ABCG8

ABCG8
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 5DO7
Identifiers
Aliases	ABCG8 , GBD4, STSL, ATP binding cassette subfamily G member 8, STSL1
External IDs	OMIM: 605460; MGI: 1914720; HomoloGene: 23361; GeneCards: ABCG8; OMA:ABCG8 - orthologs
Gene location (Human) Chr. Chromosome 2 (human) [1] Band 2p21 Start 43,831,942 bp [1] End 43,882,988 bp [1]
Gene location (Mouse) Chr. Chromosome 17 (mouse) [2] Band 17 E4|17 55.02 cM Start 84,983,730 bp [2] End 85,007,761 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right lobe of liver jejunal mucosa duodenum testicle secondary oocyte gallbladder prefrontal cortex Brodmann area 9 right frontal lobe cingulate gyrus Top expressed in jejunum duodenum intestinal villus left lobe of liver ileum epithelium of small intestine embryo tibiofemoral joint Paneth cell colon More reference expression data BioGPS n/a
Gene ontology Molecular function ATPase activity protein binding ATP binding ATPase-coupled transmembrane transporter activity metal ion binding cholesterol transfer activity protein heterodimerization activity xenobiotic transmembrane transporter activity sterol transporter activity Cellular component integral component of membrane membrane ATP-binding cassette (ABC) transporter complex plasma membrane apical plasma membrane integral component of plasma membrane receptor complex Biological process negative regulation of intestinal phytosterol absorption intestinal cholesterol absorption negative regulation of intestinal cholesterol absorption lipid transport excretion cholesterol efflux cholesterol homeostasis transmembrane transport xenobiotic transmembrane transport response to nutrient phospholipid transport sterol transport sterol homeostasis Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 64241 67470 Ensembl ENSG00000143921 ENSMUSG00000024254 UniProt Q9H221 Q9DBM0 RefSeq (mRNA) NM_022437 NM_001357321 NM_001286005 NM_026180 NM_001347418 RefSeq (protein) NP_071882 NP_001344250 NP_001272934 NP_001334347 NP_080456 Location (UCSC) Chr 2: 43.83 – 43.88 Mb Chr 17: 84.98 – 85.01 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

ATP-binding cassette sub-family G member 8 is a protein that in humans is encoded by the ABCG8 gene. ^{[5] [6] [7]}

The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the White subfamily. The protein encoded by this gene 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. Mutations in this gene may contribute to sterol accumulation and atherosclerosis, and have been observed in patients with sitosterolemia. ^[7]

A loss-of-function mutation in ABCG8 impairs the removal of sterols from cells and, in the homozygous case, leads to sitosterolemia. Heterozygous individuals show slightly increased sterol absoption, normal cholesterol levels, and slightly elevated phytosterol levels. ^[8]

A gain-of-function SNP rs11887534 increases the likelihood of gallbladder disease, especially cholesterol gallstones. This is probably because more cholesterol is pumped into the bile lumen. ^[9]

Interactive pathway map

Click on genes, proteins and metabolites below to link to respective articles. ^{[§ 1]}

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|alt=Statin pathway edit]]

Statin pathway edit

1. The interactive pathway map can be edited at WikiPathways: "Statin_Pathway_WP430".

See also

• ATP-binding cassette transporter

References

1. GRCh38: Ensembl release 89: ENSG00000143921 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000024254 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Berge KE, Tian H, Graf GA, Yu L, Grishin NV, Schultz J, et al. (December 2000). "Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters". Science. 290 (5497): 1771–1775. Bibcode:2000Sci...290.1771B. doi:10.1126/science.290.5497.1771. PMID   11099417.
6. Grünhage F, Acalovschi M, Tirziu S, Walier M, Wienker TF, Ciocan A, et al. (September 2007). "Increased gallstone risk in humans conferred by common variant of hepatic ATP-binding cassette transporter for cholesterol". Hepatology. 46 (3): 793–801. doi: 10.1002/hep.21847 . PMID   17626266. S2CID   29517167.
7. "Entrez Gene: ABCG8 ATP-binding cassette, sub-family G (WHITE), member 8 (sterolin 2)".
8. Yoo EG (March 2016). "Sitosterolemia: a review and update of pathophysiology, clinical spectrum, diagnosis, and management". Annals of Pediatric Endocrinology & Metabolism. 21 (1): 7–14. doi:10.6065/apem.2016.21.1.7. PMC   4835564 . PMID   27104173.
9. "Entry - #611465 - GALLBLADDER DISEASE 4; GBD4 - OMIM". www.omim.org.

Further reading

• Schmitz G, Langmann T, Heimerl S (October 2001). "Role of ABCG1 and other ABCG family members in lipid metabolism". Journal of Lipid Research. 42 (10): 1513–1520. doi: 10.1016/S0022-2275(20)32205-7 . PMID   11590207.
• Lu K, Lee MH, Hazard S, Brooks-Wilson A, Hidaka H, Kojima H, et al. (August 2001). "Two genes that map to the STSL locus cause sitosterolemia: genomic structure and spectrum of mutations involving sterolin-1 and sterolin-2, encoded by ABCG5 and ABCG8, respectively". American Journal of Human Genetics. 69 (2): 278–290. doi:10.1086/321294. PMC   1201544 . PMID   11452359.
• Hubacek JA, Berge KE, Cohen JC, Hobbs HH (October 2001). "Mutations in ATP-cassette binding proteins G5 (ABCG5) and G8 (ABCG8) causing sitosterolemia". Human Mutation. 18 (4): 359–360. doi: 10.1002/humu.1206 . PMID   11668628. S2CID   10011192.
• Berge KE, von Bergmann K, Lutjohann D, Guerra R, Grundy SM, Hobbs HH, et al. (March 2002). "Heritability of plasma noncholesterol sterols and relationship to DNA sequence polymorphism in ABCG5 and ABCG8". Journal of Lipid Research. 43 (3): 486–494. doi: 10.1016/S0022-2275(20)30155-3 . PMID   11893785.
• Lu K, Lee MH, Yu H, Zhou Y, Sandell SA, Salen G, et al. (April 2002). "Molecular cloning, genomic organization, genetic variations, and characterization of murine sterolin genes Abcg5 and Abcg8". Journal of Lipid Research. 43 (4): 565–578. doi:10.1016/S0022-2275(20)31486-3. PMC   1815568 . PMID   11907139.
• Iida A, Saito S, Sekine A, Mishima C, Kitamura Y, Kondo K, et al. (2002). "Catalog of 605 single-nucleotide polymorphisms (SNPs) among 13 genes encoding human ATP-binding cassette transporters: ABCA4, ABCA7, ABCA8, ABCD1, ABCD3, ABCD4, ABCE1, ABCF1, ABCG1, ABCG2, ABCG4, ABCG5, and ABCG8". Journal of Human Genetics. 47 (6): 285–310. doi: 10.1007/s100380200041 . PMID   12111378.
• Heimerl S, Langmann T, Moehle C, Mauerer R, Dean M, Beil FU, et al. (August 2002). "Mutations in the human ATP-binding cassette transporters ABCG5 and ABCG8 in sitosterolemia". Human Mutation. 20 (2): 151. doi: 10.1002/humu.9047 . PMID   12124998. S2CID   23157539.
• Remaley AT, Bark S, Walts AD, Freeman L, Shulenin S, Annilo T, et al. (July 2002). "Comparative genome analysis of potential regulatory elements in the ABCG5-ABCG8 gene cluster". Biochemical and Biophysical Research Communications. 295 (2): 276–282. doi:10.1016/S0006-291X(02)00652-6. PMID   12150943.
• Graf GA, Li WP, Gerard RD, Gelissen I, White A, Cohen JC, et al. (September 2002). "Coexpression of ATP-binding cassette proteins ABCG5 and ABCG8 permits their transport to the apical surface". The Journal of Clinical Investigation. 110 (5): 659–669. doi:10.1172/JCI16000. PMC   151110 . PMID   12208867.
• Yu L, Li-Hawkins J, Hammer RE, Berge KE, Horton JD, Cohen JC, et al. (September 2002). "Overexpression of ABCG5 and ABCG8 promotes biliary cholesterol secretion and reduces fractional absorption of dietary cholesterol". The Journal of Clinical Investigation. 110 (5): 671–680. doi:10.1172/JCI16001. PMC   151111 . PMID   12208868.
• Graf GA, Yu L, Li WP, Gerard R, Tuma PL, Cohen JC, et al. (November 2003). "ABCG5 and ABCG8 are obligate heterodimers for protein trafficking and biliary cholesterol excretion". The Journal of Biological Chemistry. 278 (48): 48275–48282. doi: 10.1074/jbc.M310223200 . PMID   14504269.
• Kajinami K, Brousseau ME, Nartsupha C, Ordovas JM, Schaefer EJ (April 2004). "ATP binding cassette transporter G5 and G8 genotypes and plasma lipoprotein levels before and after treatment with atorvastatin". Journal of Lipid Research. 45 (4): 653–656. doi: 10.1194/jlr.M300278-JLR200 . PMID   14703505.
• Hubácek JA, Berge KE, Stefková J, Pitha J, Skodová Z, Lánská V, et al. (2005). "Polymorphisms in ABCG5 and ABCG8 transporters and plasma cholesterol levels". Physiological Research. 53 (4): 395–401. PMID   15311998.
• Yu L, Gupta S, Xu F, Liverman AD, Moschetta A, Mangelsdorf DJ, et al. (March 2005). "Expression of ABCG5 and ABCG8 is required for regulation of biliary cholesterol secretion". The Journal of Biological Chemistry. 280 (10): 8742–8747. doi: 10.1074/jbc.M411080200 . PMID   15611112.
• Langheim S, Yu L, von Bergmann K, Lütjohann D, Xu F, Hobbs HH, et al. (August 2005). "ABCG5 and ABCG8 require MDR2 for secretion of cholesterol into bile". Journal of Lipid Research. 46 (8): 1732–1738. doi: 10.1194/jlr.M500115-JLR200 . PMID   15930516.
• Miettinen TA, Klett EL, Gylling H, Isoniemi H, Patel SB (February 2006). "Liver transplantation in a patient with sitosterolemia and cirrhosis". Gastroenterology. 130 (2): 542–547. doi:10.1053/j.gastro.2005.10.022. PMC   1391914 . PMID   16472606.
• Lally S, Tan CY, Owens D, Tomkin GH (May 2006). "Messenger RNA levels of genes involved in dysregulation of postprandial lipoproteins in type 2 diabetes: the role of Niemann-Pick C1-like 1, ATP-binding cassette, transporters G5 and G8, and of microsomal triglyceride transfer protein". Diabetologia. 49 (5): 1008–1016. doi: 10.1007/s00125-006-0177-8 . PMID   16518588.

External links

• ABCG8+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• Human ABCG8 genome location and ABCG8 gene details page in the UCSC Genome Browser .
• Overview of all the structural information available in the PDB for UniProt : Q9H221 (ATP-binding cassette sub-family G member 8) at the PDBe-KB .

This article incorporates text from the United States National Library of Medicine, which is in the public domain.