Description
ABCG1 (ATP-binding cassette sub-family G member 1) is a member of the ABC superfamily of transporters, specifically the ABCG (White) subfamily, that is characterized by their ABC domain organization (1). The ABC domains are around 180 amino acids (aa) in length and contain three conserved domains: Walker A motif (12 aa), Walker B motif (5 aa), and Signature motif (5 aa) (1, 2). Functional ABC transporters are comprised of two ABCs and two transmembrane domains (TMDs), where each TMD contains six TM alpha-helices (1-3). ABCG1 is considered a "half" transporter because it only has one ABC domain and one TMD (1-3). In order to be functional, ABCG1 and other half transporters can form homodimers or heterodimers (1-3). ABCG1 has a theoretical molecular weight of 102 kDa and is highly expressed in cells including macrophages, lymphocytes, and neurons (2). Additionally, ABCG1 is shown to be highly expressed in lung, kidney, brain, and spleen tissue (2). Specifically, ABCG1 is presented on the cell surface and in intracellular compartments of cholesterol-rich macrophages and, consequently, plays a crucial role in cholesterol regulation and homeostasis (3-5). ABCG1 is involved in the export, or efflux, of cholesterol and phospholipids from macrophages to high density lipoproteins (HDL) for eventual excretion via the liver.
A variety of cardiovascular and cardiometabolic diseases are associated with ABCG1 dysfunction (5-7). Macrophages can become cholesterol-containing foam cells that are generated by the uptake of low-density lipoproteins (LDL), cholesterol esterification, and compromised cholesterol efflux machinery in transporters like ABCG1 and ABCA1 (2, 5, 6, 7). Foam cells are associated with the chronic, inflammatory disease atherosclerosis which is characterized by arterial buildup of plaques that can ultimately lead to cardiovascular disease (5, 6, 7). Additionally, ABCG1 has a critical role in cardiometabolic disorders. Studies have found that diabetic mice have decreased ABCG1 expression (8). Furthermore, loss of ABCG1 in mouse pancreatic beta cells ultimately leads to impaired insulin secretion, suggesting that inhibition or modulation of ABCG1 may contribute to development of diabetes and obesity (8). Finally, other related ATP-binding cassette transporter family members, such as ABCA1 and ABCG5/8, have been associated with genetically-inherited syndromes like Tangier disease, characterized by reduced levels of HDL in the blood, and Sitosterolemia, characterized by elevated plant sterol lipid accumulation in blood and tissues (7). .
Alternate names for ABCG1 includes ABC transporter 8 (ABC8), ATP-binding cassette transporter, anti-, sub-family G (WHITE), homolog of Drosophila white, and MGC34313. .
References
1. Tarling E. J. (2013). Expanding roles of ABCG1 and sterol transport. Current opinion in lipidology. https://doi.org/10.1097/MOL.0b013e32835da122.
2. Tarr, P. T., Tarling, E. J., Bojanic, D. D., Edwards, P. A., & Baldan, A. (2009). Emerging new paradigms for ABCG transporters. Biochimica et biophysica acta.https://doi.org/10.1016/j.bbalip.2009.01.007.
3. Tarling, E. J., & Edwards, P. A. (2011). ATP binding cassette transporter G1 (ABCG1) is an intracellular sterol transporter. Proceedings of the National Academy of Sciences of the United States of America. https://doi.org/10.1073/pnas.1113021108.
4. Phillips M. C. (2014). Molecular mechanisms of cellular cholesterol efflux. The Journal of biological chemistry, 289(35), 24020-24029. https://doi.org/10.1074/jbc.R114.583658.
5. Ouimet, M., Barrett, T. J., & Fisher, E. A. (2019). HDL and Reverse Cholesterol Transport. Circulation research. https://doi.org/10.1161/CIRCRESAHA.119.312617.
6. Yu, X. H., Fu, Y. C., Zhang, D. W., Yin, K., & Tang, C. K. (2013). Foam cells in atherosclerosis. Clinica chimica acta; international journal of clinical chemistry. https://doi.org/10.1016/j.cca.2013.06.006
Bioinformatics
Entrez |
Mouse Rat Human |
Uniprot |
Human Human Human |
Product By Gene ID |
9619 |
Alternate Names |
- ABC transporter 8
- ABC8
- ABCG1
- ATP-binding cassette sub-family G member 1
- ATP-binding cassette transporter 8
- ATP-binding cassette transporter member 1 of subfamily G
- ATP-binding cassette, sub-family G (WHITE), member 1
- homolog of Drosophila white
- MGC34313
- white protein homolog (ATP-binding cassette transporter 8)
- White protein homolog
- WHITE1
- WHT1
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