PEX5 explained

Peroxisomal targeting signal 1 receptor (PTS1R) is a protein that in humans is encoded by the PEX5 gene.^[1]

PTS1R is a peroxisomal targeting sequence involved in the specific transport of molecules for oxidation inside the peroxisome. SKL binds to PTS1R in the cytosol followed by binding to the Pex14p receptor allowing importation of the peroxisomal protein through the pexsubunit transporter.

Diseases associated with dysfunctional PTS1R receptors include X-linked adrenoleukodystrophy and Zellweger syndrome.

Interactions

PEX5 has been shown to interact with PEX12,^{[2] [3]} PEX13^{[4] [5]} and PEX14.^{[3] [5] [6]}

Further reading

• Fransen M, Brees C, Baumgart E, Vanhooren JC, Baes M, Mannaerts GP, Van Veldhoven PP . Identification and characterization of the putative human peroxisomal C-terminal targeting signal import receptor . The Journal of Biological Chemistry . 270 . 13 . 7731–6 . Mar 1995 . 7706321 . 10.1074/jbc.270.13.7731 . free .
• Dodt G, Braverman N, Wong C, Moser A, Moser HW, Watkins P, Valle D, Gould SJ . Mutations in the PTS1 receptor gene, PXR1, define complementation group 2 of the peroxisome biogenesis disorders . Nature Genetics . 9 . 2 . 115–25 . Feb 1995 . 7719337 . 10.1038/ng0295-115 . 8469214 .
• Wiemer EA, Nuttley WM, Bertolaet BL, Li X, Francke U, Wheelock MJ, Anné UK, Johnson KR, Subramani S . Human peroxisomal targeting signal-1 receptor restores peroxisomal protein import in cells from patients with fatal peroxisomal disorders . The Journal of Cell Biology . 130 . 1 . 51–65 . Jul 1995 . 7790377 . 2120514 . 10.1083/jcb.130.1.51 .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . Jan 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Marynen P, Fransen M, Raeymaekers P, Mannaerts GP, Van Veldhoven PP . The gene for the peroxisomal targeting signal import receptor (PXR1) is located on human chromosome 12p13, flanked by TPI1 and D12S1089 . Genomics . 30 . 2 . 366–8 . Nov 1995 . 8586442 . 10.1006/geno.1995.0032 .
• Gould SJ, Kalish JE, Morrell JC, Bjorkman J, Urquhart AJ, Crane DI . Pex13p is an SH3 protein of the peroxisome membrane and a docking factor for the predominantly cytoplasmic PTs1 receptor . The Journal of Cell Biology . 135 . 1 . 85–95 . Oct 1996 . 8858165 . 2121023 . 10.1083/jcb.135.1.85 .
• Dodt G, Gould SJ . 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 . The Journal of Cell Biology . 135 . 6 Pt 2 . 1763–74 . Dec 1996 . 8991089 . 2133940 . 10.1083/jcb.135.6.1763 .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . Oct 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Reuber BE, Germain-Lee E, Collins CS, Morrell JC, Ameritunga R, Moser HW, Valle D, Gould SJ . Mutations in PEX1 are the most common cause of peroxisome biogenesis disorders . Nature Genetics . 17 . 4 . 445–8 . Dec 1997 . 9398847 . 10.1038/ng1297-445 . 34034756 .
• Otera H, Okumoto K, Tateishi K, Ikoma Y, Matsuda E, Nishimura M, Tsukamoto T, Osumi T, Ohashi K, Higuchi O, Fujiki Y . Peroxisome targeting signal type 1 (PTS1) receptor is involved in import of both PTS1 and PTS2: studies with PEX5-defective CHO cell mutants . Molecular and Cellular Biology . 18 . 1 . 388–99 . Jan 1998 . 9418886 . 121509 . 10.1128/mcb.18.1.388.
• Fransen M, Terlecky SR, Subramani S . Identification of a human PTS1 receptor docking protein directly required for peroxisomal protein import . Proceedings of the National Academy of Sciences of the United States of America . 95 . 14 . 8087–92 . Jul 1998 . 9653144 . 20933 . 10.1073/pnas.95.14.8087 . 1998PNAS...95.8087F . free .
• Amery L, Brees C, Baes M, Setoyama C, Miura R, Mannaerts GP, Van Veldhoven PP . C-terminal tripeptide Ser-Asn-Leu (SNL) of human D-aspartate oxidase is a functional peroxisome-targeting signal . The Biochemical Journal . 336 . Pt 2 . 367–71 . Dec 1998 . 9820813 . 1219880 . 10.1042/bj3360367.
• Shimizu N, Itoh R, Hirono Y, Otera H, Ghaedi K, Tateishi K, Tamura S, Okumoto K, Harano T, Mukai S, Fujiki Y . The peroxin Pex14p. cDNA cloning by functional complementation on a Chinese hamster ovary cell mutant, characterization, and functional analysis . The Journal of Biological Chemistry . 274 . 18 . 12593–604 . Apr 1999 . 10212238 . 10.1074/jbc.274.18.12593 . free .
• Shimozawa N, Zhang Z, Suzuki Y, Imamura A, Tsukamoto T, Osumi T, Fujiki Y, Orii T, Barth PG, Wanders RJ, Kondo N . Functional heterogeneity of C-terminal peroxisome targeting signal 1 in PEX5-defective patients . Biochemical and Biophysical Research Communications . 262 . 2 . 504–8 . Aug 1999 . 10462504 . 10.1006/bbrc.1999.1232 .
• Chang CC, Warren DS, Sacksteder KA, Gould SJ . PEX12 interacts with PEX5 and PEX10 and acts downstream of receptor docking in peroxisomal matrix protein import . The Journal of Cell Biology . 147 . 4 . 761–74 . Nov 1999 . 10562279 . 2156163 . 10.1083/jcb.147.4.761 .
• Watters D, Kedar P, Spring K, Bjorkman J, Chen P, Gatei M, Birrell G, Garrone B, Srinivasa P, Crane DI, Lavin MF . Localization of a portion of extranuclear ATM to peroxisomes . The Journal of Biological Chemistry . 274 . 48 . 34277–82 . Nov 1999 . 10567403 . 10.1074/jbc.274.48.34277 . 10072/122346 . 14334129 . free .
• Okumoto K, Abe I, Fujiki Y . 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 . The Journal of Biological Chemistry . 275 . 33 . 25700–10 . Aug 2000 . 10837480 . 10.1074/jbc.M003303200 . free .
• Gatto GJ, Geisbrecht BV, Gould SJ, Berg JM . Peroxisomal targeting signal-1 recognition by the TPR domains of human PEX5 . Nature Structural Biology . 7 . 12 . 1091–5 . Dec 2000 . 11101887 . 10.1038/81930 . 35168630 .
• Harano T, Nose S, Uezu R, Shimizu N, Fujiki Y . Hsp70 regulates the interaction between the peroxisome targeting signal type 1 (PTS1)-receptor Pex5p and PTS1 . The Biochemical Journal . 357 . Pt 1 . 157–65 . Jul 2001 . 11415446 . 1221938 . 10.1042/0264-6021:3570157 .
• Saidowsky J, Dodt G, Kirchberg K, Wegner A, Nastainczyk W, Kunau WH, Schliebs W . The di-aromatic pentapeptide repeats of the human peroxisome import receptor PEX5 are separate high affinity binding sites for the peroxisomal membrane protein PEX14 . The Journal of Biological Chemistry . 276 . 37 . 34524–9 . Sep 2001 . 11438541 . 10.1074/jbc.M104647200 . free .
• Stanley WA, Filipp FV, Kursula P, Schüller N, Erdmann R, Schliebs W, Sattler M, Wilmanns M . Recognition of a functional peroxisome type 1 target by the dynamic import receptor pex5p . Molecular Cell . 24 . 5 . 653–63 . Dec 2006 . 17157249 . 5030714 . 10.1016/j.molcel.2006.10.024 .

External links

• GeneReviews/NCBI/NIH/UW entry on Peroxisome Biogenesis Disorders, Zellweger Syndrome Spectrum
• OMIM entries on Peroxisome Biogenesis Disorders, Zellweger Syndrome Spectrum

Notes and References

1. Web site: Entrez Gene: PEX5 Peroxisomal biogenesis factor 5.
2. Chang CC, Warren DS, Sacksteder KA, Gould SJ . PEX12 interacts with PEX5 and PEX10 and acts downstream of receptor docking in peroxisomal matrix protein import . The Journal of Cell Biology . 147 . 4 . 761–74 . Nov 1999 . 10562279 . 2156163 . 10.1083/jcb.147.4.761 .
3. Okumoto K, Abe I, Fujiki Y . 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 . The Journal of Biological Chemistry . 275 . 33 . 25700–10 . Aug 2000 . 10837480 . 10.1074/jbc.M003303200 . free .
4. Gould SJ, Kalish JE, Morrell JC, Bjorkman J, Urquhart AJ, Crane DI . Pex13p is an SH3 protein of the peroxisome membrane and a docking factor for the predominantly cytoplasmic PTs1 receptor . The Journal of Cell Biology . 135 . 1 . 85–95 . Oct 1996 . 8858165 . 2121023 . 10.1083/jcb.135.1.85 .
5. Otera H, Setoguchi K, Hamasaki M, Kumashiro T, Shimizu N, Fujiki Y . 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 . Molecular and Cellular Biology . 22 . 6 . 1639–55 . Mar 2002 . 11865044 . 135613 . 10.1128/MCB.22.6.1639-1655.2002 .
6. Shimizu N, Itoh R, Hirono Y, Otera H, Ghaedi K, Tateishi K, Tamura S, Okumoto K, Harano T, Mukai S, Fujiki Y . The peroxin Pex14p. cDNA cloning by functional complementation on a Chinese hamster ovary cell mutant, characterization, and functional analysis . The Journal of Biological Chemistry . 274 . 18 . 12593–604 . Apr 1999 . 10212238 . 10.1074/jbc.274.18.12593 . free .