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 27-MAR-2024, entry version 184. 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"; 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; 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 CCDS; CCDS94538.1; -. [Q9BZC7-1] DR CCDS; CCDS94539.1; -. [Q9BZC7-4] 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. DR AlphaFoldDB; Q9BZC7; -. DR SMR; Q9BZC7; -. DR BioGRID; 106538; 122. DR IntAct; Q9BZC7; 28. 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 GlyCosmos; Q9BZC7; 26 sites, 3 glycans. DR GlyGen; Q9BZC7; 27 sites, 2 N-linked glycans (1 site), 1 O-linked glycan (1 site). DR iPTMnet; Q9BZC7; -. DR PhosphoSitePlus; Q9BZC7; -. DR SwissPalm; Q9BZC7; -. DR BioMuta; ABCA2; -. DR DMDM; 206729923; -. DR EPD; Q9BZC7; -. DR jPOST; Q9BZC7; -. DR MassIVE; Q9BZC7; -. DR PaxDb; 9606-ENSP00000344155; -. DR PeptideAtlas; Q9BZC7; -. DR ProteomicsDB; 79809; -. [Q9BZC7-1] DR ProteomicsDB; 79810; -. [Q9BZC7-2] DR ProteomicsDB; 79811; -. [Q9BZC7-3] DR Pumba; Q9BZC7; -. DR Antibodypedia; 32309; 246 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 AGR; HGNC:32; -. 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 Orphanet; 88616; Autosomal recessive non-syndromic intellectual disability. 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; 6951at2759; -. 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; 22 hits in 1154 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 150 other cell types or tissues. DR ExpressionAtlas; Q9BZC7; baseline and differential. 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: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; IDA: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:0016887; F:ATP hydrolysis activity; IEA:InterPro. 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: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:0090156; P:intracellular sphingolipid homeostasis; IDA:ARUK-UCL. 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: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: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 CDD; cd03263; ABC_subfamily_A; 2. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 2. DR InterPro; IPR003593; AAA+_ATPase. DR InterPro; IPR013525; ABC2_TM. DR InterPro; IPR003439; ABC_transporter-like_ATP-bd. DR InterPro; IPR017871; ABC_transporter-like_CS. DR InterPro; IPR026082; ABCA. DR InterPro; IPR027417; P-loop_NTPase. DR PANTHER; PTHR19229:SF225; ATP-BINDING CASSETTE SUB-FAMILY A MEMBER 2; 1. DR PANTHER; PTHR19229; ATP-BINDING CASSETTE TRANSPORTER SUBFAMILY A ABCA; 1. DR Pfam; PF12698; ABC2_membrane_3; 2. DR Pfam; PF00005; ABC_tran; 2. DR SMART; SM00382; AAA; 2. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 2. DR PROSITE; PS00211; ABC_TRANSPORTER_1; 1. DR PROSITE; PS50893; ABC_TRANSPORTER_2; 2. DR Genevisible; Q9BZC7; HS. 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 //