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Gene Review

PEX5  -  peroxisomal biogenesis factor 5

Homo sapiens

Synonyms: PBD2A, PBD2B, PTS1 receptor, PTS1-BP, PTS1R, ...
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Disease relevance of PEX5


High impact information on PEX5

  • Peroxisomal targeting signals (PTSs) are recognized by predominantly cytosolic receptors, Pex5p and Pex7p [6].
  • This unusual shuttling mechanism for the PTS1 receptor distinguishes protein import into peroxisomes from that into most other organelles, with the exception of the nucleus [6].
  • The human peroxisomal targeting signal receptor, Pex5p, is translocated into the peroxisomal matrix and recycled to the cytosol [6].
  • Mutations in PXR1 define complementation group 2 of PBDs and expression of PXR1 rescues the PTS1 import defect of fibroblasts from these patients [7].
  • The conservation of the PTS1 receptor in several yeasts has led to the cloning and characterization of the gene encoding its human homolog, PTS1R, which is mutated in a group of patients afflicted with fatal peroxisomal disorders [8].

Biological context of PEX5

  • PEX5 encodes the type-1 peroxisomal targeting signal (PTS1) receptor, one of at least 15 peroxins required for peroxisome biogenesis [9].
  • Analysis of these complexes revealed that PEX5 possesses multiple binding sites for PEX14, which appear to be distributed throughout its N-terminal half [10].
  • In addition, we found that another protein known to interact with the PTS1-binding domain of PEX5, the PEX12 zinc RING domain, also had no discernable effect on PEX5-PTS1 binding kinetics [11].
  • Among the three peroxisome-deficient mutants obtained, ZP102 was a new CHO mutant of complementation group 2, and was restored for peroxisome assembly by the transfection of human PEX5 (formerly called PXR1 or PTS1R) cDNA [12].
  • Pex5p also accumulated on peroxisomes in normal cells under conditions which inhibit protein translocation into peroxisomes (low temperature or ATP depletion), returned to the cytoplasm when translocation was restored, and reaccumulated on peroxisomes when translocation was again inhibited [9].

Anatomical context of PEX5

  • Import of proteins with a PTS1 (peroxisomal targeting signal 1) into the Leishmania glycosomal organelle involves docking of a PTS1-laden LdPEX5 [Leishmania donovani PEX5 (peroxin 5)] receptor to LdPEX14 on the surface of the glycosomal membrane [13].
  • Altered distribution or stability of the PTS1 receptor in all cells with a defect in PTS1 protein import implies that the genes mutated in these cell lines encode proteins with a direct role in peroxisomal protein import [9].
  • After unloading the cargoes, Pex5 returns to the cytosol [14].
  • To address molecular mechanisms underlying Pex5 functions, we constructed a cell-free Pex5 translocation system with a postnuclear supernatant fraction from CHO cell lines [14].
  • Moreover, we analyzed the (35)S-Pex5-associated complexes on peroxisomal membranes by blue-native polyacrylamide gel electrophoresis [14].

Associations of PEX5 with chemical compounds


Physical interactions of PEX5

  • The RING finger of Pex12p bound to Pex10p and the PTS1-receptor Pex5p [20].
  • PEX13 protein has an SH3 docking site that binds to the PTS-1 receptor [21].
  • Pex5pL-(Pex7p-PTS2 protein) complexes were detectable in wild-type CHO-K1 cells and were apparently more stable in pex14 CHO cells deficient in the entry site of the matrix proteins, whereas only the Pex7p-PTS2 protein complex was discernible in a Pex5pL-defective pex5 CHO mutant [22].
  • PEX5 binds the PTS1 through its C-terminal 40-kDa tetratricopeptide repeat domain and is essential for import of PTS1-contining proteins into peroxisomes [11].
  • Hsp70 interacted with the TPR domain of Pex5p [23].

Regulatory relationships of PEX5

  • Recombinant human PTS1 binding protein Pex5p interacted with the bacterially expressed C-terminal domain of the HSD17B4 gene product [24].

Other interactions of PEX5

  • Loss of peroxins required for protein translocation into the peroxisome (PEX2 or PEX12) resulted in accumulation of Pex5p at docking sites on the peroxisome surface [9].
  • A pentapeptide motif that is reiterated seven times in PEX5 is proposed as a determinant for the interaction with PEX14 [10].
  • Disruption of the interaction of the longer isoform of Pex5p, Pex5pL, with Pex7p abolishes peroxisome targeting signal type 2 protein import in mammals. Study with a novel Pex5-impaired Chinese hamster ovary cell mutant [25].
  • In addition, we found that the PTS1 receptor was extremely unstable in the peroxin-deficient CG1, CG4, and CG8 cells [9].
  • Import of matrix proteins into peroxisomes requires two targeting signal-specific import receptors, Pex5p and Pex7p, and their binding partners at the peroxisomal membrane, Pex13p and Pex14p [10].

Analytical, diagnostic and therapeutic context of PEX5


  1. Docosahexaenoic acid deficit is not a major pathogenic factor in peroxisome-deficient mice. Janssen, A., Baes, M., Gressens, P., Mannaerts, G.P., Declercq, P., Van Veldhoven, P.P. Lab. Invest. (2000) [Pubmed]
  2. Human peroxisomal targeting signal-1 receptor restores peroxisomal protein import in cells from patients with fatal peroxisomal disorders. Wiemer, E.A., Nuttley, W.M., Bertolaet, B.L., Li, X., Francke, U., Wheelock, M.J., Anné, U.K., Johnson, K.R., Subramani, S. J. Cell Biol. (1995) [Pubmed]
  3. Lack of association of the pregnane X receptor (PXR/NR1I2) gene with inflammatory bowel disease: parallel allelic association study and gene wide haplotype analysis. Ho, G.T., Soranzo, N., Tate, S.K., Drummond, H., Nimmo, E.R., Tenesa, A., Arnott, I.D., Satsangi, J. Gut (2006) [Pubmed]
  4. In silico prediction of pregnane x receptor activators by machine learning approache. Ung, C.Y., Li, H., Yap, C.W., Chen, Y.Z. Mol. Pharmacol. (2007) [Pubmed]
  5. Crystal structure of the PXR-T1317 complex provides a scaffold to examine the potential for receptor antagonism. Xue, Y., Chao, E., Zuercher, W.J., Willson, T.M., Collins, J.L., Redinbo, M.R. Bioorg. Med. Chem. (2007) [Pubmed]
  6. The human peroxisomal targeting signal receptor, Pex5p, is translocated into the peroxisomal matrix and recycled to the cytosol. Dammai, V., Subramani, S. Cell (2001) [Pubmed]
  7. Mutations in the PTS1 receptor gene, PXR1, define complementation group 2 of the peroxisome biogenesis disorders. Dodt, G., Braverman, N., Wong, C., Moser, A., Moser, H.W., Watkins, P., Valle, D., Gould, S.J. Nat. Genet. (1995) [Pubmed]
  8. Convergence of model systems for peroxisome biogenesis. Subramani, S. Curr. Opin. Cell Biol. (1996) [Pubmed]
  9. Multiple PEX genes are required for proper subcellular distribution and stability of Pex5p, the PTS1 receptor: evidence that PTS1 protein import is mediated by a cycling receptor. Dodt, G., Gould, S.J. J. Cell Biol. (1996) [Pubmed]
  10. Recombinant human peroxisomal targeting signal receptor PEX5. Structural basis for interaction of PEX5 with PEX14. Schliebs, W., Saidowsky, J., Agianian, B., Dodt, G., Herberg, F.W., Kunau, W.H. J. Biol. Chem. (1999) [Pubmed]
  11. PEX5 binds the PTS1 independently of Hsp70 and the peroxin PEX12. Harper, C.C., Berg, J.M., Gould, S.J. J. Biol. Chem. (2003) [Pubmed]
  12. Isolation of a new peroxisome-deficient CHO cell mutant defective in peroxisome targeting signal-1 receptor. Tsukamoto, T., Bogaki, A., Okumoto, K., Tateishi, K., Fujiki, Y., Shimozawa, N., Suzuki, Y., Kondo, N., Osumi, T. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
  13. Peroxin 5-peroxin 14 association in the protozoan Leishmania donovani involves a novel protein-protein interaction motif. Madrid, K.P., Jardim, A. Biochem. J. (2005) [Pubmed]
  14. Shuttling mechanism of peroxisome targeting signal type 1 receptor Pex5: ATP-independent import and ATP-dependent export. Miyata, N., Fujiki, Y. Mol. Cell. Biol. (2005) [Pubmed]
  15. Peroxisomal targeting signal receptor Pex5p interacts with cargoes and import machinery components in a spatiotemporally differentiated manner: conserved Pex5p WXXXF/Y motifs are critical for matrix protein import. Otera, H., Setoguchi, K., Hamasaki, M., Kumashiro, T., Shimizu, N., Fujiki, Y. Mol. Cell. Biol. (2002) [Pubmed]
  16. Pex5p, the peroxisomal cycling receptor, is a monomeric non-globular protein. Costa-Rodrigues, J., Carvalho, A.F., Fransen, M., Hambruch, E., Schliebs, W., Sá-Miranda, C., Azevedo, J.E. J. Biol. Chem. (2005) [Pubmed]
  17. Absence of functional peroxisomes does not lead to deficiency of enzymes involved in cholesterol biosynthesis. Hogenboom, S., Romeijn, G.J., Houten, S.M., Baes, M., Wanders, R.J., Waterham, H.R. J. Lipid Res. (2002) [Pubmed]
  18. Orphan nuclear receptor pregnane X receptor sensitizes oxidative stress responses in transgenic mice and cancerous cells. Gong, H., Singh, S.V., Singh, S.P., Mu, Y., Lee, J.H., Saini, S.P., Toma, D., Ren, S., Kagan, V.E., Day, B.W., Zimniak, P., Xie, W. Mol. Endocrinol. (2006) [Pubmed]
  19. Pex5p binding affinities for canonical and noncanonical PTS1 peptides. Maynard, E.L., Gatto, G.J., Berg, J.M. Proteins (2004) [Pubmed]
  20. 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. Okumoto, K., Abe, I., Fujiki, Y. J. Biol. Chem. (2000) [Pubmed]
  21. Clinical, biochemical and genetic aspects and neuronal migration in peroxisome biogenesis disorders. Suzuki, Y., Shimozawa, N., Imamura, A., Fukuda, S., Zhang, Z., Orii, T., Kondo, N. J. Inherit. Metab. Dis. (2001) [Pubmed]
  22. Molecular Mechanisms of Import of Peroxisome-targeting Signal Type 2 (PTS2) Proteins by PTS2 Receptor Pex7p and PTS1 Receptor Pex5pL. Mukai, S., Fujiki, Y. J. Biol. Chem. (2006) [Pubmed]
  23. Hsp70 regulates the interaction between the peroxisome targeting signal type 1 (PTS1)-receptor Pex5p and PTS1. Harano, T., Nose, S., Uezu, R., Shimizu, N., Fujiki, Y. Biochem. J. (2001) [Pubmed]
  24. Peroxisome targeting of porcine 17beta-hydroxysteroid dehydrogenase type IV/D-specific multifunctional protein 2 is mediated by its C-terminal tripeptide AKI. Möller, G., Lüders, J., Markus, M., Husen, B., Van Veldhoven, P.P., Adamski, J. J. Cell. Biochem. (1999) [Pubmed]
  25. Disruption of the interaction of the longer isoform of Pex5p, Pex5pL, with Pex7p abolishes peroxisome targeting signal type 2 protein import in mammals. Study with a novel Pex5-impaired Chinese hamster ovary cell mutant. Matsumura, T., Otera, H., Fujiki, Y. J. Biol. Chem. (2000) [Pubmed]
  26. Temperature-sensitive phenotype of Chinese hamster ovary cells defective in PEX5 gene. Ito, R., Huang, Y., Yao, C., Shimozawa, N., Suzuki, Y., Kondo, N., Imanaka, T., Usuda, N., Ito, M. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  27. Formation of peroxisomes from peroxisomal ghosts in a peroxisome-deficient mammalian cell mutant upon complementation by protein microinjection. Yamasaki, M., Hashiguchi, N., Fujiwara, C., Imanaka, T., Tsukamoto, T., Osumi, T. J. Biol. Chem. (1999) [Pubmed]
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