Reactome | 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

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

peroxisomal membrane

ReviewStatus

5/5

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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

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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
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
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
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