Primary structure of a novel ABC transporter with a chromosomal localization on the band encoding the multidrug resistance‐associated protein

Abstract

Complementary DNA clones encoding a novel protein, ABC-C, with the typical structural features of the ABC transporter family were identified in a human medullary thyroid carcinoma cell line. The transporter consists of 1704 amino acid residues with two homologous repeats, each harboring six putative transmembrane helices and an ATPbinding cassette motif. The mRNA is expressed highest in normal lung, but also in varying amounts in other tissues and in C-cell carcinoma. The ABC-C gene is mapped on chromosome 16p13.3, in close physical proximity to another ABC transporter, the multidrug resistance-associated protein. This related protein is assumed to confer resistance to chemotherapeutic drugs in small cell lung carcinoma. The genomic clustering of both transporters, typical also for other members of the ABC family, supports the notion that ABC-C may be involved in development of resistance to xenobiotics.

Intracellular ABC transporter A3 confers multidrug resistance in leukemia cells by lysosomal drug sequestration

“…21 It is highly conserved between mammalian species, and was found expressed predominantly in the alveolar type II cells of the lung. 11,22 In alveolar cells, ABCA3 function is essential to the formation of lamellar bodies, a lysosomal-related organelle, and indispensable for pulmonary surfactant production and/or secretion.…”

Alveolar injury and regeneration following deletion of ABCA3

“…ABCA3, located on human chromosome 16p13.3, encodes a 1,704-amino acid (190-kDA), multimembrane-spanning protein expressed at high levels in AT2 cells in the lung (1)(2)(3)(4). ABCA3 is required for packaging and secretion of surfactant lipids and is required for lung function at birth (5,6).…”

Expression of ABCA3 in Developing Lung and Other Tissues

“…Please visit this article online to view these materials. (J Histochem Cytochem 55:71-83, 2007) K E Y W O R D S ABC transporters pulmonary surfactant lamellar body bronchopulmonary dysplasia thyroid transcription factor 1 immunohistochemistry ABCA3 is a 1704 amino acid member of the ATPbinding cassette (ABC)-containing family of transport proteins associated with the translocation of various substrates across cellular membranes (Higgins 1992;Klugbauer and Hofmann 1996;Connors et al 1997;Dean et al 2001). ABCA3 was identified in type II epithelial cells of the lung where it was associated with lamellar body membranes (Zen et al 1998;Yamano et al 2001;Mulugeta et al 2002).…”