Evidence for an alternative genomic structure, mRNA and protein sequence of human ABCA13

ABC transporters form one of the major families of transport proteins. In humans, the ABC family comprises seven subfamilies named A to G, of which the A subfamily contains twelve members. Among these are several well-characterized transporters, including ABCA1, which is involved in cellular cholesterol transport and HDL formation, and ABCA4, which is a transporter for vitamin A derivatives in photoreceptor cells. The function of another subfamily member termed ABCA13 is unknown. The human ABCA13 gene has been reported to span 450 kb of genomic DNA at chromosomal locus 7p12.3 and to encode a 5058 amino acid protein that includes two unusually large exons close to the N-terminus. We now show that the gene as well as the corresponding mRNA and protein may be considerably shorter than previously thought. We used PCR and RACE to identify a genomic sequence spanning about 350 kb and encoding a protein of 2323 amino acids. This corresponds to the C-terminal half of the previously reported ABCA13 protein but lacks the residues reportedly encoded by the two very big N-terminal exons. Using immunoprecipitation and Western blot analyses we identified a protein of about 260 kDa in size likely representing the shorter protein proposed here. Computer analyses showed that our proposed sequence contains all the structural elements of an ABCA protein and agrees well with the mouse ABCA13 protein sequence. Additionally, we identified a putative promoter region containing well-conserved TATA and CAAT boxes just upstream of our transcription start site. Overall, our data provide good evidence for an alternative human ABCA13 transcript and protein.

► A new human ABCA13 sequence with an alternative transcription start is proposed. ► New sequence lacks two large N-terminal exons of current reference sequence. ► New sequence encodes functional ABCA transporter preceded by unknown core promoter. ► ABCA13 mRNA is alternatively spliced. ► ABCA13 mRNA is differently expressed and protein isoforms are found in fibroblasts.