Annotated protein:Potassium channel tetramerization domain containing 8. Gene symbol: KCTD8. Taxonomy: Rattus norvegicus (Rat). Uniprot ID: A6Y7S3
antibody wiki:
SynGO gene info:SynGO data @ KCTD8
Ontology domain:Biological Process
SynGO term:G protein-coupled neurotransmitter receptor activity involved in regulation of presynaptic membrane potential (GO:0150047)
Annotated paper:Schwenk J, et al. "Native GABA(B) receptors are heteromultimers with a family of auxiliary subunits" Nature. 2010 May 13;465(7295):231-5 PMID:20400944
Figure(s):Figure 1, 3, 4
Annotation description: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.

Co-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)

Figure 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.

Taken 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.
Evidence tracking, Biological System:Cultured neurons
Non-neuronal tissue
Intact tissue
Evidence tracking, Protein Targeting:Over-expression
Evidence tracking, Experiment Assay:Electrophysiology (generic)
IP + WB/MSMS
Annotator(s):Robin Clement
Guus Smit
Matthijs Verhage
ORCID:0000-0002-2286-1587
0000-0002-2514-0216
Lab:Department of Functional Genomics, Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands
SynGO annotation ID:5573
Dataset release (version):20231201
View annotation as GO-CAM model:Gene Ontology