Q14003 (KCNC3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Potassium voltage-gated channel subfamily C member 3

Alternative name(s):
KSHIIID
Voltage-gated potassium channel subunit Kv3.3

Gene names

Name:

KCNC3

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	757 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	This protein mediates the voltage-dependent potassium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a potassium-selective channel through which potassium ions may pass in accordance with their electrochemical gradient.
Subunit structure	Heterotetramer of potassium channel proteins By similarity.
Subcellular location	Membrane; Multi-pass membrane protein.
Domain	The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position. The tail may be important in modulation of channel activity and/or targeting of the channel to specific subcellular compartments.
Involvement in disease	Spinocerebellar ataxia 13 (SCA13) [MIM:605259]: Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA13 is an autosomal dominant cerebellar ataxia (ADCA) characterized by slow progression and variable age at onset, ranging from childhood to late adulthood. Mental retardation can be present in some patients. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.4
Sequence similarities	Belongs to the potassium channel family. C (Shaw) (TC 1.A.1.2) subfamily. Kv3.3/KCNC3 sub-subfamily. [View classification]

Ontologies

Keywords
Biological process	Ion transport Potassium transport Transport
Cellular component	Membrane
Disease	Disease mutation Neurodegeneration Spinocerebellar ataxia
Domain	Transmembrane Transmembrane helix
Ligand	Potassium
Molecular function	Ion channel Potassium channel Voltage-gated channel
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell death Inferred from electronic annotation. Source: UniProtKB-KW protein homooligomerization Inferred from electronic annotation. Source: InterPro regulation of neurotransmitter secretion Inferred from electronic annotation. Source: Compara synaptic transmission Traceable author statement. Source: Reactome
Cellular_component	axolemma Inferred from electronic annotation. Source: Compara axon terminus Inferred from electronic annotation. Source: Compara dendrite membrane Inferred from electronic annotation. Source: Compara neuromuscular junction Inferred from electronic annotation. Source: Compara neuronal cell body membrane Inferred from electronic annotation. Source: Compara voltage-gated potassium channel complex Traceable author statement PubMed 1740329. Source: ProtInc
Molecular_function	delayed rectifier potassium channel activity Inferred from Biological aspect of Ancestor. Source: RefGenome
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 757	757	Potassium voltage-gated channel subfamily C member 3		PRO_0000054055
Regions
	Topological domain	1 – 290	290	Cytoplasmic Potential
	Transmembrane	291 – 309	19	Helical; Name=Segment S1; Potential
	Transmembrane	351 – 370	20	Helical; Name=Segment S2; Potential
	Topological domain	371 – 379	9	Cytoplasmic Potential
	Transmembrane	380 – 398	19	Helical; Name=Segment S3; Potential
	Transmembrane	412 – 434	23	Helical; Voltage-sensor; Name=Segment S4; Potential
	Topological domain	435 – 447	13	Cytoplasmic Potential
	Transmembrane	448 – 469	22	Helical; Name=Segment S5; Potential
	Transmembrane	518 – 539	22	Helical; Name=Segment S6; Potential
	Topological domain	540 – 757	218	Cytoplasmic Potential
	Motif	503 – 508	6	Selectivity filter By similarity
	Compositional bias	31 – 38	8	Poly-Pro
	Compositional bias	39 – 42	4	Poly-Gln
	Compositional bias	81 – 85	5	Poly-Gly
	Compositional bias	229 – 234	6	Poly-Gly
	Compositional bias	577 – 587	11	Poly-Pro
	Compositional bias	596 – 599	4	Poly-Pro
	Compositional bias	668 – 673	6	Poly-Ala
Amino acid modifications
	Glycosylation	320	1	N-linked (GlcNAc...) Potential
	Glycosylation	336	1	N-linked (GlcNAc...) Potential
	Glycosylation	483	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	420	1	R → H in SCA13; loss of channel activity. Ref.4		VAR_029530
	Natural variant	448	1	F → L in SCA13; slow channel closing. Ref.4		VAR_029531
Experimental info
	Sequence conflict	63	1	D → G in AAC24118. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q14003 [UniParc]. Last modified November 4, 2008. Version 3. Checksum: B44306B850DFD797	FASTA	757	80,578
	10 20 30 40 50 60 MLSSVCVSSF RGRQGASKQQ PAPPPQPPES PPPPPLPPQQ QQPAQPGPAA SPAGPPAPRG 70 80 90 100 110 120 PGDRRAEPCP GLPAAAMGRH GGGGGDSGKI VINVGGVRHE TYRSTLRTLP GTRLAGLTEP 130 140 150 160 170 180 EAAARFDYDP GADEFFFDRH PGVFAYVLNY YRTGKLHCPA DVCGPLFEEE LGFWGIDETD 190 200 210 220 230 240 VEACCWMTYR QHRDAEEALD SFEAPDPAGA ANAANAAGAH DGGLDDEAGA GGGGLDGAGG 250 260 270 280 290 300 ELKRLCFQDA GGGAGGPPGG AGGAGGTWWR RWQPRVWALF EDPYSSRAAR YVAFASLFFI 310 320 330 340 350 360 LISITTFCLE THEGFIHISN KTVTQASPIP GAPPENITNV EVETEPFLTY VEGVCVVWFT 370 380 390 400 410 420 FEFLMRITFC PDKVEFLKSS LNIIDCVAIL PFYLEVGLSG LSSKAAKDVL GFLRVVRFVR 430 440 450 460 470 480 ILRIFKLTRH FVGLRVLGHT LRASTNEFLL LIIFLALGVL IFATMIYYAE RIGADPDDIL 490 500 510 520 530 540 GSNHTYFKNI PIGFWWAVVT MTTLGYGDMY PKTWSGMLVG ALCALAGVLT IAMPVPVIVN 550 560 570 580 590 600 NFGMYYSLAM AKQKLPKKKN KHIPRPPQPG SPNYCKPDPP PPPPPHPHHG SGGISPPPPI 610 620 630 640 650 660 TPPSMGVTVA GAYPAGPHTH PGLLRGGAGG LGIMGLPPLP APGEPCPLAQ EEVIEINRAD 670 680 690 700 710 720 PRPNGDPAAA ALAHEDCPAI DQPAMSPEDK SPITPGSRGR YSRDRACFLL TDYAPSPDGS 730 740 750 IRKATGAPPL PPQDWRKPGP PSFLPDLNAN AAAWISP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Kv3.3 potassium channels in lens epithelium and corneal endothelium." Rae J.L., Shepard A.R. Exp. Eye Res. 70:339-348(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Lens epithelium.
[2]	"The DNA sequence and biology of human chromosome 19." Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M. Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"A human chromosome 19 Shaw type potassium channel gene." Lee J.E., Garbutt J.H., Phillips K.L., Roses A.D. Submitted (JAN-1992) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 291-651.
[4]	"Mutations in voltage-gated potassium channel KCNC3 cause degenerative and developmental nervous system phenotypes." Waters M.F., Minassian N.A., Stevanin G., Figueroa K.P., Bannister J.P.A., Nolte D., Mock A.F., Evidente V.G.H., Fee D.B., Mueller U., Duerr A., Brice A., Papazian D.M., Pulst S.M. Nat. Genet. 38:447-451(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS SCA13 HIS-420 AND LEU-448, CHARACTERIZATION OF VARIANTS SCA13 HIS-420 AND LEU-448.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF055989 mRNA. Translation: AAC24118.1. AC008655 Genomic DNA. No translation available. Z11585 Genomic DNA. Translation: CAA77671.1.
IPI	IPI00289965.
PIR	S19552.
RefSeq	NP_004968.2. NM_004977.2.
UniGene	Hs.467146.
3D structure databases
ProteinModelPortal	Q14003.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000303282.
PTM databases
PhosphoSite	Q14003.
Polymorphism databases
DMDM	212276500.
Proteomic databases
PaxDb	Q14003.
PRIDE	Q14003.
Protocols and materials databases
DNASU	3748.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000477616; ENSP00000434241; ENSG00000131398.
GeneID	3748.
KEGG	hsa:3748.
UCSC	uc002pru.1. human.
Organism-specific databases
CTD	3748.
GeneCards	GC19M050815.
H-InvDB	HIX0202872.
HGNC	HGNC:6235. KCNC3.
HPA	HPA018041.
MIM	176264. gene. 605259. phenotype.
neXtProt	NX_Q14003.
Orphanet	98768. Spinocerebellar ataxia type 13.
PharmGKB	PA30027.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG280627.
HOGENOM	HOG000231012.
HOVERGEN	HBG105862.
InParanoid	Q14003.
KO	K04889.
OMA	GFWGIDE.
OrthoDB	EOG4W9J3M.
Enzyme and pathway databases
Reactome	REACT_13685. Neuronal System.
Gene expression databases
ArrayExpress	Q14003.
Bgee	Q14003.
CleanEx	HS_KCNC3.
Genevestigator	Q14003.
GermOnline	ENSG00000131398. Homo sapiens.
Family and domain databases
Gene3D	3.30.710.10. 1 hit.
InterPro	IPR000210. BTB/POZ-like. IPR011333. BTB/POZ_fold. IPR005821. Ion_trans_dom. IPR003091. K_chnl. 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. IPR003131. T1-type_BTB. [Graphical view]
PANTHER	PTHR11537. PTHR11537. 1 hit.
Pfam	PF00520. Ion_trans. 1 hit. PF02214. K_tetra. 1 hit. PF11404. Potassium_chann. 1 hit. [Graphical view]
PRINTS	PR00169. KCHANNEL. PR01582. KV33CHANNEL. PR01491. KVCHANNEL. PR01498. SHAWCHANNEL.
SMART	SM00225. BTB. 1 hit. [Graphical view]
SUPFAM	SSF54695. BTB/POZ_fold. 1 hit.
ProtoNet	Search...
Other
ChiTaRS	KCNC3. human.
GenomeRNAi	3748.
NextBio	14671.
SOURCE	Search...

Entry information

Entry name

KCNC3_HUMAN

Accession

Primary (citable) accession number: Q14003

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	November 4, 2008
Last modified:	May 1, 2013
This is version 119 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.