Disease relevance of PEX3

• To verify these predictions antibodies were raised against a truncated portion of the PAS3 coding region overexpressed in E. coli [1].

High impact information on PEX3

• Pex19 (a farnesylated, mostly cytosolic protein) enriches first at the Pex3 foci on the ER and then on the maturing peroxisomes [2].
• Remarkably, Pex3 (an integral membrane protein) could first be observed in the endoplasmic reticulum (ER), where it concentrates in foci that then bud off in a Pex19-dependent manner and mature into fully functional peroxisomes [2].
• Recently, the first two genes, PAS1 (ref. 3) and PAS3 (ref. 4), have been characterized [3].
• Tiny peroxisome remnants - vesicles and tubules - are discovered in pex3 mutants that lack the organelle [4].
• PAS3, a Saccharomyces cerevisiae gene encoding a peroxisomal integral membrane protein essential for peroxisome biogenesis [1].

Biological context of PEX3

• PEX3 encodes at 52 kDa peroxisomal membrane protein (PMP), essential for peroxisome biogenesis in the yeast Hansenula polymorpha [5].
• Additional changes in the N terminus of Pex3p, e.g. replacing three or four of the positively charged amino acids with negatively charged ones, led to a typical pex3 phenotype, i.e. accumulation of peroxisomal matrix proteins in the cytosol and absence of peroxisomal remnants [6].

Anatomical context of PEX3

• Here we show that in the initial stages of a sharp increase in Pex3p levels, induced in batch cultures of cells of a constructed H. polymorpha strain, which contained seven copies of PEX3 under control of the alcohol oxidase promoter (WT::PAOX.PEX3(7x)), strongly interfered with normal peroxisome proliferation [7].
• PEX3 expression was identified in all tissues analyzed, with the strongest signals in liver and in testis, and could not be induced by fenofibrate [8].

Associations of PEX3 with chemical compounds

• In glucose-grown delta pex3 cells, containing PAOX.PEX3, Pex3p was undetectable and peroxisomes were absent [5].
• Only few enzymes have been identified as peroxisomal proteins in Saccharomyces cerevisiae so far; the three enzymes involved in beta-oxidation of fatty acids, enzymes of the glyoxylate cycle, catalase A and the PAS3 gene product have been unequivocally assigned to the peroxisomal compartment [9].

Other interactions of PEX3

• However, we also found that the behavior of PMPs in the pex17 mutant was indistinguishable from PMP behavior in a pex5 mutant, which has no defect in PMP import, and was far different from PMP behavior in a pex3 mutant, which has a bona fide defect in PMP import [10].
• An exchange of the mPTS of Pex22p by that of Pex3p likewise fully preserved the function of Pex22p [11].

References