SUMMARY PARAGRAPH for PEX2
The biogenesis of peroxisomes requires a group of protein factors referred to as peroxins which are encoded by the PEX genes. Peroxisomal proteins are synthesized on free polyribosomes and imported posttranslationally. The transport of peroxisomal matrix proteins from the cytoplasm to the peroxisome is mediated by two peroxisome-targeting signal sequences (PTS1 and PTS2). Peroxisomal membrane proteins (PMPs) are imported independently of the matrix proteins by a distinct mechanism mediated by the membrane PTS signal (mPTS) (8, 9, 10, 11 and references therein).
Pex2p is a peroxisomal membrane protein required for peroxisome biogenesis and peroxisomal matrix protein import (4, 12, 13). pex2 null mutants are viable but peroxisome deficient, and mislocalize peroxisomal matrix proteins to the cytosol (4, 14).
Two subcomplexes of the peroxisomal import machinery have been defined: the docking subcomplex comprises Pex14p, Pex17p, and Pex13p, while the translocation subcomplex contains Pex2p, Pex10p, and Pex12p. The proteins of the translocation complex expose their RING finger domains to the outer face of the peroxisomal membrane, and act downstream of Pex14p, Pex17p, and Pex13p during the peroxisomal protein import process (15). Association of both subcomplexes into a larger import complex requires Pex8p, an intraperoxisomal protein. Pex8p organizes the formation of the larger import complex from the trans side of the peroxisomal membrane and thus might enable functional communication between both sides of the membrane (15).
PEX2 is transcribed from two different promoters, one induced during peroxisome proliferation and the other during the induction of mitochondrial function. The shorter transcripts initiate downstream of the first in-frame ATG, and, consistent with the different conditions of induction, the N-terminus of the shorter protein not only lacks the longer protein's acidic amino-terminal domain, but rather contains basic and hydroxylated amino acids, a signature of mitochondrial targeting sequences (3). However, it is unknown whether the shorter transcript actually gives rise to a mitochondrially targeted form of Pex2p, or what the role of such a protein in mitochondrial function might be.
The human peroxisome biogenesis disorders (PBDs) are a group of genetically heterogeneous diseases characterized by severe mental retardation, neuronal, hepatic and renal abnormalities, and death in early infancy (16). Clinical features of PBD patients vary, but all exhibit a defect in the import of one or more classes of peroxisomal matrix proteins. This cellular phenotype is shared by yeast pex mutants, and human orthologs of yeast PEX genes are defective in some groups of PBD patients (16, 17).
Mutations in human PEX2 (also known as PAF-1 or PXMP3) have been associated with Zellweger Syndrome and Refsum Disease.
Last updated: 2007-06-26