P22462 · KCNC2_RAT
- ProteinVoltage-gated potassium channel KCNC2
- GeneKcnc2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids638 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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).
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
- K+(in) = K+(out)
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).
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).
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.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 124 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 130 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 151 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 152 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 437 | K+ (UniProtKB | ChEBI); ligand shared between homotetrameric partners | ||||
Sequence: T | ||||||
Binding site | 438 | K+ (UniProtKB | ChEBI); ligand shared between homotetrameric partners | ||||
Sequence: L | ||||||
Binding site | 439 | K+ (UniProtKB | ChEBI); ligand shared between homotetrameric partners | ||||
Sequence: G | ||||||
Binding site | 440 | K+ (UniProtKB | ChEBI); ligand shared between homotetrameric partners | ||||
Sequence: Y |
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameVoltage-gated potassium channel KCNC2
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus
Accessions
- Primary accessionP22462
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Multi-pass membrane protein
Membrane ; Multi-pass membrane protein
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).
Colocalizes with parvalbumin in globus pallidus neurons (PubMed:10482766).
Localizes in thalamocortical axons and synapses (PubMed:7643197).
Isoform 1
Isoform 2
Isoform 3
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-229 | Cytoplasmic | ||||
Sequence: MGKIENNERVILNVGGTRHETYRSTLKTLPGTRLALLASSEPQGDCLTAAGDKLQPLPPPLSPPPRPPPLSPVPSGCFEGGAGNCSSHGGNGSDHPGGGREFFFDRHPGVFAYVLNYYRTGKLHCPADVCGPLFEEELAFWGIDETDVEPCCWMTYRQHRDAEEALDIFETPDLIGGDPGDDEDLGGKRLGIEDAAGLGGPDGKSGRWRKLQPRMWALFEDPYSSRAAR | ||||||
Transmembrane | 230-248 | Helical; Name=Segment S1 | ||||
Sequence: FIAFASLFFILVSITTFCL | ||||||
Transmembrane | 284-303 | Helical; Name=Segment S2 | ||||
Sequence: YVEGVCVVWFTFEFLVRIVF | ||||||
Topological domain | 304-314 | Cytoplasmic | ||||
Sequence: SPNKLEFIKNL | ||||||
Transmembrane | 315-337 | Helical; Name=Segment S3 | ||||
Sequence: LNIIDFVAILPFYLEVGLSGLSS | ||||||
Transmembrane | 346-368 | Helical; Voltage-sensor; Name=Segment S4 | ||||
Sequence: FLRVVRFVRILRIFKLTRHFVGL | ||||||
Topological domain | 369-381 | Cytoplasmic | ||||
Sequence: RVLGHTLRASTNE | ||||||
Transmembrane | 382-401 | Helical; Name=Segment S5 | ||||
Sequence: FLLLIIFLALGVLIFATMIY | ||||||
Transmembrane | 451-473 | Helical; Name=Segment S6 | ||||
Sequence: MLVGALCALAGVLTIAMPVPVIV | ||||||
Topological domain | 474-638 | Cytoplasmic | ||||
Sequence: NNFGMYYSLAMAKQKLPRKRKKHIPPAPLASSPTFCKTELNMACNSTQSDTCLGKENRLLEHNRSVLSGDDSTGSEPPLSPPERLPIRRSSTRDKNRRGETCFLLTTGDYTCASDGGIRKGYEKSRSLNNIAGLAGNALRLSPVTSPYNSPCPLRRSRSPIPSIL |
Keywords
- Cellular component
Phenotypes & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 563 | Does 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. | ||||
Sequence: S → A | ||||||
Mutagenesis | 564 | Does 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. | ||||
Sequence: S → A |
Chemistry
PTM/Processing
Features
Showing features for chain, glycosylation, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000054054 | 1-638 | Voltage-gated potassium channel KCNC2 | |||
Sequence: MGKIENNERVILNVGGTRHETYRSTLKTLPGTRLALLASSEPQGDCLTAAGDKLQPLPPPLSPPPRPPPLSPVPSGCFEGGAGNCSSHGGNGSDHPGGGREFFFDRHPGVFAYVLNYYRTGKLHCPADVCGPLFEEELAFWGIDETDVEPCCWMTYRQHRDAEEALDIFETPDLIGGDPGDDEDLGGKRLGIEDAAGLGGPDGKSGRWRKLQPRMWALFEDPYSSRAARFIAFASLFFILVSITTFCLETHEAFNIVKNKTEPVINGTSAVLQYEIETDPALTYVEGVCVVWFTFEFLVRIVFSPNKLEFIKNLLNIIDFVAILPFYLEVGLSGLSSKAAKDVLGFLRVVRFVRILRIFKLTRHFVGLRVLGHTLRASTNEFLLLIIFLALGVLIFATMIYYAERVGAQPNDPSASEHTQFKNIPIGFWWAVVTMTTLGYGDMYPQTWSGMLVGALCALAGVLTIAMPVPVIVNNFGMYYSLAMAKQKLPRKRKKHIPPAPLASSPTFCKTELNMACNSTQSDTCLGKENRLLEHNRSVLSGDDSTGSEPPLSPPERLPIRRSSTRDKNRRGETCFLLTTGDYTCASDGGIRKGYEKSRSLNNIAGLAGNALRLSPVTSPYNSPCPLRRSRSPIPSIL | ||||||
Glycosylation | 259 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 266 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Modified residue | 564 | Phosphoserine; by PKA | ||||
Sequence: S | ||||||
Modified residue | 600 | Phosphoserine | ||||
Sequence: S |
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).
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
- PTM
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).
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).
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).
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.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 47-75 | Disordered | ||||
Sequence: LTAAGDKLQPLPPPLSPPPRPPPLSPVPS | ||||||
Compositional bias | 56-74 | Pro residues | ||||
Sequence: PLPPPLSPPPRPPPLSPVP | ||||||
Motif | 437-442 | Selectivity filter | ||||
Sequence: TLGYGD | ||||||
Region | 538-572 | Disordered | ||||
Sequence: SVLSGDDSTGSEPPLSPPERLPIRRSSTRDKNRRG |
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
Belongs to the potassium channel family. C (Shaw) (TC 1.A.1.2) subfamily. Kv3.2/KCNC2 sub-subfamily.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
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.
- Name1
- SynonymsKV3.2B
- Length638
- Mass (Da)70,191
- Last updated1991-08-01 v1
- Checksum25C102B4CCE53BF4
P22462-2
- Name2
- SynonymsKV3.2C
- Differences from canonical
- 594-638: GYEKSRSLNNIAGLAGNALRLSPVTSPYNSPCPLRRSRSPIPSIL → ASTLEPMESTSQTKGDTRPEAHWNCAHLLNFGCPTGSSFPTL
P22462-3
- Name3
- SynonymsKV3.2A, KShIIIA.1
- Differences from canonical
- 594-638: GYEKSRSLNNIAGLAGNALRLSPVTSPYNSPCPLRRSRSPIPSIL → DNCKDVVITGYTQAEARSLT
P22462-4
- Name4
- Differences from canonical
- 594-638: GYEKSRSLNNIAGLAGNALRLSPVTSPYNSPCPLRRSRSPIPSIL → VLYRIYHGFLPAENGTLRFSHSKDCTGNFCY
Features
Showing features for sequence conflict, compositional bias, alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 2 | in Ref. 4; CAA44643 | ||||
Sequence: G → S | ||||||
Compositional bias | 56-74 | Pro residues | ||||
Sequence: PLPPPLSPPPRPPPLSPVP | ||||||
Alternative sequence | VSP_001018 | 594-638 | in isoform 2 | |||
Sequence: GYEKSRSLNNIAGLAGNALRLSPVTSPYNSPCPLRRSRSPIPSIL → ASTLEPMESTSQTKGDTRPEAHWNCAHLLNFGCPTGSSFPTL | ||||||
Alternative sequence | VSP_001019 | 594-638 | in isoform 3 | |||
Sequence: GYEKSRSLNNIAGLAGNALRLSPVTSPYNSPCPLRRSRSPIPSIL → DNCKDVVITGYTQAEARSLT | ||||||
Alternative sequence | VSP_001020 | 594-638 | in isoform 4 | |||
Sequence: GYEKSRSLNNIAGLAGNALRLSPVTSPYNSPCPLRRSRSPIPSIL → VLYRIYHGFLPAENGTLRFSHSKDCTGNFCY |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
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 |