AT1A2_HUMAN
ID AT1A2_HUMAN Reviewed; 1020 AA.
AC P50993; D3DVE4; Q07059; Q5JW74; Q86UZ5; Q9UQ25;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 213.
DE RecName: Full=Sodium/potassium-transporting ATPase subunit alpha-2;
DE Short=Na(+)/K(+) ATPase alpha-2 subunit;
DE EC=7.2.2.13;
DE AltName: Full=Sodium pump subunit alpha-2;
DE Flags: Precursor;
GN Name=ATP1A2; Synonyms=KIAA0778;
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].
RX PubMed=2477373; DOI=10.1016/s0021-9258(18)71525-1;
RA Shull M.M., Pugh D.G., Lingrel J.B.;
RT "Characterization of the human Na,K-ATPase alpha 2 gene and identification
RT of intragenic restriction fragment length polymorphisms.";
RL J. Biol. Chem. 264:17532-17543(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=9872452; DOI=10.1093/dnares/5.5.277;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Miyajima N., Tanaka A.,
RA Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XI. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 5:277-286(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Ovary;
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 [MRNA] OF 211-249.
RC TISSUE=Leukocyte;
RX PubMed=3035563; DOI=10.1073/pnas.84.12.4039;
RA Shull M.M., Lingrel J.B.;
RT "Multiple genes encode the human Na+,K+-ATPase catalytic subunit.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:4039-4043(1987).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 251-442.
RC TISSUE=Brain, and Placenta;
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 [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-4.
RX PubMed=2537767; DOI=10.1016/0014-5793(89)80588-5;
RA Sverdlov E.D., Bessarab D.A., Malyshev I.V., Petrukhin K.E., Smirnov Y.V.,
RA Ushkaryov Y.A., Monastyrskaya G.S., Broude N.E., Modyanov N.N.;
RT "Family of human Na+,K+-ATPase genes. Structure of the putative regulatory
RT region of the alpha+-gene.";
RL FEBS Lett. 244:481-483(1989).
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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-570 AND SER-587, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [11]
RP VARIANTS FHM2 GLN-689 AND THR-731.
RX PubMed=12953268; DOI=10.1002/ana.10674;
RA Vanmolkot K.R.J., Kors E.E., Hottenga J.-J., Terwindt G.M., Haan J.,
RA Hoefnagels W.A.J., Black D.F., Sandkuijl L.A., Frants R.R., Ferrari M.D.,
RA van den Maagdenberg A.M.J.M.;
RT "Novel mutations in the Na+, K+-ATPase pump gene ATP1A2 associated with
RT familial hemiplegic migraine and benign familial infantile convulsions.";
RL Ann. Neurol. 54:360-366(2003).
RN [12]
RP VARIANTS FHM2 PRO-764 AND ARG-887, AND CHARACTERIZATION OF VARIANTS FMH2
RP PRO-764 AND ARG-887.
RX PubMed=12539047; DOI=10.1038/ng1081;
RA De Fusco M., Marconi R., Silvestri L., Atorino L., Rampoldi L.,
RA Morgante L., Ballabio A., Aridon P., Casari G.;
RT "Haploinsufficiency of ATP1A2 encoding the Na+/K+ pump alpha2 subunit
RT associated with familial hemiplegic migraine type 2.";
RL Nat. Genet. 33:192-196(2003).
RN [13]
RP VARIANT AHC1 ASN-378.
RX PubMed=15174025; DOI=10.1002/ana.20134;
RA Swoboda K.J., Kanavakis E., Xaidara A., Johnson J.E., Leppert M.F.,
RA Schlesinger-Massart M.B., Ptacek L.J., Silver K., Youroukos S.;
RT "Alternating hemiplegia of childhood or familial hemiplegic migraine? A
RT novel ATP1A2 mutation.";
RL Ann. Neurol. 55:884-887(2004).
RN [14]
RP VARIANT FHM2 ARG-715.
RX PubMed=21352219; DOI=10.1111/j.1526-4610.2010.01793.x;
RA De Sanctis S., Grieco G.S., Breda L., Casali C., Nozzi M., Del Torto M.,
RA Chiarelli F., Verrotti A.;
RT "Prolonged sporadic hemiplegic migraine associated with a novel de novo
RT missense ATP1A2 gene mutation.";
RL Headache 51:447-450(2011).
RN [15]
RP VARIANT FHM2 TRP-1007.
RX PubMed=23838748; DOI=10.1177/0333102413495116;
RA Pisano T., Spiller S., Mei D., Guerrini R., Cianchetti C., Friedrich T.,
RA Pruna D.;
RT "Functional characterization of a novel C-terminal ATP1A2 mutation causing
RT hemiplegic migraine and epilepsy.";
RL Cephalalgia 33:1302-1310(2013).
RN [16]
RP VARIANT FHM2 SER-874.
RX PubMed=23918834; DOI=10.1177/0333102413498941;
RA Costa C., Prontera P., Sarchielli P., Tonelli A., Bassi M.T., Cupini L.M.,
RA Caproni S., Siliquini S., Donti E., Calabresi P.;
RT "A novel ATP1A2 gene mutation in familial hemiplegic migraine and
RT epilepsy.";
RL Cephalalgia 34:68-72(2014).
RN [17]
RP VARIANTS DEE98 ALA-366 AND TRP-593.
RX PubMed=27864847; DOI=10.1002/humu.23149;
RG Clinical Study Group;
RA Parrini E., Marini C., Mei D., Galuppi A., Cellini E., Pucatti D.,
RA Chiti L., Rutigliano D., Bianchini C., Virdo S., De Vita D., Bigoni S.,
RA Barba C., Mari F., Montomoli M., Pisano T., Rosati A., Guerrini R.;
RT "Diagnostic targeted resequencing in 349 patients with drug-resistant
RT pediatric epilepsies identifies causative mutations in 30 different
RT genes.";
RL Hum. Mutat. 38:216-225(2017).
RN [18]
RP VARIANT FARIMPD 957-GLU--TYR-1020 DEL, AND INVOLVEMENT IN FARIMPD.
RX PubMed=31608932; DOI=10.1093/brain/awz272;
RA Chatron N., Cabet S., Alix E., Buenerd A., Cox P., Guibaud L., Labalme A.,
RA Marks P., Osio D., Putoux A., Sanlaville D., Lesca G., Vasiljevic A.;
RT "A novel lethal recognizable polymicrogyric syndrome caused by ATP1A2
RT homozygous truncating variants.";
RL Brain 142:3367-3374(2019).
RN [19]
RP INVOLVEMENT IN FARIMPD.
RX PubMed=30690204; DOI=10.1016/j.ejmg.2019.01.014;
RA Monteiro F.P., Curry C.J., Hevner R., Elliott S., Fisher J.H., Turocy J.,
RA Dobyns W.B., Costa L.A., Freitas E., Kitajima J.P., Kok F.;
RT "Biallelic loss of function variants in ATP1A2 cause hydrops fetalis,
RT microcephaly, arthrogryposis and extensive cortical malformations.";
RL Eur. J. Med. Genet. 63:103624-103624(2020).
RN [20]
RP VARIANTS DEE98 MET-293; PHE-341; ALA-366 AND GLN-908, INVOLVEMENT IN DEE98,
RP FUNCTION, CHARACTERIZATION OF VARIANTS DEE98 MET-293; ALA-366 AND GLN-908,
RP VARIANT GLN-593, AND CHARACTERIZATION OF VARIANT GLN-593.
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, providing the energy
CC 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:A2VDL6}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:7711835}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:7711835}. Cell membrane
CC {ECO:0000269|PubMed:7711835}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:7711835}.
CC -!- DISEASE: Migraine, familial hemiplegic, 2 (FHM2) [MIM:602481]: A
CC subtype of migraine with aura associated with hemiparesis in some
CC families. Migraine is a disabling symptom complex of periodic
CC headaches, usually temporal and unilateral. Headaches are often
CC accompanied by irritability, nausea, vomiting and photophobia, preceded
CC by constriction of the cranial arteries. Migraine with aura is
CC characterized by recurrent attacks of reversible neurological symptoms
CC (aura) that precede or accompany the headache. Aura may include a
CC combination of sensory disturbances, such as blurred vision,
CC hallucinations, vertigo, numbness and difficulty in concentrating and
CC speaking. {ECO:0000269|PubMed:12539047, ECO:0000269|PubMed:12953268,
CC ECO:0000269|PubMed:21352219, ECO:0000269|PubMed:23838748,
CC ECO:0000269|PubMed:23918834}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Alternating hemiplegia of childhood 1 (AHC1) [MIM:104290]: 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:15174025}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Fetal akinesia, respiratory insufficiency, microcephaly,
CC polymicrogyria, and dysmorphic facies (FARIMPD) [MIM:619602]: An
CC autosomal recessive disease characterized by fetal akinesia, and
CC generalized joint contractures and arthrogryposis at birth. Affected
CC newborns have severe respiratory insufficiency and significant
CC dysmorphic facial features. Malformations of cortical development are
CC seen on brain imaging, most commonly polymicrogyria or other gyral
CC anomalies. Death usually occurs in infancy.
CC {ECO:0000269|PubMed:30690204, ECO:0000269|PubMed:31608932}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Developmental and epileptic encephalopathy 98 (DEE98)
CC [MIM:619605]: 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. DEE98 is an autosomal dominant form characterized by
CC onset of seizures in the first decade. {ECO:0000269|PubMed:27864847,
CC ECO:0000269|PubMed:33880529}. Note=The disease is caused by variants
CC affecting the gene represented 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 -!- SEQUENCE CAUTION:
CC Sequence=BAA34498.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; J05096; AAA51797.1; -; Genomic_DNA.
DR EMBL; AB018321; BAA34498.2; ALT_INIT; mRNA.
DR EMBL; AL121987; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471121; EAW52740.1; -; Genomic_DNA.
DR EMBL; CH471121; EAW52741.1; -; Genomic_DNA.
DR EMBL; BC052271; AAH52271.2; -; mRNA.
DR EMBL; M16795; AAA51799.1; -; mRNA.
DR EMBL; M27578; AAA35575.1; -; Genomic_DNA.
DR EMBL; M27571; AAA35575.1; JOINED; Genomic_DNA.
DR EMBL; M27576; AAA35575.1; JOINED; Genomic_DNA.
DR EMBL; Y07494; CAA68793.1; ALT_SEQ; mRNA.
DR CCDS; CCDS1196.1; -.
DR PIR; A34474; A34474.
DR RefSeq; NP_000693.1; NM_000702.3.
DR AlphaFoldDB; P50993; -.
DR SMR; P50993; -.
DR BioGRID; 106967; 39.
DR IntAct; P50993; 19.
DR MINT; P50993; -.
DR STRING; 9606.ENSP00000354490; -.
DR BindingDB; P50993; -.
DR ChEMBL; CHEMBL2095186; -.
DR DrugBank; DB09020; Bisacodyl.
DR DrugBank; DB01092; Ouabain.
DR DrugBank; DB09479; Rubidium Rb-82.
DR DrugBank; DB16690; Tegoprazan.
DR DrugCentral; P50993; -.
DR TCDB; 3.A.3.1.1; the p-type atpase (p-atpase) superfamily.
DR GlyGen; P50993; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P50993; -.
DR PhosphoSitePlus; P50993; -.
DR SwissPalm; P50993; -.
DR BioMuta; ATP1A2; -.
DR DMDM; 1703467; -.
DR EPD; P50993; -.
DR jPOST; P50993; -.
DR MassIVE; P50993; -.
DR MaxQB; P50993; -.
DR PaxDb; P50993; -.
DR PeptideAtlas; P50993; -.
DR PRIDE; P50993; -.
DR ProteomicsDB; 56274; -.
DR Antibodypedia; 34270; 170 antibodies from 27 providers.
DR DNASU; 477; -.
DR Ensembl; ENST00000361216.8; ENSP00000354490.3; ENSG00000018625.15.
DR GeneID; 477; -.
DR KEGG; hsa:477; -.
DR MANE-Select; ENST00000361216.8; ENSP00000354490.3; NM_000702.4; NP_000693.1.
DR UCSC; uc001fvc.4; human.
DR CTD; 477; -.
DR DisGeNET; 477; -.
DR GeneCards; ATP1A2; -.
DR GeneReviews; ATP1A2; -.
DR HGNC; HGNC:800; ATP1A2.
DR HPA; ENSG00000018625; Tissue enhanced (brain, skeletal muscle, tongue).
DR MalaCards; ATP1A2; -.
DR MIM; 104290; phenotype.
DR MIM; 182340; gene.
DR MIM; 602481; phenotype.
DR MIM; 619602; phenotype.
DR MIM; 619605; phenotype.
DR neXtProt; NX_P50993; -.
DR OpenTargets; ENSG00000018625; -.
DR Orphanet; 2131; Alternating hemiplegia of childhood.
DR Orphanet; 569; Familial or sporadic hemiplegic migraine.
DR Orphanet; 442835; Non-specific early-onset epileptic encephalopathy.
DR PharmGKB; PA30796; -.
DR VEuPathDB; HostDB:ENSG00000018625; -.
DR eggNOG; KOG0203; Eukaryota.
DR GeneTree; ENSGT00940000159936; -.
DR InParanoid; P50993; -.
DR OMA; RYCAMTG; -.
DR OrthoDB; 388324at2759; -.
DR PhylomeDB; P50993; -.
DR TreeFam; TF312838; -.
DR PathwayCommons; P50993; -.
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; P50993; -.
DR BioGRID-ORCS; 477; 17 hits in 1068 CRISPR screens.
DR ChiTaRS; ATP1A2; human.
DR GeneWiki; ATP1A2; -.
DR GenomeRNAi; 477; -.
DR Pharos; P50993; Tclin.
DR PRO; PR:P50993; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P50993; protein.
DR Bgee; ENSG00000018625; Expressed in lateral globus pallidus and 182 other tissues.
DR ExpressionAtlas; P50993; baseline and differential.
DR Genevisible; P50993; HS.
DR GO; GO:0005901; C:caveola; IEA:Ensembl.
DR GO; GO:0042995; C:cell projection; ISS:ARUK-UCL.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0043197; C:dendritic spine; IEA:Ensembl.
DR GO; GO:0005768; C:endosome; IEA:Ensembl.
DR GO; GO:1903561; C:extracellular vesicle; HDA:UniProtKB.
DR GO; GO:0014704; C:intercalated disc; IEA:Ensembl.
DR GO; GO:0016020; C:membrane; IDA:BHF-UCL.
DR GO; GO:0043025; C:neuronal cell body; ISS:ARUK-UCL.
DR GO; GO:0031090; C:organelle membrane; IGI: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:0030315; C:T-tubule; IGI:ARUK-UCL.
DR GO; GO:0005524; F:ATP binding; IMP:BHF-UCL.
DR GO; GO:0016887; F:ATP hydrolysis activity; IMP:BHF-UCL.
DR GO; GO:0019829; F:ATPase-coupled cation transmembrane transporter activity; IDA:ARUK-UCL.
DR GO; GO:0051087; F:chaperone binding; IPI:BHF-UCL.
DR GO; GO:0005391; F:P-type sodium:potassium-exchanging transporter activity; IDA:BHF-UCL.
DR GO; GO:0016791; F:phosphatase activity; ISS:ARUK-UCL.
DR GO; GO:0030955; F:potassium ion binding; IMP:BHF-UCL.
DR GO; GO:0046982; F:protein heterodimerization activity; ISS:ARUK-UCL.
DR GO; GO:0031402; F:sodium ion binding; IMP:BHF-UCL.
DR GO; GO:0005496; F:steroid binding; IPI:BHF-UCL.
DR GO; GO:1990239; F:steroid hormone binding; IDA:BHF-UCL.
DR GO; GO:0008344; P:adult locomotory behavior; IEA:Ensembl.
DR GO; GO:0021764; P:amygdala development; ISS:ARUK-UCL.
DR GO; GO:0046034; P:ATP metabolic process; IMP:BHF-UCL.
DR GO; GO:0001662; P:behavioral fear response; ISS:ARUK-UCL.
DR GO; GO:0060048; P:cardiac muscle contraction; TAS:BHF-UCL.
DR GO; GO:0098655; P:cation transmembrane transport; IDA:ARUK-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:0071260; P:cellular response to mechanical stimulus; IEA:Ensembl.
DR GO; GO:0071383; P:cellular response to steroid hormone stimulus; IDA:BHF-UCL.
DR GO; GO:0006883; P:cellular sodium ion homeostasis; IDA:BHF-UCL.
DR GO; GO:0040011; P:locomotion; ISS:ARUK-UCL.
DR GO; GO:0035641; P:locomotory exploration behavior; ISS:ARUK-UCL.
DR GO; GO:0086012; P:membrane depolarization during cardiac muscle cell action potential; TAS:BHF-UCL.
DR GO; GO:0086009; P:membrane repolarization; TAS:BHF-UCL.
DR GO; GO:1903170; P:negative regulation of calcium ion transmembrane transport; ISS:BHF-UCL.
DR GO; GO:1903280; P:negative regulation of calcium:sodium antiporter activity; ISS:BHF-UCL.
DR GO; GO:0051481; P:negative regulation of cytosolic calcium ion concentration; ISS:ARUK-UCL.
DR GO; GO:0045822; P:negative regulation of heart contraction; ISS:ARUK-UCL.
DR GO; GO:0045988; P:negative regulation of striated muscle contraction; IEA:Ensembl.
DR GO; GO:0001504; P:neurotransmitter uptake; ISS:ARUK-UCL.
DR GO; GO:0021989; P:olfactory cortex development; ISS:ARUK-UCL.
DR GO; GO:0045823; P:positive regulation of heart contraction; ISS:ARUK-UCL.
DR GO; GO:1990573; P:potassium ion import across plasma membrane; IDA:BHF-UCL.
DR GO; GO:0071805; P:potassium ion transmembrane transport; IGI:ARUK-UCL.
DR GO; GO:0006813; P:potassium ion transport; NAS:UniProtKB.
DR GO; GO:1902600; P:proton transmembrane transport; IBA:GO_Central.
DR GO; GO:0008217; P:regulation of blood pressure; IEA:Ensembl.
DR GO; GO:0086004; P:regulation of cardiac muscle cell contraction; IEA:Ensembl.
DR GO; GO:0010881; P:regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion; TAS:BHF-UCL.
DR GO; GO:0051946; P:regulation of glutamate uptake involved in transmission of nerve impulse; NAS:BHF-UCL.
DR GO; GO:0006937; P:regulation of muscle contraction; ISS:ARUK-UCL.
DR GO; GO:0002087; P:regulation of respiratory gaseous exchange by nervous system process; ISS:ARUK-UCL.
DR GO; GO:0006940; P:regulation of smooth muscle contraction; IEA:Ensembl.
DR GO; GO:0006942; P:regulation of striated muscle contraction; NAS:UniProtKB.
DR GO; GO:0051966; P:regulation of synaptic transmission, glutamatergic; NAS:BHF-UCL.
DR GO; GO:0002026; P:regulation of the force of heart contraction; ISS:ARUK-UCL.
DR GO; GO:0019229; P:regulation of vasoconstriction; IEA:Ensembl.
DR GO; GO:0055119; P:relaxation of cardiac muscle; TAS:BHF-UCL.
DR GO; GO:0010996; P:response to auditory stimulus; ISS:ARUK-UCL.
DR GO; GO:1903416; P:response to glycoside; ISS:BHF-UCL.
DR GO; GO:0035094; P:response to nicotine; IEA:Ensembl.
DR GO; GO:0036376; P:sodium ion export across plasma membrane; IDA:BHF-UCL.
DR GO; GO:0035725; P:sodium ion transmembrane transport; IGI:ARUK-UCL.
DR GO; GO:0006814; P:sodium ion transport; NAS:UniProtKB.
DR GO; GO:0150104; P:transport across blood-brain barrier; NAS:ARUK-UCL.
DR GO; GO:0008542; P:visual learning; IEA:Ensembl.
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 ATP-binding; Cell membrane; Disease variant; Epilepsy;
KW Intellectual disability; Ion transport; Magnesium; Membrane; Metal-binding;
KW Nucleotide-binding; Phosphoprotein; Potassium; Potassium transport;
KW Reference proteome; Sodium; Sodium transport; Sodium/potassium transport;
KW Translocase; Transmembrane; Transmembrane helix; Transport.
FT PROPEP 1..5
FT /evidence="ECO:0000250"
FT /id="PRO_0000002503"
FT CHAIN 6..1020
FT /note="Sodium/potassium-transporting ATPase subunit alpha-
FT 2"
FT /id="PRO_0000002504"
FT TOPO_DOM 6..85
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 86..106
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 107..129
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 130..150
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 151..286
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 287..306
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 307..318
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 319..336
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 337..769
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 770..789
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 790..799
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 800..820
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 821..840
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 841..863
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 864..915
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 916..935
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 936..948
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 949..967
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 968..982
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 983..1003
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1004..1020
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 1..31
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 80..82
FT /note="Interaction with phosphoinositide-3 kinase"
FT /evidence="ECO:0000250"
FT REGION 212..231
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 212..230
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 374
FT /note="4-aspartylphosphate intermediate"
FT /evidence="ECO:0000250"
FT BINDING 714
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 718
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT MOD_RES 10
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6PIE5"
FT MOD_RES 439
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P06686"
FT MOD_RES 450
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6PIE5"
FT MOD_RES 496
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P06686"
FT MOD_RES 559
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6PIE5"
FT MOD_RES 570
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 587
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 672
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6PIE5"
FT MOD_RES 826
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P09626"
FT MOD_RES 940
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000250"
FT VARIANT 293
FT /note="I -> M (in DEE98; decreased sodium/potassium-
FT exchanging ATPase activity; decreased affinity for sodium
FT ions)"
FT /evidence="ECO:0000269|PubMed:33880529"
FT /id="VAR_086441"
FT VARIANT 341
FT /note="C -> F (in DEE98)"
FT /evidence="ECO:0000269|PubMed:33880529"
FT /id="VAR_086442"
FT VARIANT 366
FT /note="G -> A (in DEE98; decreased affinity for sodium
FT ions; decreased affinity for potassium ions;
FT dbSNP:rs1057518514)"
FT /evidence="ECO:0000269|PubMed:27864847,
FT ECO:0000269|PubMed:33880529"
FT /id="VAR_078231"
FT VARIANT 378
FT /note="T -> N (in AHC1; dbSNP:rs28934002)"
FT /evidence="ECO:0000269|PubMed:15174025"
FT /id="VAR_019934"
FT VARIANT 593
FT /note="R -> Q (probable disease-associated variant found in
FT a patient with generalized tonic-clonic seizures; decreased
FT sodium/potassium-exchanging ATPase activity)"
FT /evidence="ECO:0000269|PubMed:33880529"
FT /id="VAR_086443"
FT VARIANT 593
FT /note="R -> W (in DEE98; dbSNP:rs886039530)"
FT /evidence="ECO:0000269|PubMed:27864847"
FT /id="VAR_078232"
FT VARIANT 689
FT /note="R -> Q (in FHM2; dbSNP:rs28933401)"
FT /evidence="ECO:0000269|PubMed:12953268"
FT /id="VAR_019935"
FT VARIANT 715
FT /note="G -> R (in FHM2; de novo mutation in a sporadic
FT case; dbSNP:rs1553245771)"
FT /evidence="ECO:0000269|PubMed:21352219"
FT /id="VAR_065685"
FT VARIANT 731
FT /note="M -> T (in FHM2; dbSNP:rs28933400)"
FT /evidence="ECO:0000269|PubMed:12953268"
FT /id="VAR_019936"
FT VARIANT 764
FT /note="L -> P (in FHM2; loss of function;
FT dbSNP:rs28933398)"
FT /evidence="ECO:0000269|PubMed:12539047"
FT /id="VAR_019937"
FT VARIANT 874
FT /note="G -> S (in FHM2; some patients exhibit a clinical
FT overlap between migraine and epilepsy)"
FT /evidence="ECO:0000269|PubMed:23918834"
FT /id="VAR_069991"
FT VARIANT 887
FT /note="W -> R (in FHM2; loss of function;
FT dbSNP:rs28933399)"
FT /evidence="ECO:0000269|PubMed:12539047"
FT /id="VAR_019938"
FT VARIANT 908
FT /note="R -> Q (in DEE98; decreased sodium/potassium-
FT exchanging ATPase activity)"
FT /evidence="ECO:0000269|PubMed:33880529"
FT /id="VAR_086444"
FT VARIANT 957..1020
FT /note="Missing (in FARIMPD; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:31608932"
FT /id="VAR_086445"
FT VARIANT 1007
FT /note="R -> W (in FHM2; some patients exhibit a clinical
FT overlap between migraine and epilepsy; dbSNP:rs746795369)"
FT /evidence="ECO:0000269|PubMed:23838748"
FT /id="VAR_069992"
SQ SEQUENCE 1020 AA; 112265 MW; AFBD8EA94FFB4FC3 CRC64;
MGRGAGREYS PAATTAENGG GKKKQKEKEL DELKKEVAMD DHKLSLDELG RKYQVDLSKG
LTNQRAQDVL ARDGPNALTP PPTTPEWVKF CRQLFGGFSI LLWIGAILCF LAYGIQAAME
DEPSNDNLYL GVVLAAVVIV TGCFSYYQEA KSSKIMDSFK NMVPQQALVI REGEKMQINA
EEVVVGDLVE VKGGDRVPAD LRIISSHGCK VDNSSLTGES EPQTRSPEFT HENPLETRNI
CFFSTNCVEG TARGIVIATG DRTVMGRIAT LASGLEVGRT PIAMEIEHFI QLITGVAVFL
GVSFFVLSLI LGYSWLEAVI FLIGIIVANV PEGLLATVTV CLTLTAKRMA RKNCLVKNLE
AVETLGSTST ICSDKTGTLT QNRMTVAHMW FDNQIHEADT TEDQSGATFD KRSPTWTALS
RIAGLCNRAV FKAGQENISV SKRDTAGDAS ESALLKCIEL SCGSVRKMRD RNPKVAEIPF
NSTNKYQLSI HEREDSPQSH VLVMKGAPER ILDRCSTILV QGKEIPLDKE MQDAFQNAYM
ELGGLGERVL GFCQLNLPSG KFPRGFKFDT DELNFPTEKL CFVGLMSMID PPRAAVPDAV
GKCRSAGIKV IMVTGDHPIT AKAIAKGVGI ISEGNETVED IAARLNIPMS QVNPREAKAC
VVHGSDLKDM TSEQLDEILK NHTEIVFART SPQQKLIIVE GCQRQGAIVA VTGDGVNDSP
ALKKADIGIA MGISGSDVSK QAADMILLDD NFASIVTGVE EGRLIFDNLK KSIAYTLTSN
IPEITPFLLF IIANIPLPLG TVTILCIDLG TDMVPAISLA YEAAESDIMK RQPRNSQTDK
LVNERLISMA YGQIGMIQAL GGFFTYFVIL AENGFLPSRL LGIRLDWDDR TMNDLEDSYG
QEWTYEQRKV VEFTCHTAFF ASIVVVQWAD LIICKTRRNS VFQQGMKNKI LIFGLLEETA
LAAFLSYCPG MGVALRMYPL KVTWWFCAFP YSLLIFIYDE VRKLILRRYP GGWVEKETYY
