TCDB is operated by the Saier Lab Bioinformatics Group
« See all members of the family


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:O00623
Protein Name:Peroxisome assembly protein 12
Length:359
Molecular Weight:40797.00
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_000277.1   
Entrez Gene ID: 5193   
Pfam: PF04757   
OMIM: 214100  phenotype
601539  phenotype
601758  gene+phenotype
KEGG: hsa:5193   

Gene Ontology

GO:0005779 C:integral to peroxisomal membrane
GO:0008022 F:protein C-terminus binding
GO:0008270 F:zinc ion binding
GO:0016558 P:protein import into peroxisome matrix

References (8)

[1] “Isolation of the human PEX12 gene, mutated in group 3 of the peroxisome biogenesis disorders.”  Chang C.-C.et.al.   9090384
[2] “PEX12, the pathogenic gene of group III Zellweger syndrome: cDNA cloning by functional complementation on a CHO cell mutant, patient analysis, and characterization of PEX12p.”  Okumoto K.et.al.   9632816
[3] “Complete sequencing and characterization of 21,243 full-length human cDNAs.”  Ota T.et.al.   14702039
[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] “PEX12 interacts with PEX5 and PEX10 and acts downstream of receptor docking in peroxisomal matrix protein import.”  Chang C.C.et.al.   10562279
[6] “PEX19 binds multiple peroxisomal membrane proteins, is predominantly cytoplasmic, and is required for peroxisome membrane synthesis.”  Sacksteder K.A.et.al.   10704444
[7] “Human pex19p binds peroxisomal integral membrane proteins at regions distinct from their sorting sequences.”  Fransen M.et.al.   11390669
[8] “Identification of novel mutations and sequence variation in the Zellweger syndrome spectrum of peroxisome biogenesis disorders.”  Yik W.Y.et.al.   19105186

External Searches:

Analyze:

Predict TMSs (Predict number of transmembrane segments)
Window Size: Angle:  
FASTA formatted sequence
1:	MAEHGAHFTA ASVADDQPSI FEVVAQDSLM TAVRPALQHV VKVLAESNPT HYGFLWRWFD 
61:	EIFTLLDLLL QQHYLSRTSA SFSENFYGLK RIVMGDTHKS QRLASAGLPK QQLWKSIMFL 
121:	VLLPYLKVKL EKLVSSLREE DEYSIHPPSS RWKRFYRAFL AAYPFVNMAW EGWFLVQQLR 
181:	YILGKAQHHS PLLRLAGVQL GRLTVQDIQA LEHKPAKASM MQQPARSVSE KINSALKKAV 
241:	GGVALSLSTG LSVGVFFLQF LDWWYSSENQ ETIKSLTALP TPPPPVHLDY NSDSPLLPKM 
301:	KTVCPLCRKT RVNDTVLATS GYVFCYRCVF HYVRSHQACP ITGYPTEVQH LIKLYSPEN