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Protein

Potassium voltage-gated channel subfamily C member 3

Gene

Kcnc3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Voltage-gated potassium channel that plays an important role in the rapid repolarization of fast-firing brain neurons. The channel opens in response to the voltage difference across the membrane, forming a potassium-selective channel through which potassium ions pass in accordance with their electrochemical gradient. The channel displays rapid activation and inactivation kinetics (PubMed:18539595, PubMed:26997484, PubMed:24218544). It plays a role in the regulation of the frequency, shape and duration of action potentials in Purkinje cells (PubMed:15217387, PubMed:18448641, PubMed:24218544). Required for normal survival of cerebellar neurons, probably via its role in regulating the duration and frequency of action potentials that in turn regulate the activity of voltage-gated Ca2+ channels and cellular Ca2+ homeostasis (PubMed:24218544). Required for normal motor function (PubMed:16923152, PubMed:18448641). Plays a role in the reorganization of the cortical actin cytoskeleton and the formation of actin veil structures in neuronal growth cones via its interaction with HAX1 and the Arp2/3 complex (PubMed:26997484).6 Publications

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Ion channel, Potassium channel, Voltage-gated channel

Keywords - Biological processi

Ion transport, Potassium transport, Transport

Keywords - Ligandi

Potassium

Names & Taxonomyi

Protein namesi
Recommended name:
Potassium voltage-gated channel subfamily C member 3
Alternative name(s):
KSHIIID
Voltage-gated potassium channel subunit Kv3.3
Gene namesi
Name:Kcnc3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:96669. Kcnc3.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 290CytoplasmicCuratedAdd BLAST290
Transmembranei291 – 309Helical; Name=Segment S1Sequence analysisAdd BLAST19
Transmembranei351 – 370Helical; Name=Segment S2Sequence analysisAdd BLAST20
Topological domaini371 – 379CytoplasmicSequence analysis9
Transmembranei380 – 398Helical; Name=Segment S3Sequence analysisAdd BLAST19
Transmembranei412 – 434Helical; Voltage-sensor; Name=Segment S4Sequence analysisAdd BLAST23
Topological domaini435 – 447CytoplasmicSequence analysisAdd BLAST13
Transmembranei448 – 469Helical; Name=Segment S5Sequence analysisAdd BLAST22
Transmembranei518 – 539Helical; Name=Segment S6Sequence analysisAdd BLAST22
Topological domaini540 – 769CytoplasmicSequence analysisAdd BLAST230

GO - Cellular componenti

  • axolemma Source: MGI
  • axon terminus Source: MGI
  • cell cortex Source: UniProtKB-SubCell
  • cell junction Source: UniProtKB-KW
  • cytoskeleton Source: UniProtKB-SubCell
  • dendrite Source: UniProtKB-SubCell
  • dendrite membrane Source: MGI
  • dendritic spine membrane Source: UniProtKB-SubCell
  • integral component of membrane Source: GO_Central
  • neuromuscular junction Source: MGI
  • neuronal cell body membrane Source: MGI
  • perikaryon Source: UniProtKB-SubCell
  • plasma membrane Source: MGI
  • presynaptic membrane Source: UniProtKB-SubCell
  • voltage-gated potassium channel complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Cell projection, Cytoplasm, Cytoskeleton, Membrane, Synapse

Pathology & Biotechi

Disruption phenotypei

Mice lacking both Kcnc3 and Kcnc1 are born at the expected Mendelian rate, but the pups do not thrive and all die about 26 days after birth when kept together with other littermates. Their failure to thrive may be due to motor problems; mutant pups survive when fed separately, but 45 days after birth their body weight is only 50 to 60 % of that of wild-type (PubMed:11517255). They appear uncoordinated and display severe ataxia, myoclonus and spontaneous whole-body muscle jerks, but display no obvious alterations in brain morphology (PubMed:11517255, PubMed:15217387, PubMed:16923152). Mice lacking only Kcnc3 still display ataxic gait and decreased motor skill, but to a lesser degree than mice lacking both Kcnc3 and Kcnc1 (PubMed:16923152, PubMed:18448641). Purkinje cell-specific expression of Kcnc3 restores normal motor skills (PubMed:18448641). Mutant mice are also much more sensitive to ethanol and fall sideways at ethanol concentrations that have no effect on wild-type mice (PubMed:11517255). They display increased locomotor and exploratory activity (PubMed:11517255, PubMed:15217387). Mice lacking Kcnc3 or both Kcnc3 and Kcnc1 are resistant to the tremorogenic agent harmaline (PubMed:15217387).4 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi423R → H: Loss of channel activity. Functions as dominant negative mutation that impairs function of wild-type channel subunits. Causes impaired Purkinje cell dendrite growth and premature death of cerebellar Purkinje cells. 1 Publication1
Mutagenesisi592G → R: No effect on voltage-dependent channel opening or current amplitude, but decreased rate of inactivation during prolonged depolarization. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000540561 – 769Potassium voltage-gated channel subfamily C member 3Add BLAST769

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi320N-linked (GlcNAc...)Sequence analysis1
Glycosylationi336N-linked (GlcNAc...)Sequence analysis1
Glycosylationi483N-linked (GlcNAc...)Sequence analysis1
Modified residuei625Omega-N-methylarginineCombined sources1
Modified residuei687PhosphoserineCombined sources1
Modified residuei692PhosphoserineCombined sources1
Modified residuei731PhosphoserineCombined sources1
Modified residuei734PhosphoserineCombined sources1
Modified residuei742PhosphoserineCombined sources1
Modified residuei750PhosphothreonineCombined sources1
Modified residuei754PhosphoserineCombined sources1

Post-translational modificationi

N-glycosylated.By similarity

Keywords - PTMi

Glycoprotein, Methylation, Phosphoprotein

Proteomic databases

PaxDbiQ63959.
PeptideAtlasiQ63959.
PRIDEiQ63959.

PTM databases

iPTMnetiQ63959.
PhosphoSitePlusiQ63959.

Expressioni

Tissue specificityi

Detected on Purkinje cells in the dentate, interposed and medial nucleus in cerebellum (PubMed:15217387, PubMed:18448641). Detected in brainstem (PubMed:18539595). Detected at calyces of Held in the auditory brain stem (at protein level) (PubMed:26997484). Isoform KV3.3B is highly enriched in the brain, particularly in the cerebellum, where its expression is confined to Purkinje cells and deep cerebellar nuclei. Isoform KV3.3A is not expressed in cerebellum.5 Publications

Developmental stagei

Isoform KV3.3B: Expression begins in cerebellar Purkinje cells between postnatal day 8 (P8) and P10 and continues through adulthood.1 Publication

Interactioni

Subunit structurei

Homotetramer. Heterotetramer with KCNC1 (By similarity). Interacts (via C-terminus) with HAX1. Identified in a complex with ACTR3, a subunit of the Arp2/3 complex; this interaction is indirect and depends on the presence of HAX1. Interaction with HAX1 modulates channel gating (PubMed:26997484).By similarity1 Publication

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000103540.

Structurei

3D structure databases

ProteinModelPortaliQ63959.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 79Important for normal N-type inactivation1 PublicationAdd BLAST79

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi503 – 508Selectivity filterBy similarity6

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi41 – 44Poly-Gln4
Compositional biasi82 – 86Poly-Gly5
Compositional biasi229 – 234Poly-Gly6
Compositional biasi577 – 587Poly-ProAdd BLAST11
Compositional biasi596 – 599Poly-Pro4
Compositional biasi669 – 674Poly-Ala6

Domaini

The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position.Curated
The cytoplasmic N-terminus mediates N-type inactivation.1 Publication
The C-terminal cytoplasmic tail contributes to the regulation of channel inactivation and to the interaction with HAX1 and the Arp2/3 complex.1 Publication

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3713. Eukaryota.
COG1226. LUCA.
HOGENOMiHOG000231012.
HOVERGENiHBG105862.
InParanoidiQ63959.

Family and domain databases

Gene3Di1.20.120.350. 1 hit.
InterProiIPR000210. BTB/POZ_dom.
IPR027359. Channel_four-helix_dom.
IPR005821. Ion_trans_dom.
IPR003968. K_chnl_volt-dep_Kv.
IPR003974. K_chnl_volt-dep_Kv3.
IPR005404. K_chnl_volt-dep_Kv3.3.
IPR021105. K_chnl_volt-dep_Kv3_ID.
IPR011333. SKP1/BTB/POZ.
IPR003131. T1-type_BTB.
IPR028325. VG_K_chnl.
[Graphical view]
PANTHERiPTHR11537. PTHR11537. 3 hits.
PfamiPF02214. BTB_2. 1 hit.
PF00520. Ion_trans. 1 hit.
PF11404. Potassium_chann. 1 hit.
[Graphical view]
PRINTSiPR00169. KCHANNEL.
PR01582. KV33CHANNEL.
PR01491. KVCHANNEL.
PR01498. SHAWCHANNEL.
SMARTiSM00225. BTB. 1 hit.
[Graphical view]
SUPFAMiSSF54695. SSF54695. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform KV3.3B (identifier: Q63959-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MLSSVCVWSF RGRQGTGKQQ PQPVPTPQPP ESSPPPLPPP QQQQCSQPGT
60 70 80 90 100
AASPAVPAFL RPGGRRAEPC PGLPAVAMGR HGGGGGDSGK IVINVGGVRH
110 120 130 140 150
ETYRSTLRTL PGTRLAGLTE PEAAARFDYD PGTDEFFFDR HPGVFAYVLN
160 170 180 190 200
YYRTGKLHCP ADVCGPLFEE ELGFWGIDET DVEACCWMTY RQHRDAEEAL
210 220 230 240 250
DSFEAPDSSA NANANAGGAH DAGLDDEAGA GGGGLDGAGG ELKRLCFQDA
260 270 280 290 300
GGGAGGPAGG AGGAGGTWWR RWQPRVWALF EDPYSSRAAR YVAFASLFFI
310 320 330 340 350
LISITTFCLE THEGFIHISN KTVTQASPIP GAPPENITNV EVETEPFLTY
360 370 380 390 400
VEGVCVVWFT FEFLMRVTFC PDKVEFLKSS LNIIDCVAIL PFYLEVGLSG
410 420 430 440 450
LSSKAAKDVL GFLRVVRFVR ILRIFKLTRH FVGLRVLGHT LRASTNEFLL
460 470 480 490 500
LIIFLALGVL IFATMIYYAE RIGADPDDIL GSNHTYFKNI PIGFWWAVVT
510 520 530 540 550
MTTLGYGDMY PKTWSGMLVG ALCALAGVLT IAMPVPVIVN NFGMYYSLAM
560 570 580 590 600
AKQKLPKKKN KHIPRPPQPG SPNYCKPDPP PPPPPHPHHG SGGISPPPPI
610 620 630 640 650
TPPSMGVNVA GAYPPGPHTH PGLLRGGAGG LGIMGLPPLP APGEPCPLAQ
660 670 680 690 700
EEVIETNRAV DPRPNGDPAA AALAHEDCPA IDQPAMSPED KSPITPGSRG
710 720 730 740 750
RYSRDRACFL VTDYAPSPDG SIRKGYEKSR SLSSIVGLSG VSLRLAPLAT
760
PPGSPRATRR APPTLPSIL
Length:769
Mass (Da):82,143
Last modified:July 27, 2011 - v2
Checksum:iC910236DE8AF04C9
GO
Isoform KV3.3A (identifier: Q63959-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     660-769: VDPRPNGDPA...RAPPTLPSIL → GEAGARTGGV...FGERDSETQV

Show »
Length:757
Mass (Da):81,190
Checksum:iE948AE4B942F23F6
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti13R → C in AAC60679 (PubMed:8301351).Curated1
Sequence conflicti51 – 52AA → GP in AAC60679 (PubMed:8301351).Curated2
Sequence conflicti55A → G in AAC60679 (PubMed:8301351).Curated1
Sequence conflicti256G → D in CAA43209 (PubMed:1740329).Curated1
Sequence conflicti257 – 258PA → LP in AAC60679 (PubMed:8301351).Curated2
Sequence conflicti260 – 266GAGGAGG → ARAAGA in CAA43209 (PubMed:1740329).Curated7
Sequence conflicti521A → G in AAC60679 (PubMed:8301351).Curated1
Sequence conflicti521A → G in CAA43209 (PubMed:1740329).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_001021660 – 769VDPRP…LPSIL → GEAGARTGGVGRSGGKVAGL EGMQGQGFLGSGRVGWEATA DRKDKWLEGWTPGTKSHRNR IPRTRACEHGFQPGCSQRPL VRSSRVRIFGERDSETQV in isoform KV3.3A. CuratedAdd BLAST110

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S69381 mRNA. Translation: AAC60679.1.
AC157653 Genomic DNA. No translation available.
X60796, X60797 Genomic DNA. Translation: CAA43209.1.
PIRiA42073.
UniGeneiMm.40312.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S69381 mRNA. Translation: AAC60679.1.
AC157653 Genomic DNA. No translation available.
X60796, X60797 Genomic DNA. Translation: CAA43209.1.
PIRiA42073.
UniGeneiMm.40312.

3D structure databases

ProteinModelPortaliQ63959.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000103540.

PTM databases

iPTMnetiQ63959.
PhosphoSitePlusiQ63959.

Proteomic databases

PaxDbiQ63959.
PeptideAtlasiQ63959.
PRIDEiQ63959.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

MGIiMGI:96669. Kcnc3.

Phylogenomic databases

eggNOGiKOG3713. Eukaryota.
COG1226. LUCA.
HOGENOMiHOG000231012.
HOVERGENiHBG105862.
InParanoidiQ63959.

Miscellaneous databases

PROiQ63959.
SOURCEiSearch...

Family and domain databases

Gene3Di1.20.120.350. 1 hit.
InterProiIPR000210. BTB/POZ_dom.
IPR027359. Channel_four-helix_dom.
IPR005821. Ion_trans_dom.
IPR003968. K_chnl_volt-dep_Kv.
IPR003974. K_chnl_volt-dep_Kv3.
IPR005404. K_chnl_volt-dep_Kv3.3.
IPR021105. K_chnl_volt-dep_Kv3_ID.
IPR011333. SKP1/BTB/POZ.
IPR003131. T1-type_BTB.
IPR028325. VG_K_chnl.
[Graphical view]
PANTHERiPTHR11537. PTHR11537. 3 hits.
PfamiPF02214. BTB_2. 1 hit.
PF00520. Ion_trans. 1 hit.
PF11404. Potassium_chann. 1 hit.
[Graphical view]
PRINTSiPR00169. KCHANNEL.
PR01582. KV33CHANNEL.
PR01491. KVCHANNEL.
PR01498. SHAWCHANNEL.
SMARTiSM00225. BTB. 1 hit.
[Graphical view]
SUPFAMiSSF54695. SSF54695. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiKCNC3_MOUSE
AccessioniPrimary (citable) accession number: Q63959
Secondary accession number(s): E9Q5E5, Q62088
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: July 27, 2011
Last modified: November 30, 2016
This is version 133 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.