Kv1.1

KCNA1

Available structures

PDB

Ortholog search: PDBe RCSB

List of PDB id codes
2AFL

Identifiers

Aliases

KCNA1, AEMK, EA1, HBK1, HUK1, KV1.1, MBK1, MK1, RBK1, potassium voltage-gated channel subfamily A member 1

External IDs

OMIM: 176260; MGI: 96654; HomoloGene: 183; GeneCards: KCNA1; OMA:KCNA1 - orthologs

Gene location (Human)

Chr.	Chromosome 12 (human)^[1]

Band	12p13.32	Start	4,909,905 bp^[1]
Band	12p13.32	End	4,918,256 bp^[1]

Gene location (Mouse)

Chr.	Chromosome 6 (mouse)^[2]

Band	6 F3\|6 61.57 cM	Start	126,617,360 bp^[2]
Band	6 F3\|6 61.57 cM	End	126,623,347 bp^[2]

RNA expression pattern

Bgee

Human

Mouse (ortholog)

Top expressed in

endothelial cell

Brodmann area 23

middle temporal gyrus

cerebellar hemisphere

postcentral gyrus

putamen

caudate nucleus

pons

spinal ganglia

external globus pallidus

Top expressed in

sciatic nerve

pontine nuclei

lateral geniculate nucleus

medulla oblongata

medial vestibular nucleus

cerebellar vermis

olfactory tubercle

inferior colliculus

anterior horn of spinal cord

globus pallidus

More reference expression data

BioGPS

n/a

Gene ontology
Molecular function	potassium channel activity delayed rectifier potassium channel activity voltage-gated ion channel activity potassium ion transmembrane transporter activity ion channel activity protein binding voltage-gated potassium channel activity disordered domain specific binding voltage-gated ion channel activity involved in regulation of presynaptic membrane potential voltage-gated ion channel activity involved in regulation of postsynaptic membrane potential
Cellular component	axon terminus juxtaparanode region of axon integral component of membrane cytosol perikaryon cell projection membrane plasma membrane synapse integral component of plasma membrane cell surface cell junction neuronal cell body dendrite axon potassium channel complex apical plasma membrane endoplasmic reticulum paranode region of axon presynaptic membrane cytoplasmic vesicle voltage-gated potassium channel complex calyx of Held glutamatergic synapse integral component of postsynaptic membrane integral component of presynaptic membrane
Biological process	regulation of muscle contraction detection of mechanical stimulus involved in sensory perception of pain cellular response to magnesium ion startle response regulation of membrane potential cell communication by electrical coupling neuronal signal transduction regulation of ion transmembrane transport ion transport magnesium ion homeostasis potassium ion transport brain development neuromuscular process transmembrane transport potassium ion transmembrane transport neuroblast proliferation detection of mechanical stimulus involved in sensory perception of touch protein homooligomerization hippocampus development neuronal action potential chemical synaptic transmission positive regulation of voltage-gated potassium channel activity regulation of postsynaptic membrane potential regulation of presynaptic membrane potential
Sources:Amigo / QuickGO

Orthologs

Species

Human

Mouse

Entrez


3736


16485

Ensembl


ENSG00000111262


ENSMUSG00000047976

UniProt


Q09470


P16388

RefSeq (mRNA)


NM_000217


NM_010595

RefSeq (protein)


NP_000208


NP_034725

Location (UCSC)

Chr 12: 4.91 – 4.92 Mb

Chr 6: 126.62 – 126.62 Mb

PubMed search

^[3]

^[4]

Wikidata

View/Edit Human

View/Edit Mouse

Potassium voltage-gated channel subfamily A member 1 also known as K_v1.1 is a shaker related voltage-gated potassium channel that in humans is encoded by the KCNA1 gene.^[5]^[6]^[7] Isaacs syndrome is a result of an autoimmune reaction against the K_v1.1 ion channel.^[8]

Genomics

The gene is located on the Watson (plus) strand of the short arm of chromosome 12 (12p13.32). The gene itself is 8,348 bases in length and encodes a protein of 495 amino acids (predicted molecular weight 56.466 kilodaltons).

Alternative names

The recommended name for this protein is potassium voltage-gated channel subfamily A member 1 but a number of alternatives have been used in the literature including HuK1 (human K⁺ channel I), RBK1 (rubidium potassium channel 1), MBK (mouse brain K⁺ channel), voltage gated potassium channel HBK1, voltage gated potassium channel subunit K_v1.1, voltage-gated K⁺ channel HuKI and AEMK (associated with myokymia with periodic ataxia).

Structure

The protein is believed to have six domains (S1-S6) with the loop between S5 and S6 forming the channel pore. This region also has a conserved selectivity filter motif. The functional channel is a homotetramer. The N-terminus of the protein associates with β subunits. These subunits regulate channel inactivation as well as its expression. The C-terminus is associated with a PDZ domain protein involved in channel targeting.^[9]^[10]

Function

The protein functions as a potassium selective channel through which the potassium ion may pass in consensus with the electrochemical gradient. They play a role in repolarisation of membranes.^[9]

RNA editing

The pre-mRNA of this protein is subject to RNA editing.^[11]

Type

A to I RNA editing is catalyzed by a family of adenosine deaminases acting on RNA (ADARs) that specifically recognize adenosines within double-stranded regions of pre-mRNAs (e.g. Potassium channel RNA editing signal) and deaminate them to inosine. Inosines are recognised as guanosine by the cells translational machinery. There are three members of the ADAR family ADARs 1-3 with ADAR1 and ADAR2 being the only enzymatically active members. ADAR3 is thought to have a regulatory role in the brain. ADAR1 and ADAR2 are widely expressed in tissues while ADAR3 is restricted to the brain. The double stranded regions of RNA are formed by base-pairing between residues in the region close to the editing site with residues usually in a neighboring intron but can sometimes be an exonic sequence too. The region that base pairs with the editing region is known as an Editing Complementary Sequence (ECS).

Location

The modified residue is found at amino acid 400 of the final protein. This is located in the sixth transmembrane region found, which corresponds to the inner vestibule of the pore. A stem loop hairpin structure mediates the RNA editing. ADAR2 is likely to be the preferred editing enzyme at the I/V site. Editing results in a codon alteration from ATT to GTT, resulting in an amino acid change from isoleucine to valine. ADAR2 enzyme is the major editing enzyme. The MFOLD programme predicted that the minimum region required for editing would form an imperfect inverted repeat hairpin. This region is composed of a 114 base pairs. Similar regions have been identified in mouse and rat. The edited adenosine is found in a 6-base pair duplex region. Mutation experiment in the region near the 6-base pair duplex have shown that the specific bases in this region were also essential for editing to occur. The region required for editing is unusual in that the hairpin structure is formed by exonic sequences only. In the majority of A to I editing the ECS is found within an intronic sequence.^[11]

Conservation

The editing is highly conserved having been observed in squid, fruit fly, mouse, and rat.^[11]

Regulation

Editing levels vary in different tissues: 17% in the caudate nucleus, 68% in the spinal cord, and 77% in the medulla.^[12]

Consequences

Structure

Editing results in a codon (I/V) change from (ATT) to (GTT) resulting in translation of a valine instead of an isoleucine at the position of the editing site. Valine has a larger side-chain. RNA editing at this position occurs at a highly conserved ion conducting pore of the channel. This may affect the channels role in the process of fast inactivation.^[13]

Function

Voltage-dependent potassium channels modulate excitability by opening and closing a potassium selective pore in response to voltage. The flow of potassium ions is interrupted by interaction of an inactivating particle, an auxiliary protein in humans but an intrinsic part of the channel in other species. The I to V amino acid change is thought to disrupt the hydrophobic interaction between the inactivating particle and the pore lining. This interrupts the process of fast inactivation. Activation kinetics are unaffected by RNA editing.^[11] Changes in inactivation kinetics affect the duration and frequency of the action potential. An edited channel passes more current and has a shorter action potential than the non-edited type due to the inability of the inactivating particle to interact with the residue in the ion-conducting pore of the channel. This was determined by electrophysiology analysis.^[14] The length of time the membrane is depolarised is decreased, which also reduces the efficiency of transmitter release.^[12] Since editing can cause amino acid changes in 1- 4 in potassium channel tetramers, it can have a wide variety of effects on channel inactivation.

Dysregulation

Changes in the process of fast inactivation are known to have behavioral and neurological consequences in vivo.^[11]

Clinical

Mutations in this gene cause episodic ataxia type 1.

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000111262 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000047976 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Curran ME, Landes GM, Keating MT (1992). "Molecular cloning, characterization, and genomic localization of a human potassium channel gene". Genomics. 12 (4): 729–37. doi:10.1016/0888-7543(92)90302-9. PMID 1349297.
^ Albrecht B, Weber K, Pongs O (1995). "Characterization of a voltage-activated K-channel gene cluster on human chromosome 12p13". Recept. Channels. 3 (3): 213–20. PMID 8821794.
^ Gutman GA, Chandy KG, Grissmer S, Lazdunski M, McKinnon D, Pardo LA, Robertson GA, Rudy B, Sanguinetti MC, Stühmer W, Wang X (2005). "International Union of Pharmacology. LIII. Nomenclature and molecular relationships of voltage-gated potassium channels". Pharmacol. Rev. 57 (4): 473–508. doi:10.1124/pr.57.4.10. PMID 16382104. S2CID 219195192.
^ Newsom-Davis J (1997). "Autoimmune neuromyotonia (Isaacs' syndrome): an antibody-mediated potassium channelopathy". Ann. N. Y. Acad. Sci. 835 (1): 111–9. Bibcode:1997NYASA.835..111N. doi:10.1111/j.1749-6632.1997.tb48622.x. PMID 9616766. S2CID 13231594.^{[permanent dead link]}
^ ^a ^b "Entrez Gene: KCNA1 potassium voltage-gated channel".
^ "KCNA1 - Potassium voltage-gated channel subfamily A member 1 - Homo sapiens (Human) - KCNA1 gene & protein". www.uniprot.org.
^ ^a ^b ^c ^d ^e Bhalla T, Rosenthal JJ, Holmgren M, Reenan R (October 2004). "Control of human potassium channel inactivation by editing of a small mRNA hairpin". Nat. Struct. Mol. Biol. 11 (10): 950–6. doi:10.1038/nsmb825. PMID 15361858. S2CID 34081059.
^ ^a ^b Hoopengardner B, Bhalla T, Staber C, Reenan R (August 2003). "Nervous system targets of RNA editing identified by comparative genomics". Science. 301 (5634): 832–6. Bibcode:2003Sci...301..832H. doi:10.1126/science.1086763. PMID 12907802. S2CID 782642.
^ Bhalla, Tarun; Rosenthal, Joshua J C; Holmgren, Miguel; Reenan, Robert (2004). "Control of human potassium channel inactivation by editing of a small mRNA hairpin". Nature Structural & Molecular Biology. 11 (10): 950–956. doi:10.1038/nsmb825. ISSN 1545-9993. PMID 15361858. S2CID 34081059.
^ Bezanilla, Francisco (2004). "RNA editing of a human potassium channel modifies its inactivation". Nature Structural & Molecular Biology. 11 (10): 915–916. doi:10.1038/nsmb1004-915. ISSN 1545-9993. PMID 15452561. S2CID 40545616.

External links

GeneReviews/NCBI/NIH/UW entry on Episodic Ataxia Type 1, Episodic Ataxia with Myokymia, Hereditary Cerebellar Ataxia with Neuromyotonia
Kv1.1+Potassium+Channel at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
KCNA1+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

PDB gallery

1qdw: N-TERMINAL DOMAIN, VOLTAGE-GATED POTASSIUM CHANNEL KV1.2 RESIDUES 33-119
1qdv: N-TERMINAL DOMAIN, VOLTAGE-GATED POTASSIUM CHANNEL KV1.2 RESIDUES 33-131
1exb: STRUCTURE OF THE CYTOPLASMIC BETA SUBUNIT-T1 ASSEMBLY OF VOLTAGE-DEPENDENT K CHANNELS
1dsx: KV1.2 T1 DOMAIN, RESIDUES 33-119, T46V MUTANT

Membrane transport protein: ion channels (TC 1A)

Ca²⁺: Calcium channel

Ligand-gated	Inositol trisphosphate receptor 1 2 3 Ryanodine receptor 1 2 3
Voltage-gated	L-type/Ca_vα 1.1 1.2 1.3 1.4 N-type/Ca_vα2.2 P-type/Ca_vα 2.1 Q-type/Ca_vα2.1 R-type/Ca_vα2.3 T-type/Ca_vα 3.1 3.2 3.3 α₂δ-subunits 1 2 β-subunits β1 β2 β3 β4 γ-subunits γ1 γ2 γ3 γ4 Cation channels of sperm 1 2 3 4 Two-pore channel 1 2

Na⁺: Sodium channel

Constitutively active	Epithelial sodium channel α β γ δ
Proton-gated	Amiloride-sensitive cation channel 1 2 3 4
Voltage-gated	Na_vα 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9 7A Na_vβ 1 2 3 4

K⁺: Potassium channel

Calcium-activated	BK channel α1 β1 β2 β3 β4 SK channel SK1 SK2 SK3 IK channel IK1 K_Ca 1.1 2.1 2.2 2.3 3.1 4.1 4.2 5.1
Inward-rectifier	K_ATP K_ir 1.1 2.1 2.2 2.3 2.4 2.6 GIRK/K_ir 3.1 3.2 3.3 3.4 K_ir 4.1 4.2 5.1 6.1 6.2 7.1
Tandem pore domain	K2P 1 2 3 4 5 6 7 9 10 12 13 15 16 17 18
Voltage-gated	K_vα1-6 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 2.1 2.2 3.1 3.2 3.3 3.4 4.1 4.2 4.3 5.1 6.1 6.2 6.3 6.4 K_vα7-12 7.1 7.2 7.3 7.4 7.5 8.1 8.2 9.1 9.2 9.3 10.1 10.2 11.1/hERG 11.2 11.3 12.1 12.2 12.3 K_vβ 1 2 3 KCNIP 1 2 3 4 minK/ISK minK/ISK-like MiRP 1 2 3 Shaker (gene)

Miscellaneous

Cl⁻: Chloride channel	Calcium-activated chloride channels Anoctamin ANO1 Bestrophin 1 2 Chloride Channel Accessory 1 2 3 4 CFTR CLCN 1 2 3 4 5 6 7 KA KB CLIC 1 2 3 4 5 6 L1 CLNS 1A 1B
H⁺: Proton channel	HVCN1
M⁺: CNG cation channel	α 1 2 3 4 β 1 2 3 HCN FC 1 2 3 4
M⁺: TRP cation channel	TRPA (1) TRPC 1 2 3 4 4AP 5 6 7 TRPM 1 2 3 4 5 6 7 8 TRPML 1 2 3 TRPN TRPP 1 2 TRPV 1 2 3 4 5 6
H₂O (+ solutes): Porin	Aquaporin 0 1 2 3 4 5 6 7 8 9 Voltage-dependent anion channel 1 2 3 General bacterial porin family
Cytoplasm: Gap junction	Connexin A GJA1 GJA3 GJA4 GJA5 GJA8 GJA9 GJA10 B GJB1 GJB2 GJB3 GJB4 GJB5 GJB6 GJB7 C GJC1 GJC2 GJC3 D GJD2 GJD3 GJD4 Innexin