Cloning and characterization of the gene encoding the human peroxisomal assembly protein Pex3p.

Proteins essential for the assembly of functional peroxisomes are designated peroxins and are encoded by PEX genes. In yeast, Pex3p was previously identified as a peroxisomal integral membrane protein indispensable for peroxisome biogenesis and integrity. Here we report the cloning of the orthologous human PEX3 gene. It encodes a polypeptide of 373 amino acids (42 kDa) and is expressed in all tissues examined. As shown by transfection of epitope tagged constructs and immunofluorescence analysis, human Pex3p is localized at the peroxisome. The N-terminal 40 amino acids were revealed to be sufficient to target a GFP reporter protein to the peroxisome. A positively charged five amino acid sequence within this N-terminal region is highly conserved from yeast to human Pex3p. Overexpression of human Pex3p leads to proliferation of ER membranes in COS7 cells. Since disruption of human peroxins has been shown to result in peroxisomal biogenesis disorders, PEX3 is another candidate gene being involved in this disease group.