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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Physical mapping and characterization of the human Na,K-ATPase isoform, ATP1A4.

Four isoforms of the catalytic alpha subunit of the Na,K-ATPase have been previously identified. We characterized and mapped a genomic copy of the human ATP1A4 isoform between D1S2707 and WI-9524, telomeric to a nearby isoform ATP1A2, and within a candidate region at 1q23 for familial hemiplegic migraine (FHM). Human ATP1A4 gene shares 84% identity with the mouse Atp1a4 gene, and both consist of 22 exons and 21 introns. The predicted polypeptide is 1029 amino acids and shares 82 and 79.8% identity, respectively, with human ATP1A2 and ATP1A1. ATP1A4 is larger than other isoforms and most divergent at the N-terminus. ATP1A4 and ATP1A2 are paralogous genes with the same number and organization of putative H-transmembrane domains, conserved exon-intron boundaries, and are found approximately 8.5 kb apart. Expression analysis of the ATP1A4 gene revealed a new major approximately 7.5 kb transcript in human skeletal muscle, with expression also shown in mouse muscle. Predictive analysis of promoter regions identified muscle specific regulatory elements for ATP1A4 and Atp1a4. Mutation analysis among eight affected individuals from a single large, highly penetrant FHM family was negative in ATP1A4 and ATP1A2 although multiple polymorphisms were identified.[1]

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