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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:O00628
Protein Name:Peroxisomal targeting signal 2 receptor
Length:323
Molecular Weight:35892.00
Species:Homo sapiens (Human) [9606]
Location1 / Topology2 / Orientation3: Peroxisome1
Substrate protein polypeptide chain

Cross database links:

RefSeq: NP_000279.1   
Entrez Gene ID: 5191   
Pfam: PF00400   
OMIM: 215100  phenotype
266500  phenotype
601539  phenotype
601757  gene
KEGG: hsa:5191   

Gene Ontology

GO:0005777 C:peroxisome
GO:0005053 F:peroxisome matrix targeting signal-2 binding
GO:0008611 P:ether lipid biosynthetic process
GO:0016558 P:protein import into peroxisome matrix
GO:0050896 P:response to stimulus
GO:0007601 P:visual perception

References (5)

[1] “Rhizomelic chondrodysplasia punctata is caused by deficiency of human PEX7, a homologue of the yeast PTS2 receptor.”  Purdue P.E.et.al.   9090383
[2] “Human PEX7 encodes the peroxisomal PTS2 receptor and is responsible for rhizomelic chondrodysplasia punctata.”  Braverman N.et.al.   9090381
[3] “PEX7 gene structure, alternative transcripts, and evidence for a founder haplotype for the frequent RCDP allele, L292ter.”  Braverman N.et.al.   10673331
[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] “Identification of PEX7 as the second gene involved in Refsum disease.”  van den Brink D.M.et.al.   12522768

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FASTA formatted sequence
1:	MSAVCGGAAR MLRTPGRHGY AAEFSPYLPG RLACATAQHY GIAGCGTLLI LDPDEAGLRL 
61:	FRSFDWNDGL FDVTWSENNE HVLITCSGDG SLQLWDTAKA AGPLQVYKEH AQEVYSVDWS 
121:	QTRGEQLVVS GSWDQTVKLW DPTVGKSLCT FRGHESIIYS TIWSPHIPGC FASASGDQTL 
181:	RIWDVKAAGV RIVIPAHQAE ILSCDWCKYN ENLLVTGAVD CSLRGWDLRN VRQPVFELLG 
241:	HTYAIRRVKF SPFHASVLAS CSYDFTVRFW NFSKPDSLLE TVEHHTEFTC GLDFSLQSPT 
301:	QVADCSWDET IKIYDPACLT IPA