ID ABCD3_HUMAN Reviewed; 659 AA. AC P28288; D3DT46; Q15271; Q6NUN5; Q96DA3; Q9H529; DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot. DT 01-DEC-1992, sequence version 1. DT 27-MAR-2024, entry version 225. DE RecName: Full=ATP-binding cassette sub-family D member 3; DE EC=3.1.2.- {ECO:0000269|PubMed:29397936, ECO:0000305|PubMed:24333844}; DE EC=7.6.2.- {ECO:0000269|PubMed:11248239, ECO:0000269|PubMed:29397936, ECO:0000305|PubMed:24333844}; DE AltName: Full=70 kDa peroxisomal membrane protein {ECO:0000303|PubMed:1301993}; DE Short=PMP70; GN Name=ABCD3 {ECO:0000312|HGNC:HGNC:67}; GN Synonyms=PMP70, PXMP1 {ECO:0000303|PubMed:9521874}; 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 VARIANT ASP-17. RC TISSUE=Liver; RX PubMed=1301993; DOI=10.1038/ng0492-16; RA Gaertner J., Moser H., Valle D.; RT "Mutations in the 70K peroxisomal membrane protein gene in Zellweger RT syndrome."; RL Nat. Genet. 1:16-23(1992). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Liver; RX PubMed=1536884; DOI=10.1016/0167-4781(92)90510-7; RA Kamijo K., Kamijo T., Ueno I., Osumi T., Hashimoto T.; RT "Nucleotide sequence of the human 70 kDa peroxisomal membrane protein: a RT member of ATP-binding cassette transporters."; RL Biochim. Biophys. Acta 1129:323-327(1992). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=9521874; DOI=10.1006/geno.1997.5177; RA Gaertner J., Jimenez-Sanchez G., Roerig P., Valle D.; RT "Genomic organization of the 70-kDa peroxisomal membrane protein gene RT (PXMP1)."; RL Genomics 48:203-208(1998). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). 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 2 AND 3). 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 CAUTION. RX PubMed=9539740; DOI=10.1073/pnas.95.8.4350; RA Tamura S., Okumoto K., Toyama R., Shimozawa N., Tsukamoto T., Suzuki Y., RA Osumi T., Kondo N., Fujiki Y.; RT "Human PEX1 cloned by functional complementation on a CHO cell mutant is RT responsible for peroxisome-deficient Zellweger syndrome of complementation RT group I."; RL Proc. Natl. Acad. Sci. U.S.A. 95:4350-4355(1998). RN [9] RP SUBUNIT, AND INTERACTION WITH ABCD1 AND ABCD2. RX PubMed=10551832; DOI=10.1074/jbc.274.46.32738; RA Liu L.X., Janvier K., Berteaux-Lecellier V., Cartier N., Benarous R., RA Aubourg P.; RT "Homo- and heterodimerization of peroxisomal ATP-binding cassette half- RT transporters."; RL J. Biol. Chem. 274:32738-32743(1999). RN [10] RP SUBUNIT, AND INTERACTION WITH ABCD1. RX PubMed=17609205; DOI=10.1074/jbc.m702122200; RA Hillebrand M., Verrier S.E., Ohlenbusch A., Schaefer A., Soeling H.D., RA Wouters F.S., Gaertner J.; RT "Live cell FRET microscopy: homo- and heterodimerization of two human RT peroxisomal ABC transporters, the adrenoleukodystrophy protein (ALDP, RT ABCD1) and PMP70 (ABCD3)."; RL J. Biol. Chem. 282:26997-27005(2007). RN [11] RP INTERACTION WITH PEX19. RC TISSUE=Brain; RX PubMed=10777694; DOI=10.1006/bbrc.2000.2572; RA Gloeckner C.J., Mayerhofer P.U., Landgraf P., Muntau A.C., Holzinger A., RA Gerber J.-K., Kammerer S., Adamski J., Roscher A.A.; RT "Human adrenoleukodystrophy protein and related peroxisomal ABC RT transporters interact with the peroxisomal assembly protein PEX19p."; RL Biochem. Biophys. Res. Commun. 271:144-150(2000). RN [12] RP SUBCELLULAR LOCATION, AND INTERACTION WITH PEX19. RX PubMed=10704444; DOI=10.1083/jcb.148.5.931; RA Sacksteder K.A., Jones J.M., South S.T., Li X., Liu Y., Gould S.J.; RT "PEX19 binds multiple peroxisomal membrane proteins, is predominantly RT cytoplasmic, and is required for peroxisome membrane synthesis."; RL J. Cell Biol. 148:931-944(2000). RN [13] RP FUNCTION, MUTAGENESIS OF GLY-478 AND SER-572, BIOPHYSICOCHEMICAL RP PROPERTIES, CATALYTIC ACTIVITY, AND ATP-BINDING. RX PubMed=11248239; DOI=10.1016/s0014-5793(01)02235-9; RA Roerig P., Mayerhofer P., Holzinger A., Gaertner J.; RT "Characterization and functional analysis of the nucleotide binding fold in RT human peroxisomal ATP binding cassette transporters."; RL FEBS Lett. 492:66-72(2001). RN [14] RP INTERACTION WITH PEX19, REGION, AND SUBCELLULAR LOCATION. RX PubMed=16344115; DOI=10.1016/j.bbamcr.2005.10.006; RA Kashiwayama Y., Asahina K., Shibata H., Morita M., Muntau A.C., RA Roscher A.A., Wanders R.J., Shimozawa N., Sakaguchi M., Kato H., RA Imanaka T.; RT "Role of Pex19p in the targeting of PMP70 to peroxisome."; RL Biochim. Biophys. Acta 1746:116-128(2005). RN [15] RP SUBCELLULAR LOCATION, INTERACTION WITH PEX19, AND MUTAGENESIS OF RP 21-LEU--LEU-23; 70-ILE-LEU-71 AND 307-ILE-LEU-308. RX PubMed=17761678; DOI=10.1074/jbc.m703369200; RA Kashiwayama Y., Asahina K., Morita M., Imanaka T.; RT "Hydrophobic regions adjacent to transmembrane domains 1 and 5 are RT important for the targeting of the 70-kDa peroxisomal membrane protein."; RL J. Biol. Chem. 282:33831-33844(2007). RN [16] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-260 AND LYS-399, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [17] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [18] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [19] RP FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, AND SUBCELLULAR RP LOCATION. RX PubMed=24333844; DOI=10.1016/j.bbalip.2013.12.001; RA van Roermund C.W., Ijlst L., Wagemans T., Wanders R.J., Waterham H.R.; RT "A role for the human peroxisomal half-transporter ABCD3 in the oxidation RT of dicarboxylic acids."; RL Biochim. Biophys. Acta 1841:563-568(2014). RN [20] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [21] RP FUNCTION, AND INVOLVEMENT IN CBAS5. RX PubMed=25168382; DOI=10.1093/hmg/ddu448; RA Ferdinandusse S., Jimenez-Sanchez G., Koster J., Denis S., RA Van Roermund C.W., Silva-Zolezzi I., Moser A.B., Visser W.F., Gulluoglu M., RA Durmaz O., Demirkol M., Waterham H.R., Goekcay G., Wanders R.J., Valle D.; RT "A novel bile acid biosynthesis defect due to a deficiency of peroxisomal RT ABCD3."; RL Hum. Mol. Genet. 24:361-370(2015). RN [22] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [23] RP UBIQUITINATION. RX PubMed=27597759; DOI=10.1083/jcb.201511034; RA Sargent G., van Zutphen T., Shatseva T., Zhang L., Di Giovanni V., RA Bandsma R., Kim P.K.; RT "PEX2 is the E3 ubiquitin ligase required for pexophagy during RT starvation."; RL J. Cell Biol. 214:677-690(2016). RN [24] RP FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION. RX PubMed=29397936; DOI=10.1016/j.bbrc.2018.01.153; RA Okamoto T., Kawaguchi K., Watanabe S., Agustina R., Ikejima T., Ikeda K., RA Nakano M., Morita M., Imanaka T.; RT "Characterization of human ATP-binding cassette protein subfamily D RT reconstituted into proteoliposomes."; RL Biochem. Biophys. Res. Commun. 496:1122-1127(2018). CC -!- FUNCTION: Broad substrate specificity ATP-dependent transporter of the CC ATP-binding cassette (ABC) family that catalyzes the transport of long- CC chain fatty acids (LCFA)-CoA, dicarboxylic acids-CoA, long-branched- CC chain fatty acids-CoA and bile acids from the cytosol to the peroxisome CC lumen for beta-oxydation (PubMed:11248239, PubMed:25168382, CC PubMed:24333844, PubMed:29397936). Has fatty acyl-CoA thioesterase and CC ATPase activities (PubMed:29397936). Probably hydrolyzes fatty acyl- CC CoAs into free fatty acids prior to their ATP-dependent transport into CC peroxisomes (By similarity). Thus, play a role in regulation of LCFAs CC and energy metabolism namely, in the degradation and biosynthesis of CC fatty acids by beta-oxidation (PubMed:25944712, PubMed:24333844). CC {ECO:0000250|UniProtKB:P33897, ECO:0000269|PubMed:11248239, CC ECO:0000269|PubMed:24333844, ECO:0000269|PubMed:25168382, CC ECO:0000269|PubMed:25944712, ECO:0000269|PubMed:29397936}. CC -!- CATALYTIC ACTIVITY: CC Reaction=a very long-chain fatty acyl-CoA + H2O = a very long-chain CC fatty acid + CoA + H(+); Xref=Rhea:RHEA:67072, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57287, ChEBI:CHEBI:58950, CC ChEBI:CHEBI:138261; Evidence={ECO:0000269|PubMed:29397936}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67073; CC Evidence={ECO:0000305|PubMed:29397936}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a very long-chain fatty acid(in) + ATP + H2O = a very long- CC chain fatty acid(out) + ADP + H(+) + phosphate; Xref=Rhea:RHEA:67080, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58950, ChEBI:CHEBI:456216; CC Evidence={ECO:0000269|PubMed:29397936}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67081; CC Evidence={ECO:0000305|PubMed:29397936}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a long-chain fatty acyl-CoA + H2O = a long-chain fatty acid + CC CoA + H(+); Xref=Rhea:RHEA:67680, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57287, ChEBI:CHEBI:57560, CC ChEBI:CHEBI:83139; Evidence={ECO:0000305|PubMed:24333844, CC ECO:0000305|PubMed:29397936}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67681; CC Evidence={ECO:0000305|PubMed:24333844}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a long-chain fatty acid(in) + ATP + H2O = a long-chain fatty CC acid(out) + ADP + H(+) + phosphate; Xref=Rhea:RHEA:67684, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:43474, ChEBI:CHEBI:57560, ChEBI:CHEBI:456216; CC Evidence={ECO:0000305|PubMed:24333844, ECO:0000305|PubMed:29397936}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67685; CC Evidence={ECO:0000305|PubMed:24333844}; CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + pristanoyl-CoA = 2,6,10,14-tetramethylpentadecanoate + CC CoA + H(+); Xref=Rhea:RHEA:40415, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57287, ChEBI:CHEBI:77250, CC ChEBI:CHEBI:77268; Evidence={ECO:0000305|PubMed:24333844, CC ECO:0000305|PubMed:29397936}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40416; CC Evidence={ECO:0000305|PubMed:24333844}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2,6,10,14-tetramethylpentadecanoate(in) + ATP + H2O = CC 2,6,10,14-tetramethylpentadecanoate(out) + ADP + H(+) + phosphate; CC Xref=Rhea:RHEA:67688, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:77268, CC ChEBI:CHEBI:456216; Evidence={ECO:0000305|PubMed:24333844, CC ECO:0000305|PubMed:29397936}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67689; CC Evidence={ECO:0000305|PubMed:24333844}; CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + hexadecanedioyl-CoA = CoA + H(+) + hexadecanedioate; CC Xref=Rhea:RHEA:67696, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:57287, ChEBI:CHEBI:76276, ChEBI:CHEBI:77085; CC Evidence={ECO:0000305|PubMed:24333844, ECO:0000305|PubMed:29397936}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67697; CC Evidence={ECO:0000305|PubMed:24333844}; CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + H2O + hexadecanedioate(in) = ADP + H(+) + CC hexadecanedioate(out) + phosphate; Xref=Rhea:RHEA:67692, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:43474, ChEBI:CHEBI:76276, ChEBI:CHEBI:456216; CC Evidence={ECO:0000305|PubMed:24333844, ECO:0000305|PubMed:29397936}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoyl-CoA + H2O = CC (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + CoA + H(+); CC Xref=Rhea:RHEA:67712, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:57287, ChEBI:CHEBI:58562, ChEBI:CHEBI:73862; CC Evidence={ECO:0000305|PubMed:24333844, ECO:0000305|PubMed:29397936}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67713; CC Evidence={ECO:0000305|PubMed:24333844}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate(in) + ATP + H2O = CC (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate(out) + ADP + H(+) + phosphate; CC Xref=Rhea:RHEA:67708, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:58562, CC ChEBI:CHEBI:456216; Evidence={ECO:0000305|PubMed:24333844, CC ECO:0000305|PubMed:29397936}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67709; CC Evidence={ECO:0000305|PubMed:24333844}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoyl-CoA + H2O = CC (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + CoA + H(+); CC Xref=Rhea:RHEA:67700, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:57287, ChEBI:CHEBI:74298, ChEBI:CHEBI:77016; CC Evidence={ECO:0000305|PubMed:24333844, ECO:0000305|PubMed:29397936}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67701; CC Evidence={ECO:0000305|PubMed:24333844}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate(in) + ATP + H2O = CC (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate(out) + ADP + H(+) + CC phosphate; Xref=Rhea:RHEA:67704, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, CC ChEBI:CHEBI:77016, ChEBI:CHEBI:456216; CC Evidence={ECO:0000305|PubMed:24333844, ECO:0000305|PubMed:29397936}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=8.2 uM for ATP {ECO:0000269|PubMed:11248239}; CC -!- SUBUNIT: Homodimers (PubMed:17609205). Can form heterodimers with ABCD1 CC and ABCD2 (PubMed:10777694, PubMed:10551832, PubMed:17609205). CC Dimerization is necessary to form an active transporter CC (PubMed:17609205). Interacts with PEX19; mediates the targeting of CC ABCD3 to peroxisomes (PubMed:10704444, PubMed:16344115, CC PubMed:17761678). {ECO:0000269|PubMed:10551832, CC ECO:0000269|PubMed:10704444, ECO:0000269|PubMed:10777694, CC ECO:0000269|PubMed:16344115, ECO:0000269|PubMed:17609205, CC ECO:0000269|PubMed:17761678}. CC -!- INTERACTION: CC P28288; P33897: ABCD1; NbExp=2; IntAct=EBI-80992, EBI-81045; CC P28288; P40855: PEX19; NbExp=4; IntAct=EBI-80992, EBI-594747; CC P28288-2; P09471: GNAO1; NbExp=3; IntAct=EBI-25889034, EBI-715087; CC P28288-2; Q6P4D5-2: PABIR3; NbExp=3; IntAct=EBI-25889034, EBI-9091052; CC P28288-2; P53999: SUB1; NbExp=3; IntAct=EBI-25889034, EBI-998260; CC -!- SUBCELLULAR LOCATION: Peroxisome membrane {ECO:0000269|PubMed:10704444, CC ECO:0000269|PubMed:16344115, ECO:0000269|PubMed:17761678, CC ECO:0000269|PubMed:24333844, ECO:0000269|PubMed:29397936}; Multi-pass CC membrane protein {ECO:0000255}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=P28288-1; Sequence=Displayed; CC Name=2; CC IsoId=P28288-2; Sequence=VSP_031189; CC Name=3; CC IsoId=P28288-3; Sequence=VSP_031187, VSP_031188; CC -!- PTM: Ubiquitinated by PEX2 during pexophagy in response to starvation, CC leading to its degradation. {ECO:0000269|PubMed:27597759}. CC -!- DISEASE: Congenital bile acid synthesis defect 5 (CBAS5) [MIM:616278]: CC An autosomal recessive disorder characterized by hepatosplenomegaly, CC hepatic fibrosis, progressive liver failure, and accumulation of CC peroxisomal C27-bile acid intermediates in plasma. CC {ECO:0000269|PubMed:25168382}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the ABC transporter superfamily. ABCD family. CC Peroxisomal fatty acyl CoA transporter (TC 3.A.1.203) subfamily. CC {ECO:0000305}. CC -!- CAUTION: Mutation in ABCD3 have been found in two individuals affected CC by Zellweger syndrome (PubMed:1301993). Later studies, however, showed CC unambiguously that a PEX1 defect was the underlying cause of the defect CC in peroxisome biogenesis in these patients (PubMed:9539740). CC {ECO:0000269|PubMed:1301993, ECO:0000269|PubMed:9539740}. 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; M81182; AAA60128.1; -; mRNA. DR EMBL; X58528; CAA41416.1; -; mRNA. DR EMBL; X83467; CAA58470.1; -; Genomic_DNA. DR EMBL; X83468; CAA58470.1; JOINED; Genomic_DNA. DR EMBL; X83469; CAA58470.1; JOINED; Genomic_DNA. DR EMBL; X83470; CAA58470.1; JOINED; Genomic_DNA. DR EMBL; X83471; CAA58470.1; JOINED; Genomic_DNA. DR EMBL; X83472; CAA58470.1; JOINED; Genomic_DNA. DR EMBL; X83473; CAA58470.1; JOINED; Genomic_DNA. DR EMBL; X83474; CAA58470.1; JOINED; Genomic_DNA. DR EMBL; X83475; CAA58470.1; JOINED; Genomic_DNA. DR EMBL; X83476; CAA58470.1; JOINED; Genomic_DNA. DR EMBL; X83477; CAA58470.1; JOINED; Genomic_DNA. DR EMBL; X83478; CAA58470.1; JOINED; Genomic_DNA. DR EMBL; X83479; CAA58470.1; JOINED; Genomic_DNA. DR EMBL; X83480; CAA58470.1; JOINED; Genomic_DNA. DR EMBL; X83481; CAA58470.1; JOINED; Genomic_DNA. DR EMBL; X83482; CAA58470.1; JOINED; Genomic_DNA. DR EMBL; X83483; CAA58470.1; JOINED; Genomic_DNA. DR EMBL; X83484; CAA58470.1; JOINED; Genomic_DNA. DR EMBL; X83485; CAA58470.1; JOINED; Genomic_DNA. DR EMBL; X83486; CAA58470.1; JOINED; Genomic_DNA. DR EMBL; X83487; CAA58470.1; JOINED; Genomic_DNA. DR EMBL; X83488; CAA58470.1; JOINED; Genomic_DNA. DR EMBL; X83489; CAA58470.1; JOINED; Genomic_DNA. DR EMBL; BT006644; AAP35290.1; -; mRNA. DR EMBL; AC093117; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC118469; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL138758; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471097; EAW73049.1; -; Genomic_DNA. DR EMBL; CH471097; EAW73050.1; -; Genomic_DNA. DR EMBL; CH471097; EAW73047.1; -; Genomic_DNA. DR EMBL; CH471097; EAW73048.1; -; Genomic_DNA. DR EMBL; BC009712; AAH09712.1; -; mRNA. DR EMBL; BC068509; AAH68509.1; -; mRNA. DR CCDS; CCDS44175.1; -. [P28288-3] DR CCDS; CCDS749.1; -. [P28288-1] DR PIR; S20313; S20313. DR RefSeq; NP_001116146.1; NM_001122674.1. [P28288-3] DR RefSeq; NP_002849.1; NM_002858.3. [P28288-1] DR AlphaFoldDB; P28288; -. DR SMR; P28288; -. DR BioGRID; 111783; 263. DR IntAct; P28288; 92. DR MINT; P28288; -. DR STRING; 9606.ENSP00000359233; -. DR TCDB; 3.A.1.203.1; the atp-binding cassette (abc) superfamily. DR GlyCosmos; P28288; 3 sites, No reported glycans. DR GlyGen; P28288; 4 sites, 1 O-linked glycan (1 site). DR iPTMnet; P28288; -. DR MetOSite; P28288; -. DR PhosphoSitePlus; P28288; -. DR SwissPalm; P28288; -. DR BioMuta; ABCD3; -. DR DMDM; 130358; -. DR CPTAC; CPTAC-157; -. DR EPD; P28288; -. DR jPOST; P28288; -. DR MassIVE; P28288; -. DR MaxQB; P28288; -. DR PaxDb; 9606-ENSP00000359233; -. DR PeptideAtlas; P28288; -. DR ProteomicsDB; 54454; -. [P28288-1] DR ProteomicsDB; 54455; -. [P28288-2] DR ProteomicsDB; 54456; -. [P28288-3] DR Pumba; P28288; -. DR Antibodypedia; 33667; 245 antibodies from 35 providers. DR DNASU; 5825; -. DR Ensembl; ENST00000315713.5; ENSP00000326880.5; ENSG00000117528.14. [P28288-3] DR Ensembl; ENST00000370214.9; ENSP00000359233.4; ENSG00000117528.14. [P28288-1] DR GeneID; 5825; -. DR KEGG; hsa:5825; -. DR MANE-Select; ENST00000370214.9; ENSP00000359233.4; NM_002858.4; NP_002849.1. DR UCSC; uc001dqm.5; human. [P28288-1] DR AGR; HGNC:67; -. DR CTD; 5825; -. DR DisGeNET; 5825; -. DR GeneCards; ABCD3; -. DR HGNC; HGNC:67; ABCD3. DR HPA; ENSG00000117528; Tissue enhanced (liver). DR MalaCards; ABCD3; -. DR MIM; 170995; gene. DR MIM; 616278; phenotype. DR neXtProt; NX_P28288; -. DR OpenTargets; ENSG00000117528; -. DR PharmGKB; PA24402; -. DR VEuPathDB; HostDB:ENSG00000117528; -. DR eggNOG; KOG0060; Eukaryota. DR GeneTree; ENSGT00950000182955; -. DR HOGENOM; CLU_007587_5_1_1; -. DR InParanoid; P28288; -. DR OMA; IHDMYLD; -. DR OrthoDB; 7698at2759; -. DR PhylomeDB; P28288; -. DR TreeFam; TF105205; -. DR BRENDA; 7.6.2.4; 2681. DR PathwayCommons; P28288; -. DR Reactome; R-HSA-1369062; ABC transporters in lipid homeostasis. DR Reactome; R-HSA-8980692; RHOA GTPase cycle. DR Reactome; R-HSA-9013106; RHOC GTPase cycle. DR Reactome; R-HSA-9603798; Class I peroxisomal membrane protein import. DR SignaLink; P28288; -. DR BioGRID-ORCS; 5825; 24 hits in 1166 CRISPR screens. DR ChiTaRS; ABCD3; human. DR GeneWiki; ABCD3; -. DR GenomeRNAi; 5825; -. DR Pharos; P28288; Tbio. DR PRO; PR:P28288; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; P28288; Protein. DR Bgee; ENSG00000117528; Expressed in secondary oocyte and 214 other cell types or tissues. DR ExpressionAtlas; P28288; baseline and differential. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl. DR GO; GO:0005782; C:peroxisomal matrix; IDA:UniProtKB. DR GO; GO:0005778; C:peroxisomal membrane; HDA:UniProtKB. DR GO; GO:0005777; C:peroxisome; IDA:HPA. DR GO; GO:0140359; F:ABC-type transporter activity; IEA:InterPro. DR GO; GO:0047617; F:acyl-CoA hydrolase activity; IDA:UniProtKB. DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB. DR GO; GO:0016887; F:ATP hydrolysis activity; IDA:UniProtKB. DR GO; GO:0042626; F:ATPase-coupled transmembrane transporter activity; IDA:UniProtKB. DR GO; GO:0005324; F:long-chain fatty acid transporter activity; IMP:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB. DR GO; GO:0043621; F:protein self-association; IEA:Ensembl. DR GO; GO:0015721; P:bile acid and bile salt transport; ISS:UniProtKB. DR GO; GO:0006699; P:bile acid biosynthetic process; ISS:UniProtKB. DR GO; GO:0006635; P:fatty acid beta-oxidation; IDA:UniProtKB. DR GO; GO:0006633; P:fatty acid biosynthetic process; IMP:UniProtKB. DR GO; GO:0015910; P:long-chain fatty acid import into peroxisome; IMP:UniProtKB. DR GO; GO:0007031; P:peroxisome organization; IDA:UniProtKB. DR GO; GO:1903512; P:phytanic acid metabolic process; ISS:UniProtKB. DR GO; GO:0014070; P:response to organic cyclic compound; IEA:Ensembl. DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl. DR GO; GO:0042760; P:very long-chain fatty acid catabolic process; IGI:UniProtKB. DR GO; GO:0000038; P:very long-chain fatty acid metabolic process; IDA:UniProtKB. DR CDD; cd03223; ABCD_peroxisomal_ALDP; 1. DR Gene3D; 1.20.1560.10; ABC transporter type 1, transmembrane domain; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1. DR InterPro; IPR003593; AAA+_ATPase. DR InterPro; IPR011527; ABC1_TM_dom. DR InterPro; IPR036640; ABC1_TM_sf. DR InterPro; IPR003439; ABC_transporter-like_ATP-bd. DR InterPro; IPR017871; ABC_transporter-like_CS. DR InterPro; IPR005283; FA_transporter. DR InterPro; IPR027417; P-loop_NTPase. DR NCBIfam; TIGR00954; 3a01203; 1. DR PANTHER; PTHR11384:SF62; ATP-BINDING CASSETTE SUB-FAMILY D MEMBER 3; 1. DR PANTHER; PTHR11384; ATP-BINDING CASSETTE, SUB-FAMILY D MEMBER; 1. DR Pfam; PF06472; ABC_membrane_2; 1. DR Pfam; PF00005; ABC_tran; 1. DR SMART; SM00382; AAA; 1. DR SUPFAM; SSF90123; ABC transporter transmembrane region; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. DR PROSITE; PS50929; ABC_TM1F; 1. DR PROSITE; PS00211; ABC_TRANSPORTER_1; 1. DR PROSITE; PS50893; ABC_TRANSPORTER_2; 1. DR Genevisible; P28288; HS. PE 1: Evidence at protein level; KW Acetylation; Alternative splicing; ATP-binding; Glycoprotein; Hydrolase; KW Membrane; Nucleotide-binding; Peroxisome; Phosphoprotein; KW Reference proteome; Translocase; Transmembrane; Transmembrane helix; KW Transport; Ubl conjugation. FT CHAIN 1..659 FT /note="ATP-binding cassette sub-family D member 3" FT /id="PRO_0000093309" FT TRANSMEM 84..104 FT /note="Helical" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441" FT TRANSMEM 126..146 FT /note="Helical" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441" FT TRANSMEM 224..244 FT /note="Helical" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441" FT TRANSMEM 313..333 FT /note="Helical" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441" FT DOMAIN 85..372 FT /note="ABC transmembrane type-1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441" FT DOMAIN 440..659 FT /note="ABC transporter" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434" FT REGION 1..61 FT /note="Interaction with PEX19" FT /evidence="ECO:0000269|PubMed:16344115, FT ECO:0000269|PubMed:17761678" FT BINDING 473..480 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434" FT MOD_RES 61 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P55096" FT MOD_RES 260 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 399 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 533 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P55096" FT MOD_RES 659 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P55096" FT CARBOHYD 12 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 106 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 206 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT VAR_SEQ 229..236 FT /note="GPASMMAY -> VLGKILWH (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.4" FT /id="VSP_031187" FT VAR_SEQ 237..659 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.4" FT /id="VSP_031188" FT VAR_SEQ 277..386 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_031189" FT VARIANT 17 FT /note="G -> D (in dbSNP:rs121917999)" FT /evidence="ECO:0000269|PubMed:1301993" FT /id="VAR_000091" FT MUTAGEN 21..23 FT /note="LLL->QQQ: Abolishes localization to peroxisomes." FT /evidence="ECO:0000269|PubMed:17761678" FT MUTAGEN 70..71 FT /note="IL->NQ: Abolishes localization to peroxisomes." FT /evidence="ECO:0000269|PubMed:17761678" FT MUTAGEN 307..308 FT /note="IL->AA: Abolishes localization to peroxisomes." FT /evidence="ECO:0000269|PubMed:17761678" FT MUTAGEN 478 FT /note="G->R: Decreased ATP-binding affinity." FT /evidence="ECO:0000269|PubMed:11248239" FT MUTAGEN 572 FT /note="S->I: Decreased ATPase activity." FT /evidence="ECO:0000269|PubMed:11248239" FT CONFLICT 175 FT /note="M -> K (in Ref. 2; CAA41416)" FT /evidence="ECO:0000305" FT CONFLICT 191..192 FT /note="QD -> LV (in Ref. 3; CAA58470)" FT /evidence="ECO:0000305" FT CONFLICT 336 FT /note="P -> L (in Ref. 3; CAA58470)" FT /evidence="ECO:0000305" FT CONFLICT 503 FT /note="G -> R (in Ref. 2; CAA41416)" FT /evidence="ECO:0000305" FT CONFLICT 542 FT /note="L -> Q (in Ref. 2; CAA41416)" FT /evidence="ECO:0000305" FT CONFLICT 616..634 FT /note="VGITLFTVSHRKSLWKHHE -> GWHHSLHLCLIGNLFGNIMR (in Ref. FT 3; CAA58470)" FT /evidence="ECO:0000305" SQ SEQUENCE 659 AA; 75476 MW; 2CA976FEB6EB6217 CRC64; MAAFSKYLTA RNSSLAGAAF LLLCLLHKRR RALGLHGKKS GKPPLQNNEK EGKKERAVVD KVFFSRLIQI LKIMVPRTFC KETGYLVLIA VMLVSRTYCD VWMIQNGTLI ESGIIGRSRK DFKRYLLNFI AAMPLISLVN NFLKYGLNEL KLCFRVRLTK YLYEEYLQAF TYYKMGNLDN RIANPDQLLT QDVEKFCNSV VDLYSNLSKP FLDIVLYIFK LTSAIGAQGP ASMMAYLVVS GLFLTRLRRP IGKMTITEQK YEGEYRYVNS RLITNSEEIA FYNGNKREKQ TVHSVFRKLV EHLHNFILFR FSMGFIDSII AKYLATVVGY LVVSRPFLDL SHPRHLKSTH SELLEDYYQS GRMLLRMSQA LGRIVLAGRE MTRLAGFTAR ITELMQVLKD LNHGKYERTM VSQQEKGIEG VQVIPLIPGA GEIIIADNII KFDHVPLATP NGDVLIRDLN FEVRSGANVL ICGPNGCGKS SLFRVLGELW PLFGGRLTKP ERGKLFYVPQ RPYMTLGTLR DQVIYPDGRE DQKRKGISDL VLKEYLDNVQ LGHILEREGG WDSVQDWMDV LSGGEKQRMA MARLFYHKPQ FAILDECTSA VSVDVEGYIY SHCRKVGITL FTVSHRKSLW KHHEYYLHMD GRGNYEFKQI TEDTVEFGS //