PEX1 explained
Peroxisome biogenesis factor 1, also known as PEX1, is a protein which in humans is encoded by the PEX1 gene.[1]
This gene encodes a member of the AAA protein family, a large group of ATPases associated with diverse cellular activities. This protein is cytoplasmic but is often anchored to a peroxisomal membrane where it forms a heteromeric complex and plays a role in the import of proteins into peroxisomes and peroxisome biogenesis. Mutations in this gene have been associated with complementation group 1 peroxisomal disorders such as neonatal adrenoleukodystrophy, infantile Refsum disease, and Zellweger syndrome.[1]
Interactions
PEX1 has been shown to interact with PEX6[2] [3] and PEX26.[4]
Related diseases
Mutations in the genes encoding PEX1, along with PEX6, are the leading causes of peroxisomal biogenesis disorders,[5] such as Zellweger Syndrome spectrum, infantile Refsum disease, and neonatal adrenoleukodystrophy. These genetic diseases are autosomal recessive and occur in 1 of every 50,000 births.[6] Because of the autosomal recessive inheritance of Zellweger Syndrome, PEX1 is usually found in carrier screening gene panels. A very common PEX1 variant, Gly843Asp, is a mild allele well-reported in the literature.[7]
Further reading
- Wanders RJ . Metabolic and molecular basis of peroxisomal disorders: a review . American Journal of Medical Genetics. Part A . 126A . 4 . 355–375 . May 2004 . 15098234 . 10.1002/ajmg.a.20661 . 24025032 .
- Crane DI, Maxwell MA, Paton BC . PEX1 mutations in the Zellweger spectrum of the peroxisome biogenesis disorders . Human Mutation . 26 . 3 . 167–175 . September 2005 . 16086329 . 10.1002/humu.20211 . 20330106 . free .
- Naritomi K, Izumikawa Y, Ohshiro S, Yoshida K, Shimozawa N, Suzuki Y, Orii T, Hirayama K . 6 . Gene assignment of Zellweger syndrome to 7q11.23: report of the second case associated with a pericentric inversion of chromosome 7 . Human Genetics . 84 . 1 . 79–80 . December 1989 . 2606480 . 10.1007/BF00210677 . 44388911 .
- Reuber BE, Germain-Lee E, Collins CS, Morrell JC, Ameritunga R, Moser HW, Valle D, Gould SJ . 6 . Mutations in PEX1 are the most common cause of peroxisome biogenesis disorders . Nature Genetics . 17 . 4 . 445–448 . December 1997 . 9398847 . 10.1038/ng1297-445 . 34034756 .
- Portsteffen H, Beyer A, Becker E, Epplen C, Pawlak A, Kunau WH, Dodt G . Human PEX1 is mutated in complementation group 1 of the peroxisome biogenesis disorders . Nature Genetics . 17 . 4 . 449–452 . December 1997 . 9398848 . 10.1038/ng1297-449 . 2487398 .
- Faber KN, Heyman JA, Subramani S . Two AAA family peroxins, PpPex1p and PpPex6p, interact with each other in an ATP-dependent manner and are associated with different subcellular membranous structures distinct from peroxisomes . Molecular and Cellular Biology . 18 . 2 . 936–943 . February 1998 . 9447990 . 108805 . 10.1128/mcb.18.2.936 .
- Tamura S, Okumoto K, Toyama R, Shimozawa N, Tsukamoto T, Suzuki Y, Osumi T, Kondo N, Fujiki Y . 6 . Human PEX1 cloned by functional complementation on a CHO cell mutant is responsible for peroxisome-deficient Zellweger syndrome of complementation group I . Proceedings of the National Academy of Sciences of the United States of America . 95 . 8 . 4350–4355 . April 1998 . 9539740 . 22492 . 10.1073/pnas.95.8.4350 . free . 1998PNAS...95.4350T .
- Tamura S, Shimozawa N, Suzuki Y, Tsukamoto T, Osumi T, Fujiki Y . A cytoplasmic AAA family peroxin, Pex1p, interacts with Pex6p . Biochemical and Biophysical Research Communications . 245 . 3 . 883–886 . April 1998 . 9588209 . 10.1006/bbrc.1998.8522 .
- Geisbrecht BV, Collins CS, Reuber BE, Gould SJ . Disruption of a PEX1-PEX6 interaction is the most common cause of the neurologic disorders Zellweger syndrome, neonatal adrenoleukodystrophy, and infantile Refsum disease . Proceedings of the National Academy of Sciences of the United States of America . 95 . 15 . 8630–8635 . July 1998 . 9671729 . 21127 . 10.1073/pnas.95.15.8630 . free . 1998PNAS...95.8630G .
- Collins CS, Gould SJ . Identification of a common PEX1 mutation in Zellweger syndrome . Human Mutation . 14 . 1 . 45–53 . 1999 . 10447258 . 10.1002/(SICI)1098-1004(1999)14:1<45::AID-HUMU6>3.0.CO;2-J . 22153024 . free .
- Tamura S, Matsumoto N, Imamura A, Shimozawa N, Suzuki Y, Kondo N, Fujiki Y . Phenotype-genotype relationships in peroxisome biogenesis disorders of PEX1-defective complementation group 1 are defined by Pex1p-Pex6p interaction . The Biochemical Journal . 357 . Pt 2 . 417–426 . July 2001 . 11439091 . 1221968 . 10.1042/0264-6021:3570417 .
- Preuss N, Brosius U, Biermanns M, Muntau AC, Conzelmann E, Gartner J . PEX1 mutations in complementation group 1 of Zellweger spectrum patients correlate with severity of disease . Pediatric Research . 51 . 6 . 706–714 . June 2002 . 12032265 . 10.1203/00006450-200206000-00008 . free .
- Maxwell MA, Allen T, Solly PB, Svingen T, Paton BC, Crane DI . Novel PEX1 mutations and genotype-phenotype correlations in Australasian peroxisome biogenesis disorder patients . Human Mutation . 20 . 5 . 342–351 . November 2002 . 12402331 . 10.1002/humu.10128 . 26081019 . free .
- Matsumoto N, Tamura S, Fujiki Y . The pathogenic peroxin Pex26p recruits the Pex1p-Pex6p AAA ATPase complexes to peroxisomes . Nature Cell Biology . 5 . 5 . 454–460 . May 2003 . 12717447 . 10.1038/ncb982 . 2426040 .
- Book: Dodt G, Walter C . Study of Mutant Proteins with Folding Defects in Cultured Patient Cells . Protein Misfolding and Disease . Methods Mol. Biol. . 232 . 165–73 . 2004 . 12840548 . 10.1385/1-59259-394-1:165 . 1-59259-394-1 .
External links
Notes and References
- Web site: Entrez Gene: PEX1 peroxisome biogenesis factor 1.
- Tamura S, Shimozawa N, Suzuki Y, Tsukamoto T, Osumi T, Fujiki Y . A cytoplasmic AAA family peroxin, Pex1p, interacts with Pex6p . Biochemical and Biophysical Research Communications . 245 . 3 . 883–886 . April 1998 . 9588209 . 10.1006/bbrc.1998.8522 .
- Geisbrecht BV, Collins CS, Reuber BE, Gould SJ . Disruption of a PEX1-PEX6 interaction is the most common cause of the neurologic disorders Zellweger syndrome, neonatal adrenoleukodystrophy, and infantile Refsum disease . Proceedings of the National Academy of Sciences of the United States of America . 95 . 15 . 8630–8635 . July 1998 . 9671729 . 21127 . 10.1073/pnas.95.15.8630 . 1998PNAS...95.8630G . free .
- Matsumoto N, Tamura S, Fujiki Y . The pathogenic peroxin Pex26p recruits the Pex1p-Pex6p AAA ATPase complexes to peroxisomes . Nature Cell Biology . 5 . 5 . 454–460 . May 2003 . 12717447 . 10.1038/ncb982 . 2426040 .
- Waterham HR, Ebberink MS . Genetics and molecular basis of human peroxisome biogenesis disorders . Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease . 1822 . 9 . 1430–1441 . September 2012 . 22871920 . 10.1016/j.bbadis.2012.04.006 . free .
- Braverman NE, Raymond GV, Rizzo WB, Moser AB, Wilkinson ME, Stone EM, Steinberg SJ, Wangler MF, Rush ET, Hacia JG, Bose M . 6 . Peroxisome biogenesis disorders in the Zellweger spectrum: An overview of current diagnosis, clinical manifestations, and treatment guidelines . Molecular Genetics and Metabolism . 117 . 3 . 313–321 . March 2016 . 26750748 . 5214431 . 10.1016/j.ymgme.2015.12.009 .
- Braverman NE, D'Agostino MD, Maclean GE . Peroxisome biogenesis disorders: Biological, clinical and pathophysiological perspectives . Developmental Disabilities Research Reviews . 17 . 3 . 187–196 . June 2013 . 23798008 . 10.1002/ddrr.1113 .