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Molecular and Cellular Biology, March 1999, p. 2265-2277, Vol. 19, No. 3
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Identification and Characterization of the Human Orthologue of Yeast Pex14p

Garnet K. Will,1 Monika Soukupova,1 Xinji Hong,1,dagger Kai S. Erdmann,2 Jan A. K. W. Kiel,3 Gabriele Dodt,1 Wolf-Hubert Kunau,1 and Ralf Erdmann1,*

Institut für Physiologische Chemie1 and Institut für Neurobiochemie,2 Ruhr-Universität Bochum, 44780 Bochum, Germany, and Department of Microbiology, University of Groningen, 9751 NN Haren, The Netherlands3

Received 17 June 1998/Returned for modification 21 July 1998/Accepted 10 December 1998

Pex14p is a central component of the peroxisomal protein import machinery, which has been suggested to provide the point of convergence for PTS1- and PTS2-dependent protein import in yeast cells. Here we describe the identification of a human peroxisome-associated protein (HsPex14p) which shows significant similarity to the yeast Pex14p. HsPex14p is a carbonate-resistant peroxisomal membrane protein with its C terminus exposed to the cytosol. The N terminus of the protein is not accessible to exogenously added antibodies or protease and thus might protrude into the peroxisomal lumen. HsPex14p overexpression leads to the decoration of tubular structures and mislocalization of peroxisomal catalase to the cytosol. HsPex14p binds the cytosolic receptor for the peroxisomal targeting signal 1 (PTS1), a result consistent with a function as a membrane receptor in peroxisomal protein import. Homo-oligomerization of HsPex14p or interaction of the protein with the PTS2-receptor or HsPex13p was not observed. This distinguishes the human Pex14p from its counterpart in yeast cells and thus supports recent data suggesting that not all aspects of peroxisomal protein import are conserved between yeasts and humans. The role of HsPex14p in mammalian peroxisome biogenesis makes HsPEX14 a candidate PBD gene for being responsible for an unrecognized complementation group of human peroxisome biogenesis disorders.

* Corresponding author. Present address: Freie Universität Berlin, Institut für Biochemie, Thielallee 63, 14195 Berlin, Germany. Phone: 49-30-832-28040. Fax: 49-30-838-2936. E-mail: ralferdm{at}zedat-fu-berlin.de.

dagger Present address: Freie Universität Berlin, Institut für Biochemie, 14195 Berlin, Germany.

Molecular and Cellular Biology, March 1999, p. 2265-2277, Vol. 19, No. 3
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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