PEX6

PEX6
Identifiers
Aliases	PEX6, PAF-2, PAF2, PBD4A, PDB4B, PXAAA1, HMLR2, peroxisomal biogenesis factor 6
External IDs	OMIM: 601498; MGI: 2385054; HomoloGene: 47914; GeneCards: PEX6; OMA:PEX6 - orthologs
Gene location (Human)
Chr.	Chromosome 6 (human)
End	42,979,181 bp
Gene location (Mouse)
Chr.	Chromosome 17 (mouse)
End	47,036,467 bp
RNA expression pattern
	Top expressed in
	right uterine tube; ; body of pancreas; ; mucosa of transverse colon; ; right hemisphere of cerebellum; ; right lobe of liver; ; anterior pituitary; ; right ovary; ; left ovary; ; right frontal lobe; ; right adrenal gland;
	Top expressed in
	Rostral migratory stream; ; internal carotid artery; ; left lobe of liver; ; external carotid artery; ; brown adipose tissue; ; ciliary body; ; transitional epithelium of urinary bladder; ; motor neuron; ; Paneth cell; ; vas deferens;
	More reference expression data
	; ;
	More reference expression data
Gene ontology
Molecular function	nucleotide binding; protein C-terminus binding; ATPase activity; protein binding; ATP binding; protein-containing complex binding;
Cellular component	cytoplasm; peroxisomal membrane; peroxisome; membrane; photoreceptor cell cilium; photoreceptor outer segment; cell projection; cytosol;
Biological process	protein stabilization; peroxisome organization; protein import into peroxisome matrix, translocation; protein targeting to peroxisome; protein import into peroxisome matrix;
	Sources:Amigo / QuickGO
Orthologs
	5190
	224824
	ENSG00000124587
	ENSMUSG00000002763
	Q13608
	Q99LC9
	NM_000287; NM_001316313
	NM_145488
	NP_000278; NP_001303242
	NP_663463
	Wikidata
View/Edit Human	View/Edit Mouse

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]

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.^[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]

Related diseases

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.

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000124587 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000002763 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Yahraus T, Braverman N, Dodt G, Kalish JE, Morrell JC, Moser HW, Valle D, Gould SJ (June 1996). "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. doi:10.1002/j.1460-2075.1996.tb00654.x. PMC 450231. PMID 8670792.
^ "Entrez Gene: PEX6 peroxisomal biogenesis factor 6".
^ 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.
^ Gardner BM, Chowdhury S, Lander GC, Martin A (March 2015). "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. doi:10.1016/j.jmb.2015.01.019. PMC 4355278. PMID 25659908.
^ 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.
^ Zolman BK, Bartel B (February 2004). "An Arabidopsis indole-3-butyric acid-response mutant defective in PEROXIN6, an apparent ATPase implicated in peroxisomal function". Proceedings of the National Academy of Sciences of the United States of America. 101 (6): 1786–91. Bibcode:2004PNAS..101.1786Z. doi:10.1073/pnas.0304368101. PMC 341854. PMID 14745029.
^ Gonzalez KL, Fleming WA, Kao YT, Wright ZJ, Venkova SV, Ventura MJ, Bartel B (October 2017). "Disparate peroxisome-related defects in Arabidopsis pex6 and pex26 mutants link peroxisomal retrotranslocation and oil body utilization". The Plant Journal. 92 (1): 110–128. doi:10.1111/tpj.13641. PMC 5605450. PMID 28742939.
^ Nuttall JM, Motley AM, Hettema EH (May 2014). "Deficiency of the exportomer components Pex1, Pex6, and Pex15 causes enhanced pexophagy in Saccharomyces cerevisiae". Autophagy. 10 (5): 835–45. doi:10.4161/auto.28259. PMC 5119063. PMID 24657987.
^ Waterham HR, Ebberink MS (September 2012). "Genetics and molecular basis of human peroxisome biogenesis disorders". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1822 (9): 1430–41. doi:10.1016/j.bbadis.2012.04.006. PMID 22871920.
^ 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.

External links

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000124587 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000002763 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid8670792-5] Yahraus T, Braverman N, Dodt G, Kalish JE, Morrell JC, Moser HW, Valle D, Gould SJ (June 1996). "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. doi:10.1002/j.1460-2075.1996.tb00654.x. PMC 450231. PMID 8670792.

[entrez-6] "Entrez Gene: PEX6 peroxisomal biogenesis factor 6".

[pmid9588209-7] 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.

[8] Gardner BM, Chowdhury S, Lander GC, Martin A (March 2015). "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. doi:10.1016/j.jmb.2015.01.019. PMC 4355278. PMID 25659908.

[pmid12717447-9] 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.

[10] Zolman BK, Bartel B (February 2004). "An Arabidopsis indole-3-butyric acid-response mutant defective in PEROXIN6, an apparent ATPase implicated in peroxisomal function". Proceedings of the National Academy of Sciences of the United States of America. 101 (6): 1786–91. Bibcode:2004PNAS..101.1786Z. doi:10.1073/pnas.0304368101. PMC 341854. PMID 14745029.

[11] Gonzalez KL, Fleming WA, Kao YT, Wright ZJ, Venkova SV, Ventura MJ, Bartel B (October 2017). "Disparate peroxisome-related defects in Arabidopsis pex6 and pex26 mutants link peroxisomal retrotranslocation and oil body utilization". The Plant Journal. 92 (1): 110–128. doi:10.1111/tpj.13641. PMC 5605450. PMID 28742939.

[12] Nuttall JM, Motley AM, Hettema EH (May 2014). "Deficiency of the exportomer components Pex1, Pex6, and Pex15 causes enhanced pexophagy in Saccharomyces cerevisiae". Autophagy. 10 (5): 835–45. doi:10.4161/auto.28259. PMC 5119063. PMID 24657987.

[13] Waterham HR, Ebberink MS (September 2012). "Genetics and molecular basis of human peroxisome biogenesis disorders". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1822 (9): 1430–41. doi:10.1016/j.bbadis.2012.04.006. PMID 22871920.

[14] 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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Function

Related diseases

References

Further reading

External links