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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:P28328
Protein Name:Peroxisome assembly factor 1
Length:305
Molecular Weight:34843.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:2
Location1 / Topology2 / Orientation3: Peroxisome membrane1 / Multi-pass membrane protein2
Substrate protein polypeptide chain

Cross database links:

RefSeq: NP_000309.1    NP_001073336.1    NP_001165557.1    NP_001165558.1   
Entrez Gene ID: 5828   
Pfam: PF04757   
OMIM: 170993  gene+phenotype
214100  phenotype
266510  phenotype
601539  phenotype
KEGG: hsa:5828   

Gene Ontology

GO:0005779 C:integral to peroxisomal membrane
GO:0005515 F:protein binding
GO:0008270 F:zinc ion binding
GO:0007031 P:peroxisome organization

References (7)

[1] “A human gene responsible for Zellweger syndrome that affects peroxisome assembly.”  Shimozawa N.et.al.   1546315
[2] “Genomic organization and characterization of human PEX2 encoding a 35-kDa peroxisomal membrane protein.”  Biermanns M.et.al.   10891359
[3] “DNA sequence and analysis of human chromosome 8.”  Nusbaum C.et.al.   16421571
[4] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[5] “Ring finger in the peroxisome assembly factor-1.”  Patarca R.et.al.   1426230
[6] “Lysine acetylation targets protein complexes and co-regulates major cellular functions.”  Choudhary C.et.al.   19608861
[7] “Defective PEX gene products correlate with the protein import, biochemical abnormalities, and phenotypic heterogeneity in peroxisome biogenesis disorders.”  Shimozawa N.et.al.   10528859

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FASTA formatted sequence
1:	MASRKENAKS ANRVLRISQL DALELNKALE QLVWSQFTQC FHGFKPGLLA RFEPEVKACL 
61:	WVFLWRFTIY SKNATVGQSV LNIKYKNDFS PNLRYQPPSK NQKIWYAVCT IGGRWLEERC 
121:	YDLFRNHHLA SFGKVKQCVN FVIGLLKLGG LINFLIFLQR GKFATLTERL LGIHSVFCKP 
181:	QNICEVGFEY MNRELLWHGF AEFLIFLLPL INVQKLKAKL SSWCIPLTGA PNSDNTLATS 
241:	GKECALCGEW PTMPHTIGCE HIFCYFCAKS SFLFDVYFTC PKCGTEVHSL QPLKSGIEMS 
301:	EVNAL