Biology:ATP1A3

Short description: Protein-coding gene in the species Homo sapiens

Generic protein structure example

Sodium/potassium-transporting ATPase subunit alpha-3 is an enzyme that in humans is encoded by the ATP1A3 gene.

Function

The protein encoded by this gene belongs to the family of P-type cation transport ATPases, and to the subfamily of Na⁺/K⁺-ATPases. Na⁺/K⁺-ATPase is an integral membrane protein responsible for establishing and maintaining the electrochemical gradients of Na and K ions across the plasma membrane. These gradients are essential for osmoregulation, for sodium-coupled transport of a variety of organic and inorganic molecules, and for electrical excitability of nerve and muscle. This enzyme is composed of two subunits, a large catalytic subunit (alpha) and a smaller glycoprotein subunit (beta). The catalytic subunit of Na⁺/K⁺-ATPase is encoded by multiple genes. This gene encodes an alpha 3 subunit. ATP1A3 is expressed early in human development, likely underlying pathophysiology related to several ATP1A3 related diseases.

Clinical significance

Disease causing variants of the ATP1A3 gene are known to cause a variety of movement disorders and epilepsies. The known associations include a variety of syndromes, in approximate order of presentation:

1. Malformation of Cortex Development, including polymicrogyria
2. Developmental and epileptic encephalopathy
3. Alternating hemiplegia of childhood (AHC)
4. Cerebellar ataxia, Areflexia, Pes cavus, Optic atrophy and Sensorineural hearing loss (CAPOS/CAOS syndrome)
5. Very early-onset schizophrenia
6. Rapid onset dystonia-parkinsonism (RDP, also known as DYT12)
7. Fever induced paroxysmal weakness and encephalopathy (FIPWE)
8. Recurrent episodes of cerebellar ataxia (RECA)

In mice, mutations in this gene are associated with epilepsy. By manipulating this gene in the offspring of such mice, epilepsy can be avoided.

Further reading

• "Molecular genetics of Na,K-ATPase". Prog. Nucleic Acid Res. Mol. Biol.. Progress in Nucleic Acid Research and Molecular Biology 38: 37–89. 1990. doi:10.1016/S0079-6603(08)60708-4. ISBN 978-0-12-540038-1. PMID 2158121. 
• "The family of human Na⁺,K⁺-ATPase genes. Structure of the gene for isozyme alphaII". Doklady Akademii Nauk SSSR 297 (6): 1488–94. 1988. PMID 2834163. 
• "Family of human Na⁺, K⁺-ATPase genes. Structure of the gene for the catalytic subunit (alpha III-form) and its relationship with structural features of the protein". FEBS Lett. 233 (1): 87–94. 1988. doi:10.1016/0014-5793(88)81361-9. PMID 2838329. 
• "Chromosomal localization of human Na⁺, K⁺-ATPase alpha- and beta-subunit genes". Genomics 2 (2): 128–38. 1988. doi:10.1016/0888-7543(88)90094-8. PMID 2842249. 
• "Family of Na⁺,K⁺-ATPase genes. Intra-individual tissue-specific restriction fragment length polymorphism". FEBS Lett. 221 (1): 129–33. 1987. doi:10.1016/0014-5793(87)80366-6. PMID 2887455. 
• "Localization of a human Na⁺,K⁺-ATPase alpha subunit gene to chromosome 19q12----q13.2 and linkage to the myotonic dystrophy locus". Genomics 3 (4): 380–4. 1989. doi:10.1016/0888-7543(88)90131-0. PMID 2907504. 
• "The family of human Na⁺,K⁺-ATPase genes. A partial nucleotide sequence related to the alpha-subunit". FEBS Lett. 213 (1): 73–80. 1987. doi:10.1016/0014-5793(87)81467-9. PMID 3030810. 
• "Multiple genes encode the human Na⁺,K⁺-ATPase catalytic subunit". Proc. Natl. Acad. Sci. U.S.A. 84 (12): 4039–43. 1987. doi:10.1073/pnas.84.12.4039. PMID 3035563. Bibcode: 1987PNAS...84.4039S. 
• "The family of human Na⁺,K⁺-ATPase genes. No less than five genes and/or pseudogenes related to the alpha-subunit". FEBS Lett. 217 (2): 275–8. 1987. doi:10.1016/0014-5793(87)80677-4. PMID 3036582. 
• "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1–2): 171–4. 1994. doi:10.1016/0378-1119(94)90802-8. PMID 8125298. 
• "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1–2): 149–56. 1997. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149. 
• "Rapid-onset dystonia-parkinsonism: linkage to chromosome 19q13". Ann. Neurol. 46 (2): 176–82. 1999. doi:10.1002/1531-8249(199908)46:2<176::AID-ANA6>3.0.CO;2-2. PMID 10443882. 
• "Changes in the isoforms of the sodium pump in the placenta and myometrium of women in labor". Am. J. Obstet. Gynecol. 188 (3): 759–64. 2003. doi:10.1067/mob.2003.166. PMID 12634653. 
• "Mutations in the Na⁺/⁺-ATPase alpha3 gene ATP1A3 are associated with rapid-onset dystonia parkinsonism". Neuron 43 (2): 169–75. 2004. doi:10.1016/j.neuron.2004.06.028. PMID 15260953. 
• "The expression of the human neuronal α3 Na⁺,K⁺-ATPase subunit gene is regulated by the activity of the Sp1 and NF-Y transcription factors". Biochem. J. 386 (Pt 1): 63–72. 2005. doi:10.1042/BJ20041294. PMID 15462673. 
• "A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration". Cell 125 (4): 801–14. 2006. doi:10.1016/j.cell.2006.03.032. PMID 16713569. 

External links

• GeneReview/NCBI/NIH/UW entry on Rapid-Onset Dystonia Parkinsonism
• Human ATP1A3 genome location and ATP1A3 gene details page in the UCSC Genome Browser.