KCND3

KCND3
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1S1G, 2NZ0
Identifiers
Aliases	KCND3, KCND3L, KCND3S, KSHIVB, KV4.3, SCA19, SCA22, BRGDA9, potassium voltage-gated channel subfamily D member 3
External IDs	OMIM: 605411; MGI: 1928743; HomoloGene: 21036; GeneCards: KCND3; OMA:KCND3 - orthologs
Gene location (Human) Chr. Chromosome 1 (human) Band 1p13.2 Start 111,770,662 bp End 111,989,668 bp
Gene location (Mouse) Chr. Chromosome 3 (mouse) Band 3|3 F2.2 Start 105,359,646 bp End 105,581,318 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in cerebellar vermis pars reticulata lateral nuclear group of thalamus pars compacta paraflocculus of cerebellum Brodmann area 23 middle temporal gyrus tail of epididymis parietal lobe caput epididymis Top expressed in substantia nigra ventral tegmental area lateral geniculate nucleus medial geniculate nucleus habenula vas deferens anterior amygdaloid area subiculum pineal gland supraoptic nucleus More reference expression data BioGPS More reference expression data
Gene ontology Molecular function potassium channel activity transmembrane transporter binding metal ion binding voltage-gated ion channel activity ion channel activity protein binding voltage-gated potassium channel activity A-type (transient outward) potassium channel activity voltage-gated potassium channel activity involved in cardiac muscle cell action potential repolarization voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization Cellular component integral component of membrane cell projection membrane voltage-gated potassium channel complex plasma membrane dendrite sarcolemma GABA-ergic synapse integral component of postsynaptic specialization membrane soma Biological process regulation of ion transmembrane transport ion transport potassium ion transport membrane repolarization transmembrane transport potassium ion transmembrane transport protein homooligomerization membrane repolarization during cardiac muscle cell action potential regulation of heart rate by cardiac conduction potassium ion export across plasma membrane membrane repolarization during ventricular cardiac muscle cell action potential ventricular cardiac muscle cell membrane repolarization cardiac conduction Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 3752 56543 Ensembl ENSG00000171385 ENSMUSG00000040896 UniProt Q9UK17 Q9Z0V1 RefSeq (mRNA) NM_004980 NM_172198 NM_001378969 NM_001378970 NM_001039347 NM_019931 RefSeq (protein) NP_004971 NP_751948 NP_001365898 NP_001365899 NP_001034436 NP_064315 Location (UCSC) Chr 1: 111.77 – 111.99 Mb Chr 3: 105.36 – 105.58 Mb PubMed search
Wikidata
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Potassium voltage-gated channel subfamily D member 3 also known as K_v4.3 is a protein that in humans is encoded by the KCND3 gene. It contributes to the cardiac transient outward potassium current (I_to1), the main contributing current to the repolarizing phase 1 of the cardiac action potential.

Function

Voltage-gated potassium (K_v) 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).

K_v4.3 is a member of the potassium channel, voltage-gated, shal-related subfamily, members of which form voltage-activated A-type potassium ion channels and are prominent in the repolarization phase of the action potential. This member includes two isoforms with different sizes, which are encoded by alternatively spliced transcript variants of this gene.

Clinical significance

Gain of function is believed to cause Brugada syndrome although only indirectly shown by mutations in the beta subunit KCNE3 which causes gain of function of K_v4.3.

See also

• Voltage-gated potassium channel

Further reading

• Serôdio P, Vega-Saenz de Miera E, Rudy B (1997). "Cloning of a novel component of A-type K+ channels operating at subthreshold potentials with unique expression in heart and brain". J. Neurophysiol. 75 (5): 2174–9. doi:10.1152/jn.1996.75.5.2174. PMID 8734615.
• Kong W, Po S, Yamagishi T, et al. (1999). "Isolation and characterization of the human gene encoding Ito: further diversity by alternative mRNA splicing". Am. J. Physiol. 275 (6 Pt 2): H1963–70. doi:10.1152/ajpheart.1998.275.6.H1963. PMID 9843794.
• Dilks D, Ling HP, Cockett M, et al. (1999). "Cloning and expression of the human kv4.3 potassium channel". J. Neurophysiol. 81 (4): 1974–7. doi:10.1152/jn.1999.81.4.1974. PMID 10200233. S2CID 15819057.
• Isbrandt D, Leicher T, Waldschütz R, et al. (2000). "Gene structures and expression profiles of three human KCND (Kv4) potassium channels mediating A-type currents I(TO) and I(SA)". Genomics. 64 (2): 144–54. doi:10.1006/geno.2000.6117. PMID 10729221.
• Deschênes I, Tomaselli GF (2002). "Modulation of Kv4.3 current by accessory subunits". FEBS Lett. 528 (1–3): 183–8. doi:10.1016/S0014-5793(02)03296-9. PMID 12297301.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Ren X, Shand SH, Takimoto K (2003). "Effective association of Kv channel-interacting proteins with Kv4 channel is mediated with their unique core peptide". J. Biol. Chem. 278 (44): 43564–70. doi:10.1074/jbc.M302337200. PMID 12928444.
• Hatano N, Ohya S, Muraki K, et al. (2004). "Two arginines in the cytoplasmic C-terminal domain are essential for voltage-dependent regulation of A-type K+ current in the Kv4 channel subfamily". J. Biol. Chem. 279 (7): 5450–9. doi:10.1074/jbc.M302034200. PMID 14645239.
• Scannevin RH, Wang K, Jow F, et al. (2004). "Two N-terminal domains of Kv4 K(+) channels regulate binding to and modulation by KChIP1". Neuron. 41 (4): 587–98. doi:10.1016/S0896-6273(04)00049-2. PMID 14980207. S2CID 17380435.
• Zicha S, Xiao L, Stafford S, et al. (2005). "Transmural expression of transient outward potassium current subunits in normal and failing canine and human hearts". J. Physiol. 561 (Pt 3): 735–48. doi:10.1113/jphysiol.2004.075861. PMC 1665387. PMID 15498806.
• Frank-Hansen R, Larsen LA, Andersen P, et al. (2005). "Mutations in the genes KCND2 and KCND3 encoding the ion channels Kv4.2 and Kv4.3, conducting the cardiac fast transient outward current (ITO,f), are not a frequent cause of long QT syndrome". Clin. Chim. Acta. 351 (1–2): 95–100. doi:10.1016/j.cccn.2004.08.017. PMID 15563876.
• Baltaev R, Strutz-Seebohm N, Korniychuk G, et al. (2005). "Regulation of cardiac shal-related potassium channel Kv 4.3 by serum- and glucocorticoid-inducible kinase isoforms in Xenopus oocytes". Pflügers Arch. 450 (1): 26–33. doi:10.1007/s00424-004-1369-z. PMID 15578212. S2CID 190895.
• Radicke S, Cotella D, Graf EM, et al. (2005). "Expression and function of dipeptidyl-aminopeptidase-like protein 6 as a putative β-subunit of human cardiac transient outward current encoded by Kv4.3". J. Physiol. 565 (Pt 3): 751–6. doi:10.1113/jphysiol.2005.087312. PMC 1464568. PMID 15890703.
• Gregory SG, Barlow KF, McLay KE, et al. (2006). "The DNA sequence and biological annotation of human chromosome 1". Nature. 441 (7091): 315–21. Bibcode:2006Natur.441..315G. doi:10.1038/nature04727. PMID 16710414.
• Lundby A, Olesen SP (2006). "KCNE3 is an inhibitory subunit of the Kv4.3 potassium channel". Biochem. Biophys. Res. Commun. 346 (3): 958–67. doi:10.1016/j.bbrc.2006.06.004. PMID 16782062.
• Ahmed I, Cosen-Binker LI, Leung YM, et al. (2007). "Modulation of the K(v)4.3 channel by syntaxin 1A". Biochem. Biophys. Res. Commun. 358 (3): 789–95. doi:10.1016/j.bbrc.2007.04.182. PMID 17506992.
• Potapova IA, Cohen IS, Doronin SV (2007). "Voltage-gated ion channel Kv4.3 is associated with Rap guanine nucleotide exchange factors and regulates angiotensin receptor type 1 signaling to small G-protein Rap". FEBS J. 274 (17): 4375–84. doi:10.1111/j.1742-4658.2007.05966.x. PMID 17725712.

External links

• GeneReviews/NIH/NCBI/UW entry on Brugada syndrome
• Kv4.3+Potassium+Channel at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• Overview of all the structural information available in the PDB for UniProt: Q9UK17 (Potassium voltage-gated channel subfamily D member 3) at the PDBe-KB.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.