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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)

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 a) high density lipoprotein deficiency type 1 (Tangier disease) b) high density lipoprotein deficiency type 2] (familial hypoalphalipoproteinemia) c) 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] 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 Genetics: - loss-of-function mutations present in 1:500 individuals [4]

Related

ATP-binding cassette 1 (ABC1) gene

General

ATP-binding cassette sub-family A (ABC transporter-A, ABCA) glycoprotein phosphoprotein

Properties

SIZE: entity length = 2261 aa MW = 254 kD COMPARTMENT: cellular membrane MOTIF: N-glycosylation site {N14} transmembrane domain {22-42} N-glycosylation site {N98} N-glycosylation site {N151} N-glycosylation site {N161} N-glycosylation site {N196} N-glycosylation site {N244} N-glycosylation site {N292} N-glycosylation site {N337} N-glycosylation site {N349} N-glycosylation site {N400} N-glycosylation site {N478} N-glycosylation site {N489} N-glycosylation site {N521} transmembrane domain {640-660} transmembrane domain {683-703} transmembrane domain {716-736} transmembrane domain {745-765} transmembrane domain {777-797} N-glycosylation site {N820} transmembrane domain {827-847} ABC transporter 1 {899-1131} MOTIF: ATP-binding site NAME: ATP-binding site SITE: 933-940 transmembrane domain {1041-1057} Ser phosphorylation site {S1042} Ser phosphorylation site {S1141} N-glycosylation site {N1144} Ser phosphorylation site {S1147} N-glycosylation site {N1294} transmembrane domain {1351-1371} N-glycosylation site {N1453} N-glycosylation site {N1504} N-glycosylation site {N1637} transmembrane domain {1657-1677} transmembrane domain {1703-1723} transmembrane domain {1735-1755} transmembrane domain {1768-1788} transmembrane domain {1802-1822} transmembrane domain {1852-1872} ABC transporter 2 {1912-2144} MOTIF: ATP-binding site NAME: ATP-binding site SITE: 1946-1953 N-glycosylation site {N2044} Ser phosphorylation site {S2054} N-glycosylation site {N2238}

Database Correlations

OMIM correlations MORBIDMAP 600046 UniProt O95477 Pfam PF00005 Entrez Gene 19 Kegg hsa:19

References

  1. UniProt :accession O95477 SHMPD; The Singapore human mutation and polymorphism database http://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=ABCA1
  2. Laffitte BA et al, LXRs control lipid-inducible expression of the apolipoprotein E gene in macrophages and adipocytes. PNAS 98:507, 2001 PMID: 11149950
  3. 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 PMID: 25404125 http://www.nejm.org/doi/full/10.1056/NEJMoa1409065
  4. 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: 26079414
  5. 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: 33615168 PMCID: PMC7887740