Reviewed, UniProtKB/Swiss-Prot Q09470 (KCNA1_HUMAN)

Names and origin

Protein names

Recommended name:
    Potassium voltage-gated channel subfamily A member 1
Alternative name(s):
    Voltage-gated potassium channel subunit Kv1.1
    HUKI
    HBK1

Gene names

Name:

KCNA1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	495 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	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. Binds KCNAB2 and PDZ domains of DLG1, DLG2 and DLG4 By similarity.
Subcellular location	Membrane; Multi-pass membrane protein.
Domain	The N-terminus may be important in determining the rate of inactivation of the channel while the tail may play a role in modulation of channel activity and/or targeting of the channel to specific subcellular compartments. The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position.
Post-translational modification	Palmitoylated on Cys-243; which may be required for membrane targeting. Ref.7
Involvement in disease	Defects in KCNA1 are the cause of episodic ataxia type 1 (EA1) [MIM:160120]; also known as paroxysmal or episodic ataxia with myokymia (EAM) or paroxysmal ataxia with neuromyotonia. EA1 is an autosomal dominant disorder characterized by brief episodes of ataxia and dysarthria. Neurological examination during and between the attacks demonstrates spontaneous, repetitive discharges in the distal musculature (myokymia) that arise from peripheral nerve. Nystagmus is absent. Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Defects in KCNA1 are the cause of myokymia isolated type 1 (MK1) [MIM:160120]. Myokymia is a condition characterized by spontaneous involuntary contraction of muscle fiber groups that can be observed as vermiform movement of the overlying skin. Electromyography typically shows continuous motor unit activity with spontaneous oligo- and multiplet-discharges of high intraburst frequency (myokymic discharges). Isolated spontaneous muscle twitches occur in many persons and have no grave significance. Ref.14 Ref.17
Sequence similarities	Belongs to the potassium channel family. A (Shaker) subfamily.
RNA editing	Edited at position 400. Partially edited. RNA editing varies from 17% in the caudate nucleus to 68% in the spinal cord and to 77% in the medulla. Ref.6

Ontologies

Keywords
Biological process	Ion transport Potassium transport Transport
Cellular component	Membrane
Coding sequence diversity	Polymorphism RNA editing
Disease	Disease mutation
Domain	Transmembrane
Ligand	Potassium
Molecular function	Ionic channel Potassium channel Voltage-gated channel
PTM	Glycoprotein Lipoprotein Palmitate Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	potassium ion transport Ref.10 Traceable author statement. Source: ProtInc synaptic transmission Ref.8 Traceable author statement. Source: ProtInc
Cellular component	voltage-gated potassium channel complex Ref.10 Traceable author statement. Source: ProtInc
Molecular function	delayed rectifier potassium channel activity Ref.10 Traceable author statement. Source: ProtInc potassium ion binding Inferred from electronic annotation. Source: UniProtKB-KW potassium ion transmembrane transporter activity Ref.10 Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 495	495	Potassium voltage-gated channel subfamily A member 1		PRO_0000053968
Regions
	Transmembrane	168 – 186	19	Segment S1 Potential
	Transmembrane	221 – 242	22	Segment S2 Potential
	Transmembrane	254 – 274	21	Segment S3 Potential
	Transmembrane	290 – 309	20	Segment S4 Potential
	Transmembrane	326 – 345	20	Segment S5 Potential
	Transmembrane	387 – 408	22	Segment S6 Potential
	Motif	372 – 377	6	Selectivity filter By similarity
	Motif	493 – 495	3	PDZ-binding By similarity
Amino acid modifications
	Modified residue	322	1	Phosphoserine; by PKA Potential
	Modified residue	445	1	Phosphoserine; by PKA Potential
	Lipidation	243	1	S-palmitoyl cysteine Ref.7
	Glycosylation	207	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	174	1	V → F in EA1. Ref.8 Ref.9		VAR_001508
	Natural variant	177	1	I → R in EA1. Ref.12		VAR_001509
	Natural variant	184	1	F → C in EA1; alters voltage dependence and kinetics of activation though not of C-type inactivation. Ref.9 Ref.10		VAR_020830
	Natural variant	204	1	R → H: dbSNP rs2229000.		VAR_020051
	Natural variant	226	1	T → A in EA1. Ref.11 Ref.12 Ref.13		VAR_001510
	Natural variant	226	1	T → K in MK1; induces a reduced efflux of potassium ions during depolarization which results in increased muscle cell activity; coexpression studies of the mutant protein with the wild-type protein produces significantly reduced currents suggesting a severe effect of the mutation. dbSNP rs28933383. Ref.17		VAR_037100
	Natural variant	226	1	T → M in EA1. Ref.11 Ref.12 Ref.13		VAR_020831
	Natural variant	226	1	T → R in EA1; yields currents with a largely reduced amplitude. Ref.11 Ref.12 Ref.13		VAR_037101
	Natural variant	239	1	R → S in EA1. Ref.8		VAR_001511
	Natural variant	242	1	A → P in MK1; 10% reduction of mean peak current amplitudes compared to wil-dtype; mutant and wild-type expression together is consistent with a loss-of-function effect of the mutation. dbSNP rs28933381. Ref.14		VAR_037102
	Natural variant	244	1	P → H in MK1; no difference between the mutation compared to wild-type; although coexpression experiments with wild-type RNA yielded a peak current amplitude that was 200% of wildt-ype alone; coexpression of the mutant and wild-type genes had only a small effect on current activation parameters. dbSNP rs28933382. Ref.14		VAR_037103
	Natural variant	249	1	F → I in EA1. Ref.8		VAR_001512
	Natural variant	325	1	E → D in EA1; results in non-functional homomeric channels. Ref.9 Ref.10		VAR_020832
	Natural variant	329	1	L → I in EA1. Ref.15		VAR_020833
	Natural variant	342	1	S → I in EA1; phenotype without myokymia. Ref.16		VAR_020834
	Natural variant	400	1	I → V in RNA edited version.		VAR_016805
	Natural variant	404	1	V → I in EA1; yields current amplitudes that were not different from wild-type; coexpression with wild-type partially corrected the alterations in activation parameters. Ref.12 Ref.14		VAR_001513
	Natural variant	408	1	V → A in EA1; channels have voltage dependence similar to that of wild-type channels but with faster kinetics and increased C-type inactivation. Ref.8 Ref.10		VAR_001514
Experimental info
	Mutagenesis	35 – 36	2	CC → AA: No effect on palmitoylation, no effect on current kinetics.
	Mutagenesis	243	1	C → A: Strongly decreases palmitoylation and alters current kinetics. Ref.7
	Sequence conflict	265	1	Missing Ref.5
	Sequence conflict	315	1	L → R Ref.5
	Sequence conflict	452	1	S → Y in AAA36139. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q09470-1 [UniParc]. Last modified February 10, 2009. Version 2. Checksum: 0A1B1AB87BCDDEBA	FASTA	495	56,466
	10 20 30 40 50 60 MTVMSGENVD EASAAPGHPQ DGSYPRQADH DDHECCERVV INISGLRFET QLKTLAQFPN 70 80 90 100 110 120 TLLGNPKKRM RYFDPLRNEY FFDRNRPSFD AILYYYQSGG RLRRPVNVPL DMFSEEIKFY 130 140 150 160 170 180 ELGEEAMEKF REDEGFIKEE ERPLPEKEYQ RQVWLLFEYP ESSGPARVIA IVSVMVILIS 190 200 210 220 230 240 IVIFCLETLP ELKDDKDFTG TVHRIDNTTV IYNSNIFTDP FFIVETLCII WFSFELVVRF 250 260 270 280 290 300 FACPSKTDFF KNIMNFIDIV AIIPYFITLG TEIAEQEGNQ KGEQATSLAI LRVIRLVRVF 310 320 330 340 350 360 RIFKLSRHSK GLQILGQTLK ASMRELGLLI FFLFIGVILF SSAVYFAEAE EAESHFSSIP 370 380 390 400 410 420 DAFWWAVVSM TTVGYGDMYP VTIGGKIVGS LCAIAGVLTI ALPVPVIVSN FNYFYHRETE 430 440 450 460 470 480 GEEQAQLLHV SSPNLASDSD LSRRSSSTMS KSEYMEIEED MNNSIAHYRQ VNIRTANCTT 490 ANQNCVNKSK LLTDV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human potassium channel genes: molecular cloning and functional expression." Ramaswami M., Gautam M., Kamb A., Rudy B., Tanouye M.A., Mathew M.K. Mol. Cell. Neurosci. 1:214-223(1990) Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[2]	"The finished DNA sequence of human chromosome 12." Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R. , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A. Nature 440:346-351(2006) [PubMed: 16541075] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain cortex.
[5]	"Cloning and characterization of a cDNA encoding a human brain potassium channel." Freeman S.N., Conley E.C., Brennand J.C., Russell N.J.W., Brammar W.J. Biochem. Soc. Trans. 18:891-892(1990) [PubMed: 2128063] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 263-315.
[6]	"Nervous system targets of RNA editing identified by comparative genomics." Hoopengardner B., Bhalla T., Staber C., Reenan R. Science 301:832-836(2003) [PubMed: 12907802] [Abstract] Cited for: RNA EDITING OF POSITION 400.
[7]	"The human Kv1.1 channel is palmitoylated, modulating voltage sensing: Identification of a palmitoylation consensus sequence." Gubitosi-Klug R.A., Mancuso D.J., Gross R.W. Proc. Natl. Acad. Sci. U.S.A. 102:5964-5968(2005) [PubMed: 15837928] [Abstract] Cited for: PALMITOYLATION AT CYS-243, MUTAGENESIS OF 35-CYS--CYS-36 AND CYS-243.
[8]	"Episodic ataxia/myokymia syndrome is associated with point mutations in the human potassium channel gene, KCNA1." Browne D.L., Gancher S.T., Nutt J.G., Brunt E.R.P., Smith E.A., Kramer P., Litt M. Nat. Genet. 8:136-140(1994) [PubMed: 7842011] [Abstract] Cited for: VARIANTS EA1 PHE-174; SER-239; ILE-249 AND ALA-408.
[9]	"Identification of two new KCNA1 mutations in episodic ataxia/myokymia families." Browne D.L., Brunt E.R.P., Griggs R.C., Nutt J.G., Gancher S.T., Smith E.A., Litt M. Hum. Mol. Genet. 4:1671-1672(1995) [PubMed: 8541859] [Abstract] Cited for: VARIANTS EA1 PHE-174; CYS-184 AND ASP-325.
[10]	"Episodic ataxia results from voltage-dependent potassium channels with altered functions." Adelman J.P., Bond C.T., Pessia M., Maylie J. Neuron 15:1449-1454(1995) [PubMed: 8845167] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS EA1 CYS-184; ASP-325 AND ALA-408.
[11]	"Episodic ataxia and myokymia syndrome: a new mutation of potassium channel gene Kv1.1." Comu S., Giuliani M., Narayanan V. Ann. Neurol. 40:684-687(1996) [PubMed: 8871592] [Abstract] Cited for: VARIANT EA1 MET-226.
[12]	"Three novel KCNA1 mutations in episodic ataxia type I families." Scheffer H., Brunt E.R.P., Mol G.J.J., van der Vlies P., Stulp R.P., Verlind E., Mantel G., Averyanov Y.N., Hofstra R.M.W., Buys C.H.C.M. Hum. Genet. 102:464-466(1998) [PubMed: 9600245] [Abstract] Cited for: VARIANTS EA1 ARG-177; ALA-226 AND ILE-404.
[13]	"A novel mutation in the human voltage-gated potassium channel gene (Kv1.1) associates with episodic ataxia type 1 and sometimes with partial epilepsy." Zuberi S.M., Eunson L.H., Spauschus A., De Silva R., Tolmie J., Wood N.W., McWilliam R.C., Stephenson J.P.B., Kullmann D.M., Hanna M.G. Brain 122:817-825(1999) [PubMed: 10355668] [Abstract] Cited for: VARIANT EA1 ARG-226, CHARACTERIZATION OF VARIANT EA1 ARG-226.
[14]	"Clinical, genetic, and expression studies of mutations in the potassium channel gene KCNA1 reveal new phenotypic variability." Eunson L.H., Rea R., Zuberi S.M., Youroukos S., Panayiotopoulos C.P., Liguori R., Avoni P., McWilliam R.C., Stephenson J.B.P., Hanna M.G., Kullmann D.M., Spauschus A. Ann. Neurol. 48:647-656(2000) [PubMed: 11026449] [Abstract] Cited for: VARIANTS MK1 PRO-242 AND HIS-244, VARIANT EA1 ILE-404, CHARACTERIZATION OF VARIANTS MK1 PRO-242 AND HIS-244, CHARACTERIZATION OF VARIANT EA1 ILE-404.
[15]	"Identification of a novel missense mutation L329I in the episodic ataxia type 1 gene KCNA1 -- a challenging problem." Knight M.A., Storey E., McKinlay Gardner R.J., Hand P., Forrest S.M. Hum. Mutat. 16:374-374(2000) [PubMed: 11013453] [Abstract] Cited for: VARIANT EA1 ILE-329.
[16]	"A novel mutation in KCNA1 causes episodic ataxia without myokymia." Lee H., Wang H., Jen J.C., Sabatti C., Baloh R.W., Nelson S.F. Hum. Mutat. 24:536-536(2004) [PubMed: 15532032] [Abstract] Cited for: VARIANT EA1 ILE-342.
[17]	"Functional analysis of a novel potassium channel (KCNA1) mutation in hereditary myokymia." Chen H., von Hehn C., Kaczmarek L.K., Ment L.R., Pober B.R., Hisama F.M. Neurogenetics 8:131-135(2007) [PubMed: 17136396] [Abstract] Cited for: VARIANT MK1 LYS-226, CHARACTERIZATION OF VARIANT MK1 LYS-226.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBLGenBankDDBJ

L02750 mRNA. Translation: AAA36139.1.
AC006063 Genomic DNA. No translation available.
CH471116 Genomic DNA. Translation: EAW88833.1.
BC101733 mRNA. Translation: AAI01734.1.
BC112180 mRNA. Translation: AAI12181.1.

IPI

IPI00020983.

PIR

I57680.

RefSeq

NP_000208.2.

UniGene

Hs.416139

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2AFL	model	-	A/B/C/D	326-407	[»]

SMR

Q09470. Positions 36-178, 218-419.

ModBase

Search...

PTM databases

PhosphoSite

Q09470.

Proteomic databases

PRIDE

Q09470.

Genome annotation databases

Ensembl

ENSG00000111262. Homo sapiens. [Contig view]

GeneID

3736.

NMPDR

fig|9606.3.peg.6994.

Organism-specific databases

GeneCards

GC12P004894.

H-InvDB

HIX0036857.

HGNC

HGNC:6218. KCNA1.

MIM

160120. phenotype.
176260. gene.

Orphanet

37612. Ataxia, episodic, type 1.
972. Hereditary continuous muscle fiber activity.

PharmGKB

PA30019.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

Q09470.

HOVERGEN

Q09470.

OMA

Q09470. EYQRQVW.

Gene expression databases

ArrayExpress

Q09470.

Bgee

Q09470.

CleanEx

HS_KCNA1.

GermOnline

ENSG00000111262. Homo sapiens.

Family and domain databases

InterPro

IPR000210. BTB/POZ-like.
IPR011333. BTB/POZ_fold.
IPR005821. Ion_trans.
IPR003091. K_chnl.
IPR003968. K_chnl_volt-dep_Kv.
IPR003972. K_chnl_volt-dep_Kv1.
IPR004048. K_chnl_volt-dep_Kv1.1.
IPR003131. K_chnl_volt-dep_Kv_tetra.
[Graphical view]

Gene3D

G3DSA:3.30.710.10. BTB/POZ_fold. 1 hit.

Pfam

PF00520. Ion_trans. 1 hit.
PF02214. K_tetra. 1 hit.
[Graphical view]

PRINTS

PR00169. KCHANNEL.
PR01508. KV11CHANNEL.
PR01491. KVCHANNEL.
PR01496. SHAKERCHANEL.

SMART

SM00225. BTB. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB01189. Desflurane.
DB00228. Enflurane.
DB00753. Isoflurane.
DB01028. Methoxyflurane.
DB01236. Sevoflurane.

SOURCE

Search...

Entry information

Entry name

KCNA1_HUMAN

Accession

Primary (citable) accession number: Q09470
Secondary accession number(s): A6NM83, Q3MIQ9

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	February 10, 2009
Last modified:	June 16, 2009
This is version 99 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)