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

Protein ID

ICDB_Pro_0837

Protein Name

Potassium voltage-gated channel subfamily C member 2

Gene Name

Kcnc2

Organism

Mus musculus (Mouse)

Length

642 amino acids

AlphaFoldDB

AF-Q14B80-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 (By similarity). 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 by either 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 (By similarity). Contributes to fire sustained trains of very brief action potentials at high frequency in thalamocortical and suprachiasmatic nucleus (SCN) neurons; in hippocampal and neocortical interneurons and in retinal ganglion cells . 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

Sequence

MGKIESNERVILNVGGTRHETYRSTLKTLPGTRLALLASSEPQGDCLTAAGDKLQPLPPPLSPPPRPPPLSPVPSGCFEGGAGNCSSHGGNGGNGGSDHPGGGREFFFDRHPGVFAYVLNYYRTGKLHCPADVCGPLFEEELAFWGIDETDVEPCCWMTYRQHRDAEEALDIFETPDLIGGDPGDDEDLAAKRLGIEDAAGLGGPDGKSGRWRKLQPRMWALFEDPYSSRAARFIAFASLFFILVSITTFCLETHEAFNIVKNKTEPVINGTSPVLQYEIETDPALTYVEGVCVVWFTFEFLVRIVFSPNKLEFIKNLLNIIDFVAILPFYLEVGLSGLSSKAAKDVLGFLRVVRFVRILRIFKLTRHFVGLRVLGHTLRASTNEFLLLIIFLALGVLIFATMIYYAERVGAQPNDPSASEHTQFKNIPIGFWWAVVTMTTLGYGDMYPQTWSGMLVGALCALAGVLTIAMPVPVIVNNFGMYYSLAMAKQKLPRKRKKHIPPAPLASSPTFCKTELNMACNSTQSDTCLGKENRLLEHNRSVLSGDDSTGSEPPLSPPERLPIRRSSTRDKNRRGETCFLLTTGDYTCASDGGIRKGYEKSRSLNNIAGLAGNALRLSPVTSPYNSPCPLRRSRSPIPSIL

PDB Structures

Ligand Binding

1. DICL_CP

2. DICL_Pep

Binding Site

Disease

Location

Weakly expressed in the brain at postnatal age day 7 (P7) and increased at P60 (PubMed:21912965). Not detectable in newborn hippocampus. Expressed weakly at P7 in the early developing hippocampus; increasing progressively and reaching a plateau of expression at P14 that is maintained throughout P51. Expressed in paravalbumin- and somatostain-containing inhibitory interneurons of the hippocampus; in the CA1/CA3 stratum oriens-alveus and stratum pyramidale and in cells within the hilus and subgranular layer of the dentate gyrus (DG) (PubMed:10903572; PubMed:12000114). Strongly expressed in parvalbumin (PV)-containing fast-spiking GABAergic inhibitor interneurons in deep cortical layers V and VI (PubMed:10531438). Also expressed in non-fast-spiking calbindin (CB)- and/or somatostatin (SOM)-containing interneurons in deep cortical layers V and VI (PubMed:10531438). Expressed in starburst amacrine cells of the retina in the inner nuclear layer (INL) and ganglion cell layer (GCL) (PubMed:15317859). Expressed in the suprachiasmatic nucleus (SCN) (at protein level) (PubMed:15852012; PubMed:21414897). Expressed in the early developing brain; increasing progressively until P14 (PubMed:21912965).

DOI ID

10.1101/gr.2596504; 10.1152/jn.1999.82.5.2476; 10.1111/j.1749-6632.1999.tb11295.x; 10.1523/jneurosci.19-21-09332.1999; 10.1523/jneurosci.20-24-09071.2000; 10.1038/77693; 10.1016/s0166-2236(00)01892-0; 10.1002/hipo.1104; 10.1523/jneurosci.1275-04.2004; 10.1523/jneurosci.0722-05.2005; 10.1038/nn1448; 10.1113/jphysiol.2007.141135; 10.1016/j.cell.2010.12.001; 10.1523/jneurosci.5792-10.2011; 10.1007/s12031-011-9648-6; 10.1152/jn.00102.2012

RefSeq

XP_006513748.1; XP_006513750.1; XP_006513751.1; XP_006513752.1; XP_006513753.1

Feature