PEX1:PEX6:PEX26:ZFAND6 dissociates Ub:PEX5L and PEX7 from PEX14:PEX13:PEX2:PEX10:PEX12 and translocates PEX5L and PEX7 from the peroxisomal membrane to the cytosol

Stable Identifier
R-HSA-9033499
Type
Reaction [uncertain]
Species
Homo sapiens
Compartment
General
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

Ubiquitinated PEX5 isoform L (Ub:PEX5L) is released from the peroxisomal membrane Docking and Translocation Module by PEX1:PEX6:PEX26 (the peroxisomal AAA ATPase complex, receptor export module) (Tamura et al. 2014, Law et al. 2017, also inferred from yeast homologs). PEX1 and PEX6 form a cytosolic hexameric ring that is anchored to the peroxisomal membrane by PEX26. Hydrolysis of ATP by PEX1 and PEX6 appears to cause a conformational change in PEX1:PEX6:PEX26 that removes Ub:PEX5L from the peroxisomal membrane and into the cytosol (reviewed in Saffert et al. 2017). ZFAND6 probably binds ubiquitinated PEX5 and PEX6 and acts as an export factor (Miyata et al. 2012). Export of PEX7 back to the cytosol requires export of PEX5L but PEX7 and PEX5L appear to be exported separately (Rodrigues et al. 2014).

Literature References
PubMed ID Title Journal Year
28521612 The peroxisomal AAA ATPase complex prevents pexophagy and development of peroxisome biogenesis disorders

Law, KB, Bronte-Tinkew, D, Di Pietro, E, Snowden, A, Jones, RO, Moser, A, Brumell, JH, Braverman, N, Kim, PK

Autophagy 2017
25016021 AAA peroxins and their recruiter Pex26p modulate the interactions of peroxins involved in peroxisomal protein import

Tamura, S, Matsumoto, N, Takeba, R, Fujiki, Y

J. Biol. Chem. 2014
21980954 AWP1/ZFAND6 functions in Pex5 export by interacting with cys-monoubiquitinated Pex5 and Pex6 AAA ATPase

Miyata, N, Okumoto, K, Mukai, S, Noguchi, M, Fujiki, Y

Traffic 2012
24865970 A PEX7-centered perspective on the peroxisomal targeting signal type 2-mediated protein import pathway

Rodrigues, TA, Alencastre, IS, Francisco, T, Brites, P, Fransen, M, Grou, CP, Azevedo, JE

Mol. Cell. Biol. 2014
28611990 Structure and Function of p97 and Pex1/6 Type II AAA+ Complexes

Saffert, P, Enenkel, C, Wendler, P

Front Mol Biosci 2017
9539740 Human PEX1 cloned by functional complementation on a CHO cell mutant is responsible for peroxisome-deficient Zellweger syndrome of complementation group I

Tamura, S, Okumoto, K, Toyama, R, Shimozawa, N, Tsukamoto, T, Suzuki, Y, Osumi, T, Kondo, N, Fujiki, Y

Proc. Natl. Acad. Sci. U.S.A. 1998
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
ATPase activity, coupled to movement of substances of PEX2:PEX10:PEX12:Ub:PEX5L:PEX7:PEX13:PEX14:PEX1:PEX6:PEX26:ZFAND6 [peroxisomal membrane]
Physical Entity
Activity
Orthologous Events
Authored
Reviewed
Created