Protein: Phospholipid-transporting ATPase ABCA3 (EC 7.6.2.1) (ABC-C transporter) (ATP-binding cassette sub-family A member 3) (ATP-binding cassette transporter 3) (ATP-binding cassette 3) (Xenobiotic-transporting ATPase ABCA3) (EC 7.6.2.2) [Cleaved into: 150 Kda mature form] (Q99758)
Organism: Homo sapiens (Human)
Function: Catalyzes the ATP-dependent transport of phospholipids such as phosphatidylcholine and phosphoglycerol from the cytoplasm into the lumen side of lamellar bodies, in turn participates in the lamellar bodies biogenesis and homeostasis of pulmonary surfactant. Transports preferentially phosphatidylcholine containing short acyl chains. In addition plays a role as an efflux transporter of miltefosine across macrophage membranes and free cholesterol (FC) through intralumenal vesicles by removing FC from the cell as a component of surfactant and protects cells from free cholesterol toxicity.
Subcellular location: Endosome, multivesicular body membrane {ECO:0000269|PubMed:16959783, ECO:0000269|PubMed:20863830, ECO:0000269|PubMed:27177387}; Multi-pass membrane protein {ECO:0000305}. Cytoplasmic vesicle membrane {ECO:0000269|PubMed:16959783, ECO:0000269|PubMed:17574245, ECO:0000269|PubMed:20863830, ECO:0000269|PubMed:22673903, ECO:0000269|PubMed:27177387, ECO:0000269|PubMed:31473345}. Late endosome membrane {ECO:0000269|PubMed:27177387}. Lysosome membrane {ECO:0000269|PubMed:16959783, ECO:0000269|PubMed:17574245, ECO:0000269|PubMed:20863830, ECO:0000269|PubMed:24142515}. Note=Localized in the limiting membrane of lamellar bodies in lung alveolar type II cells (PubMed:11718719, PubMed:16959783, PubMed:22673903, PubMed:24142515, PubMed:27177387). Trafficks via the Golgi, sorting vesicles (SVs) and late endosome/multivesicular body network directly to the outer membrane of lamellar bodies in AT2 lung epithelial cells or to lysosomes and lysosomal-related organelles (LROs) in other cells where undergoes proteolytic cleavage and oligosaccharide processing from high mannose type to complex type (PubMed:16959783, PubMed:20863830, PubMed:24142515, PubMed:27177387). Oligomers formation takes place in a post-endoplasmic reticulum compartment (PubMed:27352740). {ECO:0000269|PubMed:11718719, ECO:0000269|PubMed:16959783, ECO:0000269|PubMed:20863830, ECO:0000269|PubMed:22673903, ECO:0000269|PubMed:24142515, ECO:0000269|PubMed:27177387, ECO:0000269|PubMed:27352740}.
Interaction partners:
- Pulmonary surfactant-associated protein B
- Surfactant protein C
- Granulocyte-macrophage colony-stimulating factor receptor subunit alpha
- Pulmonary surfactant-associated protein A1
Sequence:
MAVLRQLALLLWKNYTLQKRKVLVTVLELFLPLLFSGILIWLRLKIQSENVPNATIYPGQSIQELPLFFTFPPPGDTWELAYIPSHSDAAKTVTETVRRALVINMRVRGFPSEKDFEDYIRYDNCSSSVLAAVVFEHPFNHSKEPLPLAVKYHLRFSYTRRNYMWTQTGSFFLKETEGWHTTSLFPLFPNPGPREPTSPDGGEPGYIREGFLAVQHAVDRAIMEYHADAATRQLFQRLTVTIKRFPYPPFIADPFLVAIQYQLPLLLLLSFTYTALTIARAVVQEKERRLKEYMRMMGLSSWLHWSAWFLLFFLFLLIAASFMTLLFCVKVKPNVAVLSRSDPSLVLAFLLCFAISTISFSFMVSTFFSKANMAAAFGGFLYFFTYIPYFFVAPRYNWMTLSQKLCSCLLSNVAMAMGAQLIGKFEAKGMGIQWRDLLSPVNVDDDFCFGQVLGMLLLDSVLYGLVTWYMEAVFPGQFGVPQPWYFFIMPSYWCGKPRAVAGKEEEDSDPEKALRNEYFEAEPEDLVAGIKIKHLSKVFRVGNKDRAAVRDLNLNLYEGQITVLLGHNGAGKTTTLSMLTGLFPPTSGRAYISGYEISQDMVQIRKSLGLCPQHDILFDNLTVAEHLYFYAQLKGLSRQKCPEEVKQMLHIIGLEDKWNSRSRFLSGGMRRKLSIGIALIAGSKVLILDEPTSGMDAISRRAIWDLLQRQKSDRTIVLTTHFMDEADLLGDRIAIMAKGELQCCGSSLFLKQKYGAGYHMTLVKEPHCNPEDISQLVHHHVPNATLESSAGAELSFILPRESTHRFEGLFAKLEKKQKELGIASFGASITTMEEVFLRVGKLVDSSMDIQAIQLPALQYQHERRASDWAVDSNLCGAMDPSDGIGALIEEERTAVKLNTGLALHCQQFWAMFLKKAAYSWREWKMVAAQVLVPLTCVTLALLAINYSSELFDDPMLRLTLGEYGRTVVPFSVPGTSQLGQQLSEHLKDALQAEGQEPREVLGDLEEFLIFRASVEGGGFNERCLVAASFRDVGERTVVNALFNNQAYHSPATALAVVDNLLFKLLCGPHASIVVSNFPQPRSALQAAKDQFNEGRKGFDIALNLLFAMAFLASTFSILAVSERAVQAKHVQFVSGVHVASFWLSALLWDLISFLIPSLLLLVVFKAFDVRAFTRDGHMADTLLLLLLYGWAIIPLMYLMNFFFLGAATAYTRLTIFNILSGIATFLMVTIMRIPAVKLEELSKTLDHVFLVLPNHCLGMAVSSFYENYETRRYCTSSEVAAHYCKKYNIQYQENFYAWSAPGVGRFVASMAASGCAYLILLFLIETNLLQRLRGILCALRRRRTLTELYTRMPVLPEDQDVADERTRILAPSPDSLLHTPLIIKELSKVYEQRVPLLAVDRLSLAVQKGECFGLLGFNGAGKTTTFKMLTGEESLTSGDAFVGGHRISSDVGKVRQRIGYCPQFDALLDHMTGREMLVMYARLRGIPERHIGACVENTLRGLLLEPHANKLVRTYSGGNKRKLSTGIALIGEPAVIFLDEPSTGMDPVARRLLWDTVARARESGKAIIITSHSMEECEALCTRLAIMVQGQFKCLGSPQHLKSKFGSGYSLRAKVQSEGQQEALEEFKAFVDLTFPGSVLEDEHQGMVHYHLPGRDLSWAKVFGILEKAKEKYGVDDYSVSQISLEQVFLSFAHLQPPTAEEGR