KCNA4

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Potassium voltage-gated channel, shaker-related subfamily, member 4
Protein KCNA4 PDB 1kn7.png
PDB rendering based on 1kn7.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols KCNA4 ; HBK4; HK1; HPCN2; HUKII; KCNA4L; KCNA8; KV1.4; PCN2
External IDs OMIM176266 MGI96661 HomoloGene20514 IUPHAR: Kv1.4 ChEMBL: 4205 GeneCards: KCNA4 Gene
RNA expression pattern
PBB GE KCNA4 207248 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 3739 16492
Ensembl ENSG00000182255 ENSMUSG00000042604
UniProt P22459 Q61423
RefSeq (mRNA) NM_002233 NM_021275
RefSeq (protein) NP_002224 NP_067250
Location (UCSC) Chr 11:
30.03 – 30.04 Mb
Chr 2:
107.29 – 107.3 Mb
PubMed search [1] [2]
Potassium channel Kv1.4 tandem inactivation domain
PDB 1kn7 EBI.jpg
solution structure of the tandem inactivation domain (residues 1-75) of potassium channel rck4 (kv1.4)
Identifiers
Symbol K_channel_TID
Pfam PF07941
InterPro IPR012897
SCOP 1kn7
SUPERFAMILY 1kn7

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.[1][2][3] It contributes to the cardiac transient outward potassium current (Ito1), the main contributing current to the repolarizing phase 1 of the cardiac action potential.[4]

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.[3]

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.[5]

Interactions[edit]

KCNA4 has been shown to interact with DLG4,[6][7][8][9] KCNA2[10] and DLG1.[6][8][11]

See also[edit]

References[edit]

  1. ^ Philipson LH, Schaefer K, LaMendola J, Bell GI, Steiner DF (Feb 1991). "Sequence of a human fetal skeletal muscle potassium channel cDNA related to RCK4". Nucleic Acids Res 18 (23): 7160. doi:10.1093/nar/18.23.7160. PMC 332806. PMID 2263489. 
  2. ^ Gutman GA, Chandy KG, Grissmer S, Lazdunski M, McKinnon D, Pardo LA, Robertson GA, Rudy B, Sanguinetti MC, Stuhmer W, Wang X (Dec 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. 
  3. ^ a b "Entrez Gene: KCNA4 potassium voltage-gated channel, shaker-related subfamily, member 4". 
  4. ^ 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". J. Mol. Cell. Cardiol. 33 (5): 851–72. doi:10.1006/jmcc.2001.1376. PMID 11343410. 
  5. ^ 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". J. Biol. Chem. 278 (18): 16142–50. doi:10.1074/jbc.M210191200. PMID 12590144. 
  6. ^ a b Inanobe, Atsushi; Fujita Akikazu; Ito Minoru; Tomoike Hitonobu; Inageda Kiyoshi; Kurachi Yoshihisa (Jun 2002). "Inward rectifier K+ channel Kir2.3 is localized at the postsynaptic membrane of excitatory synapses". Am. J. Physiol., Cell Physiol. (United States) 282 (6): C1396–403. doi:10.1152/ajpcell.00615.2001. ISSN 0363-6143. PMID 11997254. 
  7. ^ Niethammer, M; Valtschanoff J G; Kapoor T M; Allison D W; Weinberg R J; Craig A M; Sheng M (Apr 1998). "CRIPT, a novel postsynaptic protein that binds to the third PDZ domain of PSD-95/SAP90". Neuron (UNITED STATES) 20 (4): 693–707. doi:10.1016/S0896-6273(00)81009-0. ISSN 0896-6273. PMID 9581762. 
  8. ^ 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 (ENGLAND) 35 (7): 993–1000. doi:10.1016/0028-3908(96)00093-7. ISSN 0028-3908. PMID 8938729. 
  9. ^ Eldstrom, Jodene; Doerksen Kyle W; Steele David F; Fedida David (Nov 2002). "N-terminal PDZ-binding domain in Kv1 potassium channels". FEBS Lett. (Netherlands) 531 (3): 529–37. doi:10.1016/S0014-5793(02)03572-X. ISSN 0014-5793. PMID 12435606. 
  10. ^ Coleman, S K; Newcombe J; Pryke J; Dolly J O (Aug 1999). "Subunit composition of Kv1 channels in human CNS". J. Neurochem. (UNITED STATES) 73 (2): 849–58. doi:10.1046/j.1471-4159.1999.0730849.x. ISSN 0022-3042. PMID 10428084. 
  11. ^ Eldstrom, Jodene; Choi Woo Sung; Steele David F; Fedida David (Jul 2003). "SAP97 increases Kv1.5 currents through an indirect N-terminal mechanism". FEBS Lett. (Netherlands) 547 (1–3): 205–11. doi:10.1016/S0014-5793(03)00668-9. ISSN 0014-5793. PMID 12860415. 

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