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Showing Protein Phospholipid-transporting ATPase ABCA3 (HMDBP13945)

IdentificationBiological propertiesGene propertiesProtein propertiesExternal linksReferencesXMLShow 1 metabolite
Identification
HMDB Protein ID HMDBP13945
Secondary Accession Numbers None
Name Phospholipid-transporting ATPase ABCA3
Synonyms
  1. ABC-C transporter
  2. ATP-binding cassette sub-family A member 3
  3. ATP-binding cassette transporter 3
  4. Xenobiotic-transporting ATPase ABCA3
  5. ATP-binding cassette 3
Gene Name ABCA3
Protein Type Unknown
Biological Properties
General Function Not Available
Specific 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 (PubMed:16959783, PubMed:17574245, PubMed:28887056, PubMed:31473345, PubMed:27177387). Transports preferentially phosphatidylcholine containing short acyl chains (PubMed:27177387). 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 (PubMed:26903515, PubMed:25817392, PubMed:27177387).
Pathways
  • ABC transporters
Reactions Not Available
GO Classification
Biological Process
positive regulation of protein homooligomerization
phosphatidylglycerol metabolic process
xenobiotic transport
regulation of lipid biosynthetic process
drug transmembrane transport
response to drug
cellular protein metabolic process
surfactant homeostasis
response to glucocorticoid stimulus
phosphatidylcholine metabolic process
lipid transport
positive regulation of cholesterol efflux
regulation of phosphatidylcholine metabolic process
lung development
phospholipid homeostasis
drug export
organelle assembly
phospholipid transport
positive regulation of phospholipid efflux
positive regulation of phospholipid transport
Cellular Component
lamellar body
plasma membrane
cytoplasmic vesicle membrane
multivesicular body membrane
extracellular space
late endosome
lysosomal membrane
intracellular membrane-bounded organelle
integral to membrane
alveolar lamellar body
alveolar lamellar body membrane
lamellar body membrane
Molecular Function
lipid transporter activity
ATP binding
ATPase activity
ABC-type xenobiotic transporter activity
ATPase-coupled transmembrane transporter activity
phosphatidylcholine flippase activity
phosphatidylcholine transfer activity
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 1704
Molecular Weight 191360.235
Theoretical pI 7.617
Pfam Domain Function
Signals Not Available
Transmembrane Regions
  • 22-42;261-283;307-327;344-364;373-393;405-425;447-467;925-945;1100-1120;1144-1164;1183-1203;1213-1233;1245-1265;1306-1326;
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID Q99758
UniProtKB/Swiss-Prot Entry Name ABCA3_HUMAN
PDB IDs Not Available
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
  1. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  2. Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N, Szabo S, Buckhaults P, Farrell C, Meeh P, Markowitz SD, Willis J, Dawson D, Willson JK, Gazdar AF, Hartigan J, Wu L, Liu C, Parmigiani G, Park BH, Bachman KE, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE: The consensus coding sequences of human breast and colorectal cancers. Science. 2006 Oct 13;314(5797):268-74. Epub 2006 Sep 7. [PubMed:16959974 ]
  3. Martin J, Han C, Gordon LA, Terry A, Prabhakar S, She X, Xie G, Hellsten U, Chan YM, Altherr M, Couronne O, Aerts A, Bajorek E, Black S, Blumer H, Branscomb E, Brown NC, Bruno WJ, Buckingham JM, Callen DF, Campbell CS, Campbell ML, Campbell EW, Caoile C, Challacombe JF, Chasteen LA, Chertkov O, Chi HC, Christensen M, Clark LM, Cohn JD, Denys M, Detter JC, Dickson M, Dimitrijevic-Bussod M, Escobar J, Fawcett JJ, Flowers D, Fotopulos D, Glavina T, Gomez M, Gonzales E, Goodstein D, Goodwin LA, Grady DL, Grigoriev I, Groza M, Hammon N, Hawkins T, Haydu L, Hildebrand CE, Huang W, Israni S, Jett J, Jewett PB, Kadner K, Kimball H, Kobayashi A, Krawczyk MC, Leyba T, Longmire JL, Lopez F, Lou Y, Lowry S, Ludeman T, Manohar CF, Mark GA, McMurray KL, Meincke LJ, Morgan J, Moyzis RK, Mundt MO, Munk AC, Nandkeshwar RD, Pitluck S, Pollard M, Predki P, Parson-Quintana B, Ramirez L, Rash S, Retterer J, Ricke DO, Robinson DL, Rodriguez A, Salamov A, Saunders EH, Scott D, Shough T, Stallings RL, Stalvey M, Sutherland RD, Tapia R, Tesmer JG, Thayer N, Thompson LS, Tice H, Torney DC, Tran-Gyamfi M, Tsai M, Ulanovsky LE, Ustaszewska A, Vo N, White PS, Williams AL, Wills PL, Wu JR, Wu K, Yang J, Dejong P, Bruce D, Doggett NA, Deaven L, Schmutz J, Grimwood J, Richardson P, Rokhsar DS, Eichler EE, Gilna P, Lucas SM, Myers RM, Rubin EM, Pennacchio LA: The sequence and analysis of duplication-rich human chromosome 16. Nature. 2004 Dec 23;432(7020):988-94. [PubMed:15616553 ]
  4. Lundby A, Secher A, Lage K, Nordsborg NB, Dmytriyev A, Lundby C, Olsen JV: Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues. Nat Commun. 2012 Jun 6;3:876. doi: 10.1038/ncomms1871. [PubMed:22673903 ]
  5. Klugbauer N, Hofmann F: Primary structure of a novel ABC transporter with a chromosomal localization on the band encoding the multidrug resistance-associated protein. FEBS Lett. 1996 Aug 5;391(1-2):61-5. doi: 10.1016/0014-5793(96)00700-4. [PubMed:8706931 ]
  6. Connors TD, Van Raay TJ, Petry LR, Klinger KW, Landes GM, Burn TC: The cloning of a human ABC gene (ABC3) mapping to chromosome 16p13.3. Genomics. 1997 Jan 15;39(2):231-4. doi: 10.1006/geno.1996.4500. [PubMed:9027511 ]
  7. Yamano G, Funahashi H, Kawanami O, Zhao LX, Ban N, Uchida Y, Morohoshi T, Ogawa J, Shioda S, Inagaki N: ABCA3 is a lamellar body membrane protein in human lung alveolar type II cells. FEBS Lett. 2001 Nov 16;508(2):221-5. doi: 10.1016/s0014-5793(01)03056-3. [PubMed:11718719 ]
  8. Matsumura Y, Ban N, Ueda K, Inagaki N: Characterization and classification of ATP-binding cassette transporter ABCA3 mutants in fatal surfactant deficiency. J Biol Chem. 2006 Nov 10;281(45):34503-14. doi: 10.1074/jbc.M600071200. Epub 2006 Sep 7. [PubMed:16959783 ]
  9. Matsumura Y, Sakai H, Sasaki M, Ban N, Inagaki N: ABCA3-mediated choline-phospholipids uptake into intracellular vesicles in A549 cells. FEBS Lett. 2007 Jul 10;581(17):3139-44. doi: 10.1016/j.febslet.2007.05.078. Epub 2007 Jun 6. [PubMed:17574245 ]
  10. Engelbrecht S, Kaltenborn E, Griese M, Kern S: The surfactant lipid transporter ABCA3 is N-terminally cleaved inside LAMP3-positive vesicles. FEBS Lett. 2010 Oct 22;584(20):4306-12. doi: 10.1016/j.febslet.2010.09.026. Epub 2010 Sep 21. [PubMed:20863830 ]
  11. Zarbock R, Kaltenborn E, Frixel S, Wittmann T, Liebisch G, Schmitz G, Griese M: ABCA3 protects alveolar epithelial cells against free cholesterol induced cell death. Biochim Biophys Acta. 2015 Jul;1851(7):987-95. doi: 10.1016/j.bbalip.2015.03.004. Epub 2015 Mar 25. [PubMed:25817392 ]
  12. Frixel S, Lotz-Havla AS, Kern S, Kaltenborn E, Wittmann T, Gersting SW, Muntau AC, Zarbock R, Griese M: Homooligomerization of ABCA3 and its functional significance. Int J Mol Med. 2016 Aug;38(2):558-66. doi: 10.3892/ijmm.2016.2650. Epub 2016 Jun 21. [PubMed:27352740 ]
  13. Dohmen LC, Navas A, Vargas DA, Gregory DJ, Kip A, Dorlo TP, Gomez MA: Functional Validation of ABCA3 as a Miltefosine Transporter in Human Macrophages: IMPACT ON INTRACELLULAR SURVIVAL OF LEISHMANIA (VIANNIA) PANAMENSIS. J Biol Chem. 2016 Apr 29;291(18):9638-47. doi: 10.1074/jbc.M115.688168. Epub 2016 Feb 22. [PubMed:26903515 ]
  14. Hofmann N, Galetskiy D, Rauch D, Wittmann T, Marquardt A, Griese M, Zarbock R: Analysis of the Proteolytic Processing of ABCA3: Identification of Cleavage Site and Involved Proteases. PLoS One. 2016 Mar 31;11(3):e0152594. doi: 10.1371/journal.pone.0152594. eCollection 2016. [PubMed:27031696 ]
  15. Li Y, Kinting S, Hoppner S, Forstner ME, Uhl O, Koletzko B, Griese M: Metabolic labelling of choline phospholipids probes ABCA3 transport in lamellar bodies. Biochim Biophys Acta Mol Cell Biol Lipids. 2019 Dec;1864(12):158516. doi: 10.1016/j.bbalip.2019.158516. Epub 2019 Aug 29. [PubMed:31473345 ]
  16. Shulenin S, Nogee LM, Annilo T, Wert SE, Whitsett JA, Dean M: ABCA3 gene mutations in newborns with fatal surfactant deficiency. N Engl J Med. 2004 Mar 25;350(13):1296-303. doi: 10.1056/NEJMoa032178. [PubMed:15044640 ]
  17. Bullard JE, Wert SE, Whitsett JA, Dean M, Nogee LM: ABCA3 mutations associated with pediatric interstitial lung disease. Am J Respir Crit Care Med. 2005 Oct 15;172(8):1026-31. doi: 10.1164/rccm.200503-504OC. Epub 2005 Jun 23. [PubMed:15976379 ]
  18. Jackson T, Wegner DJ, White FV, Hamvas A, Cole FS, Wambach JA: Respiratory failure in a term infant with cis and trans mutations in ABCA3. J Perinatol. 2015 Mar;35(3):231-2. doi: 10.1038/jp.2014.236. [PubMed:25712598 ]
  19. Wittmann T, Schindlbeck U, Hoppner S, Kinting S, Frixel S, Kroner C, Liebisch G, Hegermann J, Aslanidis C, Brasch F, Reu S, Lasch P, Zarbock R, Griese M: Tools to explore ABCA3 mutations causing interstitial lung disease. Pediatr Pulmonol. 2016 Dec;51(12):1284-1294. doi: 10.1002/ppul.23471. Epub 2016 May 13. [PubMed:27177387 ]