock6, reintroduction of Dock6 with a nonphosphorylatable S1194A mutation rescued axon extension but not branch number, whereas reintroduction of Dock6 with a phosphomimetic S1194E mutation resulted in premature branching | SIGNOR-275669 |
Q9BZL6 | Q01105 | 1 | phosphorylation | down-regulates activity | 0.2 | In conclusion, the roles of protein kinase D2 and its substrate SET in T cell activation were investigated and we found that protein kinase D2 phosphorylates Ser171 of SET, which resulted in the reduction of its inhibitory effect on PP2A phosphatase activity. | SIGNOR-279560 |
Q9Y4K3 | P52789 | 1 | ubiquitination | down-regulates quantity | 0.2 | The Lys63-linked ubiquitination of HK2 catalyzed by the E3 ligase TRAF6 was critical for the subsequent recognition of HK2 by the autophagy receptor protein SQSTM1/p62 for the process of selective autophagic degradation. | SIGNOR-260003 |
Q96J02 | P16403 | 1 | polyubiquitination | up-regulates activity | 0.2 | ITCH interacts with and ubiquitinates linker histone H1.2 at K46. ITCH biochemically competes with RNF168 and RNF8 to polyubiquitinate histone H1.2. The results indicated that ITCH-mediated K46-Ubn is essential for the binding of histone H1.2 to chromatin. | SIGNOR-272926 |
Q13131 | Q9GZY8 | 1 | phosphorylation | up-regulates activity | 0.2 | A screen for substrates of AMPK identified mitochondrial fission factor (MFF), a mitochondrial outer-membrane receptor for DRP1, the cytoplasmic guanosine triphosphatase that catalyzes mitochondrial fission. | SIGNOR-245953 |
P49840 | P24071 | 1 | phosphorylation | down-regulates activity | 0.2 | GSK-3 is constitutively active in the absence of cytokine stimulation and can phosphorylate S263, keeping FcalphaRI in the inactive state. | SIGNOR-264856 |
P54646 | P08559 | 1 | phosphorylation | up-regulates activity | 0.2 | AMPKα phosphorylates PDHA subunit on Ser295 and Ser314 to activate PDH complex | SIGNOR-276838 |
Q15077 | P38405 | 1 | binding | up-regulates activity | 0.2 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-256947 |
P11233 | P98177 | 1 | phosphorylation | up-regulates activity | 0.2 | We conclude that Ral-mediated phosphorylation of threonines 447 and 451 is required for proper activity of AFX-WT. | SIGNOR-249665 |
Q9BPV8 | Q14344 | 1 | binding | up-regulates activity | 0.2 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-257299 |
O15530 | P00558 | 2 | phosphorylation | up-regulates activity | 0.2 | PDPK1 Phosphorylates PGK1 T243. Macrophages increase PGK1 pT243 to reduce the 3-PG affinity of PGK1, which alters the equilibrium of the PGK1-catalyzed reaction toward glycolysis, promoting tumor cell proliferation. | SIGNOR-277402 |
Q9Y243 | Q92900 | 1 | phosphorylation | up-regulates activity | 0.2 | AKT-Mediated UPF1 Phosphorylation at T151 Promotes UPF1 Helicase Activity | SIGNOR-277596 |
P43320 | P53674 | 1 | binding | up-regulates activity | 0.2 | At high concentrations or in the lens, βB2-crystallin forms hetero-oligomers with other β-crystallins. These oligomeric β-crystallins further participate in the formation of a supramolecular assembly that is important in lens function-lens transparency. | SIGNOR-252153 |
Q10571 | Q9BQG0 | 1 | binding | up-regulates activity | 0.2 | Taken together, 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-256021 |
Q13585 | P78536 | 1 | binding | up-regulates activity | 0.2 | GPR50 and ADAM17 can directly interact with each other (as both are cell membrane proteins), which was confirmed via coimmunoprecipitation (coIP; Figure 6C), indicating that ligand-independent Notch signaling activation is mediated through the GPR50-ADAM17 interaction | SIGNOR-278099 |
Q6UB99 | Q16620 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Ankrd11 knockdown decreases the levels of bdnf and Trkb mRNAs. Next, we examine whether ANKRD11 accesses the Trkb promoter in cortical neurons. We performed the chromatin immunoprecipitation assay (ChIP) using an ANKRD11 antibody followed by PCR to amplify the Trkb promoter region. We found that ANKRD11 binds to the Trkb promoter (Fig. 6E). As expected, the level of ANKRD11 binding was decreased in the Ankrd11 knockdown condition. | SIGNOR-266731 |
P23470 | Q8WV28 | 1 | dephosphorylation | up-regulates activity | 0.2 | 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-254692 |
O60858 | P22736 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | These results suggest that Trim13 activity mediates Nur77 ubiquitination, leading to its degradation. | SIGNOR-278564 |
Q13536 | P01100 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | CROC-4: a novel brain specific transcriptional activator of c-fos expressed from proliferation through to maturation of multiple neuronal cell types. | SIGNOR-261569 |
P07949 | O15530 | 1 | phosphorylation | up-regulates activity | 0.2 | Ret/ptc (rearranged in transformation/papillary thyroid carcinomas) tyrosine kinase phosphorylates and activates phosphoinositide-dependent kinase 1 (pdk1) ret/ptc phosphorylates a specific tyrosine (y9) residue located in the n-terminal region of pdk1. | SIGNOR-235863 |
P49840 | Q9Y5Q3 | 1 | phosphorylation | down-regulates | 0.2 | We showed that c-maf and mafb, like mafa, are indeed phosphorylated by gsk-3/ we demonstrated that phosphorylation by gsk-3 is conserved among the large maf proteins. It couples ubiquitination/degradation and transcriptional activation and modulates maf biological activity. | SIGNOR-159432 |
Q9Y5I2 | Q9Y5F7 | 1 | 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-265715 |
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 |
Q96JP5 | P52597 | 1 | ubiquitination | down-regulates quantity | 0.2 | Collectively, our results indicate that ZFP91 polyubiquitinated hnRNP F at Lys 185.|We found that silencing ZFP91 increased hnRNP F protein levels, but not hnRNP F mRNA levels, while ectopically expressing ZFP91 decreased hnRNP F protein levels, but not hnRNP F mRNA levels. | SIGNOR-278802 |
P11802 | Q14106 | 1 | phosphorylation | up-regulates activity | 0.2 | Taken together, these observations strongly support the notion that several different CDK-cyclin complexes are involved in the phosphorylation of Tob2 at S254.A more detailed regulatory context of Tob2 phosphorylation at S254 is provided by our findings from mass-spec and in vitro kinase analyses that suggest connections to PP2B and PP2C phosphatases and CDK-cyclin complexes, particularly CDK1, CDK2, and CDK4 (Table 1; Supplemental Table S2).One possibility is that the phosphorylation of S254 helps stabilize the interaction of Tob2 with the Ccr4–Not complex, which could contribute to Tob2's ability to recruit the entire Ccr4–Not complex and thus further enhances deadenylation. | SIGNOR-273602 |
P25098 | P21731-2 | 1 | phosphorylation | down-regulates activity | 0.2 | These data suggest a model whereby agonist-induced PKC phosphorylation of Ser(145) partially impairs TPbeta signalling while GRK2/3 phosphorylation at both Ser(239) and Ser(357) within its IC(3) and C-tail domains, respectively, sterically inhibits G-protein coupling, profoundly desensitizing signalling, and promotes beta-arrestin association and, in turn, facilitates TPbeta internalization. | SIGNOR-274088 |
O94826 | P0DMV8 | 1 | binding | up-regulates activity | 0.2 | The Tom70 receptor is a membrane-localized cochaperone that integrates the Hsp70/Hsp90 chaperones with mitochondrial preprotein targeting and translocation. In mammals, preprotein in the cytosol is associated with both Hsp90 and Hsp70 in a multichaperone complex, and docking of Hsp90 and/or Hsp70 onto Tom70 is essential for preprotein targeting. | SIGNOR-261380 |
O60260 | Q13501 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | Once activated, parkin interacts with and subsequently ubiquitinates p62 at the K13 residue, resulting in the degradation of p62 via the proteasomal dependent pathway. | SIGNOR-278524 |
Q15256 | P40763 | 1 | dephosphorylation | down-regulates activity | 0.2 | Here, we report identification of signal transducer and activator of transcription 3 (STAT3) as a substrate of PTPRT. Phosphorylation of a tyrosine at amino acid Y705 is essential for the function of STAT3, and PTPRT specifically dephosphorylated STAT3 at this position. | SIGNOR-248719 |
P01178-PRO_0000020495 | P30559 | 1 | binding | up-regulates activity | 0.2 | The neurohypophysial peptide oxytocin (OT) and OT-like hormones facilitate reproduction in all vertebrates at several levels. The major site of OT gene expression is the magnocellular neurons of the hypothalamic paraventricular and supraoptic nuclei. In response to a variety of stimuli such as suckling, parturition, or certain kinds of stress, the processed OT peptide is released from the posterior pituitary into the systemic circulation.| The OT receptor is a typical class I G protein-coupled receptor that is primarily coupled via G(q) proteins to phospholipase C-beta. | SIGNOR-268545 |
P49841 | Q7Z2W4 | 1 | phosphorylation | up-regulates activity | 0.2 | GSK3beta sequentially phosphorylated Ser 270, Ser 266, Ser 262, and Ser 257 of rat ZAP.|Inhibition of GSK3\u03b2 by inhibitor SB216763 or down-regulation of GSK3\u03b2 by RNAi reduced the antiviral activity of Zinc-finger antiviral protein. | SIGNOR-278401 |
Q15418 | Q9HC62 | 1 | phosphorylation | down-regulates activity | 0.2 | Here, we determined that d-flow activated the serine/threonine kinase p90RSK, which subsequently phosphorylated threonine 368 (T368) of SENP2. T368 phosphorylation promoted nuclear export of SENP2, leading to downregulation of eNOS expression and upregulation of proinflammatory adhesion molecule expression and apoptosis. | SIGNOR-273839 |
P00519 | P56962 | 1 | phosphorylation | down-regulates activity | 0.2 | C-Abl was identified as one of the kinases, which phosphorylates syntaxin 17.Western blot shows phosphorylation of syntaxin 17 on Tyr-156 by overexpression and activation of c-Abl. A phospho-mimicking mutant (Y156E) of syntaxin 17 showed reduced interaction with COPI vesicles. These results suggest that tyrosine phosphorylation of syntaxin 17 is likely to have a role in regulating syntaxin 17 dependent membrane trafficking in the early secretory pathway. | SIGNOR-273538 |
P20042 | Q9GZT9 | 1 | translation regulation | up-regulates quantity | 0.2 | DAP5 is involved in PHD2 translation. Distinct responses to DAP5 depletion (under hypoxia) of primary MEFs versus malignant glioma cells suggest that DAP5-mediated control of PHD2 may have special significance in cancer. Neoplastic cells may exploit DAP5 for managing chronic oxygen deprivation, possibly contributing to their adaptation to growth/proliferation under hypoxia. | SIGNOR-266386 |
Q9H0N0 | Q7Z7G8 | 1 | binding | down-regulates activity | 0.2 | Cohen syndrome-associated protein COH1 physically and functionally interacts with the small GTPase RAB6 at the Golgi complex and directs neurite outgrowth. COH1 Golgi Localization Is Mediated by Active RAB6 . COH1 Interacts with All Three Mammalian RAB6 Homologues | SIGNOR-269204 |
P47900 | P19086 | 1 | binding | up-regulates activity | 0.2 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-257273 |
P30530 | Q63HR2 | 1 | phosphorylation | up-regulates quantity | 0.2 | In this study, however, we demonstrate for the first time that Axl directly binds to and phosphorylates TNS2 at Y483.|Overall these results suggest that Axl positively regulates TNS2 expression. | SIGNOR-278471 |
O14843 | Q03113 | 1 | binding | up-regulates activity | 0.2 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-256957 |
P25098 | P25025 | 1 | phosphorylation | down-regulates activity | 0.2 | Upon activation, GRK2 phosphorylates CXCR2 and causes receptor desensitization and internalization, leading to down-regulation of neutrophil chemotaxis | SIGNOR-260647 |
P54792 | Q9P219 | 1 | binding | up-regulates | 0.2 | Daple binds to dvl and functions as a negative regulator of the wnt signalling pathway. | SIGNOR-199448 |
P03209 | Q14653 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | EBV Rta selectively down-regulates the expression of IRF3 and IRF7, the main regulators of the Type I IFNs. | SIGNOR-266644 |
P13288 | Q14653 | 1 | phosphorylation | down-regulates activity | 0.2 | BGLF4 kinase interacts physically with and phosphorylates IRF3, which is the initial activator of transcription in the innate immune response. BGLF4 suppresses IRF3-dependent transcriptional activation. Data here suggest that Ser123, Ser173, and Thr180 contribute additively to the BGLF4-mediated repression of the IRF3 transactivation activity. | SIGNOR-266647 |
O76064 | P16104 | 1 | ubiquitination | up-regulates | 0.2 | Rnf8 can ubiquitylate histone h2a and h2ax, | SIGNOR-159309 |
Q9Y5I2 | Q9Y5H1 | 1 | 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 |
Q9H3R0 | P10275 | 1 | binding | up-regulates activity | 0.2 | JMJD2C was found to be co-localized with AR and LSD1 in the epithelium of prostate carcinoma and normal prostate cells. For the detailed mechanism, JMJD2C, AR and LSD1 assembled on the chromatin to remove the methyl groups from mono-, di- and trimethylated H3K9. Importantly, JMJD2C specifically removed the demethylation of the trimethyl H3K9 marks and modulated the transcriptional activity of AR. Moreover, JMJD2C cooperated with LSD1 and activated AR-mediated gene expression via decreasing H3K9me3 at the promoter of AR targeting genes KLK2 and PSA. | SIGNOR-263879 |
P52564 | P52564 | 2 | phosphorylation | up-regulates activity | 0.2 | However, the autocatalytic activities of both mkk6 and mkk7 were enhanced by their coexpression with either mekk3 or mekk2. | SIGNOR-236122 |
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