Peroxisome biogenesis factor 2

Definition:

E3 ubiquitin-protein ligase component of a retrotranslocation channel required for peroxisome organization by mediating export of the PEX5 receptor from peroxisomes to the cytosol, thereby promoting PEX5 recycling. The retrotranslocation channel is composed of PEX2, PEX10 and PEX12; each subunit contributing transmembrane segments that coassemble into an open channel that specifically allows the passage of PEX5 through the peroxisomal membrane (By similarity). PEX2 also regulates peroxisome organization by acting as a E3 ubiquitin-protein ligase (By similarity). PEX2 ubiquitinates PEX5 during its passage through the retrotranslocation channel: catalyzes monoubiquitination of PEX5 at 'Cys-11', a modification that acts as a signal for PEX5 extraction into the cytosol (By similarity). Required for pexophagy in response to starvation by mediating ubiquitination of peroxisomal proteins, such as PEX5 and ABCD3/PMP70. Also involved in the response to reactive oxygen species (ROS) by mediating 'Lys-48'-linked polyubiquitination and subsequent degradation of PNPLA2/ATGL, thereby regulating lipolysis.

References:

[1]. Graeme Sargent, et al. PEX2 is the E3 ubiquitin ligase required for pexophagy during starvation. J Cell Biol. 2016 Sep 12;214(6):677-90. [Content Brief]

[2]. Lianggong Ding, et al. Peroxisomal β-oxidation acts as a sensor for intracellular fatty acids and regulates lipolysis. Nat Metab. 2021 Dec;3(12):1648-1661. [Content Brief]

[3]. Kanji Okumoto, et al. Distinct modes of ubiquitination of peroxisome-targeting signal type 1 (PTS1) receptor Pex5p regulate PTS1 protein import. J Biol Chem. 2014 May 16;289(20):14089-108. [Content Brief]

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