Peroxisome assembly factor 2 is a protein that in humans is encoded by the PEX6 gene.[5][6] PEX6 is an AAA ATPase that localizes to the peroxisome. PEX6 forms a hexamer with PEX1[7][8] and is recruited to the membrane by PEX26.[9]
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From yeast to plants to humans, there is only one verified function of PEX6; PEX6 (and PEX1) removes PEX5 from the peroxisomal membrane so that PEX5 may do additional rounds of peroxisomal import. Human PEX6 can genetically complement plant pex6 mutants, which highlights functional conservation.[10] Work with pex6 mutants in Arabidopsis thaliana has shown that PEX6 may have a role in consuming oil body (plant-specific lipid droplets).[11] Work with yeast pex6 mutants has shown that PEX6 is a key player in the autophagy of peroxisomes called pexophagy.[12]
Mutations in the genes encoding PEX6, along with PEX1, are the leading causes of peroxisomal biogenesis disorders,[13] 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.[14] Because of the autosomal recessive inheritance of Zellweger Syndrome, PEX6 can usually be found in larger carrier screening gene panels.
Tamura S, Shimozawa N, Suzuki Y, Tsukamoto T, Osumi T, Fujiki Y (April 1998). "A cytoplasmic AAA family peroxin, Pex1p, interacts with Pex6p". Biochemical and Biophysical Research Communications. 245 (3): 883–6. doi:10.1006/bbrc.1998.8522. PMID 9588209.
Matsumoto N, Tamura S, Fujiki Y (May 2003). "The pathogenic peroxin Pex26p recruits the Pex1p-Pex6p AAA ATPase complexes to peroxisomes". Nature Cell Biology. 5 (5): 454–60. doi:10.1038/ncb982. PMID 12717447. S2CID 2426040.
Braverman NE, Raymond GV, Rizzo WB, Moser AB, Wilkinson ME, Stone EM, Steinberg SJ, Wangler MF, Rush ET, Hacia JG, Bose M (March 2016). "Peroxisome biogenesis disorders in the Zellweger spectrum: An overview of current diagnosis, clinical manifestations, and treatment guidelines". Molecular Genetics and Metabolism. 117 (3): 313–21. doi:10.1016/j.ymgme.2015.12.009. PMC 5214431. PMID 26750748.
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- Tamura S, Shimozawa N, Suzuki Y, Tsukamoto T, Osumi T, Fujiki Y (April 1998). "A cytoplasmic AAA family peroxin, Pex1p, interacts with Pex6p". Biochemical and Biophysical Research Communications. 245 (3): 883–6. doi:10.1006/bbrc.1998.8522. PMID 9588209.
- Geisbrecht BV, Collins CS, Reuber BE, Gould SJ (July 1998). "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): 8630–5. Bibcode:1998PNAS...95.8630G. doi:10.1073/pnas.95.15.8630. PMC 21127. PMID 9671729.
- Zhang Z, Suzuki Y, Shimozawa N, Fukuda S, Imamura A, Tsukamoto T, Osumi T, Fujiki Y, Orii T, Wanders RJ, Barth PG, Moser HW, Paton BC, Besley GT, Kondo N (1999). "Genomic structure and identification of 11 novel mutations of the PEX6 (peroxisome assembly factor-2) gene in patients with peroxisome biogenesis disorders". Human Mutation. 13 (6): 487–96. doi:10.1002/(SICI)1098-1004(1999)13:6<487::AID-HUMU9>3.0.CO;2-T. PMID 10408779. S2CID 26542931.
- Matsumoto N, Tamura S, Moser A, Moser HW, Braverman N, Suzuki Y, Shimozawa N, Kondo N, Fujiki Y (2001). "The peroxin Pex6p gene is impaired in peroxisomal biogenesis disorders of complementation group 6". Journal of Human Genetics. 46 (5): 273–7. doi:10.1007/s100380170078. PMID 11355018.
- Tamura S, Matsumoto N, Imamura A, Shimozawa N, Suzuki Y, Kondo N, Fujiki Y (July 2001). "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): 417–26. doi:10.1042/0264-6021:3570417. PMC 1221968. PMID 11439091.
- Raas-Rothschild A, Wanders RJ, Mooijer PA, Gootjes J, Waterham HR, Gutman A, Suzuki Y, Shimozawa N, Kondo N, Eshel G, Espeel M, Roels F, Korman SH (April 2002). "A PEX6-defective peroxisomal biogenesis disorder with severe phenotype in an infant, versus mild phenotype resembling Usher syndrome in the affected parents". American Journal of Human Genetics. 70 (4): 1062–8. doi:10.1086/339766. PMC 379104. PMID 11873320.
- Matsumoto N, Tamura S, Fujiki Y (May 2003). "The pathogenic peroxin Pex26p recruits the Pex1p-Pex6p AAA ATPase complexes to peroxisomes". Nature Cell Biology. 5 (5): 454–60. doi:10.1038/ncb982. PMID 12717447. S2CID 2426040.
- Warner DR, Roberts EA, Greene RM, Pisano MM (December 2003). "Identification of novel Smad binding proteins". Biochemical and Biophysical Research Communications. 312 (4): 1185–90. doi:10.1016/j.bbrc.2003.11.049. PMID 14651998.
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- Furuki S, Tamura S, Matsumoto N, Miyata N, Moser A, Moser HW, Fujiki Y (January 2006). "Mutations in the peroxin Pex26p responsible for peroxisome biogenesis disorders of complementation group 8 impair its stability, peroxisomal localization, and interaction with the Pex1p x Pex6p complex". The Journal of Biological Chemistry. 281 (3): 1317–23. doi:10.1074/jbc.M510044200. PMID 16257970.
- Tamura S, Yasutake S, Matsumoto N, Fujiki Y (September 2006). "Dynamic and functional assembly of the AAA peroxins, Pex1p and Pex6p, and their membrane receptor Pex26p". The Journal of Biological Chemistry. 281 (38): 27693–704. doi:10.1074/jbc.M605159200. PMID 16854980.