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Gene Review

ABCA1  -  ATP-binding cassette, sub-family A (ABC1),...

Homo sapiens

Synonyms: ABC-1, ABC1, ATP-binding cassette 1, ATP-binding cassette sub-family A member 1, ATP-binding cassette transporter 1, ...
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Disease relevance of ABCA1


Psychiatry related information on ABCA1


High impact information on ABCA1


Chemical compound and disease context of ABCA1


Biological context of ABCA1


Anatomical context of ABCA1

  • During incubations of up to 6 h, apoE secretion from both THP1 macrophages and HMDM was stimulated by 8-Br-cAMP, which activates ABCA1 expression [1].
  • Inhibition of ABCA1 in HMDM prevented the occurrence of anti-apoE-immunoreactive granular structures in the plasma membrane [1].
  • The dynamics of ABCA1-mediated apoA-I lipidation were investigated in intact human fibroblasts induced with 22(R)-hydroxycholesterol and 9-cis-retinoic acid (stimulated cells) [23].
  • Trypsin limited-digestion of purified ABCA1 in the detergent-soluble form suggested that it retained conformation similar to ABCA1 expressed in the membranes of human fibroblast WI-38 cells [24].
  • The expression of syntaxins and ABCA1 in cultured human monocytes during M-CSF differentiation and cholesterol loading was investigated and syntaxins 3, 6, and 13 were found induced in foam cells together with ABCA1 [25].

Associations of ABCA1 with chemical compounds

  • The ATP-binding cassette transporter A1 (ABCA1) mediates efflux of cellular cholesterol to lipid-poor apolipoproteins but not to HDL particles that constitute the bulk of plasma HDL [26].
  • The putative ABCA1 inhibitor glyburide and antisense oligonucleotides directed against ABCA1 mRNA significantly reduced apoE secretion from THP1 macrophages and HMDM [1].
  • Here we investigated the contribution of the adenosine triphosphate binding cassette transporters ABCA1 and ABC8 to the secretion of apoE from either primary human monocyte-derived macrophages (HMDM) or human THP1 macrophages [1].
  • This implies that lipidation of apolipoprotein A-I by the ABCA1 pathway is required for generating HDL particles and clearing sterol from macrophages [15].
  • Treatment of intact cells with either phosphatidylcholine-specific phospholipase C or sphingomyelinase affected neither (125)I-apoA-I binding nor (125)I-apoA-I/ABCA1 cross-linking [23].
  • Functional analyses of the coding polymorphisms showed an effect of the V825I substitution on ABCA1 function, with the 825I variant having higher activity in mediating cholesterol efflux than the wild-type (825V) [27].
  • We describe a novel bihelical peptide with asymmetry in the lipid affinity of its helices and properties similar to apoA-I in terms of specificity for cholesterol efflux by the ABCA1 transporter and low cytotoxicity [28].

Physical interactions of ABCA1


Enzymatic interactions of ABCA1


Regulatory relationships of ABCA1

  • These results suggest that the interaction of apolipoproteins with ABCA1-expressing cells activates JAK2, which in turn activates a process that enhances apolipoprotein interactions with ABCA1 and lipid removal from cells [30].
  • ZNF202 is inversely regulated with its target genes ABCA1 and apoE during macrophage differentiation and foam cell formation [34].
  • Downregulated CD36 and oxLDL uptake and stimulated ABCA1/G1 and cholesterol efflux as anti-atherosclerotic mechanisms of interleukin-10 [35].
  • We conclude that ABCA1 transduces signals from apoA-I by complexing and activating Cdc42 and downstream kinases and, therefore, acts as a full apoA-I receptor [16].
  • Genes of cholesterol metabolism in human atheroma: overexpression of perilipin and genes promoting cholesterol storage and repression of ABCA1 expression [4].

Other interactions of ABCA1

  • ATP-binding cassette transporter A1 contains a novel C-terminal VFVNFA motif that is required for its cholesterol efflux and ApoA-I binding activities [36].
  • We show here that treatment of human NPC1(-/-) fibroblasts with the liver X receptor (LXR) agonist TO-901317 increases ABCA1 expression and activity in human NPC1(-/-) fibroblasts, as indicated by near normalization of efflux of radiolabeled phosphatidylcholine and a marked increase in efflux of cholesterol mass to apoA-I [37].
  • The association of FADD with ABCA1 provides an unexpected link between high density lipoprotein metabolism and an adaptor molecule mainly described in death receptor signal transduction [2].
  • This transcriptional effect required the presence of the SCAN domain in ZNF202 and the functional integrity of a TATA box at position -24 of ABCA1, whereas the presence of GnT binding motifs was nonessential [19].
  • ABC2, therefore, is a glycosylated ABC transporter protein, and may play an especially important role in the brain [38].

Analytical, diagnostic and therapeutic context of ABCA1


  1. ATP binding cassette transporter ABCA1 modulates the secretion of apolipoprotein E from human monocyte-derived macrophages. Von Eckardstein, A., Langer, C., Engel, T., Schaukal, I., Cignarella, A., Reinhardt, J., Lorkowski, S., Li, Z., Zhou, X., Cullen, P., Assmann, G. FASEB J. (2001) [Pubmed]
  2. Molecular and functional interaction of the ATP-binding cassette transporter A1 with Fas-associated death domain protein. Buechler, C., Bared, S.M., Aslanidis, C., Ritter, M., Drobnik, W., Schmitz, G. J. Biol. Chem. (2002) [Pubmed]
  3. ABCA1, ApoA-I and type II DM. Saleheen, D. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  4. Genes of cholesterol metabolism in human atheroma: overexpression of perilipin and genes promoting cholesterol storage and repression of ABCA1 expression. Forcheron, F., Legedz, L., Chinetti, G., Feugier, P., Letexier, D., Bricca, G., Beylot, M. Arterioscler. Thromb. Vasc. Biol. (2005) [Pubmed]
  5. A common variant in the ABCA1 gene is associated with a lower risk for premature coronary heart disease in familial hypercholesterolaemia. Cenarro, A., Artieda, M., Castillo, S., Mozas, P., Reyes, G., Tejedor, D., Alonso, R., Mata, P., Pocoví, M., Civeira, F. J. Med. Genet. (2003) [Pubmed]
  6. Cyclosporin A decreases apolipoprotein E secretion from human macrophages via a protein phosphatase 2B-dependent and ATP-binding cassette transporter A1 (ABCA1)-independent pathway. Kockx, M., Guo, D.L., Traini, M., Gaus, K., Kay, J., Wimmer-Kleikamp, S., Rentero, C., Burnett, J.R., Le Goff, W., Van Eck, M., Stow, J.L., Jessup, W., Kritharides, L. J. Biol. Chem. (2009) [Pubmed]
  7. ABCA2 is a strong genetic risk factor for early-onset Alzheimer's disease. Macé, S., Cousin, E., Ricard, S., Génin, E., Spanakis, E., Lafargue-Soubigou, C., Génin, B., Fournel, R., Roche, S., Haussy, G., Massey, F., Soubigou, S., Bréfort, G., Benoit, P., Brice, A., Campion, D., Hollis, M., Pradier, L., Benavides, J., Deleuze, J.F. Neurobiol. Dis. (2005) [Pubmed]
  8. Moderate alcohol consumption increases cholesterol efflux mediated by ABCA1. Beulens, J.W., Sierksma, A., van Tol, A., Fournier, N., van Gent, T., Paul, J.L., Hendriks, H.F. J. Lipid Res. (2004) [Pubmed]
  9. Regulation of ABCA1 expression in human keratinocytes and murine epidermis. Jiang, Y.J., Lu, B., Kim, P., Elias, P.M., Feingold, K.R. J. Lipid Res. (2006) [Pubmed]
  10. An ATP-driven efflux pump is a novel pathogenicity factor in rice blast disease. Urban, M., Bhargava, T., Hamer, J.E. EMBO J. (1999) [Pubmed]
  11. Biochemistry of mammalian peroxisomes revisited. Wanders, R.J., Waterham, H.R. Annu. Rev. Biochem. (2006) [Pubmed]
  12. ATP-binding cassette transporters in bacteria. Davidson, A.L., Chen, J. Annu. Rev. Biochem. (2004) [Pubmed]
  13. Mammalian ABC transporters in health and disease. Borst, P., Elferink, R.O. Annu. Rev. Biochem. (2002) [Pubmed]
  14. Naturally occurring mutations in the largest extracellular loops of ABCA1 can disrupt its direct interaction with apolipoprotein A-I. Fitzgerald, M.L., Morris, A.L., Rhee, J.S., Andersson, L.P., Mendez, A.J., Freeman, M.W. J. Biol. Chem. (2002) [Pubmed]
  15. ABCA1-mediated transport of cellular cholesterol and phospholipids to HDL apolipoproteins. Oram, J.F., Vaughan, A.M. Curr. Opin. Lipidol. (2000) [Pubmed]
  16. Apolipoprotein A-I activates Cdc42 signaling through the ABCA1 transporter. Nofer, J.R., Remaley, A.T., Feuerborn, R., Wolinnska, I., Engel, T., von Eckardstein, A., Assmann, G. J. Lipid Res. (2006) [Pubmed]
  17. Synthetic amphipathic helical peptides promote lipid efflux from cells by an ABCA1-dependent and an ABCA1-independent pathway. Remaley, A.T., Thomas, F., Stonik, J.A., Demosky, S.J., Bark, S.E., Neufeld, E.B., Bocharov, A.V., Vishnyakova, T.G., Patterson, A.P., Eggerman, T.L., Santamarina-Fojo, S., Brewer, H.B. J. Lipid Res. (2003) [Pubmed]
  18. Probucol inhibits ABCA1-mediated cellular lipid efflux. Favari, E., Zanotti, I., Zimetti, F., Ronda, N., Bernini, F., Rothblat, G.H. Arterioscler. Thromb. Vasc. Biol. (2004) [Pubmed]
  19. The zinc finger protein 202 (ZNF202) is a transcriptional repressor of ATP binding cassette transporter A1 (ABCA1) and ABCG1 gene expression and a modulator of cellular lipid efflux. Porsch-Ozcurumez, M., Langmann, T., Heimerl, S., Borsukova, H., Kaminski, W.E., Drobnik, W., Honer, C., Schumacher, C., Schmitz, G. J. Biol. Chem. (2001) [Pubmed]
  20. Glycosphingolipid accumulation inhibits cholesterol efflux via the ABCA1/apolipoprotein A-I pathway: 1-phenyl-2-decanoylamino-3-morpholino-1-propanol is a novel cholesterol efflux accelerator. Glaros, E.N., Kim, W.S., Quinn, C.M., Wong, J., Gelissen, I., Jessup, W., Garner, B. J. Biol. Chem. (2005) [Pubmed]
  21. Phosphorylation of a pest sequence in ABCA1 promotes calpain degradation and is reversed by ApoA-I. Martinez, L.O., Agerholm-Larsen, B., Wang, N., Chen, W., Tall, A.R. J. Biol. Chem. (2003) [Pubmed]
  22. A potent synthetic LXR agonist is more effective than cholesterol loading at inducing ABCA1 mRNA and stimulating cholesterol efflux. Sparrow, C.P., Baffic, J., Lam, M.H., Lund, E.G., Adams, A.D., Fu, X., Hayes, N., Jones, A.B., Macnaul, K.L., Ondeyka, J., Singh, S., Wang, J., Zhou, G., Moller, D.E., Wright, S.D., Menke, J.G. J. Biol. Chem. (2002) [Pubmed]
  23. Molecular and cellular physiology of apolipoprotein A-I lipidation by the ATP-binding cassette transporter A1 (ABCA1). Denis, M., Haidar, B., Marcil, M., Bouvier, M., Krimbou, L., Genest, J. J. Biol. Chem. (2004) [Pubmed]
  24. Purification and ATPase Activity of Human ABCA1. Takahashi, K., Kimura, Y., Kioka, N., Matsuo, M., Ueda, K. J. Biol. Chem. (2006) [Pubmed]
  25. Association of ABCA1 with syntaxin 13 and flotillin-1 and enhanced phagocytosis in tangier cells. Bared, S.M., Buechler, C., Boettcher, A., Dayoub, R., Sigruener, A., Grandl, M., Rudolph, C., Dada, A., Schmitz, G. Mol. Biol. Cell (2004) [Pubmed]
  26. ATP-binding cassette transporters G1 and G4 mediate cellular cholesterol efflux to high-density lipoproteins. Wang, N., Lan, D., Chen, W., Matsuura, F., Tall, A.R. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  27. Functional polymorphism in ABCA1 influences age of symptom onset in coronary artery disease patients. Kyriakou, T., Pontefract, D.E., Viturro, E., Hodgkinson, C.P., Laxton, R.C., Bogari, N., Cooper, G., Davies, M., Giblett, J., Day, I.N., Simpson, I.A., Albrecht, C., Ye, S. Hum. Mol. Genet. (2007) [Pubmed]
  28. Asymmetry in the lipid affinity of bihelical amphipathic peptides. A structural determinant for the specificity of ABCA1-dependent cholesterol efflux by peptides. Sethi, A.A., Stonik, J.A., Thomas, F., Demosky, S.J., Amar, M., Neufeld, E., Brewer, H.B., Davidson, W.S., D'Souza, W., Sviridov, D., Remaley, A.T. J. Biol. Chem. (2008) [Pubmed]
  29. Apolipoprotein A-I-stimulated apolipoprotein E secretion from human macrophages is independent of cholesterol efflux. Kockx, M., Rye, K.A., Gaus, K., Quinn, C.M., Wright, J., Sloane, T., Sviridov, D., Fu, Y., Sullivan, D., Burnett, J.R., Rust, S., Assmann, G., Anantharamaiah, G.M., Palgunachari, M.N., Katz, S.L., Phillips, M.C., Dean, R.T., Jessup, W., Kritharides, L. J. Biol. Chem. (2004) [Pubmed]
  30. Janus kinase 2 modulates the apolipoprotein interactions with ABCA1 required for removing cellular cholesterol. Tang, C., Vaughan, A.M., Oram, J.F. J. Biol. Chem. (2004) [Pubmed]
  31. Molecular interactions between apoE and ABCA1: impact on apoE lipidation. Krimbou, L., Denis, M., Haidar, B., Carrier, M., Marcil, M., Genest, J. J. Lipid Res. (2004) [Pubmed]
  32. Apolipoprotein A-I activates protein kinase C alpha signaling to phosphorylate and stabilize ATP binding cassette transporter A1 for the high density lipoprotein assembly. Yamauchi, Y., Hayashi, M., Abe-Dohmae, S., Yokoyama, S. J. Biol. Chem. (2003) [Pubmed]
  33. The myeloperoxidase product hypochlorous acid oxidizes HDL in the human artery wall and impairs ABCA1-dependent cholesterol transport. Bergt, C., Pennathur, S., Fu, X., Byun, J., O'Brien, K., McDonald, T.O., Singh, P., Anantharamaiah, G.M., Chait, A., Brunzell, J., Geary, R.L., Oram, J.F., Heinecke, J.W. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  34. ZNF202 is inversely regulated with its target genes ABCA1 and apoE during macrophage differentiation and foam cell formation. Langmann, T., Schumacher, C., Morham, S.G., Honer, C., Heimerl, S., Moehle, C., Schmitz, G. J. Lipid Res. (2003) [Pubmed]
  35. Downregulated CD36 and oxLDL uptake and stimulated ABCA1/G1 and cholesterol efflux as anti-atherosclerotic mechanisms of interleukin-10. Rubic, T., Lorenz, R.L. Cardiovasc. Res. (2006) [Pubmed]
  36. ATP-binding cassette transporter A1 contains a novel C-terminal VFVNFA motif that is required for its cholesterol efflux and ApoA-I binding activities. Fitzgerald, M.L., Okuhira, K., Short, G.F., Manning, J.J., Bell, S.A., Freeman, M.W. J. Biol. Chem. (2004) [Pubmed]
  37. Correction of Apolipoprotein A-I-mediated Lipid Efflux and High Density Lipoprotein Particle Formation in Human Niemann-Pick Type C Disease Fibroblasts. Boadu, E., Choi, H.Y., Lee, D.W., Waddington, E.I., Chan, T., Asztalos, B., Vance, J.E., Chan, A., Castro, G., Francis, G.A. J. Biol. Chem. (2006) [Pubmed]
  38. Cloning, characterization and tissue distribution of the rat ATP-binding cassette (ABC) transporter ABC2/ABCA2. Zhao, L.X., Zhou, C.J., Tanaka, A., Nakata, M., Hirabayashi, T., Amachi, T., Shioda, S., Ueda, K., Inagaki, N. Biochem. J. (2000) [Pubmed]
  39. Protein kinase A site-specific phosphorylation regulates ATP-binding cassette A1 (ABCA1)-mediated phospholipid efflux. See, R.H., Caday-Malcolm, R.A., Singaraja, R.R., Zhou, S., Silverston, A., Huber, M.T., Moran, J., James, E.R., Janoo, R., Savill, J.M., Rigot, V., Zhang, L.H., Wang, M., Chimini, G., Wellington, C.L., Tafuri, S.R., Hayden, M.R. J. Biol. Chem. (2002) [Pubmed]
  40. Dominant expression of ATP-binding cassette transporter-1 on basolateral surface of Caco-2 cells stimulated by LXR/RXR ligands. Ohama, T., Hirano, K., Zhang, Z., Aoki, R., Tsujii, K., Nakagawa-Toyama, Y., Tsukamoto, K., Ikegami, C., Matsuyama, A., Ishigami, M., Sakai, N., Hiraoka, H., Ueda, K., Yamashita, S., Matsuzawa, Y. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  41. A promoter variant of the ATP-binding cassette transporter A1 gene alters the HDL cholesterol level in the general Japanese population. Shioji, K., Nishioka, J., Naraba, H., Kokubo, Y., Mannami, T., Inamoto, N., Kamide, K., Takiuchi, S., Yoshii, M., Miwa, Y., Kawano, Y., Miyata, T., Miyazaki, S., Goto, Y., Nonogi, H., Tago, N., Iwai, N. J. Hum. Genet. (2004) [Pubmed]
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