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    ATP1A2 ATPase, Na+/K+ transporting, alpha 2 polypeptide [ Homo sapiens ]

    Gene ID: 477, updated on 19-May-2012
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    Summary

    Official Symbol
    ATP1A2provided by HGNC
    Official Full Name
    ATPase, Na+/K+ transporting, alpha 2 polypeptideprovided by HGNC
    Primary source
    HGNC:800
    Locus tag
    RP11-536C5.4
    See related
    Ensembl:ENSG00000018625; HPRD:01665; MIM:182340; Vega:OTTHUMG00000024080
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    FHM2; MHP2; MGC59864
    Summary
    The protein encoded by this gene belongs to the family of P-type cation transport ATPases, and to the subfamily of Na+/K+ -ATPases. Na+/K+ -ATPase is an integral membrane protein responsible for establishing and maintaining the electrochemical gradients of Na and K ions across the plasma membrane. These gradients are essential for osmoregulation, for sodium-coupled transport of a variety of organic and inorganic molecules, and for electrical excitability of nerve and muscle. This enzyme is composed of two subunits, a large catalytic subunit (alpha) and a smaller glycoprotein subunit (beta). The catalytic subunit of Na+/K+ -ATPase is encoded by multiple genes. This gene encodes an alpha 2 subunit. Mutations in this gene result in familial basilar or hemiplegic migraines, and in a rare syndrome known as alternating hemiplegia of childhood. [provided by RefSeq, Oct 2008]
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    Genomic context

    Location :
    1q21-q23
    Sequence :
    Chromosome: 1; NC_000001.10 (160085520..160113381)
    See ATP1A2 in Epigenomics, MapViewer

    Chromosome 1 - NC_000001.10Genomic Context describing neighboring genes Neighboring gene potassium inwardly-rectifying channel, subfamily J, member 9 Neighboring gene immunoglobulin superfamily, member 8 Neighboring gene ATPase, Na+/K+ transporting, alpha 4 polypeptide Neighboring gene calsequestrin 1 (fast-twitch, skeletal muscle)

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    Genomic regions, transcripts, and products

    Go to nucleotideGraphics FASTA GenBank

    Go to reference sequence details
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    Bibliography

    Related articles in PubMed

    1. Inhibition of phosphorylation of na+,k+-ATPase by mutations causing familial hemiplegic migraine. Schack VR, et al. J Biol Chem, 2012 Jan 13. PMID 22117059.
    2. Neurovascular changes in prolonged migraine aura in FHM with a novel ATP1A2 gene mutation. Iizuka T, et al. J Neurol Neurosurg Psychiatry, 2012 Feb. PMID 22013243.
    3. Systematic and quantitative assessment of the ubiquitin-modified proteome. Kim W, et al. Mol Cell, 2011 Oct 21. PMID 21906983.
    4. The genetic features of 24 patients affected by familial and sporadic hemiplegic migraine. Gallanti A, et al. Neurol Sci, 2011 May. PMID 21533730.
    5. A new Italian FHM2 family: clinical aspects and functional analysis of the disease-associated mutation. Santoro L, et al. Cephalalgia, 2011 May. PMID 21398422.

    See all (91) citations in PubMed

    See citations in PubMed for homologs of this gene provided by HomoloGene

    GeneRIFs: Gene References Into Functions What's a GeneRIF?

    1. cerebral blood flow changes during attacks of hemiplegic migraine with prolonged aura longer than 24 h in patients with familial hemiplegic migraine with a novel gene mutation; authors identified a novel heterozygous p.H916L mutation in the ATP1A2 gene...
      Title: Neurovascular changes in prolonged migraine aura in FHM with a novel ATP1A2 gene mutation.
    2. Altered dopamine signaling in Na,K-ATPasealpha2 transgenic mice contributes to reduced startle reactivity, lack of habituation, disruption of navigational circuitry, and impaired egocentric learning.
      Title: Targeted mutations in the Na,K-ATPase α 2 isoform confer ouabain resistance and result in abnormal behavior in mice.
    3. Inhibition of phosphorylation of na+,k+-ATPase by mutations causing familial hemiplegic migraine.
      Title: Inhibition of phosphorylation of na+,k+-ATPase by mutations causing familial hemiplegic migraine.
    4. Na(+)/K(+)-ATPase haploinsufficiency caused by the ATP1A2 p.G301R mutation is responsible for familial hemiplegic migraine in the described family.
      Title: A new Italian FHM2 family: clinical aspects and functional analysis of the disease-associated mutation.
    5. these results demonstrate a more frequent involvement of the ATP1A2 gene in the sporadic as well as familial forms of hemiplegic migraine in Italian patients without permanent cerebellar signs
      Title: The genetic features of 24 patients affected by familial and sporadic hemiplegic migraine.
    6. Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator)
      Title: Association of single-nucleotide polymorphisms from 17 candidate genes with baseline symptom-limited exercise test duration and decrease in duration over 20 years: the Coronary Artery Risk Development in Young Adults (CARDIA) fitness study.
    7. ATP1A2 gene is involved in early-onset sporadic hemiplegic migraine, in particular when associated with neurologic signs
      Title: De novo mutations in ATP1A2 and CACNA1A are frequent in early-onset sporadic hemiplegic migraine.
    8. Using the human alpha2 isoform, a novel model for ion transport by the Na+/K+-ATPase is established by electrophysiological studies of C-terminal mutations in familial hemiplegic migraine 2.
      Title: Neurological disease mutations compromise a C-terminal ion pathway in the Na(+)/K(+)-ATPase.
    9. Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
      Title: Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
    10. deletion of two tyrosines at the carboxy terminus of the human Na(+)/K(+)-ATPase alpha(2) subunit decreases the affinity for extracellular and intracellular Na(+).
      Title: Hyperpolarization-activated inward leakage currents caused by deletion or mutation of carboxy-terminal tyrosines of the Na+/K+-ATPase {alpha} subunit.
    Submit: New GeneRIF Correction See all (61)
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    Phenotypes

    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Alternating hemiplegia of childhood

    Migraine, familial basilar

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    Interactions

    Products Interactant Other Gene Complex Source Pubs Description
    P50993 P13693 TPT1    HPRD  PubMed  
    BioGRID:106967 BioGRID:113164 UBC    BioGRID  PubMed Affinity Capture-MS 
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    General gene information

    Markers

    Genotypes

    Homology

    Pathways from BioSystems

    • Aldosterone-regulated sodium reabsorption, organism-specific biosystem (from KEGG)
      Aldosterone-regulated sodium reabsorption, organism-specific biosystemSodium transport across the tight epithelia of Na+ reabsorbing tissues such as the distal part of the kidney nephron and colon is the major factor determining total-body Na+ levels, and thus, long-te...
    • Aldosterone-regulated sodium reabsorption, conserved biosystem (from KEGG)
      Aldosterone-regulated sodium reabsorption, conserved biosystemSodium transport across the tight epithelia of Na+ reabsorbing tissues such as the distal part of the kidney nephron and colon is the major factor determining total-body Na+ levels, and thus, long-te...
    • Bile secretion, organism-specific biosystem (from KEGG)
      Bile secretion, organism-specific biosystemBile is a vital secretion, essential for digestion and absorption of fats and fat-soluble vitamins in the small intestine. Moreover, bile is an important route of elimination for excess cholesterol a...
    • Bile secretion, conserved biosystem (from KEGG)
      Bile secretion, conserved biosystemBile is a vital secretion, essential for digestion and absorption of fats and fat-soluble vitamins in the small intestine. Moreover, bile is an important route of elimination for excess cholesterol a...
    • Carbohydrate digestion and absorption, organism-specific biosystem (from KEGG)
      Carbohydrate digestion and absorption, organism-specific biosystemDietary carbohydrate in humans and omnivorous animals is a major nutrient. The carbohydrates that we ingest vary from the lactose in milk to complex carbohydrates. These carbohydrates are digested t...
    • Carbohydrate digestion and absorption, conserved biosystem (from KEGG)
      Carbohydrate digestion and absorption, conserved biosystemDietary carbohydrate in humans and omnivorous animals is a major nutrient. The carbohydrates that we ingest vary from the lactose in milk to complex carbohydrates. These carbohydrates are digested t...
    • Cardiac muscle contraction, organism-specific biosystem (from KEGG)
      Cardiac muscle contraction, organism-specific biosystemContraction of the heart is a complex process initiated by the electrical excitation of cardiac myocytes (excitation-contraction coupling, ECC). In cardiac myocytes, Ca2+ influx induced by activation...
    • Cardiac muscle contraction, conserved biosystem (from KEGG)
      Cardiac muscle contraction, conserved biosystemContraction of the heart is a complex process initiated by the electrical excitation of cardiac myocytes (excitation-contraction coupling, ECC). In cardiac myocytes, Ca2+ influx induced by activation...
    • Endocrine and other factor-regulated calcium reabsorption, organism-specific biosystem (from KEGG)
      Endocrine and other factor-regulated calcium reabsorption, organism-specific biosystemCalcium (Ca2+) is essential for numerous physiological functions including intracellular signalling processes, neuronal excitability, muscle contraction and bone formation. Therefore, its homeostasis...
    • Endocrine and other factor-regulated calcium reabsorption, conserved biosystem (from KEGG)
      Endocrine and other factor-regulated calcium reabsorption, conserved biosystemCalcium (Ca2+) is essential for numerous physiological functions including intracellular signalling processes, neuronal excitability, muscle contraction and bone formation. Therefore, its homeostasis...
    • Gastric acid secretion, organism-specific biosystem (from KEGG)
      Gastric acid secretion, organism-specific biosystemGastric acid is a key factor in normal upper gastrointestinal functions, including protein digestion and calcium and iron absorption, as well as providing some protection against bacterial infections...
    • Gastric acid secretion, conserved biosystem (from KEGG)
      Gastric acid secretion, conserved biosystemGastric acid is a key factor in normal upper gastrointestinal functions, including protein digestion and calcium and iron absorption, as well as providing some protection against bacterial infections...
    • Ion channel transport, organism-specific biosystem (from REACTOME)
      Ion channel transport, organism-specific biosystemIon channels mediate the flow of ions across the plasma membrane of cells. They are integral membrane proteins, typically a multimer of proteins, which, when arranged in the membrane, create a pore f...
    • Ion transport by P-type ATPases, organism-specific biosystem (from REACTOME)
      Ion transport by P-type ATPases, organism-specific biosystemThe P-type ATPases (E1-E2 ATPases) are a large group of evolutionarily related ion pumps that are found in bacteria, archaea and eukaryotes. They are referred to as P-type ATPases because they catal...
    • Mineral absorption, organism-specific biosystem (from KEGG)
      Mineral absorption, organism-specific biosystemMinerals are one of the five fundamental groups of nutrients needed to sustain life. Of the minerals, calcium plays innumerable roles in our bodies, serving as a main component of bone as well as an ...
    • Mineral absorption, conserved biosystem (from KEGG)
      Mineral absorption, conserved biosystemMinerals are one of the five fundamental groups of nutrients needed to sustain life. Of the minerals, calcium plays innumerable roles in our bodies, serving as a main component of bone as well as an ...
    • Pancreatic secretion, organism-specific biosystem (from KEGG)
      Pancreatic secretion, organism-specific biosystemThe pancreas performs both exocrine and endocrine functions. The exocrine pancreas consists of two parts, the acinar and duct cells. The primary functions of pancreatic acinar cells are to synthesiz...
    • Pancreatic secretion, conserved biosystem (from KEGG)
      Pancreatic secretion, conserved biosystemThe pancreas performs both exocrine and endocrine functions. The exocrine pancreas consists of two parts, the acinar and duct cells. The primary functions of pancreatic acinar cells are to synthesiz...
    • Protein digestion and absorption, organism-specific biosystem (from KEGG)
      Protein digestion and absorption, organism-specific biosystemProtein is a dietary component essential for nutritional homeostasis in humans. Normally, ingested protein undergoes a complex series of degradative processes following the action of gastric, pancrea...
    • Protein digestion and absorption, conserved biosystem (from KEGG)
      Protein digestion and absorption, conserved biosystemProtein is a dietary component essential for nutritional homeostasis in humans. Normally, ingested protein undergoes a complex series of degradative processes following the action of gastric, pancrea...
    • Proximal tubule bicarbonate reclamation, organism-specific biosystem (from KEGG)
      Proximal tubule bicarbonate reclamation, organism-specific biosystemOne of the major tasks of the renal proximal tubule (PT) is to secrete acid into the tubule lumen, thereby reabsorbing approximately 80% of the filtered bicarbonate (HCO3(-)), as well as generating "...
    • Proximal tubule bicarbonate reclamation, conserved biosystem (from KEGG)
      Proximal tubule bicarbonate reclamation, conserved biosystemOne of the major tasks of the renal proximal tubule (PT) is to secrete acid into the tubule lumen, thereby reabsorbing approximately 80% of the filtered bicarbonate (HCO3(-)), as well as generating "...
    • Salivary secretion, organism-specific biosystem (from KEGG)
      Salivary secretion, organism-specific biosystemSaliva has manifold functions in maintaining the integrity of the oral tissues, in protecting teeth from caries, in the tasting and ingestion of food, in speech and in the tolerance of tenures, for e...
    • Salivary secretion, conserved biosystem (from KEGG)
      Salivary secretion, conserved biosystemSaliva has manifold functions in maintaining the integrity of the oral tissues, in protecting teeth from caries, in the tasting and ingestion of food, in speech and in the tolerance of tenures, for e...
    • Transmembrane transport of small molecules, organism-specific biosystem (from REACTOME)
      Transmembrane transport of small molecules, organism-specific biosystem
      Transmembrane transport of small molecules

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    ATP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    ATPase activity, coupled to transmembrane movement of ions, phosphorylative mechanism IEA
    Inferred from Electronic Annotation
    more info
    		  
    cation-transporting ATPase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    hydrolase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    hydrolase activity, acting on acid anhydrides, catalyzing transmembrane movement of substances IEA
    Inferred from Electronic Annotation
    more info
    		  
    metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    monovalent inorganic cation transmembrane transporter activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    nucleotide binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    sodium:potassium-exchanging ATPase activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    sodium:potassium-exchanging ATPase activity TAS
    Traceable Author Statement
    more info
    		  
    Process Evidence Code Pubs
    ATP biosynthetic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    ATP hydrolysis coupled proton transport IEA
    Inferred from Electronic Annotation
    more info
    		  
    adult locomotory behavior IEA
    Inferred from Electronic Annotation
    more info
    		  
    ion transmembrane transport TAS
    Traceable Author Statement
    more info
    		  
    locomotion IEA
    Inferred from Electronic Annotation
    more info
    		  
    negative regulation of heart contraction IEA
    Inferred from Electronic Annotation
    more info
    		  
    negative regulation of striated muscle contraction IEA
    Inferred from Electronic Annotation
    more info
    		  
    neurotransmitter uptake IEA
    Inferred from Electronic Annotation
    more info
    		  
    potassium ion transport NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    reduction of cytosolic calcium ion concentration IEA
    Inferred from Electronic Annotation
    more info
    		  
    regulation of blood pressure IEA
    Inferred from Electronic Annotation
    more info
    		  
    regulation of respiratory gaseous exchange by neurological system process IEA
    Inferred from Electronic Annotation
    more info
    		  
    regulation of smooth muscle contraction IEA
    Inferred from Electronic Annotation
    more info
    		  
    regulation of striated muscle contraction NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    regulation of the force of heart contraction IEA
    Inferred from Electronic Annotation
    more info
    		  
    regulation of vasoconstriction IEA
    Inferred from Electronic Annotation
    more info
    		  
    sodium ion transport NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    transmembrane transport TAS
    Traceable Author Statement
    more info
    		  
    visual learning IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    caveola IEA
    Inferred from Electronic Annotation
    more info
    		  
    cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    dendritic spine IEA
    Inferred from Electronic Annotation
    more info
    		  
    endosome IEA
    Inferred from Electronic Annotation
    more info
    		  
    integral to membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    membrane fraction IEA
    Inferred from Electronic Annotation
    more info
    		  
    microsome IEA
    Inferred from Electronic Annotation
    more info
    		  
    neuron projection IEA
    Inferred from Electronic Annotation
    more info
    		  
    plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    plasma membrane TAS
    Traceable Author Statement
    more info
    		  
    sarcolemma IEA
    Inferred from Electronic Annotation
    more info
    		  
    sodium:potassium-exchanging ATPase complex IC
    Inferred by Curator
    more info
    		 PubMed 
    synapse IEA
    Inferred from Electronic Annotation
    more info
    		  
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    General protein information

    Preferred Names
    sodium/potassium-transporting ATPase subunit alpha-2
    Names
    sodium/potassium-transporting ATPase subunit alpha-2
    sodium-potassium ATPase
    sodium pump subunit alpha-2
    Na(+)/K(+) ATPase alpha-2 subunit
    Na+/K+ ATPase, alpha-B polypeptide
    Na+/K+ ATPase, alpha-A(+) catalytic polypeptide
    sodium/potassium-transporting ATPase alpha-2 chain
    NP_000693.1
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    NCBI Reference Sequences (RefSeq)

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_008014.1 RefSeqGene

      Range
      4973..32834
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_6

    mRNA and Protein(s)

    1. NM_000702.3 → NP_000693.1  sodium/potassium-transporting ATPase subunit alpha-2 proprotein

      Status: REVIEWED

      Source sequence(s)
      BC013680, BC052271, DA221602, EB386326
      Consensus CDS
      CCDS1196.1
      UniProtKB/Swiss-Prot
      P50993
      Related
      ENSP00000354490, OTTHUMP00000025754, ENST00000361216, OTTHUMT00000060642
      Conserved Domains (6) summary
      TIGR01106
      Location:37 – 1020
      Blast Score: 5431
      ATPase-IIC_X-K; sodium or proton efflux -- potassium uptake antiporter, P-type ATPase, alpha subunit
      pfam00122
      Location:133 – 364
      Blast Score: 501
      E1-E2_ATPase; E1-E2 ATPase
      pfam00689
      Location:796 – 1005
      Blast Score: 337
      Cation_ATPase_C; Cation transporting ATPase, C-terminus
      pfam13246
      Location:425 – 518
      Blast Score: 306
      Hydrolase_like2; Putative hydrolase of sodium-potassium ATPase alpha subunit
      cl02930
      Location:38 – 112
      Blast Score: 230
      Cation_ATPase_N; Cation transporter/ATPase, N-terminus
      cl11391
      Location:603 – 749
      Blast Score: 108
      HAD_like; Haloacid Dehalogenase-like Hydrolases

    RefSeqs of Annotated Genomes: Build 37.3

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh37.p5 Primary Assembly

    Genomic

    1. NC_000001.10 Reference GRCh37.p5 Primary Assembly

      Range
      160085520..160113381
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000133.1 Alternate HuRef

      Range
      131442647..131470507
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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    Related Sequences

    Nucleotide Protein
    Heading Accession and Version
    genomic AL121987.34 CAI15271.1
      CAI15272.1
      CAI15273.1
    genomic CH471121.2 EAW52739.1
      EAW52740.1
      EAW52741.1
      EAW52742.1
    genomic J05096.1 AAA51797.1
    genomic M27578.1 AAA35575.1
    mRNA AB018321.2 BAA34498.2
    mRNA AK091617.1 BAG52393.1
    mRNA AK124581.1 BAG54055.1
    mRNA AK126573.1 BAG54347.1
    mRNA AK295048.1 BAG58098.1
    mRNA AK295729.1 BAG58570.1
    mRNA AK299460.1 BAG61427.1
    mRNA AK308773.1 None
    mRNA AK314296.1 BAG36951.1
    mRNA AL831991.1 None
    mRNA AL831997.1 None
    mRNA AY946014.1 AAX55909.1
    mRNA BC013680.1 None
    mRNA BC047533.1 None
    mRNA BC052271.1 AAH52271.2
    mRNA DA221602.1 None
    mRNA EB386326.1 None
    mRNA M16795.1 AAA51799.1
    mRNA Y07494.1 CAA68793.1
    Protein Accession Links
    GenPept Link UniProtKB Link
    P50993.1 GenPept UniProtKB/Swiss-Prot:P50993
    Q58I22 GenPept UniProtKB/TrEMBL:Q58I22
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    Additional Links

    Additional Links

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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