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 27-MAR-2024, entry version 194. 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 cleavage 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"; 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; 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 PDB; 7W01; EM; 3.30 A; A=1-1704. DR PDB; 7W02; EM; 3.30 A; A=1-1704. DR PDBsum; 7W01; -. DR PDBsum; 7W02; -. DR AlphaFoldDB; Q99758; -. DR EMDB; EMD-32233; -. DR EMDB; EMD-32234; -. DR SMR; Q99758; -. DR BioGRID; 106539; 47. 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 GlyCosmos; Q99758; 6 sites, No reported glycans. DR GlyGen; Q99758; 6 sites. DR iPTMnet; Q99758; -. DR PhosphoSitePlus; Q99758; -. DR SwissPalm; Q99758; -. DR BioMuta; ABCA3; -. DR DMDM; 85700402; -. DR jPOST; Q99758; -. DR MassIVE; Q99758; -. DR MaxQB; Q99758; -. DR PaxDb; 9606-ENSP00000301732; -. DR PeptideAtlas; Q99758; -. DR ProteomicsDB; 66998; -. DR ProteomicsDB; 78463; -. [Q99758-1] DR Antibodypedia; 1409; 99 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 AGR; HGNC:33; -. DR CTD; 21; -. DR DisGeNET; 21; -. DR GeneCards; ABCA3; -. DR HGNC; HGNC:33; ABCA3. DR HPA; ENSG00000167972; Tissue enhanced (brain, 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 OrthoDB; 6951at2759; -. 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; 17 hits in 1158 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 147 other cell types or tissues. DR ExpressionAtlas; Q99758; baseline and differential. 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: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:MGI. 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:0019538; P:protein metabolic process; TAS:Reactome. 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 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; ATP-BINDING CASSETTE TRANSPORTER SUBFAMILY A ABCA; 1. DR PANTHER; PTHR19229:SF98; PHOSPHOLIPID-TRANSPORTING ATPASE ABCA3; 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; Q99758; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; ATP-binding; Cytoplasmic vesicle; KW Disease variant; Disulfide bond; Endosome; Glycoprotein; Lipid transport; KW Lysosome; Membrane; Nucleotide-binding; Reference proteome; Repeat; KW Translocase; 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; uncertain 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; uncertain significance; does not FT affect protein oligomerization; 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; uncertain significance; does not FT affect protein oligomerization; 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; uncertain significance; does not FT affect lamellar bodies membrane location; does not affect FT proteolytic cleavage; affects lamellar bodies formation; FT does not affect cholesterol and phosphatidylcholine FT transport; decreases vesicles formation; does not affect FT free cholesterol induced cell 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; uncertain significance)" FT /evidence="ECO:0000269|PubMed:16728712" FT /id="VAR_084245" FT VARIANT 605 FT /note="R -> Q (in SMDP3; uncertain 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; uncertain 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; uncertain 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" FT HELIX 3..19 FT /evidence="ECO:0007829|PDB:7W01" FT HELIX 22..29 FT /evidence="ECO:0007829|PDB:7W01" FT TURN 32..36 FT /evidence="ECO:0007829|PDB:7W01" FT HELIX 38..44 FT /evidence="ECO:0007829|PDB:7W01" FT STRAND 59..61 FT /evidence="ECO:0007829|PDB:7W01" FT STRAND 69..71 FT /evidence="ECO:0007829|PDB:7W01" FT STRAND 74..76 FT /evidence="ECO:0007829|PDB:7W01" FT STRAND 79..83 FT /evidence="ECO:0007829|PDB:7W01" FT HELIX 88..98 FT /evidence="ECO:0007829|PDB:7W01" FT STRAND 106..109 FT /evidence="ECO:0007829|PDB:7W01" FT HELIX 113..121 FT /evidence="ECO:0007829|PDB:7W01" FT STRAND 128..133 FT /evidence="ECO:0007829|PDB:7W01" FT HELIX 140..142 FT /evidence="ECO:0007829|PDB:7W02" FT STRAND 148..152 FT /evidence="ECO:0007829|PDB:7W01" FT STRAND 194..197 FT /evidence="ECO:0007829|PDB:7W01" FT STRAND 206..209 FT /evidence="ECO:0007829|PDB:7W01" FT HELIX 211..224 FT /evidence="ECO:0007829|PDB:7W01" FT HELIX 230..236 FT /evidence="ECO:0007829|PDB:7W01" FT STRAND 237..244 FT /evidence="ECO:0007829|PDB:7W01" FT HELIX 255..271 FT /evidence="ECO:0007829|PDB:7W01" FT TURN 272..276 FT /evidence="ECO:0007829|PDB:7W01" FT HELIX 277..287 FT /evidence="ECO:0007829|PDB:7W01" FT HELIX 290..295 FT /evidence="ECO:0007829|PDB:7W01" FT TURN 296..298 FT /evidence="ECO:0007829|PDB:7W01" FT HELIX 303..327 FT /evidence="ECO:0007829|PDB:7W01" FT STRAND 336..338 FT /evidence="ECO:0007829|PDB:7W01" FT HELIX 343..364 FT /evidence="ECO:0007829|PDB:7W01" FT HELIX 371..377 FT /evidence="ECO:0007829|PDB:7W01" FT HELIX 380..384 FT /evidence="ECO:0007829|PDB:7W01" FT HELIX 387..389 FT /evidence="ECO:0007829|PDB:7W01" FT TURN 390..392 FT /evidence="ECO:0007829|PDB:7W01" FT HELIX 394..396 FT /evidence="ECO:0007829|PDB:7W02" FT HELIX 401..407 FT /evidence="ECO:0007829|PDB:7W01" FT HELIX 411..426 FT /evidence="ECO:0007829|PDB:7W01" FT STRAND 437..439 FT /evidence="ECO:0007829|PDB:7W01" FT STRAND 441..444 FT /evidence="ECO:0007829|PDB:7W01" FT HELIX 450..473 FT /evidence="ECO:0007829|PDB:7W01" FT STRAND 477..479 FT /evidence="ECO:0007829|PDB:7W01" FT TURN 484..487 FT /evidence="ECO:0007829|PDB:7W01" FT STRAND 524..526 FT /evidence="ECO:0007829|PDB:7W01" FT STRAND 528..537 FT /evidence="ECO:0007829|PDB:7W01" FT STRAND 540..542 FT /evidence="ECO:0007829|PDB:7W01" FT STRAND 549..552 FT /evidence="ECO:0007829|PDB:7W01" FT STRAND 555..564 FT /evidence="ECO:0007829|PDB:7W01" FT STRAND 568..574 FT /evidence="ECO:0007829|PDB:7W01" FT HELIX 575..580 FT /evidence="ECO:0007829|PDB:7W01" FT STRAND 589..595 FT /evidence="ECO:0007829|PDB:7W01" FT TURN 597..599 FT /evidence="ECO:0007829|PDB:7W01" FT HELIX 601..604 FT /evidence="ECO:0007829|PDB:7W01" FT TURN 605..607 FT /evidence="ECO:0007829|PDB:7W01" FT STRAND 609..611 FT /evidence="ECO:0007829|PDB:7W01" FT HELIX 623..633 FT /evidence="ECO:0007829|PDB:7W01" FT HELIX 642..651 FT /evidence="ECO:0007829|PDB:7W01" FT TURN 656..659 FT /evidence="ECO:0007829|PDB:7W01" FT TURN 662..664 FT /evidence="ECO:0007829|PDB:7W02" FT STRAND 667..669 FT /evidence="ECO:0007829|PDB:7W01" FT HELIX 670..678 FT /evidence="ECO:0007829|PDB:7W01" FT TURN 679..681 FT /evidence="ECO:0007829|PDB:7W01" FT STRAND 684..688 FT /evidence="ECO:0007829|PDB:7W01" FT STRAND 692..694 FT /evidence="ECO:0007829|PDB:7W02" FT HELIX 699..709 FT /evidence="ECO:0007829|PDB:7W01" FT STRAND 714..718 FT /evidence="ECO:0007829|PDB:7W01" FT HELIX 725..728 FT /evidence="ECO:0007829|PDB:7W01" FT STRAND 731..745 FT /evidence="ECO:0007829|PDB:7W01" FT HELIX 747..754 FT /evidence="ECO:0007829|PDB:7W01" FT STRAND 757..761 FT /evidence="ECO:0007829|PDB:7W02" FT HELIX 770..780 FT /evidence="ECO:0007829|PDB:7W01" FT STRAND 781..783 FT /evidence="ECO:0007829|PDB:7W01" FT STRAND 786..788 FT /evidence="ECO:0007829|PDB:7W01" FT STRAND 796..798 FT /evidence="ECO:0007829|PDB:7W02" FT HELIX 800..802 FT /evidence="ECO:0007829|PDB:7W01" FT HELIX 806..815 FT /evidence="ECO:0007829|PDB:7W01" FT TURN 818..821 FT /evidence="ECO:0007829|PDB:7W01" FT STRAND 826..830 FT /evidence="ECO:0007829|PDB:7W02" FT HELIX 832..842 FT /evidence="ECO:0007829|PDB:7W01" FT TURN 847..851 FT /evidence="ECO:0007829|PDB:7W01" FT HELIX 901..916 FT /evidence="ECO:0007829|PDB:7W01" FT STRAND 919..922 FT /evidence="ECO:0007829|PDB:7W01" FT TURN 923..929 FT /evidence="ECO:0007829|PDB:7W01" FT HELIX 931..942 FT /evidence="ECO:0007829|PDB:7W01" FT TURN 943..945 FT /evidence="ECO:0007829|PDB:7W01" FT STRAND 957..959 FT /evidence="ECO:0007829|PDB:7W02" FT STRAND 962..965 FT /evidence="ECO:0007829|PDB:7W02" FT STRAND 967..971 FT /evidence="ECO:0007829|PDB:7W02" FT STRAND 975..979 FT /evidence="ECO:0007829|PDB:7W01" FT HELIX 980..987 FT /evidence="ECO:0007829|PDB:7W01" FT STRAND 991..993 FT /evidence="ECO:0007829|PDB:7W01" FT STRAND 996..999 FT /evidence="ECO:0007829|PDB:7W02" FT HELIX 1005..1014 FT /evidence="ECO:0007829|PDB:7W01" FT HELIX 1019..1022 FT /evidence="ECO:0007829|PDB:7W01" FT STRAND 1028..1032 FT /evidence="ECO:0007829|PDB:7W01" FT STRAND 1035..1042 FT /evidence="ECO:0007829|PDB:7W01" FT STRAND 1046..1048 FT /evidence="ECO:0007829|PDB:7W01" FT HELIX 1049..1064 FT /evidence="ECO:0007829|PDB:7W01" FT STRAND 1071..1073 FT /evidence="ECO:0007829|PDB:7W01" FT HELIX 1083..1089 FT /evidence="ECO:0007829|PDB:7W01" FT TURN 1090..1092 FT /evidence="ECO:0007829|PDB:7W01" FT HELIX 1097..1105 FT /evidence="ECO:0007829|PDB:7W01" FT TURN 1109..1111 FT /evidence="ECO:0007829|PDB:7W01" FT HELIX 1112..1115 FT /evidence="ECO:0007829|PDB:7W01" FT HELIX 1118..1124 FT /evidence="ECO:0007829|PDB:7W01" FT HELIX 1127..1133 FT /evidence="ECO:0007829|PDB:7W01" FT HELIX 1138..1151 FT /evidence="ECO:0007829|PDB:7W01" FT HELIX 1155..1166 FT /evidence="ECO:0007829|PDB:7W01" FT HELIX 1170..1172 FT /evidence="ECO:0007829|PDB:7W01" FT HELIX 1178..1198 FT /evidence="ECO:0007829|PDB:7W01" FT HELIX 1199..1202 FT /evidence="ECO:0007829|PDB:7W01" FT HELIX 1206..1229 FT /evidence="ECO:0007829|PDB:7W01" FT STRAND 1234..1237 FT /evidence="ECO:0007829|PDB:7W02" FT HELIX 1242..1248 FT /evidence="ECO:0007829|PDB:7W01" FT TURN 1249..1251 FT /evidence="ECO:0007829|PDB:7W01" FT HELIX 1255..1273 FT /evidence="ECO:0007829|PDB:7W01" FT HELIX 1278..1287 FT /evidence="ECO:0007829|PDB:7W01" FT STRAND 1293..1296 FT /evidence="ECO:0007829|PDB:7W01" FT STRAND 1298..1302 FT /evidence="ECO:0007829|PDB:7W01" FT HELIX 1307..1310 FT /evidence="ECO:0007829|PDB:7W01" FT TURN 1311..1313 FT /evidence="ECO:0007829|PDB:7W01" FT HELIX 1316..1325 FT /evidence="ECO:0007829|PDB:7W01" FT HELIX 1359..1367 FT /evidence="ECO:0007829|PDB:7W01" FT STRAND 1375..1378 FT /evidence="ECO:0007829|PDB:7W01" FT STRAND 1387..1400 FT /evidence="ECO:0007829|PDB:7W01" FT STRAND 1404..1406 FT /evidence="ECO:0007829|PDB:7W02" FT STRAND 1410..1412 FT /evidence="ECO:0007829|PDB:7W01" FT HELIX 1422..1429 FT /evidence="ECO:0007829|PDB:7W01" FT STRAND 1439..1446 FT /evidence="ECO:0007829|PDB:7W02" FT TURN 1447..1449 FT /evidence="ECO:0007829|PDB:7W01" FT TURN 1451..1453 FT /evidence="ECO:0007829|PDB:7W01" FT STRAND 1457..1460 FT /evidence="ECO:0007829|PDB:7W01" FT HELIX 1473..1482 FT /evidence="ECO:0007829|PDB:7W01" FT TURN 1488..1490 FT /evidence="ECO:0007829|PDB:7W01" FT HELIX 1491..1501 FT /evidence="ECO:0007829|PDB:7W01" FT HELIX 1505..1507 FT /evidence="ECO:0007829|PDB:7W01" FT TURN 1511..1513 FT /evidence="ECO:0007829|PDB:7W01" FT TURN 1517..1519 FT /evidence="ECO:0007829|PDB:7W01" FT HELIX 1521..1524 FT /evidence="ECO:0007829|PDB:7W01" FT TURN 1525..1529 FT /evidence="ECO:0007829|PDB:7W01" FT STRAND 1534..1537 FT /evidence="ECO:0007829|PDB:7W01" FT STRAND 1539..1544 FT /evidence="ECO:0007829|PDB:7W01" FT HELIX 1547..1562 FT /evidence="ECO:0007829|PDB:7W01" FT STRAND 1566..1568 FT /evidence="ECO:0007829|PDB:7W01" FT HELIX 1576..1579 FT /evidence="ECO:0007829|PDB:7W01" FT STRAND 1582..1584 FT /evidence="ECO:0007829|PDB:7W01" FT STRAND 1586..1588 FT /evidence="ECO:0007829|PDB:7W01" FT STRAND 1591..1593 FT /evidence="ECO:0007829|PDB:7W01" FT HELIX 1598..1605 FT /evidence="ECO:0007829|PDB:7W01" FT STRAND 1610..1614 FT /evidence="ECO:0007829|PDB:7W02" FT STRAND 1617..1619 FT /evidence="ECO:0007829|PDB:7W01" FT HELIX 1620..1633 FT /evidence="ECO:0007829|PDB:7W01" FT STRAND 1645..1648 FT /evidence="ECO:0007829|PDB:7W01" FT HELIX 1661..1672 FT /evidence="ECO:0007829|PDB:7W01" FT STRAND 1675..1677 FT /evidence="ECO:0007829|PDB:7W01" FT HELIX 1685..1689 FT /evidence="ECO:0007829|PDB:7W01" FT HELIX 1690..1695 FT /evidence="ECO:0007829|PDB:7W01" 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 //