{"id":"gomodel:SYNGO_5573","individuals":[{"id":"gomodel:SYNGO_557309ae9a67-a60d-4f0f-a061-14fe35574b85","type":[{"type":"class","id":"RGD:1312020","label":"Kctd8 Rnor"}],"root-type":[{"type":"class","id":"CHEBI:33695","label":"information biomacromolecule"},{"type":"class","id":"CHEBI:24431","label":"chemical entity"}],"annotations":[{"key":"contributor","value":"https://orcid.org/0000-0002-2514-0216"},{"key":"date","value":"2024-03-06"},{"key":"providedBy","value":"https://syngo.vu.nl"},{"key":"contributor","value":"https://orcid.org/0000-0002-2286-1587"}]},{"id":"gomodel:SYNGO_557328929304-81c1-4758-b4eb-354a0feea758","type":[{"type":"class","id":"ECO:0007695","label":"cell-based assay evidence used in manual assertion"}],"root-type":[{"type":"class","id":"ECO:0000000","label":"evidence"}],"annotations":[{"key":"source","value":"PMID:20400944"},{"key":"date","value":"2024-03-06"},{"key":"contributor","value":"https://orcid.org/0000-0002-2514-0216"},{"key":"providedBy","value":"https://syngo.vu.nl"},{"key":"contributor","value":"https://orcid.org/0000-0002-2286-1587"}]},{"id":"gomodel:SYNGO_55734a837fb8-1f49-4f4a-9750-aafcdb49e498","type":[{"type":"class","id":"ECO:0000314","label":"direct assay evidence used in manual assertion"}],"root-type":[{"type":"class","id":"ECO:0000000","label":"evidence"}],"annotations":[{"key":"contributor","value":"https://orcid.org/0000-0002-2286-1587"},{"key":"providedBy","value":"https://syngo.vu.nl"},{"key":"date","value":"2024-03-06"},{"key":"contributor","value":"https://orcid.org/0000-0002-2514-0216"},{"key":"source","value":"PMID:20400944"}]},{"id":"gomodel:SYNGO_5573e14a0a89-897b-4675-a47b-bc2324b25709","type":[{"type":"class","id":"ECO:0006063","label":"over expression analysis evidence used in manual assertion"}],"root-type":[{"type":"class","id":"ECO:0000000","label":"evidence"}],"annotations":[{"key":"date","value":"2024-03-06"},{"key":"providedBy","value":"https://syngo.vu.nl"},{"key":"contributor","value":"https://orcid.org/0000-0002-2286-1587"},{"key":"source","value":"PMID:20400944"},{"key":"contributor","value":"https://orcid.org/0000-0002-2514-0216"}]},{"id":"gomodel:SYNGO_5573e37254b5-e5f0-4246-8b20-7917319f3d84","type":[{"type":"class","id":"GO:0099528","label":"G protein-coupled neurotransmitter receptor activity"}],"root-type":[{"type":"class","id":"GO:0003674","label":"molecular_function"},{"type":"class","id":"obo:go/extensions/reacto.owl#molecular_event","label":"Molecular Event"}],"annotations":[{"key":"contributor","value":"https://orcid.org/0000-0002-2286-1587"},{"key":"date","value":"2026-01-08"},{"key":"contributor","value":"https://orcid.org/0000-0002-2514-0216"},{"key":"providedBy","value":"https://syngo.vu.nl"},{"key":"comment","value":"Automated change 2026-01-08: GO:0150047 replaced by GO:0099528"}]},{"id":"gomodel:SYNGO_5573f82a2467-92fc-492a-9781-62519e7da473","type":[{"type":"class","id":"ECO:0006006","label":"electrophysiology assay evidence used in manual assertion"}],"root-type":[{"type":"class","id":"ECO:0000000","label":"evidence"}],"annotations":[{"key":"date","value":"2024-03-06"},{"key":"source","value":"PMID:20400944"},{"key":"contributor","value":"https://orcid.org/0000-0002-2514-0216"},{"key":"contributor","value":"https://orcid.org/0000-0002-2286-1587"},{"key":"providedBy","value":"https://syngo.vu.nl"}]}],"facts":[{"subject":"gomodel:SYNGO_5573e37254b5-e5f0-4246-8b20-7917319f3d84","property":"RO:0002333","property-label":"RO:0002333","object":"gomodel:SYNGO_557309ae9a67-a60d-4f0f-a061-14fe35574b85","annotations":[{"key":"evidence","value":"gomodel:SYNGO_557328929304-81c1-4758-b4eb-354a0feea758","value-type":"IRI"},{"key":"evidence","value":"gomodel:SYNGO_55734a837fb8-1f49-4f4a-9750-aafcdb49e498","value-type":"IRI"},{"key":"evidence","value":"gomodel:SYNGO_5573e14a0a89-897b-4675-a47b-bc2324b25709","value-type":"IRI"},{"key":"evidence","value":"gomodel:SYNGO_5573f82a2467-92fc-492a-9781-62519e7da473","value-type":"IRI"},{"key":"contributor","value":"https://orcid.org/0000-0002-2286-1587"},{"key":"contributor","value":"https://orcid.org/0000-0002-2514-0216"},{"key":"date","value":"2024-03-06"},{"key":"providedBy","value":"https://syngo.vu.nl"}]}],"annotations":[{"key":"state","value":"production"},{"key":"contributor","value":"https://orcid.org/0000-0002-2286-1587"},{"key":"contributor","value":"https://orcid.org/0000-0002-2514-0216"},{"key":"date","value":"2026-01-08"},{"key":"title","value":"SYNGO_MF_5573"},{"key":"providedBy","value":"https://syngo.vu.nl"},{"key":"comment","value":"Automated change 2026-01-08: GO:0150047 replaced by GO:0099528"},{"key":"comment","value":"Rationale: Figure 1: identification of KCTD8, KCTD12, KCTD12B and KCTD16 as subunits of native GABAB receptors by AP+ MS of both GABAB1 and GABAB2 receptors. No KCTD-specific peptides were detected in affinity purifications with anti-GABAB1 and anti-GABAB2 from brains of GABAB1 and GABAB2 knockout mice, respectively.\n\nCo-assembly of the identified KCTD proteins with native GABAB receptors was further corroborated by reverse affinity purifications (Supplementary Fig. 3C + 6), western blot analysis of native gel separations of brain membrane fractions (Fig. 1C) and affinity purifications of membrane fractions of HEK293 cells expressing various combinations of differentially tagged GABAB1, GABAB2 and KCTD12 proteins (Supplementary Fig. 7a)\n\nFigure 4b: Experiment in CHO cells co-expressing GABAB, Kir3.1/3.2 channels and the different KCTD proteins. GABAB-activated Kir3 currents elicited by 25-s applications of baclofen demonstrate differences in kinetics of Kir3 currents in cells expressing KCTD8 compared to without.\n\nTaken together, the KCTD proteins endow GABAB receptors with subtype-specific properties of their G-protein signalling, regulating the the activity of voltage-gated calcium and inward-rectifier potassium channels. Given predominant localization of KCTD8 to the presynaptic plasma membrane as well as some localization to presynaptic active zone (annotations #4578 and #4949), as well as presynaptic expression of GABAB receptors, Kir3 channels and CaV channels the GO-term \"G protein-coupled neurotransmitter receptor activity involved in regulation of presynaptic membrane potential\" was selected.. Experimental description: \"To test whether co-assembled KCTD proteins alter the functional properties of GABAB receptors, GABAB(1,2) or GABAB(1,2)-KCTD heteromultimers were co-expressed in Xenopus oocytes or Chinese hamster ovary (CHO) cells together with the Gbc-regulated effector ion channels Kir3 or Cav2.1/Cav2.2 (corresponding to P/Q-type and N-type channels).\"\n\n\"Finally, the KCTD effects were examined in cultured hippocampal neurons, which show robust Kir3-mediated GABAB responses18 and express KCTD proteins 8, 12 and 16 (Supplementary Fig. 11).\"\n\nGenebank accession number: NP_001093642.1 (primary sequence in Supplementary Fig. 4)"},{"key":"https://w3id.org/biolink/vocab/in_taxon","value":"http://purl.obolibrary.org/obo/NCBITaxon_10116"}]}