ATP-binding cassette sub-family A member 1; ATP-binding cassette transporter 1; ATP-binding cassette 1; ABC-1; cholesterol efflux regulatory protein (ABCA1, ABC1, CERP)
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Function
- cAMP-dependent & sulfonylurea-sensitive anion transporter
- key gatekeeper influencing intracellular cholesterol transport
- facilitates efflux of free cholesterol from cells
- efflux of cholesteral from macrophages[3]
- interacts with MEGF10
- phosphorylation on Ser-2054 regulates phospholipid efflux
Structure
- multifunctional polypeptide with two homologous halves, each containing an hydrophobic membrane-anchoring domain & an ATP binding cassette domain (ABC domain)
- belongs to the ABC transporter family, ABCA subfamily contains 2 ABC transporter domains
Compartment
membrane (putative)
Expression
- widely expressed, but most abundant in macrophages
- highly induced in lipid-laden macrophages
- induced by bacterial lipopolysaccharides (LPS)
- LPS regulates expression (LXR-independent)
- repressed by ZNF202
Pathology
- defects in ABCA1 are a cause of
- high density lipoprotein deficiency type 1 (Tangier disease)
- high density lipoprotein deficiency type 2] (familial hypoalphalipoproteinemia)
- low levels of expression (or function) may be associated with increased risk of cardiovascular disease[3]
- mutations also associated with a form of cerebral amyloid angiopathy & risk of Alzheimer's disease[4]
Genetics
Pharmacology
- a small molecule, CL2-57, stimulates ABCA1 activity with positive effects on liver & plasma triglycerides[5]
- CL2-57 improves glucose tolerance & insulin sensitivity & reduces weight gain
More general terms
References
- ↑ UniProt http://www.uniprot.org/uniprot/O95477.html SHMPD; The Singapore human mutation and polymorphism database http://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=ABCA1
- ↑ Laffitte BA et al, LXRs control lipid-inducible expression of the apolipoprotein E gene in macrophages and adipocytes. PNAS 98:507, 2001 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11149950
- ↑ 3.0 3.1 3.2 Husten L, Fairchild DG, Di Francesco L HDL Function, Not Level, Looks Like the Key Physician's First Watch, Nov 19, 2014 David G. Fairchild, MD, MPH, Editor-in-Chief Massachusetts Medical Society http://www.jwatch.org
Rohatgi A et al HDL Cholesterol Efflux Capacity and Incident Cardiovascular Events. N Engl J Med. Nov 18, 2014 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25404125 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1409065 - ↑ 4.0 4.1 4.2 Nordestgaard LT, Tybjaerg-Hansen A, Nordestgaard BG et al Loss-of-function mutation in ABCA1 and risk of Alzheimer's disease and cerebrovascular disease. Alzheimers Dement. 2015 Dec;11(12):1430-8 PMID: https://www.ncbi.nlm.nih.gov/pubmed/26079414
- ↑ 5.0 5.1 University of Arizona Health Sciences. Cholesterol may be key to new therapies for Alzheimer's disease, diabetes. ScienceDaily, 25 March 2021 https://www.sciencedaily.com/releases/2021/03/210325150226.htm
Aissa MB, Lewandowski CT, Ratia KM et al Discovery of Nonlipogenic ABCA1 Inducing Compounds with Potential in Alzheimer's Disease and Type 2 Diabetes. ACS Pharmacology & Translational Science, 2021; 4 (1): 143 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33615168 PMCID: PMC7887740
Database
- Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:19
- OMIM: https://mirror.omim.org/entry/205400
- OMIM: https://mirror.omim.org/entry/600046
- OMIM: https://mirror.omim.org/entry/604091
- UniProt: http://www.uniprot.org/uniprot/O95477.html
- Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=19