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).