InterPro domain: IPR024111

This entry include PEX5 (also known as PTS1R) from animals, fungi and plants. This entry also includes PEX5L from vertebrates. PEX5 binds to the C-terminal PTS1-type tripeptide peroxisomal targeting signal (SKL-type) and plays an essential role in peroxisomal protein import [ 1 , 2 , 3 ]. Based on subcellular localization and binding properties mammalian PEX5 may function as a regulator in an early step of the PTS1 protein import process [ 4 ]. PEX5L acts as an accessory subunit of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, regulating their cell-surface expression and cyclic nucleotide dependence [ 5 , 6 ]. Interestingly, although PEX5 and PEX5L have structurally similar binding at their TPR domains, they bind to different substrates in vivo [ 7 ].

Peroxisomal proteins catalyse metabolic reactions. The import of proteins from the cytosol into the peroxisomes matrix depends on more than a dozen peroxin (PEX) proteins, among which PEX5 and PEX7 serve as receptors that shuttle proteins bearing one of two peroxisome-targeting signals (PTSs) into the organelle. PEX5 is the PTS1 receptor, while PEX7 is the PTS2 receptor. In plants, PEX7 depends on PEX5 binding to deliver PTS2 cargo into the peroxisome, and PEX7 also facilitates PEX5 accumulation and import of PTS1 cargo into peroxisomes [ 7 , 8 ].

1. Temperature-sensitive phenotype of Chinese hamster ovary cells defective in PEX5 gene. Biochem. Biophys. Res. Commun. 288, 321-7
2. Identification of Pex5pM, and retarded maturation of 3-ketoacyl-CoA thiolase and acyl-CoA oxidase in CHO cells expressing mutant Pex5p isoforms. J. Biochem. 138, 781-90
3. 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. Mol. Cell. Biol. 22, 1639-55
4. Identification of PEX5p-related novel peroxisome-targeting signal 1 (PTS1)-binding proteins in mammals. Biochem. J. 357, 635-46
5. Structure and stoichiometry of an accessory subunit TRIP8b interaction with hyperpolarization-activated cyclic nucleotide-gated channels. Proc Natl Acad Sci U S A 109, 7899-904
6. The structure and function of TRIP8b, an auxiliary subunit of hyperpolarization-activated cyclic-nucleotide gated channels. Channels (Austin) 14, 110-122
7. The Arabidopsis peroxisomal targeting signal type 2 receptor PEX7 is necessary for peroxisome function and dependent on PEX5. Mol Biol Cell 16, 573-83
8. Interdependence of the peroxisome-targeting receptors in Arabidopsis thaliana: PEX7 facilitates PEX5 accumulation and import of PTS1 cargo into peroxisomes. Mol Biol Cell 21, 1263-71