Protein Details: Potassium voltage-gated channel subfamily C member 2

Protein ID

ICDB_Pro_0411

Protein Name

Potassium voltage-gated channel subfamily C member 2

Gene Name

Kcnc2

Organism

Rattus norvegicus (Rat)

Length

638 amino acids

AlphaFoldDB

AF-P22462-F1-model_v4.pdb

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 . Can form functional homotetrameric channels 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 and 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 . 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)

Sequence

MGKIENNERVILNVGGTRHETYRSTLKTLPGTRLALLASSEPQGDCLTAAGDKLQPLPPPLSPPPRPPPLSPVPSGCFEGGAGNCSSHGGNGSDHPGGGREFFFDRHPGVFAYVLNYYRTGKLHCPADVCGPLFEEELAFWGIDETDVEPCCWMTYRQHRDAEEALDIFETPDLIGGDPGDDEDLGGKRLGIEDAAGLGGPDGKSGRWRKLQPRMWALFEDPYSSRAARFIAFASLFFILVSITTFCLETHEAFNIVKNKTEPVINGTSAVLQYEIETDPALTYVEGVCVVWFTFEFLVRIVFSPNKLEFIKNLLNIIDFVAILPFYLEVGLSGLSSKAAKDVLGFLRVVRFVRILRIFKLTRHFVGLRVLGHTLRASTNEFLLLIIFLALGVLIFATMIYYAERVGAQPNDPSASEHTQFKNIPIGFWWAVVTMTTLGYGDMYPQTWSGMLVGALCALAGVLTIAMPVPVIVNNFGMYYSLAMAKQKLPRKRKKHIPPAPLASSPTFCKTELNMACNSTQSDTCLGKENRLLEHNRSVLSGDDSTGSEPPLSPPERLPIRRSSTRDKNRRGETCFLLTTGDYTCASDGGIRKGYEKSRSLNNIAGLAGNALRLSPVTSPYNSPCPLRRSRSPIPSIL

PDB Structures

Ligand Binding

1. DICL_CP

2. DICL_Pep

Binding Site

Disease

Location

Expressed in neurons of the visual cortex during postnatal development (PubMed:18708127). Expressed in neurons of the globus pallidus at postnatal age day 7 (P7); onward (PubMed:10482766). Expressed in thalamic relay neurons. Expressed in neurons in layer IV and deeper cortical layers of the neocortex. Expressed in hippocampal interneurons (PubMed:7643197). Expressed in nonpyramidal interneurons in the basolateral amygdala (PubMed:16413129). Expressed in retinal ganglion cells (at protein level) (PubMed:22831914). Widely expressed in the brain (PubMed:1879548; PubMed:8120636). Expressed in numerous thalamic relay neurons throughout the dorsal thalamus. Expressed in interneurons of the deep layers V-VI of the cerebral cortex; the CA1 and CA3 pyramidal and dentate gyrus (DG) granule cells of the hippocampus; in neurons of the caudate-putamen; globus pallidus and subthalamic nucleus. Also expressed in the optic layer of interior colliculus; the inferior colliculus; the red nucleus; the medial geniculate; the ventral lateral lemiscus; the reticulotegmental nucleus and in the deep cerebellar nuclei (PubMed:1374908; PubMed:18708127; PubMed:7643197; PubMed:8120636). Expressed in globus pallidus (GP) neurons (PubMed:10414968).

DOI ID

10.1073/pnas.87.13.5227; 10.1073/pnas.88.9.4060-b; 10.1016/0014-5793(91)81026-5; 10.1002/j.1460-2075.1992.tb05312.x; 10.1073/pnas.89.10.4603; 10.1523/jneurosci.14-03-00949.1994; 10.1523/jneurosci.15-08-05486.1995; 10.1007/s002329900278; 10.1152/jn.1999.82.3.1512; 10.1523/jneurosci.19-15-06394.1999; 10.1111/j.1749-6632.1999.tb11295.x; 10.1016/s0166-2236(00)01892-0; 10.1111/j.1469-7793.2001.0345k.x; 10.1074/jbc.m310501200; 10.1016/j.neuroscience.2005.11.047; 10.1016/j.neuroscience.2008.08.008; 10.1016/j.neuroscience.2008.07.035; 10.1016/j.ceca.2012.06.007

RefSeq

NP_631962.1 [P22462-3]; NP_631963.1 [P22462-1]; XP_006241389.1 [P22462-1]; XP_017450149.1 [P22462-1]; XP_017450150.1 [P22462-2]; XP_017450152.1

Feature