Peroxisomal targeting signal 1 receptor

Definition:

Receptor that mediates peroxisomal import of proteins containing a C-terminal PTS1-type tripeptide peroxisomal targeting signal (SKL-type). Binds to cargo proteins containing a PTS1 peroxisomal targeting signal in the cytosol, and translocates them into the peroxisome matrix by passing through the PEX13-PEX14 docking complex along with cargo proteins. PEX5 receptor is then retrotranslocated into the cytosol, leading to release of bound cargo in the peroxisome matrix, and reset for a subsequent peroxisome import cycle.; [Isoform 1]: In addition to promoting peroxisomal translocation of proteins containing a PTS1 peroxisomal targeting signal, mediates peroxisomal import of proteins containing a C-terminal PTS2-type peroxisomal targeting signal via its interaction with PEX7. Interaction with PEX7 only takes place when PEX7 is associated with cargo proteins containing a PTS2 peroxisomal targeting signal. PEX7 along with PTS2-containing cargo proteins are then translocated through the PEX13-PEX14 docking complex together with PEX5.; [Isoform 2]: Does not mediate translocation of peroxisomal import of proteins containing a C-terminal PTS2-type peroxisomal targeting signal.

References:

[1]. Courtney C Harper, et al. PEX5 binds the PTS1 independently of Hsp70 and the peroxin PEX12. J Biol Chem. 2003 Mar 7;278(10):7897-901. [Content Brief]

[2]. Jiangwei Zhang, et al. ATM functions at the peroxisome to induce pexophagy in response to ROS. Nat Cell Biol. 2015 Oct;17(10):1259-1269. [Content Brief]

[3]. G J Gatto Jr, et al. Peroxisomal targeting signal-1 recognition by the TPR domains of human PEX5. Nat Struct Biol. 2000 Dec;7(12):1091-5. [Content Brief]

[4]. Will A Stanley, et al. Recognition of a functional peroxisome type 1 target by the dynamic import receptor pex5p. Mol Cell. 2006 Dec 8;24(5):653-663. [Content Brief]

[5]. G Dodt, et al. Mutations in the PTS1 receptor gene, PXR1, define complementation group 2 of the peroxisome biogenesis disorders. Nat Genet. 1995 Feb;9(2):115-25. [Content Brief]

[6]. Muhammad Ali, et al. A missense allele of PEX5 is responsible for the defective import of PTS2 cargo proteins into peroxisomes. Hum Genet. 2021 Apr;140(4):649-666. [Content Brief]

[7]. N Braverman, et al. An isoform of pex5p, the human PTS1 receptor, is required for the import of PTS2 proteins into peroxisomes. Hum Mol Genet. 1998 Aug;7(8):1195-205. [Content Brief]

[8]. M Fransen, et al. Identification and characterization of the putative human peroxisomal C-terminal targeting signal import receptor. J Biol Chem. 1995 Mar 31;270(13):7731-6. [Content Brief]

[9]. V Dammai, et al. The human peroxisomal targeting signal receptor, Pex5p, is translocated into the peroxisomal matrix and recycled to the cytosol. Cell. 2001 Apr 20;105(2):187-96. [Content Brief]

[10]. G Dodt, et al. Domain mapping of human PEX5 reveals functional and structural similarities to Saccharomyces cerevisiae Pex18p and Pex21p. J Biol Chem. 2001 Nov 9;276(45):41769-81. [Content Brief]

[11]. Non Miyata, et al. Shuttling mechanism of peroxisome targeting signal type 1 receptor Pex5: ATP-independent import and ATP-dependent export. Mol Cell Biol. 2005 Dec;25(24):10822-32. [Content Brief]

[12]. Kanji Okumoto, et al. Distinct modes of ubiquitination of peroxisome-targeting signal type 1 (PTS1) receptor Pex5p regulate PTS1 protein import. J Biol Chem. 2014 May 16;289(20):14089-108. [Content Brief]

[13]. E A Wiemer, et al. Human peroxisomal targeting signal-1 receptor restores peroxisomal protein import in cells from patients with fatal peroxisomal disorders. J Cell Biol. 1995 Jul;130(1):51-65. [Content Brief]

[14]. Marta O Freitas, et al. PEX5 protein binds monomeric catalase blocking its tetramerization and releases it upon binding the N-terminal domain of PEX14. J Biol Chem. 2011 Nov 25;286(47):40509-19. [Content Brief]

[15]. Will A Stanley, et al. A previously unobserved conformation for the human Pex5p receptor suggests roles for intrinsic flexibility and rigid domain motions in ligand binding. BMC Struct Biol. 2007 Apr 11;7:24. [Content Brief]

[16]. Markus Kunze, et al. Mechanistic insights into PTS2-mediated peroxisomal protein import: the co-receptor PEX5L drastically increases the interaction strength between the cargo protein and the receptor PEX7. J Biol Chem. 2015 Feb 20;290(8):4928-4940. [Content Brief]

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