PEX1

PEX1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1WLF
Identifiers
Aliases	PEX1 , PBD1A, PBD1B, ZWS, ZWS1, HMLR1, peroxisomal biogenesis factor 1
External IDs	OMIM: 602136; MGI: 1918632; HomoloGene: 27006; GeneCards: PEX1; OMA:PEX1 - orthologs
Gene location (Human) Chr. Chromosome 7 (human) [1] Band 7q21.2 Start 92,487,020 bp [1] End 92,528,520 bp [1]
Gene location (Mouse) Chr. Chromosome 5 (mouse) [2] Band 5|5 A1 Start 3,646,066 bp [2] End 3,687,232 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in Achilles tendon body of pancreas gastric mucosa skin of leg right hemisphere of cerebellum skin of abdomen rectum C1 segment left lobe of thyroid gland tibial nerve Top expressed in zygote secondary oocyte neural layer of retina hand left lobe of liver primary oocyte tail of embryo epithelium of small intestine superior frontal gyrus yolk sac More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein-containing complex binding nucleotide binding protein C-terminus binding protein binding ATP binding ATPase activity Cellular component cytoplasm cytosol peroxisomal membrane peroxisome extracellular exosome membrane Biological process protein targeting to peroxisome protein transport microtubule-based peroxisome localization peroxisome organization protein import into peroxisome matrix transport Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 5189 71382 Ensembl ENSG00000127980 ENSMUSG00000005907 UniProt O43933 Q5BL07 RefSeq (mRNA) NM_000466 NM_001282677 NM_001282678 NM_001293806 NM_027777 NM_177211 RefSeq (protein) NP_000457 NP_001269606 NP_001269607 NP_001280735 NP_082053 Location (UCSC) Chr 7: 92.49 – 92.53 Mb Chr 5: 3.65 – 3.69 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Peroxisome biogenesis factor 1, also known as PEX1, is a protein which in humans is encoded by the PEX1 gene. ^[5]

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. ^[5]

Interactions

PEX1 has been shown to interact with PEX6 ^{[6] [7]} and PEX26. ^[8]

Related diseases

Mutations in the genes encoding PEX1, along with PEX6, 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, PEX1 is usually found in carrier screening gene panels. A very common PEX1 variant, Gly843Asp, is a mild allele well-reported in the literature. ^[11]

References

1. GRCh38: Ensembl release 89: ENSG00000127980 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000005907 – 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.
5. "Entrez Gene: PEX1 peroxisome biogenesis factor 1".
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): 883–886. doi:10.1006/bbrc.1998.8522. PMID   9588209.
7. 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): 8630–8635. Bibcode:1998PNAS...95.8630G. doi: 10.1073/pnas.95.15.8630 . PMC   21127 . PMID   9671729.
8. 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): 454–460. doi:10.1038/ncb982. PMID   12717447. S2CID   2426040.
9. 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): 1430–1441. doi: 10.1016/j.bbadis.2012.04.006 . PMID   22871920.
10. Braverman NE, Raymond GV, Rizzo WB, Moser AB, Wilkinson ME, Stone EM, et al. (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): 313–321. doi:10.1016/j.ymgme.2015.12.009. PMC   5214431 . PMID   26750748.
11. Braverman NE, D'Agostino MD, Maclean GE (June 2013). "Peroxisome biogenesis disorders: Biological, clinical and pathophysiological perspectives". Developmental Disabilities Research Reviews. 17 (3): 187–196. doi:10.1002/ddrr.1113. PMID   23798008.

Further reading

• Wanders RJ (May 2004). "Metabolic and molecular basis of peroxisomal disorders: a review". American Journal of Medical Genetics. Part A. 126A (4): 355–375. doi:10.1002/ajmg.a.20661. PMID   15098234. S2CID   24025032.
• Crane DI, Maxwell MA, Paton BC (September 2005). "PEX1 mutations in the Zellweger spectrum of the peroxisome biogenesis disorders". Human Mutation. 26 (3): 167–175. doi: 10.1002/humu.20211 . PMID   16086329. S2CID   20330106.
• Naritomi K, Izumikawa Y, Ohshiro S, Yoshida K, Shimozawa N, Suzuki Y, et al. (December 1989). "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. doi:10.1007/BF00210677. PMID   2606480. S2CID   44388911.
• Reuber BE, Germain-Lee E, Collins CS, Morrell JC, Ameritunga R, Moser HW, et al. (December 1997). "Mutations in PEX1 are the most common cause of peroxisome biogenesis disorders". Nature Genetics. 17 (4): 445–448. doi:10.1038/ng1297-445. PMID   9398847. S2CID   34034756.
• Portsteffen H, Beyer A, Becker E, Epplen C, Pawlak A, Kunau WH, Dodt G (December 1997). "Human PEX1 is mutated in complementation group 1 of the peroxisome biogenesis disorders". Nature Genetics. 17 (4): 449–452. doi:10.1038/ng1297-449. PMID   9398848. S2CID   2487398.
• Faber KN, Heyman JA, Subramani S (February 1998). "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. doi:10.1128/mcb.18.2.936. PMC   108805 . PMID   9447990.
• Tamura S, Okumoto K, Toyama R, Shimozawa N, Tsukamoto T, Suzuki Y, et al. (April 1998). "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. Bibcode:1998PNAS...95.4350T. doi: 10.1073/pnas.95.8.4350 . PMC   22492 . PMID   9539740.
• 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): 883–886. 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): 8630–8635. Bibcode:1998PNAS...95.8630G. doi: 10.1073/pnas.95.15.8630 . PMC   21127 . PMID   9671729.
• Collins CS, Gould SJ (1999). "Identification of a common PEX1 mutation in Zellweger syndrome". Human Mutation. 14 (1): 45–53. doi: 10.1002/(SICI)1098-1004(1999)14:1<45::AID-HUMU6>3.0.CO;2-J . PMID   10447258. S2CID   22153024.
• 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): 417–426. doi:10.1042/0264-6021:3570417. PMC   1221968 . PMID   11439091.
• Preuss N, Brosius U, Biermanns M, Muntau AC, Conzelmann E, Gartner J (June 2002). "PEX1 mutations in complementation group 1 of Zellweger spectrum patients correlate with severity of disease". Pediatric Research. 51 (6): 706–714. doi: 10.1203/00006450-200206000-00008 . PMID   12032265.
• Maxwell MA, Allen T, Solly PB, Svingen T, Paton BC, Crane DI (November 2002). "Novel PEX1 mutations and genotype-phenotype correlations in Australasian peroxisome biogenesis disorder patients". Human Mutation. 20 (5): 342–351. doi: 10.1002/humu.10128 . PMID   12402331. S2CID   26081019.
• 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): 454–460. doi:10.1038/ncb982. PMID   12717447. S2CID   2426040.
• Dodt G, Walter C (2004). "Study of Mutant Proteins with Folding Defects in Cultured Patient Cells". Protein Misfolding and Disease. Methods Mol. Biol. Vol. 232. pp. 165–73. doi:10.1385/1-59259-394-1:165. ISBN   1-59259-394-1. PMID   12840548.

External links

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