ABCA7_HUMAN
ID ABCA7_HUMAN Reviewed; 2146 AA.
AC Q8IZY2; Q96S58; Q9BZC4; Q9NR73; Q9UKP8;
DT 03-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 04-DEC-2007, sequence version 3.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Phospholipid-transporting ATPase ABCA7 {ECO:0000305};
DE EC=7.6.2.1 {ECO:0000269|PubMed:24097981};
DE AltName: Full=ABCA-SSN {ECO:0000303|PubMed:11355874};
DE AltName: Full=ATP-binding cassette sub-family A member 7 {ECO:0000305};
DE AltName: Full=Autoantigen SS-N {ECO:0000303|Ref.6};
DE AltName: Full=Macrophage ABC transporter {ECO:0000303|PubMed:10873640};
GN Name=ABCA7 {ECO:0000312|HGNC:HGNC:37};
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 [MRNA] (ISOFORM 1), VARIANTS GLN-1349; ALA-1527 AND
RP SER-2045, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND INDUCTION.
RC TISSUE=Macrophage;
RX PubMed=10873640; DOI=10.1006/bbrc.2000.2954;
RA Kaminski W.E., Orso E., Diederich W., Klucken J., Drobnik W., Schmitz G.;
RT "Identification of a novel human sterol-sensitive ATP-binding cassette
RT transporter (ABCA7).";
RL Biochem. Biophys. Res. Commun. 273:532-538(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ALA-1527.
RX PubMed=11095984; DOI=10.1006/bbrc.2000.3880;
RA Kaminski W.E., Piehler A., Schmitz G.;
RT "Genomic organization of the human cholesterol-responsive ABC transporter
RT ABCA7: tandem linkage with the minor histocompatibility antigen HA-1
RT gene.";
RL Biochem. Biophys. Res. Commun. 278:782-789(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND VARIANTS GLN-1349; ALA-1527 AND
RP SER-2045.
RC TISSUE=Thymus;
RX PubMed=11355874; DOI=10.1006/bbrc.2001.4891;
RA Tanaka A.R., Ikeda Y., Abe-Dohmae S., Arakawa R., Sadanami K., Kidera A.,
RA Nakagawa S., Nagase T., Aoki R., Kioka N., Amachi T., Yokoyama S., Ueda K.;
RT "Human ABCA1 contains a large amino-terminal extracellular domain
RT homologous to an epitope of Sjogren's Syndrome.";
RL Biochem. Biophys. Res. Commun. 283:1019-1025(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS GLY-188; ALA-1527 AND
RP SER-2045, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC TISSUE=Spleen;
RX PubMed=11435699; DOI=10.1159/000056914;
RA Broccardo C., Osorio J., Luciani M.-F., Schriml L.M., Prades C.,
RA Shulenin S., Arnould I., Naudin L., Lafargue C., Rosier M., Jordan B.,
RA Mattei M.-G., Dean M., Denefle P., Chimini G.;
RT "Comparative analysis of the promoter structure and genomic organization of
RT the human and mouse ABCA7 gene encoding a novel ABCA transporter.";
RL Cytogenet. Cell Genet. 92:264-270(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 195-352 (ISOFORMS 1/2).
RC TISSUE=Cervix carcinoma;
RA Niwa M., Maruyama M., Fujimoto T., Dohi K., Maruyama I.N.;
RT "Isolation of autoantigen cDNAs by lambda phage surface display.";
RL Submitted (APR-1999) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP FUNCTION, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=14592415; DOI=10.1016/j.bbrc.2003.10.002;
RA Ikeda Y., Abe-Dohmae S., Munehira Y., Aoki R., Kawamoto S., Furuya A.,
RA Shitara K., Amachi T., Kioka N., Matsuo M., Yokoyama S., Ueda K.;
RT "Posttranscriptional regulation of human ABCA7 and its function for the
RT apoA-I-dependent lipid release.";
RL Biochem. Biophys. Res. Commun. 311:313-318(2003).
RN [8]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=12917409; DOI=10.1074/jbc.m307831200;
RA Wang N., Lan D., Gerbod-Giannone M., Linsel-Nitschke P., Jehle A.W.,
RA Chen W., Martinez L.O., Tall A.R.;
RT "ATP-binding cassette transporter A7 (ABCA7) binds apolipoprotein A-I and
RT mediates cellular phospholipid but not cholesterol efflux.";
RL J. Biol. Chem. 278:42906-42912(2003).
RN [9]
RP FUNCTION, AND INDUCTION.
RX PubMed=12925201; DOI=10.1046/j.1523-1747.2003.12404.x;
RA Kielar D., Kaminski W.E., Liebisch G., Piehler A., Wenzel J.J., Moehle C.,
RA Heimerl S., Langmann T., Friedrich S.O., Boettcher A., Barlage S.,
RA Drobnik W., Schmitz G.;
RT "Adenosine triphosphate binding cassette (ABC) transporters are expressed
RT and regulated during terminal keratinocyte differentiation: a potential
RT role for ABCA7 in epidermal lipid reorganization.";
RL J. Invest. Dermatol. 121:465-474(2003).
RN [10]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=14570867; DOI=10.1074/jbc.m309888200;
RA Abe-Dohmae S., Ikeda Y., Matsuo M., Hayashi M., Okuhira K., Ueda K.,
RA Yokoyama S.;
RT "Human ABCA7 supports apolipoprotein-mediated release of cellular
RT cholesterol and phospholipid to generate high density lipoprotein.";
RL J. Biol. Chem. 279:604-611(2004).
RN [11]
RP CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND FUNCTION.
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 [12]
RP FUNCTION.
RX PubMed=26260791; DOI=10.1074/jbc.m115.655076;
RA Satoh K., Abe-Dohmae S., Yokoyama S., St George-Hyslop P., Fraser P.E.;
RT "ATP-binding cassette transporter A7 (ABCA7) loss of function alters
RT Alzheimer amyloid processing.";
RL J. Biol. Chem. 290:24152-24165(2015).
RN [13]
RP INVOLVEMENT IN AD9.
RX PubMed=26141617; DOI=10.1016/s1474-4422(15)00133-7;
RA Cuyvers E., De Roeck A., Van den Bossche T., Van Cauwenberghe C.,
RA Bettens K., Vermeulen S., Mattheijssens M., Peeters K., Engelborghs S.,
RA Vandenbulcke M., Vandenberghe R., De Deyn P.P., Van Broeckhoven C.,
RA Sleegers K.;
RT "Mutations in ABCA7 in a Belgian cohort of Alzheimer's disease patients: a
RT targeted resequencing study.";
RL Lancet Neurol. 14:814-822(2015).
RN [14]
RP INVOLVEMENT IN AD9.
RX PubMed=25807283; DOI=10.1038/ng.3246;
RG DemGene;
RA Steinberg S., Stefansson H., Jonsson T., Johannsdottir H., Ingason A.,
RA Helgason H., Sulem P., Magnusson O.T., Gudjonsson S.A., Unnsteinsdottir U.,
RA Kong A., Helisalmi S., Soininen H., Lah J.J., Aarsland D., Fladby T.,
RA Ulstein I.D., Djurovic S., Sando S.B., White L.R., Knudsen G.P.,
RA Westlye L.T., Selbaek G., Giegling I., Hampel H., Hiltunen M., Levey A.I.,
RA Andreassen O.A., Rujescu D., Jonsson P.V., Bjornsson S., Snaedal J.,
RA Stefansson K.;
RT "Loss-of-function variants in ABCA7 confer risk of Alzheimer's disease.";
RL Nat. Genet. 47:445-447(2015).
RN [15]
RP TISSUE SPECIFICITY.
RX PubMed=27472885; DOI=10.3233/jad-160456;
RA Fu Y., Hsiao J.H., Paxinos G., Halliday G.M., Kim W.S.;
RT "ABCA7 Mediates Phagocytic Clearance of Amyloid-beta in the Brain.";
RL J. Alzheimers Dis. 54:569-584(2016).
RN [16]
RP VARIANTS GLY-188; ALA-319; ARG-395; HIS-463; THR-718; GLN-1349; ARG-1686
RP AND SER-2045.
RX PubMed=12111378; DOI=10.1007/s100380200041;
RA Iida A., Saito S., Sekine A., Mishima C., Kitamura Y., Kondo K.,
RA Harigae S., Osawa S., Nakamura Y.;
RT "Catalog of 605 single-nucleotide polymorphisms (SNPs) among 13 genes
RT encoding human ATP-binding cassette transporters: ABCA4, ABCA7, ABCA8,
RT ABCD1, ABCD3, ABCD4, ABCE1, ABCF1, ABCG1, ABCG2, ABCG4, ABCG5, and ABCG8.";
RL J. Hum. Genet. 47:285-310(2002).
RN [17]
RP VARIANT AD9 GLN-880.
RX PubMed=29577078; DOI=10.1212/nxg.0000000000000224;
RA May P., Pichler S., Hartl D., Bobbili D.R., Mayhaus M., Spaniol C.,
RA Kurz A., Balling R., Schneider J.G., Riemenschneider M.;
RT "Rare ABCA7 variants in 2 German families with Alzheimer disease.";
RL Neurol. Genet. 4:E224-E224(2018).
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). Transports
CC preferentially phosphatidylserine over phosphatidylcholine
CC (PubMed:24097981). Plays a role in lipid homeostasis and macrophage-
CC mediated phagocytosis (PubMed:14592415, PubMed:12917409,
CC PubMed:12925201, PubMed:14570867). Binds APOA1 and may function in
CC apolipoprotein-mediated phospholipid efflux from cells
CC (PubMed:12917409, PubMed:14570867, PubMed:14592415). May also mediate
CC cholesterol efflux (PubMed:14570867). May regulate cellular ceramide
CC homeostasis during keratinocyte differentiation (PubMed:12925201).
CC Involved in lipid raft organization and CD1D localization on thymocytes
CC and antigen-presenting cells, which plays an important role in natural
CC killer T-cell development and activation (By similarity). Plays a role
CC in phagocytosis of apoptotic cells by macrophages (By similarity).
CC Macrophage phagocytosis is stimulated by APOA1 or APOA2, probably by
CC stabilization of ABCA7 (By similarity). Also involved in phagocytic
CC clearance of amyloid-beta by microglia cells and macrophages (By
CC similarity). Further limits amyloid-beta production by playing a role
CC in the regulation of amyloid-beta A4 precursor protein (APP)
CC endocytosis and/or processing (PubMed:26260791). Amyloid-beta is the
CC main component of amyloid plaques found in the brains of Alzheimer
CC patients (PubMed:26260791). {ECO:0000250|UniProtKB:Q91V24,
CC ECO:0000269|PubMed:12917409, ECO:0000269|PubMed:12925201,
CC ECO:0000269|PubMed:14570867, ECO:0000269|PubMed:14592415,
CC ECO:0000269|PubMed:24097981, ECO:0000269|PubMed:26260791}.
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:0000305|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:0000305|PubMed:24097981};
CC -!- ACTIVITY REGULATION: ATPase activity is decreased by cholesterol and
CC ceramide. ATPase activity is stimulated by phosphatidylserine,
CC phosphatidylcholine and sphingomyelin, but phosphatidylserine is more
CC effective. {ECO:0000269|PubMed:24097981}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12917409,
CC ECO:0000269|PubMed:14592415}; Multi-pass membrane protein
CC {ECO:0000255}. Golgi apparatus membrane {ECO:0000250|UniProtKB:Q91V24};
CC Multi-pass membrane protein {ECO:0000255}. Early endosome membrane
CC {ECO:0000250|UniProtKB:Q91V24}; Multi-pass membrane protein
CC {ECO:0000255}. Cytoplasm {ECO:0000250|UniProtKB:Q91V24}. Cell
CC projection, ruffle membrane {ECO:0000250|UniProtKB:Q91V24}. Cell
CC projection, phagocytic cup {ECO:0000250|UniProtKB:Q91V24}.
CC Note=Localizes to cell membrane ruffles and phagocytic cups of
CC macrophages stimulated with C1q or apoptotic cells. Localizes to the
CC cytoplasm of resting macrophages, probably in Golgi and endosomes.
CC Localizes to the apical brush border of cells in the proximal tubules
CC of kidney (By similarity). {ECO:0000250|UniProtKB:Q91V24}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm
CC {ECO:0000269|PubMed:14592415}. Endoplasmic reticulum
CC {ECO:0000269|PubMed:14592415}. Note=May localize to the endoplasmic
CC reticulum. {ECO:0000269|PubMed:14592415}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Type 1;
CC IsoId=Q8IZY2-1; Sequence=Displayed;
CC Name=2; Synonyms=Type 2;
CC IsoId=Q8IZY2-2; Sequence=VSP_020701, VSP_020702;
CC -!- TISSUE SPECIFICITY: Expressed in leukocytes (at protein level)
CC (PubMed:10873640). Widely expressed (PubMed:10873640). Highly expressed
CC in myelo-lymphatic tissues including peripheral leukocytes, thymus,
CC spleen and bone marrow (PubMed:10873640, PubMed:11435699). Expressed in
CC the hippocampus and the cerebellum (PubMed:27472885). Isoform 2:
CC Abundant in lymph node, spleen, thymus and trachea (PubMed:14592415).
CC Isoform 1: Strongly expressed in brain and bone marrow
CC (PubMed:14592415). {ECO:0000269|PubMed:10873640,
CC ECO:0000269|PubMed:11435699, ECO:0000269|PubMed:14592415,
CC ECO:0000269|PubMed:27472885}.
CC -!- DEVELOPMENTAL STAGE: Expressed in fetal tissues. Strongly expressed in
CC fetal liver. {ECO:0000269|PubMed:10873640,
CC ECO:0000269|PubMed:11435699}.
CC -!- INDUCTION: Up-regulated in macrophages upon cholesterol uptake and
CC inversely regulated upon cholesterol deloading from the cells (at
CC protein level). Up-regulated in keratinocytes during terminal
CC differentiation. {ECO:0000269|PubMed:10873640,
CC ECO:0000269|PubMed:12925201}.
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:Q91V24}.
CC -!- DISEASE: Alzheimer disease 9 (AD9) [MIM:608907]: A familial, late-onset
CC form of Alzheimer disease. Alzheimer disease is a neurodegenerative
CC disorder characterized by progressive dementia, loss of cognitive
CC abilities, and deposition of fibrillar amyloid proteins as
CC intraneuronal neurofibrillary tangles, extracellular amyloid plaques
CC and vascular amyloid deposits. The major constituents of these plaques
CC are neurotoxic amyloid-beta protein 40 and amyloid-beta protein 42,
CC that are produced by the proteolysis of the transmembrane APP protein.
CC The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved
CC products, such as C31, are also implicated in neuronal death.
CC {ECO:0000269|PubMed:25807283, ECO:0000269|PubMed:26141617,
CC ECO:0000269|PubMed:29577078}. Note=Disease susceptibility is associated
CC with variants affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: [Isoform 2]: Inactive for apoA-I-mediated lipid release.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the ABC transporter superfamily. ABCA family.
CC {ECO:0000305}.
CC -!- CAUTION: There are conflicting results concerning the role of ABCA7 in
CC lipid transport. ABCA7 was described to play a role in apolipoprotein-
CC mediated phospholipid and cholesterol efflux when expressed in HEK293
CC cells (PubMed:12917409, PubMed:27472885). However, another report shows
CC that ABCA7 deficiency does not influence cholesterol and phospholipid
CC efflux in mouse primary macrophages, but leads to lower serum HDL
CC cholesterol levels and a reduction in fat mass in female mice (By
CC similarity). {ECO:0000250|UniProtKB:Q91V24,
CC ECO:0000269|PubMed:12917409, ECO:0000269|PubMed:27472885}.
CC -!- WEB RESOURCE: Name=ABCMdb; Note=Database for mutations in ABC proteins;
CC URL="http://abcm2.hegelab.org/search";
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DR EMBL; AF250238; AAF85794.1; -; mRNA.
DR EMBL; AF311102; AAN04657.1; -; Genomic_DNA.
DR EMBL; AF311058; AAN04657.1; JOINED; Genomic_DNA.
DR EMBL; AF311059; AAN04657.1; JOINED; Genomic_DNA.
DR EMBL; AF311060; AAN04657.1; JOINED; Genomic_DNA.
DR EMBL; AF311061; AAN04657.1; JOINED; Genomic_DNA.
DR EMBL; AF311062; AAN04657.1; JOINED; Genomic_DNA.
DR EMBL; AF311063; AAN04657.1; JOINED; Genomic_DNA.
DR EMBL; AF311064; AAN04657.1; JOINED; Genomic_DNA.
DR EMBL; AF311065; AAN04657.1; JOINED; Genomic_DNA.
DR EMBL; AF311066; AAN04657.1; JOINED; Genomic_DNA.
DR EMBL; AF311067; AAN04657.1; JOINED; Genomic_DNA.
DR EMBL; AF311068; AAN04657.1; JOINED; Genomic_DNA.
DR EMBL; AF311057; AAN04657.1; JOINED; Genomic_DNA.
DR EMBL; AF311069; AAN04657.1; JOINED; Genomic_DNA.
DR EMBL; AF311070; AAN04657.1; JOINED; Genomic_DNA.
DR EMBL; AF311071; AAN04657.1; JOINED; Genomic_DNA.
DR EMBL; AF311072; AAN04657.1; JOINED; Genomic_DNA.
DR EMBL; AF311073; AAN04657.1; JOINED; Genomic_DNA.
DR EMBL; AF311074; AAN04657.1; JOINED; Genomic_DNA.
DR EMBL; AF311075; AAN04657.1; JOINED; Genomic_DNA.
DR EMBL; AF311076; AAN04657.1; JOINED; Genomic_DNA.
DR EMBL; AF311077; AAN04657.1; JOINED; Genomic_DNA.
DR EMBL; AF311078; AAN04657.1; JOINED; Genomic_DNA.
DR EMBL; AF311079; AAN04657.1; JOINED; Genomic_DNA.
DR EMBL; AF311080; AAN04657.1; JOINED; Genomic_DNA.
DR EMBL; AF311081; AAN04657.1; JOINED; Genomic_DNA.
DR EMBL; AF311082; AAN04657.1; JOINED; Genomic_DNA.
DR EMBL; AF311083; AAN04657.1; JOINED; Genomic_DNA.
DR EMBL; AF311084; AAN04657.1; JOINED; Genomic_DNA.
DR EMBL; AF311085; AAN04657.1; JOINED; Genomic_DNA.
DR EMBL; AF311086; AAN04657.1; JOINED; Genomic_DNA.
DR EMBL; AF311087; AAN04657.1; JOINED; Genomic_DNA.
DR EMBL; AF311088; AAN04657.1; JOINED; Genomic_DNA.
DR EMBL; AF311089; AAN04657.1; JOINED; Genomic_DNA.
DR EMBL; AF311090; AAN04657.1; JOINED; Genomic_DNA.
DR EMBL; AF311091; AAN04657.1; JOINED; Genomic_DNA.
DR EMBL; AF311092; AAN04657.1; JOINED; Genomic_DNA.
DR EMBL; AF311093; AAN04657.1; JOINED; Genomic_DNA.
DR EMBL; AF311094; AAN04657.1; JOINED; Genomic_DNA.
DR EMBL; AF311095; AAN04657.1; JOINED; Genomic_DNA.
DR EMBL; AF311096; AAN04657.1; JOINED; Genomic_DNA.
DR EMBL; AF311097; AAN04657.1; JOINED; Genomic_DNA.
DR EMBL; AF311098; AAN04657.1; JOINED; Genomic_DNA.
DR EMBL; AF311099; AAN04657.1; JOINED; Genomic_DNA.
DR EMBL; AF311100; AAN04657.1; JOINED; Genomic_DNA.
DR EMBL; AF311101; AAN04657.1; JOINED; Genomic_DNA.
DR EMBL; AB055390; BAB62294.1; -; mRNA.
DR EMBL; AF328787; AAK00959.1; -; mRNA.
DR EMBL; AC011558; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AF140342; AAF06727.1; -; mRNA.
DR CCDS; CCDS12055.1; -. [Q8IZY2-1]
DR RefSeq; NP_061985.2; NM_019112.3. [Q8IZY2-1]
DR RefSeq; XP_011525930.1; XM_011527628.2.
DR AlphaFoldDB; Q8IZY2; -.
DR SMR; Q8IZY2; -.
DR BioGRID; 115629; 21.
DR IntAct; Q8IZY2; 14.
DR MINT; Q8IZY2; -.
DR STRING; 9606.ENSP00000263094; -.
DR SwissLipids; SLP:000000346; -.
DR TCDB; 3.A.1.211.10; the atp-binding cassette (abc) superfamily.
DR GlyConnect; 1022; 1 N-Linked glycan (1 site).
DR GlyGen; Q8IZY2; 7 sites, 1 N-linked glycan (1 site), 1 O-linked glycan (1 site).
DR iPTMnet; Q8IZY2; -.
DR PhosphoSitePlus; Q8IZY2; -.
DR BioMuta; ABCA7; -.
DR DMDM; 161784300; -.
DR jPOST; Q8IZY2; -.
DR MassIVE; Q8IZY2; -.
DR MaxQB; Q8IZY2; -.
DR PaxDb; Q8IZY2; -.
DR PeptideAtlas; Q8IZY2; -.
DR PRIDE; Q8IZY2; -.
DR ProteomicsDB; 71441; -. [Q8IZY2-1]
DR ProteomicsDB; 71442; -. [Q8IZY2-2]
DR Antibodypedia; 22516; 181 antibodies from 31 providers.
DR DNASU; 10347; -.
DR Ensembl; ENST00000263094.11; ENSP00000263094.6; ENSG00000064687.13. [Q8IZY2-1]
DR GeneID; 10347; -.
DR KEGG; hsa:10347; -.
DR MANE-Select; ENST00000263094.11; ENSP00000263094.6; NM_019112.4; NP_061985.2.
DR UCSC; uc002lqw.5; human. [Q8IZY2-1]
DR CTD; 10347; -.
DR DisGeNET; 10347; -.
DR GeneCards; ABCA7; -.
DR HGNC; HGNC:37; ABCA7.
DR HPA; ENSG00000064687; Tissue enhanced (bone marrow, lymphoid tissue, pituitary gland).
DR MalaCards; ABCA7; -.
DR MIM; 605414; gene.
DR MIM; 608907; phenotype.
DR neXtProt; NX_Q8IZY2; -.
DR NIAGADS; ENSG00000064687; -.
DR OpenTargets; ENSG00000064687; -.
DR Orphanet; 1020; Early-onset autosomal dominant Alzheimer disease.
DR Orphanet; 238616; NON RARE IN EUROPE: Alzheimer disease.
DR PharmGKB; PA24382; -.
DR VEuPathDB; HostDB:ENSG00000064687; -.
DR eggNOG; KOG0059; Eukaryota.
DR GeneTree; ENSGT00940000161439; -.
DR HOGENOM; CLU_000604_19_0_1; -.
DR InParanoid; Q8IZY2; -.
DR OMA; GQAQEPL; -.
DR OrthoDB; 131191at2759; -.
DR PhylomeDB; Q8IZY2; -.
DR TreeFam; TF105191; -.
DR PathwayCommons; Q8IZY2; -.
DR Reactome; R-HSA-1369062; ABC transporters in lipid homeostasis.
DR SignaLink; Q8IZY2; -.
DR SIGNOR; Q8IZY2; -.
DR BioGRID-ORCS; 10347; 22 hits in 1080 CRISPR screens.
DR ChiTaRS; ABCA7; human.
DR GeneWiki; ABCA7; -.
DR GenomeRNAi; 10347; -.
DR Pharos; Q8IZY2; Tbio.
DR PRO; PR:Q8IZY2; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q8IZY2; protein.
DR Bgee; ENSG00000064687; Expressed in granulocyte and 144 other tissues.
DR ExpressionAtlas; Q8IZY2; baseline and differential.
DR Genevisible; Q8IZY2; HS.
DR GO; GO:0030054; C:cell junction; IDA:HPA.
DR GO; GO:0009986; C:cell surface; ISS:Alzheimers_University_of_Toronto.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0097386; C:glial cell projection; ISS:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0001891; C:phagocytic cup; ISS:Alzheimers_University_of_Toronto.
DR GO; GO:0005886; C:plasma membrane; IDA:Alzheimers_University_of_Toronto.
DR GO; GO:0032587; C:ruffle membrane; ISS:Alzheimers_University_of_Toronto.
DR GO; GO:0140359; F:ABC-type transporter activity; IEA:InterPro.
DR GO; GO:0034188; F:apolipoprotein A-I receptor activity; IDA:Alzheimers_University_of_Toronto.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042626; F:ATPase-coupled transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0140328; F:floppase activity; IDA:UniProtKB.
DR GO; GO:0005319; F:lipid transporter activity; IBA:GO_Central.
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:0150094; P:amyloid-beta clearance by cellular catabolic process; ISS:UniProtKB.
DR GO; GO:0034205; P:amyloid-beta formation; IMP:UniProtKB.
DR GO; GO:0038027; P:apolipoprotein A-I-mediated signaling pathway; IDA:Alzheimers_University_of_Toronto.
DR GO; GO:0033344; P:cholesterol efflux; IDA:Alzheimers_University_of_Toronto.
DR GO; GO:0034380; P:high-density lipoprotein particle assembly; IDA:Alzheimers_University_of_Toronto.
DR GO; GO:0006869; P:lipid transport; IBA:GO_Central.
DR GO; GO:0007613; P:memory; ISS:Alzheimers_University_of_Toronto.
DR GO; GO:0042985; P:negative regulation of amyloid precursor protein biosynthetic process; ISS:Alzheimers_University_of_Toronto.
DR GO; GO:1902430; P:negative regulation of amyloid-beta formation; ISS:Alzheimers_University_of_Toronto.
DR GO; GO:0045806; P:negative regulation of endocytosis; ISS:UniProtKB.
DR GO; GO:0043409; P:negative regulation of MAPK cascade; ISS:ARUK-UCL.
DR GO; GO:1903898; P:negative regulation of PERK-mediated unfolded protein response; ISS:ARUK-UCL.
DR GO; GO:0018149; P:peptide cross-linking; ISS:Alzheimers_University_of_Toronto.
DR GO; GO:0006909; P:phagocytosis; IEA:UniProtKB-KW.
DR GO; GO:0033700; P:phospholipid efflux; IDA:Alzheimers_University_of_Toronto.
DR GO; GO:0045332; P:phospholipid translocation; IDA:BHF-UCL.
DR GO; GO:0044857; P:plasma membrane raft organization; ISS:UniProtKB.
DR GO; GO:1900223; P:positive regulation of amyloid-beta clearance; ISS:Alzheimers_University_of_Toronto.
DR GO; GO:0010875; P:positive regulation of cholesterol efflux; ISS:Alzheimers_University_of_Toronto.
DR GO; GO:1901076; P:positive regulation of engulfment of apoptotic cell; ISS:Alzheimers_University_of_Toronto.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:Alzheimers_University_of_Toronto.
DR GO; GO:0050766; P:positive regulation of phagocytosis; ISS:Alzheimers_University_of_Toronto.
DR GO; GO:1902995; P:positive regulation of phospholipid efflux; ISS:Alzheimers_University_of_Toronto.
DR GO; GO:2000010; P:positive regulation of protein localization to cell surface; ISS:UniProtKB.
DR GO; GO:0034504; P:protein localization to nucleus; ISS:Alzheimers_University_of_Toronto.
DR GO; GO:1902991; P:regulation of amyloid precursor protein catabolic process; IMP:UniProtKB.
DR GO; GO:0019216; P:regulation of lipid metabolic process; ISS:ARUK-UCL.
DR GO; GO:0008542; P:visual learning; ISS:ARUK-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; IPR030369; ABCA7.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR19229; PTHR19229; 1.
DR PANTHER; PTHR19229:SF49; PTHR19229:SF49; 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 Alternative splicing; Alzheimer disease; Amyloidosis; ATP-binding;
KW Cell membrane; Cell projection; Cytoplasm; Disulfide bond;
KW Endoplasmic reticulum; Endosome; Glycoprotein; Golgi apparatus;
KW Lipid transport; Membrane; Neurodegeneration; Nucleotide-binding;
KW Phagocytosis; Reference proteome; Repeat; Translocase; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..2146
FT /note="Phospholipid-transporting ATPase ABCA7"
FT /id="PRO_0000250674"
FT TRANSMEM 22..42
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 43..549
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 550..570
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 593..613
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 626..646
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 655..675
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 687..707
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 727..747
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 849..869
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1243..1263
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1264..1537
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 1538..1558
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1584..1604
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1621..1641
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1649..1669
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1683..1703
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1729..1749
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 807..1038
FT /note="ABC transporter 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT DOMAIN 1793..2025
FT /note="ABC transporter 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT REGION 1048..1072
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1185..1209
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2104..2146
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1048..1066
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 841..848
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT BINDING 1827..1834
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT CARBOHYD 312
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 75..225
FT /evidence="ECO:0000250"
FT DISULFID 1345..1359
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..138
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11355874"
FT /id="VSP_020701"
FT VAR_SEQ 139..166
FT /note="AQPQPTKQSPLEPPMLDVAELLTSLLRT -> MVCLGTGQSAGPLVSVQNHC
FT PPCGLSPQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11355874"
FT /id="VSP_020702"
FT VARIANT 188
FT /note="E -> G (in dbSNP:rs3764645)"
FT /evidence="ECO:0000269|PubMed:11435699,
FT ECO:0000269|PubMed:12111378"
FT /id="VAR_027581"
FT VARIANT 319
FT /note="T -> A (in dbSNP:rs3752232)"
FT /evidence="ECO:0000269|PubMed:12111378"
FT /id="VAR_027582"
FT VARIANT 395
FT /note="H -> R (in dbSNP:rs3764647)"
FT /evidence="ECO:0000269|PubMed:12111378"
FT /id="VAR_027583"
FT VARIANT 463
FT /note="R -> H (in dbSNP:rs3752233)"
FT /evidence="ECO:0000269|PubMed:12111378"
FT /id="VAR_027584"
FT VARIANT 676
FT /note="A -> T (in dbSNP:rs59851484)"
FT /id="VAR_060985"
FT VARIANT 718
FT /note="N -> T (in dbSNP:rs3752239)"
FT /evidence="ECO:0000269|PubMed:12111378"
FT /id="VAR_027585"
FT VARIANT 880
FT /note="R -> Q (in AD9; dbSNP:rs143718918)"
FT /evidence="ECO:0000269|PubMed:29577078"
FT /id="VAR_081204"
FT VARIANT 1349
FT /note="R -> Q (in dbSNP:rs3745842)"
FT /evidence="ECO:0000269|PubMed:10873640,
FT ECO:0000269|PubMed:11355874, ECO:0000269|PubMed:12111378"
FT /id="VAR_027586"
FT VARIANT 1527
FT /note="G -> A (in dbSNP:rs3752246)"
FT /evidence="ECO:0000269|PubMed:10873640,
FT ECO:0000269|PubMed:11095984, ECO:0000269|PubMed:11355874,
FT ECO:0000269|PubMed:11435699"
FT /id="VAR_027587"
FT VARIANT 1686
FT /note="Q -> R (in dbSNP:rs4147918)"
FT /evidence="ECO:0000269|PubMed:12111378"
FT /id="VAR_027588"
FT VARIANT 2045
FT /note="A -> S (in dbSNP:rs4147934)"
FT /evidence="ECO:0000269|PubMed:10873640,
FT ECO:0000269|PubMed:11355874, ECO:0000269|PubMed:11435699,
FT ECO:0000269|PubMed:12111378"
FT /id="VAR_027589"
FT CONFLICT 1503
FT /note="P -> R (in Ref. 1; AAF85794 and 3; BAB62294)"
FT /evidence="ECO:0000305"
FT CONFLICT 1525
FT /note="S -> F (in Ref. 1; AAF85794, 2; AAN04657 and 3;
FT BAB62294)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 2146 AA; 234350 MW; 6EA624088E74FEE6 CRC64;
MAFWTQLMLL LWKNFMYRRR QPVQLLVELL WPLFLFFILV AVRHSHPPLE HHECHFPNKP
LPSAGTVPWL QGLICNVNNT CFPQLTPGEE PGRLSNFNDS LVSRLLADAR TVLGGASAHR
TLAGLGKLIA TLRAARSTAQ PQPTKQSPLE PPMLDVAELL TSLLRTESLG LALGQAQEPL
HSLLEAAEDL AQELLALRSL VELRALLQRP RGTSGPLELL SEALCSVRGP SSTVGPSLNW
YEASDLMELV GQEPESALPD SSLSPACSEL IGALDSHPLS RLLWRRLKPL ILGKLLFAPD
TPFTRKLMAQ VNRTFEELTL LRDVREVWEM LGPRIFTFMN DSSNVAMLQR LLQMQDEGRR
QPRPGGRDHM EALRSFLDPG SGGYSWQDAH ADVGHLVGTL GRVTECLSLD KLEAAPSEAA
LVSRALQLLA EHRFWAGVVF LGPEDSSDPT EHPTPDLGPG HVRIKIRMDI DVVTRTNKIR
DRFWDPGPAA DPLTDLRYVW GGFVYLQDLV ERAAVRVLSG ANPRAGLYLQ QMPYPCYVDD
VFLRVLSRSL PLFLTLAWIY SVTLTVKAVV REKETRLRDT MRAMGLSRAV LWLGWFLSCL
GPFLLSAALL VLVLKLGDIL PYSHPGVVFL FLAAFAVATV TQSFLLSAFF SRANLAAACG
GLAYFSLYLP YVLCVAWRDR LPAGGRVAAS LLSPVAFGFG CESLALLEEQ GEGAQWHNVG
TRPTADVFSL AQVSGLLLLD AALYGLATWY LEAVCPGQYG IPEPWNFPFR RSYWCGPRPP
KSPAPCPTPL DPKVLVEEAP PGLSPGVSVR SLEKRFPGSP QPALRGLSLD FYQGHITAFL
GHNGAGKTTT LSILSGLFPP SGGSAFILGH DVRSSMAAIR PHLGVCPQYN VLFDMLTVDE
HVWFYGRLKG LSAAVVGPEQ DRLLQDVGLV SKQSVQTRHL SGGMQRKLSV AIAFVGGSQV
VILDEPTAGV DPASRRGIWE LLLKYREGRT LILSTHHLDE AELLGDRVAV VAGGRLCCCG
SPLFLRRHLG SGYYLTLVKA RLPLTTNEKA DTDMEGSVDT RQEKKNGSQG SRVGTPQLLA
LVQHWVPGAR LVEELPHELV LVLPYTGAHD GSFATLFREL DTRLAELRLT GYGISDTSLE
EIFLKVVEEC AADTDMEDGS CGQHLCTGIA GLDVTLRLKM PPQETALENG EPAGSAPETD
QGSGPDAVGR VQGWALTRQQ LQALLLKRFL LARRSRRGLF AQIVLPALFV GLALVFSLIV
PPFGHYPALR LSPTMYGAQV SFFSEDAPGD PGRARLLEAL LQEAGLEEPP VQHSSHRFSA
PEVPAEVAKV LASGNWTPES PSPACQCSRP GARRLLPDCP AAAGGPPPPQ AVTGSGEVVQ
NLTGRNLSDF LVKTYPRLVR QGLKTKKWVN EVRYGGFSLG GRDPGLPSGQ ELGRSVEELW
ALLSPLPGGA LDRVLKNLTA WAHSLDAQDS LKIWFNNKGW HSMVAFVNRA SNAILRAHLP
PGPARHAHSI TTLNHPLNLT KEQLSEGALM ASSVDVLVSI CVVFAMSFVP ASFTLVLIEE
RVTRAKHLQL MGGLSPTLYW LGNFLWDMCN YLVPACIVVL IFLAFQQRAY VAPANLPALL
LLLLLYGWSI TPLMYPASFF FSVPSTAYVV LTCINLFIGI NGSMATFVLE LFSDQKLQEV
SRILKQVFLI FPHFCLGRGL IDMVRNQAMA DAFERLGDRQ FQSPLRWEVV GKNLLAMVIQ
GPLFLLFTLL LQHRSQLLPQ PRVRSLPLLG EEDEDVARER ERVVQGATQG DVLVLRNLTK
VYRGQRMPAV DRLCLGIPPG ECFGLLGVNG AGKTSTFRMV TGDTLASRGE AVLAGHSVAR
EPSAAHLSMG YCPQSDAIFE LLTGREHLEL LARLRGVPEA QVAQTAGSGL ARLGLSWYAD
RPAGTYSGGN KRKLATALAL VGDPAVVFLD EPTTGMDPSA RRFLWNSLLA VVREGRSVML
TSHSMEECEA LCSRLAIMVN GRFRCLGSPQ HLKGRFAAGH TLTLRVPAAR SQPAAAFVAA
EFPGAELREA HGGRLRFQLP PGGRCALARV FGELAVHGAE HGVEDFSVSQ TMLEEVFLYF
SKDQGKDEDT EEQKEAGVGV DPAPGLQHPK RVSQFLDDPS TAETVL
