ABCA1: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
No edit summary
No edit summary
Line 50: Line 50:


==Overview==
==Overview==
'''ATP-binding cassette transporter ABCA1 (member 1 of human transporter sub-family ABCA'''), also known as the cholesterol efflux regulatory protein (CERP) is a [[protein]] which in humans is encoded by the ''ABCA1'' [[gene]].<ref name="pmid8088782">{{cite journal | author = Luciani MF, Denizot F, Savary S, Mattei MG, Chimini G | title = Cloning of two novel ABC transporters mapping on human chromosome 9 | journal = Genomics | volume = 21 | issue = 1 | pages = 150–9 | year = 1994 | month = May | pmid = 8088782 | doi = 10.1006/geno.1994.1237 | url =  }}</ref> This transporter is a major regulator of cellular [[cholesterol]] and [[phospholipid]] [[homeostasis]]. The membrane-associated protein encoded by this gene is a member of the superfamily of [[ATP-binding cassette transporter|ATP-binding cassette (ABC) transporters]].  ABC proteins transport various molecules across extra- and intracellular membranes.  ABC genes are divided into seven distinct subfamilies (ABCA, MDR/TAP, MRP, ALD, OABP, GCN20, White).  This protein is a member of the ABCA subfamily.  Members of the ABCA subfamily comprise the only major ABC subfamily found exclusively in multicellular eukaryotes.  With cholesterol as its substrate, this protein functions as a cholesterol [[efflux]] pump in the cellular lipid removal pathway.  Mutations in this gene have been associated with [[Tangier's disease]] and familial [[high-density lipoprotein]] deficiency.<ref>{{cite web | title = Entrez Gene: ABCA1 ATP-binding cassette, sub-family A (ABC1), member 1| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=19| accessdate =}}</ref>
{{See also|ATP-binding cassette transporter}}
{{See also|ATP-binding cassette transporter}}
'''ATP-binding cassette transporter ABCA1 (member 1 of human transporter sub-family ABCA'''), also known as the cholesterol efflux regulatory protein (CERP) is a [[protein]] which in humans is encoded by the ''ABCA1'' [[gene]].<ref name="pmid8088782">{{cite journal | author = Luciani MF, Denizot F, Savary S, Mattei MG, Chimini G | title = Cloning of two novel ABC transporters mapping on human chromosome 9 | journal = Genomics | volume = 21 | issue = 1 | pages = 150–9 | year = 1994 | month = May | pmid = 8088782 | doi = 10.1006/geno.1994.1237 | url =  }}</ref> This transporter is a major regulator of cellular [[cholesterol]] and [[phospholipid]] [[homeostasis]]. The membrane-associated protein encoded by this gene is a member of the superfamily of [[ATP-binding cassette transporter|ATP-binding cassette (ABC) transporters]].  ABC proteins transport various molecules across extra- and intracellular membranes.  ABC genes are divided into seven distinct subfamilies (ABCA, MDR/TAP, MRP, ALD, OABP, GCN20, White).  This protein is a member of the ABCA subfamily.  Members of the ABCA subfamily comprise the only major ABC subfamily found exclusively in multicellular eukaryotes.  With cholesterol as its substrate, this protein functions as a cholesterol [[efflux]] pump in the cellular lipid removal pathway.  Mutations in this gene have been associated with [[Tangier's disease]] and familial [[high-density lipoprotein]] deficiency.<ref>{{cite web | title = Entrez Gene: ABCA1 ATP-binding cassette, sub-family A (ABC1), member 1| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=19| accessdate =}}</ref>


==Tangier Disease==
==Tangier Disease==

Revision as of 02:02, 31 July 2013

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Synonyms and keywords: CERP; cholesterol efflux regulatory protein

ATP-binding cassette, sub-family A (ABC1), member 1
Identifiers
Symbols ABCA1 ; ABC-1; ABC1; CERP; FLJ14958; HDLDT1; TGD
External IDs Template:OMIM5 Template:MGI HomoloGene: 21130
RNA expression pattern
More reference expression data
Orthologs
Template:GNF Ortholog box
Species Human Mouse
Entrez n/a n/a
Ensembl n/a n/a
UniProt n/a n/a
RefSeq (mRNA) n/a n/a
RefSeq (protein) n/a n/a
Location (UCSC) n/a n/a
PubMed search n/a n/a

Overview

ATP-binding cassette transporter ABCA1 (member 1 of human transporter sub-family ABCA), also known as the cholesterol efflux regulatory protein (CERP) is a protein which in humans is encoded by the ABCA1 gene.[1] This transporter is a major regulator of cellular cholesterol and phospholipid homeostasis. The membrane-associated 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 intracellular membranes. ABC genes are divided into seven distinct subfamilies (ABCA, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the ABCA subfamily. Members of the ABCA subfamily comprise the only major ABC subfamily found exclusively in multicellular eukaryotes. With cholesterol as its substrate, this protein functions as a cholesterol efflux pump in the cellular lipid removal pathway. Mutations in this gene have been associated with Tangier's disease and familial high-density lipoprotein deficiency.[2]

See also: ATP-binding cassette transporter

Tangier Disease

ABCA1 was discovered as the mutation causing Tangier Disease by several groups in 1998. Gerd Schmitz's group in Germany[3] and Michael Hayden's group in British Columbia[4] were using standard genetics techniques and DNA from family pedigrees to locate the mutation. Richard Lawn's group at CV Therapeutics in Palo Alto, CA used cDNA microarrays, which were relatively new at the time, to assess gene expression profiles from cell lines created from normal and effected individuals.[5] They showed cell lines from patients with Tangier's disease showed differential regulation of the ABCA1 gene. Subsequent sequencing of the gene identified the mutations. This group received an award from the American Heart Association for their discovery.[6]

Function

The membrane-associated 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 intracellular membranes. ABC genes are divided into seven distinct subfamilies (ABCA, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the ABCA subfamily. Members of the ABCA subfamily comprise the only major ABC subfamily found exclusively in multicellular eukaryotes. With cholesterol as its substrate, this protein functions as a cholesterol efflux pump in the cellular lipid removal pathway.[7][8]

Physiological role

ABCA1 mediates the efflux of cholesterol and phospholipids to lipid-poor apolipoproteins (apo-A1 and apoE), which then form nascent high-density lipoproteins (HDL). It also mediates the transport of lipids between Golgi and cell membrane. Since this protein is needed throughout the body it is expressed ubiquitously as a 220-kDa protein. It is present in higher quantities in tissues that shuttle or are involved in the turnover of lipids such as the liver, the small intestine and adipose tissue.[9]

Factors that act upon the ABCA1 transporter's expression or its posttranslational modification are also molecules that are involved in its subsequent function like fatty acids, cholesterol and also cytokines and cyclic adenosine monophosphate.[10]

Overexpression of ABCA1 has been reported to induce resistance to the anti-inflammatory, dietary polyphenolic antioxidant Curcumin[11] Downregulation of ABCA1 in senescent macrophages disrupts the cell's ability to remove cholesterol from it's cytosoplasm, leading the cells to promote the pathologic angiogenesis that "plays a central role in common age-associated diseases such as atherosclerosis, cancer, and macular degeneration" [12]

Clinical significance

Mutations in this gene have been associated with Tangier disease and familial high-density lipoprotein deficiency. ABCA1 has been shown to be reduced in Tangier disease which features physiological deficiencies of HDL.[13][14]

Interactions

ABCA1 has been shown to interact with Apolipoprotein A1,[15] FADD,[16] XPC[17] and SNTB2.[18]

References

  1. ↑ Luciani MF, Denizot F, Savary S, Mattei MG, Chimini G (1994). "Cloning of two novel ABC transporters mapping on human chromosome 9". Genomics. 21 (1): 150–9. doi:10.1006/geno.1994.1237. PMID 8088782. Unknown parameter |month= ignored (help)
  2. ↑ "Entrez Gene: ABCA1 ATP-binding cassette, sub-family A (ABC1), member 1".
  3. ↑ Bodzioch M, Orsó E, Klucken J, Langmann T, Böttcher A, Diederich W, Drobnik W, Barlage S, Büchler C, Porsch-Ozcürümez M, Kaminski WE, Hahmann HW, Oette K, Rothe G, Aslanidis C, Lackner KJ, Schmitz G (1999). "The gene encoding ATP-binding cassette transporter 1 is mutated in Tangier disease". Nature Genetics. 22 (4): 347–51. doi:10.1038/11914. PMID 10431237. Unknown parameter |month= ignored (help)
  4. ↑ Brooks-Wilson A, Marcil M, Clee SM, Zhang LH, Roomp K, van Dam M, Yu L, Brewer C, Collins JA, Molhuizen HO, Loubser O, Ouelette BF, Fichter K, Ashbourne-Excoffon KJ, Sensen CW, Scherer S, Mott S, Denis M, Martindale D, Frohlich J, Morgan K, Koop B, Pimstone S, Kastelein JJ, Genest J, Hayden MR (1999). "Mutations in ABC1 in Tangier disease and familial high-density lipoprotein deficiency". Nature Genetics. 22 (4): 336–45. doi:10.1038/11905. PMID 10431236. Unknown parameter |month= ignored (help)
  5. ↑ Lawn RM, Wade DP, Garvin MR, Wang X, Schwartz K, Porter JG, Seilhamer JJ, Vaughan AM, Oram JF (1999). "The Tangier disease gene product ABC1 controls the cellular apolipoprotein-mediated lipid removal pathway". The Journal of Clinical Investigation. 104 (8): R25–31. doi:10.1172/JCI8119. PMC 481052. PMID 10525055. Unknown parameter |month= ignored (help)
  6. ↑ "American Heart Association Selects CV Therapeutics' Discovery of Role Of 'Good' Cholesterol-Regulating Gene as Top Ten 1999 Research Advances In Heart Disease". PR Newswire Association. 2000-01-03. Retrieved 2009-05-08.
  7. ↑ "Entrez Gene: ABCA1 ATP-binding cassette, sub-family A (ABC1), member 1".
  8. ↑ Schmitz G, Langmann T (2001). "Structure, function and regulation of the ABC1 gene product". Curr. Opin. Lipidol. 12 (2): 129–40. doi:10.1097/00041433-200104000-00006. PMID 11264984. Unknown parameter |month= ignored (help)
  9. ↑ E. M. Wagner, F. Basso, C. S. Kim, M. J. A. Amar, "ABC lipid transporters", in AccessScience@McGraw-Hill
  10. ↑ Yokoyama S (2006). "ABCA1 and biogenesis of HDL". J. Atheroscler. Thromb. 13 (1): 1–15. doi:10.5551/jat.13.1. PMID 16505586. Unknown parameter |month= ignored (help)
  11. ↑ Bachmeier BE, Iancu CM, Killian PH, Kronski E, Mirisola V, Angelini G, Jochum M, Nerlich AG,Pfeffer U. (2009). "Overexpression of the ATP binding cassette gene ABCA1 determines resistance to Curcumin in M14 melanoma cells". Mol Cancer. 8: 129–141. doi:10.1186/1476-4598-8-129. PMC 2804606. PMID 20030852.
  12. ↑ Sene A, Khan AA,; et al. (2013). "Impaired Cholesterol Efflux in Senescent Macrophages Promotes Age-Related Macular Degeneration". Cell Metabolism. 17: 549–561.
  13. ↑ Ordovas JM (2000). "ABC1: the gene for Tangier disease and beyond". Nutr. Rev. 58 (3 Pt 1): 76–9. doi:10.1111/j.1753-4887.2000.tb01843.x. PMID 10812922. Unknown parameter |month= ignored (help)
  14. ↑ Oram JF, Vaughan AM (2000). "ABCA1-mediated transport of cellular cholesterol and phospholipids to HDL apolipoproteins". Curr. Opin. Lipidol. 11 (3): 253–60. doi:10.1097/00041433-200006000-00005. PMID 10882340. Unknown parameter |month= ignored (help)
  15. ↑ Fitzgerald, Michael L (2002). "Naturally occurring mutations in the largest extracellular loops of ABCA1 can disrupt its direct interaction with apolipoprotein A-I". J. Biol. Chem. United States. 277 (36): 33178–87. doi:10.1074/jbc.M204996200. ISSN 0021-9258. PMID 12084722. Unknown parameter |month= ignored (help); Unknown parameter |coauthors= ignored (help)
  16. ↑ Buechler, Christa (2002). "Molecular and functional interaction of the ATP-binding cassette transporter A1 with Fas-associated death domain protein". J. Biol. Chem. United States. 277 (44): 41307–10. doi:10.1074/jbc.C200436200. ISSN 0021-9258. PMID 12235128. Unknown parameter |month= ignored (help); Unknown parameter |coauthors= ignored (help)
  17. ↑ Shimizu, Yuichiro (2003). "Xeroderma pigmentosum group C protein interacts physically and functionally with thymine DNA glycosylase". EMBO J. England. 22 (1): 164–73. doi:10.1093/emboj/cdg016. ISSN 0261-4189. PMC 140069. PMID 12505994. Unknown parameter |month= ignored (help); Unknown parameter |coauthors= ignored (help)
  18. ↑ Buechler, Christa (2002). "The carboxyterminus of the ATP-binding cassette transporter A1 interacts with a beta2-syntrophin/utrophin complex". Biochem. Biophys. Res. Commun. United States. 293 (2): 759–65. doi:10.1016/S0006-291X(02)00303-0. ISSN 0006-291X. PMID 12054535. Unknown parameter |month= ignored (help); Unknown parameter |coauthors= ignored (help)

Template:WikiDoc Sources

Retrieved from "https://www.wikidoc.org/index.php?title=ABCA1&oldid=889255"