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ABCA3_HUMAN
ID   ABCA3_HUMAN             Reviewed;        1704 AA.
AC   Q99758; B2RU09; Q54A95; Q6P5P9; Q92473;
DT   30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT   24-JAN-2006, sequence version 2.
DT   03-AUG-2022, entry version 185.
DE   RecName: Full=Phospholipid-transporting ATPase ABCA3 {ECO:0000305};
DE            EC=7.6.2.1 {ECO:0000269|PubMed:17574245, ECO:0000269|PubMed:28887056, ECO:0000269|PubMed:31473345};
DE   AltName: Full=ABC-C transporter;
DE   AltName: Full=ATP-binding cassette sub-family A member 3 {ECO:0000305};
DE   AltName: Full=ATP-binding cassette transporter 3;
DE            Short=ATP-binding cassette 3;
DE   AltName: Full=Xenobiotic-transporting ATPase ABCA3 {ECO:0000305};
DE            EC=7.6.2.2 {ECO:0000305|PubMed:26903515};
DE   Contains:
DE     RecName: Full=150 Kda mature form {ECO:0000305|PubMed:27031696};
GN   Name=ABCA3 {ECO:0000312|HGNC:HGNC:33}; Synonyms=ABC3;
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), AND TISSUE SPECIFICITY.
RC   TISSUE=Thyroid carcinoma;
RX   PubMed=8706931; DOI=10.1016/0014-5793(96)00700-4;
RA   Klugbauer N., Hofmann F.;
RT   "Primary structure of a novel ABC transporter with a chromosomal
RT   localization on the band encoding the multidrug resistance-associated
RT   protein.";
RL   FEBS Lett. 391:61-65(1996).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX   PubMed=9027511; DOI=10.1006/geno.1996.4500;
RA   Connors T.D., van Raay T.J., Petry L.R., Klinger K.W., Landes G.M.,
RA   Burn T.C.;
RT   "The cloning of a human ABC gene (ABC3) mapping to chromosome 16p13.3.";
RL   Genomics 39:231-234(1997).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND SUBCELLULAR
RP   LOCATION.
RC   TISSUE=Lung;
RX   PubMed=11718719; DOI=10.1016/s0014-5793(01)03056-3;
RA   Yamano G., Funahashi H., Kawanami O., Zhao L., Ban N., Uchida Y.,
RA   Morohoshi T., Ogawa J., Shioda S., Inagaki N.;
RT   "ABCA3 is a lamellar body membrane protein in human lung alveolar type II
RT   cells.";
RL   FEBS Lett. 508:221-225(2001).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS HIS-140 AND SER-766.
RG   SeattleSNPs variation discovery resource;
RL   Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15616553; DOI=10.1038/nature03187;
RA   Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA   Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA   Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA   Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA   Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA   Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA   Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA   Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA   Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA   Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA   Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA   Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA   Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA   Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA   Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA   Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA   Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA   Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA   Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA   DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA   Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA   Myers R.M., Rubin E.M., Pennacchio L.A.;
RT   "The sequence and analysis of duplication-rich human chromosome 16.";
RL   Nature 432:988-994(2004).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC   TISSUE=Brain, and Lung;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [8]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 117-197, AND SUBCELLULAR LOCATION.
RX   PubMed=22673903; DOI=10.1038/ncomms1871;
RA   Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA   Olsen J.V.;
RT   "Quantitative maps of protein phosphorylation sites across 14 different rat
RT   organs and tissues.";
RL   Nat. Commun. 3:876-876(2012).
RN   [9]
RP   FUNCTION, PROTEOLYTIC CLEAVAGE, GLYCOSYLATION, SUBCELLULAR LOCATION,
RP   CHARACTERIZATION OF VARIANTS SMDP3 PRO-101; ASP-568; PRO-982; SER-1221;
RP   PRO-1553; PRO-1580 AND PRO-1591, AND MUTAGENESIS OF GLY-1221 AND LEU-1580.
RX   PubMed=16959783; DOI=10.1074/jbc.m600071200;
RA   Matsumura Y., Ban N., Ueda K., Inagaki N.;
RT   "Characterization and classification of ATP-binding cassette transporter
RT   ABCA3 mutants in fatal surfactant deficiency.";
RL   J. Biol. Chem. 281:34503-34514(2006).
RN   [10]
RP   FUNCTION, CATALYTIC ACTIVITY, CHARACTERIZATION OF VARIANT SMDP3 ASP-568,
RP   AND SUBCELLULAR LOCATION.
RX   PubMed=17574245; DOI=10.1016/j.febslet.2007.05.078;
RA   Matsumura Y., Sakai H., Sasaki M., Ban N., Inagaki N.;
RT   "ABCA3-mediated choline-phospholipids uptake into intracellular vesicles in
RT   A549 cells.";
RL   FEBS Lett. 581:3139-3144(2007).
RN   [11]
RP   PROTEOLYTIC CLEAVAGE, SUBCELLULAR LOCATION, AND CHARACTERIZATION OF
RP   VARIANTS SMDP3 LYS-215 AND VAL-292.
RX   PubMed=20863830; DOI=10.1016/j.febslet.2010.09.026;
RA   Engelbrecht S., Kaltenborn E., Griese M., Kern S.;
RT   "The surfactant lipid transporter ABCA3 is N-terminally cleaved inside
RT   LAMP3-positive vesicles.";
RL   FEBS Lett. 584:4306-4312(2010).
RN   [12]
RP   GLYCOSYLATION AT ASN-124 AND ASN-140, SUBCELLULAR LOCATION, AND MUTAGENESIS
RP   OF ASN-53; ASN-124; ASN-140 AND ASN-945.
RX   PubMed=24142515; DOI=10.1152/ajplung.00184.2013;
RA   Beers M.F., Zhao M., Tomer Y., Russo S.J., Zhang P., Gonzales L.W.,
RA   Guttentag S.H., Mulugeta S.;
RT   "Disruption of N-linked glycosylation promotes proteasomal degradation of
RT   the human ATP-binding cassette transporter ABCA3.";
RL   Am. J. Physiol. 305:L970-L980(2013).
RN   [13]
RP   FUNCTION, CHARACTERIZATION OF VARIANTS SMDP3 LYS-215 AND VAL-292, AND
RP   CATALYTIC ACTIVITY.
RX   PubMed=25817392; DOI=10.1016/j.bbalip.2015.03.004;
RA   Zarbock R., Kaltenborn E., Frixel S., Wittmann T., Liebisch G., Schmitz G.,
RA   Griese M.;
RT   "ABCA3 protects alveolar epithelial cells against free cholesterol induced
RT   cell death.";
RL   Biochim. Biophys. Acta 1851:987-995(2015).
RN   [14]
RP   SUBUNIT, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS SMDP3 LYS-215;
RP   CYS-280 AND LYS-288, AND MUTAGENESIS OF SER-693.
RX   PubMed=27352740; DOI=10.3892/ijmm.2016.2650;
RA   Frixel S., Lotz-Havla A.S., Kern S., Kaltenborn E., Wittmann T.,
RA   Gersting S.W., Muntau A.C., Zarbock R., Griese M.;
RT   "Homooligomerization of ABCA3 and its functional significance.";
RL   Int. J. Mol. Med. 38:558-566(2016).
RN   [15]
RP   INDUCTION, FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=26903515; DOI=10.1074/jbc.m115.688168;
RA   Dohmen L.C., Navas A., Vargas D.A., Gregory D.J., Kip A., Dorlo T.P.,
RA   Gomez M.A.;
RT   "Functional Validation of ABCA3 as a Miltefosine Transporter in Human
RT   Macrophages: IMPACT ON INTRACELLULAR SURVIVAL OF LEISHMANIA (VIANNIA)
RT   PANAMENSIS.";
RL   J. Biol. Chem. 291:9638-9647(2016).
RN   [16]
RP   IDENTIFICATION BY MASS SPECTROMETRY, PROTEOLYTIC CLEAVAGE, SITE, AND
RP   MUTAGENESIS OF 173-LEU-LYS-174.
RX   PubMed=27031696; DOI=10.1371/journal.pone.0152594;
RA   Hofmann N., Galetskiy D., Rauch D., Wittmann T., Marquardt A., Griese M.,
RA   Zarbock R.;
RT   "Analysis of the Proteolytic Processing of ABCA3: Identification of
RT   Cleavage Site and Involved Proteases.";
RL   PLoS ONE 11:e0152594-e0152594(2016).
RN   [17]
RP   FUNCTION, CATALYTIC ACTIVITY, AND CHARACTERIZATION OF VARIANTS SMDP3
RP   VAL-292 AND ASN-1388.
RX   PubMed=28887056; DOI=10.1016/j.bbamcr.2017.08.013;
RA   Hoeppner S., Kinting S., Torrano A.A., Schindlbeck U., Braeuchle C.,
RA   Zarbock R., Wittmann T., Griese M.;
RT   "Quantification of volume and lipid filling of intracellular vesicles
RT   carrying the ABCA3 transporter.";
RL   Biochim. Biophys. Acta 1864:2330-2335(2017).
RN   [18]
RP   CATALYTIC ACTIVITY, FUNCTION, SUBCELLULAR LOCATION, CHARACTERIZATION OF
RP   VARIANTS SMDP3 ASP-568 AND PRO-1580, AND ACTIVITY REGULATION.
RX   PubMed=31473345; DOI=10.1016/j.bbalip.2019.158516;
RA   Li Y., Kinting S., Hoeppner S., Forstner M.E., Uhl O., Koletzko B.,
RA   Griese M.;
RT   "Metabolic labelling of choline phospholipids probes ABCA3 transport in
RT   lamellar bodies.";
RL   Biochim. Biophys. Acta 1864:158516-158516(2019).
RN   [19]
RP   VARIANTS SMDP3 PRO-101; ASP-568; PRO-982; SER-1221; PRO-1553; PRO-1580 AND
RP   PRO-1591.
RX   PubMed=15044640; DOI=10.1056/nejmoa032178;
RA   Shulenin S., Nogee L.M., Annilo T., Wert S.E., Whitsett J.A., Dean M.;
RT   "ABCA3 gene mutations in newborns with fatal surfactant deficiency.";
RL   N. Engl. J. Med. 350:1296-1303(2004).
RN   [20]
RP   VARIANTS SMDP3 VAL-292; LYS-690; LYS-1076; MET-1114; LEU-1301 AND GLU-1302.
RX   PubMed=15976379; DOI=10.1164/rccm.200503-504oc;
RA   Bullard J.E., Wert S.E., Whitsett J.A., Dean M., Nogee L.M.;
RT   "ABCA3 mutations associated with pediatric interstitial lung disease.";
RL   Am. J. Respir. Crit. Care Med. 172:1026-1031(2005).
RN   [21]
RP   VARIANTS SMDP3 LEU-43; LYS-215; PRO-579; GLN-605 AND 1561-ARG--ARG-1704
RP   DEL, AND VARIANT LYS-288.
RX   PubMed=16728712; DOI=10.1164/rccm.200509-1535oc;
RA   Brasch F., Schimanski S., Muehlfeld C., Barlage S., Langmann T.,
RA   Aslanidis C., Boettcher A., Dada A., Schroten H., Mildenberger E.,
RA   Prueter E., Ballmann M., Ochs M., Johnen G., Griese M., Schmitz G.;
RT   "Alteration of the pulmonary surfactant system in full-term infants with
RT   hereditary ABCA3 deficiency.";
RL   Am. J. Respir. Crit. Care Med. 174:571-580(2006).
RN   [22]
RP   VARIANTS [LARGE SCALE ANALYSIS] MET-290; ASP-801 AND GLN-1069.
RX   PubMed=16959974; DOI=10.1126/science.1133427;
RA   Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA   Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA   Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA   Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA   Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA   Velculescu V.E.;
RT   "The consensus coding sequences of human breast and colorectal cancers.";
RL   Science 314:268-274(2006).
RN   [23]
RP   VARIANTS SMDP3 CYS-280; MET-1399 AND 1589-GLN--ARG-1704 DEL.
RX   PubMed=25712598; DOI=10.1038/jp.2014.236;
RA   Jackson T., Wegner D.J., White F.V., Hamvas A., Cole F.S., Wambach J.A.;
RT   "Respiratory failure in a term infant with cis and trans mutations in
RT   ABCA3.";
RL   J. Perinatol. 35:231-232(2015).
RN   [24]
RP   VARIANT SMDP3 ASN-1388, CHARACTERIZATION OF VARIANT SMDP3 ASN-1388,
RP   PROTEOLYTIC CLEAVAGE, GLYCOSYLATION, SUBCELLULAR LOCATION, FUNCTION, AND
RP   CATALYTIC ACTIVITY.
RX   PubMed=27177387; DOI=10.1002/ppul.23471;
RA   Wittmann T., Schindlbeck U., Hoeppner S., Kinting S., Frixel S.,
RA   Kroener C., Liebisch G., Hegermann J., Aslanidis C., Brasch F., Reu S.,
RA   Lasch P., Zarbock R., Griese M.;
RT   "Tools to explore ABCA3 mutations causing interstitial lung disease.";
RL   Pediatr. Pulmonol. 51:1284-1294(2016).
CC   -!- FUNCTION: Catalyzes the ATP-dependent transport of phospholipids such
CC       as phosphatidylcholine and phosphoglycerol from the cytoplasm into the
CC       lumen side of lamellar bodies, in turn participates in the lamellar
CC       bodies biogenesis and homeostasis of pulmonary surfactant
CC       (PubMed:16959783, PubMed:17574245, PubMed:28887056, PubMed:31473345,
CC       PubMed:27177387). Transports preferentially phosphatidylcholine
CC       containing short acyl chains (PubMed:27177387). In addition plays a
CC       role as an efflux transporter of miltefosine across macrophage
CC       membranes and free cholesterol (FC) through intralumenal vesicles by
CC       removing FC from the cell as a component of surfactant and protects
CC       cells from free cholesterol toxicity (PubMed:26903515, PubMed:25817392,
CC       PubMed:27177387). {ECO:0000269|PubMed:16959783,
CC       ECO:0000269|PubMed:17574245, ECO:0000269|PubMed:25817392,
CC       ECO:0000269|PubMed:26903515, ECO:0000269|PubMed:27177387,
CC       ECO:0000269|PubMed:28887056, ECO:0000269|PubMed:31473345}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + H2O + xenobioticSide 1 = ADP + phosphate +
CC         xenobioticSide 2.; EC=7.6.2.2;
CC         Evidence={ECO:0000305|PubMed:26903515};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a 1,2-diacyl-sn-glycero-3-phosphocholine(in) + ATP + H2O = a
CC         1,2-diacyl-sn-glycero-3-phosphocholine(out) + ADP + H(+) + phosphate;
CC         Xref=Rhea:RHEA:66272, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:57643,
CC         ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:17574245,
CC         ECO:0000269|PubMed:27177387, ECO:0000269|PubMed:28887056,
CC         ECO:0000269|PubMed:31473345};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66273;
CC         Evidence={ECO:0000269|PubMed:17574245, ECO:0000269|PubMed:27177387,
CC         ECO:0000269|PubMed:28887056, ECO:0000269|PubMed:31473345};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + H2O + phospholipidSide 1 = ADP + phosphate +
CC         phospholipidSide 2.; EC=7.6.2.1;
CC         Evidence={ECO:0000269|PubMed:17574245, ECO:0000269|PubMed:27177387,
CC         ECO:0000269|PubMed:28887056, ECO:0000269|PubMed:31473345};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=1,2-dihexadecanoyl-sn-glycero-3-phosphocholine(in) + ATP + H2O
CC         = 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine(out) + ADP + H(+) +
CC         phosphate; Xref=Rhea:RHEA:66340, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC         ChEBI:CHEBI:72999, ChEBI:CHEBI:456216;
CC         Evidence={ECO:0000269|PubMed:27177387};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66341;
CC         Evidence={ECO:0000269|PubMed:27177387};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + cholesterol(in) + H2O = ADP + cholesterol(out) + H(+) +
CC         phosphate; Xref=Rhea:RHEA:39051, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:16113, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:43474, ChEBI:CHEBI:456216;
CC         Evidence={ECO:0000269|PubMed:25817392};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39052;
CC         Evidence={ECO:0000269|PubMed:25817392};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=1,2-diacyl-sn-glycero-3-phospho-(1'-sn-glycerol)(in) + ATP +
CC         H2O = 1,2-diacyl-sn-glycero-3-phospho-(1'-sn-glycerol)(out) + ADP +
CC         H(+) + phosphate; Xref=Rhea:RHEA:66344, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC         ChEBI:CHEBI:64716, ChEBI:CHEBI:456216;
CC         Evidence={ECO:0000250|UniProtKB:Q8R420};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66345;
CC         Evidence={ECO:0000250|UniProtKB:Q8R420};
CC   -!- ACTIVITY REGULATION: The ATP-dependent phosphatidylcholine transport is
CC       competitively inhibited by miltefosine. {ECO:0000269|PubMed:31473345}.
CC   -!- SUBUNIT: Homooligomer; disulfide-linked. {ECO:0000269|PubMed:31473345}.
CC   -!- SUBCELLULAR LOCATION: Endosome, multivesicular body membrane
CC       {ECO:0000269|PubMed:16959783, ECO:0000269|PubMed:20863830,
CC       ECO:0000269|PubMed:27177387}; Multi-pass membrane protein
CC       {ECO:0000305}. Cytoplasmic vesicle membrane
CC       {ECO:0000269|PubMed:16959783, ECO:0000269|PubMed:17574245,
CC       ECO:0000269|PubMed:20863830, ECO:0000269|PubMed:22673903,
CC       ECO:0000269|PubMed:27177387, ECO:0000269|PubMed:31473345}. Late
CC       endosome membrane {ECO:0000269|PubMed:27177387}. Lysosome membrane
CC       {ECO:0000269|PubMed:16959783, ECO:0000269|PubMed:17574245,
CC       ECO:0000269|PubMed:20863830, ECO:0000269|PubMed:24142515}.
CC       Note=Localized in the limiting membrane of lamellar bodies in lung
CC       alveolar type II cells (PubMed:22673903, PubMed:16959783,
CC       PubMed:24142515, PubMed:27177387, PubMed:11718719). Trafficks via the
CC       Golgi, sorting vesicles (SVs) and late endosome/multivesicular body
CC       network directly to the outer membrane of lamellar bodies in AT2 lung
CC       epithelial cells or to lysosomes and lysosomal-related organelles
CC       (LROs) in other cells where undergoes proteolytic cleveage and
CC       oligosaccharide processing from high mannose type to complex type
CC       (PubMed:24142515, PubMed:20863830, PubMed:16959783, PubMed:27177387).
CC       Oligomers formation takes place in a post-endoplasmic reticulum
CC       compartment (PubMed:27352740). {ECO:0000269|PubMed:11718719,
CC       ECO:0000269|PubMed:16959783, ECO:0000269|PubMed:20863830,
CC       ECO:0000269|PubMed:22673903, ECO:0000269|PubMed:24142515,
CC       ECO:0000269|PubMed:27177387, ECO:0000269|PubMed:27352740}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q99758-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q99758-2; Sequence=VSP_056262, VSP_056263;
CC   -!- TISSUE SPECIFICITY: Expressed in brain, pancreas, skeletal muscle and
CC       heart (PubMed:8706931). Highly expressed in the lung in an AT2-cell-
CC       specific manner (PubMed:11718719, PubMed:8706931). Weakly expressed in
CC       placenta, kidney and liver (PubMed:8706931). Also expressed in
CC       medullary thyroid carcinoma cells (MTC) and in C-cell carcinoma
CC       (PubMed:8706931). {ECO:0000269|PubMed:11718719,
CC       ECO:0000269|PubMed:8706931}.
CC   -!- INDUCTION: Up-regulated in Leishmania Viannia (L.V.) panamensis-
CC       infected macrophages exposed to miltefosine (PubMed:26903515). Down-
CC       regulated by L. V. panamensis infection (PubMed:26903515).
CC       {ECO:0000269|PubMed:26903515}.
CC   -!- DOMAIN: Multifunctional polypeptide with two homologous halves, each
CC       containing a hydrophobic membrane-anchoring domain and an ATP binding
CC       cassette (ABC) domain. {ECO:0000250}.
CC   -!- PTM: N-glycosylated (PubMed:16959783, PubMed:24142515,
CC       PubMed:27177387). Localization at intracellular vesicles is accompanied
CC       by processing of oligosaccharide from high mannose type to complex type
CC       (PubMed:16959783, PubMed:27177387). N-linked glycosylation at Asn-124
CC       and Asn-140 is required for stability and efficient anterograde
CC       trafficking and prevents from proteasomal degradation
CC       (PubMed:24142515). {ECO:0000269|PubMed:16959783,
CC       ECO:0000269|PubMed:24142515, ECO:0000269|PubMed:27177387}.
CC   -!- PTM: Proteolytically cleaved by CTSL and to a lower extent by CTSB
CC       within multivesicular bodies (MVB) and lamellar bodies (LB) leading to
CC       a mature form of 150 kDa. {ECO:0000269|PubMed:16959783,
CC       ECO:0000269|PubMed:20863830, ECO:0000269|PubMed:27031696,
CC       ECO:0000269|PubMed:27177387}.
CC   -!- DISEASE: Pulmonary surfactant metabolism dysfunction 3 (SMDP3)
CC       [MIM:610921]: A rare lung disorder due to impaired surfactant
CC       homeostasis. It is characterized by alveolar filling with floccular
CC       material that stains positive using the periodic acid-Schiff method and
CC       is derived from surfactant phospholipids and protein components.
CC       Excessive lipoproteins accumulation in the alveoli results in severe
CC       respiratory distress. {ECO:0000269|PubMed:15044640,
CC       ECO:0000269|PubMed:15976379, ECO:0000269|PubMed:16728712,
CC       ECO:0000269|PubMed:16959783, ECO:0000269|PubMed:17574245,
CC       ECO:0000269|PubMed:20863830, ECO:0000269|PubMed:25712598,
CC       ECO:0000269|PubMed:25817392, ECO:0000269|PubMed:27177387,
CC       ECO:0000269|PubMed:27352740, ECO:0000269|PubMed:28887056,
CC       ECO:0000269|PubMed:31473345}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the ABC transporter superfamily. ABCA family.
CC       {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=SeattleSNPs;
CC       URL="http://pga.gs.washington.edu/data/abca3/";
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; U78735; AAC50967.1; -; mRNA.
DR   EMBL; X97187; CAA65825.1; -; mRNA.
DR   EMBL; AB070929; BAB86781.1; -; mRNA.
DR   EMBL; DQ073080; AAY57325.1; -; Genomic_DNA.
DR   EMBL; CH471112; EAW85515.1; -; Genomic_DNA.
DR   EMBL; BC020724; AAH20724.1; -; mRNA.
DR   EMBL; BC062779; AAH62779.1; -; mRNA.
DR   EMBL; AC009065; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC098805; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC106820; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC140895; AAI40896.1; -; mRNA.
DR   EMBL; BC146866; AAI46867.1; -; mRNA.
DR   CCDS; CCDS10466.1; -. [Q99758-1]
DR   PIR; A59188; A59188.
DR   PIR; S71363; S71363.
DR   RefSeq; NP_001080.2; NM_001089.2. [Q99758-1]
DR   AlphaFoldDB; Q99758; -.
DR   SMR; Q99758; -.
DR   BioGRID; 106539; 46.
DR   IntAct; Q99758; 20.
DR   MINT; Q99758; -.
DR   STRING; 9606.ENSP00000301732; -.
DR   DrugBank; DB00619; Imatinib.
DR   TCDB; 3.A.1.211.5; the atp-binding cassette (abc) superfamily.
DR   GlyGen; Q99758; 6 sites.
DR   iPTMnet; Q99758; -.
DR   PhosphoSitePlus; Q99758; -.
DR   BioMuta; ABCA3; -.
DR   DMDM; 85700402; -.
DR   jPOST; Q99758; -.
DR   MassIVE; Q99758; -.
DR   MaxQB; Q99758; -.
DR   PaxDb; Q99758; -.
DR   PeptideAtlas; Q99758; -.
DR   PRIDE; Q99758; -.
DR   ProteomicsDB; 66998; -.
DR   ProteomicsDB; 78463; -. [Q99758-1]
DR   Antibodypedia; 1409; 78 antibodies from 19 providers.
DR   DNASU; 21; -.
DR   Ensembl; ENST00000301732.10; ENSP00000301732.5; ENSG00000167972.14. [Q99758-1]
DR   Ensembl; ENST00000567910.1; ENSP00000454397.1; ENSG00000167972.14. [Q99758-2]
DR   GeneID; 21; -.
DR   KEGG; hsa:21; -.
DR   MANE-Select; ENST00000301732.10; ENSP00000301732.5; NM_001089.3; NP_001080.2.
DR   UCSC; uc002cpy.2; human. [Q99758-1]
DR   CTD; 21; -.
DR   DisGeNET; 21; -.
DR   GeneCards; ABCA3; -.
DR   HGNC; HGNC:33; ABCA3.
DR   HPA; ENSG00000167972; Tissue enhanced (lung).
DR   MalaCards; ABCA3; -.
DR   MIM; 601615; gene.
DR   MIM; 610921; phenotype.
DR   neXtProt; NX_Q99758; -.
DR   OpenTargets; ENSG00000167972; -.
DR   Orphanet; 2032; Idiopathic pulmonary fibrosis.
DR   Orphanet; 70587; Infant acute respiratory distress syndrome.
DR   Orphanet; 440402; Interstitial lung disease due to ABCA3 deficiency.
DR   PharmGKB; PA24378; -.
DR   VEuPathDB; HostDB:ENSG00000167972; -.
DR   eggNOG; KOG0059; Eukaryota.
DR   GeneTree; ENSGT00940000155289; -.
DR   HOGENOM; CLU_113155_0_0_1; -.
DR   InParanoid; Q99758; -.
DR   OMA; WKNWIVL; -.
DR   PhylomeDB; Q99758; -.
DR   TreeFam; TF105191; -.
DR   PathwayCommons; Q99758; -.
DR   Reactome; R-HSA-1369062; ABC transporters in lipid homeostasis.
DR   Reactome; R-HSA-5683678; Defective ABCA3 causes SMDP3.
DR   Reactome; R-HSA-5683826; Surfactant metabolism.
DR   Reactome; R-HSA-5688399; Defective ABCA3 causes SMDP3.
DR   SignaLink; Q99758; -.
DR   SIGNOR; Q99758; -.
DR   BioGRID-ORCS; 21; 16 hits in 1078 CRISPR screens.
DR   ChiTaRS; ABCA3; human.
DR   GeneWiki; ABCA3; -.
DR   GenomeRNAi; 21; -.
DR   Pharos; Q99758; Tbio.
DR   PRO; PR:Q99758; -.
DR   Proteomes; UP000005640; Chromosome 16.
DR   RNAct; Q99758; protein.
DR   Bgee; ENSG00000167972; Expressed in lower lobe of lung and 145 other tissues.
DR   ExpressionAtlas; Q99758; baseline and differential.
DR   Genevisible; Q99758; HS.
DR   GO; GO:0097208; C:alveolar lamellar body; IDA:MGI.
DR   GO; GO:0097233; C:alveolar lamellar body membrane; IDA:UniProtKB.
DR   GO; GO:0030659; C:cytoplasmic vesicle membrane; IDA:UniProtKB.
DR   GO; GO:0005615; C:extracellular space; HDA:UniProtKB.
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:0042599; C:lamellar body; IDA:UniProtKB.
DR   GO; GO:0097232; C:lamellar body membrane; IDA:UniProtKB.
DR   GO; GO:0005770; C:late endosome; IDA:UniProtKB.
DR   GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0032585; C:multivesicular body membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005886; C:plasma membrane; IDA:ARUK-UCL.
DR   GO; GO:0008559; F:ABC-type xenobiotic transporter activity; IMP:UniProtKB.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0016887; F:ATP hydrolysis activity; IDA:UniProtKB.
DR   GO; GO:0042626; F:ATPase-coupled transmembrane transporter activity; IBA:GO_Central.
DR   GO; GO:0005319; F:lipid transporter activity; IBA:GO_Central.
DR   GO; GO:0140345; F:phosphatidylcholine flippase activity; IMP:UniProtKB.
DR   GO; GO:0120019; F:phosphatidylcholine transfer activity; IMP:UniProtKB.
DR   GO; GO:0006869; P:lipid transport; IBA:GO_Central.
DR   GO; GO:0030324; P:lung development; ISS:UniProtKB.
DR   GO; GO:0070925; P:organelle assembly; ISS:UniProtKB.
DR   GO; GO:0046470; P:phosphatidylcholine metabolic process; IMP:UniProtKB.
DR   GO; GO:0046471; P:phosphatidylglycerol metabolic process; ISS:UniProtKB.
DR   GO; GO:0055091; P:phospholipid homeostasis; IEA:Ensembl.
DR   GO; GO:0015914; P:phospholipid transport; IMP:UniProtKB.
DR   GO; GO:0010875; P:positive regulation of cholesterol efflux; IMP:UniProtKB.
DR   GO; GO:1902995; P:positive regulation of phospholipid efflux; IMP:UniProtKB.
DR   GO; GO:2001140; P:positive regulation of phospholipid transport; IMP:UniProtKB.
DR   GO; GO:0032464; P:positive regulation of protein homooligomerization; IDA:UniProtKB.
DR   GO; GO:0046890; P:regulation of lipid biosynthetic process; IEA:Ensembl.
DR   GO; GO:0150172; P:regulation of phosphatidylcholine metabolic process; IMP:UniProtKB.
DR   GO; GO:0051384; P:response to glucocorticoid; IEA:Ensembl.
DR   GO; GO:0009410; P:response to xenobiotic stimulus; TAS:ProtInc.
DR   GO; GO:0043129; P:surfactant homeostasis; ISS:UniProtKB.
DR   GO; GO:0046618; P:xenobiotic export from cell; IMP:UniProtKB.
DR   GO; GO:0006855; P:xenobiotic transmembrane transport; IMP:UniProtKB.
DR   GO; GO:0042908; P:xenobiotic transport; IMP:UniProtKB.
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; IPR027417; P-loop_NTPase.
DR   PANTHER; PTHR19229; PTHR19229; 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; Cytoplasmic vesicle; Disease variant;
KW   Disulfide bond; Endosome; Glycoprotein; Lipid transport; Lysosome;
KW   Membrane; Nucleotide-binding; Reference proteome; Repeat; Translocase;
KW   Transmembrane; Transmembrane helix; Transport.
FT   CHAIN           1..1704
FT                   /note="Phospholipid-transporting ATPase ABCA3"
FT                   /id="PRO_0000093293"
FT   CHAIN           175..1704
FT                   /note="150 Kda mature form"
FT                   /evidence="ECO:0000305|PubMed:27031696"
FT                   /id="PRO_0000452297"
FT   TRANSMEM        22..42
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        261..283
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        307..327
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        344..364
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        373..393
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        405..425
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        447..467
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        925..945
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1100..1120
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1144..1164
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1183..1203
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1213..1233
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1245..1265
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1306..1326
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          530..763
FT                   /note="ABC transporter 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT   DOMAIN          1381..1614
FT                   /note="ABC transporter 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT   BINDING         566..573
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT   BINDING         1416..1423
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT   SITE            174..175
FT                   /note="Cleavage; by CTSL"
FT                   /evidence="ECO:0000269|PubMed:27031696"
FT   CARBOHYD        14
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        53
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        124
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255, ECO:0000269|PubMed:24142515"
FT   CARBOHYD        140
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255, ECO:0000269|PubMed:24142515"
FT   CARBOHYD        620
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        783
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   VAR_SEQ         206..209
FT                   /note="YIRE -> EKLG (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_056262"
FT   VAR_SEQ         210..1704
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_056263"
FT   VARIANT         43
FT                   /note="R -> L (in SMDP3; unknown pathological
FT                   significance)"
FT                   /evidence="ECO:0000269|PubMed:16728712"
FT                   /id="VAR_084240"
FT   VARIANT         101
FT                   /note="L -> P (in SMDP3; loss of intracellular vesicle
FT                   membrane location; loss of proteolytic cleavage; does not
FT                   affect N-glycosylation; loss of ATP hydrolysis activity;
FT                   decreases ATP binding in vitro; dbSNP:rs121909182)"
FT                   /evidence="ECO:0000269|PubMed:15044640,
FT                   ECO:0000269|PubMed:16959783"
FT                   /id="VAR_023497"
FT   VARIANT         140
FT                   /note="N -> H (in dbSNP:rs45447801)"
FT                   /evidence="ECO:0000269|Ref.4"
FT                   /id="VAR_025061"
FT   VARIANT         215
FT                   /note="Q -> K (in SMDP3; loss of lamellar bodies membrane
FT                   location; loss of proteolytic cleavage; increases cellular
FT                   free cholesterol and phosphatidylcholine transport; loss of
FT                   vesicles formation; increases free cholesterol induced cell
FT                   death; loss of protein oligomerization; dbSNP:rs879159551)"
FT                   /evidence="ECO:0000269|PubMed:16728712,
FT                   ECO:0000269|PubMed:20863830, ECO:0000269|PubMed:25817392,
FT                   ECO:0000269|PubMed:27352740"
FT                   /id="VAR_084241"
FT   VARIANT         280
FT                   /note="R -> C (in SMDP3; unknown pathological significance;
FT                   does not affect protein oligomerization;
FT                   dbSNP:rs201299260)"
FT                   /evidence="ECO:0000269|PubMed:25712598,
FT                   ECO:0000269|PubMed:27352740"
FT                   /id="VAR_084242"
FT   VARIANT         288
FT                   /note="R -> K (in SMDP3; unknown pathological significance;
FT                   does not affects protein oligomerization;
FT                   dbSNP:rs117603931)"
FT                   /evidence="ECO:0000269|PubMed:16728712,
FT                   ECO:0000269|PubMed:27352740"
FT                   /id="VAR_084243"
FT   VARIANT         290
FT                   /note="L -> M (in a breast cancer sample; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:16959974"
FT                   /id="VAR_035728"
FT   VARIANT         292
FT                   /note="E -> V (in SMDP3; unknown pathological significance;
FT                   does not affect lamellar bodies membrane location; does not
FT                   affect proteolytic cleavage; affects lamellar bodies
FT                   formation; does not affect cholesterol and
FT                   phosphatidylcholine transport; decreases vesicles
FT                   formation; does not affect free cholesterol induced cell
FT                   death; dbSNP:rs149989682)"
FT                   /evidence="ECO:0000269|PubMed:15976379,
FT                   ECO:0000269|PubMed:20863830, ECO:0000269|PubMed:25817392,
FT                   ECO:0000269|PubMed:28887056"
FT                   /id="VAR_084244"
FT   VARIANT         568
FT                   /note="N -> D (in SMDP3; does not affect location in
FT                   intracellular vesicle membrane; does not affect proteolytic
FT                   cleavage; does not affect N-glycosylation; loss of ATP
FT                   hydrolysis activity; decreases ATP binding in vitro; does
FT                   not affect protein expression; does not affect
FT                   multivesicular bodies and lamellar bodies location; affects
FT                   multivesicular bodies and lamellar bodies development; loss
FT                   of phosphatidylcholine transport; does not affect
FT                   cholesterol transport; dbSNP:rs121909184)"
FT                   /evidence="ECO:0000269|PubMed:15044640,
FT                   ECO:0000269|PubMed:16959783, ECO:0000269|PubMed:17574245,
FT                   ECO:0000269|PubMed:31473345"
FT                   /id="VAR_023498"
FT   VARIANT         579
FT                   /note="L -> P (in SMDP3; unknown pathological
FT                   significance)"
FT                   /evidence="ECO:0000269|PubMed:16728712"
FT                   /id="VAR_084245"
FT   VARIANT         605
FT                   /note="R -> Q (in SMDP3; unknown pathological significance;
FT                   dbSNP:rs760006956)"
FT                   /evidence="ECO:0000269|PubMed:16728712"
FT                   /id="VAR_084246"
FT   VARIANT         690
FT                   /note="E -> K (in SMDP3)"
FT                   /evidence="ECO:0000269|PubMed:15976379"
FT                   /id="VAR_084247"
FT   VARIANT         766
FT                   /note="P -> S (in dbSNP:rs45592239)"
FT                   /evidence="ECO:0000269|Ref.4"
FT                   /id="VAR_025062"
FT   VARIANT         801
FT                   /note="E -> D (in a breast cancer sample; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:16959974"
FT                   /id="VAR_035729"
FT   VARIANT         982
FT                   /note="L -> P (in SMDP3; loss of intracellular vesicle
FT                   membrane location; loss of proteolytic cleavage; does not
FT                   affect N-glycosylation; dbSNP:rs1402761450)"
FT                   /evidence="ECO:0000269|PubMed:15044640,
FT                   ECO:0000269|PubMed:16959783"
FT                   /id="VAR_084248"
FT   VARIANT         1069
FT                   /note="H -> Q (in a breast cancer sample; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:16959974"
FT                   /id="VAR_035730"
FT   VARIANT         1076
FT                   /note="N -> K (in SMDP3; unknown pathological
FT                   significance)"
FT                   /evidence="ECO:0000269|PubMed:15976379"
FT                   /id="VAR_084249"
FT   VARIANT         1114
FT                   /note="T -> M (in SMDP3; dbSNP:rs891579143)"
FT                   /evidence="ECO:0000269|PubMed:15976379"
FT                   /id="VAR_084250"
FT   VARIANT         1221
FT                   /note="G -> S (in SMDP3; does not affect intracellular
FT                   vesicle membrane location; does not affect proteolytic
FT                   cleavage; does not affect N-glycosylation; loss of ATP
FT                   hydrolysis activity)"
FT                   /evidence="ECO:0000269|PubMed:15044640,
FT                   ECO:0000269|PubMed:16959783"
FT                   /id="VAR_084251"
FT   VARIANT         1301
FT                   /note="P -> L (in SMDP3; dbSNP:rs762699052)"
FT                   /evidence="ECO:0000269|PubMed:15976379"
FT                   /id="VAR_084252"
FT   VARIANT         1302
FT                   /note="G -> E (in SMDP3; unknown pathological
FT                   significance)"
FT                   /evidence="ECO:0000269|PubMed:15976379"
FT                   /id="VAR_084253"
FT   VARIANT         1388
FT                   /note="K -> N (in SMDP3; decreases phosphatidylcholine
FT                   transport; increases protein abundance; does not affect
FT                   folding in the endoplasmic reticulum; decreases proteolytic
FT                   processing; affects lamellar bodies development; reduces
FT                   free cholesterol transport)"
FT                   /evidence="ECO:0000269|PubMed:27177387,
FT                   ECO:0000269|PubMed:28887056"
FT                   /id="VAR_084254"
FT   VARIANT         1399
FT                   /note="V -> M (in SMDP3; dbSNP:rs763166660)"
FT                   /evidence="ECO:0000269|PubMed:25712598"
FT                   /id="VAR_084255"
FT   VARIANT         1553
FT                   /note="L -> P (in SMDP3; loss of intracellular vesicle
FT                   membrane location; loss of proteolytic cleavage; does not
FT                   affect N-glycosylation; dbSNP:rs121909183)"
FT                   /evidence="ECO:0000269|PubMed:15044640,
FT                   ECO:0000269|PubMed:16959783"
FT                   /id="VAR_023499"
FT   VARIANT         1561..1704
FT                   /note="Missing (in SMDP3)"
FT                   /evidence="ECO:0000269|PubMed:16728712"
FT                   /id="VAR_084256"
FT   VARIANT         1580
FT                   /note="L -> P (in SMDP3; does not affect location in
FT                   intracellular vesicle membrane; does not affect proteolytic
FT                   cleavage; does not affect N-glycosylation; loss of ATP
FT                   hydrolysis activity; decreases ATP binding in vitro;
FT                   affects the intracellular vesicles development; decreases
FT                   phosphatidylcholine transport)"
FT                   /evidence="ECO:0000269|PubMed:15044640,
FT                   ECO:0000269|PubMed:16959783, ECO:0000269|PubMed:31473345"
FT                   /id="VAR_084257"
FT   VARIANT         1589..1704
FT                   /note="Missing (in SMDP3)"
FT                   /evidence="ECO:0000269|PubMed:25712598"
FT                   /id="VAR_084258"
FT   VARIANT         1591
FT                   /note="Q -> P (in SMDP3; loss of intracellular vesicle
FT                   membrane location; loss of proteolytic cleavage; does not
FT                   affect N-glycosylation; dbSNP:rs28936691)"
FT                   /evidence="ECO:0000269|PubMed:15044640,
FT                   ECO:0000269|PubMed:16959783"
FT                   /id="VAR_023500"
FT   MUTAGEN         53
FT                   /note="N->Q: Does not affect N-glycosylation. Does not
FT                   affect protein expression. Does not affect lamellar body
FT                   membrane location."
FT                   /evidence="ECO:0000269|PubMed:24142515"
FT   MUTAGEN         124
FT                   /note="N->Q: Loss of N-glycosylation. Reduces protein
FT                   expression by 50%. Affects anterograde trafficking; when
FT                   associated with Q-140. Reduces protein expression by 85%;
FT                   when associated with Q-140. Does not affect lamellar body
FT                   membrane location."
FT                   /evidence="ECO:0000269|PubMed:24142515"
FT   MUTAGEN         140
FT                   /note="N->Q: Loss of N-glycosylation. Reduces protein
FT                   expression by 50%. Affects anterograde trafficking; when
FT                   associated with Q-124. Reduces protein expression by 85%;
FT                   when associated with Q-140. Does not affect lamellar body
FT                   membrane location."
FT                   /evidence="ECO:0000269|PubMed:24142515"
FT   MUTAGEN         173..174
FT                   /note="LK->AA: Loss of proteolytic processing."
FT                   /evidence="ECO:0000269|PubMed:27031696"
FT   MUTAGEN         693
FT                   /note="S->L: Does not affect protein oligomerization."
FT                   /evidence="ECO:0000269|PubMed:27352740"
FT   MUTAGEN         945
FT                   /note="N->Q: Does not affect lamellar body membrane
FT                   location. Does not affect protein expression. Does not
FT                   affect proteolytic processing."
FT                   /evidence="ECO:0000269|PubMed:24142515"
FT   MUTAGEN         1221
FT                   /note="G->A: Decreases ATP hydrolysis activity of 15%
FT                   compared to the wild-type."
FT                   /evidence="ECO:0000269|PubMed:16959783"
FT   MUTAGEN         1221
FT                   /note="G->T: Decreases ATP hydrolysis activity of 36%
FT                   compared to the wild-type."
FT                   /evidence="ECO:0000269|PubMed:16959783"
FT   MUTAGEN         1221
FT                   /note="G->V: Decreases ATP hydrolysis activity of 18%
FT                   compared to the wild-type."
FT                   /evidence="ECO:0000269|PubMed:16959783"
FT   MUTAGEN         1580
FT                   /note="L->A: Decreases ATP hydrolysis activity of 13%
FT                   compared to the wild-type."
FT                   /evidence="ECO:0000269|PubMed:16959783"
FT   MUTAGEN         1580
FT                   /note="L->F: Decreases ATP hydrolysis activity of 13%
FT                   compared to the wild-type."
FT                   /evidence="ECO:0000269|PubMed:16959783"
FT   MUTAGEN         1580
FT                   /note="L->V: Decreases ATP hydrolysis activity of 56%
FT                   compared to the wild-type."
FT                   /evidence="ECO:0000269|PubMed:16959783"
FT   CONFLICT        36
FT                   /note="S -> P (in Ref. 1; AAC50967)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        196
FT                   /note="P -> L (in Ref. 1; AAC50967)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   1704 AA;  191362 MW;  606735C504839D0D CRC64;
     MAVLRQLALL LWKNYTLQKR KVLVTVLELF LPLLFSGILI WLRLKIQSEN VPNATIYPGQ
     SIQELPLFFT FPPPGDTWEL AYIPSHSDAA KTVTETVRRA LVINMRVRGF PSEKDFEDYI
     RYDNCSSSVL AAVVFEHPFN HSKEPLPLAV KYHLRFSYTR RNYMWTQTGS FFLKETEGWH
     TTSLFPLFPN PGPREPTSPD GGEPGYIREG FLAVQHAVDR AIMEYHADAA TRQLFQRLTV
     TIKRFPYPPF IADPFLVAIQ YQLPLLLLLS FTYTALTIAR AVVQEKERRL KEYMRMMGLS
     SWLHWSAWFL LFFLFLLIAA SFMTLLFCVK VKPNVAVLSR SDPSLVLAFL LCFAISTISF
     SFMVSTFFSK ANMAAAFGGF LYFFTYIPYF FVAPRYNWMT LSQKLCSCLL SNVAMAMGAQ
     LIGKFEAKGM GIQWRDLLSP VNVDDDFCFG QVLGMLLLDS VLYGLVTWYM EAVFPGQFGV
     PQPWYFFIMP SYWCGKPRAV AGKEEEDSDP EKALRNEYFE AEPEDLVAGI KIKHLSKVFR
     VGNKDRAAVR DLNLNLYEGQ ITVLLGHNGA GKTTTLSMLT GLFPPTSGRA YISGYEISQD
     MVQIRKSLGL CPQHDILFDN LTVAEHLYFY AQLKGLSRQK CPEEVKQMLH IIGLEDKWNS
     RSRFLSGGMR RKLSIGIALI AGSKVLILDE PTSGMDAISR RAIWDLLQRQ KSDRTIVLTT
     HFMDEADLLG DRIAIMAKGE LQCCGSSLFL KQKYGAGYHM TLVKEPHCNP EDISQLVHHH
     VPNATLESSA GAELSFILPR ESTHRFEGLF AKLEKKQKEL GIASFGASIT TMEEVFLRVG
     KLVDSSMDIQ AIQLPALQYQ HERRASDWAV DSNLCGAMDP SDGIGALIEE ERTAVKLNTG
     LALHCQQFWA MFLKKAAYSW REWKMVAAQV LVPLTCVTLA LLAINYSSEL FDDPMLRLTL
     GEYGRTVVPF SVPGTSQLGQ QLSEHLKDAL QAEGQEPREV LGDLEEFLIF RASVEGGGFN
     ERCLVAASFR DVGERTVVNA LFNNQAYHSP ATALAVVDNL LFKLLCGPHA SIVVSNFPQP
     RSALQAAKDQ FNEGRKGFDI ALNLLFAMAF LASTFSILAV SERAVQAKHV QFVSGVHVAS
     FWLSALLWDL ISFLIPSLLL LVVFKAFDVR AFTRDGHMAD TLLLLLLYGW AIIPLMYLMN
     FFFLGAATAY TRLTIFNILS GIATFLMVTI MRIPAVKLEE LSKTLDHVFL VLPNHCLGMA
     VSSFYENYET RRYCTSSEVA AHYCKKYNIQ YQENFYAWSA PGVGRFVASM AASGCAYLIL
     LFLIETNLLQ RLRGILCALR RRRTLTELYT RMPVLPEDQD VADERTRILA PSPDSLLHTP
     LIIKELSKVY EQRVPLLAVD RLSLAVQKGE CFGLLGFNGA GKTTTFKMLT GEESLTSGDA
     FVGGHRISSD VGKVRQRIGY CPQFDALLDH MTGREMLVMY ARLRGIPERH IGACVENTLR
     GLLLEPHANK LVRTYSGGNK RKLSTGIALI GEPAVIFLDE PSTGMDPVAR RLLWDTVARA
     RESGKAIIIT SHSMEECEAL CTRLAIMVQG QFKCLGSPQH LKSKFGSGYS LRAKVQSEGQ
     QEALEEFKAF VDLTFPGSVL EDEHQGMVHY HLPGRDLSWA KVFGILEKAK EKYGVDDYSV
     SQISLEQVFL SFAHLQPPTA EEGR
 
 
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