The human ATP binding cassette gene ABCA13, located on chromosome 7p12.3, encodes a 5058 amino acid protein with an extracellular domain encoded in part by a 4.8-kb conserved exon

Abstract

The ABCA subfamily of ATP-binding cassette (ABC) transporters includes eleven members to date. In this study, we describe a new, unusually large gene on chromosome 7p12.3, ABCA13. This gene spans over 450 kb and is split into 62 exons. The predicted ABCA13 protein consists of 5,058 ami- no acid residues making it the largest ABC protein described to date. Like the other ABCA subfamily members, ABCA13 contains a hydrophobic, predicted transmembrane segment at the N-terminus, followed by a large hydrophilic region. In the case of ABCA13, the hydrophilic region is unexpectedly large, more than 3,500 amino acids, encoded by 30 exons, two of which are 4.8 and 1.7 kb in length. These two large exons are adjacent to each other and are conserved in the mouse Abca13 gene. Tissue profiling of the major transcript reveals the highest expression in human trachea, testis, and bone marrow. The expression of the gene was also determined in 60 tumor cell lines and the highest expression was detected in the SR leukemia, SNB-19 CNS tumor and DU-145 prostate tumor cell lines. ABCA13 has high similarity with other ABCA subfamily genes which are associated with human inherited diseases: ABCA1 with the cholesterol transport disorders Tangier disease and familial hypoalphalipoproteinemia, and ABCA4 with several retinal degeneration disorders. The ABCA13 gene maps to chromosome 7p12.3, a region that contains an inherited disorder affecting the pancreas (Shwachman-Diamond syndrome) as well as a locus involved in T-cell tumor invasion and metastasis (INM7), and therefore is a positional candidate for these pathologies.

Identification and characterization of a novel ABCA subfamily member, ABCA12, located in the lamellar ichthyosis region on 2q34

“…Although not all nodes of the tree have strong bootstrap support, the two subgroups are well defined. ABCA12 is most closely related to ABCA13, the largest ABC transporter identified to date (Prades et al, 2002). The function of ABCA13, located on chromosome 7p12, is unknown.…”

“…This includes ABCA1 mapped in 9q31, ABCA2 (9q34), ABCA3 (16p13.3), ABCA4 (1p22), ABCA7 (19p13.3) and ABCA5, ABCA6, ABCA8, ABCA9 and ABCA10 (17q24.3). In addition, we have performed initial characterization of ABCA13, located on 7p12.3 (Prades et al, 2002). A sequence previously designated ABCA11 is in fact a pseudogene.…”

The ABCA subfamily—gene and protein structures, functions and associated hereditary diseases

“…Human ABCA13 is the largest ABC transporter protein described to date, with a length of 5,058 amino acids and a predicted molecular weight of >450 kDa [41]. A characteristic feature of ABCA13 is the extraordinarily long Nterminal cytoplasmic tail, which is encoded by 30 exons and spans more than 3,500 amino acids.…”

“…However, the expression levels of ABCA13 mRNA in healthy tissues are very low, and the transcript was only detectable in a small number of tissues, including the trachea, testis, and bone marrow [41]. The murine ABCA13 promoter region was found to contain transcription factor binding sites associated with myeloid and lymphoid cell types [6].…”

The Effects of Neurological Disorder-Related Codon Variations of ABCA13 on the Function of the ABC Protein

“…ABCA13 is the largest member of the ABC protein family and has a long N-terminal, including more than 3,500 amino acids. It is expressed as mRNA in the human trachea, testis, bone marrow, brain, and other tissues, [1][2][3] but its physiological function remains unknown.…”