UniProtKB - Q14B80 (KCNC2_MOUSE)
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Protein
Potassium voltage-gated channel subfamily C member 2
Gene
Kcnc2
Organism
Mus musculus (Mouse)
Status
Functioni
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:10561420, PubMed:10414303, PubMed:11124984, PubMed:10903572, PubMed:11506885, PubMed:15317859, PubMed:15917463, PubMed:17761775, PubMed:21414897). Homotetramer channels mediate delayed-rectifier voltage-dependent potassium currents that activate rapidly at high-threshold voltages and inactivate slowly (PubMed:10414303). 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 (PubMed:10531438, PubMed:12000114). 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 (PubMed:10561420, PubMed:10903572, PubMed:11506885, PubMed:17761775). 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 (PubMed:10903572). 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 (PubMed:15917463). Required for long-range synchronization of gamma oscillations over distance in the neocortex (PubMed:22539821). Contributes to the modulation of the circadian rhythm of spontaneous action potential firing in suprachiasmatic nucleus (SCN) neurons in a light-dependent manner (PubMed:21414897).By similarity2 Publications10 Publications
Enzyme regulationi
Inhibited by millimolar levels of tetraethylammonium (TEA). Contrary to other channels, inhibited only by millimolar levels of 4-aminopyridine (4-AP). Inhibited by Stichodactyla helianthus peptide ShK.By similarity1 Publication
Kineticsi
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. 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.By similarity1 Publication
GO - Molecular functioni
- delayed rectifier potassium channel activity Source: UniProtKB
- ion channel binding Source: UniProtKB
- voltage-gated potassium channel activity Source: UniProtKB
GO - Biological processi
- action potential Source: MGI
- cellular response to nitric oxide Source: UniProtKB
- nitric oxide-cGMP-mediated signaling pathway Source: UniProtKB
- potassium ion transmembrane transport Source: UniProtKB
- protein heterooligomerization Source: UniProtKB
- protein homooligomerization Source: UniProtKB
- regulation of ion transmembrane transport Source: UniProtKB-KW
Keywordsi
Molecular function | Ion channel, Potassium channel, Voltage-gated channel |
Biological process | Ion transport, Potassium transport, Transport |
Ligand | Potassium |
Enzyme and pathway databases
Reactomei | R-MMU-1296072. Voltage gated Potassium channels. R-MMU-381676. Glucagon-like Peptide-1 (GLP1) regulates insulin secretion. |
Names & Taxonomyi
Protein namesi | Recommended name: Potassium voltage-gated channel subfamily C member 2ImportedAlternative name(s): Shaw-like potassium channelBy similarity Voltage-gated potassium channel Kv3.21 Publication |
Gene namesi | Name:Kcnc2Imported |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:96668. Kcnc2. |
Subcellular locationi
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 233 | CytoplasmicSequence analysisAdd BLAST | 233 | |
Transmembranei | 234 – 254 | Helical; Name=Segment S1Sequence analysisAdd BLAST | 21 | |
Transmembranei | 287 – 307 | Helical; Name=Segment S2Sequence analysisAdd BLAST | 21 | |
Topological domaini | 308 – 317 | CytoplasmicSequence analysis | 10 | |
Transmembranei | 318 – 338 | Helical; Name=Segment S3Sequence analysisAdd BLAST | 21 | |
Transmembranei | 350 – 372 | Helical; Voltage-sensor; Name=Segment S4Sequence analysisAdd BLAST | 23 | |
Topological domaini | 373 – 385 | CytoplasmicSequence analysisAdd BLAST | 13 | |
Transmembranei | 386 – 406 | Helical; Name=Segment S5Sequence analysisAdd BLAST | 21 | |
Transmembranei | 457 – 477 | Helical; Name=Segment S6Sequence analysisAdd BLAST | 21 | |
Topological domaini | 478 – 642 | CytoplasmicSequence analysisAdd BLAST | 165 |
Keywords - Cellular componenti
Cell junction, Cell membrane, Cell projection, Membrane, Postsynaptic cell membrane, Synapse, SynaptosomePathology & Biotechi
Disruption phenotypei
Mice are healthy, grow normally, are fertile and show no evidence of severe sensory or motor abnormalities (PubMed:11124984). Show increased seizure susceptibility and reduced long-range synchronization of gamma oscillations over distance in the neocortex (PubMed:22539821). Thalamocortical neurons show a strong attenuation in maximal peak firing rates, with larger spikes and slower action potential repolarization (PubMed:17761775). Neocortical GABAergic interneurons display broader spikes and sustain lower trains of high-frequency spikes without accommodation or spike doublets in rapid succession (PubMed:11124984, PubMed:22539821). Histamine H2 receptor- and PKA-induced hippocampal inhibitory interneurons display no maximal sustainable firing frequency modulation (PubMed:10903572). Double knockout of KCNC2 and KCNC1 exhibited disrupted daily rhythms in wheel-running behavior (PubMed:21414897). Display smaller outward currents and slower deactivation in starburst amacrine cells compared with KCNC2 knockout mice (PubMed:15317859). Neocortical GABAergic interneuron terminals display also a reduced rate of spike repolarization, broader spike, increased calcium influx and release of GABA neurotransmitter (PubMed:15917463). Suprachiasmatic nucleus (SCN) neurons display a reduction in the magnitude of fast delayed rectifier potassium currents, wider action potentials, reduced spontaneous firing activity during the day and reduced NMDA-evoked increase firing responses during the night (PubMed:21414897).7 Publications
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000310417 | 1 – 642 | Potassium voltage-gated channel subfamily C member 2Add BLAST | 642 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 263 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 270 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Modified residuei | 604 | PhosphoserineCombined sources | 1 |
Post-translational modificationi
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 (PubMed:10903572).By similarity1 Publication
Keywords - PTMi
Glycoprotein, PhosphoproteinProteomic databases
PaxDbi | Q14B80. |
PRIDEi | Q14B80. |
PTM databases
iPTMneti | Q14B80. |
PhosphoSitePlusi | Q14B80. |
Expressioni
Tissue specificityi
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:12000114, PubMed:10903572). 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).7 Publications
Developmental stagei
Weakly expressed in the brain at 14 dpc (at protein level) (PubMed:21912965). Expressed in the brain at 14 dpc (PubMed:21912965).1 Publication
Gene expression databases
ExpressionAtlasi | Q14B80. baseline and differential. |
Interactioni
Subunit structurei
Homotetramer and heterotetramer with other channel-forming alpha subunits, such as KCNC1 (PubMed:10531438). Interacts with KCNC1 (PubMed:10531438, PubMed:12000114). 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 (By similarity).By similarity2 Publications
GO - Molecular functioni
- ion channel binding Source: UniProtKB
Protein-protein interaction databases
STRINGi | 10090.ENSMUSP00000089814. |
Family & Domainsi
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 441 – 446 | Selectivity filterBy similarity | 6 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 56 – 103 | Gly/Pro-rich (insert)Add BLAST | 48 |
Domaini
The transmembrane segment S4 functions as 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.By similarity
Sequence similaritiesi
Belongs to the potassium channel family. C (Shaw) (TC 1.A.1.2) subfamily. Kv3.2/KCNC2 sub-subfamily. [View classification]Curated
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG3713. Eukaryota. COG1226. LUCA. |
GeneTreei | ENSGT00760000118846. |
HOGENOMi | HOG000231012. |
HOVERGENi | HBG105862. |
InParanoidi | Q14B80. |
PhylomeDBi | Q14B80. |
Family and domain databases
Gene3Di | 1.20.120.350. 1 hit. |
InterProi | View protein in InterPro IPR000210. BTB/POZ_dom. IPR005821. Ion_trans_dom. IPR003968. K_chnl_volt-dep_Kv. IPR003974. K_chnl_volt-dep_Kv3. IPR011333. SKP1/BTB/POZ_sf. IPR003131. T1-type_BTB. IPR028325. VG_K_chnl. IPR027359. Volt_channel_dom_sf. |
PANTHERi | PTHR11537. PTHR11537. 1 hit. |
Pfami | View protein in Pfam PF02214. BTB_2. 1 hit. PF00520. Ion_trans. 1 hit. |
PRINTSi | PR00169. KCHANNEL. PR01491. KVCHANNEL. PR01498. SHAWCHANNEL. |
SMARTi | View protein in SMART SM00225. BTB. 1 hit. |
SUPFAMi | SSF54695. SSF54695. 2 hits. |
i Sequence
Sequence statusi: Complete.
Q14B80-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MGKIESNERV ILNVGGTRHE TYRSTLKTLP GTRLALLASS EPQGDCLTAA
60 70 80 90 100
GDKLQPLPPP LSPPPRPPPL SPVPSGCFEG GAGNCSSHGG NGGNGGSDHP
110 120 130 140 150
GGGREFFFDR HPGVFAYVLN YYRTGKLHCP ADVCGPLFEE ELAFWGIDET
160 170 180 190 200
DVEPCCWMTY RQHRDAEEAL DIFETPDLIG GDPGDDEDLA AKRLGIEDAA
210 220 230 240 250
GLGGPDGKSG RWRKLQPRMW ALFEDPYSSR AARFIAFASL FFILVSITTF
260 270 280 290 300
CLETHEAFNI VKNKTEPVIN GTSPVLQYEI ETDPALTYVE GVCVVWFTFE
310 320 330 340 350
FLVRIVFSPN KLEFIKNLLN IIDFVAILPF YLEVGLSGLS SKAAKDVLGF
360 370 380 390 400
LRVVRFVRIL RIFKLTRHFV GLRVLGHTLR ASTNEFLLLI IFLALGVLIF
410 420 430 440 450
ATMIYYAERV GAQPNDPSAS EHTQFKNIPI GFWWAVVTMT TLGYGDMYPQ
460 470 480 490 500
TWSGMLVGAL CALAGVLTIA MPVPVIVNNF GMYYSLAMAK QKLPRKRKKH
510 520 530 540 550
IPPAPLASSP TFCKTELNMA CNSTQSDTCL GKENRLLEHN RSVLSGDDST
560 570 580 590 600
GSEPPLSPPE RLPIRRSSTR DKNRRGETCF LLTTGDYTCA SDGGIRKGYE
610 620 630 640
KSRSLNNIAG LAGNALRLSP VTSPYNSPCP LRRSRSPIPS IL
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | BC116289 mRNA. Translation: AAI16290.1. BC116290 mRNA. Translation: AAI16291.1. |
RefSeqi | XP_006513748.1. XM_006513685.3. XP_006513750.1. XM_006513687.3. XP_006513751.1. XM_006513688.1. XP_006513752.1. XM_006513689.3. XP_006513753.1. XM_006513690.2. |
UniGenei | Mm.336242. |
Genome annotation databases
Ensembli | ENSMUST00000092175; ENSMUSP00000089814; ENSMUSG00000035681. |
GeneIDi | 268345. |
UCSCi | uc007hao.1. mouse. |
Similar proteinsi
Entry informationi
Entry namei | KCNC2_MOUSE | |
Accessioni | Q14B80Primary (citable) accession number: Q14B80 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 13, 2007 |
Last sequence update: | August 22, 2006 | |
Last modified: | February 28, 2018 | |
This is version 92 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |