PMID:15260953

Citation	de Carvalho Aguiar, P, Sweadner, KJ, Penniston, JT, Zaremba, J, Liu, L, Caton, M, Linazasoro, G, Borg, M, Tijssen, MA, Bressman, SB, Dobyns, WB, Brashear, A and Ozelius, LJ (2004) Mutations in the Na+/K+ -ATPase alpha3 gene ATP1A3 are associated with rapid-onset dystonia parkinsonism. Neuron 43:169-75
Abstract	Rapid-onset dystonia-parkinsonism (RDP, DYT12) is a distinctive autosomal-dominant movement disorder with variable expressivity and reduced penetrance characterized by abrupt onset of dystonia, usually accompanied by signs of parkinsonism. The sudden onset of symptoms over hours to a few weeks, often associated with physical or emotional stress, suggests a trigger initiating a nervous system insult resulting in permanent neurologic disability. We report the finding of six missense mutations in the gene for the Na+/K+ -ATPase alpha3 subunit (ATP1A3) in seven unrelated families with RDP. Functional studies and structural analysis of the protein suggest that these mutations impair enzyme activity or stability. This finding implicates the Na+/K+ pump, a crucial protein responsible for the electrochemical gradient across the cell membrane, in dystonia and parkinsonism.
Links	PubMed Online version:10.1016/j.neuron.2004.06.028
Keywords	Amino Acid Sequence; Cell Line; Dystonia/complications; Dystonia/genetics; Dystonia/metabolism; Humans; Molecular Conformation; Mutation, Missense; Parkinsonian Disorders/complications; Parkinsonian Disorders/genetics; Parkinsonian Disorders/metabolism; Sodium-Potassium-Exchanging ATPase/genetics; Sodium-Potassium-Exchanging ATPase/metabolism; Structure-Activity Relationship
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:AT1A3	located_in	GO:0005886: plasma membrane	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
HUMAN:AT1A3	located_in	GO:0016021: integral component of membrane	ECO:0000303: author statement without traceable support used in manual assertion		C		Seeded From UniProt	complete
HUMAN:AT1A3	located_in	GO:0005783: endoplasmic reticulum	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
HUMAN:AT1A3	located_in	GO:0005794: Golgi apparatus	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
HUMAN:AT1A3	enables	GO:0005391: P-type sodium:potassium-exchanging transporter activity	ECO:0000315: mutant phenotype evidence used in manual assertion		F		Seeded From UniProt	complete
HUMAN:AT1A3	enables	GO:0005391: sodium:potassium-exchanging ATPase activity	ECO:0000315: mutant phenotype evidence used in manual assertion		F		Seeded From UniProt	complete
HUMAN:AT1A3	part_of	GO:0005794: Golgi apparatus	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
HUMAN:AT1A3	part_of	GO:0005783: endoplasmic reticulum	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
HUMAN:AT1A3	enables	GO:0005524: ATP binding	ECO:0000303: author statement without traceable support used in manual assertion		F		Seeded From UniProt	complete
HUMAN:AT1A3	part_of	GO:0005886: plasma membrane	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
HUMAN:AT1A3	part_of	GO:0005890: sodium:potassium-exchanging ATPase complex	ECO:0000305: curator inference used in manual assertion	GO:0005391	C		Seeded From UniProt	complete
HUMAN:AT1A3	part_of	GO:0016021: integral component of membrane	ECO:0000303: author statement without traceable support used in manual assertion		C		Seeded From UniProt	complete

References

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