P28288 (ABCD3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
ATP-binding cassette sub-family D member 3

Alternative name(s):
70 kDa peroxisomal membrane protein
Short name=PMP70

Gene names

Name:	ABCD3
Synonyms:	PMP70, PXMP1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	659 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Probable transporter. The nucleotide-binding fold acts as an ATP-binding subunit with ATPase activity. Ref.11
Subunit structure	Can form heterodimers with ABCD1/ALD and ABCD2/ALDR. Dimerization is necessary to form an active transporter. Interacts with PEX19. Ref.8 Ref.9 Ref.10
Subcellular location	Peroxisome membrane; Multi-pass membrane protein Ref.10.
Miscellaneous	Mutation in ABCD3 have been found in two individuals affected by Zellweger syndrome. However, the role of ABCD3 in the causation of Zellweger syndrome remains uncertain.
Sequence similarities	Belongs to the ABC transporter superfamily. ABCD family. Peroxisomal fatty acyl CoA transporter (TC 3.A.1.203) subfamily. [View classification] Contains 1 ABC transmembrane type-1 domain. Contains 1 ABC transporter domain.

Ontologies

Keywords
Biological process	Transport
Cellular component	Membrane Peroxisome
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transmembrane Transmembrane helix
Ligand	ATP-binding Nucleotide-binding
PTM	Acetylation Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	fatty acid beta-oxidation Inferred from genetic interaction PubMed 9425230. Source: UniProtKB peroxisome organization Inferred from direct assay PubMed 9425230. Source: UniProtKB transmembrane transport Traceable author statement. Source: Reactome very long-chain fatty acid catabolic process Inferred from genetic interaction PubMed 9425230. Source: UniProtKB
Cellular_component	cytosol Traceable author statement. Source: Reactome integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW mitochondrial inner membrane Inferred from electronic annotation. Source: Compara peroxisomal matrix Inferred from direct assay PubMed 9765053. Source: UniProtKB peroxisomal membrane Inferred from direct assay PubMed 17609205PubMed 21525035. Source: UniProtKB
Molecular_function	ATP binding Inferred from direct assay Ref.11. Source: UniProtKB ATPase activity Inferred from direct assay Ref.11. Source: UniProtKB ATPase activity, coupled to transmembrane movement of substances Inferred from electronic annotation. Source: InterPro protein homodimerization activity Inferred from direct assay PubMed 17609205. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ABCD1	P33897	2	EBI-80992,EBI-81045
PEX19	P40855	2	EBI-80992,EBI-594747

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P28288-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P28288-2)

The sequence of this isoform differs from the canonical sequence as follows:
     277-386: Missing.

Note: No experimental confirmation available.

Isoform 3 (identifier: P28288-3)

The sequence of this isoform differs from the canonical sequence as follows:
     229-236: GPASMMAY → VLGKILWH
     237-659: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 659	658	ATP-binding cassette sub-family D member 3		PRO_0000093309
Regions
	Transmembrane	84 – 104	21	Helical; Potential
	Transmembrane	126 – 146	21	Helical; Potential
	Transmembrane	224 – 244	21	Helical; Potential
	Transmembrane	313 – 333	21	Helical; Potential
	Domain	85 – 372	288	ABC transmembrane type-1
	Domain	440 – 659	220	ABC transporter
	Nucleotide binding	473 – 480	8	ATP Potential
	Region	2 – 199	198	Interaction with PEX19
	Region	2 – 124	123	Targeting to peroxisomes
Amino acid modifications
	Modified residue	260	1	N6-acetyllysine Ref.12
	Modified residue	399	1	N6-acetyllysine Ref.12
	Glycosylation	12	1	N-linked (GlcNAc...) Potential
	Glycosylation	106	1	N-linked (GlcNAc...) Potential
	Glycosylation	206	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	229 – 236	8	GPASMMAY → VLGKILWH in isoform 3.		VSP_031187
	Alternative sequence	237 – 659	423	Missing in isoform 3.		VSP_031188
	Alternative sequence	277 – 386	110	Missing in isoform 2.		VSP_031189
	Natural variant	17	1	G → D in a patient with Zellweger syndrome. Ref.1		VAR_000091
Experimental info
	Mutagenesis	478	1	G → R: Decreased ATP-binding affinity. Ref.11
	Mutagenesis	572	1	S → I: Decreased ATPase activity. Ref.11
	Sequence conflict	175	1	M → K in CAA41416. Ref.2
	Sequence conflict	191 – 192	2	QD → LV in CAA58470. Ref.3
	Sequence conflict	336	1	P → L in CAA58470. Ref.3
	Sequence conflict	503	1	G → R in CAA41416. Ref.2
	Sequence conflict	542	1	L → Q in CAA41416. Ref.2
	Sequence conflict	616 – 634	19	VGITL…WKHHE → GWHHSLHLCLIGNLFGNIMR in CAA58470. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified December 1, 1992. Version 1. Checksum: 2CA976FEB6EB6217	FASTA	659	75,476
	10 20 30 40 50 60 MAAFSKYLTA RNSSLAGAAF LLLCLLHKRR RALGLHGKKS GKPPLQNNEK EGKKERAVVD 70 80 90 100 110 120 KVFFSRLIQI LKIMVPRTFC KETGYLVLIA VMLVSRTYCD VWMIQNGTLI ESGIIGRSRK 130 140 150 160 170 180 DFKRYLLNFI AAMPLISLVN NFLKYGLNEL KLCFRVRLTK YLYEEYLQAF TYYKMGNLDN 190 200 210 220 230 240 RIANPDQLLT QDVEKFCNSV VDLYSNLSKP FLDIVLYIFK LTSAIGAQGP ASMMAYLVVS 250 260 270 280 290 300 GLFLTRLRRP IGKMTITEQK YEGEYRYVNS RLITNSEEIA FYNGNKREKQ TVHSVFRKLV 310 320 330 340 350 360 EHLHNFILFR FSMGFIDSII AKYLATVVGY LVVSRPFLDL SHPRHLKSTH SELLEDYYQS 370 380 390 400 410 420 GRMLLRMSQA LGRIVLAGRE MTRLAGFTAR ITELMQVLKD LNHGKYERTM VSQQEKGIEG 430 440 450 460 470 480 VQVIPLIPGA GEIIIADNII KFDHVPLATP NGDVLIRDLN FEVRSGANVL ICGPNGCGKS 490 500 510 520 530 540 SLFRVLGELW PLFGGRLTKP ERGKLFYVPQ RPYMTLGTLR DQVIYPDGRE DQKRKGISDL 550 560 570 580 590 600 VLKEYLDNVQ LGHILEREGG WDSVQDWMDV LSGGEKQRMA MARLFYHKPQ FAILDECTSA 610 620 630 640 650 VSVDVEGYIY SHCRKVGITL FTVSHRKSLW KHHEYYLHMD GRGNYEFKQI TEDTVEFGS
	Isoform 2 [UniParc]. Checksum: 1E0139B8A2EEB7E9	FASTA	549	62,726
	10 20 30 40 50 60 MAAFSKYLTA RNSSLAGAAF LLLCLLHKRR RALGLHGKKS GKPPLQNNEK EGKKERAVVD 70 80 90 100 110 120 KVFFSRLIQI LKIMVPRTFC KETGYLVLIA VMLVSRTYCD VWMIQNGTLI ESGIIGRSRK 130 140 150 160 170 180 DFKRYLLNFI AAMPLISLVN NFLKYGLNEL KLCFRVRLTK YLYEEYLQAF TYYKMGNLDN 190 200 210 220 230 240 RIANPDQLLT QDVEKFCNSV VDLYSNLSKP FLDIVLYIFK LTSAIGAQGP ASMMAYLVVS 250 260 270 280 290 300 GLFLTRLRRP IGKMTITEQK YEGEYRYVNS RLITNSFTAR ITELMQVLKD LNHGKYERTM 310 320 330 340 350 360 VSQQEKGIEG VQVIPLIPGA GEIIIADNII KFDHVPLATP NGDVLIRDLN FEVRSGANVL 370 380 390 400 410 420 ICGPNGCGKS SLFRVLGELW PLFGGRLTKP ERGKLFYVPQ RPYMTLGTLR DQVIYPDGRE 430 440 450 460 470 480 DQKRKGISDL VLKEYLDNVQ LGHILEREGG WDSVQDWMDV LSGGEKQRMA MARLFYHKPQ 490 500 510 520 530 540 FAILDECTSA VSVDVEGYIY SHCRKVGITL FTVSHRKSLW KHHEYYLHMD GRGNYEFKQI TEDTVEFGS
	Isoform 3 [UniParc]. Checksum: 314231AA2705E8AB	FASTA	236	27,121
	10 20 30 40 50 60 MAAFSKYLTA RNSSLAGAAF LLLCLLHKRR RALGLHGKKS GKPPLQNNEK EGKKERAVVD 70 80 90 100 110 120 KVFFSRLIQI LKIMVPRTFC KETGYLVLIA VMLVSRTYCD VWMIQNGTLI ESGIIGRSRK 130 140 150 160 170 180 DFKRYLLNFI AAMPLISLVN NFLKYGLNEL KLCFRVRLTK YLYEEYLQAF TYYKMGNLDN 190 200 210 220 230 RIANPDQLLT QDVEKFCNSV VDLYSNLSKP FLDIVLYIFK LTSAIGAQVL GKILWH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Mutations in the 70K peroxisomal membrane protein gene in Zellweger syndrome." Gaertner J., Moser H., Valle D. Nat. Genet. 1:16-23(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ASP-17. Tissue: Liver.
[2]	"Nucleotide sequence of the human 70 kDa peroxisomal membrane protein: a member of ATP-binding cassette transporters." Kamijo K., Kamijo T., Ueno I., Osumi T., Hashimoto T. Biochim. Biophys. Acta 1129:323-327(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Liver.
[3]	"Genomic organization of the 70-kDa peroxisomal membrane protein gene (PXMP1)." Gaertner J., Jimenez-Sanchez G., Roerig P., Valle D. Genomics 48:203-208(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
[5]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3). Tissue: Brain and Lung.
[8]	"Homo- and heterodimerization of peroxisomal ATP-binding cassette half-transporters." Liu L.X., Janvier K., Berteaux-Lecellier V., Cartier N., Benarous R., Aubourg P. J. Biol. Chem. 274:32738-32743(1999) [PubMed] [Europe PMC] [Abstract] Cited for: SUBUNIT.
[9]	"Human adrenoleukodystrophy protein and related peroxisomal ABC transporters interact with the peroxisomal assembly protein PEX19p." Gloeckner C.J., Mayerhofer P.U., Landgraf P., Muntau A.C., Holzinger A., Gerber J.-K., Kammerer S., Adamski J., Roscher A.A. Biochem. Biophys. Res. Commun. 271:144-150(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PEX19. Tissue: Brain.
[10]	"PEX19 binds multiple peroxisomal membrane proteins, is predominantly cytoplasmic, and is required for peroxisome membrane synthesis." Sacksteder K.A., Jones J.M., South S.T., Li X., Liu Y., Gould S.J. J. Cell Biol. 148:931-944(2000) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH PEX19.
[11]	"Characterization and functional analysis of the nucleotide binding fold in human peroxisomal ATP binding cassette transporters." Roerig P., Mayerhofer P., Holzinger A., Gaertner J. FEBS Lett. 492:66-72(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF GLY-478 AND SER-572.
[12]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-260 AND LYS-399, MASS SPECTROMETRY.
[13]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Web resources

ABCMdb

Database for mutations in ABC proteins

Cross-references

Sequence databases
EMBL GenBank DDBJ	M81182 mRNA. Translation: AAA60128.1. X58528 mRNA. Translation: CAA41416.1. X83467 , X83468, X83469, X83470, X83471, X83472, X83473, X83474, X83475, X83476, X83477, X83478, X83479, X83480, X83481, X83482, X83483, X83484, X83485, X83486, X83487, X83488, X83489 Genomic DNA. Translation: CAA58470.1. BT006644 mRNA. Translation: AAP35290.1. AL138758, AC093117, AC118469 Genomic DNA. Translation: CAC15960.2. CH471097 Genomic DNA. Translation: EAW73049.1. CH471097 Genomic DNA. Translation: EAW73050.1. CH471097 Genomic DNA. Translation: EAW73047.1. CH471097 Genomic DNA. Translation: EAW73048.1. BC009712 mRNA. Translation: AAH09712.1. BC068509 mRNA. Translation: AAH68509.1.
IPI	IPI00002372. IPI00185503. IPI00884932.
PIR	S20313.
RefSeq	NP_001116146.1. NM_001122674.1. NP_002849.1. NM_002858.3.
UniGene	Hs.700576.
3D structure databases
ProteinModelPortal	P28288.
ModBase	Search...
Protein-protein interaction databases
IntAct	P28288. 10 interactions.
STRING	9606.ENSP00000359233.
Protein family/group databases
TCDB	3.A.1.203.1. ATP-binding cassette (ABC) superfamily.
PTM databases
PhosphoSite	P28288.
Polymorphism databases
DMDM	130358.
Proteomic databases
PaxDb	P28288.
PeptideAtlas	P28288.
PRIDE	P28288.
Protocols and materials databases
DNASU	5825.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000315713; ENSP00000326880; ENSG00000117528. ENST00000370214; ENSP00000359233; ENSG00000117528. ENST00000394233; ENSP00000377780; ENSG00000117528.
GeneID	5825.
KEGG	hsa:5825.
UCSC	uc001dqm.4. human. uc001dqn.4. human. uc009wdr.3. human.
Organism-specific databases
CTD	5825.
GeneCards	GC01P094883.
HGNC	HGNC:67. ABCD3.
HPA	HPA032027.
MIM	170995. gene+phenotype.
neXtProt	NX_P28288.
PharmGKB	PA24402.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG4178.
HOGENOM	HOG000206081.
HOVERGEN	HBG050438.
InParanoid	P28288.
KO	K05677.
OrthoDB	EOG4ZPDTZ.
PhylomeDB	P28288.
Enzyme and pathway databases
Reactome	REACT_15518. Transmembrane transport of small molecules.
Gene expression databases
ArrayExpress	P28288.
Bgee	P28288.
CleanEx	HS_ABCD3.
Genevestigator	P28288.
GermOnline	ENSG00000117528. Homo sapiens.
Family and domain databases
InterPro	IPR003593. AAA+_ATPase. IPR010509. ABC_Ald_N. IPR003439. ABC_transporter-like. IPR017871. ABC_transporter_CS. IPR017940. ABC_transporter_type1. IPR011527. ABC_transptrTM_dom_typ1. IPR005283. FA_transporter. [Graphical view]
Pfam	PF06472. ABC_membrane_2. 1 hit. PF00005. ABC_tran. 1 hit. [Graphical view]
SMART	SM00382. AAA. 1 hit. [Graphical view]
SUPFAM	SSF90123. ABC_TM_1. 1 hit.
TIGRFAMs	TIGR00954. 3a01203. 1 hit.
PROSITE	PS50929. ABC_TM1F. 1 hit. PS00211. ABC_TRANSPORTER_1. 1 hit. PS50893. ABC_TRANSPORTER_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	ABCD3. human.
GenomeRNAi	5825.
NextBio	22689.
SOURCE	Search...

Entry information

Entry name

ABCD3_HUMAN

Accession

Primary (citable) accession number: P28288
Secondary accession number(s): D3DT46 , Q15271, Q6NUN5, Q96DA3, Q9H529

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 1992
Last sequence update:	December 1, 1992
Last modified:	May 1, 2013
This is version 139 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.