P22462 · KCNC2_RAT

  • Protein
    Voltage-gated potassium channel KCNC2
  • Gene
    Kcnc2
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

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 (PubMed:10414968, PubMed:10482766, PubMed:11506885, PubMed:22831914).
Homotetramer channels mediate delayed-rectifier voltage-dependent potassium currents that activate rapidly at high-threshold voltages and inactivate slowly (PubMed:10414303, PubMed:10482766, PubMed:11281123, PubMed:14679187, PubMed:1879548, PubMed:2367536, PubMed:7643197, PubMed:8120636).
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:1879548, PubMed:2367536, PubMed:7643197, PubMed:8120636).
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 (PubMed:10482766, PubMed:14679187).
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 (PubMed:11281123, PubMed:14679187).
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:10414968, PubMed:10482766, PubMed:11506885, PubMed:22831914).
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).

Catalytic activity

Activity regulation

Inhibited by Stichodactyla helianthus peptide ShK (By similarity).
Inhibited by millimolar levels of tetraethylammonium (TEA). Contrary to other channels, inhibited only by millimolar levels of 4-aminopyridine (4-AP) (PubMed:10414303, PubMed:10482766, PubMed:1879548, PubMed:2367536, PubMed:7643197).

Kinetics

Homotetrameric channels expressed in xenopus oocytes or in mammalian non-neuronal cells display delayed-rectifier voltage-dependent potassium currents, that are rapidly activated during membrane depolarization, i.e within a risetime of a few msec. After that, inactivates very slowly, i.e within about >800 msec. Their activation requires a threshold potential at about -10 mV, with a midpoint activation at about 12.1 mV and a steepness parameter of about 8.4 mV (PubMed:10414303, PubMed:11281123, PubMed:14679187, PubMed:1879548, PubMed:2367536, PubMed:7643197, PubMed:8120636).
The voltage-dependence of activation and inactivation and other channel characteristics vary depending on the experimental conditions, the expression system, the presence or absence of ancillary subunits and post-translational modifications (PubMed:10414303, PubMed:11281123, PubMed:14679187, PubMed:7643197).

Features

Showing features for binding site.

TypeIDPosition(s)Description
Binding site124Zn2+ (UniProtKB | ChEBI)
Binding site130Zn2+ (UniProtKB | ChEBI)
Binding site151Zn2+ (UniProtKB | ChEBI)
Binding site152Zn2+ (UniProtKB | ChEBI)
Binding site437K+ (UniProtKB | ChEBI); ligand shared between homotetrameric partners
Binding site438K+ (UniProtKB | ChEBI); ligand shared between homotetrameric partners
Binding site439K+ (UniProtKB | ChEBI); ligand shared between homotetrameric partners
Binding site440K+ (UniProtKB | ChEBI); ligand shared between homotetrameric partners

GO annotations

AspectTerm
Cellular Componentapical plasma membrane
Cellular Componentaxolemma
Cellular Componentaxon
Cellular Componentaxon terminus
Cellular Componentbasolateral plasma membrane
Cellular Componentdendrite
Cellular Componentdendrite membrane
Cellular ComponentGABA-ergic synapse
Cellular Componentmembrane
Cellular Componentneuronal cell body
Cellular Componentneuronal cell body membrane
Cellular Componentperikaryon
Cellular Componentplasma membrane
Cellular Componentpostsynaptic membrane
Cellular Componentpresynaptic membrane
Cellular Componentsynapse
Cellular Componentterminal bouton
Cellular Componentvesicle
Cellular Componentvoltage-gated potassium channel complex
Molecular Functiondelayed rectifier potassium channel activity
Molecular Functionmetal ion binding
Molecular Functiontransmembrane transporter binding
Molecular Functionvoltage-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential
Molecular Functionvoltage-gated potassium channel activity
Biological Processaction potential
Biological Processcellular response to ammonium ion
Biological Processcellular response to nitric oxide
Biological Processcellular response to toxic substance
Biological Processglobus pallidus development
Biological Processmembrane hyperpolarization
Biological Processmonoatomic ion transmembrane transport
Biological Processnitric oxide-cGMP-mediated signaling
Biological Processoptic nerve development
Biological Processpositive regulation of potassium ion transmembrane transport
Biological Processpotassium ion transmembrane transport
Biological Processpotassium ion transport
Biological Processprotein heterooligomerization
Biological Processprotein homooligomerization
Biological Processregulation of action potential firing rate
Biological Processresponse to amine
Biological Processresponse to ethanol
Biological Processresponse to light intensity
Biological Processresponse to magnesium ion
Biological Processresponse to nerve growth factor
Biological Processresponse to organic cyclic compound
Biological Processresponse to toxic substance

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Voltage-gated potassium channel KCNC2
  • Alternative names
    • Potassium channel voltage-gated Shaw-related subfamily C member 2
    • Potassium voltage-gated channel subfamily C member 2
    • Shaw-like potassium channel
    • Voltage-gated potassium channel subunit Kv3.2

Gene names

    • Name
      Kcnc2

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus

Accessions

  • Primary accession
    P22462
  • Secondary accessions
    • P22461
    • P22463
    • Q63735

Proteomes

Organism-specific databases

Subcellular Location

Cell membrane
; Multi-pass membrane protein
Membrane
; Multi-pass membrane protein
Perikaryon
Cell projection, axon
Synapse
Synapse, synaptosome
Note: 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 (By similarity).
Colocalizes with parvalbumin in globus pallidus neurons (PubMed:10482766).
Localizes in thalamocortical axons and synapses (PubMed:7643197).

Isoform 1

Apical cell membrane

Isoform 2

Apical cell membrane

Isoform 3

Features

Showing features for topological domain, transmembrane.

TypeIDPosition(s)Description
Topological domain1-229Cytoplasmic
Transmembrane230-248Helical; Name=Segment S1
Transmembrane284-303Helical; Name=Segment S2
Topological domain304-314Cytoplasmic
Transmembrane315-337Helical; Name=Segment S3
Transmembrane346-368Helical; Voltage-sensor; Name=Segment S4
Topological domain369-381Cytoplasmic
Transmembrane382-401Helical; Name=Segment S5
Transmembrane451-473Helical; Name=Segment S6
Topological domain474-638Cytoplasmic

Keywords

Phenotypes & Variants

Features

Showing features for mutagenesis.

TypeIDPosition(s)Description
Mutagenesis563Does not abolish channel activity inhibition in presence of nitric oxide (NO); when associated with A-564. Absence of channel activity inhibition in presence of cAMP; when associated with A-564.
Mutagenesis564Does not abolish channel activity inhibition in presence of nitric oxide (NO); when associated with A-564. Absence of channel activity inhibition in presence of cAMP; when associated with A-563.

Chemistry

PTM/Processing

Features

Showing features for chain, glycosylation, modified residue.

TypeIDPosition(s)Description
ChainPRO_00000540541-638Voltage-gated potassium channel KCNC2
Glycosylation259N-linked (GlcNAc...) asparagine
Glycosylation266N-linked (GlcNAc...) asparagine
Modified residue564Phosphoserine; by PKA
Modified residue600Phosphoserine

Post-translational modification

Phosphorylated by PKA in cortical synaptosomes (PubMed:7643197).
cAMP-dependent phosphorylation inhibits channel activity (PubMed:7643197).
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 (By similarity).

Keywords

Proteomic databases

PTM databases

Expression

Tissue specificity

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).

Induction

Up-regulated in visual cortex during the second postnatal week from dark-reared animals (at protein level). Down-regulated in visual cortex by active visual experience until postnatal day P40 of dark-reared animals (PubMed:18708127).
Down-regulated by chronic action potential activity deprivation in organotypic culture of the visual cortex (PubMed:18775767).

Gene expression databases

Interaction

Subunit

Homotetramer and heterotetramer with other channel-forming alpha subunits, such as KCNC1. Interacts with KCNC1 (PubMed:10482766, PubMed:14679187).
Homotetramer or heterotetramer channel activity is regulated by association with modulating ancillary subunits such as KCNE1, KCNE2 and KCNE3, creating a functionally diverse range of channel complexes. Interacts with KCNE1, KCNE2 and KCNE3 (PubMed:14679187).

Protein-protein interaction databases

Structure

Family & Domains

Features

Showing features for region, compositional bias, motif.

TypeIDPosition(s)Description
Region47-75Disordered
Compositional bias56-74Pro residues
Motif437-442Selectivity filter
Region538-572Disordered

Domain

The transmembrane segment S4 functions as a voltage-sensor and is characterized by a series of positively charged amino acids at every third position. Channel opening and closing is effected by a conformation change that affects the position and orientation of the voltage-sensor paddle formed by S3 and S4 within the membrane. A transmembrane electric field that is positive inside would push the positively charged S4 segment outwards, thereby opening the pore, while a field that is negative inside would pull the S4 segment inwards and close the pore. Changes in the position and orientation of S4 are then transmitted to the activation gate formed by the inner helix bundle via the S4-S5 linker region.

Sequence similarities

Keywords

Phylogenomic databases

Family and domain databases

Sequence & Isoforms

Align isoforms (4)
  • Sequence status
    Complete

This entry describes 4 isoforms produced by Alternative splicing.

P22462-1

This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

  • Name
    1
  • Synonyms
    KV3.2B
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Length
    638
  • Mass (Da)
    70,191
  • Last updated
    1991-08-01 v1
  • Checksum
    25C102B4CCE53BF4
MGKIENNERVILNVGGTRHETYRSTLKTLPGTRLALLASSEPQGDCLTAAGDKLQPLPPPLSPPPRPPPLSPVPSGCFEGGAGNCSSHGGNGSDHPGGGREFFFDRHPGVFAYVLNYYRTGKLHCPADVCGPLFEEELAFWGIDETDVEPCCWMTYRQHRDAEEALDIFETPDLIGGDPGDDEDLGGKRLGIEDAAGLGGPDGKSGRWRKLQPRMWALFEDPYSSRAARFIAFASLFFILVSITTFCLETHEAFNIVKNKTEPVINGTSAVLQYEIETDPALTYVEGVCVVWFTFEFLVRIVFSPNKLEFIKNLLNIIDFVAILPFYLEVGLSGLSSKAAKDVLGFLRVVRFVRILRIFKLTRHFVGLRVLGHTLRASTNEFLLLIIFLALGVLIFATMIYYAERVGAQPNDPSASEHTQFKNIPIGFWWAVVTMTTLGYGDMYPQTWSGMLVGALCALAGVLTIAMPVPVIVNNFGMYYSLAMAKQKLPRKRKKHIPPAPLASSPTFCKTELNMACNSTQSDTCLGKENRLLEHNRSVLSGDDSTGSEPPLSPPERLPIRRSSTRDKNRRGETCFLLTTGDYTCASDGGIRKGYEKSRSLNNIAGLAGNALRLSPVTSPYNSPCPLRRSRSPIPSIL

P22462-2

  • Name
    2
  • Synonyms
    KV3.2C
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical
    • 594-638: GYEKSRSLNNIAGLAGNALRLSPVTSPYNSPCPLRRSRSPIPSIL → ASTLEPMESTSQTKGDTRPEAHWNCAHLLNFGCPTGSSFPTL

P22462-3

  • Name
    3
  • Synonyms
    KV3.2A, KShIIIA.1
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical
    • 594-638: GYEKSRSLNNIAGLAGNALRLSPVTSPYNSPCPLRRSRSPIPSIL → DNCKDVVITGYTQAEARSLT

P22462-4

  • Name
    4
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical
    • 594-638: GYEKSRSLNNIAGLAGNALRLSPVTSPYNSPCPLRRSRSPIPSIL → VLYRIYHGFLPAENGTLRFSHSKDCTGNFCY

Features

Showing features for sequence conflict, compositional bias, alternative sequence.

TypeIDPosition(s)Description
Sequence conflict2in Ref. 4; CAA44643
Compositional bias56-74Pro residues
Alternative sequenceVSP_001018594-638in isoform 2
Alternative sequenceVSP_001019594-638in isoform 3
Alternative sequenceVSP_001020594-638in isoform 4

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
M34052
EMBL· GenBank· DDBJ
AAA42142.1
EMBL· GenBank· DDBJ
mRNA
M59211
EMBL· GenBank· DDBJ
AAA41819.1
EMBL· GenBank· DDBJ
mRNA
M59313
EMBL· GenBank· DDBJ
AAA41820.1
EMBL· GenBank· DDBJ
mRNA Sequence problems.
X62839
EMBL· GenBank· DDBJ
CAA44643.1
EMBL· GenBank· DDBJ
mRNA
M84203
EMBL· GenBank· DDBJ
AAA42143.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

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