KCNC2

The Shaker gene family of Drosophila encodes components of voltage-gated potassium channels and is comprised of four subfamilies. Based on sequence similarity, this gene is similar to one of these subfamilies, namely the Shaw subfamily. The protein encoded by this gene belongs to the delayed rectifier class of channel proteins and is an integral membrane protein that mediates the voltage-dependent potassium ion permeability of excitable membranes. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2012]

Potassium Voltage-Gated Channel Subfamily C Member 2

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 (PubMed:15709110).
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 (PubMed:15709110).
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).

Action potentialIEA:Ensembl
Cellular response to ammonium ionIEA:Ensembl
Cellular response to nitric oxideISS:UniProtKB
Cellular response to toxic substanceIEA:Ensembl
Globus pallidus developmentIEA:Ensembl
Nitric oxide-cGMP-mediated signaling pathwayISS:UniProtKB
Positive regulation of voltage-gated potassium channel activityIEA:Ensembl
Potassium ion transmembrane transportISS:UniProtKB
Protein heterooligomerizationISS:UniProtKB
Protein homooligomerizationISS:UniProtKB
Response to amineIEA:Ensembl
Response to ethanolIEA:Ensembl
Response to light intensityIEA:Ensembl
Response to magnesium ionIEA:Ensembl
Response to nerve growth factorIEA:Ensembl
Response to organic cyclic compoundIEA:Ensembl

Cell membrane; Membrane; Perikaryon; Cell projection, axon; Cell projection, dendrite; Cell junction, synapse, postsynaptic cell membrane; Cell junction, synapse, presynaptic cell membrane; Cell junction, synapse, synaptosome; Cell junction, synapse; Apical cell membrane; Basolateral cell membrane. Colocalizes with parvalbumin in globus pallidus neurons. Localizes in thalamocortical axons and synapses. Localizes on the surface of cell somata, proximal dendrites and axonal membranes. Also detected throughout the neuropil. Localized in starburst cell somata and proximal dendrite processes. Colocalized with GABA in presynaptic terminals. Clustered in patches in somatic and proximal dendritic membrane as well as in axons and presnypatic terminals of GABAergic interneurons; some of these patches are found near postsynaptic sites.

A chromosomal aberration involving KCNC2 has been found in a mother and her two children with varying degrees of neurodevelopmental delay and cerebellar ataxia. One child also exhibits episodes of unresponsiveness suggestive of absence seizures and facial dysmorphism. Deletion at 12q21.1 deletes exons 3-5 of KCNC2.

Cytoplasmic: 1-229
Helical: 230-250
Extracellular: 284-303
Helical: 304-313
Cytoplasmic: 314-334
Helical: 346-368
Extracellular: 369-381
Helical: 382-402
Helical: 453-473
Cytoplasmic: 474-638

Phosphorylated by PKA in cortical synaptosomes. cAMP-dependent phosphorylation inhibits channel activity (By similarity).
Histamine H2 receptor- and PKA-induced phosphorylation extends action potential spike duration, reduces action potential spike amplitude, sustains maximum firing frequency in hippocampal interneurons; also reduces the incidence of high-frequency oscillations in hippocampal CA3 pyramidal cell layers.