PEX5S,L binds cargo proteins containing PTS1

Stable Identifier
Reaction [binding]
Homo sapiens
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It is unclear how the long isoform of PEX5 (PEX5L) and the short isoform of PEX5 (PEX5S) are generated. A current hypothesis suggests alternative mRNA splicing. Both isoforms can bind the peroxisome targeting signal 1 (PTS1) located at the C-terminus of most of the proteins that are targeted to the peroxisomal matrix (Dodt et al. 1995, Fransen et al. 1995, Wiemer et al. 1995, Gatto et al. 2000, Brocard et al. 2003, Gatto et al. 2003, Harper et al. 2003, Ghosh and Berg 2010, Freitas et al. 2011, Okumoto et al. 2011). PTS1 typically contains Ser-Lys-Leu (SKL) at the C-terminus but substantial variation in sequences and affinities for PEX5 are observed and upstream residues can modulate binding to PEX5 (Lametschwandtner et al. 1998, Ghosh and Berg 2010, reviewed in Brocard and Hartig 2006).
A minority of peroxisomal matrix proteins contain PTS2. While the PEX5S isoform binds proteins containing PTS1, the PEX5L isoform binds either proteins containing PTS1 or PEX7 bound to proteins containing PTS2 (Braverman et al. 1998). Some proteins appear to be imported as oligomers, however this is rather inefficient as PEX5 appears to have a preference for monomeric substrates (Otera and Fujiki 2012, Freitas et al. 2011, Freitas et al. 2015, also inferred from mouse homologs). Mutations in PEX5 cause defects in peroxisomal import and comprise complementation group 2 of peroxisomal biogenesis disorders (also called Zellweger spectrum disorders) (Dodt et al. 1995, Wiemer et al. 1995). A specific mutation affecting only the PEX5L isoform is the cause of rhizomelic chondrodysplasia punctate type 5 (Barøy et al. 2015).

Literature References
PubMed ID Title Journal Year
20178365 A proteome-wide perspective on peroxisome targeting signal 1(PTS1)-Pex5p affinities

Ghosh, D, Berg, JM

J. Am. Chem. Soc. 2010
9653144 Identification of a human PTS1 receptor docking protein directly required for peroxisomal protein import

Fransen, M, Terlecky, SR, Subramani, S

Proc. Natl. Acad. Sci. U.S.A. 1998
12456682 PEX5 binds the PTS1 independently of Hsp70 and the peroxin PEX12

Harper, CC, Berg, JM, Gould, SJ

J. Biol. Chem. 2003
12578380 Correlating structure and affinity for PEX5:PTS1 complexes

Gatto, GJ, Maynard, EL, Guerrerio, AL, Geisbrecht, BV, Gould, SJ, Berg, JM

Biochemistry 2003
25854684 The peroxisomal protein import machinery displays a preference for monomeric substrates

Freitas, MO, Francisco, T, Rodrigues, TA, Lismont, C, Domingues, P, Pinto, MP, Grou, CP, Fransen, M, Azevedo, JE

Open Biol 2015
21976670 PEX5 protein binds monomeric catalase blocking its tetramerization and releases it upon binding the N-terminal domain of PEX14

Freitas, MO, Francisco, T, Rodrigues, TA, Alencastre, IS, Pinto, MP, Grou, CP, Carvalho, AF, Fransen, M, Sá-Miranda, C, Azevedo, JE

J. Biol. Chem. 2011
12559034 Protein structure and import into the peroxisomal matrix

Brocard, CB, Jedeszko, C, Song, HC, Terlecky, SR, Walton, PA

Traffic 2003
11101887 Peroxisomal targeting signal-1 recognition by the TPR domains of human PEX5

Gatto, GJ, Geisbrecht, BV, Gould, SJ, Berg, JM

Nat. Struct. Biol. 2000
9837948 The difference in recognition of terminal tripeptides as peroxisomal targeting signal 1 between yeast and human is due to different affinities of their receptor Pex5p to the cognate signal and to residues adjacent to it

Lametschwandtner, G, Brocard, C, Fransen, M, Van Veldhoven, PP, Berger, J, Hartig, A

J. Biol. Chem. 1998
8824437 Characterization of the yeast and human receptors for the carboxy-terminal tripeptide peroxisomal targeting signal

Wiemer, EA, Terlecky, SR, Nuttley, WM, Subramani, S

Cold Spring Harb. Symp. Quant. Biol. 1995
7719337 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, HW, Watkins, P, Valle, D, Gould, SJ

Nat. Genet. 1995
22002062 Two proteases, trypsin domain-containing 1 (Tysnd1) and peroxisomal lon protease (PsLon), cooperatively regulate fatty acid β-oxidation in peroxisomal matrix

Okumoto, K, Kametani, Y, Fujiki, Y

J. Biol. Chem. 2011
17007944 Peroxisome targeting signal 1: is it really a simple tripeptide?

Brocard, C, Hartig, A

Biochim. Biophys. Acta 2006
26220973 A novel type of rhizomelic chondrodysplasia punctata, RCDP5, is caused by loss of the PEX5 long isoform

Barøy, T, Koster, J, Strømme, P, Ebberink, MS, Misceo, D, Ferdinandusse, S, Holmgren, A, Hughes, T, Merckoll, E, Westvik, J, Woldseth, B, Walter, J, Wood, N, Tvedt, B, Stadskleiv, K, Wanders, RJ, Waterham, HR, Frengen, E

Hum. Mol. Genet. 2015
7790377 Human peroxisomal targeting signal-1 receptor restores peroxisomal protein import in cells from patients with fatal peroxisomal disorders

Wiemer, EA, Nuttley, WM, Bertolaet, BL, Li, X, Francke, U, Wheelock, MJ, Anné, UK, Johnson, KR, Subramani, S

J. Cell Biol. 1995
9668159 An isoform of pex5p, the human PTS1 receptor, is required for the import of PTS2 proteins into peroxisomes

Braverman, N, Dodt, G, Gould, SJ, Valle, D

Hum. Mol. Genet. 1998
22747494 Pex5p imports folded tetrameric catalase by interaction with Pex13p

Otera, H, Fujiki, Y

Traffic 2012
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