ABCA1_HUMAN
ID ABCA1_HUMAN Reviewed; 2261 AA.
AC O95477; Q5VX33; Q96S56; Q96T85; Q9NQV4; Q9UN06; Q9UN07; Q9UN08; Q9UN09;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 05-OCT-2010, sequence version 3.
DT 03-AUG-2022, entry version 224.
DE RecName: Full=Phospholipid-transporting ATPase ABCA1 {ECO:0000305};
DE EC=7.6.2.1 {ECO:0000269|PubMed:24097981};
DE AltName: Full=ATP-binding cassette sub-family A member 1;
DE AltName: Full=ATP-binding cassette transporter 1;
DE Short=ABC-1;
DE Short=ATP-binding cassette 1;
DE AltName: Full=Cholesterol efflux regulatory protein;
GN Name=ABCA1 {ECO:0000312|HGNC:HGNC:29}; Synonyms=ABC1, CERP;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND VARIANT ARG-1587.
RX PubMed=10884428; DOI=10.1073/pnas.97.14.7987;
RA Santamarina-Fojo S., Peterson K.M., Knapper C.L., Qiu Y., Freeman L.A.,
RA Cheng J.-F., Osorio J., Remaley A.T., Yang X.-P., Haudenschild C.C.,
RA Prades C., Chimini G., Blackmon E.E., Francois T.L., Duverger N.,
RA Rubin E.M., Rosier M., Denefle P., Fredrickson D.S., Brewer H.B. Jr.;
RT "Complete genomic sequence of the human ABCA1 gene: analysis of the human
RT and mouse ATP-binding cassette A promoter.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:7987-7992(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT ARG-1587.
RC TISSUE=Skin;
RA Schwartz K., Lawn R.M., Wade D.P.;
RT "ABCA1 gene expression and apoA-I-mediated cholesterol efflux are regulated
RT by LXR.";
RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ARG-1587.
RX PubMed=11352567; DOI=10.1006/geno.2000.6467;
RA Qiu Y., Cavelier L., Chiu S., Yang X., Rubin E., Cheng J.-F.;
RT "Human and mouse ABCA1 comparative sequencing and transgenesis studies
RT revealing novel regulatory sequences.";
RL Genomics 73:66-76(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Tanaka A.R., Abe-Dohmae S., Arakawa R., Sadanami K., Kidera A., Kioka N.,
RA Amachi T., Yokoyama S., Ueda K.;
RT "A new topological model of functional human ABCA1-signal peptide cleavage
RT and glycosylation of a large extracellular domain.";
RL Submitted (FEB-2001) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 21-2261, AND VARIANTS THR-1555; ARG-1587;
RP PRO-1648 AND PRO-2168.
RX PubMed=10092505; DOI=10.1006/bbrc.1999.0406;
RA Langmann T., Klucken J., Reil M., Liebisch G., Luciani M.-F., Chimini G.,
RA Kaminski W.E., Schmitz G.;
RT "Molecular cloning of the human ATP-binding cassette transporter 1 (hABC1):
RT evidence for sterol-dependent regulation in macrophages.";
RL Biochem. Biophys. Res. Commun. 257:29-33(1999).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 21-2261, AND VARIANTS THR-1555;
RP ARG-1587; PRO-1648 AND PRO-2168.
RX PubMed=10431238; DOI=10.1038/11921;
RA Rust S., Rosier M., Funke H., Real J., Amoura Z., Piette J.-C.,
RA Deleuze J.-F., Brewer H.B. Jr., Duverger N., Denefle P., Assmann G.;
RT "Tangier disease is caused by mutations in the gene encoding ATP-binding
RT cassette transporter 1.";
RL Nat. Genet. 22:352-355(1999).
RN [8]
RP PHOSPHORYLATION AT SER-1042 AND SER-2054.
RX PubMed=12196520; DOI=10.1074/jbc.m204923200;
RA See R.H., Caday-Malcolm R.A., Singaraja R.R., Zhou S., Silverston A.,
RA Huber M.T., Moran J., James E.R., Janoo R., Savill J.M., Rigot V.,
RA Zhang L.H., Wang M., Chimini G., Wellington C.L., Tafuri S.R., Hayden M.R.;
RT "Protein kinase A site-specific phosphorylation regulates ATP-binding
RT cassette A1 (ABCA1)-mediated phospholipid efflux.";
RL J. Biol. Chem. 277:41835-41842(2002).
RN [9]
RP REPRESSION BY ZNF202.
RX PubMed=11279031; DOI=10.1074/jbc.m100218200;
RA Porsch-Oezcueruemez M., Langmann T., Heimerl S., Borsukova H.,
RA Kaminski W.E., Drobnik W., Honer C., Schumacher C., Schmitz G.;
RT "The zinc finger protein 202 (ZNF202) is a transcriptional repressor of ATP
RT binding cassette transporter A1 (ABCA1) and ABCG1 gene expression and a
RT modulator of cellular lipid efflux.";
RL J. Biol. Chem. 276:12427-12433(2001).
RN [10]
RP INDUCTION BY LPS.
RX PubMed=12032171;
RA Kaplan R., Gan X., Menke J.G., Wright S.D., Cai T.-Q.;
RT "Bacterial lipopolysaccharide induces expression of ABCA1 but not ABCG1 via
RT an LXR-independent pathway.";
RL J. Lipid Res. 43:952-959(2002).
RN [11]
RP INTERACTION WITH MEGF10.
RX PubMed=17205124; DOI=10.1371/journal.pone.0000120;
RA Hamon Y., Trompier D., Ma Z., Venegas V., Pophillat M., Mignotte V.,
RA Zhou Z., Chimini G.;
RT "Cooperation between engulfment receptors: the case of ABCA1 and MEGF10.";
RL PLoS ONE 1:E120-E120(2006).
RN [12]
RP INTERACTION WITH ABCA12 AND NR1H2.
RX PubMed=23931754; DOI=10.1016/j.cmet.2013.07.003;
RA Fu Y., Mukhamedova N., Ip S., D'Souza W., Henley K.J., DiTommaso T.,
RA Kesani R., Ditiatkovski M., Jones L., Lane R.M., Jennings G., Smyth I.M.,
RA Kile B.T., Sviridov D.;
RT "ABCA12 regulates ABCA1-dependent cholesterol efflux from macrophages and
RT the development of atherosclerosis.";
RL Cell Metab. 18:225-238(2013).
RN [13]
RP REVIEW ON VARIANTS.
RX PubMed=12763760; DOI=10.1161/01.atv.0000078520.89539.77;
RA Singaraja R.R., Brunham L.R., Visscher H., Kastelein J.J.P., Hayden M.R.;
RT "Efflux and atherosclerosis: the clinical and biochemical impact of
RT variations in the ABCA1 gene.";
RL Arterioscler. Thromb. Vasc. Biol. 23:1322-1332(2003).
RN [14]
RP POLYMORPHISM, AND INVOLVEMENT IN HDLCQ13.
RX PubMed=18354102; DOI=10.1056/nejmoa0706728;
RA Kathiresan S., Melander O., Anevski D., Guiducci C., Burtt N.P., Roos C.,
RA Hirschhorn J.N., Berglund G., Hedblad B., Groop L., Altshuler D.M.,
RA Newton-Cheh C., Orho-Melander M.;
RT "Polymorphisms associated with cholesterol and risk of cardiovascular
RT events.";
RL N. Engl. J. Med. 358:1240-1249(2008).
RN [15]
RP PALMITOYLATION AT CYS-3; CYS-23; CYS-1110 AND CYS-1111, SUBCELLULAR
RP LOCATION, MUTAGENESIS OF CYS-3; CYS-23; CYS-1110 AND CYS-1111, AND
RP CHARACTERIZATION OF VARIANT FHA1 THR-1091.
RX PubMed=19556522; DOI=10.1161/circresaha.108.193011;
RA Singaraja R.R., Kang M.H., Vaid K., Sanders S.S., Vilas G.L.,
RA Arstikaitis P., Coutinho J., Drisdel R.C., El-Husseini Ael D., Green W.N.,
RA Berthiaume L., Hayden M.R.;
RT "Palmitoylation of ATP-binding cassette transporter A1 is essential for its
RT trafficking and function.";
RL Circ. Res. 105:138-147(2009).
RN [16]
RP DISULFIDE BONDS, SUBCELLULAR LOCATION, AND TOPOLOGY.
RX PubMed=19258317; DOI=10.1074/jbc.m900580200;
RA Hozoji M., Kimura Y., Kioka N., Ueda K.;
RT "Formation of two intramolecular disulfide bonds is necessary for ApoA-I-
RT dependent cholesterol efflux mediated by ABCA1.";
RL J. Biol. Chem. 284:11293-11300(2009).
RN [17]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-98 AND ASN-244.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [18]
RP CATALYTIC ACTIVITY, ACTIVITY REGULATION, MUTAGENESIS OF SER-100; PHE-593;
RP LYS-939; THR-1512 AND LYS-1952, FUNCTION, VARIANTS TGD SER-590; ILE-929;
RP SER-935; ARG-1477 AND TRP-2081, CHARACTERIZATION OF VARIANTS TGD SER-590;
RP ILE-929; SER-935; ARG-1477 AND TRP-2081, VARIANT FHA1 LEU-2150,
RP CHARACTERIZATION OF VARIANT FHA1 LEU-2150, AND SUBCELLULAR LOCATION.
RX PubMed=24097981; DOI=10.1074/jbc.m113.508812;
RA Quazi F., Molday R.S.;
RT "Differential phospholipid substrates and directional transport by ATP-
RT binding cassette proteins ABCA1, ABCA7, and ABCA4 and disease-causing
RT mutants.";
RL J. Biol. Chem. 288:34414-34426(2013).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [20]
RP FUNCTION, INTERACTION WITH APOE, AND CHARACTERIZATION OF VARIANT TGD
RP ARG-1477.
RX PubMed=14754908; DOI=10.1194/jlr.m300418-jlr200;
RA Krimbou L., Denis M., Haidar B., Carrier M., Marcil M., Genest J. Jr.;
RT "Molecular interactions between apoE and ABCA1: impact on apoE
RT lipidation.";
RL J. Lipid Res. 45:839-848(2004).
RN [21]
RP INTERACTION WITH ABCA8.
RX PubMed=28882873; DOI=10.1161/atvbaha.117.309574;
RA Trigueros-Motos L., van Capelleveen J.C., Torta F., Castano D., Zhang L.H.,
RA Chai E.C., Kang M., Dimova L.G., Schimmel A.W.M., Tietjen I., Radomski C.,
RA Tan L.J., Thiam C.H., Narayanaswamy P., Wu D.H., Dorninger F., Yakala G.K.,
RA Barhdadi A., Angeli V., Dube M.P., Berger J., Dallinga-Thie G.M.,
RA Tietge U.J.F., Wenk M.R., Hayden M.R., Hovingh G.K., Singaraja R.R.;
RT "ABCA8 Regulates Cholesterol Efflux and High-Density Lipoprotein
RT Cholesterol Levels.";
RL Arterioscler. Thromb. Vasc. Biol. 37:2147-2155(2017).
RN [22]
RP VARIANTS FHA1 THR-1091 AND 1893-GLU-ASP-1894 DEL, AND FUNCTION.
RX PubMed=10533863; DOI=10.1016/s0140-6736(99)07026-9;
RA Marcil M., Brooks-Wilson A., Clee S.M., Roomp K., Zhang L.-H., Yu L.,
RA Collins J.A., van Dam M., Molhuizen H.O.F., Loubser O., Ouellette B.F.F.,
RA Sensen C.W., Fichter K., Mott S., Denis M., Boucher B., Pimstone S.,
RA Genest J. Jr., Kastelein J.J.P., Hayden M.R.;
RT "Mutations in the ABC1 gene in familial HDL deficiency with defective
RT cholesterol efflux.";
RL Lancet 354:1341-1346(1999).
RN [23]
RP VARIANTS TGD ARG-597 AND ARG-1477, AND VARIANT FHA1 LEU-693 DEL.
RX PubMed=10431236; DOI=10.1038/11905;
RA Brooks-Wilson A., Marcil M., Clee S.M., Zhang L.-H., Roomp K., van Dam M.,
RA Yu L., Brewer C., Collins J.A., Molhuizen H.O.F., Loubser O.,
RA Ouelette B.F.F., Fichter K., Ashbourne-Excoffon K.J.D., Sensen C.W.,
RA Scherer S., Mott S., Denis M., Martindale D., Frohlich J., Morgan K.,
RA Koop B., Pimstone S., Kastelein J.J.P., Hayden M.R.;
RT "Mutations in ABC1 in Tangier disease and familial high-density lipoprotein
RT deficiency.";
RL Nat. Genet. 22:336-345(1999).
RN [24]
RP VARIANTS TGD SER-590; SER-935 AND VAL-937, AND VARIANTS ALA-399 AND
RP MET-883.
RX PubMed=10431237; DOI=10.1038/11914;
RA Bodzioch M., Orso E., Klucken J., Langmann T., Boettcher A., Diederich W.,
RA Drobnik W., Barlage S., Buechler C., Porsch-Oezcueruemez M., Kaminski W.E.,
RA Hahmann H.W., Oette K., Rothe G., Aslanidis C., Lackner K.J., Schmitz G.;
RT "The gene encoding ATP-binding cassette transporter 1 is mutated in Tangier
RT disease.";
RL Nat. Genet. 22:347-351(1999).
RN [25]
RP VARIANTS TGD ARG-597; ILE-929 AND ARG-1477, AND VARIANTS FHA1 LEU-693 DEL;
RP THR-1091; 1893-GLU-ASP-1894 DEL AND LEU-2150.
RX PubMed=11086027; DOI=10.1172/jci10727;
RA Clee S.M., Kastelein J.J.P., van Dam M., Marcil M., Roomp K., Zwarts K.Y.,
RA Collins J.A., Roelants R., Tamasawa N., Stulc T., Suda T., Ceska R.,
RA Boucher B., Rondeau C., DeSouich C., Brooks-Wilson A., Molhuizen H.O.F.,
RA Frohlich J., Genest J. Jr., Hayden M.R.;
RT "Age and residual cholesterol efflux affect HDL cholesterol levels and
RT coronary artery disease in ABCA1 heterozygotes.";
RL J. Clin. Invest. 106:1263-1270(2000).
RN [26]
RP VARIANTS TGD ASN-1289 AND HIS-1800.
RX PubMed=10706591;
RA Brousseau M.E., Schaefer E.J., Dupuis J., Eustace B., Van Eerdewegh P.,
RA Goldkamp A.L., Thurston L.M., FitzGerald M.G., Yasek-McKenna D.,
RA O'Neill G., Eberhart G.P., Weiffenbach B., Ordovas J.M., Freeman M.W.,
RA Brown R.H. Jr., Gu J.Z.;
RT "Novel mutations in the gene encoding ATP-binding cassette 1 in four
RT tangier disease kindreds.";
RL J. Lipid Res. 41:433-441(2000).
RN [27]
RP VARIANT TGD ASP-1046, AND VARIANTS LYS-219; CYS-230; ILE-825; MET-883 AND
RP ARG-1587.
RX PubMed=10938021; DOI=10.1161/01.atv.20.8.1983;
RA Wang J., Burnett J.R., Near S., Young K., Zinman B., Hanley A.J.G.,
RA Connelly P.W., Harris S.B., Hegele R.A.;
RT "Common and rare ABCA1 variants affecting plasma HDL cholesterol.";
RL Arterioscler. Thromb. Vasc. Biol. 20:1983-1989(2000).
RN [28]
RP VARIANT TGD TRP-587, AND VARIANT PRO-2168.
RX PubMed=11257260; DOI=10.1016/s0021-9150(00)00587-6;
RA Bertolini S., Pisciotta L., Seri M., Cusano R., Cantafora A., Calabresi L.,
RA Franceschini G., Ravazzolo R., Calandra S.;
RT "A point mutation in ABC1 gene in a patient with severe premature coronary
RT heart disease and mild clinical phenotype of Tangier disease.";
RL Atherosclerosis 154:599-605(2001).
RN [29]
RP VARIANTS LYS-219; MET-883 AND ASP-1172.
RX PubMed=11257261; DOI=10.1016/s0021-9150(00)00722-x;
RA Brousseau M.E., Bodzioch M., Schaefer E.J., Goldkamp A.L., Kielar D.,
RA Probst M., Ordovas J.M., Aslanidis C., Lackner K.J., Bloomfield Rubins H.,
RA Collins D., Robins S.J., Wilson P.W.F., Schmitz G.;
RT "Common variants in the gene encoding ATP-binding cassette transporter 1 in
RT men with low HDL cholesterol levels and coronary heart disease.";
RL Atherosclerosis 154:607-611(2001).
RN [30]
RP VARIANT TGD LEU-1506.
RX PubMed=11476961; DOI=10.1016/s0925-4439(01)00053-9;
RA Lapicka-Bodzioch K., Bodzioch M., Kruell M., Kielar D., Probst M., Kiec B.,
RA Andrikovics H., Boettcher A., Hubacek J., Aslanidis C., Suttorp N.,
RA Schmitz G.;
RT "Homogeneous assay based on 52 primer sets to scan for mutations of the
RT ABCA1 gene and its application in genetic analysis of a new patient with
RT familial high-density lipoprotein deficiency syndrome.";
RL Biochim. Biophys. Acta 1537:42-48(2001).
RN [31]
RP VARIANTS TGD ASN-1289 AND TRP-2081, AND VARIANT LYS-219.
RX PubMed=11476965; DOI=10.1016/s0925-4439(01)00058-8;
RA Huang W., Moriyama K., Koga T., Hua H., Ageta M., Kawabata S., Mawatari K.,
RA Imamura T., Eto T., Kawamura M., Teramoto T., Sasaki J.;
RT "Novel mutations in ABCA1 gene in Japanese patients with Tangier disease
RT and familial high density lipoprotein deficiency with coronary heart
RT disease.";
RL Biochim. Biophys. Acta 1537:71-78(2001).
RN [32]
RP VARIANTS LYS-219; ALA-399; MET-771; PRO-774; ASN-776; ILE-825; MET-883;
RP ASP-1172; ARG-1587 AND CYS-1731.
RX PubMed=11238261; DOI=10.1161/01.cir.103.9.1198;
RA Clee S.M., Zwinderman A.H., Engert J.C., Zwarts K.Y., Molhuizen H.O.F.,
RA Roomp K., Jukema J.W., van Wijland M., van Dam M., Hudson T.J.,
RA Brooks-Wilson A., Genest J. Jr., Kastelein J.J.P., Hayden M.R.;
RT "Common genetic variation in ABCA1 is associated with altered lipoprotein
RT levels and a modified risk for coronary artery disease.";
RL Circulation 103:1198-1205(2001).
RN [33]
RP VARIANT FHA1 LEU-85.
RX PubMed=12204794; DOI=10.1016/s0021-9150(02)00106-5;
RA Hong S.H., Rhyne J., Zeller K., Miller M.;
RT "ABCA1(Alabama): a novel variant associated with HDL deficiency and
RT premature coronary artery disease.";
RL Atherosclerosis 164:245-250(2002).
RN [34]
RP VARIANTS FHA1 TYR-1099 AND SER-2009.
RX PubMed=12009425; DOI=10.1016/s0925-4439(02)00066-2;
RA Hong S.H., Rhyne J., Zeller K., Miller M.;
RT "Novel ABCA1 compound variant associated with HDL cholesterol deficiency.";
RL Biochim. Biophys. Acta 1587:60-64(2002).
RN [35]
RP VARIANT TGD THR-255, AND VARIANT ATHEROSCLEROSIS ASP-1611.
RX PubMed=11785958; DOI=10.1006/bbrc.2001.6219;
RA Nishida Y., Hirano K., Tsukamoto K., Nagano M., Ikegami C., Roomp K.,
RA Ishihara M., Sakane N., Zhang Z., Tsujii K., Matsuyama A., Ohama T.,
RA Matsuura F., Ishigami M., Sakai N., Hiraoka H., Hattori H., Wellington C.,
RA Yoshida Y., Misugi S., Hayden M.R., Egashira T., Yamashita S.,
RA Matsuzawa Y.;
RT "Expression and functional analyses of novel mutations of ATP-binding
RT cassette transporter-1 in Japanese patients with high-density lipoprotein
RT deficiency.";
RL Biochem. Biophys. Res. Commun. 290:713-721(2002).
RN [36]
RP VARIANT TGD LEU-590.
RX PubMed=12407001;
RA Hong S.H., Riley W., Rhyne J., Friel G., Miller M.;
RT "Lack of association between increased carotid intima-media thickening and
RT decreased HDL-cholesterol in a family with a novel ABCA1 variant, G2265T.";
RL Clin. Chem. 48:2066-2070(2002).
RN [37]
RP VARIANTS TGD HIS-935 AND SER-935.
RX PubMed=12111381; DOI=10.1007/s100380200044;
RA Guo Z., Inazu A., Yu W., Suzumura T., Okamoto M., Nohara A.,
RA Higashikata T., Sano R., Wakasugi K., Hayakawa T., Yoshida K., Suehiro T.,
RA Schmitz G., Mabuchi H.;
RT "Double deletions and missense mutations in the first nucleotide-binding
RT fold of the ATP-binding cassette transporter A1 (ABCA1) gene in Japanese
RT patients with Tangier disease.";
RL J. Hum. Genet. 47:325-329(2002).
RN [38]
RP VARIANT TGD TRP-1680.
RX PubMed=12111371; DOI=10.1007/s100380200051;
RA Ishii J., Nagano M., Kujiraoka T., Ishihara M., Egashira T., Takada D.,
RA Tsuji M., Hattori H., Emi M.;
RT "Clinical variant of Tangier disease in Japan: mutation of the ABCA1 gene
RT in hypoalphalipoproteinemia with corneal lipidosis.";
RL J. Hum. Genet. 47:366-369(2002).
RN [39]
RP VARIANT TGD GLN-1851.
RX PubMed=14576201; DOI=10.1161/01.res.0000102957.84247.8f;
RA Hong S.H., Rhyne J., Miller M.;
RT "Novel polypyrimidine variation (IVS46: del T -39._.-46) in ABCA1 causes
RT exon skipping and contributes to HDL cholesterol deficiency in a family
RT with premature coronary disease.";
RL Circ. Res. 93:1006-1012(2003).
RN [40]
RP VARIANTS ILE-825 AND MET-883, AND ASSOCIATION OF VARIANTS ILE-825 AND
RP MET-883 WITH HIGHER PLASMA HDL CHOLESTEROL.
RX PubMed=12709788; DOI=10.1007/s00439-003-0943-3;
RA Tan J.H., Low P.S., Tan Y.S., Tong M.C., Saha N., Yang H., Heng C.K.;
RT "ABCA1 gene polymorphisms and their associations with coronary artery
RT disease and plasma lipids in males from three ethnic populations in
RT Singapore.";
RL Hum. Genet. 113:106-117(2003).
RN [41]
RP VARIANTS LYS-219; MET-771; ILE-825; MET-883; ASP-1172; PHE-1181 AND
RP ARG-1587.
RX PubMed=12966036; DOI=10.1093/hmg/ddg314;
RA Morabia A., Cayanis E., Costanza M.C., Ross B.M., Flaherty M.S.,
RA Alvin G.B., Das K., Gilliam T.C.;
RT "Association of extreme blood lipid profile phenotypic variation with 11
RT reverse cholesterol transport genes and 10 non-genetic cardiovascular
RT disease risk factors.";
RL Hum. Mol. Genet. 12:2733-2743(2003).
RN [42]
RP VARIANT LYS-219.
RX PubMed=12624133; DOI=10.1136/jmg.40.3.163;
RA Cenarro A., Artieda M., Castillo S., Mozas P., Reyes G., Tejedor D.,
RA Alonso R., Mata P., Pocovi M., Civeira F.;
RT "A common variant in the ABCA1 gene is associated with a lower risk for
RT premature coronary heart disease in familial hypercholesterolaemia.";
RL J. Med. Genet. 40:163-168(2003).
RN [43]
RP VARIANTS TGD LEU-590; ARG-840 AND CYS-1068, AND VARIANTS MET-771; SER-2163
RP AND ILE-2244.
RX PubMed=15262183; DOI=10.1016/j.atherosclerosis.2004.02.019;
RA Probst M.C., Thumann H., Aslanidis C., Langmann T., Buechler C., Patsch W.,
RA Baralle F.E., Dallinga-Thie G.M., Geisel J., Keller C., Menys V.C.,
RA Schmitz G.;
RT "Screening for functional sequence variations and mutations in ABCA1.";
RL Atherosclerosis 175:269-279(2004).
RN [44]
RP VARIANTS TGD LYS-284; CYS-482; HIS-1800; SER-1901 AND HIS-2196.
RX PubMed=15019541; DOI=10.1016/j.atherosclerosis.2003.11.009;
RA Pisciotta L., Hamilton-Craig I., Tarugi P., Bellocchio A., Fasano T.,
RA Alessandrini P., Bon G.B., Siepi D., Mannarino E., Cattin L., Averna M.,
RA Cefalu A.B., Cantafora A., Calandra S., Bertolini S.;
RT "Familial HDL deficiency due to ABCA1 gene mutations with or without other
RT genetic lipoprotein disorders.";
RL Atherosclerosis 172:309-320(2004).
RN [45]
RP VARIANTS TGD PHE-1379 AND ASP-1704, AND CHARACTERIZATION OF VARIANTS TGD
RP PHE-1379 AND ASP-1704.
RX PubMed=15158913; DOI=10.1016/j.bbadis.2004.01.007;
RA Albrecht C., Baynes K., Sardini A., Schepelmann S., Eden E.R., Davies S.W.,
RA Higgins C.F., Feher M.D., Owen J.S., Soutar A.K.;
RT "Two novel missense mutations in ABCA1 result in altered trafficking and
RT cause severe autosomal recessive HDL deficiency.";
RL Biochim. Biophys. Acta 1689:47-57(2004).
RN [46]
RP VARIANT TGD HIS-1800, AND VARIANTS LYS-219; CYS-364; MET-771; PRO-774;
RP ASN-776; ILE-825; MET-883; SER-1065; ASP-1172; VAL-1216 AND ARG-1587.
RX PubMed=15520867; DOI=10.1172/jci200420361;
RA Frikke-Schmidt R., Nordestgaard B.G., Jensen G.B., Tybjaerg-Hansen A.;
RT "Genetic variation in ABC transporter A1 contributes to HDL cholesterol in
RT the general population.";
RL J. Clin. Invest. 114:1343-1353(2004).
RN [47]
RP VARIANT TGD HIS-1800, AND VARIANTS ALA-248; GLN-401; TRP-496; SER-590;
RP GLN-638; SER-774; GLY-815; PHE-1181; THR-1341; GLY-1376; GLN-1615;
RP THR-1670; GLN-1680 AND GLU-2243.
RX PubMed=15297675; DOI=10.1126/science.1099870;
RA Cohen J.C., Kiss R.S., Pertsemlidis A., Marcel Y.L., McPherson R.,
RA Hobbs H.H.;
RT "Multiple rare alleles contribute to low plasma levels of HDL
RT cholesterol.";
RL Science 305:869-872(2004).
RN [48]
RP VARIANT SCOTT SYNDROME GLN-1925, AND CHARACTERIZATION OF VARIANT SCOTT
RP SYNDROME GLN-1925.
RX PubMed=15790791; DOI=10.1182/blood-2004-05-2056;
RA Albrecht C., McVey J.H., Elliott J.I., Sardini A., Kasza I., Mumford A.D.,
RA Naoumova R.P., Tuddenham E.G., Szabo K., Higgins C.F.;
RT "A novel missense mutation in ABCA1 results in altered protein trafficking
RT and reduced phosphatidylserine translocation in a patient with Scott
RT syndrome.";
RL Blood 106:542-549(2005).
RN [49]
RP VARIANT ASN-776, AND ASSOCIATION OF VARIANT ASN-776 WITH INCREASED RISK OF
RP ISCHEMIC HEART DISEASE.
RX PubMed=16226177; DOI=10.1016/j.jacc.2005.06.066;
RA Frikke-Schmidt R., Nordestgaard B.G., Schnohr P., Steffensen R.,
RA Tybjaerg-Hansen A.;
RT "Mutation in ABCA1 predicted risk of ischemic heart disease in the
RT Copenhagen City Heart Study Population.";
RL J. Am. Coll. Cardiol. 46:1516-1520(2005).
RN [50]
RP VARIANT FHA1 TRP-1897.
RX PubMed=15722566; DOI=10.1194/jlr.d400038-jlr200;
RA Fasano T., Bocchi L., Pisciotta L., Bertolini S., Calandra S.;
RT "Denaturing high-performance liquid chromatography in the detection of
RT ABCA1 gene mutations in familial HDL deficiency.";
RL J. Lipid Res. 46:817-822(2005).
RN [51]
RP VARIANTS [LARGE SCALE ANALYSIS] ASP-210; TYR-917; THR-1407 AND THR-2109.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [52]
RP VARIANT CYS-230.
RX PubMed=27535533; DOI=10.1038/nature19057;
RG Exome Aggregation Consortium;
RA Lek M., Karczewski K.J., Minikel E.V., Samocha K.E., Banks E., Fennell T.,
RA O'Donnell-Luria A.H., Ware J.S., Hill A.J., Cummings B.B., Tukiainen T.,
RA Birnbaum D.P., Kosmicki J.A., Duncan L.E., Estrada K., Zhao F., Zou J.,
RA Pierce-Hoffman E., Berghout J., Cooper D.N., Deflaux N., DePristo M.,
RA Do R., Flannick J., Fromer M., Gauthier L., Goldstein J., Gupta N.,
RA Howrigan D., Kiezun A., Kurki M.I., Moonshine A.L., Natarajan P.,
RA Orozco L., Peloso G.M., Poplin R., Rivas M.A., Ruano-Rubio V., Rose S.A.,
RA Ruderfer D.M., Shakir K., Stenson P.D., Stevens C., Thomas B.P., Tiao G.,
RA Tusie-Luna M.T., Weisburd B., Won H.H., Yu D., Altshuler D.M.,
RA Ardissino D., Boehnke M., Danesh J., Donnelly S., Elosua R., Florez J.C.,
RA Gabriel S.B., Getz G., Glatt S.J., Hultman C.M., Kathiresan S., Laakso M.,
RA McCarroll S., McCarthy M.I., McGovern D., McPherson R., Neale B.M.,
RA Palotie A., Purcell S.M., Saleheen D., Scharf J.M., Sklar P.,
RA Sullivan P.F., Tuomilehto J., Tsuang M.T., Watkins H.C., Wilson J.G.,
RA Daly M.J., MacArthur D.G.;
RT "Analysis of protein-coding genetic variation in 60,706 humans.";
RL Nature 536:285-291(2016).
CC -!- FUNCTION: Catalyzes the translocation of specific phospholipids from
CC the cytoplasmic to the extracellular/lumenal leaflet of membrane
CC coupled to the hydrolysis of ATP (PubMed:24097981). Thereby,
CC participates in phospholipid transfer to apoliproteins to form nascent
CC high density lipoproteins/HDLs (PubMed:14754908). Transports
CC preferentially phosphatidylcholine over phosphatidylserine
CC (PubMed:24097981). May play a similar role in the efflux of
CC intracellular cholesterol to apoliproteins and the formation of nascent
CC high density lipoproteins/HDLs (PubMed:10533863, PubMed:14754908,
CC PubMed:24097981). {ECO:0000269|PubMed:10533863,
CC ECO:0000269|PubMed:14754908, ECO:0000269|PubMed:24097981}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + phospholipidSide 1 = ADP + phosphate +
CC phospholipidSide 2.; EC=7.6.2.1;
CC Evidence={ECO:0000269|PubMed:24097981};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphocholine(out) + ATP + H2O = a
CC 1,2-diacyl-sn-glycero-3-phosphocholine(in) + ADP + H(+) + phosphate;
CC Xref=Rhea:RHEA:38583, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:57643,
CC ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:24097981};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38584;
CC Evidence={ECO:0000269|PubMed:24097981};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-L-serine(out) + ATP + H2O =
CC a 1,2-diacyl-sn-glycero-3-phospho-L-serine(in) + ADP + H(+) +
CC phosphate; Xref=Rhea:RHEA:38567, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57262, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:24097981};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38568;
CC Evidence={ECO:0000269|PubMed:24097981};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a sphingomyelin(in) + ATP + H2O = a sphingomyelin(out) + ADP +
CC H(+) + phosphate; Xref=Rhea:RHEA:38903, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17636, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:24097981};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38904;
CC Evidence={ECO:0000269|PubMed:24097981};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + cholesterol(in) + H2O = ADP + cholesterol(out) + H(+) +
CC phosphate; Xref=Rhea:RHEA:39051, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16113, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000305|PubMed:10533863, ECO:0000305|PubMed:14754908,
CC ECO:0000305|PubMed:24097981};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39052;
CC Evidence={ECO:0000305|PubMed:10533863, ECO:0000305|PubMed:14754908,
CC ECO:0000305|PubMed:24097981};
CC -!- ACTIVITY REGULATION: ATPase activity is decreased by cholesterol and
CC ceramide. ATPase activity is stimulated by phosphatidylcholine and to a
CC lesser degree by phosphatidylserine and sphingomyelin. Phospholipid
CC translocase activity is highly reduced by berylium fluoride and
CC aluminum flouride and reduced by N-ethylmaleimide.
CC {ECO:0000269|PubMed:24097981}.
CC -!- SUBUNIT: Interacts with MEGF10 (PubMed:17205124). May interact with
CC APOE1; functionally associated with APOE1 in the biogenesis of HDLs
CC (PubMed:14754908). Interacts with ABCA8; this interaction potentiates
CC cholesterol efflux (PubMed:28882873). Interacts with ABCA12 and NR1H2;
CC this interaction is required for ABCA1 localization to the cell surface
CC and is necessary for its normal activity and stability
CC (PubMed:23931754). {ECO:0000269|PubMed:14754908,
CC ECO:0000269|PubMed:17205124, ECO:0000269|PubMed:23931754,
CC ECO:0000269|PubMed:28882873}.
CC -!- INTERACTION:
CC O95477; Q86UK0: ABCA12; NbExp=4; IntAct=EBI-784112, EBI-9541582;
CC O95477; P02647: APOA1; NbExp=8; IntAct=EBI-784112, EBI-701692;
CC O95477; P27824: CANX; NbExp=8; IntAct=EBI-784112, EBI-355947;
CC O95477; P60953: CDC42; NbExp=2; IntAct=EBI-784112, EBI-81752;
CC O95477; Q13424: SNTA1; NbExp=2; IntAct=EBI-784112, EBI-717191;
CC O95477; Q13884: SNTB1; NbExp=3; IntAct=EBI-784112, EBI-295843;
CC O95477; Q86Y82: STX12; NbExp=9; IntAct=EBI-784112, EBI-2691717;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:19258317,
CC ECO:0000269|PubMed:19556522, ECO:0000269|PubMed:24097981}; Multi-pass
CC membrane protein {ECO:0000305|PubMed:19258317}. Endosome
CC {ECO:0000269|PubMed:24097981}.
CC -!- TISSUE SPECIFICITY: Widely expressed, but most abundant in macrophages.
CC -!- INDUCTION: By bacterial lipopolysaccharides (LPS). LPS regulates
CC expression through a liver X receptor (LXR) -independent mechanism.
CC Repressed by ZNF202. {ECO:0000269|PubMed:11279031,
CC ECO:0000269|PubMed:12032171}.
CC -!- DOMAIN: Multifunctional polypeptide with two homologous halves, each
CC containing a hydrophobic membrane-anchoring domain and an ATP binding
CC cassette (ABC) domain.
CC -!- PTM: Phosphorylation on Ser-2054 regulates phospholipid efflux.
CC {ECO:0000269|PubMed:12196520}.
CC -!- PTM: Palmitoylated by ZDHHC8 (PubMed:19556522). Palmitoylation is
CC essential for localization to the plasma membrane (PubMed:19556522).
CC {ECO:0000269|PubMed:19556522}.
CC -!- POLYMORPHISM: Genetic variations in ABCA1 define the high density
CC lipoprotein cholesterol level quantitative trait locus 13 (HDLCQ13)
CC [MIM:600046]. {ECO:0000269|PubMed:18354102}.
CC -!- DISEASE: Tangier disease (TGD) [MIM:205400]: An autosomal recessive
CC disorder characterized by near absence of plasma high density
CC lipoproteins, low serum HDL cholesterol, and massive tissue deposition
CC of cholesterol esters. Clinical features include large yellow-orange
CC tonsils, hepatomegaly, splenomegaly, enlarged lymph nodes, and often
CC sensory polyneuropathy. {ECO:0000269|PubMed:10431236,
CC ECO:0000269|PubMed:10431237, ECO:0000269|PubMed:10706591,
CC ECO:0000269|PubMed:10938021, ECO:0000269|PubMed:11086027,
CC ECO:0000269|PubMed:11257260, ECO:0000269|PubMed:11476961,
CC ECO:0000269|PubMed:11476965, ECO:0000269|PubMed:11785958,
CC ECO:0000269|PubMed:12111371, ECO:0000269|PubMed:12111381,
CC ECO:0000269|PubMed:12407001, ECO:0000269|PubMed:14576201,
CC ECO:0000269|PubMed:14754908, ECO:0000269|PubMed:15019541,
CC ECO:0000269|PubMed:15158913, ECO:0000269|PubMed:15262183,
CC ECO:0000269|PubMed:15297675, ECO:0000269|PubMed:15520867,
CC ECO:0000269|PubMed:24097981}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Hypoalphalipoproteinemia, primary, 1 (FHA1) [MIM:604091]: An
CC autosomal dominant disorder characterized by decreased plasma high
CC density lipoproteins, moderately low HDL cholesterol, a reduction in
CC cellular cholesterol efflux, and susceptibility to premature coronary
CC artery disease. {ECO:0000269|PubMed:10431236,
CC ECO:0000269|PubMed:10533863, ECO:0000269|PubMed:11086027,
CC ECO:0000269|PubMed:12009425, ECO:0000269|PubMed:12204794,
CC ECO:0000269|PubMed:15722566, ECO:0000269|PubMed:19556522,
CC ECO:0000269|PubMed:24097981}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the ABC transporter superfamily. ABCA family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD49849.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAA10005.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=ABCMdb; Note=Database for mutations in ABC proteins;
CC URL="http://abcm2.hegelab.org/search";
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF275948; AAF86276.1; -; Genomic_DNA.
DR EMBL; AL353685; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL359846; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AF285167; AAF98175.1; -; mRNA.
DR EMBL; AF287262; AAK43526.1; -; Genomic_DNA.
DR EMBL; AB055982; BAB63210.1; -; mRNA.
DR EMBL; AJ012376; CAA10005.1; ALT_INIT; mRNA.
DR EMBL; AF165281; AAD49849.1; ALT_INIT; mRNA.
DR EMBL; AF165286; AAD49851.1; -; Genomic_DNA.
DR EMBL; AF165282; AAD49851.1; JOINED; Genomic_DNA.
DR EMBL; AF165283; AAD49851.1; JOINED; Genomic_DNA.
DR EMBL; AF165284; AAD49851.1; JOINED; Genomic_DNA.
DR EMBL; AF165285; AAD49851.1; JOINED; Genomic_DNA.
DR EMBL; AF165306; AAD49852.1; -; Genomic_DNA.
DR EMBL; AF165287; AAD49852.1; JOINED; Genomic_DNA.
DR EMBL; AF165288; AAD49852.1; JOINED; Genomic_DNA.
DR EMBL; AF165289; AAD49852.1; JOINED; Genomic_DNA.
DR EMBL; AF165290; AAD49852.1; JOINED; Genomic_DNA.
DR EMBL; AF165291; AAD49852.1; JOINED; Genomic_DNA.
DR EMBL; AF165292; AAD49852.1; JOINED; Genomic_DNA.
DR EMBL; AF165293; AAD49852.1; JOINED; Genomic_DNA.
DR EMBL; AF165294; AAD49852.1; JOINED; Genomic_DNA.
DR EMBL; AF165295; AAD49852.1; JOINED; Genomic_DNA.
DR EMBL; AF165296; AAD49852.1; JOINED; Genomic_DNA.
DR EMBL; AF165297; AAD49852.1; JOINED; Genomic_DNA.
DR EMBL; AF165298; AAD49852.1; JOINED; Genomic_DNA.
DR EMBL; AF165299; AAD49852.1; JOINED; Genomic_DNA.
DR EMBL; AF165300; AAD49852.1; JOINED; Genomic_DNA.
DR EMBL; AF165301; AAD49852.1; JOINED; Genomic_DNA.
DR EMBL; AF165302; AAD49852.1; JOINED; Genomic_DNA.
DR EMBL; AF165303; AAD49852.1; JOINED; Genomic_DNA.
DR EMBL; AF165304; AAD49852.1; JOINED; Genomic_DNA.
DR EMBL; AF165305; AAD49852.1; JOINED; Genomic_DNA.
DR EMBL; AF165309; AAD49854.1; -; Genomic_DNA.
DR EMBL; AF165307; AAD49854.1; JOINED; Genomic_DNA.
DR EMBL; AF165308; AAD49854.1; JOINED; Genomic_DNA.
DR EMBL; AF165310; AAD49853.1; -; Genomic_DNA.
DR CCDS; CCDS6762.1; -.
DR RefSeq; NP_005493.2; NM_005502.3.
DR PDB; 5XJY; EM; 4.10 A; A=1-2261.
DR PDB; 7ROQ; EM; 4.10 A; A=1-2261.
DR PDBsum; 5XJY; -.
DR PDBsum; 7ROQ; -.
DR AlphaFoldDB; O95477; -.
DR SMR; O95477; -.
DR BioGRID; 106537; 30.
DR DIP; DIP-29211N; -.
DR IntAct; O95477; 34.
DR MINT; O95477; -.
DR STRING; 9606.ENSP00000363868; -.
DR ChEMBL; CHEMBL2362986; -.
DR DrugBank; DB00171; ATP.
DR DrugBank; DB01016; Glyburide.
DR DrugBank; DB01599; Probucol.
DR DrugBank; DB00675; Tamoxifen.
DR DrugBank; DB11635; Tocofersolan.
DR DrugBank; DB00163; Vitamin E.
DR DrugCentral; O95477; -.
DR SwissLipids; SLP:000000345; -.
DR TCDB; 3.A.1.211.14; the atp-binding cassette (abc) superfamily.
DR GlyConnect; 1020; 1 N-Linked glycan (1 site).
DR GlyGen; O95477; 22 sites, 1 N-linked glycan (1 site), 1 O-linked glycan (1 site).
DR iPTMnet; O95477; -.
DR PhosphoSitePlus; O95477; -.
DR SwissPalm; O95477; -.
DR BioMuta; ABCA1; -.
DR EPD; O95477; -.
DR jPOST; O95477; -.
DR MassIVE; O95477; -.
DR MaxQB; O95477; -.
DR PaxDb; O95477; -.
DR PeptideAtlas; O95477; -.
DR PRIDE; O95477; -.
DR ProteomicsDB; 50908; -.
DR Antibodypedia; 14760; 592 antibodies from 38 providers.
DR DNASU; 19; -.
DR Ensembl; ENST00000374736.8; ENSP00000363868.3; ENSG00000165029.17.
DR GeneID; 19; -.
DR KEGG; hsa:19; -.
DR MANE-Select; ENST00000374736.8; ENSP00000363868.3; NM_005502.4; NP_005493.2.
DR UCSC; uc004bcl.4; human.
DR CTD; 19; -.
DR DisGeNET; 19; -.
DR GeneCards; ABCA1; -.
DR GeneReviews; ABCA1; -.
DR HGNC; HGNC:29; ABCA1.
DR HPA; ENSG00000165029; Low tissue specificity.
DR MalaCards; ABCA1; -.
DR MIM; 205400; phenotype.
DR MIM; 600046; gene.
DR MIM; 604091; phenotype.
DR neXtProt; NX_O95477; -.
DR OpenTargets; ENSG00000165029; -.
DR Orphanet; 425; Apolipoprotein A-I deficiency.
DR Orphanet; 31150; Tangier disease.
DR PharmGKB; PA24373; -.
DR VEuPathDB; HostDB:ENSG00000165029; -.
DR eggNOG; KOG0059; Eukaryota.
DR GeneTree; ENSGT00940000154658; -.
DR HOGENOM; CLU_000604_19_0_1; -.
DR InParanoid; O95477; -.
DR OMA; CLFICIA; -.
DR OrthoDB; 131191at2759; -.
DR PhylomeDB; O95477; -.
DR TreeFam; TF105191; -.
DR PathwayCommons; O95477; -.
DR Reactome; R-HSA-1989781; PPARA activates gene expression.
DR Reactome; R-HSA-5682113; Defective ABCA1 causes TGD.
DR Reactome; R-HSA-8963896; HDL assembly.
DR Reactome; R-HSA-9029569; NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux.
DR SignaLink; O95477; -.
DR SIGNOR; O95477; -.
DR BioGRID-ORCS; 19; 17 hits in 1073 CRISPR screens.
DR ChiTaRS; ABCA1; human.
DR GeneWiki; ABCA1; -.
DR GenomeRNAi; 19; -.
DR Pharos; O95477; Tclin.
DR PRO; PR:O95477; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; O95477; protein.
DR Bgee; ENSG00000165029; Expressed in adrenal tissue and 188 other tissues.
DR ExpressionAtlas; O95477; baseline and differential.
DR Genevisible; O95477; HS.
DR GO; GO:0030139; C:endocytic vesicle; IDA:BHF-UCL.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0005768; C:endosome; IDA:UniProtKB.
DR GO; GO:0009897; C:external side of plasma membrane; IEA:Ensembl.
DR GO; GO:0005794; C:Golgi apparatus; IEA:Ensembl.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:BHF-UCL.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0097708; C:intracellular vesicle; IDA:ARUK-UCL.
DR GO; GO:0045121; C:membrane raft; IDA:BHF-UCL.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:BHF-UCL.
DR GO; GO:0045335; C:phagocytic vesicle; IDA:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0140359; F:ABC-type transporter activity; IEA:InterPro.
DR GO; GO:0034186; F:apolipoprotein A-I binding; IPI:BHF-UCL.
DR GO; GO:0034188; F:apolipoprotein A-I receptor activity; IDA:BHF-UCL.
DR GO; GO:0034185; F:apolipoprotein binding; IPI:BHF-UCL.
DR GO; GO:0005524; F:ATP binding; IDA:BHF-UCL.
DR GO; GO:0051117; F:ATPase binding; IPI:BHF-UCL.
DR GO; GO:0042626; F:ATPase-coupled transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0015485; F:cholesterol binding; IC:BHF-UCL.
DR GO; GO:0120020; F:cholesterol transfer activity; IDA:BHF-UCL.
DR GO; GO:0140328; F:floppase activity; IDA:UniProtKB.
DR GO; GO:0005319; F:lipid transporter activity; IBA:GO_Central.
DR GO; GO:0031210; F:phosphatidylcholine binding; IDA:BHF-UCL.
DR GO; GO:0090554; F:phosphatidylcholine floppase activity; IDA:BHF-UCL.
DR GO; GO:0090556; F:phosphatidylserine floppase activity; IDA:BHF-UCL.
DR GO; GO:0005548; F:phospholipid transporter activity; IGI:ARUK-UCL.
DR GO; GO:0008320; F:protein transmembrane transporter activity; ISS:ARUK-UCL.
DR GO; GO:0005102; F:signaling receptor binding; IPI:BHF-UCL.
DR GO; GO:0031267; F:small GTPase binding; IPI:BHF-UCL.
DR GO; GO:0046623; F:sphingolipid floppase activity; IDA:BHF-UCL.
DR GO; GO:0019905; F:syntaxin binding; IPI:BHF-UCL.
DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IMP:BHF-UCL.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEA:Ensembl.
DR GO; GO:0071404; P:cellular response to low-density lipoprotein particle stimulus; NAS:BHF-UCL.
DR GO; GO:0071300; P:cellular response to retinoic acid; IEA:Ensembl.
DR GO; GO:0033344; P:cholesterol efflux; IDA:BHF-UCL.
DR GO; GO:0042632; P:cholesterol homeostasis; IDA:BHF-UCL.
DR GO; GO:0008203; P:cholesterol metabolic process; IDA:BHF-UCL.
DR GO; GO:0016197; P:endosomal transport; IDA:BHF-UCL.
DR GO; GO:0140115; P:export across plasma membrane; ISS:ARUK-UCL.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IMP:BHF-UCL.
DR GO; GO:0034380; P:high-density lipoprotein particle assembly; IMP:UniProtKB.
DR GO; GO:0032367; P:intracellular cholesterol transport; IMP:BHF-UCL.
DR GO; GO:0006869; P:lipid transport; IBA:GO_Central.
DR GO; GO:0007040; P:lysosome organization; IDA:BHF-UCL.
DR GO; GO:0010887; P:negative regulation of cholesterol storage; TAS:BHF-UCL.
DR GO; GO:0010745; P:negative regulation of macrophage derived foam cell differentiation; TAS:BHF-UCL.
DR GO; GO:0002790; P:peptide secretion; IEA:Ensembl.
DR GO; GO:0006911; P:phagocytosis, engulfment; IEA:Ensembl.
DR GO; GO:0033700; P:phospholipid efflux; IDA:BHF-UCL.
DR GO; GO:0055091; P:phospholipid homeostasis; IMP:BHF-UCL.
DR GO; GO:0045332; P:phospholipid translocation; IDA:BHF-UCL.
DR GO; GO:0060155; P:platelet dense granule organization; IMP:BHF-UCL.
DR GO; GO:0010875; P:positive regulation of cholesterol efflux; IEA:Ensembl.
DR GO; GO:0090108; P:positive regulation of high-density lipoprotein particle assembly; ISS:UniProtKB.
DR GO; GO:0006497; P:protein lipidation; IEA:Ensembl.
DR GO; GO:0009306; P:protein secretion; IMP:ARUK-UCL.
DR GO; GO:0071806; P:protein transmembrane transport; ISS:ARUK-UCL.
DR GO; GO:0032489; P:regulation of Cdc42 protein signal transduction; IMP:BHF-UCL.
DR GO; GO:0090107; P:regulation of high-density lipoprotein particle assembly; TAS:BHF-UCL.
DR GO; GO:0034616; P:response to laminar fluid shear stress; IDA:BHF-UCL.
DR GO; GO:0043691; P:reverse cholesterol transport; IMP:BHF-UCL.
DR GO; GO:0023061; P:signal release; IMP:BHF-UCL.
DR Gene3D; 3.40.50.300; -; 2.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR003439; ABC_transporter-like_ATP-bd.
DR InterPro; IPR017871; ABC_transporter-like_CS.
DR InterPro; IPR026082; ABCA.
DR InterPro; IPR030365; ABCA1.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR19229; PTHR19229; 1.
DR PANTHER; PTHR19229:SF34; PTHR19229:SF34; 1.
DR Pfam; PF00005; ABC_tran; 2.
DR SMART; SM00382; AAA; 2.
DR SUPFAM; SSF52540; SSF52540; 2.
DR PROSITE; PS00211; ABC_TRANSPORTER_1; 1.
DR PROSITE; PS50893; ABC_TRANSPORTER_2; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Atherosclerosis; ATP-binding; Cell membrane;
KW Cholesterol metabolism; Disease variant; Disulfide bond; Endosome;
KW Glycoprotein; Lipid metabolism; Lipoprotein; Membrane; Nucleotide-binding;
KW Palmitate; Phosphoprotein; Reference proteome; Repeat; Steroid metabolism;
KW Sterol metabolism; Translocase; Transmembrane; Transmembrane helix;
KW Transport.
FT CHAIN 1..2261
FT /note="Phospholipid-transporting ATPase ABCA1"
FT /id="PRO_0000093288"
FT TRANSMEM 22..42
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 43..639
FT /note="Extracellular"
FT TRANSMEM 640..660
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 683..703
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 716..736
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 745..765
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 777..797
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 827..847
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1041..1057
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1351..1371
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1372..1656
FT /note="Extracellular"
FT TRANSMEM 1657..1677
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1703..1723
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1735..1755
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1768..1788
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1802..1822
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1852..1872
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 899..1131
FT /note="ABC transporter 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT DOMAIN 1912..2144
FT /note="ABC transporter 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT REGION 1283..1312
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1283..1308
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 933..940
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT BINDING 1946..1953
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT MOD_RES 1042
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:12196520"
FT MOD_RES 1296
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P41233"
FT MOD_RES 2054
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:12196520"
FT LIPID 3
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:19556522"
FT LIPID 23
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:19556522"
FT LIPID 1110
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:19556522"
FT LIPID 1111
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:19556522"
FT CARBOHYD 14
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 98
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CARBOHYD 151
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 161
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 196
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 244
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CARBOHYD 292
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 337
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 349
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 400
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 478
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 489
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 521
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 820
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1144
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1294
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1453
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1504
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1637
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2044
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2238
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 75..309
FT /evidence="ECO:0000269|PubMed:19258317"
FT DISULFID 1463..1477
FT /evidence="ECO:0000269|PubMed:19258317"
FT VARIANT 85
FT /note="P -> L (in FHA1; Alabama; dbSNP:rs145183203)"
FT /evidence="ECO:0000269|PubMed:12204794"
FT /id="VAR_017529"
FT VARIANT 210
FT /note="E -> D (in a colorectal cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035724"
FT VARIANT 219
FT /note="R -> K (associated with a decreased severity of CAD;
FT dbSNP:rs2230806)"
FT /evidence="ECO:0000269|PubMed:10938021,
FT ECO:0000269|PubMed:11238261, ECO:0000269|PubMed:11257261,
FT ECO:0000269|PubMed:11476965, ECO:0000269|PubMed:12624133,
FT ECO:0000269|PubMed:12966036, ECO:0000269|PubMed:15520867"
FT /id="VAR_012618"
FT VARIANT 230
FT /note="R -> C (in dbSNP:rs9282541)"
FT /evidence="ECO:0000269|PubMed:10938021,
FT ECO:0000269|PubMed:27535533"
FT /id="VAR_012619"
FT VARIANT 248
FT /note="P -> A (in dbSNP:rs142625938)"
FT /evidence="ECO:0000269|PubMed:15297675"
FT /id="VAR_062481"
FT VARIANT 255
FT /note="A -> T (in TGD; deficient cellular cholesterol
FT efflux; dbSNP:rs758100110)"
FT /evidence="ECO:0000269|PubMed:11785958"
FT /id="VAR_012620"
FT VARIANT 284
FT /note="E -> K (in TGD)"
FT /evidence="ECO:0000269|PubMed:15019541"
FT /id="VAR_062482"
FT VARIANT 364
FT /note="S -> C (in dbSNP:rs775035559)"
FT /evidence="ECO:0000269|PubMed:15520867"
FT /id="VAR_062483"
FT VARIANT 399
FT /note="V -> A (in dbSNP:rs9282543)"
FT /evidence="ECO:0000269|PubMed:10431237,
FT ECO:0000269|PubMed:11238261"
FT /id="VAR_009145"
FT VARIANT 401
FT /note="K -> Q (in dbSNP:rs138487227)"
FT /evidence="ECO:0000269|PubMed:15297675"
FT /id="VAR_062484"
FT VARIANT 482
FT /note="Y -> C (in TGD)"
FT /evidence="ECO:0000269|PubMed:15019541"
FT /id="VAR_062485"
FT VARIANT 496
FT /note="R -> W (associated with increased plasma HDL
FT cholesterol; dbSNP:rs147675550)"
FT /evidence="ECO:0000269|PubMed:15297675"
FT /id="VAR_062486"
FT VARIANT 587
FT /note="R -> W (in TGD; dbSNP:rs2853574)"
FT /evidence="ECO:0000269|PubMed:11257260"
FT /id="VAR_009146"
FT VARIANT 590
FT /note="W -> L (in TGD; dbSNP:rs137854496)"
FT /evidence="ECO:0000269|PubMed:12407001,
FT ECO:0000269|PubMed:15262183"
FT /id="VAR_062487"
FT VARIANT 590
FT /note="W -> S (in TGD; moderately decreased protein
FT abundance; highly decreased ATPase activity; highly
FT decreased phospholipid translocase activity;
FT dbSNP:rs137854496)"
FT /evidence="ECO:0000269|PubMed:10431237,
FT ECO:0000269|PubMed:15297675, ECO:0000269|PubMed:24097981"
FT /id="VAR_009147"
FT VARIANT 597
FT /note="Q -> R (in TGD; dbSNP:rs2853578)"
FT /evidence="ECO:0000269|PubMed:10431236,
FT ECO:0000269|PubMed:11086027"
FT /id="VAR_009148"
FT VARIANT 638
FT /note="R -> Q (associated with reduced plasma HDL
FT cholesterol; dbSNP:rs374190304)"
FT /evidence="ECO:0000269|PubMed:15297675"
FT /id="VAR_062488"
FT VARIANT 693
FT /note="Missing (in FHA1)"
FT /evidence="ECO:0000269|PubMed:10431236,
FT ECO:0000269|PubMed:11086027"
FT /id="VAR_009149"
FT VARIANT 771
FT /note="V -> M (associated with HDL cholesterol;
FT dbSNP:rs2066718)"
FT /evidence="ECO:0000269|PubMed:11238261,
FT ECO:0000269|PubMed:12966036, ECO:0000269|PubMed:15262183,
FT ECO:0000269|PubMed:15520867"
FT /id="VAR_012621"
FT VARIANT 774
FT /note="T -> P (in dbSNP:rs35819696)"
FT /evidence="ECO:0000269|PubMed:11238261,
FT ECO:0000269|PubMed:15520867"
FT /id="VAR_012622"
FT VARIANT 774
FT /note="T -> S"
FT /evidence="ECO:0000269|PubMed:15297675"
FT /id="VAR_062489"
FT VARIANT 776
FT /note="K -> N (may be associated with increased risk of
FT ischemic heart disease; dbSNP:rs138880920)"
FT /evidence="ECO:0000269|PubMed:11238261,
FT ECO:0000269|PubMed:15520867, ECO:0000269|PubMed:16226177"
FT /id="VAR_012623"
FT VARIANT 815
FT /note="E -> G (associated with reduced plasma HDL
FT cholesterol; dbSNP:rs145582736)"
FT /evidence="ECO:0000269|PubMed:15297675"
FT /id="VAR_062490"
FT VARIANT 825
FT /note="V -> I (associated with higher plasma cholesterol;
FT dbSNP:rs2066715)"
FT /evidence="ECO:0000269|PubMed:10938021,
FT ECO:0000269|PubMed:11238261, ECO:0000269|PubMed:12709788,
FT ECO:0000269|PubMed:12966036, ECO:0000269|PubMed:15520867"
FT /id="VAR_012624"
FT VARIANT 840
FT /note="W -> R (in TGD; dbSNP:rs1322998567)"
FT /evidence="ECO:0000269|PubMed:15262183"
FT /id="VAR_062491"
FT VARIANT 883
FT /note="I -> M (associated with higher plasma cholesterol;
FT dbSNP:rs2066714)"
FT /evidence="ECO:0000269|PubMed:10431237,
FT ECO:0000269|PubMed:10938021, ECO:0000269|PubMed:11238261,
FT ECO:0000269|PubMed:11257261, ECO:0000269|PubMed:12709788,
FT ECO:0000269|PubMed:12966036, ECO:0000269|PubMed:15520867"
FT /id="VAR_012625"
FT VARIANT 917
FT /note="D -> Y (in a colorectal cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035725"
FT VARIANT 929
FT /note="T -> I (in TGD; moderately decreased protein
FT abundance; highly decreased ATPase activity; highly
FT decreased phospholipid translocase activity; loss protein
FT subcellular localization to the plasma membrane)"
FT /evidence="ECO:0000269|PubMed:11086027,
FT ECO:0000269|PubMed:24097981"
FT /id="VAR_012626"
FT VARIANT 935
FT /note="N -> H (in TGD; dbSNP:rs28937314)"
FT /evidence="ECO:0000269|PubMed:12111381"
FT /id="VAR_037968"
FT VARIANT 935
FT /note="N -> S (in TGD; moderately decreased protein
FT abundance; highly decreased ATPase activity; highly
FT decreased phospholipid translocase activity;
FT dbSNP:rs28937313)"
FT /evidence="ECO:0000269|PubMed:10431237,
FT ECO:0000269|PubMed:12111381, ECO:0000269|PubMed:24097981"
FT /id="VAR_009150"
FT VARIANT 937
FT /note="A -> V (in TGD; dbSNP:rs137854495)"
FT /evidence="ECO:0000269|PubMed:10431237"
FT /id="VAR_009151"
FT VARIANT 1046
FT /note="A -> D (in TGD; dbSNP:rs141021096)"
FT /evidence="ECO:0000269|PubMed:10938021"
FT /id="VAR_012627"
FT VARIANT 1054
FT /note="V -> I (in dbSNP:rs13306072)"
FT /id="VAR_037969"
FT VARIANT 1065
FT /note="P -> S"
FT /evidence="ECO:0000269|PubMed:15520867"
FT /id="VAR_062492"
FT VARIANT 1068
FT /note="R -> C (in TGD; dbSNP:rs745593394)"
FT /evidence="ECO:0000269|PubMed:15262183"
FT /id="VAR_062493"
FT VARIANT 1091
FT /note="M -> T (in FHA1; loss of localization to plasma
FT membrane; decreased cholesterol efflux; decreased
FT phospholipid efflux)"
FT /evidence="ECO:0000269|PubMed:10533863,
FT ECO:0000269|PubMed:11086027, ECO:0000269|PubMed:19556522"
FT /id="VAR_012628"
FT VARIANT 1099
FT /note="D -> Y (in FHA1; dbSNP:rs28933692)"
FT /evidence="ECO:0000269|PubMed:12009425"
FT /id="VAR_017530"
FT VARIANT 1172
FT /note="E -> D (associated with premature coronary heart
FT disease; dbSNP:rs33918808)"
FT /evidence="ECO:0000269|PubMed:11238261,
FT ECO:0000269|PubMed:11257261, ECO:0000269|PubMed:12966036,
FT ECO:0000269|PubMed:15520867"
FT /id="VAR_012629"
FT VARIANT 1181
FT /note="S -> F (associated with reduced plasma HDL
FT cholesterol; dbSNP:rs76881554)"
FT /evidence="ECO:0000269|PubMed:12966036,
FT ECO:0000269|PubMed:15297675"
FT /id="VAR_017016"
FT VARIANT 1216
FT /note="G -> V (in dbSNP:rs562403512)"
FT /evidence="ECO:0000269|PubMed:15520867"
FT /id="VAR_062494"
FT VARIANT 1289
FT /note="D -> N (in TGD; dbSNP:rs137854500)"
FT /evidence="ECO:0000269|PubMed:10706591,
FT ECO:0000269|PubMed:11476965"
FT /id="VAR_009152"
FT VARIANT 1341
FT /note="R -> T (associated with reduced plasma HDL
FT cholesterol; dbSNP:rs147743782)"
FT /evidence="ECO:0000269|PubMed:15297675"
FT /id="VAR_062495"
FT VARIANT 1376
FT /note="S -> G (in dbSNP:rs145689805)"
FT /evidence="ECO:0000269|PubMed:15297675"
FT /id="VAR_062496"
FT VARIANT 1379
FT /note="L -> F (in TGD; the mutant protein is retained in
FT the endoplasmic reticulum while the wild-type protein is
FT located at the plasma membrane)"
FT /evidence="ECO:0000269|PubMed:15158913"
FT /id="VAR_062497"
FT VARIANT 1407
FT /note="A -> T (in a colorectal cancer sample; somatic
FT mutation; dbSNP:rs189206655)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035726"
FT VARIANT 1477
FT /note="C -> R (in TGD; loss of interaction with APOE;
FT unable to generate APOE-containing high density
FT lipoproteins; moderately decreased protein abundance;
FT moderately decreased ATPase activity; moderately decreased
FT phospholipid translocase activity; dbSNP:rs137854494)"
FT /evidence="ECO:0000269|PubMed:10431236,
FT ECO:0000269|PubMed:11086027, ECO:0000269|PubMed:14754908,
FT ECO:0000269|PubMed:24097981"
FT /id="VAR_009153"
FT VARIANT 1506
FT /note="S -> L (in TGD; dbSNP:rs137854497)"
FT /evidence="ECO:0000269|PubMed:11476961"
FT /id="VAR_012630"
FT VARIANT 1517
FT /note="I -> R (in TGD)"
FT /id="VAR_009154"
FT VARIANT 1555
FT /note="I -> T (in dbSNP:rs1997618)"
FT /evidence="ECO:0000269|PubMed:10092505,
FT ECO:0000269|PubMed:10431238"
FT /id="VAR_012638"
FT VARIANT 1587
FT /note="K -> R (associated with HDL cholesterol;
FT dbSNP:rs2230808)"
FT /evidence="ECO:0000269|PubMed:10092505,
FT ECO:0000269|PubMed:10431238, ECO:0000269|PubMed:10884428,
FT ECO:0000269|PubMed:10938021, ECO:0000269|PubMed:11238261,
FT ECO:0000269|PubMed:11352567, ECO:0000269|PubMed:12966036,
FT ECO:0000269|PubMed:15520867, ECO:0000269|Ref.2"
FT /id="VAR_012631"
FT VARIANT 1611
FT /note="N -> D (probable disease-associated variant;
FT associated with atherosclerosis; deficient cellular
FT cholesterol efflux)"
FT /evidence="ECO:0000269|PubMed:11785958"
FT /id="VAR_012632"
FT VARIANT 1615
FT /note="R -> Q (associated with reduced plasma HDL
FT cholesterol; dbSNP:rs1251839800)"
FT /evidence="ECO:0000269|PubMed:15297675"
FT /id="VAR_062498"
FT VARIANT 1648
FT /note="L -> P (in dbSNP:rs1883024)"
FT /evidence="ECO:0000269|PubMed:10092505,
FT ECO:0000269|PubMed:10431238"
FT /id="VAR_012639"
FT VARIANT 1670
FT /note="A -> T (associated with reduced plasma HDL
FT cholesterol; dbSNP:rs1203589782)"
FT /evidence="ECO:0000269|PubMed:15297675"
FT /id="VAR_062499"
FT VARIANT 1680
FT /note="R -> Q (associated with increased plasma HDL
FT cholesterol; dbSNP:rs150125857)"
FT /evidence="ECO:0000269|PubMed:15297675"
FT /id="VAR_062500"
FT VARIANT 1680
FT /note="R -> W (in TGD; dbSNP:rs137854498)"
FT /evidence="ECO:0000269|PubMed:12111371"
FT /id="VAR_037970"
FT VARIANT 1704
FT /note="V -> D (in TGD; the mutant protein is retained in
FT the endoplasmic reticulum while the wild-type protein is
FT located at the plasma membrane)"
FT /evidence="ECO:0000269|PubMed:15158913"
FT /id="VAR_062501"
FT VARIANT 1731
FT /note="S -> C (in dbSNP:rs760507032)"
FT /evidence="ECO:0000269|PubMed:11238261"
FT /id="VAR_012633"
FT VARIANT 1800
FT /note="N -> H (in TGD; dbSNP:rs146292819)"
FT /evidence="ECO:0000269|PubMed:10706591,
FT ECO:0000269|PubMed:15019541, ECO:0000269|PubMed:15297675,
FT ECO:0000269|PubMed:15520867"
FT /id="VAR_009155"
FT VARIANT 1851
FT /note="R -> Q (in TGD; dbSNP:rs1055285452)"
FT /evidence="ECO:0000269|PubMed:14576201"
FT /id="VAR_062502"
FT VARIANT 1893..1894
FT /note="Missing (in FHA1)"
FT /evidence="ECO:0000269|PubMed:10533863,
FT ECO:0000269|PubMed:11086027"
FT /id="VAR_012634"
FT VARIANT 1897
FT /note="R -> W (in FHA1; uncertain pathological
FT significance; dbSNP:rs760768125)"
FT /evidence="ECO:0000269|PubMed:15722566"
FT /id="VAR_062503"
FT VARIANT 1901
FT /note="R -> S (in TGD)"
FT /evidence="ECO:0000269|PubMed:15019541"
FT /id="VAR_062504"
FT VARIANT 1925
FT /note="R -> Q (in Scott syndrome; shows impaired
FT trafficking of the mutant protein to the plasma membrane;
FT dbSNP:rs142688906)"
FT /evidence="ECO:0000269|PubMed:15790791"
FT /id="VAR_062505"
FT VARIANT 2009
FT /note="F -> S (in FHA1; dbSNP:rs137854499)"
FT /evidence="ECO:0000269|PubMed:12009425"
FT /id="VAR_037971"
FT VARIANT 2081
FT /note="R -> W (in TGD; highly decreased protein abundance;
FT highly decreased ATPase activity; highly decreased
FT phospholipid translocase activity; loss protein subcellular
FT localization to the plasma membrane; dbSNP:rs137854501)"
FT /evidence="ECO:0000269|PubMed:11476965,
FT ECO:0000269|PubMed:24097981"
FT /id="VAR_012635"
FT VARIANT 2109
FT /note="A -> T (in a colorectal cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035727"
FT VARIANT 2150
FT /note="P -> L (in FHA1; moderately decreased protein
FT abundance; does not affect ATPase activity; moderately
FT decreased phospholipid translocase activity;
FT dbSNP:rs369098049)"
FT /evidence="ECO:0000269|PubMed:11086027,
FT ECO:0000269|PubMed:24097981"
FT /id="VAR_012636"
FT VARIANT 2163
FT /note="F -> S (could be associated with reduced plasma HDL
FT cholesterol)"
FT /evidence="ECO:0000269|PubMed:15262183"
FT /id="VAR_062506"
FT VARIANT 2168
FT /note="L -> P (in dbSNP:rs2853577)"
FT /evidence="ECO:0000269|PubMed:10092505,
FT ECO:0000269|PubMed:10431238, ECO:0000269|PubMed:11257260"
FT /id="VAR_012637"
FT VARIANT 2196
FT /note="Q -> H (in TGD; dbSNP:rs564764153)"
FT /evidence="ECO:0000269|PubMed:15019541"
FT /id="VAR_062507"
FT VARIANT 2243
FT /note="D -> E (in dbSNP:rs34879708)"
FT /evidence="ECO:0000269|PubMed:15297675"
FT /id="VAR_062508"
FT VARIANT 2244
FT /note="V -> I (could be associated with reduced plasma HDL
FT cholesterol; dbSNP:rs144588452)"
FT /evidence="ECO:0000269|PubMed:15262183"
FT /id="VAR_062509"
FT MUTAGEN 3
FT /note="C->S: Mild decrease of palmitoylation. Loss of
FT localization to plasma membrane. Decreased cholesterol
FT efflux. Decreased phospholipid efflux. Decreased
FT palmitoylation; when associated with S-23, S-1110 and S-
FT 1111."
FT /evidence="ECO:0000269|PubMed:19556522"
FT MUTAGEN 23
FT /note="C->S: Mild decrease of palmitoylation. Loss of
FT localization to plasma membrane. Decreased palmitoylation;
FT when associated with S-3, S-1110 and S-1111."
FT /evidence="ECO:0000269|PubMed:19556522"
FT MUTAGEN 100
FT /note="S->C: Highly decreased protein abundance. Highly
FT decreased ATPase activity. Highly decreased phospholipid
FT translocase activity."
FT /evidence="ECO:0000269|PubMed:24097981"
FT MUTAGEN 593
FT /note="F->L: Moderately decreased protein abundance. Highly
FT decreased ATPase activity. Highly decreased phospholipid
FT translocase activity."
FT /evidence="ECO:0000269|PubMed:24097981"
FT MUTAGEN 939
FT /note="K->M: Inhibits ATPase activity; when associated with
FT M-1952. Decreases translocase activity; when associated
FT with M-1952. Does not affect protein subcellular
FT localization in plasma membrane and endosome; when
FT associated with M-1952."
FT /evidence="ECO:0000269|PubMed:24097981"
FT MUTAGEN 1110
FT /note="C->S: Decreased palmitoylation; when associated with
FT S-3, S-23 and S-1111."
FT /evidence="ECO:0000269|PubMed:19556522"
FT MUTAGEN 1111
FT /note="C->S: Decreased palmitoylation; when associated with
FT S-3, S-23 and S-1110."
FT /evidence="ECO:0000269|PubMed:19556522"
FT MUTAGEN 1512
FT /note="T->M: Moderately decreased protein abundance. Does
FT not affect ATPase activity. Moderately decreased
FT phospholipid translocase activity."
FT /evidence="ECO:0000269|PubMed:24097981"
FT MUTAGEN 1952
FT /note="K->M: Inhibits ATPase activity; when associated with
FT M-939. Decreases translocase activity; when associated with
FT M-939. Does not affect protein subcellular localization in
FT plasma membrane and endosome; when associated with M-939."
FT /evidence="ECO:0000269|PubMed:24097981"
FT CONFLICT 793
FT /note="Y -> C (in Ref. 3; AAK43526)"
FT /evidence="ECO:0000305"
FT CONFLICT 831
FT /note="D -> N (in Ref. 3; AAK43526)"
FT /evidence="ECO:0000305"
FT CONFLICT 1005
FT /note="E -> K (in Ref. 3; AAK43526)"
FT /evidence="ECO:0000305"
FT CONFLICT 1745..1746
FT /note="Missing (in Ref. 7; AAD49852)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 2261 AA; 254302 MW; 21A2CF8F3F518D6D CRC64;
MACWPQLRLL LWKNLTFRRR QTCQLLLEVA WPLFIFLILI SVRLSYPPYE QHECHFPNKA
MPSAGTLPWV QGIICNANNP CFRYPTPGEA PGVVGNFNKS IVARLFSDAR RLLLYSQKDT
SMKDMRKVLR TLQQIKKSSS NLKLQDFLVD NETFSGFLYH NLSLPKSTVD KMLRADVILH
KVFLQGYQLH LTSLCNGSKS EEMIQLGDQE VSELCGLPRE KLAAAERVLR SNMDILKPIL
RTLNSTSPFP SKELAEATKT LLHSLGTLAQ ELFSMRSWSD MRQEVMFLTN VNSSSSSTQI
YQAVSRIVCG HPEGGGLKIK SLNWYEDNNY KALFGGNGTE EDAETFYDNS TTPYCNDLMK
NLESSPLSRI IWKALKPLLV GKILYTPDTP ATRQVMAEVN KTFQELAVFH DLEGMWEELS
PKIWTFMENS QEMDLVRMLL DSRDNDHFWE QQLDGLDWTA QDIVAFLAKH PEDVQSSNGS
VYTWREAFNE TNQAIRTISR FMECVNLNKL EPIATEVWLI NKSMELLDER KFWAGIVFTG
ITPGSIELPH HVKYKIRMDI DNVERTNKIK DGYWDPGPRA DPFEDMRYVW GGFAYLQDVV
EQAIIRVLTG TEKKTGVYMQ QMPYPCYVDD IFLRVMSRSM PLFMTLAWIY SVAVIIKGIV
YEKEARLKET MRIMGLDNSI LWFSWFISSL IPLLVSAGLL VVILKLGNLL PYSDPSVVFV
FLSVFAVVTI LQCFLISTLF SRANLAAACG GIIYFTLYLP YVLCVAWQDY VGFTLKIFAS
LLSPVAFGFG CEYFALFEEQ GIGVQWDNLF ESPVEEDGFN LTTSVSMMLF DTFLYGVMTW
YIEAVFPGQY GIPRPWYFPC TKSYWFGEES DEKSHPGSNQ KRISEICMEE EPTHLKLGVS
IQNLVKVYRD GMKVAVDGLA LNFYEGQITS FLGHNGAGKT TTMSILTGLF PPTSGTAYIL
GKDIRSEMST IRQNLGVCPQ HNVLFDMLTV EEHIWFYARL KGLSEKHVKA EMEQMALDVG
LPSSKLKSKT SQLSGGMQRK LSVALAFVGG SKVVILDEPT AGVDPYSRRG IWELLLKYRQ
GRTIILSTHH MDEADVLGDR IAIISHGKLC CVGSSLFLKN QLGTGYYLTL VKKDVESSLS
SCRNSSSTVS YLKKEDSVSQ SSSDAGLGSD HESDTLTIDV SAISNLIRKH VSEARLVEDI
GHELTYVLPY EAAKEGAFVE LFHEIDDRLS DLGISSYGIS ETTLEEIFLK VAEESGVDAE
TSDGTLPARR NRRAFGDKQS CLRPFTEDDA ADPNDSDIDP ESRETDLLSG MDGKGSYQVK
GWKLTQQQFV ALLWKRLLIA RRSRKGFFAQ IVLPAVFVCI ALVFSLIVPP FGKYPSLELQ
PWMYNEQYTF VSNDAPEDTG TLELLNALTK DPGFGTRCME GNPIPDTPCQ AGEEEWTTAP
VPQTIMDLFQ NGNWTMQNPS PACQCSSDKI KKMLPVCPPG AGGLPPPQRK QNTADILQDL
TGRNISDYLV KTYVQIIAKS LKNKIWVNEF RYGGFSLGVS NTQALPPSQE VNDAIKQMKK
HLKLAKDSSA DRFLNSLGRF MTGLDTKNNV KVWFNNKGWH AISSFLNVIN NAILRANLQK
GENPSHYGIT AFNHPLNLTK QQLSEVALMT TSVDVLVSIC VIFAMSFVPA SFVVFLIQER
VSKAKHLQFI SGVKPVIYWL SNFVWDMCNY VVPATLVIII FICFQQKSYV SSTNLPVLAL
LLLLYGWSIT PLMYPASFVF KIPSTAYVVL TSVNLFIGIN GSVATFVLEL FTDNKLNNIN
DILKSVFLIF PHFCLGRGLI DMVKNQAMAD ALERFGENRF VSPLSWDLVG RNLFAMAVEG
VVFFLITVLI QYRFFIRPRP VNAKLSPLND EDEDVRRERQ RILDGGGQND ILEIKELTKI
YRRKRKPAVD RICVGIPPGE CFGLLGVNGA GKSSTFKMLT GDTTVTRGDA FLNKNSILSN
IHEVHQNMGY CPQFDAITEL LTGREHVEFF ALLRGVPEKE VGKVGEWAIR KLGLVKYGEK
YAGNYSGGNK RKLSTAMALI GGPPVVFLDE PTTGMDPKAR RFLWNCALSV VKEGRSVVLT
SHSMEECEAL CTRMAIMVNG RFRCLGSVQH LKNRFGDGYT IVVRIAGSNP DLKPVQDFFG
LAFPGSVLKE KHRNMLQYQL PSSLSSLARI FSILSQSKKR LHIEDYSVSQ TTLDQVFVNF
AKDQSDDDHL KDLSLHKNQT VVDVAVLTSF LQDEKVKESY V
