8y1p

Structural highlights

Disease

ABCA7_HUMAN Early-onset autosomal dominant Alzheimer disease. Disease susceptibility is associated with variants affecting the gene represented in this entry.

Function

ABCA7_HUMAN Catalyzes the translocation of specific phospholipids from the cytoplasmic to the extracellular/lumenal leaflet of membrane coupled to the hydrolysis of ATP (PubMed:24097981). Transports preferentially phosphatidylserine over phosphatidylcholine (PubMed:24097981). Plays a role in lipid homeostasis and macrophage-mediated phagocytosis (PubMed:12917409, PubMed:12925201, PubMed:14570867, PubMed:14592415). Binds APOA1 and may function in apolipoprotein-mediated phospholipid efflux from cells (PubMed:12917409, PubMed:14570867, PubMed:14592415). May also mediate cholesterol efflux (PubMed:14570867). May regulate cellular ceramide homeostasis during keratinocyte differentiation (PubMed:12925201). Involved in lipid raft organization and CD1D localization on thymocytes and antigen-presenting cells, which plays an important role in natural killer T-cell development and activation (By similarity). Plays a role in phagocytosis of apoptotic cells by macrophages (By similarity). Macrophage phagocytosis is stimulated by APOA1 or APOA2, probably by stabilization of ABCA7 (By similarity). Also involved in phagocytic clearance of amyloid-beta by microglia cells and macrophages (By similarity). Further limits amyloid-beta production by playing a role in the regulation of amyloid-beta A4 precursor protein (APP) endocytosis and/or processing (PubMed:26260791). Amyloid-beta is the main component of amyloid plaques found in the brains of Alzheimer patients (PubMed:26260791).[UniProtKB:Q91V24]^{[1] [2] [3] [4] [5] [6]}

References

1. ↑ Wang N, Lan D, Gerbod-Giannone M, Linsel-Nitschke P, Jehle AW, Chen W, Martinez LO, Tall AR. ATP-binding cassette transporter A7 (ABCA7) binds apolipoprotein A-I and mediates cellular phospholipid but not cholesterol efflux. J Biol Chem. 2003 Oct 31;278(44):42906-12. Epub 2003 Aug 12. PMID:12917409 doi:http://dx.doi.org/10.1074/jbc.M307831200
2. ↑ Kielar D, Kaminski WE, Liebisch G, Piehler A, Wenzel JJ, Mohle C, Heimerl S, Langmann T, Friedrich SO, Bottcher A, Barlage S, Drobnik W, Schmitz G. Adenosine triphosphate binding cassette (ABC) transporters are expressed and regulated during terminal keratinocyte differentiation: a potential role for ABCA7 in epidermal lipid reorganization. J Invest Dermatol. 2003 Sep;121(3):465-74. PMID:12925201 doi:http://dx.doi.org/12404
3. ↑ Abe-Dohmae S, Ikeda Y, Matsuo M, Hayashi M, Okuhira K, Ueda K, Yokoyama S. Human ABCA7 supports apolipoprotein-mediated release of cellular cholesterol and phospholipid to generate high density lipoprotein. J Biol Chem. 2004 Jan 2;279(1):604-11. Epub 2003 Oct 21. PMID:14570867 doi:http://dx.doi.org/10.1074/jbc.M309888200
4. ↑ Ikeda Y, Abe-Dohmae S, Munehira Y, Aoki R, Kawamoto S, Furuya A, Shitara K, Amachi T, Kioka N, Matsuo M, Yokoyama S, Ueda K. Posttranscriptional regulation of human ABCA7 and its function for the apoA-I-dependent lipid release. Biochem Biophys Res Commun. 2003 Nov 14;311(2):313-8. doi: , 10.1016/j.bbrc.2003.10.002. PMID:14592415 doi:http://dx.doi.org/10.1016/j.bbrc.2003.10.002
5. ↑ Quazi F, Molday RS. Differential phospholipid substrates and directional transport by ATP-binding cassette proteins ABCA1, ABCA7, and ABCA4 and disease-causing mutants. J Biol Chem. 2013 Nov 29;288(48):34414-26. doi: 10.1074/jbc.M113.508812. Epub, 2013 Oct 4. PMID:24097981 doi:http://dx.doi.org/10.1074/jbc.M113.508812
6. ↑ Satoh K, Abe-Dohmae S, Yokoyama S, St George-Hyslop P, Fraser PE. ATP-binding cassette transporter A7 (ABCA7) loss of function alters Alzheimer amyloid processing. J Biol Chem. 2015 Oct 2;290(40):24152-65. doi: 10.1074/jbc.M115.655076. Epub 2015 , Aug 10. PMID:26260791 doi:http://dx.doi.org/10.1074/jbc.M115.655076