O14678 (ABCD4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
ATP-binding cassette sub-family D member 4

Alternative name(s):
PMP70-related protein
Short name=P70R
Peroxisomal membrane protein 1-like
Short name=PXMP1-L
Peroxisomal membrane protein 69
Short name=PMP69

Gene names

Name:	ABCD4
Synonyms:	PXMP1L

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	606 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	May be involved in intracellular processing of vitamin B12 (cobalamin). Could play a role in the lysosomal release of vitamin B12 into the cytoplasm. Ref.7
Subunit structure	Homodimer or heterodimer Potential.
Subcellular location	Peroxisome membrane; Multi-pass membrane protein.
Tissue specificity	Ubiquitous.
Involvement in disease	Methylmalonic aciduria and homocystinuria type cblJ (MAHCJ) [MIM:614857]: A disorder of cobalamin metabolism characterized by decreased levels of the coenzymes adenosylcobalamin (AdoCbl) and methylcobalamin (MeCbl). Clinical features include feeding difficulties, poor growth, hypotonia, lethargy, anemia, and developmental delay. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7
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	Polymorphism
Disease	Disease mutation
Domain	Transmembrane Transmembrane helix
Ligand	ATP-binding Nucleotide-binding
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cobalamin metabolic process Inferred from mutant phenotype Ref.7. Source: UniProtKB
Cellular_component	ATP-binding cassette (ABC) transporter complex Non-traceable author statement Ref.1. Source: UniProtKB endoplasmic reticulum membrane Inferred from electronic annotation. Source: Compara integral to membrane Non-traceable author statement Ref.1. Source: UniProtKB peroxisomal membrane Inferred from electronic annotation. Source: UniProtKB-SubCell peroxisome Inferred from direct assay PubMed 14533738Ref.3. Source: UniProtKB
Molecular_function	ATP binding Non-traceable author statement Ref.1. Source: UniProtKB ATPase activity, coupled to transmembrane movement of substances Non-traceable author statement Ref.1. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 606	606	ATP-binding cassette sub-family D member 4		PRO_0000093312
Regions
	Transmembrane	43 – 63	21	Helical; Potential
	Transmembrane	76 – 96	21	Helical; Potential
	Transmembrane	190 – 210	21	Helical; Potential
	Transmembrane	279 – 299	21	Helical; Potential
	Transmembrane	314 – 334	21	Helical; Potential
	Domain	39 – 332	294	ABC transmembrane type-1
	Domain	389 – 603	215	ABC transporter
	Nucleotide binding	421 – 428	8	ATP Potential
Natural variations
	Natural variant	172	1	V → I. Corresponds to variant rs34992370 [ dbSNP | Ensembl ].		VAR_048134
	Natural variant	304	1	A → T. Ref.4 Ref.5 Ref.6 Ref.8 Corresponds to variant rs4148077 [ dbSNP | Ensembl ].		VAR_020778
	Natural variant	319	1	Y → C in MAHCJ. Ref.7		VAR_069097
	Natural variant	350	1	T → R. Corresponds to variant rs35073715 [ dbSNP | Ensembl ].		VAR_048135
	Natural variant	368	1	E → K. Ref.4 Ref.5 Ref.6 Ref.8 Corresponds to variant rs3742801 [ dbSNP | Ensembl ].		VAR_020222
Experimental info
	Sequence conflict	606	1	E → D in CAG33385. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	O14678 [UniParc]. Last modified January 1, 1998. Version 1. Checksum: 2D88DEFED0EA0777	FASTA	606	68,597
	10 20 30 40 50 60 MAVAGPAPGA GARPRLDLQF LQRFLQILKV LFPSWSSQNA LMFLTLLCLT LLEQFVIYQV 70 80 90 100 110 120 GLIPSQYYGV LGNKDLEGFK TLTFLAVMLI VLNSTLKSFD QFTCNLLYVS WRKDLTEHLH 130 140 150 160 170 180 RLYFRGRAYY TLNVLRDDID NPDQRISQDV ERFCRQLSSM ASKLIISPFT LVYYTYQCFQ 190 200 210 220 230 240 STGWLGPVSI FGYFILGTVV NKTLMGPIVM KLVHQEKLEG DFRFKHMQIR VNAEPAAFYR 250 260 270 280 290 300 AGHVEHMRTD RRLQRLLQTQ RELMSKELWL YIGINTFDYL GSILSYVVIA IPIFSGVYGD 310 320 330 340 350 360 LSPAELSTLV SKNAFVCIYL ISCFTQLIDL STTLSDVAGY THRIGQLRET LLDMSLKSQD 370 380 390 400 410 420 CEILGESEWG LDTPPGWPAA EPADTAFLLE RVSISAPSSD KPLIKDLSLK ISEGQSLLIT 430 440 450 460 470 480 GNTGTGKTSL LRVLGGLWTS TRGSVQMLTD FGPHGVLFLP QKPFFTDGTL REQVIYPLKE 490 500 510 520 530 540 VYPDSGSADD ERILRFLELA GLSNLVARTE GLDQQVDWNW YDVLSPGEMQ RLSFARLFYL 550 560 570 580 590 600 QPKYAVLDEA TSALTEEVES ELYRIGQQLG MTFISVGHRQ SLEKFHSLVL KLCGGGRWEL MRIKVE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Primary structure of human PMP69, a putative peroxisomal ABC-transporter." Holzinger A., Kammerer S., Roscher A.A. Biochem. Biophys. Res. Commun. 237:152-157(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Genomic organization and chromosomal localization of the human peroxisomal membrane protein-1-like protein (PXMP1-L) gene encoding a peroxisomal ABC transporter." Holzinger A., Roscher A.A., Landgraf P., Lichtner P., Kammerer S. FEBS Lett. 426:238-242(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[3]	"Identification of a fourth half ABC transporter in the human peroxisomal membrane." Shani N., Jimenez-Sanchez G., Steel G., Dean M., Valle D. Hum. Mol. Genet. 6:1925-1931(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[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], VARIANTS THR-304 AND LYS-368.
[5]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS THR-304 AND LYS-368.
[6]	"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], VARIANTS THR-304 AND LYS-368. Tissue: Muscle.
[7]	"Mutations in ABCD4 cause a new inborn error of vitamin B12 metabolism." Coelho D., Kim J.C., Miousse I.R., Fung S., du Moulin M., Buers I., Suormala T., Burda P., Frapolli M., Stucki M., Nurnberg P., Thiele H., Robenek H., Hohne W., Longo N., Pasquali M., Mengel E., Watkins D. , Shoubridge E.A., Majewski J., Rosenblatt D.S., Fowler B., Rutsch F., Baumgartner M.R. Nat. Genet. 44:1152-1155(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, VARIANT MAHCJ CYS-319.
[8]	"Catalog of 605 single-nucleotide polymorphisms (SNPs) among 13 genes encoding human ATP-binding cassette transporters: ABCA4, ABCA7, ABCA8, ABCD1, ABCD3, ABCD4, ABCE1, ABCF1, ABCG1, ABCG2, ABCG4, ABCG5, and ABCG8." Iida A., Saito S., Sekine A., Mishima C., Kitamura Y., Kondo K., Harigae S., Osawa S., Nakamura Y. J. Hum. Genet. 47:285-310(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS THR-304 AND LYS-368.

Web resources

ABCMdb

Database for mutations in ABC proteins

Cross-references

Sequence databases
EMBL GenBank DDBJ	Y14318 , Y14319, Y14320, Y14321, Y14322, Y14323 Genomic DNA. Translation: CAA74699.1. AF009746 mRNA. Translation: AAB83967.1. BT007412 mRNA. Translation: AAP36080.1. CR457104 mRNA. Translation: CAG33385.1. BC012815 mRNA. Translation: AAH12815.1.
IPI	IPI00023165.
PIR	JC5604.
RefSeq	NP_005041.1. NM_005050.3.
UniGene	Hs.94395.
3D structure databases
ProteinModelPortal	O14678.
ModBase	Search...
Protein-protein interaction databases
IntAct	O14678. 4 interactions.
STRING	9606.ENSP00000349396.
PTM databases
PhosphoSite	O14678.
Proteomic databases
PaxDb	O14678.
PRIDE	O14678.
Protocols and materials databases
DNASU	5826.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000356924; ENSP00000349396; ENSG00000119688.
GeneID	5826.
KEGG	hsa:5826.
UCSC	uc001xpr.2. human.
Organism-specific databases
CTD	5826.
GeneCards	GC14M074751.
HGNC	HGNC:68. ABCD4.
HPA	HPA003396.
MIM	603214. gene. 614857. phenotype.
neXtProt	NX_O14678.
PharmGKB	PA24403.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG4178.
HOGENOM	HOG000007546.
HOVERGEN	HBG106060.
InParanoid	O14678.
KO	K05678.
OMA	CLTLLEQ.
OrthoDB	EOG46WZ81.
PhylomeDB	O14678.
Gene expression databases
ArrayExpress	O14678.
Bgee	O14678.
CleanEx	HS_ABCD4.
Genevestigator	O14678.
GermOnline	ENSG00000119688. 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. [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.
PROSITE	PS50929. ABC_TM1F. 1 hit. PS00211. ABC_TRANSPORTER_1. 1 hit. PS50893. ABC_TRANSPORTER_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	ABCD4. human.
GenomeRNAi	5826.
NextBio	22693.
SOURCE	Search...

Entry information

Entry name

ABCD4_HUMAN

Accession

Primary (citable) accession number: O14678
Secondary accession number(s): Q6IAQ0, Q96E75

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	January 1, 1998
Last modified:	May 1, 2013
This is version 115 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.