KCNA4

Last updated
KCNA4
Protein KCNA4 PDB 1kn7.png
Identifiers
Aliases KCNA4 , HBK4, HK1, HPCN2, HUKII, KCNA4L, KCNA8, KV1.4, PCN2, potassium voltage-gated channel subfamily A member 4, MCIDDS
External IDs OMIM: 176266 MGI: 96661 HomoloGene: 20514 GeneCards: KCNA4
Orthologs
SpeciesHumanMouse
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: 30.01 – 30.02 Mb Chr 2: 107.12 – 107.13 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse
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
SymbolK_channel_TID
Pfam PF07941
InterPro IPR012897
SCOP2 1kn7 / SCOPe / SUPFAM
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary

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]

Contents

Description

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

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

See also

Related Research Articles

<span class="mw-page-title-main">Kv1.1</span>

Potassium voltage-gated channel subfamily A member 1 also known as Kv1.1 is a shaker related voltage-gated potassium channel that in humans is encoded by the KCNA1 gene. Isaacs syndrome is a result of an autoimmune reaction against the Kv1.1 ion channel.

<span class="mw-page-title-main">Voltage-gated potassium channel</span> Class of transport proteins

Voltage-gated potassium channels (VGKCs) are transmembrane channels specific for potassium and sensitive to voltage changes in the cell's membrane potential. During action potentials, they play a crucial role in returning the depolarized cell to a resting state.

K<sub>ir</sub>2.1 Protein-coding gene in the species Homo sapiens

The Kir2.1 inward-rectifier potassium channel is a lipid-gated ion channel encoded by the KCNJ2 gene.

<span class="mw-page-title-main">DLG4</span> Mammalian protein found in Homo sapiens

PSD-95 also known as SAP-90 is a protein that in humans is encoded by the DLG4 gene.

<span class="mw-page-title-main">DLG1</span> Protein-coding gene in the species Homo sapiens

Discs large homolog 1 (DLG1), also known as synapse-associated protein 97 or SAP97, is a scaffold protein that in humans is encoded by the SAP97 gene.

<span class="mw-page-title-main">CASK</span> Protein-coding gene in humans

Peripheral plasma membrane protein CASK is a protein that in humans is encoded by the CASK gene. This gene is also known by several other names: CMG 2, calcium/calmodulin-dependent serine protein kinase 3 and membrane-associated guanylate kinase 2. CASK gene mutations are the cause of XL-ID with or without nystagmus and MICPCH, an X-linked neurological disorder.

<span class="mw-page-title-main">DLG3</span> Protein-coding gene in humans

Disks large homolog 3 (DLG3) also known as neuroendocrine-DLG or synapse-associated protein 102 (SAP-102) is a protein that in humans is encoded by the DLG3 gene. DLG3 is a member of the membrane-associated guanylate kinase (MAGUK) superfamily of proteins.

<span class="mw-page-title-main">DLG2</span> Protein-coding gene in the species Homo sapiens

Disks large homolog 2 (DLG2) also known as channel-associated protein of synapse-110 (chapsyn-110) or postsynaptic density protein 93 (PSD-93) is a protein that in humans is encoded by the DLG2 gene.

<span class="mw-page-title-main">GRIN2B</span> Protein-coding gene in the species Homo sapiens

Glutamate [NMDA] receptor subunit epsilon-2, also known as N-methyl D-aspartate receptor subtype 2B, is a protein that in humans is encoded by the GRIN2B gene.

<span class="mw-page-title-main">GRIN2A</span> Protein-coding gene in the species Homo sapiens

Glutamate [NMDA] receptor subunit epsilon-1 is a protein that in humans is encoded by the GRIN2A gene. With 1464 amino acids, the canonical GluN2A subunit isoform is large. GluN2A-short isoforms specific to primates can be produced by alternative splicing and contain 1281 amino acids.

<span class="mw-page-title-main">KCNA5</span> Protein-coding gene in humans

Potassium voltage-gated channel, shaker-related subfamily, member 5, also known as KCNA5 or Kv1.5, is a protein that in humans is encoded by the KCNA5 gene.

<span class="mw-page-title-main">KCND2</span> Protein-coding gene in the species Homo sapiens

Potassium voltage-gated channel subfamily D member 2 is a protein that in humans is encoded by the KCND2 gene. It contributes to the cardiac transient outward potassium current (Ito1), the main contributing current to the repolarizing phase 1 of the cardiac action potential.

<span class="mw-page-title-main">KCNA2</span> Protein-coding gene in the species Homo sapiens

Potassium voltage-gated channel subfamily A member 2 also known as Kv1.2 is a protein that in humans is encoded by the KCNA2 gene.

<span class="mw-page-title-main">KCNJ4</span> Protein-coding gene in the species Homo sapiens

Potassium inwardly-rectifying channel, subfamily J, member 4, also known as KCNJ4 or Kir2.3, is a human gene.

<span class="mw-page-title-main">KCNAB1</span> Protein-coding gene in the species Homo sapiens

Voltage-gated potassium channel subunit beta-1 is a protein that in humans is encoded by the KCNAB1 gene.

<span class="mw-page-title-main">DLGAP1</span> Protein-coding gene in the species Homo sapiens

Disks large-associated protein 1 (DAP-1), also known as guanylate kinase-associated protein (GKAP), is a protein that in humans is encoded by the DLGAP1 gene. DAP-1 is known to be highly enriched in synaptosomal preparations of the brain, and present in the post-synaptic density.

<span class="mw-page-title-main">KCNAB2</span> Protein-coding gene in the species Homo sapiens

Voltage-gated potassium channel subunit beta-2 is a protein that in humans is encoded by the KCNAB2 gene.

<span class="mw-page-title-main">DLGAP2</span> Protein-coding gene in the species Homo sapiens

Disks large-associated protein 2 is a protein that in humans is encoded by the DLGAP2 gene.

<span class="mw-page-title-main">CRIPT</span> Protein-coding gene in the species Homo sapiens

Cysteine-rich PDZ-binding protein is a protein that in humans is encoded by the CRIPT gene.

The membrane-associated guanylate kinases (MAGUK) are a superfamily of proteins. The MAGUKs are defined by their inclusion of PDZ, SH3 and GUK domains, although many of them also contain regions homologous of CaMKII, WW and L27 domains. The GUK domain that they have is structurally very similar to that of the guanylate kinases, however it is known to be catalytically inactive as the P-Loop which binds ATP is absent. It is thought that the MAGUKs have subfunctionalized the GUK domain for their own purposes, primarily based on its ability to form protein–protein interactions with cytoskeleton proteins, microtubule/actin based machinery and molecules involved in signal transduction.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000182255 - Ensembl, May 2017
  2. 1 2 3 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. 1 2 "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. 1 2 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. 1 2 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

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
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