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UniProtKB/Swiss-Prot entry P50993


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name AT1A2_HUMAN
Primary accession number P50993
Secondary accession numbers Q07059 Q5JW74 Q86UZ5 Q9UQ25
Integrated into Swiss-Prot on October 1, 1996
Sequence was last modified on October 1, 1996 (Sequence version 1)
Annotations were last modified on    June 16, 2009 (Entry version 94)
Name and origin of the protein
Protein name Sodium/potassium-transporting ATPase subunit alpha-2 [Precursor]
Synonyms Sodium pump subunit alpha-2
EC 3.6.3.9
Na(+)/K(+) ATPase alpha-2 subunit
Gene name
Name: ATP1A2
Synonyms: KIAA0778
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
PubMed=2477373 [NCBI, ExPASy, EBI, Israel, Japan]
Shull M.M., Pugh D.G., Lingrel J.B.;
"Characterization of the human Na,K-ATPase alpha 2 gene and identification of intragenic restriction fragment length polymorphisms.";
J. Biol. Chem. 264:17532-17543(1989).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Brain;
DOI=10.1093/dnares/5.5.277; PubMed=9872452 [NCBI, ExPASy, EBI, Israel, Japan]
Nagase T., Ishikawa K., Suyama M., Kikuno R., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.;
"Prediction of the coding sequences of unidentified human genes. XI. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro.";
DNA Res. 5:277-286(1998).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
DOI=10.1038/nature04727; PubMed=16710414 [NCBI, ExPASy, EBI, Israel, Japan]
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
"The DNA sequence and biological annotation of human chromosome 1.";
Nature 441:315-321(2006).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.;
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Ovary;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[6]
NUCLEOTIDE SEQUENCE [MRNA] OF 211-249.
TISSUE=Leukocyte;
DOI=10.1073/pnas.84.12.4039; PubMed=3035563 [NCBI, ExPASy, EBI, Israel, Japan]
Shull M.M., Lingrel J.B.;
"Multiple genes encode the human Na+,K+-ATPase catalytic subunit.";
Proc. Natl. Acad. Sci. U.S.A. 84:4039-4043(1987).
[7]
NUCLEOTIDE SEQUENCE [MRNA] OF 251-442.
TISSUE=Brain, and Placenta;
DOI=10.1016/0014-5793(87)80677-4; PubMed=3036582 [NCBI, ExPASy, EBI, Israel, Japan]
Sverdlov E.D., Monastyrskaya G.S., Broude N.E., Ushkaryov Y.A., Allikmets R.L., Melkov A.M., Smirnov Y.V., Malyshev I.V., Dulubova I.E., Petrukhin K.E., Gryshin A.V., Kiyatkin N.I., Kostina M.B., Sverdlov V.E., Modyanov N.N., Ovchinnikov Y.A.;
"The family of human Na+,K+-ATPase genes. No less than five genes and/or pseudogenes related to the alpha-subunit.";
FEBS Lett. 217:275-278(1987).
[8]
NUCLEOTIDE SEQUENCE [MRNA] OF 1-4.
DOI=10.1016/0014-5793(89)80588-5; PubMed=2537767 [NCBI, ExPASy, EBI, Israel, Japan]
Sverdlov E.D., Bessarab D.A., Malyshev I.V., Petrukhin K.E., Smirnov Y.V., Ushkaryov Y.A., Monastyrskaya G.S., Broude N.E., Modyanov N.N.;
"Family of human Na+,K+-ATPase genes. Structure of the putative regulatory region of the alpha+-gene.";
FEBS Lett. 244:481-483(1989).
[9]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-570 AND SER-587, AND MASS SPECTROMETRY.
DOI=10.1073/pnas.0805139105; PubMed=18669648 [NCBI, ExPASy, EBI, Israel, Japan]
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.;
"A quantitative atlas of mitotic phosphorylation.";
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
[10]
VARIANTS FHM2 GLN-689 AND THR-731.
DOI=10.1002/ana.10674; PubMed=12953268 [NCBI, ExPASy, EBI, Israel, Japan]
Vanmolkot K.R.J., Kors E.E., Hottenga J.-J., Terwindt G.M., Haan J., Hoefnagels W.A.J., Black D.F., Sandkuijl L.A., Frants R.R., Ferrari M.D., van den Maagdenberg A.M.J.M.;
"Novel mutations in the Na+, K+-ATPase pump gene ATP1A2 associated with familial hemiplegic migraine and benign familial infantile convulsions.";
Ann. Neurol. 54:360-366(2003).
[11]
VARIANTS FHM2 PRO-764 AND ARG-887, AND CHARACTERIZATION OF VARIANTS FMH2 PRO-764 AND ARG-887.
DOI=10.1038/ng1081; PubMed=12539047 [NCBI, ExPASy, EBI, Israel, Japan]
De Fusco M., Marconi R., Silvestri L., Atorino L., Rampoldi L., Morgante L., Ballabio A., Aridon P., Casari G.;
"Haploinsufficiency of ATP1A2 encoding the Na+/K+ pump alpha2 subunit associated with familial hemiplegic migraine type 2.";
Nat. Genet. 33:192-196(2003).
[12]
VARIANT AHC ASN-378.
DOI=10.1002/ana.20134; PubMed=15174025 [NCBI, ExPASy, EBI, Israel, Japan]
Swoboda K.J., Kanavakis E., Xaidara A., Johnson J.E., Leppert M.F., Schlesinger-Massart M.B., Ptacek L.J., Silver K., Youroukos S.;
"Alternating hemiplegia of childhood or familial hemiplegic migraine? A novel ATP1A2 mutation.";
Ann. Neurol. 55:884-887(2004).
Comments
  • FUNCTION: This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium, providing the energy for active transport of various nutrients.
  • CATALYTIC ACTIVITY: ATP + H2O + Na+(In) + K+(Out) = ADP + phosphate + Na+(Out) + K+(In).
  • SUBUNIT: Composed of three subunits: alpha (catalytic), beta and gamma.
  • SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
  • DISEASE: Defects in ATP1A2 are the cause of familial hemiplegic migraine 2 (FHM2) [MIM:602481]. Familial hemiplegic migraine is a rare, severe, autosomal dominant subtype of migraine characterized by aura and some hemiparesis.
  • DISEASE: Defects in ATP1A2 are a cause of alternating hemiplegia of childhood (AHC) [MIM:104290]. AHC is typically distinguished from familial hemiplegic migraine by infantile onset of the symptoms and high prevalence of associated neurological deficits that become increasingly obvious with age.
  • SIMILARITY: Belongs to the cation transport ATPase (P-type) family. Type IIC subfamily.
  • WEB RESOURCE: Name=GeneReviews; URL="http://www.genetests.org/query?gene=ATP1A2";.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
J05096; AAA51797.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AB018321; BAA34498.2; ALT_INIT; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AL121987; CAI15271.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
CH471121; EAW52740.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC052271; AAH52271.2; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M16795; AAA51799.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M27578; AAA35575.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M27571; AAA35575.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M27576; AAA35575.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
Y07494; CAA68793.1; ALT_SEQ; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
IPI IPI00003021; -.
PIR A34474; A34474.
RefSeq NP_000693.1; -.
UniGene Hs.34114
3D structure databases
HSSP P06685; 1MO7. [HSSP ENTRY / PDB]
SMR P50993; 384-590.
ModBase P50993.
PTM databases
PhosphoSite P50993; -.
Enzyme and pathway databases
BRENDA 3.6.3.9; 247.
Organism-specific databases
GeneCards GC01P158353; -.
H-InvDB HIX0018896; -.
HGNC HGNC:800; ATP1A2.
GenAtlas ATP1A2.
MIM 104290; phenotype. [NCBI / EBI]
182340; gene. [NCBI / EBI]
602481; phenotype. [NCBI / EBI]
Orphanet 2131; Alternating hemiplegia.
569; Hemiplegic migraine, familial or sporadic.
PharmGKB PA30796; -.
HUGE KIAA0778.
Gene expression databases
ArrayExpress P50993; -.
Bgee P50993; -.
CleanEx HS_ATP1A2; -.
GermOnline ENSG00000018625; Homo sapiens.
Ontologies
GO
GO:0005737; Cellular component: cytoplasm (inferred from direct assay from UniProtKB).
GO:0005890; Cellular component: sodium:potassium-exchanging ATPase complex (inferred by curator from UniProtKB).
GO:0005524; Molecular function: ATP binding (inferred by curator from UniProtKB).
GO:0000287; Molecular function: magnesium ion binding (inferred from electronic annotation from UniProtKB-KW).
GO:0015077; Molecular function: monovalent inorganic cation transmembrane transporter activity (inferred from electronic annotation from InterPro).
GO:0030955; Molecular function: potassium ion binding (inferred from electronic annotation from UniProtKB-KW).
GO:0031402; Molecular function: sodium ion binding (inferred from electronic annotation from UniProtKB-KW).
GO:0005391; Molecular function: sodium:potassium-exchanging ATPase activity (inferred from mutant phenotype from UniProtKB).
GO:0006754; Biological process: ATP biosynthetic process (inferred from electronic annotation from InterPro).
GO:0006813; Biological process: potassium ion transport (non-traceable author statement from UniProtKB).
GO:0030641; Biological process: regulation of cellular pH (inferred from sequence or structural similarity from UniProtKB).
GO:0006942; Biological process: regulation of striated muscle contraction (non-traceable author statement from UniProtKB).
GO:0006814; Biological process: sodium ion transport (non-traceable author statement from UniProtKB).
GO:0030317; Biological process: sperm motility (inferred from sequence or structural similarity from UniProtKB).
QuickGo view.
Family and domain databases
InterPro IPR008250; ATPase_P-typ_ATPase-assoc-reg.
IPR005775; ATPase_P-typ_cation-ex_asu_euk.
IPR006069; ATPase_P-typ_cation-exchng_asu.
IPR006068; ATPase_P-typ_cation-transptr_C.
IPR004014; ATPase_P-typ_cation-transptr_N.
IPR001757; ATPase_P-typ_ion-transptr.
IPR018303; ATPase_P-typ_phosphor_site.
IPR005834; Dehalogen-like_hydro.
Graphical view of domain structure.
PANTHER PTHR11939; ATPase_P; 1.
Pfam PF00689; Cation_ATPase_C; 1.
PF00690; Cation_ATPase_N; 1.
PF00122; E1-E2_ATPase; 1.
PF00702; Hydrolase; 1.
Pfam graphical view of domain structure.
PRINTS PR00119; CATATPASE.
PR00121; NAKATPASE.
TIGRFAMs TIGR01106; ATPase-IIC_X-K; 1.
TIGR01494; ATPase_P-type; 4.
PROSITE PS00154; ATPASE_E1_E2; 1.
Proteomic databases
PRIDE P50993; -.
Genome annotation databases
Ensembl ENSG00000018625; Homo sapiens. [Contig view]
GeneID 477; -.
KEGG hsa:477; -.
Phylogenomic databases
HOGENOM P50993; -.
HOVERGEN P50993; -.
OMA P50993; CHLNLPS.
Other
NextBio 1977; -.
SOURCE ATP1A2; Homo sapiens.
ProtoNet P50993.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
ATP-binding; Disease mutation; Hydrolase; Ion transport; Magnesium; Membrane; Metal-binding; Nucleotide-binding; Phosphoprotein; Potassium; Potassium transport; Sodium; Sodium transport; Sodium/potassium transport; Transmembrane; Transport.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom    To Length Description FTId
PROPEP   1      5  5     By similarity. PRO_0000002503
CHAIN   6   1020  1015     Sodium/potassium-transporting ATPase subunit alpha-2. PRO_0000002504
TOPO_DOM   6     85  80     Cytoplasmic (Potential). 
TRANSMEM   86    106  21     Potential. 
TOPO_DOM   107    129  23     Lumenal (Potential). 
TRANSMEM   130    150  21     Potential. 
TOPO_DOM   151    286  136     Cytoplasmic (Potential). 
TRANSMEM   287    306  20     Potential. 
TOPO_DOM   307    318  12     Lumenal (Potential). 
TRANSMEM   319    336  18     Potential. 
TOPO_DOM   337    769  433     Cytoplasmic (Potential). 
TRANSMEM   770    789  20     Potential. 
TOPO_DOM   790    799  10     Lumenal (Potential). 
TRANSMEM   800    820  21     Potential. 
TOPO_DOM   821    840  20     Cytoplasmic (Potential). 
TRANSMEM   841    863  23     Potential. 
TOPO_DOM   864    915  52     Lumenal (Potential). 
TRANSMEM   916    935  20     Potential. 
TOPO_DOM   936    948  13     Cytoplasmic (Potential). 
TRANSMEM   949    967  19     Potential. 
TOPO_DOM   968    982  15     Lumenal (Potential). 
TRANSMEM   983   1003  21     Potential. 
TOPO_DOM   1004   1020  17     Cytoplasmic (Potential). 
REGION   80     82  3     Interaction with phosphoinositide-3 kinase (By similarity). 
ACT_SITE   374    374        4-aspartylphosphate intermediate (By similarity). 
METAL   714    714        Magnesium (By similarity). 
METAL   718    718        Magnesium (By similarity). 
MOD_RES   570    570        Phosphothreonine. 
MOD_RES   587    587        Phosphoserine. 
MOD_RES   650    650        Phosphoserine (By similarity). 
MOD_RES   940    940        Phosphoserine; by PKA (By similarity). 
VARIANT   378    378  1     T -> N (in AHC). VAR_019934 
VARIANT   689    689  1     R -> Q (in FHM2). VAR_019935 
VARIANT   731    731  1     M -> T (in FHM2). VAR_019936 
VARIANT   764    764  1     L -> P (in FHM2; loss of function). VAR_019937 
VARIANT   887    887  1     W -> R (in FHM2; loss of function). VAR_019938 
Sequence information
Length: 1020 AA [This is the length of the unprocessed precursor] Molecular weight: 112265 Da [This is the MW of the unprocessed precursor] CRC64: AFBD8EA94FFB4FC3 [This is a checksum on the sequence]
        10         20         30         40         50         60 
MGRGAGREYS PAATTAENGG GKKKQKEKEL DELKKEVAMD DHKLSLDELG RKYQVDLSKG 

        70         80         90        100        110        120 
LTNQRAQDVL ARDGPNALTP PPTTPEWVKF CRQLFGGFSI LLWIGAILCF LAYGIQAAME 

       130        140        150        160        170        180 
DEPSNDNLYL GVVLAAVVIV TGCFSYYQEA KSSKIMDSFK NMVPQQALVI REGEKMQINA 

       190        200        210        220        230        240 
EEVVVGDLVE VKGGDRVPAD LRIISSHGCK VDNSSLTGES EPQTRSPEFT HENPLETRNI 

       250        260        270        280        290        300 
CFFSTNCVEG TARGIVIATG DRTVMGRIAT LASGLEVGRT PIAMEIEHFI QLITGVAVFL 

       310        320        330        340        350        360 
GVSFFVLSLI LGYSWLEAVI FLIGIIVANV PEGLLATVTV CLTLTAKRMA RKNCLVKNLE 

       370        380        390        400        410        420 
AVETLGSTST ICSDKTGTLT QNRMTVAHMW FDNQIHEADT TEDQSGATFD KRSPTWTALS 

       430        440        450        460        470        480 
RIAGLCNRAV FKAGQENISV SKRDTAGDAS ESALLKCIEL SCGSVRKMRD RNPKVAEIPF 

       490        500        510        520        530        540 
NSTNKYQLSI HEREDSPQSH VLVMKGAPER ILDRCSTILV QGKEIPLDKE MQDAFQNAYM 

       550        560        570        580        590        600 
ELGGLGERVL GFCQLNLPSG KFPRGFKFDT DELNFPTEKL CFVGLMSMID PPRAAVPDAV 

       610        620        630        640        650        660 
GKCRSAGIKV IMVTGDHPIT AKAIAKGVGI ISEGNETVED IAARLNIPMS QVNPREAKAC 

       670        680        690        700        710        720 
VVHGSDLKDM TSEQLDEILK NHTEIVFART SPQQKLIIVE GCQRQGAIVA VTGDGVNDSP 

       730        740        750        760        770        780 
ALKKADIGIA MGISGSDVSK QAADMILLDD NFASIVTGVE EGRLIFDNLK KSIAYTLTSN 

       790        800        810        820        830        840 
IPEITPFLLF IIANIPLPLG TVTILCIDLG TDMVPAISLA YEAAESDIMK RQPRNSQTDK 

       850        860        870        880        890        900 
LVNERLISMA YGQIGMIQAL GGFFTYFVIL AENGFLPSRL LGIRLDWDDR TMNDLEDSYG 

       910        920        930        940        950        960 
QEWTYEQRKV VEFTCHTAFF ASIVVVQWAD LIICKTRRNS VFQQGMKNKI LIFGLLEETA 

       970        980        990       1000       1010       1020 
LAAFLSYCPG MGVALRMYPL KVTWWFCAFP YSLLIFIYDE VRKLILRRYP GGWVEKETYY 

P50993 in FASTA format

View entry in raw text format (no links)
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