Molecular structure and characterization of a novel murine ABC transporter, Abca13.
We report the isolation and structural characterization of the full-length gene and cDNA for a novel mouse ATP-binding cassette (ABC) transporter, Abca13. The mRNA, isolated from mouse kidney, is 6.7 kb in size and encodes a protein consisting of 2143 amino acids with a predicted molecular weight of 240 kDa. The Abca13 gene consists of 44 exons which span 360 kb of genomic sequence. Abca13 has been mapped to mouse chromosome 11.a2, revealing the human orthologue highly conserved on a syntenic region of human chromosome 7p12. The deduced mouse Abca13 protein shows highest amino acid sequence homology to human ABCA1 (50%), ABCA4 (50%), and ABCA12 (56%). Analysis of the putative Abca13 promoter region revealed potential transcription factor binding sites associated with myeloid- and lymphoid-derived cell types. mRNA transcript levels were highest in mouse submaxillary gland, epididymus, ovary, and thymus; with lower levels in a variety of other tissues. An alternative transcript was discovered in mouse kidney devoid of exon 11. The removal of exon 11 by post-transcriptional splicing causes a frameshift in the open reading frame and results in a premature termination codon. We hypothesize that the excision of exon 11 may serve as a regulatory mechanism in kidney, and perhaps other tissues as well. The molecular characterization of the mouse Abca13 gene will establish the foundation for future functional studies of the human ABCA13 transporter.
Barros
Scott A
SA
Curriculum in Toxicology, University of North Carolina at Chapel Hill, 27514, USA.
Tennant
Raymond W
RW
Cannon
Ronald E
RE
D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification; D005091:Exons; D005260:Female; D015870:Gene Expression; D005796:Genes / Q000235:genetics; D006801:Humans; D007438:Introns; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D024363:Transcription Initiation Site
D018528:ATP-Binding Cassette Transporters; C474964:Abca13 protein, mouse; D018076:DNA, Complementary; D012333:RNA, Messenger