CLONING AND CHARACTERIZATION OF THE GENE ENCODING THE HUMAN PEROXISOMAL ASSEMBLY PROTEIN PEX3P

Proteins essential for the assembly of functional peroxisomes are desi gnated peroxins and are encoded by PEX genes. In yeast, Pex3p was prev iously identified as a peroxisomal integral membrane protein indispens able for peroxisome biogenesis and integrity. Here we report the cloni ng of the orthologous human PEX3 gene. It encodes a polypeptide of 373 amino acids (42 kDa) and is expressed in all tissues examined. As sho wn by transfection of epitope tagged constructs and immunofluorescence analysis, human Pex3p is localized at the peroxisome, The IV-terminal 40 amino acids were revealed to be sufficient to target a GFP reporte r protein to the peroxisome, A positively charged five amino acid sequ ence within this N-terminal region is highly conserved from yeast to h uman 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 c andidate gene being involved in this disease group. (C) 1998 Federatio n of European Biochemical Societies.