Phosphoglycerate Mutase 5 (PGAM5)

BXLBv68; Bcl-XL-binding protein v68; Serine/threonine-protein phosphatase PGAM5, mitochondrial

SPN	J130
HGNC	28763
MGI	1919792
PubMed	22265414
RGD	1312028
UniProt	Q96HS1

Keap1 is a BTB-Kelch substrate adaptor protein for a Cul3-dependent ubiquitin ligase complex that functions as a sensor for thiol-reactive chemopreventive compounds and oxidative stress. PGAM5, as a novel substrate for Keap1. The N terminus of the PGAM5 protein contains a conserved NXESGE motif that binds to the substrate binding pocket in the Kelch domain of Keap1, whereas the C-terminal PGAM domain binds Bcl-X_L. Keap1-dependent ubiquitination of PGAM5 results in proteasome-dependent degradation of PGAM5. Quinone-induced oxidative stress and the chemopreventive agent sulforaphane inhibit Keap1-dependent ubiquitination of PGAM5. The identification of PGAM5 as a novel substrate of Keap1 suggests that Keap1 regulates both transcriptional and post-transcriptional responses of mammalian cells to oxidative stress.

Reference

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J. Biol. Chem. 276:20898-20906(2001) [PubMed] [Europe PMC] [Abstract]

"PGAM5 tethers a ternary complex containing Keap1 and Nrf2 to mitochondria."
Exp. Cell Res. 314:1789-1803(2008) [PubMed] [Europe PMC] [Abstract]

"Mitochondrial phosphoglycerate mutase 5 uses alternate catalytic activity as a protein serine/threonine phosphatase to activate ASK1."
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Submitted (SEP-2010) to the PDB data bank