ABCG
The ABCG subfamily consists of six reverse-configured half transporters with a unique structural organization. The NBD is situated at the N-terminal half of the transporter, followed by the TMD. Thewhite locus of Drosophila is one of the most extensively studied ABC proteins. The white protein (with brown and scarlet) transports precursors of eye pigments (guanine and tryptophan) in the eye cells of the fly (H. Chen et al., 1996). In addition, it can potentially transport biogenic amines, 5-hydroxytryptamine (5-HT), and dopamine that are essential in Drosophila for olfactory learning and memory (Myers, 2017) .
The ABCG1 protein in mammals is involved in cholesterol transport regulation (Klucken et al., 2000), and the gene is on chromosome 21q22.3 in humans. ABCG1 is a significant player in cholesterol efflux from macrophages to extracellular lipid acceptors that include high-density lipoprotein (HDL) and phosphatidylcholine (PC) vesicles (Wang, Lan, Chen, Matsuura, & Tall, 2004). In addition, ABCG1 may have a role in T-cell proliferation and provide a protective role for apoptosis in macrophages (Bensinger et al., 2008; Wojcik, Skaflen, Srinivasan, & Hedrick, 2008).
Other notable ABCG genes are ABCG2 , which serves as a drug-resistance gene, and ABCG5 and ABCG8 , which encode sterols transporters in the intestine and liver. The excretion of sterols in the liver and intestines is facilitated by the ABCG5/ABCG8 heterodimer (G5G8). Specific mutations in G5G8 cause sitosterolemia, a genetic disease characterized by the accumulation of plant sterols and cholesterol, leading to premature atherosclerosis (Lee et al., 2016). A genome-wide association study (GWAS) revealed that a single nucleotide polymorphism, p.D19His in ABCG8, is a susceptibility factor for human gallstone disease (Buch et al., 2007). Abcg3 is only found in rodents and has an unknown function. The last member of this family, ABCG4, is expressed in the brain, spinal cord, heart, and thymus in humans and the retina. ABCG4 facilitates the efflux of cellular cholesterol to high-density lipoproteins (Wang et al., 2004). Thus, the dual processes of ’gene birth’ and ’gene death’ are involved in the evolution of ABCG genes. By studying the evolution of these transporters in other vertebrate species, we can facilitate developing animal models for functional and clinical studies (K. Moitra, Silverton, Limpert, Im, & Dean, 2011).