ABCD3_HUMAN
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 03-AUG-2022, entry version 216.
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 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 -!- 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";
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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; 227.
DR IntAct; P28288; 89.
DR MINT; P28288; -.
DR STRING; 9606.ENSP00000359233; -.
DR TCDB; 3.A.1.203.1; the atp-binding cassette (abc) superfamily.
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; P28288; -.
DR PeptideAtlas; P28288; -.
DR PRIDE; P28288; -.
DR ProteomicsDB; 54454; -. [P28288-1]
DR ProteomicsDB; 54455; -. [P28288-2]
DR ProteomicsDB; 54456; -. [P28288-3]
DR Antibodypedia; 33667; 219 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 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; FRYGLVH; -.
DR OrthoDB; 309052at2759; -.
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; 23 hits in 1085 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 212 other tissues.
DR ExpressionAtlas; P28288; baseline and differential.
DR Genevisible; P28288; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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:UniProtKB.
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 Gene3D; 1.20.1560.10; -; 1.
DR Gene3D; 3.40.50.300; -; 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 Pfam; PF06472; ABC_membrane_2; 1.
DR Pfam; PF00005; ABC_tran; 1.
DR SMART; SM00382; AAA; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR SUPFAM; SSF90123; SSF90123; 1.
DR TIGRFAMs; TIGR00954; 3a01203; 1.
DR PROSITE; PS50929; ABC_TM1F; 1.
DR PROSITE; PS00211; ABC_TRANSPORTER_1; 1.
DR PROSITE; PS50893; ABC_TRANSPORTER_2; 1.
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.
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
