Potassium voltage-gated channel subfamily A member 4 also known as Kv1.4 is a protein that in humans is encoded by the KCNA4 gene.[5][6][7] It contributes to the cardiac transient outward potassium current (Ito1), the main contributing current to the repolarizing phase 1 of the cardiac action potential.[8]

AliasesKCNA4, HBK4, HK1, HPCN2, HUKII, KCNA4L, KCNA8, KV1.4, PCN2, potassium voltage-gated channel subfamily A member 4, MCIDDS
External IDsOMIM: 176266 MGI: 96661 HomoloGene: 20514 GeneCards: KCNA4
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC)Chr 11: 30.01 – 30.02 MbChr 2: 107.12 – 107.13 Mb
PubMed search[3][4]
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Potassium channel Kv1.4 tandem inactivation domain
solution structure of the tandem inactivation domain (residues 1-75) of potassium channel rck4 (kv1.4)
Available protein structures:
Pfam  structures / ECOD  
PDBsumstructure summary

Description edit

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 A-type potassium current class, the members of which may be important in the regulation of the fast repolarizing phase of action potentials in heart and thus may influence the duration of cardiac action potential. The coding region of this gene is intronless, and the gene is clustered with genes KCNA3 and KCNA10 on chromosome 1 in humans.[7]

KCNA4 (Kv1.4) contains a tandem inactivation domain at the N terminus. It is composed of two subdomains. Inactivation domain 1 (ID1, residues 1-38) consists of a flexible N terminus anchored at a 5-turn helix, and is thought to work by occluding the ion pathway, as is the case with a classical ball domain. Inactivation domain 2 (ID2, residues 40-50) is a 2.5 turn helix with a high proportion of hydrophobic residues that probably serves to attach ID1 to the cytoplasmic face of the channel. In this way, it can promote rapid access of ID1 to the receptor site in the open channel. ID1 and ID2 function together to bring about fast inactivation of the Kv1.4 channel, which is important for the role of the channel in short-term plasticity.[9]

Interactions edit

KCNA4 has been shown to interact with DLG4,[10][11][12][13] KCNA2[14] and DLG1.[10][12][15]

See also edit

References edit

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000182255 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000042604 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Philipson LH, Schaefer K, LaMendola J, Bell GI, Steiner DF (December 1990). "Sequence of a human fetal skeletal muscle potassium channel cDNA related to RCK4". Nucleic Acids Research. 18 (23): 7160. doi:10.1093/nar/18.23.7160. PMC 332806. PMID 2263489.
  6. ^ Gutman GA, Chandy KG, Grissmer S, Lazdunski M, McKinnon D, Pardo LA, et al. (December 2005). "International Union of Pharmacology. LIII. Nomenclature and molecular relationships of voltage-gated potassium channels". Pharmacological Reviews. 57 (4): 473–508. doi:10.1124/pr.57.4.10. PMID 16382104. S2CID 219195192.
  7. ^ a b "Entrez Gene: KCNA4 potassium voltage-gated channel, shaker-related subfamily, member 4".
  8. ^ Oudit GY, Kassiri Z, Sah R, Ramirez RJ, Zobel C, Backx PH (May 2001). "The molecular physiology of the cardiac transient outward potassium current (I(to)) in normal and diseased myocardium". Journal of Molecular and Cellular Cardiology. 33 (5): 851–72. doi:10.1006/jmcc.2001.1376. PMID 11343410. S2CID 829154.
  9. ^ Wissmann R, Bildl W, Oliver D, Beyermann M, Kalbitzer HR, Bentrop D, Fakler B (May 2003). "Solution structure and function of the "tandem inactivation domain" of the neuronal A-type potassium channel Kv1.4". The Journal of Biological Chemistry. 278 (18): 16142–50. doi:10.1074/jbc.M210191200. PMID 12590144.
  10. ^ a b Inanobe A, Fujita A, Ito M, Tomoike H, Inageda K, Kurachi Y (June 2002). "Inward rectifier K+ channel Kir2.3 is localized at the postsynaptic membrane of excitatory synapses". American Journal of Physiology. Cell Physiology. 282 (6): C1396-403. doi:10.1152/ajpcell.00615.2001. PMID 11997254.
  11. ^ Niethammer M, Valtschanoff JG, Kapoor TM, Allison DW, Weinberg RJ, Craig AM, Sheng M (April 1998). "CRIPT, a novel postsynaptic protein that binds to the third PDZ domain of PSD-95/SAP90". Neuron. 20 (4): 693–707. doi:10.1016/S0896-6273(00)81009-0. PMID 9581762. S2CID 16068361.
  12. ^ a b Kim E, Sheng M (1996). "Differential K+ channel clustering activity of PSD-95 and SAP97, two related membrane-associated putative guanylate kinases". Neuropharmacology. 35 (7): 993–1000. doi:10.1016/0028-3908(96)00093-7. PMID 8938729. S2CID 23755452.
  13. ^ Eldstrom J, Doerksen KW, Steele DF, Fedida D (November 2002). "N-terminal PDZ-binding domain in Kv1 potassium channels". FEBS Letters. 531 (3): 529–37. doi:10.1016/S0014-5793(02)03572-X. PMID 12435606. S2CID 40689829.
  14. ^ Coleman SK, Newcombe J, Pryke J, Dolly JO (August 1999). "Subunit composition of Kv1 channels in human CNS". Journal of Neurochemistry. 73 (2): 849–58. doi:10.1046/j.1471-4159.1999.0730849.x. PMID 10428084. S2CID 20632070.
  15. ^ Eldstrom J, Choi WS, Steele DF, Fedida D (July 2003). "SAP97 increases Kv1.5 currents through an indirect N-terminal mechanism". FEBS Letters. 547 (1–3): 205–11. doi:10.1016/S0014-5793(03)00668-9. PMID 12860415. S2CID 34857270.

Further reading edit

External links edit

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

This article incorporates text from the public domain Pfam and InterPro: IPR012897