PEX2

PEX2, or peroxisomal biogenesis factor 2, is a protein that functions as a component of the peroxisomal protein import machinery. In humans and other eukaryotes, PEX2 is a peroxisomal membrane protein that contributes to the assembly and maintenance of peroxisomes, organelles essential for fatty acid metabolism and detoxification of reactive oxygen species.

Functionally, PEX2 is part of a peroxisomal RING finger E3 ubiquitin ligase complex together with PEX10 and PEX12. This complex ubiquitinates the peroxisomal import receptor PEX5, enabling its recycling after the import of matrix proteins. Proper PEX5 cycling is required for continuous import of enzymes into the peroxisome. PEX2 also participates in quality control of peroxisomal proteins and supports overall peroxisome biogenesis.

Structurally, PEX2 is an integral membrane protein of the peroxisome and contains a RING finger domain. It interacts with the cytosolic ubiquitination machinery, including PEX4, an E2 ubiquitin-conjugating enzyme, to mediate ubiquitination events necessary for receptor recycling and protein import.

Genetics and disease associations: Mutations in PEX2 can lead to peroxisome biogenesis disorders (PBDs), including Zellweger spectrum disorders and related phenotypes. Affected individuals may present with neurologic, craniofacial, hepatic, and metabolic abnormalities, reflecting impaired peroxisome function. The severity of disease varies with the specific mutation and residual peroxisomal activity.

In model organisms, PEX2 homologs are conserved and play a similar role in peroxisome biogenesis. In Saccharomyces cerevisiae, Pex2 is essential for peroxisome formation, and disruption disrupts matrix protein import and peroxisome maintenance.

See also: Peroxisome, peroxins (PEX genes), Zellweger spectrum disorders.