ABCA2_HUMAN
ID ABCA2_HUMAN Reviewed; 2435 AA.
AC Q9BZC7; A6NED5; Q5SPY5; Q5W9G5; Q76MW7; Q9HC28;
DT 11-JUL-2001, integrated into UniProtKB/Swiss-Prot.
DT 12-SEP-2018, sequence version 4.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=ATP-binding cassette sub-family A member 2 {ECO:0000305};
DE EC=7.6.2.- {ECO:0000305|PubMed:15999530};
DE AltName: Full=ATP-binding cassette transporter 2;
DE Short=ATP-binding cassette 2;
GN Name=ABCA2 {ECO:0000312|HGNC:HGNC:32}; Synonyms=ABC2, KIAA1062;
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] (ISOFORM 3).
RX PubMed=11178988; DOI=10.1006/bbrc.2001.4305;
RA Kaminski W.E., Piehler A., Pullmann K., Porsch-Oezcueruemez M., Duong C.,
RA Bared G.M., Buchler C., Schmitz G.;
RT "Complete coding sequence, promoter region, and genomic structure of the
RT human ABCA2 gene and evidence for sterol-dependent regulation in
RT macrophages.";
RL Biochem. Biophys. Res. Commun. 281:249-258(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), TISSUE SPECIFICITY, AND SUBCELLULAR
RP LOCATION.
RC TISSUE=Brain;
RX PubMed=11309290;
RA Vulevic B., Chen Z., Boyd J.T., Davis W. Jr., Walsh E.S., Belinsky M.G.,
RA Tew K.D.;
RT "Cloning and characterization of human adenosine 5'-triphosphate-binding
RT cassette, sub-family A, transporter 2.";
RL Cancer Res. 61:3339-3347(2001).
RN [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 651-2435 (ISOFORM 2), AND
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 665-2435 (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=10470851; DOI=10.1093/dnares/6.3.197;
RA Kikuno R., Nagase T., Ishikawa K., Hirosawa M., Miyajima N., Tanaka A.,
RA Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIV. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 6:197-205(1999).
RN [5]
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-22 (ISOFORMS 3 AND 4), AND SUBCELLULAR
RP LOCATION.
RX PubMed=15093135; DOI=10.1016/j.bbaexp.2004.01.007;
RA Ile K.E., Davis W. Jr., Boyd J.T., Soulika A.M., Tew K.D.;
RT "Identification of a novel first exon of the human ABCA2 transporter gene
RT encoding a unique N-terminus.";
RL Biochim. Biophys. Acta 1678:22-32(2004).
RN [7]
RP INDUCTION, AND FUNCTION.
RX PubMed=15238223; DOI=10.1016/j.bbalip.2004.04.009;
RA Davis W. Jr., Boyd J.T., Ile K.E., Tew K.D.;
RT "Human ATP-binding cassette transporter-2 (ABCA2) positively regulates low-
RT density lipoprotein receptor expression and negatively regulates
RT cholesterol esterification in Chinese hamster ovary cells.";
RL Biochim. Biophys. Acta 1683:89-100(2004).
RN [8]
RP FUNCTION.
RX PubMed=15999530;
RA Beljanski V., Soulika A., Tucker J.M., Townsend D.M., Davis W. Jr.,
RA Tew K.D.;
RT "Characterization of the ATPase activity of human ATP-binding cassette
RT transporter-2 (ABCA2).";
RL In Vivo 19:657-660(2005).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1327 AND SER-1331, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-2412, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [11]
RP FUNCTION.
RX PubMed=21810484; DOI=10.1016/j.bbalip.2011.07.010;
RA Davis W. Jr.;
RT "The ATP-binding cassette transporter-2 (ABCA2) regulates cholesterol
RT homeostasis and low-density lipoprotein receptor metabolism in N2a
RT neuroblastoma cells.";
RL Biochim. Biophys. Acta 1811:1152-1164(2011).
RN [12]
RP FUNCTION.
RX PubMed=22086926; DOI=10.1074/jbc.m111.288258;
RA Michaki V., Guix F.X., Vennekens K., Munck S., Dingwall C., Davis J.B.,
RA Townsend D.M., Tew K.D., Feiguin F., De Strooper B., Dotti C.G., Wahle T.;
RT "Down-regulation of the ATP-binding cassette transporter 2 (Abca2) reduces
RT amyloid-beta production by altering Nicastrin maturation and intracellular
RT localization.";
RL J. Biol. Chem. 287:1100-1111(2012).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1238, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [14]
RP FUNCTION.
RX PubMed=24201375; DOI=10.1016/j.bbalip.2013.10.019;
RA Davis W. Jr.;
RT "The ATP-binding cassette transporter-2 (ABCA2) regulates esterification of
RT plasma membrane cholesterol by modulation of sphingolipid metabolism.";
RL Biochim. Biophys. Acta 1841:168-179(2014).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1331, AND IDENTIFICATION BY
RP 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 [16]
RP FUNCTION.
RX PubMed=26510981; DOI=10.2174/156720501209151019105834;
RA Davis W. Jr.;
RT "The ATP-Binding Cassette Transporter-2 (ABCA2) Overexpression Modulates
RT Sphingosine Levels and Transcription of the Amyloid Precursor Protein (APP)
RT Gene.";
RL Curr. Alzheimer Res. 12:847-859(2015).
RN [17]
RP METHYLATION AT GLN-271, AND MUTAGENESIS OF GLN-271.
RX PubMed=26797129; DOI=10.1074/jbc.m115.711952;
RA Kusevic D., Kudithipudi S., Jeltsch A.;
RT "Substrate specificity of the HEMK2 protein glutamine methyltransferase and
RT identification of novel substrates.";
RL J. Biol. Chem. 291:6124-6133(2016).
RN [18]
RP INVOLVEMENT IN IDPOGSA.
RX PubMed=29302074; DOI=10.1038/s41380-017-0012-2;
RA Hu H., Kahrizi K., Musante L., Fattahi Z., Herwig R., Hosseini M.,
RA Oppitz C., Abedini S.S., Suckow V., Larti F., Beheshtian M., Lipkowitz B.,
RA Akhtarkhavari T., Mehvari S., Otto S., Mohseni M., Arzhangi S., Jamali P.,
RA Mojahedi F., Taghdiri M., Papari E., Soltani Banavandi M.J., Akbari S.,
RA Tonekaboni S.H., Dehghani H., Ebrahimpour M.R., Bader I., Davarnia B.,
RA Cohen M., Khodaei H., Albrecht B., Azimi S., Zirn B., Bastami M.,
RA Wieczorek D., Bahrami G., Keleman K., Vahid L.N., Tzschach A., Gaertner J.,
RA Gillessen-Kaesbach G., Varaghchi J.R., Timmermann B., Pourfatemi F.,
RA Jankhah A., Chen W., Nikuei P., Kalscheuer V.M., Oladnabi M., Wienker T.F.,
RA Ropers H.H., Najmabadi H.;
RT "Genetics of intellectual disability in consanguineous families.";
RL Mol. Psychiatry 24:1027-1039(2019).
RN [19]
RP VARIANT IDPOGSA 343-ALA--CYS-2435 DEL, AND INVOLVEMENT IN IDPOGSA.
RX PubMed=30237576; DOI=10.1038/s41436-018-0138-x;
RA Maddirevula S., Alzahrani F., Al-Owain M., Al Muhaizea M.A., Kayyali H.R.,
RA AlHashem A., Rahbeeni Z., Al-Otaibi M., Alzaidan H.I., Balobaid A.,
RA El Khashab H.Y., Bubshait D.K., Faden M., Yamani S.A., Dabbagh O.,
RA Al-Mureikhi M., Jasser A.A., Alsaif H.S., Alluhaydan I., Seidahmed M.Z.,
RA Alabbasi B.H., Almogarri I., Kurdi W., Akleh H., Qari A., Al Tala S.M.,
RA Alhomaidi S., Kentab A.Y., Salih M.A., Chedrawi A., Alameer S., Tabarki B.,
RA Shamseldin H.E., Patel N., Ibrahim N., Abdulwahab F., Samira M., Goljan E.,
RA Abouelhoda M., Meyer B.F., Hashem M., Shaheen R., AlShahwan S.,
RA Alfadhel M., Ben-Omran T., Al-Qattan M.M., Monies D., Alkuraya F.S.;
RT "Autozygome and high throughput confirmation of disease genes candidacy.";
RL Genet. Med. 21:736-742(2019).
CC -!- FUNCTION: Probable lipid transporter that modulates cholesterol
CC sequestration in the late endosome/lysosome by regulating the
CC intracellular sphingolipid metabolism, in turn participates in
CC cholesterol homeostasis (PubMed:15238223, PubMed:21810484,
CC PubMed:24201375) (Probable). May alter the transbilayer distribution of
CC ceramide in the intraluminal membrane lipid bilayer, favoring its
CC retention in the outer leaflet that results in increased acid
CC ceramidase activity in the late endosome/lysosome, facilitating
CC ceramide deacylation to sphingosine leading to the sequestration of
CC free cholesterol in lysosomes (PubMed:24201375). In addition regulates
CC amyloid-beta production either by activating a signaling pathway that
CC regulates amyloid precursor protein transcription through the
CC modulation of sphingolipid metabolism or through its role in gamma-
CC secretase processing of APP (PubMed:22086926, PubMed:26510981). May
CC play a role in myelin formation (By similarity).
CC {ECO:0000250|UniProtKB:P41234, ECO:0000269|PubMed:15238223,
CC ECO:0000269|PubMed:21810484, ECO:0000269|PubMed:22086926,
CC ECO:0000269|PubMed:24201375, ECO:0000269|PubMed:26510981,
CC ECO:0000305|PubMed:15999530}.
CC -!- SUBCELLULAR LOCATION: Endosome membrane {ECO:0000269|PubMed:11309290,
CC ECO:0000269|PubMed:15093135}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:11309290}. Lysosome membrane
CC {ECO:0000269|PubMed:11309290, ECO:0000269|PubMed:15093135}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:11309290}. Note=Forms discrete,
CC punctate intracellular vesicles. {ECO:0000269|PubMed:11309290}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q9BZC7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9BZC7-2; Sequence=VSP_035283, VSP_035284;
CC Name=3; Synonyms=1A form {ECO:0000303|PubMed:15093135};
CC IsoId=Q9BZC7-3; Sequence=VSP_040937;
CC Name=4 {ECO:0000303|PubMed:15093135}; Synonyms=1B form
CC {ECO:0000303|PubMed:15093135};
CC IsoId=Q9BZC7-4; Sequence=VSP_060910, VSP_040937;
CC -!- TISSUE SPECIFICITY: [Isoform 3]: Highly expressed in the
CC brain,peripheral blood leukocytes and ovary, whereas lower levels of
CC expression is observed in kidney and liver.
CC {ECO:0000269|PubMed:11309290, ECO:0000269|PubMed:15093135}.
CC -!- TISSUE SPECIFICITY: [Isoform 4]: Weakly expressed in brain and highly
CC in peripheral blood leukocytes. {ECO:0000269|PubMed:15093135}.
CC -!- INDUCTION: Increased under sterol-deprived conditions and decreased by
CC the addition of exogenous sterols. {ECO:0000269|PubMed:15238223}.
CC -!- PTM: Methylated at Gln-271 by N6AMT1. {ECO:0000269|PubMed:26797129}.
CC -!- DISEASE: Intellectual developmental disorder with poor growth and with
CC or without seizures or ataxia (IDPOGSA) [MIM:618808]: An autosomal
CC recessive disorder characterized by global developmental delay apparent
CC from infancy, impaired intellectual development, hypotonia, and poor
CC overall growth with microcephaly. Additional variable features include
CC dysmorphic features, cataracts, ataxia and seizures.
CC {ECO:0000269|PubMed:29302074, ECO:0000269|PubMed:30237576}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the ABC transporter superfamily. ABCA family.
CC {ECO:0000305}.
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; AF327657; AAK14334.1; -; mRNA.
DR EMBL; AF327705; AAK14335.1; -; Genomic_DNA.
DR EMBL; AF327658; AAK14335.1; JOINED; Genomic_DNA.
DR EMBL; AF327659; AAK14335.1; JOINED; Genomic_DNA.
DR EMBL; AF327660; AAK14335.1; JOINED; Genomic_DNA.
DR EMBL; AF327661; AAK14335.1; JOINED; Genomic_DNA.
DR EMBL; AF327662; AAK14335.1; JOINED; Genomic_DNA.
DR EMBL; AF327663; AAK14335.1; JOINED; Genomic_DNA.
DR EMBL; AF327664; AAK14335.1; JOINED; Genomic_DNA.
DR EMBL; AF327665; AAK14335.1; JOINED; Genomic_DNA.
DR EMBL; AF327666; AAK14335.1; JOINED; Genomic_DNA.
DR EMBL; AF327667; AAK14335.1; JOINED; Genomic_DNA.
DR EMBL; AF327668; AAK14335.1; JOINED; Genomic_DNA.
DR EMBL; AF327669; AAK14335.1; JOINED; Genomic_DNA.
DR EMBL; AF327670; AAK14335.1; JOINED; Genomic_DNA.
DR EMBL; AF327671; AAK14335.1; JOINED; Genomic_DNA.
DR EMBL; AF327672; AAK14335.1; JOINED; Genomic_DNA.
DR EMBL; AF327673; AAK14335.1; JOINED; Genomic_DNA.
DR EMBL; AF327674; AAK14335.1; JOINED; Genomic_DNA.
DR EMBL; AF327675; AAK14335.1; JOINED; Genomic_DNA.
DR EMBL; AF327676; AAK14335.1; JOINED; Genomic_DNA.
DR EMBL; AF327677; AAK14335.1; JOINED; Genomic_DNA.
DR EMBL; AF327678; AAK14335.1; JOINED; Genomic_DNA.
DR EMBL; AF327679; AAK14335.1; JOINED; Genomic_DNA.
DR EMBL; AF327680; AAK14335.1; JOINED; Genomic_DNA.
DR EMBL; AF327681; AAK14335.1; JOINED; Genomic_DNA.
DR EMBL; AF327682; AAK14335.1; JOINED; Genomic_DNA.
DR EMBL; AF327683; AAK14335.1; JOINED; Genomic_DNA.
DR EMBL; AF327684; AAK14335.1; JOINED; Genomic_DNA.
DR EMBL; AF327685; AAK14335.1; JOINED; Genomic_DNA.
DR EMBL; AF327686; AAK14335.1; JOINED; Genomic_DNA.
DR EMBL; AF327687; AAK14335.1; JOINED; Genomic_DNA.
DR EMBL; AF327688; AAK14335.1; JOINED; Genomic_DNA.
DR EMBL; AF327689; AAK14335.1; JOINED; Genomic_DNA.
DR EMBL; AF327690; AAK14335.1; JOINED; Genomic_DNA.
DR EMBL; AF327691; AAK14335.1; JOINED; Genomic_DNA.
DR EMBL; AF327692; AAK14335.1; JOINED; Genomic_DNA.
DR EMBL; AF327693; AAK14335.1; JOINED; Genomic_DNA.
DR EMBL; AF327694; AAK14335.1; JOINED; Genomic_DNA.
DR EMBL; AF327695; AAK14335.1; JOINED; Genomic_DNA.
DR EMBL; AF327696; AAK14335.1; JOINED; Genomic_DNA.
DR EMBL; AF327697; AAK14335.1; JOINED; Genomic_DNA.
DR EMBL; AF327698; AAK14335.1; JOINED; Genomic_DNA.
DR EMBL; AF327699; AAK14335.1; JOINED; Genomic_DNA.
DR EMBL; AF327700; AAK14335.1; JOINED; Genomic_DNA.
DR EMBL; AF327701; AAK14335.1; JOINED; Genomic_DNA.
DR EMBL; AF327702; AAK14335.1; JOINED; Genomic_DNA.
DR EMBL; AF327703; AAK14335.1; JOINED; Genomic_DNA.
DR EMBL; AF327704; AAK14335.1; JOINED; Genomic_DNA.
DR EMBL; AF178941; AAG09372.1; -; mRNA.
DR EMBL; AL807752; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AB028985; BAA83014.2; -; mRNA.
DR EMBL; AB177854; BAD66832.1; -; mRNA.
DR CCDS; CCDS43909.1; -. [Q9BZC7-3]
DR PIR; A59189; A59189.
DR RefSeq; NP_001597.2; NM_001606.4. [Q9BZC7-3]
DR RefSeq; NP_997698.1; NM_212533.2. [Q9BZC7-4]
DR RefSeq; XP_006717059.1; XM_006716996.3. [Q9BZC7-1]
DR AlphaFoldDB; Q9BZC7; -.
DR SMR; Q9BZC7; -.
DR BioGRID; 106538; 120.
DR IntAct; Q9BZC7; 26.
DR MINT; Q9BZC7; -.
DR STRING; 9606.ENSP00000344155; -.
DR TCDB; 3.A.1.211.3; the atp-binding cassette (abc) superfamily.
DR GlyConnect; 1021; 2 N-Linked glycans (1 site).
DR GlyGen; Q9BZC7; 27 sites, 2 N-linked glycans (1 site), 1 O-linked glycan (1 site).
DR iPTMnet; Q9BZC7; -.
DR PhosphoSitePlus; Q9BZC7; -.
DR BioMuta; ABCA2; -.
DR DMDM; 206729923; -.
DR EPD; Q9BZC7; -.
DR jPOST; Q9BZC7; -.
DR MassIVE; Q9BZC7; -.
DR PaxDb; Q9BZC7; -.
DR PeptideAtlas; Q9BZC7; -.
DR PRIDE; Q9BZC7; -.
DR ProteomicsDB; 79809; -. [Q9BZC7-1]
DR ProteomicsDB; 79810; -. [Q9BZC7-2]
DR ProteomicsDB; 79811; -. [Q9BZC7-3]
DR Antibodypedia; 32309; 230 antibodies from 27 providers.
DR DNASU; 20; -.
DR Ensembl; ENST00000341511.11; ENSP00000344155.6; ENSG00000107331.18. [Q9BZC7-3]
DR Ensembl; ENST00000371605.7; ENSP00000360666.3; ENSG00000107331.18. [Q9BZC7-1]
DR Ensembl; ENST00000614293.5; ENSP00000481105.2; ENSG00000107331.18. [Q9BZC7-4]
DR GeneID; 20; -.
DR KEGG; hsa:20; -.
DR MANE-Select; ENST00000341511.11; ENSP00000344155.6; NM_001606.5; NP_001597.2. [Q9BZC7-3]
DR UCSC; uc011mem.1; human. [Q9BZC7-1]
DR CTD; 20; -.
DR DisGeNET; 20; -.
DR GeneCards; ABCA2; -.
DR HGNC; HGNC:32; ABCA2.
DR HPA; ENSG00000107331; Tissue enriched (brain).
DR MalaCards; ABCA2; -.
DR MIM; 600047; gene.
DR MIM; 618808; phenotype.
DR neXtProt; NX_Q9BZC7; -.
DR OpenTargets; ENSG00000107331; -.
DR PharmGKB; PA24377; -.
DR VEuPathDB; HostDB:ENSG00000107331; -.
DR eggNOG; KOG0059; Eukaryota.
DR GeneTree; ENSGT00940000158560; -.
DR HOGENOM; CLU_000604_19_0_1; -.
DR InParanoid; Q9BZC7; -.
DR OMA; QYFDSMC; -.
DR OrthoDB; 131191at2759; -.
DR PhylomeDB; Q9BZC7; -.
DR TreeFam; TF105191; -.
DR PathwayCommons; Q9BZC7; -.
DR Reactome; R-HSA-1369062; ABC transporters in lipid homeostasis.
DR SignaLink; Q9BZC7; -.
DR BioGRID-ORCS; 20; 13 hits in 1074 CRISPR screens.
DR ChiTaRS; ABCA2; human.
DR GeneWiki; ABCA2; -.
DR GenomeRNAi; 20; -.
DR Pharos; Q9BZC7; Tbio.
DR PRO; PR:Q9BZC7; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q9BZC7; protein.
DR Bgee; ENSG00000107331; Expressed in C1 segment of cervical spinal cord and 148 other tissues.
DR ExpressionAtlas; Q9BZC7; baseline and differential.
DR Genevisible; Q9BZC7; HS.
DR GO; GO:0043190; C:ATP-binding cassette (ABC) transporter complex; NAS:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISS:UniProtKB.
DR GO; GO:0005768; C:endosome; IDA:UniProtKB.
DR GO; GO:0010008; C:endosome membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IDA:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005815; C:microtubule organizing center; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0140359; F:ABC-type transporter activity; IEA:InterPro.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0042626; F:ATPase-coupled transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0099038; F:ceramide floppase activity; IDA:ARUK-UCL.
DR GO; GO:0061135; F:endopeptidase regulator activity; IMP:ARUK-UCL.
DR GO; GO:0005319; F:lipid transporter activity; IBA:GO_Central.
DR GO; GO:0000166; F:nucleotide binding; NAS:UniProtKB.
DR GO; GO:0090156; P:cellular sphingolipid homeostasis; IDA:ARUK-UCL.
DR GO; GO:0032289; P:central nervous system myelin formation; ISS:UniProtKB.
DR GO; GO:0099040; P:ceramide translocation; IDA:ARUK-UCL.
DR GO; GO:0042632; P:cholesterol homeostasis; IEP:UniProtKB.
DR GO; GO:0001573; P:ganglioside metabolic process; ISS:UniProtKB.
DR GO; GO:0006687; P:glycosphingolipid metabolic process; ISS:UniProtKB.
DR GO; GO:0006629; P:lipid metabolic process; NAS:UniProtKB.
DR GO; GO:0006869; P:lipid transport; IBA:GO_Central.
DR GO; GO:0007626; P:locomotory behavior; ISS:ARUK-UCL.
DR GO; GO:0090370; P:negative regulation of cholesterol efflux; IDA:ARUK-UCL.
DR GO; GO:0032384; P:negative regulation of intracellular cholesterol transport; IDA:ARUK-UCL.
DR GO; GO:1905598; P:negative regulation of low-density lipoprotein receptor activity; IDA:ARUK-UCL.
DR GO; GO:0071072; P:negative regulation of phospholipid biosynthetic process; IDA:ARUK-UCL.
DR GO; GO:1905601; P:negative regulation of receptor-mediated endocytosis involved in cholesterol transport; IDA:ARUK-UCL.
DR GO; GO:0090155; P:negative regulation of sphingolipid biosynthetic process; IDA:ARUK-UCL.
DR GO; GO:0045939; P:negative regulation of steroid metabolic process; ISS:ARUK-UCL.
DR GO; GO:0042986; P:positive regulation of amyloid precursor protein biosynthetic process; IDA:ARUK-UCL.
DR GO; GO:1902993; P:positive regulation of amyloid precursor protein catabolic process; IMP:ARUK-UCL.
DR GO; GO:1902004; P:positive regulation of amyloid-beta formation; IMP:ARUK-UCL.
DR GO; GO:0032805; P:positive regulation of low-density lipoprotein particle receptor catabolic process; IDA:ARUK-UCL.
DR GO; GO:0010872; P:regulation of cholesterol esterification; IMP:UniProtKB.
DR GO; GO:0032383; P:regulation of intracellular cholesterol transport; IMP:UniProtKB.
DR GO; GO:1901873; P:regulation of post-translational protein modification; IMP:ARUK-UCL.
DR GO; GO:0060049; P:regulation of protein glycosylation; ISS:ARUK-UCL.
DR GO; GO:1904375; P:regulation of protein localization to cell periphery; ISS:ARUK-UCL.
DR GO; GO:2000008; P:regulation of protein localization to cell surface; ISS:ARUK-UCL.
DR GO; GO:0019218; P:regulation of steroid metabolic process; IDA:ARUK-UCL.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0070723; P:response to cholesterol; IEP:UniProtKB.
DR GO; GO:0048545; P:response to steroid hormone; IEP:UniProtKB.
DR GO; GO:0009410; P:response to xenobiotic stimulus; TAS:UniProtKB.
DR GO; GO:0006684; P:sphingomyelin metabolic process; ISS:UniProtKB.
DR GO; GO:0046512; P:sphingosine biosynthetic process; IDA:ARUK-UCL.
DR GO; GO:0055085; P:transmembrane transport; NAS:UniProtKB.
DR GO; GO:0150104; P:transport across blood-brain barrier; NAS: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; IPR030366; ABCA2.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR19229; PTHR19229; 1.
DR PANTHER; PTHR19229:SF225; PTHR19229:SF225; 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; ATP-binding; Disease variant; Endosome; Epilepsy;
KW Glycoprotein; Intellectual disability; Lysosome; Membrane; Methylation;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Repeat;
KW Translocase; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..2435
FT /note="ATP-binding cassette sub-family A member 2"
FT /id="PRO_0000093290"
FT TRANSMEM 22..42
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 54..74
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 699..719
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 750..770
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 782..802
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 813..833
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 857..877
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 893..913
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1456..1476
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1792..1812
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1841..1861
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1872..1892
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1905..1925
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1991..2011
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 990..1221
FT /note="ABC transporter 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT DOMAIN 2050..2285
FT /note="ABC transporter 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT REGION 1223..1243
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1325..1357
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1586..1610
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1325..1343
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1586..1600
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 1024..1031
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT BINDING 2087..2094
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT MOD_RES 271
FT /note="N5-methylglutamine"
FT /evidence="ECO:0000269|PubMed:26797129"
FT MOD_RES 1238
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1327
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983"
FT MOD_RES 1331
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 2412
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT CARBOHYD 14
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 89
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 168
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 173
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 305
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 368
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 379
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 420
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 432
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 476
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 484
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 494
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 530
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 544
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 590
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 600
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 628
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1408
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1496
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1549
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1557
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1612
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1677
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1775
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2054
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..22
FT /note="MGFLHQLQLLLWKNVTLKRRSP -> MGRKTSRVQQGPPRSPACSAHGERSW
FT GLEFPPFRWLLGIAGRTHLAALPPFQ (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15093135"
FT /id="VSP_060910"
FT VAR_SEQ 53..54
FT /note="EA -> EVS (in isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:11178988,
FT ECO:0000303|PubMed:11309290, ECO:0000305|PubMed:15093135"
FT /id="VSP_040937"
FT VAR_SEQ 2059..2090
FT /note="YKSRKIGRILAVDRLCLGVRPGECFGLLGVNG -> GSGHVGWGLGGVGQGQ
FT GGGAPAVEVEPGWAGP (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10470851"
FT /id="VSP_035283"
FT VAR_SEQ 2091..2435
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10470851"
FT /id="VSP_035284"
FT VARIANT 343..2435
FT /note="Missing (in IDPOGSA; dbSNP:rs1588524458)"
FT /evidence="ECO:0000269|PubMed:30237576"
FT /id="VAR_082138"
FT VARIANT 583
FT /note="P -> H (in dbSNP:rs908828)"
FT /id="VAR_044526"
FT VARIANT 674
FT /note="F -> V (in dbSNP:rs2090625)"
FT /id="VAR_044527"
FT MUTAGEN 271
FT /note="Q->R: Abolishes methylation by N6AMT1."
FT /evidence="ECO:0000269|PubMed:26797129"
FT CONFLICT 2079
FT /note="P -> L (in Ref. 1; AAK14335)"
FT /evidence="ECO:0000305"
FT CONFLICT Q9BZC7-3:55
FT /note="S -> P (in Ref. 1; AAK14334/AAK14335 and 2;
FT AAG09372)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 2435 AA; 269833 MW; D707CC83F30BE2BF CRC64;
MGFLHQLQLL LWKNVTLKRR SPWVLAFEIF IPLVLFFILL GLRQKKPTIS VKEAFYTAAP
LTSAGILPVM QSLCPDGQRD EFGFLQYANS TVTQLLERLD RVVEEGNLFD PARPSLGSEL
EALRQHLEAL SAGPGTSGSH LDRSTVSSFS LDSVARNPQE LWRFLTQNLS LPNSTAQALL
AARVDPPEVY HLLFGPSSAL DSQSGLHKGQ EPWSRLGGNP LFRMEELLLA PALLEQLTCT
PGSGELGRIL TVPESQKGAL QGYRDAVCSG QAAARARRFS GLSAELRNQL DVAKVSQQLG
LDAPNGSDSS PQAPPPRRLQ ALLGDLLDAQ KVLQDVDVLS ALALLLPQGA CTGRTPGPPA
SGAGGAANGT GAGAVMGPNA TAEEGAPSAA ALATPDTLQG QCSAFVQLWA GLQPILCGNN
RTIEPEALRR GNMSSLGFTS KEQRNLGLLV HLMTSNPKIL YAPAGSEVDR VILKANETFA
FVGNVTHYAQ VWLNISAEIR SFLEQGRLQQ HLRWLQQYVA ELRLHPEALN LSLDELPPAL
RQDNFSLPSG MALLQQLDTI DNAACGWIQF MSKVSVDIFK GFPDEESIVN YTLNQAYQDN
VTVFASVIFQ TRKDGSLPPH VHYKIRQNSS FTEKTNEIRR AYWRPGPNTG GRFYFLYGFV
WIQDMMERAI IDTFVGHDVV EPGSYVQMFP YPCYTRDDFL FVIEHMMPLC MVISWVYSVA
MTIQHIVAEK EHRLKEVMKT MGLNNAVHWV AWFITGFVQL SISVTALTAI LKYGQVLMHS
HVVIIWLFLA VYAVATIMFC FLVSVLYSKA KLASACGGII YFLSYVPYMY VAIREEVAHD
KITAFEKCIA SLMSTTAFGL GSKYFALYEV AGVGIQWHTF SQSPVEGDDF NLLLAVTMLM
VDAVVYGILT WYIEAVHPGM YGLPRPWYFP LQKSYWLGSG RTEAWEWSWP WARTPRLSVM
EEDQACAMES RRFEETRGME EEPTHLPLVV CVDKLTKVYK DDKKLALNKL SLNLYENQVV
SFLGHNGAGK TTTMSILTGL FPPTSGSATI YGHDIRTEMD EIRKNLGMCP QHNVLFDRLT
VEEHLWFYSR LKSMAQEEIR REMDKMIEDL ELSNKRHSLV QTLSGGMKRK LSVAIAFVGG
SRAIILDEPT AGVDPYARRA IWDLILKYKP GRTILLSTHH MDEADLLGDR IAIISHGKLK
CCGSPLFLKG TYGDGYRLTL VKRPAEPGGP QEPGLASSPP GRAPLSSCSE LQVSQFIRKH
VASCLLVSDT STELSYILPS EAAKKGAFER LFQHLERSLD ALHLSSFGLM DTTLEEVFLK
VSEEDQSLEN SEADVKESRK DVLPGAEGPA SGEGHAGNLA RCSELTQSQA SLQSASSVGS
ARGDEGAGYT DVYGDYRPLF DNPQDPDNVS LQEVEAEALS RVGQGSRKLD GGWLKVRQFH
GLLVKRFHCA RRNSKALFSQ ILLPAFFVCV AMTVALSVPE IGDLPPLVLS PSQYHNYTQP
RGNFIPYANE ERREYRLRLS PDASPQQLVS TFRLPSGVGA TCVLKSPANG SLGPTLNLSS
GESRLLAARF FDSMCLESFT QGLPLSNFVP PPPSPAPSDS PASPDEDLQA WNVSLPPTAG
PEMWTSAPSL PRLVREPVRC TCSAQGTGFS CPSSVGGHPP QMRVVTGDIL TDITGHNVSE
YLLFTSDRFR LHRYGAITFG NVLKSIPASF GTRAPPMVRK IAVRRAAQVF YNNKGYHSMP
TYLNSLNNAI LRANLPKSKG NPAAYGITVT NHPMNKTSAS LSLDYLLQGT DVVIAIFIIV
AMSFVPASFV VFLVAEKSTK AKHLQFVSGC NPIIYWLANY VWDMLNYLVP ATCCVIILFV
FDLPAYTSPT NFPAVLSLFL LYGWSITPIM YPASFWFEVP SSAYVFLIVI NLFIGITATV
ATFLLQLFEH DKDLKVVNSY LKSCFLIFPN YNLGHGLMEM AYNEYINEYY AKIGQFDKMK
SPFEWDIVTR GLVAMAVEGV VGFLLTIMCQ YNFLRRPQRM PVSTKPVEDD VDVASERQRV
LRGDADNDMV KIENLTKVYK SRKIGRILAV DRLCLGVRPG ECFGLLGVNG AGKTSTFKML
TGDESTTGGE AFVNGHSVLK ELLQVQQSLG YCPQCDALFD ELTAREHLQL YTRLRGISWK
DEARVVKWAL EKLELTKYAD KPAGTYSGGN KRKLSTAIAL IGYPAFIFLD EPTTGMDPKA
RRFLWNLILD LIKTGRSVVL TSHSMEECEA LCTRLAIMVN GRLRCLGSIQ HLKNRFGDGY
MITVRTKSSQ SVKDVVRFFN RNFPEAMLKE RHHTKVQYQL KSEHISLAQV FSKMEQVSGV
LGIEDYSVSQ TTLDNVFVNF AKKQSDNLEQ QETEPPSALQ SPLGCLLSLL RPRSAPTELR
ALVADEPEDL DTEDEGLISF EEERAQLSFN TDTLC
