ABCA1
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| Location (UCSC) | Chr 9: 104.78 – 104.93 Mb | Chr 4: 53.03 – 53.16 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
| View/Edit Human | View/Edit Mouse |
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.[5] This transporter is a major regulator of cellular cholesterol and phospholipid homeostasis.
Tangier disease
It was discovered that a mutation in the ABCA1 protein is responsible for causing
Function
The membrane-associated protein encoded by this gene is a member of the superfamily of
While the complete 3D-structure of ABCA1 remains relatively unknown, there has been some determination of the c-terminus. The ABCA1 c-terminus contains a PDZ domain, responsible for mediating protein-protein interactions, as well as a VFVNFA motif essential for lipid efflux activity.[10]
Physiological role
ABCA1 mediates the efflux of cholesterol and phospholipids to lipid-poor apolipoproteins (apoA1 and apoE) (reverse cholesterol transport), 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.[13]
Factors that act upon the ABCA1 transporter's expression or its
Interactions between members of the apoliprotein family and ABCA1 activate multiple signalling pathways, including the
Overexpression of ABCA1 has been reported to induce resistance to the anti-inflammatory diarylheptanoid antioxidant curcumin.[19] Downregulation of ABCA1 in senescent macrophages disrupts the cell's ability to remove cholesterol from its cytoplasm, leading the cells to promote pathologic
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.[22][23] Leukocytes' ABCA1 gene expression is upregulated in postmenopausal women receiving
Interactive pathway map
Click on genes, proteins and metabolites below to link to respective articles. [§ 1]
- ^ The interactive pathway map can be edited at WikiPathways: "Statin_Pathway_WP430".
Interactions
ABCA1 has been shown to
See also
- ATP-binding cassette transporter
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000165029 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000015243 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 8088782.
- S2CID 26890624.
- S2CID 1497231.
- PMID 10525055.
- ^ "American Heart Association Selects CV Therapeutics' Discovery of Role Of 'Good' Cholesterol-Regulating Gene as Top Ten 1999 Research Advances In Heart Disease" (Press release). CV Therapeutics; Incyte Pharmaceuticals. January 3, 2000. Retrieved May 28, 2018.
- ^ PMID 16704350.
- ^ "Entrez Gene: ABCA1 ATP-binding cassette, sub-family A (ABC1), member 1".
- S2CID 23837673.
- .
- PMID 16505586.
- S2CID 203413137.
- PMID 19287193.
- PMID 28455345.
- S2CID 23391447.
- PMID 20030852.
- PMID 23562078.
- ^ http://www.faqs.org/patents/app/20130317090[full citation needed][permanent dead link]
- PMID 10812922.
- PMID 10882340.
- S2CID 203464.
- PMID 35899587.
- PMID 35978482.
- PMID 12084722.
- PMID 12235128.
- PMID 12054535.
- PMID 12505994.
Further reading
- Tam SP, Mok L, Chimini G, Vasa M, Deeley RG (September 2006). "ABCA1 mediates high-affinity uptake of 25-hydroxycholesterol by membrane vesicles and rapid efflux of oxysterol by intact cells". American Journal of Physiology. Cell Physiology. 291 (3): C490 – C502. S2CID 24019526.
- Oram JF (August 2002). "ATP-binding cassette transporter A1 and cholesterol trafficking". Current Opinion in Lipidology. 13 (4): 373–381. S2CID 20345477.
- Hong SH, Rhyne J, Zeller K, Miller M (October 2002). "ABCA1(Alabama): a novel variant associated with HDL deficiency and premature coronary artery disease". Atherosclerosis. 164 (2): 245–250. PMID 12204794.
- Kozak M (August 2002). "Emerging links between initiation of translation and human diseases". Mammalian Genome. 13 (8): 401–410. S2CID 25690586.
- Joyce C, Freeman L, Brewer HB, Santamarina-Fojo S (June 2003). "Study of ABCA1 function in transgenic mice". Arteriosclerosis, Thrombosis, and Vascular Biology. 23 (6): 965–971. PMID 12615681.
- Singaraja RR, Brunham LR, Visscher H, Kastelein JJ, Hayden MR (August 2003). "Efflux and atherosclerosis: the clinical and biochemical impact of variations in the ABCA1 gene". Arteriosclerosis, Thrombosis, and Vascular Biology. 23 (8): 1322–1332. PMID 12763760.
- Nofer JR, Remaley AT (October 2005). "Tangier disease: still more questions than answers". Cellular and Molecular Life Sciences. 62 (19–20): 2150–2160. S2CID 279676.
- Yokoyama S (February 2006). "ABCA1 and biogenesis of HDL". Journal of Atherosclerosis and Thrombosis. 13 (1): 1–15. PMID 16505586.
- Schmitz G, Schambeck CM (2006). "Molecular defects in the ABCA1 pathway affect platelet function". Pathophysiology of Haemostasis and Thrombosis. 35 (1–2): 166–174. S2CID 71978568.
External links
- ABCA1 human gene location in the UCSC Genome Browser.
- ABCA1 human gene details in the UCSC Genome Browser.
Lipids: lipoprotein particle metabolism | ||
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| Lipoprotein particle classes and subclasses |
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| Apolipoproteins | ||
| Extracellular enzymes | ||
| Lipid transfer proteins | ||
| Cell surface receptors | ||
ATP-binding cassette transporter | ||