Annotated protein:Potassium channel tetramerization domain containing 16. Gene symbol: KCTD16. Taxonomy: Rattus norvegicus (Rat). Uniprot ID: A0A8I6A6D0
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SynGO gene info:SynGO data @ KCTD16
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) and western blot analysis of native gel separations of brain membrane fractions (Fig. 1C)

Figure 4b: Experiments in CHO cells, co-expressing co-expressing GABAB, Kir3.1/3.2 channels and the different KCTD proteins. GABAB-activated Kir3 currents elicited by 25-s applications of baclofen the pronounced differences in kinetics upon expression of KCTD16 compared to without.

Figure 4c: KCDT16 significantly influenced the agonist concentration dependence of the GABAB responses as determined by apparent dose- response relationships with baclofen.

Taken together, the paper demonstrates that 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. As KCTD16 GABAB receptors, Kir3 channels and CaV channels all localize to both the pre- and postsynaptic membrane, the GO-term "G protein-coupled neurotransmitter receptor activity involved in regulation of presynaptic membrane potential" was selected, as well as "G protein-coupled neurotransmitter receptor activity involved in regulation of postsynaptic membrane potential" (annotation #5556)
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:5575
Dataset release (version):20231201
View annotation as GO-CAM model:Gene Ontology