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ATP1A3
Identifiers
Aliases	ATP1A3, AHC2, DYT12, RDP, CAPOS, ATPase Na+/K+ transporting subunit alpha 3, ATP1A1, DEE99
External IDs	OMIM: 182350; MGI: 88107; HomoloGene: 113729; GeneCards: ATP1A3; OMA:ATP1A3 - orthologs
Gene location (Human) Chr. Chromosome 19 (human) Band 19q13.2 Start 41,966,582 bp End 41,997,497 bp
Gene location (Mouse) Chr. Chromosome 7 (mouse) Band 7 A3|7 13.73 cM Start 24,677,592 bp End 24,705,383 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in superior frontal gyrus primary visual cortex right hemisphere of cerebellum prefrontal cortex apex of heart dorsolateral prefrontal cortex right frontal lobe Brodmann area 9 Hypothalamus anterior cingulate cortex Top expressed in primary visual cortex dentate gyrus of hippocampal formation granule cell neural layer of retina superior frontal gyrus subiculum dorsomedial hypothalamic nucleus pontine nuclei cerebellar cortex dorsal tegmental nucleus habenula More reference expression data BioGPS More reference expression data
Gene ontology Molecular function steroid hormone binding nucleotide binding chaperone binding P-type sodium:potassium-exchanging transporter activity metal ion binding P-type sodium:potassium-exchanging transporter activity involved in regulation of cardiac muscle cell membrane potential heparan sulfate proteoglycan binding D1 dopamine receptor binding hydrolase activity ATP binding amyloid-beta binding P-type potassium transmembrane transporter activity ion antiporter activity involved in regulation of presynaptic membrane potential Cellular component cytoplasm integral component of membrane dendritic spine neck extracellular vesicle Golgi apparatus membrane myelin sheath plasma membrane synapse sodium:potassium-exchanging ATPase complex axon dendritic spine head endoplasmic reticulum sarcolemma nucleus neuronal cell body membrane soma Biological process visual learning cellular response to steroid hormone stimulus regulation of cardiac conduction cardiac muscle contraction sodium ion transport cellular sodium ion homeostasis adult locomotory behavior sodium ion export across plasma membrane cell communication by electrical coupling involved in cardiac conduction response to glycoside ion transport memory cellular potassium ion homeostasis potassium ion transport ion transmembrane transport ionotropic glutamate receptor signaling pathway transport regulation of cardiac muscle cell membrane potential establishment or maintenance of transmembrane electrochemical gradient cerebral cortex development cellular response to retinoic acid cellular response to thyroid hormone stimulus regulation of resting membrane potential regulation of presynaptic membrane potential cellular response to amyloid-beta neuron projection maintenance potassium ion import across plasma membrane Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 478 232975 Ensembl ENSG00000105409 ENSMUSG00000040907 UniProt P13637 Q6PIC6 RefSeq (mRNA) NM_001256213 NM_001256214 NM_152296 NM_001290469 NM_144921 NM_001374627 RefSeq (protein) NP_001243142 NP_001243143 NP_689509 NP_001277398 NP_001361556 Location (UCSC) Chr 19: 41.97 – 42 Mb Chr 7: 24.68 – 24.71 Mb PubMed search
Wikidata
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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 99 (DEE99);
3. Alternating hemiplegia of childhood 2 (AHC2);
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.

References

1. ^ GRCh38: Ensembl release 89: ENSG00000105409 – Ensembl, May 2017
2. ^ GRCm38: Ensembl release 89: ENSMUSG00000040907 – 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. Brashear A, Dobyns WB, de Carvalho Aguiar P, Borg M, Frijns CJ, Gollamudi S, Green A, Guimaraes J, Haake BC, Klein C, Linazasoro G, Münchau A, Raymond D, Riley D, Saunders-Pullman R, Tijssen MA, Webb D, Zaremba J, Bressman SB, Ozelius LJ (Mar 2007). "The phenotypic spectrum of rapid-onset dystonia-parkinsonism (RDP) and mutations in the ATP1A3 gene". Brain. 130 (Pt 3): 828–35. doi:10.1093/brain/awl340. PMID 17282997.
6. ^ "Entrez Gene: ATP1A3 ATPase, Na/K transporting, alpha 3 polypeptide".
7. ^ Smith RS, Florio M, Akula SK, Neil JE, Wang Y, Hill RS, et al. (2021-06-22). "Early role for a Na + ,K + -ATPase ( ATP1A3 ) in brain development". Proceedings of the National Academy of Sciences. 118 (25): e2023333118. Bibcode:2021PNAS..11823333S. doi:10.1073/pnas.2023333118. PMC 8237684. PMID 34161264.
8. Papandreou A, Danti FR, Spaull R, Leuzzi V, Mctague A, Kurian MA (February 2020). "The expanding spectrum of movement disorders in genetic epilepsies". Developmental Medicine and Child Neurology. 62 (2): 178–191. doi:10.1111/dmcn.14407. PMID 31784983. S2CID 208498567.
9. "UniProt". www.uniprot.org. Retrieved 2023-10-31.
10. "UniProt".
11. Smedemark-Margulies N, Brownstein CA, Vargas S, Tembulkar SK, Towne MC, Shi J, Gonzalez-Cuevas E, Liu KX, Bilguvar K, Kleiman RJ, Han MJ, Torres A, Berry GT, Yu TW, Beggs AH, Agrawal PB, Gonzalez-Heydrich J (September 2016). "A novel de novo mutation in ATP1A3 and childhood-onset schizophrenia". Cold Spring Harbor Molecular Case Studies. 2 (5): a001008. doi:10.1101/mcs.a001008. PMC 5002930. PMID 27626066.
12. Clapcote SJ, Duffy S, Xie G, Kirshenbaum G, Bechard AR, Rodacker Schack V, Petersen J, Sinai L, Saab BJ, Lerch JP, Minassian BA, Ackerley CA, Sled JG, Cortez MA, Henderson JT, Vilsen B, Roder JC (August 2009). "Mutation I810N in the alpha3 isoform of Na,K-ATPase causes impairments in the sodium pump and hyperexcitability in the CNS". Proc. Natl. Acad. Sci. U.S.A. 106 (33): 14085–90. Bibcode:2009PNAS..10614085C. doi:10.1073/pnas.0904817106. PMC 2729024. PMID 19666602.

Further reading

• Lingrel JB, Orlowski J, Shull MM, Price EM (1990). "Molecular genetics of Na,K-ATPase". Prog. Nucleic Acid Res. Mol. Biol. Progress in Nucleic Acid Research and Molecular Biology. 38: 37–89. doi:10.1016/S0079-6603(08)60708-4. ISBN 978-0-12-540038-1. PMID 2158121.
• Sverdlov ED, Monastyrskaia GS, Broude NE, Ushkarev IuA, Melkov AM (1988). "The family of human Na,K-ATPase genes. Structure of the gene for isozyme alphaII" [The family of human Na,-ATPase genes. Structure of the gene for isozyme alphaII]. Doklady Akademii Nauk SSSR. 297 (6): 1488–94. PMID 2834163.
• Monastyrskaya GS, Broude NE, Melkov AM, Malyshev IV, Allikmets RL, Kostina MB, Dulubova IE (1988). "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. Bibcode:1988FEBSL.233...87O. doi:10.1016/0014-5793(88)81361-9. PMID 2838329. S2CID 1378625.
• Yang-Feng TL, Schneider JW, Lindgren V, Shull MM, Benz EJ, Lingrel JB, Francke U (1988). "Chromosomal localization of human Na, K-ATPase alpha- and beta-subunit genes". Genomics. 2 (2): 128–38. doi:10.1016/0888-7543(88)90094-8. PMID 2842249.
• Sverdlov ED, Broude NE, Sverdlov VE, Monastyrskaya GS, Grishin AV, Petrukhin KE, Akopyanz NS, Modyanov NN (1987). "Family of Na,K-ATPase genes. Intra-individual tissue-specific restriction fragment length polymorphism". FEBS Lett. 221 (1): 129–33. Bibcode:1987FEBSL.221..129S. doi:10.1016/0014-5793(87)80366-6. PMID 2887455. S2CID 32756405.
• Harley HG, Brook JD, Jackson CL, Glaser T, Walsh KV, Sarfarazi M, Kent R, Lager M, Koch M, Harper PS (1989). "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. doi:10.1016/0888-7543(88)90131-0. PMID 2907504.
• Monastyrskaya GS, Broude NE, Allikmets RL, Melkov AM, Malyshev IV, Dulubova IE, Petrukhin KE (1987). "The family of human Na,K-ATPase genes. A partial nucleotide sequence related to the alpha-subunit". FEBS Lett. 213 (1): 73–80. Bibcode:1987FEBSL.213...73O. doi:10.1016/0014-5793(87)81467-9. PMID 3030810. S2CID 35674738.
• Shull MM, Lingrel JB (1987). "Multiple genes encode the human Na,K-ATPase catalytic subunit". Proc. Natl. Acad. Sci. U.S.A. 84 (12): 4039–43. Bibcode:1987PNAS...84.4039S. doi:10.1073/pnas.84.12.4039. PMC 305017. PMID 3035563.
• Sverdlov ED, Monastyrskaya GS, Broude NE, Allikmets RL, Melkov AM, Malyshev IV, Dulobova IE, Petrukhin KE (1987). "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. Bibcode:1987FEBSL.217..275S. doi:10.1016/0014-5793(87)80677-4. PMID 3036582. S2CID 44449386.
• Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
• Kramer PL, Mineta M, Klein C, Schilling K, de Leon D, Farlow MR, Breakefield XO, Bressman SB, Dobyns WB, Ozelius LJ, Brashear A (1999). "Rapid-onset dystonia-parkinsonism: linkage to chromosome 19q13". Ann. Neurol. 46 (2): 176–82. doi:10.1002/1531-8249(199908)46:2<176::AID-ANA6>3.0.CO;2-2. PMID 10443882. S2CID 10773650.
• Esplin MS, Fausett MB, Faux DS, Graves SW (2003). "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. doi:10.1067/mob.2003.166. PMID 12634653.
• de Carvalho Aguiar P, Sweadner KJ, Penniston JT, Zaremba J, Liu L, Caton M, Linazasoro G, Borg M, Tijssen MA, Bressman SB, Dobyns WB, Brashear A, Ozelius LJ (2004). "Mutations in the Na/-ATPase alpha3 gene ATP1A3 are associated with rapid-onset dystonia parkinsonism". Neuron. 43 (2): 169–75. doi:10.1016/j.neuron.2004.06.028. PMID 15260953. S2CID 15874616.
• Benfante R, Antonini RA, Vaccari M, Flora A, Chen F, Clementi F, Fornasari D (2005). "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. doi:10.1042/BJ20041294. PMC 1134767. PMID 15462673.
• Lim J, Hao T, Shaw C, Patel AJ, Szabó G, Rual JF, Fisk CJ, Li N, Smolyar A, Hill DE, Barabási AL, Vidal M, Zoghbi HY (2006). "A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration". Cell. 125 (4): 801–14. doi:10.1016/j.cell.2006.03.032. PMID 16713569. S2CID 13709685.

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.

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