PEX12 explained
Peroxisome assembly protein 12 is a protein that in humans is encoded by the PEX12 gene.[1]
Function
PEX12 is needed for protein import into peroxisomes.[2] This gene belongs to the peroxin-12 family. Peroxins (PEXs) are proteins that are essential for the assembly of functional peroxisomes.
Clinical significance
The peroxisome biogenesis disorders (PBDs; MIM 601539) are a group of genetically heterogeneous diseases that are usually lethal in early infancy. Although the clinical features of PBD patients vary, cells from all PBD patients exhibit a defect in the import of one or more classes of peroxisomal matrix proteins into the organelle. This cellular phenotype is shared by yeast 'pex' mutants, and human orthologs of yeast PEX genes defective in some PBD complementation groups (CGs).[3]
Interactions
PEX12 has been shown to interact with PEX10,[4] [5] PEX5[4] [5] and PEX19.[6] [7]
Further reading
- Okumoto K, Fujiki Y . PEX12 encodes an integral membrane protein of peroxisomes . Nat. Genet. . 17 . 3 . 265–6 . 1997 . 9354782 . 10.1038/ng1197-265 . 30206958 .
- Schrader M, Reuber BE, Morrell JC, etal . Expression of PEX11beta mediates peroxisome proliferation in the absence of extracellular stimuli . J. Biol. Chem. . 273 . 45 . 29607–14 . 1998 . 9792670 . 10.1074/jbc.273.45.29607 . free .
- Chang CC, Gould SJ . Phenotype-genotype relationships in complementation group 3 of the peroxisome-biogenesis disorders . Am. J. Hum. Genet. . 63 . 5 . 1294–306 . 1998 . 9792857 . 10.1086/302103 . 1377540 .
- South ST, Gould SJ . Peroxisome Synthesis in the Absence of Preexisting Peroxisomes . J. Cell Biol. . 144 . 2 . 255–66 . 1999 . 9922452 . 10.1083/jcb.144.2.255 . 2132891 .
- Chang CC, Warren DS, Sacksteder KA, Gould SJ . Pex12 Interacts with Pex5 and Pex10 and Acts Downstream of Receptor Docking in Peroxisomal Matrix Protein Import . J. Cell Biol. . 147 . 4 . 761–74 . 1999 . 10562279 . 10.1083/jcb.147.4.761 . 2156163 .
- Sacksteder KA, Jones JM, South ST, etal . Pex19 Binds Multiple Peroxisomal Membrane Proteins, Is Predominantly Cytoplasmic, and Is Required for Peroxisome Membrane Synthesis . J. Cell Biol. . 148 . 5 . 931–44 . 2000 . 10704444 . 10.1083/jcb.148.5.931 . 2174547 .
- Okumoto K, Abe I, Fujiki Y . Molecular anatomy of the peroxin Pex12p: ring finger domain is essential for Pex12p function and interacts with the peroxisome-targeting signal type 1-receptor Pex5p and a ring peroxin, Pex10p . J. Biol. Chem. . 275 . 33 . 25700–10 . 2000 . 10837480 . 10.1074/jbc.M003303200 . free .
- Fransen M, Wylin T, Brees C, etal . Human Pex19p Binds Peroxisomal Integral Membrane Proteins at Regions Distinct from Their Sorting Sequences . Mol. Cell. Biol. . 21 . 13 . 4413–24 . 2001 . 11390669 . 10.1128/MCB.21.13.4413-4424.2001 . 87101 .
- Fransen M, Brees C, Ghys K, etal . Analysis of mammalian peroxin interactions using a non-transcription-based bacterial two-hybrid assay . Mol. Cell. Proteomics . 1 . 3 . 243–52 . 2002 . 12096124 . 10.1074/mcp.M100025-MCP200 . free .
- Harper CC, Berg JM, Gould SJ . PEX5 binds the PTS1 independently of Hsp70 and the peroxin PEX12 . J. Biol. Chem. . 278 . 10 . 7897–901 . 2003 . 12456682 . 10.1074/jbc.M206651200 . free .
- Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
- Gootjes J, Schmohl F, Waterham HR, Wanders RJ . Novel mutations in the PEX12 gene of patients with a peroxisome biogenesis disorder . Eur. J. Hum. Genet. . 12 . 2 . 115–20 . 2004 . 14571262 . 10.1038/sj.ejhg.5201090 . free .
- Gootjes J, Schmohl F, Mooijer PA, etal . Identification of the molecular defect in patients with peroxisomal mosaicism using a novel method involving culturing of cells at 40 degrees C: implications for other inborn errors of metabolism . Hum. Mutat. . 24 . 2 . 130–9 . 2004 . 15241794 . 10.1002/humu.20062 . 17284974 . free .
- Gerhard DS, Wagner L, Feingold EA, etal . The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC) . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 .
- Mano S, Nakamori C, Nito K, etal . The Arabidopsis pex12 and pex13 mutants are defective in both PTS1- and PTS2-dependent protein transport to peroxisomes . Plant J. . 47 . 4 . 604–18 . 2007 . 16813573 . 10.1111/j.1365-313X.2006.02809.x . free .
- Zeharia A, Ebberink MS, Wanders RJ, etal . A novel PEX12 mutation identified as the cause of a peroxisomal biogenesis disorder with mild clinical phenotype, mild biochemical abnormalities in fibroblasts and a mosaic catalase immunofluorescence pattern, even at 40 degrees C . J. Hum. Genet. . 52 . 7 . 599–606 . 2007 . 17534573 . 10.1007/s10038-007-0157-y . free .
External links
Notes and References
- Chang CC, Lee WH, Moser H, Valle D, Gould SJ . Isolation of the human PEX12 gene, mutated in group 3 of the peroxisome biogenesis disorders . Nat Genet . 15 . 4 . 385–8 . April 1997 . 9090384 . 10.1038/ng0497-385 . 20825062 .
- Okumoto K, Shimozawa N, Kawai A, Tamura S, Tsukamoto T, Osumi T, Moser H, Wanders RJ, Suzuki Y, Kondo N, Fujiki Y . PEX12, the pathogenic gene of group III Zellweger syndrome: cDNA cloning by functional complementation on a CHO cell mutant, patient analysis, and characterization of PEX12p . Mol. Cell. Biol. . 18 . 7 . 4324–36 . July 1998 . 9632816 . 109016 . 10.1128/MCB.18.7.4324.
- Web site: Entrez Gene: PEX12 peroxisomal biogenesis factor 12.
- Chang CC, Warren DS, Sacksteder KA, Gould SJ . PEX12 interacts with PEX5 and PEX10 and acts downstream of receptor docking in peroxisomal matrix protein import . J. Cell Biol. . 147 . 4 . 761–74 . November 1999 . 10562279 . 10.1083/jcb.147.4.761 . 2156163 .
- Okumoto K, Abe I, Fujiki Y . Molecular anatomy of the peroxin Pex12p: ring finger domain is essential for Pex12p function and interacts with the peroxisome-targeting signal type 1-receptor Pex5p and a ring peroxin, Pex10p . J. Biol. Chem. . 275 . 33 . 25700–10 . August 2000 . 10837480 . 10.1074/jbc.M003303200 . free .
- Sacksteder KA, Jones JM, South ST, Li X, Liu Y, Gould SJ . PEX19 binds multiple peroxisomal membrane proteins, is predominantly cytoplasmic, and is required for peroxisome membrane synthesis . J. Cell Biol. . 148 . 5 . 931–44 . March 2000 . 10704444 . 2174547 . 10.1083/jcb.148.5.931 .
- Fransen M, Wylin T, Brees C, Mannaerts GP, Van Veldhoven PP . Human pex19p binds peroxisomal integral membrane proteins at regions distinct from their sorting sequences . Mol. Cell. Biol. . 21 . 13 . 4413–24 . July 2001 . 11390669 . 87101 . 10.1128/MCB.21.13.4413-4424.2001 .