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{{for|[[Stroke]] risk assessment in [[Transient ischemic attack|TIA]]|ABCD² score}}{{for|the film|ABCD 2}}
{{PBB_Controls
{{Infobox_gene}}
| update_page = yes
'''ATP-binding cassette sub-family D member 2''' is a membrane pump/transporter [[protein]] that in humans is encoded by the ''ABCD2'' [[gene]].<ref name="pmid8577752">{{cite journal | vauthors = Lombard-Platet G, Savary S, Sarde CO, Mandel JL, Chimini G | title = A close relative of the adrenoleukodystrophy (ALD) gene codes for a peroxisomal protein with a specific expression pattern | journal = Proc Natl Acad Sci U S A | volume = 93 | issue = 3 | pages = 1265–9 | date = March 1996 | pmid = 8577752 | pmc = 40068 | doi = 10.1073/pnas.93.3.1265 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: ABCD2 ATP-binding cassette, sub-family D (ALD), member 2| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=225| accessdate = }}</ref>
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
}}


<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{GNF_Protein_box
| image =
| image_source =
| PDB =
| Name = ATP-binding cassette, sub-family D (ALD), member 2
| HGNCid = 66
| Symbol = ABCD2
| AltSymbols =; ABC39; ALDL1; ALDR; ALDRP; hALDR
| OMIM = 601081
| ECnumber = 
| Homologene = 55873
| MGIid = 1349467
| GeneAtlas_image1 = PBB_GE_ABCD2_207583_at_tn.png
| Function = {{GNF_GO|id=GO:0000166 |text = nucleotide binding}} {{GNF_GO|id=GO:0005515 |text = protein binding}} {{GNF_GO|id=GO:0005524 |text = ATP binding}} {{GNF_GO|id=GO:0016887 |text = ATPase activity}} {{GNF_GO|id=GO:0042626 |text = ATPase activity, coupled to transmembrane movement of substances}}
| Component = {{GNF_GO|id=GO:0005777 |text = peroxisome}} {{GNF_GO|id=GO:0005887 |text = integral to plasma membrane}} {{GNF_GO|id=GO:0016020 |text = membrane}} {{GNF_GO|id=GO:0043190 |text = ATP-binding cassette (ABC) transporter complex}}
| Process = {{GNF_GO|id=GO:0006631 |text = fatty acid metabolic process}} {{GNF_GO|id=GO:0006810 |text = transport}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 225
    | Hs_Ensembl = ENSG00000173208
    | Hs_RefseqProtein = NP_005155
    | Hs_RefseqmRNA = NM_005164
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 12
    | Hs_GenLoc_start = 38232814
    | Hs_GenLoc_end = 38300237
    | Hs_Uniprot = Q9UBJ2
    | Mm_EntrezGene = 26874
    | Mm_Ensembl = ENSMUSG00000055782
    | Mm_RefseqmRNA = NM_011994
    | Mm_RefseqProtein = NP_036124
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 15
    | Mm_GenLoc_start = 90973638
    | Mm_GenLoc_end = 91019574
    | Mm_Uniprot = Q3TU16
  }}
}}
'''ATP-binding cassette, sub-family D (ALD), member 2''', also known as '''ABCD2''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: ABCD2 ATP-binding cassette, sub-family D (ALD), member 2| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=225| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
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. The function of this peroxisomal membrane protein is unknown; however this protein is speculated to function as a dimerization partner of ABCD1 and/or other peroxisomal ABC transporters.<ref name="entrez"/>
{{PBB_Summary
| section_title =
| summary_text = 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. The function of this peroxisomal membrane protein is unknown; however this protein is speculated to function as a dimerization partner of ABCD1 and/or other peroxisomal ABC transporters. Mutations in this gene have been observed in patients with adrenoleukodystrophy, a severe demyelinating disease. This gene has been identified as a candidate for a modifier gene, accounting for the extreme variation among adrenoleukodystrophy phenotypes. This gene is also a candidate for a complement group of Zellweger syndrome, a genetically heterogeneous disorder of peroxisomal biogenesis.<ref name="entrez">{{cite web | title = Entrez Gene: ABCD2 ATP-binding cassette, sub-family D (ALD), member 2| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=225| accessdate = }}</ref>
}}


==See also==
== Clinical significance ==
 
Mutations in this gene have been observed in patients with [[adrenoleukodystrophy]], a severe demyelinating disease. This gene has been identified as a candidate for a modifier gene, accounting for the extreme variation among adrenoleukodystrophy phenotypes. This gene is also a candidate for a complement group of [[Zellweger syndrome]], a genetically heterogeneous disorder of peroxisomal biogenesis.<ref name="entrez"/>
 
== See also ==
* [[ATP-binding cassette transporter]]
* [[ATP-binding cassette transporter]]


==References==
== Interactions ==
{{reflist|2}}


==Further reading==
ABCD2 has been shown to [[Protein-protein interaction|interact]] with [[PEX19]].<ref name = pmid11883941>{{cite journal | vauthors = Mayerhofer PU, Kattenfeld T, Roscher AA, Muntau AC | title = Two splice variants of human PEX19 exhibit distinct functions in peroxisomal assembly | journal = Biochem. Biophys. Res. Commun. | volume = 291 | issue = 5 | pages = 1180–6 | date = March 2002 | pmid = 11883941 | doi = 10.1006/bbrc.2002.6568 }}</ref><ref name = pmid10777694>{{cite journal | vauthors = Gloeckner CJ, Mayerhofer PU, Landgraf P, Muntau AC, Holzinger A, Gerber JK, Kammerer S, Adamski J, Roscher AA | title = Human adrenoleukodystrophy protein and related peroxisomal ABC transporters interact with the peroxisomal assembly protein PEX19p | journal = Biochem. Biophys. Res. Commun. | volume = 271 | issue = 1 | pages = 144–50 | date = April 2000 | pmid = 10777694 | doi = 10.1006/bbrc.2000.2572 }}</ref>
 
== References ==
{{reflist}}
 
== Further reading ==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading
* {{cite journal | vauthors = Petroni A, Cappa M, Carissimi R, Blasevich M, Uziel G | title = Effect of testosterone metabolites on ABC half-transporter relative gene expression in X-linked adrenoleukodystrophy. | journal = J. Inherit. Metab. Dis. | volume = 30 | issue = 5 | pages = 828 | year = 2007 | pmid = 17602313 | doi = 10.1007/s10545-007-0591-1 }}
| citations =
* {{cite journal | vauthors = Weinhofer I, Kunze M, Rampler H, Bookout AL, Forss-Petter S, Berger J | title = Liver X receptor alpha interferes with SREBP1c-mediated Abcd2 expression. Novel cross-talk in gene regulation. | journal = J. Biol. Chem. | volume = 280 | issue = 50 | pages = 41243–51 | year = 2006 | pmid = 16249184 | doi = 10.1074/jbc.M509450200 }}
*{{cite journal | author=Petroni A, Cappa M, Carissimi R, ''et al.'' |title=Effect of testosterone metabolites on ABC half-transporter relative gene expression in X-linked adrenoleukodystrophy. |journal=J. Inherit. Metab. Dis. |volume=30 |issue= 5 |pages= 828 |year= 2007 |pmid= 17602313 |doi= 10.1007/s10545-007-0591-1 }}
* {{cite journal | vauthors = Mayerhofer PU, Kattenfeld T, Roscher AA, Muntau AC | title = Two splice variants of human PEX19 exhibit distinct functions in peroxisomal assembly. | journal = Biochem. Biophys. Res. Commun. | volume = 291 | issue = 5 | pages = 1180–6 | year = 2002 | pmid = 11883941 | doi = 10.1006/bbrc.2002.6568 }}
*{{cite journal | author=Weinhofer I, Kunze M, Rampler H, ''et al.'' |title=Liver X receptor alpha interferes with SREBP1c-mediated Abcd2 expression. Novel cross-talk in gene regulation. |journal=J. Biol. Chem. |volume=280 |issue= 50 |pages= 41243-51 |year= 2006 |pmid= 16249184 |doi= 10.1074/jbc.M509450200 }}
* {{cite journal | vauthors = Gloeckner CJ, Mayerhofer PU, Landgraf P, Muntau AC, Holzinger A, Gerber JK, Kammerer S, Adamski J, Roscher AA | title = Human adrenoleukodystrophy protein and related peroxisomal ABC transporters interact with the peroxisomal assembly protein PEX19p. | journal = Biochem. Biophys. Res. Commun. | volume = 271 | issue = 1 | pages = 144–50 | year = 2000 | pmid = 10777694 | doi = 10.1006/bbrc.2000.2572 }}
*{{cite journal | author=Gerhard DS, Wagner L, Feingold EA, ''et al.'' |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121-7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 }}
* {{cite journal | vauthors = Sacksteder KA, Jones JM, South ST, Li X, Liu Y, Gould SJ | title = PEX19 binds multiple peroxisomal membrane proteins, is predominantly cytoplasmic, and is required for peroxisome membrane synthesis. | journal = J. Cell Biol. | volume = 148 | issue = 5 | pages = 931–44 | year = 2000 | pmid = 10704444 | pmc = 2174547 | doi = 10.1083/jcb.148.5.931 }}
*{{cite journal  | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
* {{cite journal | vauthors = Liu LX, Janvier K, Berteaux-Lecellier V, Cartier N, Benarous R, Aubourg P | title = Homo- and heterodimerization of peroxisomal ATP-binding cassette half-transporters. | journal = J. Biol. Chem. | volume = 274 | issue = 46 | pages = 32738–43 | year = 2000 | pmid = 10551832 | doi = 10.1074/jbc.274.46.32738 }}
*{{cite journal  | author=Mayerhofer PU, Kattenfeld T, Roscher AA, Muntau AC |title=Two splice variants of human PEX19 exhibit distinct functions in peroxisomal assembly. |journal=Biochem. Biophys. Res. Commun. |volume=291 |issue= 5 |pages= 1180-6 |year= 2002 |pmid= 11883941 |doi= 10.1006/bbrc.2002.6568 }}
* {{cite journal | vauthors = Holzinger A, Mayerhofer P, Berger J, Lichtner P, Kammerer S, Roscher AA | title = Full length cDNA cloning, promoter sequence, and genomic organization of the human adrenoleukodystrophy related (ALDR) gene functionally redundant to the gene responsible for X-linked adrenoleukodystrophy. | journal = Biochem. Biophys. Res. Commun. | volume = 258 | issue = 2 | pages = 436–42 | year = 1999 | pmid = 10329405 | doi = 10.1006/bbrc.1999.0535 }}
*{{cite journal | author=Gloeckner CJ, Mayerhofer PU, Landgraf P, ''et al.'' |title=Human adrenoleukodystrophy protein and related peroxisomal ABC transporters interact with the peroxisomal assembly protein PEX19p. |journal=Biochem. Biophys. Res. Commun. |volume=271 |issue= 1 |pages= 144-50 |year= 2000 |pmid= 10777694 |doi= 10.1006/bbrc.2000.2572 }}
* {{cite journal | vauthors = Netik A, Forss-Petter S, Holzinger A, Molzer B, Unterrainer G, Berger J | title = Adrenoleukodystrophy-related protein can compensate functionally for adrenoleukodystrophy protein deficiency (X-ALD): implications for therapy. | journal = Hum. Mol. Genet. | volume = 8 | issue = 5 | pages = 907–13 | year = 1999 | pmid = 10196381 | doi = 10.1093/hmg/8.5.907 }}
*{{cite journal | author=Sacksteder KA, Jones JM, South ST, ''et al.'' |title=PEX19 binds multiple peroxisomal membrane proteins, is predominantly cytoplasmic, and is required for peroxisome membrane synthesis. |journal=J. Cell Biol. |volume=148 |issue= 5 |pages= 931-44 |year= 2000 |pmid= 10704444 |doi= }}
* {{cite journal | vauthors = Holzinger A, Kammerer S, Berger J, Roscher AA | title = cDNA cloning and mRNA expression of the human adrenoleukodystrophy related protein (ALDRP), a peroxisomal ABC transporter. | journal = Biochem. Biophys. Res. Commun. | volume = 239 | issue = 1 | pages = 261–4 | year = 1997 | pmid = 9345306 | doi = 10.1006/bbrc.1997.7391 }}
*{{cite journal | author=Liu LX, Janvier K, Berteaux-Lecellier V, ''et al.'' |title=Homo- and heterodimerization of peroxisomal ATP-binding cassette half-transporters. |journal=J. Biol. Chem. |volume=274 |issue= 46 |pages= 32738-43 |year= 2000 |pmid= 10551832 |doi= }}
* {{cite journal | vauthors = Savary S, Troffer-Charlier N, Gyapay G, Mattei MG, Chimini G | title = Chromosomal localization of the adrenoleukodystrophy-related gene in man and mice. | journal = Eur. J. Hum. Genet. | volume = 5 | issue = 2 | pages = 99–101 | year = 1997 | pmid = 9195160 | doi =  }}
*{{cite journal | author=Holzinger A, Mayerhofer P, Berger J, ''et al.'' |title=Full length cDNA cloning, promoter sequence, and genomic organization of the human adrenoleukodystrophy related (ALDR) gene functionally redundant to the gene responsible for X-linked adrenoleukodystrophy. |journal=Biochem. Biophys. Res. Commun. |volume=258 |issue= 2 |pages= 436-42 |year= 1999 |pmid= 10329405 |doi= 10.1006/bbrc.1999.0535 }}
*{{cite journal | author=Netik A, Forss-Petter S, Holzinger A, ''et al.'' |title=Adrenoleukodystrophy-related protein can compensate functionally for adrenoleukodystrophy protein deficiency (X-ALD): implications for therapy. |journal=Hum. Mol. Genet. |volume=8 |issue= 5 |pages= 907-13 |year= 1999 |pmid= 10196381 |doi= }}
*{{cite journal | author=Holzinger A, Kammerer S, Berger J, Roscher AA |title=cDNA cloning and mRNA expression of the human adrenoleukodystrophy related protein (ALDRP), a peroxisomal ABC transporter. |journal=Biochem. Biophys. Res. Commun. |volume=239 |issue= 1 |pages= 261-4 |year= 1997 |pmid= 9345306 |doi= 10.1006/bbrc.1997.7391 }}
*{{cite journal | author=Savary S, Troffer-Charlier N, Gyapay G, ''et al.'' |title=Chromosomal localization of the adrenoleukodystrophy-related gene in man and mice. |journal=Eur. J. Hum. Genet. |volume=5 |issue= 2 |pages= 99-101 |year= 1997 |pmid= 9195160 |doi=  }}
*{{cite journal  | author=Lombard-Platet G, Savary S, Sarde CO, ''et al.'' |title=A close relative of the adrenoleukodystrophy (ALD) gene codes for a peroxisomal protein with a specific expression pattern. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=93 |issue= 3 |pages= 1265-9 |year= 1996 |pmid= 8577752 |doi=  }}
}}
{{refend}}
{{refend}}


== External links ==
== External links ==
* {{MeshName|ABCD2+protein,+human}}
* {{MeshName|ABCD2+protein,+human}}
* {{UCSC gene info|ABCD2}}


{{membrane-protein-stub}}
{{NLM content}}
{{NLM content}}
{{Membrane transport proteins}}
{{ABC transporters}}
 
{{DEFAULTSORT:Abcd2}}
[[Category:ABC transporters]]
[[Category:ABC transporters]]
{{WikiDoc Sources}}
 
 
{{membrane-protein-stub}}

Latest revision as of 03:11, 27 October 2017

VALUE_ERROR (nil)
Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

n/a

n/a

RefSeq (protein)

n/a

n/a

Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

ATP-binding cassette sub-family D member 2 is a membrane pump/transporter protein that in humans is encoded by the ABCD2 gene.[1][2]

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. The function of this peroxisomal membrane protein is unknown; however this protein is speculated to function as a dimerization partner of ABCD1 and/or other peroxisomal ABC transporters.[2]

Clinical significance

Mutations in this gene have been observed in patients with adrenoleukodystrophy, a severe demyelinating disease. This gene has been identified as a candidate for a modifier gene, accounting for the extreme variation among adrenoleukodystrophy phenotypes. This gene is also a candidate for a complement group of Zellweger syndrome, a genetically heterogeneous disorder of peroxisomal biogenesis.[2]

See also

Interactions

ABCD2 has been shown to interact with PEX19.[3][4]

References

  1. Lombard-Platet G, Savary S, Sarde CO, Mandel JL, Chimini G (March 1996). "A close relative of the adrenoleukodystrophy (ALD) gene codes for a peroxisomal protein with a specific expression pattern". Proc Natl Acad Sci U S A. 93 (3): 1265–9. doi:10.1073/pnas.93.3.1265. PMC 40068. PMID 8577752.
  2. 2.0 2.1 2.2 "Entrez Gene: ABCD2 ATP-binding cassette, sub-family D (ALD), member 2".
  3. 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.
  4. 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

  • Petroni A, Cappa M, Carissimi R, Blasevich M, Uziel G (2007). "Effect of testosterone metabolites on ABC half-transporter relative gene expression in X-linked adrenoleukodystrophy". J. Inherit. Metab. Dis. 30 (5): 828. doi:10.1007/s10545-007-0591-1. PMID 17602313.
  • Weinhofer I, Kunze M, Rampler H, Bookout AL, Forss-Petter S, Berger J (2006). "Liver X receptor alpha interferes with SREBP1c-mediated Abcd2 expression. Novel cross-talk in gene regulation". J. Biol. Chem. 280 (50): 41243–51. doi:10.1074/jbc.M509450200. PMID 16249184.
  • Mayerhofer PU, Kattenfeld T, Roscher AA, Muntau AC (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.
  • Gloeckner CJ, Mayerhofer PU, Landgraf P, Muntau AC, Holzinger A, Gerber JK, Kammerer S, Adamski J, Roscher AA (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.
  • Sacksteder KA, Jones JM, South ST, Li X, Liu Y, Gould SJ (2000). "PEX19 binds multiple peroxisomal membrane proteins, is predominantly cytoplasmic, and is required for peroxisome membrane synthesis". J. Cell Biol. 148 (5): 931–44. doi:10.1083/jcb.148.5.931. PMC 2174547. PMID 10704444.
  • Liu LX, Janvier K, Berteaux-Lecellier V, Cartier N, Benarous R, Aubourg P (2000). "Homo- and heterodimerization of peroxisomal ATP-binding cassette half-transporters". J. Biol. Chem. 274 (46): 32738–43. doi:10.1074/jbc.274.46.32738. PMID 10551832.
  • Holzinger A, Mayerhofer P, Berger J, Lichtner P, Kammerer S, Roscher AA (1999). "Full length cDNA cloning, promoter sequence, and genomic organization of the human adrenoleukodystrophy related (ALDR) gene functionally redundant to the gene responsible for X-linked adrenoleukodystrophy". Biochem. Biophys. Res. Commun. 258 (2): 436–42. doi:10.1006/bbrc.1999.0535. PMID 10329405.
  • Netik A, Forss-Petter S, Holzinger A, Molzer B, Unterrainer G, Berger J (1999). "Adrenoleukodystrophy-related protein can compensate functionally for adrenoleukodystrophy protein deficiency (X-ALD): implications for therapy". Hum. Mol. Genet. 8 (5): 907–13. doi:10.1093/hmg/8.5.907. PMID 10196381.
  • Holzinger A, Kammerer S, Berger J, Roscher AA (1997). "cDNA cloning and mRNA expression of the human adrenoleukodystrophy related protein (ALDRP), a peroxisomal ABC transporter". Biochem. Biophys. Res. Commun. 239 (1): 261–4. doi:10.1006/bbrc.1997.7391. PMID 9345306.
  • Savary S, Troffer-Charlier N, Gyapay G, Mattei MG, Chimini G (1997). "Chromosomal localization of the adrenoleukodystrophy-related gene in man and mice". Eur. J. Hum. Genet. 5 (2): 99–101. PMID 9195160.

External links

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