ABCD1

ABCD1
Identifiers
Aliases	ABCD1, ABC42, ALD, ALDP, AMN, ATP binding cassette subfamily D member 1
External IDs	OMIM: 300371 MGI: 1349215 HomoloGene: 55426 GeneCards: ABCD1
Gene ontology Molecular function • ATPase activity, coupled to transmembrane movement of substances • nucleotide binding • protein homodimerization activity • transporter activity • ATPase activity • protein binding • identical protein binding • enzyme binding • peroxisomal fatty-acyl-CoA transporter activity • ATP binding • long-chain fatty acid transporter activity Cellular component • cytoplasm • integral component of membrane • cytosol • membrane • peroxisomal membrane • peroxisome • mitochondrion • integral component of peroxisomal membrane • perinuclear region of cytoplasm Biological process • peroxisomal long-chain fatty acid import • linoleic acid metabolic process • peroxisome organization • alpha-linolenic acid metabolic process • long-chain fatty acid catabolic process • peroxisomal membrane transport • fatty acid beta-oxidation using acyl-CoA oxidase • transmembrane transport • transport • very long-chain fatty acid catabolic process • fatty acid beta-oxidation Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	215	11666
Ensembl	ENSG00000101986	ENSMUSG00000031378
UniProt	P33897	P48410
RefSeq (mRNA)	NM_000033	NM_007435
RefSeq (protein)	NP_000024.2	NP_031461.1
Location (UCSC)	Chr X: 153.72 – 153.74 Mb	Chr X: 73.72 – 73.74 Mb
PubMed search	[1]	[2]
Wikidata

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ABCD1 is a protein that transfers fatty acids into peroxisomes.

Function

The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the ALD subfamily, which is involved in peroxisomal import of fatty acids and/or fatty acyl-CoAs in the organelle. All known peroxisomal ABC transporters are half transporters which require a partner half transporter molecule to form a functional homodimeric or heterodimeric transporter. This peroxisomal membrane protein is likely involved in the peroxisomal transport or catabolism of very long chain fatty acids.^[3]

Clinical significance

Defects in this gene have been identified as the underlying cause of adrenoleukodystrophy, an X-chromosome recessively inherited demyelinating disorder of the nervous system.^[3]

Model organisms

Abcd1 knockout mouse phenotype

Characteristic	Phenotype
Homozygote viability	Normal
Fertility	Normal
Body weight	Normal
Anxiety	Normal
Neurological assessment	Normal
Grip strength	Normal
Hot plate	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Plasma immunoglobulins	Normal
Haematology	Normal
Micronucleus test	Normal
Heart weight	Normal
Skin Histopathology	Normal
Brain histopathology	Normal
Salmonella infection	Normal[4]
Citrobacter infection	Normal[5]
All tests and analysis from[6][7]

Model organisms have been used in the study of ABCD1 function. A conditional knockout mouse line, called Abcd1^{tm1a(EUCOMM)Wtsi[8][9]} was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists — at the Wellcome Trust Sanger Institute.^[10][11][12]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.^[6][13] Twenty four tests were carried out on mutant mice but no significant abnormalities were observed.^[6]

Interactions

ABCD1 has been shown to interact with PEX19.^[14][15]

References

1. "Human PubMed Reference:".
2. "Mouse PubMed Reference:".
3. "Entrez Gene: ABCD1 ATP-binding cassette, sub-family D (ALD), member 1".
4. "Salmonella infection data for Abcd1". Wellcome Trust Sanger Institute.
5. "Citrobacter infection data for Abcd1". Wellcome Trust Sanger Institute.
6. Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88 (S248). doi:10.1111/j.1755-3768.2010.4142.x.
7. Mouse Resources Portal, Wellcome Trust Sanger Institute.
8. "International Knockout Mouse Consortium".
9. "Mouse Genome Informatics".
10. Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (June 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
11. Dolgin E (June 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
12. Collins FS, Rossant J, Wurst W (January 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
13. van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism.". Genome Biol. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.
14. Mayerhofer PU, Kattenfeld T, Roscher AA, Muntau AC (March 2002). "Two splice variants of human PEX19 exhibit distinct functions in peroxisomal assembly". Biochem. Biophys. Res. Commun. 291 (5): 1180–6. doi:10.1006/bbrc.2002.6568. PMID 11883941.
15. Gloeckner CJ, Mayerhofer PU, Landgraf P, Muntau AC, Holzinger A, Gerber JK, Kammerer S, Adamski J, Roscher AA (April 2000). "Human adrenoleukodystrophy protein and related peroxisomal ABC transporters interact with the peroxisomal assembly protein PEX19p". Biochem. Biophys. Res. Commun. 271 (1): 144–50. doi:10.1006/bbrc.2000.2572. PMID 10777694.

Further reading

• Aubourg P, Mosser J, Douar AM, Sarde CO, Lopez J, Mandel JL (1993). "Adrenoleukodystrophy gene: unexpected homology to a protein involved in peroxisome biogenesis". Biochimie. 75 (3–4): 293–302. doi:10.1016/0300-9084(93)90089-B. PMID 8507690.
• Moser HW, Powers JM, Smith KD (1996). "Adrenoleukodystrophy: molecular genetics, pathology, and Lorenzo's oil". Brain Pathol. 5 (3): 259–266. doi:10.1111/j.1750-3639.1995.tb00602.x. PMID 8520725.
• Dodd A, Rowland SA, Hawkes SL, Kennedy MA, Love DR (1997). "Mutations in the adrenoleukodystrophy gene". Hum. Mutat. 9 (6): 500–511. doi:10.1002/(SICI)1098-1004(1997)9:6<500::AID-HUMU2>3.0.CO;2-5. PMID 9195223.
• Kemp S, Pujol A, Waterham HR, van Geel BM, Boehm CD, Raymond GV, Cutting GR, Wanders RJ, Moser HW (2002). "ABCD1 mutations and the X-linked adrenoleukodystrophy mutation database: role in diagnosis and clinical correlations". Hum. Mutat. 18 (6): 499–515. doi:10.1002/humu.1227. PMID 11748843.
• Lan F (2002). "Molecular diagnostics in China". Clin. Chem. Lab. Med. 39 (12): 1190–1194. doi:10.1515/CCLM.2001.188. PMID 11798073.
• Feil R, Aubourg P, Mosser J, Douar AM, Le Paslier D, Philippe C, Mandel JL (1992). "Adrenoleukodystrophy: a complex chromosomal rearrangement in the Xq28 red/green-color-pigment gene region indicates two possible gene localizations". Am. J. Hum. Genet. 49 (6): 1361–71. PMC 1686466. PMID 1746561.
• Moser HW, Moser AE, Singh I, O'Neill BP (1985). "Adrenoleukodystrophy: survey of 303 cases: biochemistry, diagnosis, and therapy". Ann. Neurol. 16 (6): 628–641. doi:10.1002/ana.410160603. PMID 6524872.
• Migeon BR, Moser HW, Moser AB, Axelman J, Sillence D, Norum RA (1982). "Adrenoleukodystrophy: evidence for X linkage, inactivation, and selection favoring the mutant allele in heterozygous cells". Proc. Natl. Acad. Sci. U.S.A. 78 (8): 5066–5070. doi:10.1073/pnas.78.8.5066. PMC 320333. PMID 6795626.
• Kok F, Neumann S, Sarde CO, Zheng S, Wu KH, Wei HM, Bergin J, Watkins PA, Gould S, Sack G (1995). "Mutational analysis of patients with X-linked adrenoleukodystrophy". Hum. Mutat. 6 (2): 104–115. doi:10.1002/humu.1380060203. PMID 7581394.
• Watkins PA, Gould SJ, Smith MA, Braiterman LT, Wei HM, Kok F, Moser AB, Moser HW, Smith KD (1995). "Altered expression of ALDP in X-linked adrenoleukodystrophy". Am. J. Hum. Genet. 57 (2): 292–301. PMC 1801558. PMID 7668254.
• Braun A, Ambach H, Kammerer S, Rolinski B, Stöckler S, Rabl W, Gärtner J, Zierz S, Roscher AA (1995). "Mutations in the gene for X-linked adrenoleukodystrophy in patients with different clinical phenotypes". Am. J. Hum. Genet. 56 (4): 854–61. PMC 1801211. PMID 7717396.
• Berger J, Molzer B, Faé I, Bernheimer H (1995). "X-linked adrenoleukodystrophy (ALD): a novel mutation of the ALD gene in 6 members of a family presenting with 5 different phenotypes". Biochem. Biophys. Res. Commun. 205 (3): 1638–1643. doi:10.1006/bbrc.1994.2855. PMID 7811247.
• Ligtenberg MJ, Kemp S, Sarde CO, van Geel BM, Kleijer WJ, Barth PG, Mandel JL, van Oost BA, Bolhuis PA (1995). "Spectrum of mutations in the gene encoding the adrenoleukodystrophy protein". Am. J. Hum. Genet. 56 (1): 44–50. PMC 1801307. PMID 7825602.
• Fuchs S, Sarde CO, Wedemann H, Schwinger E, Mandel JL, Gal A (1995). "Missense mutations are frequent in the gene for X-chromosomal adrenoleukodystrophy (ALD)". Hum. Mol. Genet. 3 (10): 1903–1905. doi:10.1093/hmg/3.10.1903. PMID 7849723.
• Cartier N, Sarde CO, Douar AM, Mosser J, Mandel JL, Aubourg P (1994). "Abnormal messenger RNA expression and a missense mutation in patients with X-linked adrenoleukodystrophy". Hum. Mol. Genet. 2 (11): 1949–1951. doi:10.1093/hmg/2.11.1949. PMID 7904210.
• Sarde CO, Mosser J, Kioschis P, Kretz C, Vicaire S, Aubourg P, Poustka A, Mandel JL (1994). "Genomic organization of the adrenoleukodystrophy gene". Genomics. 22 (1): 13–20. doi:10.1006/geno.1994.1339. PMID 7959759.
• Kobayashi T, Yamada T, Yasutake T, Shinnoh N, Goto I, Iwaki T (1994). "Adrenoleukodystrophy gene encodes an 80 kDa membrane protein". Biochem. Biophys. Res. Commun. 201 (2): 1029–1034. doi:10.1006/bbrc.1994.1805. PMID 8002973.
• Mosser J, Lutz Y, Stoeckel ME, Sarde CO, Kretz C, Douar AM, Lopez J, Aubourg P, Mandel JL (1994). "The gene responsible for adrenoleukodystrophy encodes a peroxisomal membrane protein". Hum. Mol. Genet. 3 (2): 265–271. doi:10.1093/hmg/3.2.265. PMID 8004093.
• Fanen P, Guidoux S, Sarde CO, Mandel JL, Goossens M, Aubourg P (1994). "Identification of mutations in the putative ATP-binding domain of the adrenoleukodystrophy gene". J. Clin. Invest. 94 (2): 516–520. doi:10.1172/JCI117363. PMC 296124. PMID 8040304.
• Mosser J, Douar AM, Sarde CO, Kioschis P, Feil R, Moser H, Poustka AM, Mandel JL, Aubourg P (1993). "Putative X-linked adrenoleukodystrophy gene shares unexpected homology with ABC transporters". Nature. 361 (6414): 726–730. doi:10.1038/361726a0. PMID 8441467.

External links

• GeneReviews/NIH/NCBI/UW entry on X-Linked Adrenoleukodystrophy
• ABCD1 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)
• Human ABCD1 genome location and ABCD1 gene details page in the UCSC Genome Browser.
• Human AMN genome location and AMN gene details page in the UCSC Genome Browser.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.