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 [, ]. 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 [, , ]. Based on subcellular localization and binding properties mammalian PEX5 may function as a regulator in an early step of the PTS1 protein import process []. PEX5L acts as an accessory subunit of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, regulating their cell-surface expression and cyclic nucleotide dependence [, ]. Interestingly, although PEX5 and PEX5L have structurally similar binding at their TPR domains, they bind to different substrates in vivo [].
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 [, ]. This entry represents PEX7 from animals, fungi and plants. In plants it plays important roles in embryonic development, seedling establishment, and vegetative growth []. Budding yeast PEX7 homologue, Pas7, is necessary for import of thiolase (a PTS2-containing protein) []. In humans PEX7 has been linked to several diseases, such as Rhizomelic chondrodysplasia punctata 1 (RCDP1) []and Peroxisome biogenesis disorder 9B (PBD9B) [].
Peroxisomal proteins, called peroxins, participate in the process of peroxisome assembly. Specific amino acid sequences (PTS or peroxisomal targeting signal) at the C terminus (PTS1) or N terminus (PTS2) are present in peroxisomal matrix proteins, which signals them to be imported. The protein receptors Pex5 and Pex7 accompany their cargoes (containing a PTS1 or a PTS2 amino acid sequence, respectively) into the peroxisome. Ubiquitination appears to be crucial for the export of Pex5 from the peroxisome to the cytosol. The monoubiquitination of the PTS1-receptor Pex5p is catalyzed by the E2 enzyme Pex4.Pex22 anchors Pex4 to the peroxisome membrane [, ]. Moreover, Pex4 requires the interaction with Pex22 to display full activity []. The N-terminal portion of Pex22 has a membrane anchoring function, whereas the C-terminal domain harbours its biological activity. The soluble C-terminal domain of Pex22 is essential for peroxisomal biogenesis and efficient monoubiquitination of the import receptor Pex5 [].
This entry represents the PEX5-related proteins (PEX5L, also known as TRIP8b) from vertebrates. It acts as an accessory subunit of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, regulating their cell-surface expression and cyclic nucleotide dependence [, ]. Interestingly, although PEX5L and PEX5 have structurally similar binding at their TPR domains, they bind to different substrates in vivo [].
Peroxisome biogenesis factor 1, also known as peroxin-1 or PEX1, is a component of the peroxisomal protein import machinery. In addition to its role in import, PEX1 together with PEX6, mediates the ATP-dependent relocation and recycling of the peroxisomal targeting signal-1 (PTS1) import receptor PEX5 from the peroxisomal membrane to the cytosol [, , ].
Peroxin-13 (Pex13), located in the peroxisomal membrane, is a component of the peroxisomal translocation machinery with peroxin-14 and peroxin-17. Both termini of peroxin-13 are oriented to the cytosol. It is required for peroxisomal association of peroxin-14 []. Both human and budding yeast Pex13 bind to the PTS1 signal recognition factor Pex5. However, they bind to Pex5 through different binding sites []. In budding yeasts, Pex13 is also involved in the PTS2 signal recognition through its interaction with Pex7 [].
This superfamily represents the CDC48 domain 2-like domain, which can be found in the N-terminal of the peroxisome biogenesis factor 1 and the domain 2 of the AAA ATPases.CDC48 from yeasts is an AAA ATPase that is involved in protein export from the endoplasmic reticulum to the cytoplasm [].Peroxisome biogenesis factor 1, also known as peroxin-1 or PEX1, is a component of the peroxisomal protein import machinery. In addition to its role in import, PEX1 together with PEX6, mediates the ATP-dependent relocation and recycling of the peroxisomal targeting signal-1 (PTS1) import receptor PEX5 from the peroxisomal membrane to the cytosol [, , ].
Two types of peroxisomal targeting signal, PTS1 and PTS2, have been identified as amino acid sequences necessary for peroxisome sorting. The peroxisomal proteins containing PTS are recognised by specific receptors and are delivered to the peroxisomal membrane.Peroxisomal targeting signal 1 receptor (PTS1R, also known as PEX5) binds to the C-terminal PTS1-type tripeptide peroxisomal targeting signal (SKL-type) and plays an essential role in peroxisomal protein import [, , ]. Proteins related to PTS1R (generally known as PEX5-related proteins) have been identified in mammals. Based on subcellular localization and binding properties they may function as a regulator in an early step of the PTS1 protein import process []. This entry represents PEX5 (also known as PTS1R) from animals.
