PEX6 explained

Peroxisome assembly factor 2 is a protein that in humans is encoded by the PEX6 gene.^{[1] [2]} PEX6 is an AAA ATPase that localizes to the peroxisome. PEX6 forms a hexamer with PEX1^{[3] [4]} and is recruited to the membrane by PEX26.^[5]

Function

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.^[6] Work with pex6 mutants in Arabidopsis thaliana has shown that PEX6 may have a role in consuming oil body (plant-specific lipid droplets).^[7] Work with yeast pex6 mutants has shown that PEX6 is a key player in the autophagy of peroxisomes called pexophagy.^[8]

Related diseases

Mutations in the genes encoding PEX6, along with PEX1, are the leading causes of peroxisomal biogenesis disorders,^[9] 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.^[10] Because of the autosomal recessive inheritance of Zellweger Syndrome, PEX6 can usually be found in larger carrier screening gene panels.

Further reading

• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . January 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Fukuda S, Shimozawa N, Suzuki Y, Zhang Z, Tomatsu S, Tsukamoto T, Hashiguchi N, Osumi T, Masuno M, Imaizumi K, Kuroki Y, Fujiki Y, Orii T, Kondo N . Human peroxisome assembly factor-2 (PAF-2): a gene responsible for group C peroxisome biogenesis disorder in humans . American Journal of Human Genetics . 59 . 6 . 1210–20 . December 1996 . 8940266 . 1914864 .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . October 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• 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 . 883–6 . 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 . 8630–5 . July 1998 . 9671729 . 21127 . 10.1073/pnas.95.15.8630 . 1998PNAS...95.8630G . free .
• 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 . 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 . 1999 . 10408779 . 10.1002/(SICI)1098-1004(1999)13:6<487::AID-HUMU9>3.0.CO;2-T . 26542931 . free .
• Matsumoto N, Tamura S, Moser A, Moser HW, Braverman N, Suzuki Y, Shimozawa N, Kondo N, Fujiki Y . The peroxin Pex6p gene is impaired in peroxisomal biogenesis disorders of complementation group 6 . Journal of Human Genetics . 46 . 5 . 273–7 . 2001 . 11355018 . 10.1007/s100380170078 . 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 . 417–26 . July 2001 . 11439091 . 1221968 . 10.1042/0264-6021:3570417 .
• 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 . 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 . April 2002 . 11873320 . 379104 . 10.1086/339766 .
• Matsumoto N, Tamura S, Fujiki Y . The pathogenic peroxin Pex26p recruits the Pex1p-Pex6p AAA ATPase complexes to peroxisomes . Nature Cell Biology . 5 . 5 . 454–60 . May 2003 . 12717447 . 10.1038/ncb982 . 2426040 .
• Warner DR, Roberts EA, Greene RM, Pisano MM . Identification of novel Smad binding proteins . Biochemical and Biophysical Research Communications . 312 . 4 . 1185–90 . December 2003 . 14651998 . 10.1016/j.bbrc.2003.11.049 .
• Colland F, Jacq X, Trouplin V, Mougin C, Groizeleau C, Hamburger A, Meil A, Wojcik J, Legrain P, Gauthier JM . Functional proteomics mapping of a human signaling pathway . Genome Research . 14 . 7 . 1324–32 . July 2004 . 15231748 . 442148 . 10.1101/gr.2334104 .
• Furuki S, Tamura S, Matsumoto N, Miyata N, Moser A, Moser HW, Fujiki Y . 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 . January 2006 . 16257970 . 10.1074/jbc.M510044200 . free .
• Tamura S, Yasutake S, Matsumoto N, Fujiki Y . 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 . September 2006 . 16854980 . 10.1074/jbc.M605159200 . free .

External links

• GeneReviews/NCBI/NIH/UW entry on Peroxisome Biogenesis Disorders, Zellweger Syndrome Spectrum
• OMIM entries on Peroxisome Biogenesis Disorders, Zellweger Syndrome Spectrum

Notes and References

1. Yahraus T, Braverman N, Dodt G, Kalish JE, Morrell JC, Moser HW, Valle D, Gould SJ . The peroxisome biogenesis disorder group 4 gene, PXAAA1, encodes a cytoplasmic ATPase required for stability of the PTS1 receptor . The EMBO Journal . 15 . 12 . 2914–23 . June 1996 . 8670792 . 450231 . 10.1002/j.1460-2075.1996.tb00654.x.
2. Web site: Entrez Gene: PEX6 peroxisomal biogenesis factor 6.
3. 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 . 883–6 . April 1998 . 9588209 . 10.1006/bbrc.1998.8522 .
4. Gardner BM, Chowdhury S, Lander GC, Martin A . The Pex1/Pex6 complex is a heterohexameric AAA+ motor with alternating and highly coordinated subunits . Journal of Molecular Biology . 427 . 6 Pt B . 1375–88 . March 2015 . 25659908 . 10.1016/j.jmb.2015.01.019 . 4355278.
5. Matsumoto N, Tamura S, Fujiki Y . The pathogenic peroxin Pex26p recruits the Pex1p-Pex6p AAA ATPase complexes to peroxisomes . Nature Cell Biology . 5 . 5 . 454–60 . May 2003 . 12717447 . 10.1038/ncb982 . 2426040 .
6. Zolman BK, Bartel B . An Arabidopsis indole-3-butyric acid-response mutant defective in PEROXIN6, an apparent ATPase implicated in peroxisomal function . en . Proceedings of the National Academy of Sciences of the United States of America . 101 . 6 . 1786–91 . February 2004 . 14745029 . 10.1073/pnas.0304368101 . 341854. 2004PNAS..101.1786Z . free .
7. Gonzalez KL, Fleming WA, Kao YT, Wright ZJ, Venkova SV, Ventura MJ, Bartel B . Disparate peroxisome-related defects in Arabidopsis pex6 and pex26 mutants link peroxisomal retrotranslocation and oil body utilization . en . The Plant Journal . 92 . 1 . 110–128 . October 2017 . 28742939 . 10.1111/tpj.13641 . 5605450.
8. Nuttall JM, Motley AM, Hettema EH . Deficiency of the exportomer components Pex1, Pex6, and Pex15 causes enhanced pexophagy in Saccharomyces cerevisiae . Autophagy . 10 . 5 . 835–45 . May 2014 . 24657987 . 10.4161/auto.28259 . 5119063.
9. Waterham HR, Ebberink MS . Genetics and molecular basis of human peroxisome biogenesis disorders . Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease . 1822 . 9 . 1430–41 . September 2012 . 22871920 . 10.1016/j.bbadis.2012.04.006 . free .
10. Braverman NE, Raymond GV, Rizzo WB, Moser AB, Wilkinson ME, Stone EM, Steinberg SJ, Wangler MF, Rush ET, Hacia JG, Bose M . 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 . March 2016 . 26750748 . 10.1016/j.ymgme.2015.12.009 . 5214431.