Voltage-gated potassium channel KCNC2

UniProt Q96PR1 Organism Homo sapiens Gene KCNC2

Also known as: KCNC2

Function

Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain. Contributes to the regulation of the fast action potential repolarization and in sustained high-frequency firing in neurons of the central nervous system. Homotetramer channels mediate delayed-rectifier voltage-dependent potassium currents that activate rapidly at high-threshold voltages and inactivate slowly. Forms tetrameric channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (Probable). Can form functional homotetrameric and heterotetrameric channels that contain variable proportions of KCNC1, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel. Channel properties may be modulated either by the association with ancillary subunits, such as KCNE1, KCNE2 or KCNE3 or indirectly by nitric oxide (NO) through a cGMP- and PKG-mediated signaling cascade, slowing channel activation and deactivation of delayed rectifier potassium channels (By similarity). Contributes to fire sustained trains of very brief action potentials at high frequency in retinal ganglion cells, thalamocortical and suprachiasmatic nucleus (SCN) neurons and in hippocampal and neocortical interneurons. Sustained maximal action potential firing frequency in inhibitory hippocampal interneurons is negatively modulated by histamine H2 receptor activation in a cAMP- and protein kinase (PKA) phosphorylation-dependent manner. Plays a role in maintaining the fidelity of synaptic transmission in neocortical GABAergic interneurons by generating action potential (AP) repolarization at nerve terminals, thus reducing spike-evoked calcium influx and GABA neurotransmitter release. Required for long-range synchronization of gamma oscillations over distance in the neocortex. Contributes to the modulation of the circadian rhythm of spontaneous action potential firing in suprachiasmatic nucleus (SCN) neurons in a light-dependent manner (By similarity).

Classification

Family (Pfam): PF02214 BTB_2, PF00520 Ion_trans
InterPro: BTB/POZ_dom, Ion_trans_dom, K_chnl_volt-dep_Kv, K_chnl_volt-dep_Kv3, SKP1/BTB/POZ_sf, T1-type_BTB, VG_K_chnl, Volt_channel_dom_sf
Functional cluster: Homeobox & Zinc-Finger Transcription Factors

Gene Ontology · 44

Disease associations

developmental and epileptic encephalopathy 103 MONDO:0030957

Drugs targeting this protein · 6

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Voltage-gated potassium channel KCNC2 2 shared papers
Ataxin-7-like protein 3B 1 shared papers
Voltage-gated potassium channel KCNC2 2 shared papers

Literature · 13 cited papers

Emerging evidence of genotype-phenotype associations of developmental and epileptic encephalopathy due to KCNC2 mutation: Identification of novel R405G. Front. Mol. Neurosci. · 2022
Spectrum of phenotypic, genetic, and functional characteristics in patients with epilepsy with KCNC2 pathogenic variants. Neurology · 2022
A recurrent de novo variant supports KCNC2 involvement in the pathogenesis of developmental and epileptic encephalopathy. Am. J. Med. Genet. A · 2021
Whole-exome sequencing in NF1-related West syndrome leads to the identification of KCNC2 as a novel candidate gene for epilepsy. Neuropediatrics · 2020
A de novo heterozygous mutation in KCNC2 gene implicated in severe developmental and epileptic encephalopathy. Eur. J. Med. Genet. · 2020
Deletion of chromosome 12q21 affecting KCNC2 and ATXN7L3B in a family with neurodevelopmental delay and ataxia. J. Neurol. Neurosurg. Psych. · 2013
The finished DNA sequence of human chromosome 12. Nature · 2006
Stichodactyla helianthus peptide, a pharmacological tool for studying Kv3.2 channels. Mol. Pharmacol. · 2005
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat. Genet. · 2004
Kv3 channels: voltage-gated K+ channels designed for high-frequency repetitive firing. Trends Neurosci. · 2001
Contributions of Kv3 channels to neuronal excitability. Ann. N. Y. Acad. Sci. · 1999
… and 1 more in the literature graph

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