ID AT1A3_HUMAN Reviewed; 1013 AA. AC P13637; B7Z2T0; B7Z401; F5H6J6; Q16732; Q16735; Q969K5; DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot. DT 17-OCT-2006, sequence version 3. DT 28-JAN-2026, entry version 248. DE RecName: Full=Sodium/potassium-transporting ATPase subunit alpha-3; DE Short=Na(+)/K(+) ATPase alpha-3 subunit; DE EC=7.2.2.13; DE AltName: Full=Na(+)/K(+) ATPase alpha(III) subunit; DE AltName: Full=Sodium pump subunit alpha-3; GN Name=ATP1A3; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1). RX PubMed=2838329; DOI=10.1016/0014-5793(88)81361-9; RA Ovchinnikov Y.A., Monastyrskaya G.S., Broude N.E., Ushkaryov Y.A., RA Melkov A.M., Smirnov Y.V., Malyshev I.V., Allikmets R.L., Kostina M.B., RA Dulubova I.E., Kiyatkin N.I., Grishin A.V., Modyanov N.N., Sverdlov E.D.; RT "Family of human Na+, K+-ATPase genes. Structure of the gene for the RT catalytic subunit (alpha III-form) and its relationship with structural RT features of the protein."; RL FEBS Lett. 233:87-94(1988). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1). RC TISSUE=Brain; RX PubMed=2834163; RA Sverdlov E.D., Monastyrskaya G.S., Broude N.E., Ushkarev Y.A., Melkov A.M., RA Smirnov Y.V., Malyshev I.V., Allikmets R.L., Kostina M.B., Dulubova I.E., RA Kiyatkin N.I., Grishin A.V., Modyanov N.N., Ovchinnikov Y.A.; RT "Family of human Na(+),K(+)-ATPase genes. Structure of the gene of isoform RT alpha-III."; RL Dokl. Akad. Nauk SSSR 297:1488-1494(1987). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3). RC TISSUE=Brain, and Thalamus; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057824; DOI=10.1038/nature02399; RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A., RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., RA Rubin E.M., Lucas S.M.; RT "The DNA sequence and biology of human chromosome 19."; RL Nature 428:529-535(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 120-387; 494-538 AND 545-1013. RX PubMed=3030810; DOI=10.1016/0014-5793(87)81467-9; RA Ovchinnikov Y.A., Monastyrskaya G.S., Broude N.E., Allikmets R.L., RA Ushkaryov Y.A., Melkov A.M., Smirnov Y.V., Malyshev I.V., Dulubova I.E., RA Petrukhin K.E., Gryshin A.V., Sverdlov V.E., Kiyatkin N.I., Kostina M.B., RA Modyanov N.N., Sverdlov E.D.; RT "The family of human Na+,K+-ATPase genes. A partial nucleotide sequence RT related to the alpha-subunit."; RL FEBS Lett. 213:73-80(1987). RN [7] RP ERRATUM OF PUBMED:3030810. RA Ovchinnikov Y.A., Monastyrskaya G.S., Broude N.E., Allikmets R.L., RA Ushkaryov Y.A., Melkov A.M., Smirnov Y.V., Malyshev I.V., Dulubova I.E., RA Petrukhin K.E., Gryshin A.V., Sverdlov V.E., Kiyatkin N.I., Kostina M.B., RA Modyanov N.N., Sverdlov E.D.; RL FEBS Lett. 214:375-375(1987). RN [8] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 243-434. RX PubMed=3036582; DOI=10.1016/0014-5793(87)80677-4; RA Sverdlov E.D., Monastyrskaya G.S., Broude N.E., Ushkaryov Y.A., RA Allikmets R.L., Melkov A.M., Smirnov Y.V., Malyshev I.V., Dulubova I.E., RA Petrukhin K.E., Gryshin A.V., Kiyatkin N.I., Kostina M.B., Sverdlov V.E., RA Modyanov N.N., Ovchinnikov Y.A.; RT "The family of human Na+,K+-ATPase genes. No less than five genes and/or RT pseudogenes related to the alpha-subunit."; RL FEBS Lett. 217:275-278(1987). RN [9] RP SUBCELLULAR LOCATION. RX PubMed=7711835; DOI=10.3109/09687689409160435; RA Hundal H.S., Maxwell D.L., Ahmed A., Darakhshan F., Mitsumoto Y., Klip A.; RT "Subcellular distribution and immunocytochemical localization of Na,K- RT ATPase subunit isoforms in human skeletal muscle."; RL Mol. Membr. Biol. 11:255-262(1994). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [11] RP VARIANTS DYT12 THR-274; LYS-277; MET-613; SER-758; LEU-780 AND TYR-801. RX PubMed=15260953; DOI=10.1016/j.neuron.2004.06.028; RA de Carvalho Aguiar P., Sweadner K.J., Penniston J.T., Zaremba J., Liu L., RA Caton M., Linazasoro G., Borg M., Tijssen M.A.J., Bressman S.B., RA Dobyns W.B., Brashear A., Ozelius L.J.; RT "Mutations in the Na(+)/K(+)-ATPase alpha-3 gene ATP1A3 are associated with RT rapid-onset dystonia parkinsonism."; RL Neuron 43:169-175(2004). RN [12] RP VARIANT DYT12 TYR-1013 EXT, AND CHARACTERIZATION OF VARIANT DYT12 TYR-1013 RP EXT. RX PubMed=19351654; DOI=10.1093/hmg/ddp170; RA Blanco-Arias P., Einholm A.P., Mamsa H., Concheiro C., RA Gutierrez-de-Teran H., Romero J., Toustrup-Jensen M.S., Carracedo A., RA Jen J.C., Vilsen B., Sobrido M.J.; RT "A C-terminal mutation of ATP1A3 underscores the crucial role of sodium RT affinity in the pathophysiology of rapid-onset dystonia-parkinsonism."; RL Hum. Mol. Genet. 18:2370-2377(2009). RN [13] RP VARIANT DYT12 ASN-923. RX PubMed=19652145; DOI=10.1212/wnl.0b013e3181b04acd; RA Anselm I.A., Sweadner K.J., Gollamudi S., Ozelius L.J., Darras B.T.; RT "Rapid-onset dystonia-parkinsonism in a child with a novel atp1a3 gene RT mutation."; RL Neurology 73:400-401(2009). RN [14] RP VARIANTS AHC2 ASN-274; ASP-322; PRO-371; CYS-755; ARG-772; ILE-773; RP ASN-801; LYS-815 AND TYR-923. RX PubMed=22850527; DOI=10.1016/s1474-4422(12)70182-5; RA Rosewich H., Thiele H., Ohlenbusch A., Maschke U., Altmuller J., RA Frommolt P., Zirn B., Ebinger F., Siemes H., Nurnberg P., Brockmann K., RA Gartner J.; RT "Heterozygous de-novo mutations in ATP1A3 in patients with alternating RT hemiplegia of childhood: a whole-exome sequencing gene-identification RT study."; RL Lancet Neurol. 11:764-773(2012). RN [15] RP VARIANTS AHC2 TYR-137; PHE-137; LEU-140; ASN-220; ASN-274; PHE-333; RP SER-755; SER-773; ASN-801; ARG-806; SER-810; PRO-811; LYS-815; VAL-919 DEL; RP ARG-947; ASP-955 AND TYR-992, AND CHARACTERIZATION OF VARIANTS AHC2 RP PHE-137; PHE-333; ASN-801; PRO-811 AND LYS-815. RX PubMed=22842232; DOI=10.1038/ng.2358; RA Heinzen E.L., Swoboda K.J., Hitomi Y., Gurrieri F., Nicole S., de Vries B., RA Tiziano F.D., Fontaine B., Walley N.M., Heavin S., Panagiotakaki E., RA Neri G., Koelewijn S., Kamphorst J., Geilenkirchen M., Pelzer N., Laan L., RA Haan J., Ferrari M., van den Maagdenberg A.M., Zucca C., Bassi M.T., RA Franchini F., Vavassori R., Giannotta M., Gobbi G., Granata T., RA Nardocci N., De Grandis E., Veneselli E., Stagnaro M., Vigevano F., RA Oechsler C., Arzimanoglou A., Ninan M., Neville B., Ebinger F., Fons C., RA Campistol J., Kemlink D., Nevsimalova S., Peeters-Scholte C., Casaer P., RA Casari G., Sange G., Spiel G., Martinelli Boneschi F., Schyns T., RA Crawley F., Poncelin D., Fiori S., Abiusi E., Di Pietro L., Sweney M.T., RA Newcomb T.M., Viollet L., Huff C., Jorde L.B., Reyna S.P., Murphy K.J., RA Shianna K.V., Gumbs C.E., Little L., Silver K., Ptacek L.J., Ferrari M.D., RA Bye A.M., Herkes G.K., Whitelaw C.M., Webb D., Lynch B.J., Uldall P., RA King M.D., Scheffer I.E., Sisodiya S.M., Mikati M.A., Goldstein D.B.; RT "De novo mutations in ATP1A3 cause alternating hemiplegia of childhood."; RL Nat. Genet. 44:1030-1034(2012). RN [16] RP VARIANTS AHC2 CYS-755; ASN-801; LYS-815 AND TYR-927. RX PubMed=23409136; DOI=10.1371/journal.pone.0056120; RA Ishii A., Saito Y., Mitsui J., Ishiura H., Yoshimura J., Arai H., RA Yamashita S., Kimura S., Oguni H., Morishita S., Tsuji S., Sasaki M., RA Hirose S.; RT "Identification of ATP1A3 mutations by exome sequencing as the cause of RT alternating hemiplegia of childhood in Japanese patients."; RL PLoS ONE 8:E56120-E56120(2013). RN [17] RP INVOLVEMENT IN CAPOS, AND VARIANT CAPOS LYS-818. RX PubMed=24468074; DOI=10.1186/1750-1172-9-15; RA Demos M.K., van Karnebeek C.D., Ross C.J., Adam S., Shen Y., Zhan S.H., RA Shyr C., Horvath G., Suri M., Fryer A., Jones S.J., Friedman J.M.; RT "A novel recurrent mutation in ATP1A3 causes CAPOS syndrome."; RL Orphanet J. Rare Dis. 9:15-15(2014). RN [18] RP CHARACTERIZATION OF VARIANTS AHC2 TYR-137; ASN-220; ASN-127; ASN-801; RP LYS-815 AND ARG-947. RX PubMed=24631656; DOI=10.1016/j.bbadis.2014.03.002; RA Weigand K.M., Messchaert M., Swarts H.G., Russel F.G., Koenderink J.B.; RT "Alternating Hemiplegia of Childhood mutations have a differential effect RT on Na(+),K(+)-ATPase activity and ouabain binding."; RL Biochim. Biophys. Acta 1842:1010-1016(2014). RN [19] RP VARIANT THR-320, AND VARIANT AHC2 ARG-947. RX PubMed=26993267; DOI=10.1136/jmedgenet-2015-103263; RA Trump N., McTague A., Brittain H., Papandreou A., Meyer E., Ngoh A., RA Palmer R., Morrogh D., Boustred C., Hurst J.A., Jenkins L., Kurian M.A., RA Scott R.H.; RT "Improving diagnosis and broadening the phenotypes in early-onset seizure RT and severe developmental delay disorders through gene panel analysis."; RL J. Med. Genet. 53:310-317(2016). RN [20] RP VARIANTS DEE99 ARG-292; VAL-316; PRO-361; TYR-609; LYS-764 DEL; ARG-775; RP ASN-801; PHE-857 DEL; TYR-887; PRO-888; TRP-893; PRO-924 AND PRO-972 DEL, RP INVOLVEMENT IN DEE99, FUNCTION, AND CHARACTERIZATION OF VARIANTS DEE99 RP ARG-292; VAL-316; TYR-887 AND PRO-972 DEL. RX PubMed=33880529; DOI=10.1093/brain/awab052; RG ATP1A2/A3-collaborators; RA Vetro A., Nielsen H.N., Holm R., Hevner R.F., Parrini E., Powis Z., RA Moeller R.S., Bellan C., Simonati A., Lesca G., Helbig K.L., Palmer E.E., RA Mei D., Ballardini E., Van Haeringen A., Syrbe S., Leuzzi V., Cioni G., RA Curry C.J., Costain G., Santucci M., Chong K., Mancini G.M.S., RA Clayton-Smith J., Bigoni S., Scheffer I.E., Dobyns W.B., Vilsen B., RA Guerrini R.; RT "ATP1A2- and ATP1A3-associated early profound epileptic encephalopathy and RT polymicrogyria."; RL Brain 144:1435-1450(2021). CC -!- FUNCTION: This is the catalytic component of the active enzyme, which CC catalyzes the hydrolysis of ATP coupled with the exchange of sodium and CC potassium ions across the plasma membrane. This action creates the CC electrochemical gradient of sodium and potassium ions, providing the CC energy for active transport of various nutrients. CC {ECO:0000269|PubMed:33880529}. CC -!- CATALYTIC ACTIVITY: CC Reaction=K(+)(out) + Na(+)(in) + ATP + H2O = K(+)(in) + Na(+)(out) + CC ADP + phosphate + H(+); Xref=Rhea:RHEA:18353, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29101, ChEBI:CHEBI:29103, CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; CC EC=7.2.2.13; CC -!- SUBUNIT: The sodium/potassium-transporting ATPase is composed of a CC catalytic alpha subunit, an auxiliary non-catalytic beta subunit and an CC additional regulatory subunit. Interacts with regulatory subunit FXYD1. CC {ECO:0000250|UniProtKB:P06687}. CC -!- INTERACTION: CC P13637; Q6XD76: ASCL4; NbExp=3; IntAct=EBI-948169, EBI-10254793; CC P13637; Q9UMX3: BOK; NbExp=3; IntAct=EBI-948169, EBI-7105206; CC P13637; Q9UQM7: CAMK2A; NbExp=3; IntAct=EBI-948169, EBI-1383687; CC P13637; Q6NXG1: ESRP1; NbExp=3; IntAct=EBI-948169, EBI-10213520; CC P13637; Q99504: EYA3; NbExp=3; IntAct=EBI-948169, EBI-9089567; CC P13637; Q0VD86: INCA1; NbExp=3; IntAct=EBI-948169, EBI-6509505; CC P13637; Q6ZQX7-4: LIAT1; NbExp=3; IntAct=EBI-948169, EBI-25830459; CC P13637; Q9GZQ6: NPFFR1; NbExp=3; IntAct=EBI-948169, EBI-18212103; CC P13637; Q96PV4: PNMA5; NbExp=3; IntAct=EBI-948169, EBI-10171633; CC P13637; P12757: SKIL; NbExp=3; IntAct=EBI-948169, EBI-2902468; CC P13637; Q08AE8: SPIRE1; NbExp=3; IntAct=EBI-948169, EBI-1055655; CC P13637; Q9H7C4: SYNC; NbExp=3; IntAct=EBI-948169, EBI-11285923; CC P13637; P15923-3: TCF3; NbExp=3; IntAct=EBI-948169, EBI-12000326; CC P13637; Q12888: TP53BP1; NbExp=3; IntAct=EBI-948169, EBI-396540; CC P13637; Q08AM6: VAC14; NbExp=3; IntAct=EBI-948169, EBI-2107455; CC P13637; Q6ZSB9: ZBTB49; NbExp=3; IntAct=EBI-948169, EBI-2859943; CC P13637; P17024: ZNF20; NbExp=3; IntAct=EBI-948169, EBI-717634; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:7711835}; CC Multi-pass membrane protein {ECO:0000269|PubMed:7711835}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=P13637-1; Sequence=Displayed; CC Name=2; CC IsoId=P13637-2; Sequence=VSP_046956; CC Name=3; CC IsoId=P13637-3; Sequence=VSP_046957; CC -!- DISEASE: Dystonia 12 (DYT12) [MIM:128235]: An autosomal dominant CC dystonia-parkinsonism disorder. Dystonia is defined by the presence of CC sustained involuntary muscle contractions, often leading to abnormal CC postures. DYT12 patients develop dystonia and parkinsonism between 15 CC and 45 years of age. The disease is characterized by an unusually rapid CC evolution of signs and symptoms. The sudden onset of symptoms over CC hours to a few weeks, often associated with physical or emotional CC stress, suggests a trigger initiating a nervous system insult resulting CC in permanent neurologic disability. {ECO:0000269|PubMed:15260953, CC ECO:0000269|PubMed:19351654, ECO:0000269|PubMed:19652145}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Alternating hemiplegia of childhood 2 (AHC2) [MIM:614820]: A CC rare syndrome of episodic hemi- or quadriplegia lasting minutes to CC days. Most cases are accompanied by dystonic posturing, choreoathetoid CC movements, nystagmus, other ocular motor abnormalities, autonomic CC disturbances, and progressive cognitive impairment. It is typically CC distinguished from familial hemiplegic migraine by infantile onset and CC high prevalence of associated neurological deficits that become CC increasingly obvious with age. {ECO:0000269|PubMed:22842232, CC ECO:0000269|PubMed:22850527, ECO:0000269|PubMed:23409136, CC ECO:0000269|PubMed:24631656, ECO:0000269|PubMed:26993267}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Cerebellar ataxia, areflexia, pes cavus, optic atrophy, and CC sensorineural hearing loss (CAPOS) [MIM:601338]: An autosomal dominant CC neurologic disorder characterized by relapsing and partially remitting, CC early-onset cerebellar ataxia following a febrile illness. Other CC features include progressive optic atrophy and sensorineural hearing CC loss, generalized hypotonia, areflexia and pes cavus without evidence CC of a peripheral neuropathy on neurophysiological studies. CC {ECO:0000269|PubMed:24468074}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Developmental and epileptic encephalopathy 99 (DEE99) CC [MIM:619606]: A form of epileptic encephalopathy, a heterogeneous group CC of early-onset epilepsies characterized by refractory seizures, CC neurodevelopmental impairment, and poor prognosis. Development is CC normal prior to seizure onset, after which cognitive and motor delays CC become apparent. DEE99 is an autosomal dominant form characterized by CC onset of seizures in early childhood. {ECO:0000269|PubMed:33880529}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- SIMILARITY: Belongs to the cation transport ATPase (P-type) (TC 3.A.3) CC family. Type IIC subfamily. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M37457; AAA51798.1; -; Genomic_DNA. DR EMBL; M37436; AAA51798.1; JOINED; Genomic_DNA. DR EMBL; M37437; AAA51798.1; JOINED; Genomic_DNA. DR EMBL; M37438; AAA51798.1; JOINED; Genomic_DNA. DR EMBL; M37462; AAA51798.1; JOINED; Genomic_DNA. DR EMBL; M37439; AAA51798.1; JOINED; Genomic_DNA. DR EMBL; M37440; AAA51798.1; JOINED; Genomic_DNA. DR EMBL; M37441; AAA51798.1; JOINED; Genomic_DNA. DR EMBL; M37442; AAA51798.1; JOINED; Genomic_DNA. DR EMBL; M37443; AAA51798.1; JOINED; Genomic_DNA. DR EMBL; M37444; AAA51798.1; JOINED; Genomic_DNA. DR EMBL; M37445; AAA51798.1; JOINED; Genomic_DNA. DR EMBL; M37447; AAA51798.1; JOINED; Genomic_DNA. DR EMBL; M37448; AAA51798.1; JOINED; Genomic_DNA. DR EMBL; M37449; AAA51798.1; JOINED; Genomic_DNA. DR EMBL; M37450; AAA51798.1; JOINED; Genomic_DNA. DR EMBL; M37451; AAA51798.1; JOINED; Genomic_DNA. DR EMBL; M37452; AAA51798.1; JOINED; Genomic_DNA. DR EMBL; M37453; AAA51798.1; JOINED; Genomic_DNA. DR EMBL; M37454; AAA51798.1; JOINED; Genomic_DNA. DR EMBL; M37455; AAA51798.1; JOINED; Genomic_DNA. DR EMBL; M37456; AAA51798.1; JOINED; Genomic_DNA. DR EMBL; X12910; CAA31390.1; -; Genomic_DNA. DR EMBL; X12911; CAA31390.1; JOINED; Genomic_DNA. DR EMBL; X12912; CAA31390.1; JOINED; Genomic_DNA. DR EMBL; X12913; CAA31390.1; JOINED; Genomic_DNA. DR EMBL; X12914; CAA31390.1; JOINED; Genomic_DNA. DR EMBL; X12915; CAA31390.1; JOINED; Genomic_DNA. DR EMBL; X12916; CAA31390.1; JOINED; Genomic_DNA. DR EMBL; X12917; CAA31390.1; JOINED; Genomic_DNA. DR EMBL; X12919; CAA31390.1; JOINED; Genomic_DNA. DR EMBL; X12920; CAA31390.1; JOINED; Genomic_DNA. DR EMBL; X12921; CAA31390.1; JOINED; Genomic_DNA. DR EMBL; X12922; CAA31390.1; JOINED; Genomic_DNA. DR EMBL; X12923; CAA31390.1; JOINED; Genomic_DNA. DR EMBL; AK295078; BAH11966.1; -; mRNA. DR EMBL; AK296557; BAH12387.1; -; mRNA. DR EMBL; AC010616; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC009282; AAH09282.1; -; mRNA. DR EMBL; BC009394; AAH09394.1; -; mRNA. DR EMBL; BC015566; AAH15566.1; -; mRNA. DR EMBL; M28286; AAA52285.1; -; Genomic_DNA. DR EMBL; M28284; AAA52285.1; JOINED; Genomic_DNA. DR EMBL; M28285; AAA52285.1; JOINED; Genomic_DNA. DR EMBL; M28293; AAA52286.1; -; Genomic_DNA. DR EMBL; M28287; AAA52286.1; JOINED; Genomic_DNA. DR EMBL; M35821; AAA52286.1; JOINED; Genomic_DNA. DR EMBL; M35822; AAA52286.1; JOINED; Genomic_DNA. DR EMBL; M28289; AAA52286.1; JOINED; Genomic_DNA. DR EMBL; M28290; AAA52286.1; JOINED; Genomic_DNA. DR EMBL; M28291; AAA52286.1; JOINED; Genomic_DNA. DR EMBL; M28292; AAA52286.1; JOINED; Genomic_DNA. DR EMBL; M27577; AAA58380.1; -; Genomic_DNA. DR EMBL; M27570; AAA58380.1; JOINED; Genomic_DNA. DR EMBL; M27573; AAA58380.1; JOINED; Genomic_DNA. DR CCDS; CCDS12594.1; -. [P13637-1] DR CCDS; CCDS58663.1; -. [P13637-2] DR CCDS; CCDS58664.1; -. [P13637-3] DR PIR; S00801; S00801. DR RefSeq; NP_001243142.1; NM_001256213.2. [P13637-2] DR RefSeq; NP_001243143.1; NM_001256214.2. [P13637-3] DR RefSeq; NP_689509.1; NM_152296.5. [P13637-1] DR PDB; 8D3U; EM; 3.70 A; A=18-1013. DR PDB; 8D3V; EM; 3.40 A; A=1-1013. DR PDB; 8D3W; EM; 3.50 A; A=1-1013. DR PDB; 8D3X; EM; 4.10 A; A=1-1013. DR PDB; 8D3Y; EM; 3.90 A; A=1-1013. DR PDBsum; 8D3U; -. DR PDBsum; 8D3V; -. DR PDBsum; 8D3W; -. DR PDBsum; 8D3X; -. DR PDBsum; 8D3Y; -. DR AlphaFoldDB; P13637; -. DR EMDB; EMD-27164; -. DR EMDB; EMD-27165; -. DR EMDB; EMD-27166; -. DR EMDB; EMD-27167; -. DR EMDB; EMD-27168; -. DR SMR; P13637; -. DR BioGRID; 106968; 340. DR CORUM; P13637; -. DR FunCoup; P13637; 1050. DR IntAct; P13637; 221. DR MINT; P13637; -. DR STRING; 9606.ENSP00000444688; -. DR ChEMBL; CHEMBL2095186; -. DR DrugBank; DB09020; Bisacodyl. DR DrugBank; DB01396; Digitoxin. DR DrugBank; DB00390; Digoxin. DR DrugBank; DB06157; Istaroxime. DR DrugBank; DB12843; Oleandrin. DR DrugBank; DB01250; Olsalazine. DR DrugBank; DB01092; Ouabain. DR DrugBank; DB12350; Rostafuroxin. DR DrugBank; DB09479; Rubidium Rb-82. DR DrugBank; DB16690; Tegoprazan. DR DrugCentral; P13637; -. DR TCDB; 3.A.3.1.1; the p-type atpase (p-atpase) superfamily. DR GlyGen; P13637; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P13637; -. DR PhosphoSitePlus; P13637; -. DR SwissPalm; P13637; -. DR BioMuta; ATP1A3; -. DR DMDM; 116241260; -. DR jPOST; P13637; -. DR MassIVE; P13637; -. DR PaxDb; 9606-ENSP00000444688; -. DR PeptideAtlas; P13637; -. DR ProteomicsDB; 27209; -. DR ProteomicsDB; 52946; -. [P13637-1] DR ProteomicsDB; 6459; -. DR Antibodypedia; 30869; 215 antibodies from 31 providers. DR DNASU; 478; -. DR Ensembl; ENST00000543770.5; ENSP00000437577.1; ENSG00000105409.20. [P13637-2] DR Ensembl; ENST00000545399.6; ENSP00000444688.1; ENSG00000105409.20. [P13637-3] DR Ensembl; ENST00000648268.1; ENSP00000498113.1; ENSG00000105409.20. [P13637-1] DR GeneID; 478; -. DR KEGG; hsa:478; -. DR MANE-Select; ENST00000648268.1; ENSP00000498113.1; NM_152296.5; NP_689509.1. DR UCSC; uc002osg.4; human. [P13637-1] DR AGR; HGNC:801; -. DR ClinPGx; PA64; -. DR CTD; 478; -. DR DisGeNET; 478; -. DR GeneCards; ATP1A3; -. DR GeneReviews; ATP1A3; -. DR HGNC; HGNC:801; ATP1A3. DR HPA; ENSG00000105409; Group enriched (brain, heart muscle, retina). DR MalaCards; ATP1A3; -. DR MIM; 128235; phenotype. DR MIM; 182350; gene. DR MIM; 601338; phenotype. DR MIM; 614820; phenotype. DR MIM; 619606; phenotype. DR OpenTargets; ENSG00000105409; -. DR Orphanet; 2131; Alternating hemiplegia of childhood. DR Orphanet; 1171; Cerebellar ataxia-areflexia-pes cavus-optic atrophy-sensorineural hearing loss syndrome. DR Orphanet; 442835; Non-specific early-onset epileptic encephalopathy. DR Orphanet; 71517; Rapid-onset dystonia-parkinsonism. DR VEuPathDB; HostDB:ENSG00000105409; -. DR eggNOG; KOG0203; Eukaryota. DR GeneTree; ENSGT00940000160476; -. DR InParanoid; P13637; -. DR OMA; FGIDDYI; -. DR OrthoDB; 3352408at2759; -. DR PAN-GO; P13637; 7 GO annotations based on evolutionary models. DR PhylomeDB; P13637; -. DR PathwayCommons; P13637; -. DR Reactome; R-HSA-5578775; Ion homeostasis. DR Reactome; R-HSA-936837; Ion transport by P-type ATPases. DR Reactome; R-HSA-9679191; Potential therapeutics for SARS. DR SignaLink; P13637; -. DR SIGNOR; P13637; -. DR Agora; ENSG00000105409; Agora Nominated Target for Alzheimer's Disease. DR BioGRID-ORCS; 478; 18 hits in 1153 CRISPR screens. DR CD-CODE; FB4E32DD; Presynaptic clusters and postsynaptic densities. DR ChiTaRS; ATP1A3; human. DR GeneWiki; ATP1A3; -. DR GenomeRNAi; 478; -. DR Pharos; P13637; Tclin. DR PRO; PR:P13637; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; P13637; protein. DR Bgee; ENSG00000105409; Expressed in superior frontal gyrus and 96 other cell types or tissues. DR ExpressionAtlas; P13637; baseline and differential. DR GO; GO:0030424; C:axon; IDA:ARUK-UCL. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB. DR GO; GO:1903561; C:extracellular vesicle; HDA:UniProtKB. DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; ISS:ARUK-UCL. DR GO; GO:0098984; C:neuron to neuron synapse; ISS:ARUK-UCL. DR GO; GO:0043025; C:neuronal cell body; IDA:ARUK-UCL. DR GO; GO:0032809; C:neuronal cell body membrane; IC:ARUK-UCL. DR GO; GO:0031090; C:organelle membrane; IGI:ARUK-UCL. DR GO; GO:0001917; C:photoreceptor inner segment; ISS:ARUK-UCL. DR GO; GO:0060342; C:photoreceptor inner segment membrane; ISS:ARUK-UCL. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0005890; C:sodium:potassium-exchanging ATPase complex; IDA:BHF-UCL. DR GO; GO:0045202; C:synapse; ISS:UniProtKB. DR GO; GO:0001540; F:amyloid-beta binding; IDA:ARUK-UCL. DR GO; GO:0005524; F:ATP binding; NAS:UniProtKB. DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0005391; F:P-type sodium:potassium-exchanging transporter activity; IDA:BHF-UCL. DR GO; GO:0051087; F:protein-folding chaperone binding; IPI:BHF-UCL. DR GO; GO:1990239; F:steroid hormone binding; NAS:BHF-UCL. DR GO; GO:0086064; P:cell communication by electrical coupling involved in cardiac conduction; TAS:BHF-UCL. DR GO; GO:1904646; P:cellular response to amyloid-beta; ISS:ARUK-UCL. DR GO; GO:0071383; P:cellular response to steroid hormone stimulus; NAS:BHF-UCL. DR GO; GO:0030007; P:intracellular potassium ion homeostasis; IDA:BHF-UCL. DR GO; GO:0006883; P:intracellular sodium ion homeostasis; IDA:BHF-UCL. DR GO; GO:1990535; P:neuron projection maintenance; IGI:ARUK-UCL. DR GO; GO:1990573; P:potassium ion import across plasma membrane; IDA:BHF-UCL. DR GO; GO:1902600; P:proton transmembrane transport; IBA:GO_Central. DR GO; GO:0060075; P:regulation of resting membrane potential; TAS:ARUK-UCL. DR GO; GO:1903416; P:response to glycoside; NAS:BHF-UCL. DR GO; GO:0036376; P:sodium ion export across plasma membrane; IDA:BHF-UCL. DR CDD; cd02608; P-type_ATPase_Na-K_like; 1. DR FunFam; 2.70.150.10:FF:000106; Sodium/potassium-transporting ATPase subunit alpha; 1. DR FunFam; 3.40.1110.10:FF:000001; Sodium/potassium-transporting ATPase subunit alpha; 1. DR FunFam; 3.40.50.1000:FF:000004; Sodium/potassium-transporting ATPase subunit alpha; 1. DR FunFam; 1.20.1110.10:FF:000095; Sodium/potassium-transporting ATPase subunit alpha-1; 2. DR Gene3D; 3.40.1110.10; Calcium-transporting ATPase, cytoplasmic domain N; 1. DR Gene3D; 2.70.150.10; Calcium-transporting ATPase, cytoplasmic transduction domain A; 1. DR Gene3D; 1.20.1110.10; Calcium-transporting ATPase, transmembrane domain; 1. DR Gene3D; 3.40.50.1000; HAD superfamily/HAD-like; 1. DR InterPro; IPR006068; ATPase_P-typ_cation-transptr_C. DR InterPro; IPR004014; ATPase_P-typ_cation-transptr_N. DR InterPro; IPR023299; ATPase_P-typ_cyto_dom_N. DR InterPro; IPR018303; ATPase_P-typ_P_site. DR InterPro; IPR023298; ATPase_P-typ_TM_dom_sf. DR InterPro; IPR008250; ATPase_P-typ_transduc_dom_A_sf. DR InterPro; IPR059000; ATPase_P-type_domA. DR InterPro; IPR050510; Cation_transp_ATPase_P-type. DR InterPro; IPR036412; HAD-like_sf. DR InterPro; IPR023214; HAD_sf. DR InterPro; IPR005775; P-type_ATPase_IIC. DR InterPro; IPR001757; P_typ_ATPase. DR InterPro; IPR044492; P_typ_ATPase_HD_dom. DR NCBIfam; TIGR01106; ATPase-IIC_X-K; 1. DR NCBIfam; TIGR01494; ATPase_P-type; 2. DR PANTHER; PTHR43294; SODIUM/POTASSIUM-TRANSPORTING ATPASE SUBUNIT ALPHA; 1. DR PANTHER; PTHR43294:SF15; SODIUM_POTASSIUM-TRANSPORTING ATPASE SUBUNIT ALPHA-3; 1. DR Pfam; PF13246; Cation_ATPase; 1. DR Pfam; PF00689; Cation_ATPase_C; 1. DR Pfam; PF00690; Cation_ATPase_N; 1. DR Pfam; PF00122; E1-E2_ATPase; 1. DR PRINTS; PR00119; CATATPASE. DR PRINTS; PR00121; NAKATPASE. DR SFLD; SFLDG00002; C1.7:_P-type_atpase_like; 1. DR SFLD; SFLDS00003; Haloacid_Dehalogenase; 1. DR SFLD; SFLDF00027; p-type_atpase; 1. DR SMART; SM00831; Cation_ATPase_N; 1. DR SUPFAM; SSF81653; Calcium ATPase, transduction domain A; 1. DR SUPFAM; SSF81665; Calcium ATPase, transmembrane domain M; 1. DR SUPFAM; SSF56784; HAD-like; 1. DR SUPFAM; SSF81660; Metal cation-transporting ATPase, ATP-binding domain N; 1. DR PROSITE; PS00154; ATPASE_E1_E2; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; ATP-binding; Cell membrane; Deafness; KW Disease variant; Dystonia; Epilepsy; Intellectual disability; KW Ion transport; Magnesium; Membrane; Metal-binding; Nucleotide-binding; KW Parkinsonism; Phosphoprotein; Potassium; Potassium transport; KW Proteomics identification; Reference proteome; Sodium; Sodium transport; KW Sodium/potassium transport; Translocase; Transmembrane; KW Transmembrane helix; Transport. FT CHAIN 1..1013 FT /note="Sodium/potassium-transporting ATPase subunit alpha- FT 3" FT /id="PRO_0000046298" FT TOPO_DOM 1..77 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 78..98 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 99..121 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 122..142 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 143..278 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 279..298 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 299..310 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 311..328 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 329..762 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 763..782 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 783..792 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 793..813 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 814..833 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 834..856 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 857..908 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 909..928 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 929..941 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 942..960 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 961..975 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 976..996 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 997..1013 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT REGION 1..24 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 72..74 FT /note="Interaction with phosphoinositide-3 kinase" FT /evidence="ECO:0000250" FT ACT_SITE 366 FT /note="4-aspartylphosphate intermediate" FT /evidence="ECO:0000250" FT BINDING 707 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250" FT BINDING 711 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250" FT MOD_RES 37 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P06687" FT MOD_RES 56 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q6PIC6" FT MOD_RES 218 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q6PIC6" FT MOD_RES 265 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q6PIC6" FT MOD_RES 442 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P06687" FT MOD_RES 548 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q6PIC6" FT MOD_RES 933 FT /note="Phosphoserine; by PKA" FT /evidence="ECO:0000250" FT VAR_SEQ 1..2 FT /note="MG -> MGGWEEERNRRAT (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_046956" FT VAR_SEQ 1..2 FT /note="MG -> MGSGGSDSYRIATSQ (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_046957" FT VARIANT 137 FT /note="S -> F (in AHC2; dbSNP:rs542652468)" FT /evidence="ECO:0000269|PubMed:22842232" FT /id="VAR_068935" FT VARIANT 137 FT /note="S -> Y (in AHC2; strong decrease in ATPase activity; FT dbSNP:rs542652468)" FT /evidence="ECO:0000269|PubMed:22842232, FT ECO:0000269|PubMed:24631656" FT /id="VAR_068936" FT VARIANT 140 FT /note="Q -> L (in AHC2; dbSNP:rs606231427)" FT /evidence="ECO:0000269|PubMed:22842232" FT /id="VAR_068937" FT VARIANT 220 FT /note="D -> N (in AHC2; no effect on ATPase activity; FT dbSNP:rs1396898460)" FT /evidence="ECO:0000269|PubMed:22842232, FT ECO:0000269|PubMed:24631656" FT /id="VAR_068938" FT VARIANT 274 FT /note="I -> N (in AHC2; strong decrease in ATPase activity; FT dbSNP:rs80356532)" FT /evidence="ECO:0000269|PubMed:22842232, FT ECO:0000269|PubMed:22850527, ECO:0000269|PubMed:24631656" FT /id="VAR_068939" FT VARIANT 274 FT /note="I -> T (in DYT12; dbSNP:rs80356532)" FT /evidence="ECO:0000269|PubMed:15260953" FT /id="VAR_026735" FT VARIANT 277 FT /note="E -> K (in DYT12; dbSNP:rs80356533)" FT /evidence="ECO:0000269|PubMed:15260953" FT /id="VAR_026736" FT VARIANT 292 FT /note="L -> R (in DEE99; decreased affinity for sodium FT ions; decreased affinity for potassium ions; FT dbSNP:rs2145977887)" FT /evidence="ECO:0000269|PubMed:33880529" FT /id="VAR_086446" FT VARIANT 316 FT /note="G -> V (in DEE99; decreased affinity for sodium FT ions; decreased affinity for potassium ions; FT dbSNP:rs2145977758)" FT /evidence="ECO:0000269|PubMed:33880529" FT /id="VAR_086447" FT VARIANT 320 FT /note="A -> T (found in a patient with tonic-clonic FT seizures and profound developmental delay with paroxysmal FT movement disorder; likely pathogenic; dbSNP:rs879255368)" FT /evidence="ECO:0000269|PubMed:26993267" FT /id="VAR_078699" FT VARIANT 322 FT /note="V -> D (in AHC2; dbSNP:rs606231428)" FT /evidence="ECO:0000269|PubMed:22850527" FT /id="VAR_070767" FT VARIANT 333 FT /note="C -> F (in AHC2; decreased ATPase activity; FT dbSNP:rs606231430)" FT /evidence="ECO:0000269|PubMed:22842232" FT /id="VAR_068940" FT VARIANT 361 FT /note="S -> P (in DEE99; dbSNP:rs2145972497)" FT /evidence="ECO:0000269|PubMed:33880529" FT /id="VAR_086448" FT VARIANT 371 FT /note="L -> P (in AHC2; dbSNP:rs606231433)" FT /evidence="ECO:0000269|PubMed:22850527" FT /id="VAR_070768" FT VARIANT 609 FT /note="D -> Y (in DEE99)" FT /evidence="ECO:0000269|PubMed:33880529" FT /id="VAR_086449" FT VARIANT 613 FT /note="T -> M (in DYT12; dbSNP:rs80356534)" FT /evidence="ECO:0000269|PubMed:15260953" FT /id="VAR_026737" FT VARIANT 755 FT /note="G -> C (in AHC2; dbSNP:rs557052809)" FT /evidence="ECO:0000269|PubMed:22850527, FT ECO:0000269|PubMed:23409136" FT /id="VAR_070769" FT VARIANT 755 FT /note="G -> S (in AHC2; dbSNP:rs557052809)" FT /evidence="ECO:0000269|PubMed:22842232" FT /id="VAR_068941" FT VARIANT 758 FT /note="I -> S (in DYT12; dbSNP:rs80356535)" FT /evidence="ECO:0000269|PubMed:15260953" FT /id="VAR_026738" FT VARIANT 764 FT /note="Missing (in DEE99)" FT /evidence="ECO:0000269|PubMed:33880529" FT /id="VAR_086450" FT VARIANT 772 FT /note="S -> R (in AHC2; dbSNP:rs534926223)" FT /evidence="ECO:0000269|PubMed:22850527" FT /id="VAR_070770" FT VARIANT 773 FT /note="N -> I (in AHC2; dbSNP:rs606231437)" FT /evidence="ECO:0000269|PubMed:22850527" FT /id="VAR_070771" FT VARIANT 773 FT /note="N -> S (in AHC2; dbSNP:rs606231437)" FT /evidence="ECO:0000269|PubMed:22842232" FT /id="VAR_068942" FT VARIANT 775 FT /note="P -> R (in DEE99)" FT /evidence="ECO:0000269|PubMed:33880529" FT /id="VAR_086451" FT VARIANT 780 FT /note="F -> L (in DYT12; dbSNP:rs80356536)" FT /evidence="ECO:0000269|PubMed:15260953" FT /id="VAR_026739" FT VARIANT 801 FT /note="D -> N (in AHC2 and DEE99; strong decrease in ATPase FT activity; dbSNP:rs80356537)" FT /evidence="ECO:0000269|PubMed:22842232, FT ECO:0000269|PubMed:22850527, ECO:0000269|PubMed:23409136, FT ECO:0000269|PubMed:24631656, ECO:0000269|PubMed:33880529" FT /id="VAR_068943" FT VARIANT 801 FT /note="D -> Y (in DYT12; dbSNP:rs80356537)" FT /evidence="ECO:0000269|PubMed:15260953" FT /id="VAR_026740" FT VARIANT 806 FT /note="M -> R (in AHC2; dbSNP:rs549006436)" FT /evidence="ECO:0000269|PubMed:22842232" FT /id="VAR_068944" FT VARIANT 810 FT /note="I -> S (in AHC2; dbSNP:rs536681257)" FT /evidence="ECO:0000269|PubMed:22842232" FT /id="VAR_068945" FT VARIANT 811 FT /note="S -> P (in AHC2; decreased ATPase activity; FT dbSNP:rs387907282)" FT /evidence="ECO:0000269|PubMed:22842232" FT /id="VAR_068946" FT VARIANT 815 FT /note="E -> K (in AHC2; strong decrease in ATPase activity; FT dbSNP:rs387907281)" FT /evidence="ECO:0000269|PubMed:22842232, FT ECO:0000269|PubMed:22850527, ECO:0000269|PubMed:23409136, FT ECO:0000269|PubMed:24631656" FT /id="VAR_068947" FT VARIANT 818 FT /note="E -> K (in CAPOS; dbSNP:rs587777771)" FT /evidence="ECO:0000269|PubMed:24468074" FT /id="VAR_070772" FT VARIANT 857 FT /note="Missing (in DEE99)" FT /evidence="ECO:0000269|PubMed:33880529" FT /id="VAR_086452" FT VARIANT 887 FT /note="D -> Y (in DEE99; decreased sodium/potassium- FT exchanging ATPase activity)" FT /evidence="ECO:0000269|PubMed:33880529" FT /id="VAR_086453" FT VARIANT 888 FT /note="L -> P (in DEE99)" FT /evidence="ECO:0000269|PubMed:33880529" FT /id="VAR_086454" FT VARIANT 893 FT /note="G -> W (in DEE99)" FT /evidence="ECO:0000269|PubMed:33880529" FT /id="VAR_086455" FT VARIANT 919 FT /note="Missing (in AHC2; dbSNP:rs606231443)" FT /evidence="ECO:0000269|PubMed:22842232" FT /id="VAR_068948" FT VARIANT 923 FT /note="D -> N (in DYT12; dbSNP:rs267606670)" FT /evidence="ECO:0000269|PubMed:19652145" FT /id="VAR_068949" FT VARIANT 923 FT /note="D -> Y (in AHC2; dbSNP:rs267606670)" FT /evidence="ECO:0000269|PubMed:22850527" FT /id="VAR_070773" FT VARIANT 924 FT /note="L -> P (in DEE99; dbSNP:rs1555859157)" FT /evidence="ECO:0000269|PubMed:33880529" FT /id="VAR_086456" FT VARIANT 927 FT /note="C -> Y (in AHC2; dbSNP:rs606231444)" FT /evidence="ECO:0000269|PubMed:23409136" FT /id="VAR_070774" FT VARIANT 947 FT /note="G -> R (in AHC2; strong decrease in ATPase activity; FT dbSNP:rs398122887)" FT /evidence="ECO:0000269|PubMed:22842232, FT ECO:0000269|PubMed:24631656, ECO:0000269|PubMed:26993267" FT /id="VAR_068950" FT VARIANT 955 FT /note="A -> D (in AHC2; dbSNP:rs606231446)" FT /evidence="ECO:0000269|PubMed:22842232" FT /id="VAR_068951" FT VARIANT 972 FT /note="Missing (in DEE99; decreased sodium/potassium- FT exchanging ATPase activity)" FT /evidence="ECO:0000269|PubMed:33880529" FT /id="VAR_086457" FT VARIANT 992 FT /note="D -> Y (in AHC2; dbSNP:rs606231447)" FT /evidence="ECO:0000269|PubMed:22842232" FT /id="VAR_068952" FT VARIANT 1013 FT /note="Y -> YY (in DYT12; there is a drastic 40- to 50-fold FT reduction in Na(+) affinity in the mutant protein)" FT /evidence="ECO:0000269|PubMed:19351654" FT /id="VAR_068953" FT CONFLICT 1..2 FT /note="MG -> MEIH (in Ref. 2; CAA31390)" FT /evidence="ECO:0000305" FT CONFLICT 144 FT /note="S -> R (in Ref. 3; BAH12387)" FT /evidence="ECO:0000305" FT CONFLICT 336 FT /note="L -> V (in Ref. 1; AAA51798, 2; CAA31390, 6; FT AAA52285 and 8; AAA58380)" FT /evidence="ECO:0000305" FT CONFLICT 380 FT /note="H -> T (in Ref. 6; AAA52285)" FT /evidence="ECO:0000305" FT CONFLICT 421 FT /note="A -> P (in Ref. 8; AAA58380)" FT /evidence="ECO:0000305" FT CONFLICT 430 FT /note="I -> M (in Ref. 2; CAA31390)" FT /evidence="ECO:0000305" FT CONFLICT 555..557 FT /note="FPK -> YPQ (in Ref. 1; AAA51798, 2; CAA31390 and 6; FT AAA52286)" FT /evidence="ECO:0000305" FT CONFLICT 577 FT /note="G -> P (in Ref. 1; AAA51798)" FT /evidence="ECO:0000305" FT CONFLICT 583 FT /note="D -> G (in Ref. 1; AAA51798, 2; CAA31390 and 6; FT AAA52286)" FT /evidence="ECO:0000305" FT CONFLICT 919 FT /note="V -> A (in Ref. 6; AAA52286)" FT /evidence="ECO:0000305" FT CONFLICT 944 FT /note="L -> M (in Ref. 6; AAA52286)" FT /evidence="ECO:0000305" FT CONFLICT 982 FT /note="F -> S (in Ref. 2; CAA31390)" FT /evidence="ECO:0000305" FT CONFLICT 1006 FT /note="W -> S (in Ref. 1; AAA51798)" FT /evidence="ECO:0000305" FT STRAND 34..36 FT /evidence="ECO:0007829|PDB:8D3V" FT HELIX 38..42 FT /evidence="ECO:0007829|PDB:8D3V" FT HELIX 43..45 FT /evidence="ECO:0007829|PDB:8D3V" FT TURN 49..51 FT /evidence="ECO:0007829|PDB:8D3V" FT HELIX 57..65 FT /evidence="ECO:0007829|PDB:8D3V" FT HELIX 80..86 FT /evidence="ECO:0007829|PDB:8D3V" FT HELIX 89..91 FT /evidence="ECO:0007829|PDB:8D3V" FT HELIX 92..106 FT /evidence="ECO:0007829|PDB:8D3V" FT HELIX 120..139 FT /evidence="ECO:0007829|PDB:8D3V" FT HELIX 142..148 FT /evidence="ECO:0007829|PDB:8D3V" FT HELIX 149..152 FT /evidence="ECO:0007829|PDB:8D3V" FT STRAND 158..162 FT /evidence="ECO:0007829|PDB:8D3V" FT STRAND 167..171 FT /evidence="ECO:0007829|PDB:8D3V" FT HELIX 172..174 FT /evidence="ECO:0007829|PDB:8D3W" FT STRAND 177..184 FT /evidence="ECO:0007829|PDB:8D3V" FT STRAND 190..198 FT /evidence="ECO:0007829|PDB:8D3V" FT STRAND 200..204 FT /evidence="ECO:0007829|PDB:8D3V" FT STRAND 207..209 FT /evidence="ECO:0007829|PDB:8D3V" FT STRAND 215..217 FT /evidence="ECO:0007829|PDB:8D3V" FT HELIX 226..228 FT /evidence="ECO:0007829|PDB:8D3V" FT STRAND 230..233 FT /evidence="ECO:0007829|PDB:8D3V" FT STRAND 238..250 FT /evidence="ECO:0007829|PDB:8D3V" FT STRAND 254..256 FT /evidence="ECO:0007829|PDB:8D3V" FT HELIX 273..303 FT /evidence="ECO:0007829|PDB:8D3V" FT TURN 306..308 FT /evidence="ECO:0007829|PDB:8D3V" FT HELIX 309..321 FT /evidence="ECO:0007829|PDB:8D3V" FT HELIX 326..343 FT /evidence="ECO:0007829|PDB:8D3V" FT STRAND 347..351 FT /evidence="ECO:0007829|PDB:8D3V" FT HELIX 352..355 FT /evidence="ECO:0007829|PDB:8D3V" FT STRAND 356..359 FT /evidence="ECO:0007829|PDB:8D3V" FT STRAND 362..366 FT /evidence="ECO:0007829|PDB:8D3V" FT HELIX 367..371 FT /evidence="ECO:0007829|PDB:8D3V" FT STRAND 377..383 FT /evidence="ECO:0007829|PDB:8D3V" FT STRAND 386..389 FT /evidence="ECO:0007829|PDB:8D3V" FT STRAND 403..405 FT /evidence="ECO:0007829|PDB:8D3W" FT HELIX 406..415 FT /evidence="ECO:0007829|PDB:8D3V" FT STRAND 416..418 FT /evidence="ECO:0007829|PDB:8D3W" FT STRAND 428..430 FT /evidence="ECO:0007829|PDB:8D3V" FT TURN 432..434 FT /evidence="ECO:0007829|PDB:8D3V" FT HELIX 441..451 FT /evidence="ECO:0007829|PDB:8D3V" FT HELIX 457..463 FT /evidence="ECO:0007829|PDB:8D3V" FT STRAND 466..470 FT /evidence="ECO:0007829|PDB:8D3W" FT TURN 474..476 FT /evidence="ECO:0007829|PDB:8D3V" FT STRAND 482..484 FT /evidence="ECO:0007829|PDB:8D3V" FT STRAND 488..490 FT /evidence="ECO:0007829|PDB:8D3V" FT STRAND 493..495 FT /evidence="ECO:0007829|PDB:8D3V" FT HELIX 501..507 FT /evidence="ECO:0007829|PDB:8D3V" FT STRAND 508..513 FT /evidence="ECO:0007829|PDB:8D3V" FT STRAND 516..519 FT /evidence="ECO:0007829|PDB:8D3V" FT HELIX 522..536 FT /evidence="ECO:0007829|PDB:8D3V" FT TURN 537..539 FT /evidence="ECO:0007829|PDB:8D3V" FT STRAND 540..545 FT /evidence="ECO:0007829|PDB:8D3V" FT STRAND 548..550 FT /evidence="ECO:0007829|PDB:8D3W" FT TURN 552..554 FT /evidence="ECO:0007829|PDB:8D3V" FT STRAND 563..565 FT /evidence="ECO:0007829|PDB:8D3V" FT STRAND 573..575 FT /evidence="ECO:0007829|PDB:8D3V" FT STRAND 577..582 FT /evidence="ECO:0007829|PDB:8D3V" FT HELIX 589..598 FT /evidence="ECO:0007829|PDB:8D3V" FT STRAND 602..606 FT /evidence="ECO:0007829|PDB:8D3V" FT HELIX 611..621 FT /evidence="ECO:0007829|PDB:8D3V" FT HELIX 631..638 FT /evidence="ECO:0007829|PDB:8D3V" FT HELIX 642..644 FT /evidence="ECO:0007829|PDB:8D3V" FT HELIX 647..649 FT /evidence="ECO:0007829|PDB:8D3W" FT STRAND 652..656 FT /evidence="ECO:0007829|PDB:8D3V" FT HELIX 657..660 FT /evidence="ECO:0007829|PDB:8D3V" FT HELIX 665..674 FT /evidence="ECO:0007829|PDB:8D3V" FT STRAND 676..682 FT /evidence="ECO:0007829|PDB:8D3V" FT HELIX 685..695 FT /evidence="ECO:0007829|PDB:8D3V" FT HELIX 696..698 FT /evidence="ECO:0007829|PDB:8D3V" FT STRAND 702..705 FT /evidence="ECO:0007829|PDB:8D3V" FT HELIX 709..711 FT /evidence="ECO:0007829|PDB:8D3V" FT HELIX 712..717 FT /evidence="ECO:0007829|PDB:8D3V" FT STRAND 718..724 FT /evidence="ECO:0007829|PDB:8D3V" FT TURN 725..727 FT /evidence="ECO:0007829|PDB:8D3V" FT HELIX 730..735 FT /evidence="ECO:0007829|PDB:8D3V" FT STRAND 736..743 FT /evidence="ECO:0007829|PDB:8D3V" FT HELIX 746..771 FT /evidence="ECO:0007829|PDB:8D3V" FT HELIX 774..785 FT /evidence="ECO:0007829|PDB:8D3V" FT HELIX 794..801 FT /evidence="ECO:0007829|PDB:8D3V" FT TURN 802..806 FT /evidence="ECO:0007829|PDB:8D3V" FT HELIX 808..814 FT /evidence="ECO:0007829|PDB:8D3V" FT TURN 819..822 FT /evidence="ECO:0007829|PDB:8D3V" FT TURN 829..831 FT /evidence="ECO:0007829|PDB:8D3V" FT HELIX 837..843 FT /evidence="ECO:0007829|PDB:8D3V" FT TURN 844..846 FT /evidence="ECO:0007829|PDB:8D3V" FT HELIX 847..865 FT /evidence="ECO:0007829|PDB:8D3V" FT HELIX 870..872 FT /evidence="ECO:0007829|PDB:8D3V" FT TURN 874..876 FT /evidence="ECO:0007829|PDB:8D3V" FT HELIX 877..880 FT /evidence="ECO:0007829|PDB:8D3V" FT HELIX 898..926 FT /evidence="ECO:0007829|PDB:8D3V" FT STRAND 930..932 FT /evidence="ECO:0007829|PDB:8D3V" FT HELIX 934..936 FT /evidence="ECO:0007829|PDB:8D3V" FT HELIX 942..958 FT /evidence="ECO:0007829|PDB:8D3V" FT HELIX 964..967 FT /evidence="ECO:0007829|PDB:8D3V" FT HELIX 975..979 FT /evidence="ECO:0007829|PDB:8D3V" FT HELIX 982..1001 FT /evidence="ECO:0007829|PDB:8D3V" FT HELIX 1006..1010 FT /evidence="ECO:0007829|PDB:8D3V" SQ SEQUENCE 1013 AA; 111749 MW; BF28CD9F1E11AF48 CRC64; MGDKKDDKDS PKKNKGKERR DLDDLKKEVA MTEHKMSVEE VCRKYNTDCV QGLTHSKAQE ILARDGPNAL TPPPTTPEWV KFCRQLFGGF SILLWIGAIL CFLAYGIQAG TEDDPSGDNL YLGIVLAAVV IITGCFSYYQ EAKSSKIMES FKNMVPQQAL VIREGEKMQV NAEEVVVGDL VEIKGGDRVP ADLRIISAHG CKVDNSSLTG ESEPQTRSPD CTHDNPLETR NITFFSTNCV EGTARGVVVA TGDRTVMGRI ATLASGLEVG KTPIAIEIEH FIQLITGVAV FLGVSFFILS LILGYTWLEA VIFLIGIIVA NVPEGLLATV TVCLTLTAKR MARKNCLVKN LEAVETLGST STICSDKTGT LTQNRMTVAH MWFDNQIHEA DTTEDQSGTS FDKSSHTWVA LSHIAGLCNR AVFKGGQDNI PVLKRDVAGD ASESALLKCI ELSSGSVKLM RERNKKVAEI PFNSTNKYQL SIHETEDPND NRYLLVMKGA PERILDRCST ILLQGKEQPL DEEMKEAFQN AYLELGGLGE RVLGFCHYYL PEEQFPKGFA FDCDDVNFTT DNLCFVGLMS MIDPPRAAVP DAVGKCRSAG IKVIMVTGDH PITAKAIAKG VGIISEGNET VEDIAARLNI PVSQVNPRDA KACVIHGTDL KDFTSEQIDE ILQNHTEIVF ARTSPQQKLI IVEGCQRQGA IVAVTGDGVN DSPALKKADI GVAMGIAGSD VSKQAADMIL LDDNFASIVT GVEEGRLIFD NLKKSIAYTL TSNIPEITPF LLFIMANIPL PLGTITILCI DLGTDMVPAI SLAYEAAESD IMKRQPRNPR TDKLVNERLI SMAYGQIGMI QALGGFFSYF VILAENGFLP GNLVGIRLNW DDRTVNDLED SYGQQWTYEQ RKVVEFTCHT AFFVSIVVVQ WADLIICKTR RNSVFQQGMK NKILIFGLFE ETALAAFLSY CPGMDVALRM YPLKPSWWFC AFPYSFLIFV YDEIRKLILR RNPGGWVEKE TYY //