AT1A3_HUMAN
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 03-AUG-2022, entry version 231.
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 AND LYS-815.
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=ATP + H2O + K(+)(out) + Na(+)(in) = ADP + H(+) + K(+)(in) +
CC Na(+)(out) + phosphate; 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}.
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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_001256213.1. [P13637-2]
DR RefSeq; NP_001243143.1; NM_001256214.1. [P13637-3]
DR RefSeq; NP_689509.1; NM_152296.4. [P13637-1]
DR AlphaFoldDB; P13637; -.
DR SMR; P13637; -.
DR BioGRID; 106968; 315.
DR IntAct; P13637; 31.
DR MINT; P13637; -.
DR STRING; 9606.ENSP00000444688; -.
DR ChEMBL; CHEMBL2095186; -.
DR DrugBank; DB09020; Bisacodyl.
DR DrugBank; DB01092; Ouabain.
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 EPD; P13637; -.
DR jPOST; P13637; -.
DR MassIVE; P13637; -.
DR MaxQB; P13637; -.
DR PaxDb; P13637; -.
DR PeptideAtlas; P13637; -.
DR PRIDE; P13637; -.
DR ProteomicsDB; 27209; -.
DR ProteomicsDB; 52946; -. [P13637-1]
DR ProteomicsDB; 6459; -.
DR Antibodypedia; 30869; 210 antibodies from 30 providers.
DR DNASU; 478; -.
DR Ensembl; ENST00000543770.5; ENSP00000437577.1; ENSG00000105409.19. [P13637-2]
DR Ensembl; ENST00000545399.6; ENSP00000444688.1; ENSG00000105409.19. [P13637-3]
DR Ensembl; ENST00000648268.1; ENSP00000498113.1; ENSG00000105409.19. [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 CTD; 478; -.
DR DisGeNET; 478; -.
DR GeneCards; ATP1A3; -.
DR GeneReviews; ATP1A3; -.
DR HGNC; HGNC:801; ATP1A3.
DR HPA; ENSG00000105409; Group enriched (brain, 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 neXtProt; NX_P13637; -.
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 PharmGKB; PA64; -.
DR VEuPathDB; HostDB:ENSG00000105409; -.
DR eggNOG; KOG0203; Eukaryota.
DR GeneTree; ENSGT00940000160476; -.
DR InParanoid; P13637; -.
DR OMA; RRFLTYH; -.
DR PhylomeDB; P13637; -.
DR TreeFam; TF312838; -.
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 BioGRID-ORCS; 478; 18 hits in 1071 CRISPR screens.
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 94 other tissues.
DR ExpressionAtlas; P13637; baseline and differential.
DR Genevisible; P13637; HS.
DR GO; GO:0030424; C:axon; IDA:ARUK-UCL.
DR GO; GO:0044305; C:calyx of Held; IEA:Ensembl.
DR GO; GO:0044327; C:dendritic spine head; IEA:Ensembl.
DR GO; GO:0044326; C:dendritic spine neck; IEA:Ensembl.
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:0016021; C:integral component of membrane; NAS:UniProtKB.
DR GO; GO:0099056; C:integral component of presynaptic membrane; IEA:Ensembl.
DR GO; GO:0016020; C:membrane; ISS:ARUK-UCL.
DR GO; GO:0043209; C:myelin sheath; IEA:Ensembl.
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:0019829; F:ATPase-coupled cation transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0051087; F:chaperone binding; IPI:BHF-UCL.
DR GO; GO:0031748; F:D1 dopamine receptor binding; IEA:Ensembl.
DR GO; GO:0099520; F:ion antiporter activity involved in regulation of presynaptic membrane potential; IMP:SynGO.
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: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:0030007; P:cellular potassium ion homeostasis; IDA:BHF-UCL.
DR GO; GO:1904646; P:cellular response to amyloid-beta; ISS:ARUK-UCL.
DR GO; GO:0071300; P:cellular response to retinoic acid; IEA:Ensembl.
DR GO; GO:0071383; P:cellular response to steroid hormone stimulus; NAS:BHF-UCL.
DR GO; GO:0097067; P:cellular response to thyroid hormone stimulus; IEA:Ensembl.
DR GO; GO:0006883; P:cellular sodium ion homeostasis; IDA:BHF-UCL.
DR GO; GO:0021987; P:cerebral cortex development; IEA:Ensembl.
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 Gene3D; 3.40.1110.10; -; 1.
DR Gene3D; 3.40.50.1000; -; 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; 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 Pfam; PF00689; Cation_ATPase_C; 1.
DR Pfam; PF00690; Cation_ATPase_N; 1.
DR SFLD; SFLDF00027; p-type_atpase; 1.
DR SMART; SM00831; Cation_ATPase_N; 1.
DR SUPFAM; SSF56784; SSF56784; 1.
DR SUPFAM; SSF81653; SSF81653; 1.
DR SUPFAM; SSF81660; SSF81660; 1.
DR SUPFAM; SSF81665; SSF81665; 1.
DR TIGRFAMs; TIGR01106; ATPase-IIC_X-K; 1.
DR TIGRFAMs; TIGR01494; ATPase_P-type; 2.
DR PROSITE; PS00154; ATPASE_E1_E2; 1.
PE 1: Evidence at protein level;
KW 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 Reference proteome; Sodium; Sodium transport; Sodium/potassium transport;
KW Translocase; Transmembrane; 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 /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 /evidence="ECO:0000269|PubMed:33880529"
FT /id="VAR_086447"
FT VARIANT 320
FT /note="A -> T (probable disease-associated variant found in
FT a patient with tonic-clonic seizures associated with
FT profound developmental delay and paroxysmal movement
FT disorder; 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)"
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)"
FT /evidence="ECO:0000269|PubMed:33880529"
FT /id="VAR_086456"
FT VARIANT 927
FT /note="C -> Y (in AHC2; dbSNP:rs606231444)"
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"
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
