InterPro domain: IPR026082

ATP-binding cassette transporters (ABC) are multipass transmembrane proteins that use the energy of ATP hydrolysis to transport substrates across membrane bilayers. Members of ABC transporter subfamily A are full-length transporters [ 1 ], which consist of a single long polypeptide chain organised into two tandemly arranged halves. Each half contains a membrane-spanning domain (MSD) followed by a cytoplasmic nucleotide binding domain (NBD) [ 2 ]. Several members of this group have been shown to mediate the transport of a variety of physiologic lipid compounds, such as sterols, phospholipids and bile acids [ 3 , 4 ].

ABCA7 plays a role in clearance of apoptotic cells by affecting their phagocytosis [ 5 ]. In the human visual cycle, ABCA4 acts as an inward-directed retinoid flipase, retinoid substrates imported by ABCA4 from the extracellular or intradiscal (rod) membrane surfaces to the cytoplasmic membrane surface are all-trans-retinaldehyde (ATR) and N-retinyl-phosphatidyl-ethanolamine (NR-PE). Once transported to the cytoplasmic surface, ATR is reduced to vitamin A by trans-retinol dehydrogenase (tRDH) and then transferred to the retinal pigment epithelium (RPE) where it is converted to 11-cis-retinal. ABCA4 may also play a role in photoresponse, removing ATR/NR-PE from the extracellular photoreceptor surfaces during bleach recovery [ 6 ]. It has been suggested that ABCA9 plays a role in monocyte differentiation and lipid homeostasis [ 7 ].

1. Mammalian P4-ATPases and ABC transporters and their role in phospholipid transport. Biochim. Biophys. Acta 1831, 555-74
2. Membrane topology of the ATP binding cassette transporter ABCR and its relationship to ABC1 and related ABCA transporters: identification of N-linked glycosylation sites. J. Biol. Chem. 276, 23539-46
3. ABC A-subfamily transporters: structure, function and disease. Biochim. Biophys. Acta 1762, 510-24
4. ABCA8 Regulates Cholesterol Efflux and High-Density Lipoprotein Cholesterol Levels. Arterioscler Thromb Vasc Biol 37, 2147-2155
5. ATP-binding cassette transporter A7 enhances phagocytosis of apoptotic cells and associated ERK signaling in macrophages. J. Cell Biol. 174, 547-56
6. Retinal stimulates ATP hydrolysis by purified and reconstituted ABCR, the photoreceptor-specific ATP-binding cassette transporter responsible for Stargardt disease. J. Biol. Chem. 274, 8269-81
7. Molecular structure of a novel cholesterol-responsive A subclass ABC transporter, ABCA9. Biochem. Biophys. Res. Commun. 295, 408-16