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3.A.20.1.1
The peroxisomal importing translocon with receptors: Pex5p and Pex7p; and receptor facilitator: Pex4p. Peroxisomal biogenesis factor PEX26 is a membrane anchor for the multi-subunit PEX1-PEX6 protein complex that controls ubiquitination and dislocation of PEX5 cargo receptors for peroxisomal matrix protein import. PEX26 associates with the peroxisomal translocation pore via PEX14 (Guder et al. 2018). Luminal peroxisomal proteins are imported from the cytosol by mobile receptors, which then recycle back to the cytosol by a poorly understood process (Feng et al. 2022). Recycling requires receptor modification by a membrane-embedded ubiquitin ligase complex comprising three RING finger domain-containing proteins (Pex2, Pex10 and Pex12). Feng et al. 2022 reported a cryo-EM structure of the ligase complex, which together with biochemical and in vivo experiments reveals its function as a retrotranslocation channel for peroxisomal import receptors. Each subunit of the complex contributes five transmembrane segments that co-assemble into an open channel. The three ring finger domains form a cytosolic tower, with ring finger 2 (RF2) positioned above the channel pore. The N terminus of a recycling receptor is inserted from the peroxisomal lumen into the pore and monoubiquitylated by RF2 to enable extraction into the cytosol. If recycling is compromised, receptors are polyubiquitylated by the concerted action of RF10 and RF12 and degraded. This polyubiquitylation pathway also maintains the homeostasis of other peroxisomal import factors. Thus, a crucial step during peroxisomal protein import is clarified, and it explains why mutations in the ligase complex cause human disease (Feng et al. 2022).

Accession Number:P29340
Protein Name:Ubiquitin-conjugating enzyme E2-21 kDa
Length:183
Molecular Weight:21118.00
Species:Saccharomyces cerevisiae (Baker's yeast) [4932]
Location1 / Topology2 / Orientation3: Peroxisome1
Substrate protein polypeptide chain

Cross database links:

DIP: DIP-4411N
RefSeq: NP_011649.1   
Entrez Gene ID: 853034   
Pfam: PF00179   
KEGG: sce:YGR133W   

Gene Ontology

GO:0005777 C:peroxisome
GO:0005524 F:ATP binding
GO:0005515 F:protein binding
GO:0004842 F:ubiquitin-protein ligase activity
GO:0051865 P:protein autoubiquitination
GO:0016562 P:protein import into peroxisome matrix, rece...
GO:0006513 P:protein monoubiquitination
GO:0000209 P:protein polyubiquitination
GO:0051246 P:regulation of protein metabolic process

References (3)

[1] “The Pas2 protein essential for peroxisome biogenesis is related to ubiquitin-conjugating enzymes.”  Wiebel F.F.et.al.   1326082
[2] “The nucleotide sequence of Saccharomyces cerevisiae chromosome VII.”  Tettelin H.et.al.   9169869
[3] “Approaching a complete repository of sequence-verified protein-encoding clones for Saccharomyces cerevisiae.”  Hu Y.et.al.   17322287
Structure:
2Y9M   2Y9P   4BWF     

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FASTA formatted sequence
1:	MPNFWILENR RSYTSDTCMS RIVKEYKVIL KTLASDDPIA NPYRGIIESL NPIDETDLSK 
61:	WEAIISGPSD TPYENHQFRI LIEVPSSYPM NPPKISFMQN NILHCNVKSA TGEICLNILK 
121:	PEEWTPVWDL LHCVHAVWRL LREPVCDSPL DVDIGNIIRC GDMSAYQGIV KYFLAERERI 
181:	NNH