ABCG8 Membrane Protein Introduction

Introduction of ABCG8

ABCG8 is ATP-binding cassette subfamily G member 8 which is encoded by the ABCG8 gene in humans. It belongs to the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins are able to transport various kinds of molecules across extra- and intra-cellular membranes. They can be classified into seven distinct subfamilies including ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, and White. The protein encoded by ABCG8 belongs to White family, and functions as a half-transporter to limit intestinal absorption and promote biliary excretion of sterols. It is expressed in a tissue-specific manner in the liver, colon, and intestine. This gene is tandemly arrayed on chromosome 2, in a head-to-head orientation with family member ABCG5.

Basic Information of ABCG8
Protein Name ATP-binding cassette sub-family G member 8
Gene Name ABCG8
Aliases Sterolin-2
Organism Homo sapiens (Human)
UniProt ID Q9H221
Transmembrane Times 6
Length (aa) 673

Function of ABCG8 Membrane Protein

ABCG8 is ATP-binding cassette sub-family G member 8 which belongs to the ABCG subfamily. They all are half transporters which are composed of a single nucleotide-binding domain and a single transmembrane domain. It has been reported that mutations in this gene may contribute to sterol accumulation and atherosclerosis. In addition, it has been observed in patients with sitosterolemia. Like another member, ABCG5 forms an obligate heterodimer via interacting with ABCG8, and the heterodimer can mediate Mg2+ and ATP-dependent sterol transport across the cell membranes. Furthermore, both ABCG5 and ABCG8 play critical roles in the regulation of sterol absorption and excretion which were identified as new pathways of sterol transport.

Structure of the G5G8 heterodimer. Fig.1 Structure of the G5G8 heterodimer. (Lee, 2016)

Application of ABCG8 Membrane Protein in Literature

  1. Bardawil T., et al. Mutations in the ABCG8 gene are associated with sitosterolaemia in the homozygous form and xanthelasmas in the heterozygous form. Eur J Dermatol. 2017, 27(5): 519-523. PubMed ID: 28739549

    This article identifies a novel ABCG8 mutation by exome sequencing in this family, and indicates ABCG8’s gene dosage effect.

  2. Castro-Torres I.G., et al. The Hypocholesterolemic Effects of Eryngium carlinae F. Delaroche Are Mediated by the Involvement of the Intestinal Transporters ABCG5 and ABCG8. Evid Based Complement Alternat Med. 2017, 2017: 3176232. PubMed ID: 29387127

    This article shows that the intestinal transporter ABCG5 and ABCG8 mediate the hypocholesterolemic effects of Eryngium carlinae F. Delaroche.

  3. Patel S.B., et al. ABCG5 and ABCG8: more than a defense against xenosterols. J Lipid Res. 2018, 59(7): 1103-1113. PubMed ID: 29728459

    This review summarizes the current state of ABCG5 and ABCG8, also the remaining key conceptual and mechanistic issues are highlighted.

  4. Tada H., et al. First case of sitosterolemia caused by double heterozygous mutations in ABCG5 and ABCG8 genes. J Clin Lipidol. 2018, 12(5): 1164-1168.e4. PubMed ID: 30007774

    This article shows us the first case of sitosterolemia which is caused by heterozygous mutations in ABCG5 and ABCG8.

  5. Frigerio P., et al. Distribution of the ATP-binding cassette transporter ABCG8 IVS1-2A>G genotype and clinical characteristics of gallbladder patients in Northeastern Mexico: A pilot study. Biomed Rep. 2018, 9(3): 266-270. PubMed ID: 30271604

    These studies indicate that between the presence of site mutation in ABCG8, and the presence of gallstones, no association was observed.

ABCG8 Preparation Options

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  1. Lee J Y, et al. (2016). Crystal structure of the human sterol transporter ABCG5/ABCG8. Nature. 533(7604): 561-4.

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