ATP1A2 explained

Sodium/potassium-transporting ATPase subunit alpha-2 is a protein which in humans is encoded by the ATP1A2 gene.^{[1] [2]}

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 2 subunit.^[2]

Clinical significance

Mutations in ATP1A2 have been found to cause hemiplegic migraine and epilepsy in an autosomal dominant fashion, sometimes co-occurring in families.^[3] Additionally, it has been associated with an unusual form of migraine called alternating hemiplegia of childhood.^{[4] [5] [6]}

Further reading

• Book: Lingrel JB, Orlowski J, Shull MM, Price EM . Molecular genetics of Na,K-ATPase. . Prog. Nucleic Acid Res. Mol. Biol. . 38 . 37–89 . 1990 . 2158121 . 10.1016/S0079-6603(08)60708-4 . Progress in Nucleic Acid Research and Molecular Biology . 9780125400381 .
• Dunbar LA, Caplan MJ . Ion pumps in polarized cells: sorting and regulation of the Na+, K+- and H+, K+-ATPases . The Journal of Biological Chemistry . 276 . 32 . 29617–20 . August 2001 . 11404365 . 10.1074/jbc.R100023200 . free .
• Shull MM, Pugh DG, Lingrel JB . Characterization of the human Na,K-ATPase alpha 2 gene and identification of intragenic restriction fragment length polymorphisms . The Journal of Biological Chemistry . 264 . 29 . 17532–43 . October 1989 . 10.1016/S0021-9258(18)71525-1 . 2477373 . free .
• Sverdlov ED, Bessarab DA, Malyshev IV, Petrukhin KE, Monastyrskaya GS, Broude NE, Modyanov NN . Family of human Na+,K+-ATPase genes. Structure of the putative regulatory region of the alpha+-gene . FEBS Letters . 244 . 2 . 481–3 . February 1989 . 2537767 . 10.1016/0014-5793(89)80588-5 . 85369528 . free .
• Yang-Feng TL, Schneider JW, Lindgren V, Shull MM, Benz EJ, Lingrel JB, Francke U . Chromosomal localization of human Na+, K+-ATPase alpha- and beta-subunit genes . Genomics . 2 . 2 . 128–38 . February 1988 . 2842249 . 10.1016/0888-7543(88)90094-8 .
• Shull MM, Lingrel JB . Multiple genes encode the human Na+,K+-ATPase catalytic subunit . Proceedings of the National Academy of Sciences of the United States of America . 84 . 12 . 4039–43 . June 1987 . 3035563 . 305017 . 10.1073/pnas.84.12.4039 . 1987PNAS...84.4039S . free .
• Sverdlov ED, Monastyrskaya GS, Broude NE, Allikmets RL, Melkov AM, Malyshev IV, Dulobova IE, Petrukhin KE . 6 . The family of human Na+,K+-ATPase genes. No less than five genes and/or pseudogenes related to the alpha-subunit . FEBS Letters . 217 . 2 . 275–8 . June 1987 . 3036582 . 10.1016/0014-5793(87)80677-4 . free .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . January 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Zahler R, Gilmore-Hebert M, Baldwin JC, Franco K, Benz EJ . Expression of alpha isoforms of the Na,K-ATPase in human heart . Biochimica et Biophysica Acta (BBA) - Biomembranes . 1149 . 2 . 189–94 . July 1993 . 8391840 . 10.1016/0005-2736(93)90200-J .
• Stengelin MK, Hoffman JF . Na,K-ATPase subunit isoforms in human reticulocytes: evidence from reverse transcription-PCR for the presence of alpha1, alpha3, beta2, beta3, and gamma . Proceedings of the National Academy of Sciences of the United States of America . 94 . 11 . 5943–8 . May 1997 . 9159180 . 20886 . 10.1073/pnas.94.11.5943 . 1997PNAS...94.5943S . free .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . October 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Ducros A, Joutel A, Vahedi K, Cecillon M, Ferreira A, Bernard E, Verier A, Echenne B, Lopez de Munain A, Bousser MG, Tournier-Lasserve E . 6 . Mapping of a second locus for familial hemiplegic migraine to 1q21-q23 and evidence of further heterogeneity . Annals of Neurology . 42 . 6 . 885–90 . December 1997 . 9403481 . 10.1002/ana.410420610 . 20915050 .
• Terwindt GM, Ophoff RA, Lindhout D, Haan J, Halley DJ, Sandkuijl LA, Brouwer OF, Frants RR, Ferrari MD . 6 . Partial cosegregation of familial hemiplegic migraine and a benign familial infantile epileptic syndrome . Epilepsia . 38 . 8 . 915–21 . August 1997 . 9579893 . 10.1111/j.1528-1157.1997.tb01257.x . free .
• Nagase T, Ishikawa K, Suyama M, Kikuno R, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O . 6 . Prediction of the coding sequences of unidentified human genes. XI. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro . DNA Research . 5 . 5 . 277–86 . October 1998 . 9872452 . 10.1093/dnares/5.5.277 . free .
• Katzmarzyk PT, Rankinen T, Pérusse L, Dériaz O, Tremblay A, Borecki I, Rao DC, Bouchard C . 6 . Linkage and association of the sodium potassium-adenosine triphosphatase alpha2 and beta1 genes with respiratory quotient and resting metabolic rate in the Québec Family Study . The Journal of Clinical Endocrinology and Metabolism . 84 . 6 . 2093–7 . June 1999 . 10.1210/jcem.84.6.5774 . 10372716 . free .
• Rankinen T, Pérusse L, Borecki I, Chagnon YC, Gagnon J, Leon AS, Skinner JS, Wilmore JH, Rao DC, Bouchard C . 6 . The Na(+)-K(+)-ATPase alpha2 gene and trainability of cardiorespiratory endurance: the HERITAGE family study . Journal of Applied Physiology . 88 . 1 . 346–51 . January 2000 . 10642400 . 10.1152/jappl.2000.88.1.346 .
• Ukkola O, Joanisse DR, Tremblay A, Bouchard C . Na+-K+-ATPase alpha 2-gene and skeletal muscle characteristics in response to long-term overfeeding . Journal of Applied Physiology . 94 . 5 . 1870–4 . May 2003 . 12496141 . 10.1152/japplphysiol.00942.2002 . 10.1.1.546.5874 .

External links

• GeneReviews/NCBI/NIH/UW entry on Familial Hemiplegic Migraine

Notes and References

1. Web site: ATP1A2 - Sodium/potassium-transporting ATPase subunit alpha-2 precursor - Homo sapiens (Human) - ATP1A2 gene & protein . www.uniprot.org . 9 April 2022 . en.
2. Web site: Entrez Gene: ATP1A2 ATPase, Na⁺/K⁺ transporting, alpha 2 (+) polypeptide.
3. Papandreou A, Danti FR, Spaull R, Leuzzi V, Mctague A, Kurian MA . The expanding spectrum of movement disorders in genetic epilepsies . Developmental Medicine and Child Neurology . 62 . 2 . 178–191 . February 2020 . 31784983 . 10.1111/dmcn.14407 . 208498567 .
4. Kanavakis E, Xaidara A, Papathanasiou-Klontza D, Papadimitriou A, Velentza S, Youroukos S . Alternating hemiplegia of childhood: a syndrome inherited with an autosomal dominant trait . Developmental Medicine and Child Neurology . 45 . 12 . 833–6 . December 2003 . 14667076 . 10.1017/S0012162203001543 .
5. Swoboda KJ, Kanavakis E, Xaidara A, Johnson JE, Leppert MF, Schlesinger-Massart MB, Ptacek LJ, Silver K, Youroukos S . 6 . Alternating hemiplegia of childhood or familial hemiplegic migraine? A novel ATP1A2 mutation . Annals of Neurology . 55 . 6 . 884–7 . June 2004 . 15174025 . 10.1002/ana.20134 . 13430399 .
6. Bassi MT, Bresolin N, Tonelli A, Nazos K, Crippa F, Baschirotto C, Zucca C, Bersano A, Dolcetta D, Boneschi FM, Barone V, Casari G . 6 . A novel mutation in the ATP1A2 gene causes alternating hemiplegia of childhood . Journal of Medical Genetics . 41 . 8 . 621–8 . August 2004 . 15286158 . 1735877 . 10.1136/jmg.2003.017863 .