ATP1A3

Sodyum/potasyum taşıyan ATPase alt birimi alpha-3, insanlarda ATP1A3 geniyle kodlanmış enzimdir.^[1][2] Beyindeki sodyum ve potasyum seviyelerinin düzenlenmesiyle ilgilidir.^[3]

İşlev

Bu gen tarafından kodlanan protein P-type cation transport ATPaseler ailesine ve Na⁺/K⁺-ATPaseler alt ailesine aittir. Na⁺/K⁺-ATPase, plazma membran boyunca Na ve K iyonlarının elektromanyetik meyillerini kurma ve yönetmede sorumlu, bütüncül membran proteindir. Bu meyiller, osmoregülasyon, çeşitli organik ve inorganik moleküllerin sodyum bağlı taşıması, sinir ve kas sistemlerinin elektriksel uyarılabilirliği gibi işlemlerde zorunludur. Enzim iki alt birimden oluşur. Bir büyük katalitik alt birim(alfa) ve daha küçük olan glikoprotein alt birim.(beta) Na⁺/K⁺-ATPasenin katalitik alt birimi birden çok genden oluşur. Bu gen bir alfa 3 alt birimini kodlar.^[2]

Klinik Durumlar

ATP1A3'teki mutasyonlar genellikle hızlı başlangıçlı distoni(ikincil parkinson, RDP ya da DYT12)'de görülür. Bu tanıya sahip kişilerde genetik test önerilir.

Bu genin mutasyonu farelerde epilepsi ile ilgilidir. Farelerde bu genin tahrif edilmesi epilepsiyi önlemektedir.^[4],

Çocukluk çağı alternan hemiplejinin genetik nedeni olması muhtemeldir.^[5]

Kaynakça

1. Brashear A, Dobyns WB, de Carvalho Aguiar P, Borg M, Frijns CJ, Gollamudi S, Green A, Guimaraes J, Haake BC, Klein C, Linazasoro G, Munchau 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. 
2. "Entrez Gene: ATP1A3 ATPase, Na⁺/K⁺ transporting, alpha 3 polypeptide". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=478. 
3. http://www.beslenmedestegi.com/hastaliklar/sara-hastaligi-nedir
4. 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. DOI:10.1073/pnas.0904817106. PMC 2729024. PMID 19666602. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2729024. 
5. Heinzen EL, Swoboda KJ, Hitomi Y, Gurrieri F, Nicole S, de Vries B, Tiziano FD, Fontaine B, Walley NM, Heavin S, et al. (July 2012). "De novo mutations in ATP1A3 cause alternating hemiplegia of childhood". Nat Genet 44 (9): 1030–4. DOI:10.1038/ng.2358. PMC 3442240. PMID 22842232. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3442240. 

İleri Okuma (İngilizce)

• 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 ve diğ. (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. 
• Ovchinnikov YuA, Monastyrskaya GS, Broude NE ve diğ. (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. DOI:10.1016/0014-5793(88)81361-9. PMID 2838329. 
• Yang-Feng TL, Schneider JW, Lindgren V ve diğ. (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 ve diğ. (1987). "Family of Na⁺,K⁺-ATPase genes. Intra-individual tissue-specific restriction fragment length polymorphism". FEBS Lett. 221 (1): 129–33. DOI:10.1016/0014-5793(87)80366-6. PMID 2887455. 
• Harley HG, Brook JD, Jackson CL ve diğ. (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. 
• Ovchinnikov YuA, Monastyrskaya GS, Broude NE ve diğ. (1987). "The family of human Na⁺,K⁺-ATPase genes. A partial nucleotide sequence related to the alpha-subunit". FEBS Lett. 213 (1): 73–80. DOI:10.1016/0014-5793(87)81467-9. PMID 3030810. 
• 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. DOI:10.1073/pnas.84.12.4039. PMC 305017. PMID 3035563. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=305017. 
• Sverdlov ED, Monastyrskaya GS, Broude NE ve diğ. (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. DOI:10.1016/0014-5793(87)80677-4. PMID 3036582. 
• 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 ve diğ. (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 ve diğ. (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. 
• Strausberg RL, Feingold EA, Grouse LH ve diğ. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. DOI:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241. 
• 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.[phone]. PMID 12634653. 
• Ota T, Suzuki Y, Nishikawa T ve diğ. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. DOI:10.1038/ng1285. PMID 14702039. 
• de Carvalho Aguiar P (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. 
• Benfante R, Antonini RA, Vaccari M ve diğ. (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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1134767. 
• Gerhard DS, Wagner L, Feingold EA ve diğ. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. DOI:10.1101/gr.2596504. PMC 528928. PMID 15489334. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=528928. 
• Lim J, Hao T, Shaw C ve diğ. (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. 

Dış bağlantılar(İngilizce)

• GeneReview/NCBI/NIH/UW entry on Rapid-Onset Dystonia Parkinsonism