KCNA3 potassium voltage-gated channel subfamily A member 3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: KCNA3provided by HGNC
Official Full Name: potassium voltage-gated channel subfamily A member 3provided by HGNC
Primary source: HGNC:HGNC:6221
See related: Ensembl:ENSG00000177272 MIM:176263
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: MK3; HGK5; HLK3; PCN3; HPCN3; KV1.3; HUKIII
Summary: Potassium channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. Four sequence-related potassium channel genes - shaker, shaw, shab, and shal - have been identified in Drosophila, and each has been shown to have human homolog(s). This gene encodes a member of the potassium channel, voltage-gated, shaker-related subfamily. This member contains six membrane-spanning domains with a shaker-type repeat in the fourth segment. It belongs to the delayed rectifier class, members of which allow nerve cells to efficiently repolarize following an action potential. It plays an essential role in T-cell proliferation and activation. This gene appears to be intronless and it is clustered together with KCNA2 and KCNA10 genes on chromosome 1. [provided by RefSeq, Jul 2008]
Expression: Broad expression in lymph node (RPKM 7.8), appendix (RPKM 6.0) and 17 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 1p13.3

Exon count:: 4

Annotation release	Status	Assembly	Chr	Location
109	current	GRCh38.p12 (GCF_000001405.38)	1	NC_000001.11 (110653560..110675033, complement)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (111196182..111217655, complement)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

T-cell dependency on Kv1.3 or KCa3.1 might be irreversibly modulated by antigen exposure.
Title: Potassium channels Kv1.3 and KCa3.1 cooperatively and compensatorily regulate antigen-specific memory T cell functions.
In this work, we showed that although both Kv1.1 and Kv1.3 channels are expressed in U87 (glioblastoma), MDA-MB-231 (breast cancer) and LS174 (colon adenocarcinoma) cells, these respond differently to KAaH1 or KAaH2, two homologous Kv1 blockers from scorpion venom
Title: Functional role of Kv1.1 and Kv1.3 channels in the neoplastic progression steps of three cancer cell lines, elucidated by scorpion peptides.
Kv1.3 methylation may serve as diagnostic and prognostic markers in colorectal cancer.
Title: Epigenetic regulation of voltage-gated potassium ion channel molecule Kv1.3 in mechanisms of colorectal cancer.
the tertiary structure of the C-terminal domain of Kv1.3 is necessary and sufficient for Kv1.3- KCNE4 interaction.
Title: The C-terminal domain of Kv1.3 regulates functional interactions with the KCNE4 subunit.
results identify a caveolin-binding domain in Kv1 channels and highlight the mechanisms that govern the regulation of channel surface localization during cellular processes
Title: Caveolin interaction governs Kv1.3 lipid raft targeting.
we report that Kv1.3-NPs reduced NFAT activation and CD40L expression exclusively in CD45RO(+) T cells. Furthermore, Kv1.3-NPs suppressed cytokine release and induced a phenotype switch of T cells from predominantly memory to naive.
Title: Nanovesicle-targeted Kv1.3 knockdown in memory T cells suppresses CD40L expression and memory phenotype.
The implication of Kv1.3 in a wide repertoire of human pathologies indicates this channel is an important therapeutic target.
Title: The voltage-gated potassium channel Kv1.3 is a promising multitherapeutic target against human pathologies.
Results contribute to the characterization of leukemic B cells, as it shows that upregulation of Kv1.3 in pathologic B lymphocytes is linked to the oncogenic B-RAF signaling.
Title: Biophysical characterization and expression analysis of Kv1.3 potassium channel in primary human leukemic B cells.
Data suggest that C-terminus is necessary for Kv1.3-induced cell proliferation; the mechanism involves accessibility of key docking sites at the C terminus; phosphorylation of Tyr-447 by MAP kinase signal cascade appears crucial.
Title: Molecular Determinants of Kv1.3 Potassium Channels-induced Proliferation.
concluded that Kv1.3 may stimulate macrophage migration through the activation of ERK.
Title: Kv1.3 potassium channel mediates macrophage migration in atherosclerosis by regulating ERK activity.

Submit: New GeneRIF Correction See all GeneRIFs (85)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

NHGRI GWAS Catalog

Description
Identification of germline susceptibility loci in ETV6-RUNX1-rearranged childhood acute lymphoblastic leukemia. NHGRI GWA Catalog NHGRI GWA CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 gp120-mediated enhancement of potassium voltage-gated channel KV1.3 protein is required for microglia neurotoxicity through the p38 MAPK signaling pathway	PubMed

Go to the HIV-1, Human Interaction Database

Pathways from BioSystems

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Brain-Derived Neurotrophic Factor (BDNF) signaling pathway, organism-specific biosystem (from WikiPathways)
Brain-Derived Neurotrophic Factor (BDNF) signaling pathway, organism-specific biosystemBrain-derived neurotrophic factor (BDNF) is a neurotrophin essential for growth, differentiation, plasticity, and survival of neurons. BDNF is also required for processes such as energy metabolism, b...
Neuronal System, organism-specific biosystem (from REACTOME)
Neuronal System, organism-specific biosystemThe human brain contains at least 100 billion neurons, each with the ability to influence many other cells. Clearly, highly sophisticated and efficient mechanisms are needed to enable communication a...
Potassium Channels, organism-specific biosystem (from REACTOME)
Potassium Channels, organism-specific biosystemPotassium channels are tetrameric ion channels that are widely distributed and are found in all cell types. Potassium channels control resting membrane potential in neurons, contribute to regulation ...
Voltage gated Potassium channels, organism-specific biosystem (from REACTOME)
Voltage gated Potassium channels, organism-specific biosystemVoltage-gated K+ channels (Kv) determine the excitability of heart, brain and skeletal muscle cells. Kv form octameric channel with alpha subunits that forms the pore of the channel and associated be...

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D1S3253 (e-PCR)
- UniSTS:60186

SHGC-75313 (e-PCR)
- UniSTS:8991

D1S3456 (e-PCR)
- UniSTS:154711

Homology

Homologs of the KCNA3 gene: The KCNA3 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, fruit fly, mosquito, C.elegans, and frog.
Orthologs from Annotation Pipeline: 130 organisms have orthologs with human gene KCNA3
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
delayed rectifier potassium channel activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
outward rectifier potassium channel activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
voltage-gated ion channel activity	TAS Traceable Author Statement more info	PubMed
voltage-gated potassium channel activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed

Process	Evidence Code	Pubs
potassium ion export across plasma membrane	IBA Inferred from Biological aspect of Ancestor more info	PubMed
potassium ion transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info	PubMed
potassium ion transport	TAS Traceable Author Statement more info	PubMed
protein homooligomerization	IEA Inferred from Electronic Annotation more info
regulation of ion transmembrane transport	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
axon	IBA Inferred from Biological aspect of Ancestor more info	PubMed
calyx of Held	IEA Inferred from Electronic Annotation more info
glutamatergic synapse	IEA Inferred from Electronic Annotation more info
integral component of membrane	IBA Inferred from Biological aspect of Ancestor more info	PubMed
integral component of postsynaptic membrane	IEA Inferred from Electronic Annotation more info
integral component of presynaptic membrane	IEA Inferred from Electronic Annotation more info
membrane raft	IEA Inferred from Electronic Annotation more info
plasma membrane	TAS Traceable Author Statement more info
voltage-gated potassium channel complex	IBA Inferred from Biological aspect of Ancestor more info	PubMed

General protein information

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Preferred Names: potassium voltage-gated channel subfamily A member 3

Names: potassium channel 3; potassium channel, voltage gated shaker related subfamily A, member 3; potassium voltage-gated channel, shaker-related subfamily, member 3; type n potassium channel; voltage-gated K(+) channel HuKIII; voltage-gated potassium channel protein Kv1.3; voltage-gated potassium channel subunit Kv1.3

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_002232.5 → NP_002223.3 potassium voltage-gated channel subfamily A member 3

See identical proteins and their annotated locations for NP_002223.3

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the functional protein.

Source sequence(s)

AL365361, BC035059, CA438434

Consensus CDS

CCDS828.2

UniProtKB/Swiss-Prot

P22001

Related

ENSP00000358784.2, ENST00000369769.3

Conserved Domains (4) summary

smart00225
Location:106 → 200

BTB; Broad-Complex, Tramtrack and Bric a brac

pfam00520
Location:290 → 490

Ion_trans; Ion transport protein

pfam02214
Location:106 → 197

BTB_2; BTB/POZ domain

pfam07885
Location:404 → 481

Ion_trans_2; Ion channel

RNA

NR_109845.1 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate exon structure compared to variant 1. This variant is represented as non-coding because it lacks a large portion of the coding region, including the translational start codon, found in variant 1.

Source sequence(s)

AL365361, BM995500, HY035404
NR_109846.1 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (3) uses an alternate exon structure compared to variant 1. This variant is represented as non-coding because it lacks a large portion of the coding region, including the translational start codon, found in variant 1.

Source sequence(s)

AL365361, BM995500, DB086905