Recombinant Human Serine/threonine-protein phosphatase PGAM5,mitochondrial (PGAM5) (G166A,V167A,K169A) Protein

Function

Mitochondrial serine/threonine phosphatase that dephosphorylates various substrates and thus plays a role in different biological processes including cellular senescence or mitophagy (PubMed:24746696, PubMed:32439975). Modulates cellular senescence by regulating mitochondrial dynamics. Mechanistically, participates in mitochondrial fission through dephosphorylating DNM1L/DRP1 (PubMed:32439975). Additionally, dephosphorylates MFN2 in a stress-sensitive manner and consequently protects it from ubiquitination and degradation to promote mitochondrial network formation (PubMed:37498743). Regulates mitophagy independent of PARKIN by interacting with and dephosphorylating FUNDC1, which interacts with LC3 (PubMed:24746696). Regulates anti-oxidative response by forming a tertiary complex with KEAP1 and NRF2 (PubMed:18387606). Regulates necroptosis by acting as a RIPK3 target and recruiting the RIPK1-RIPK3-MLKL necrosis 'attack' complex to mitochondria (PubMed:22265414)

Subcellular Location

Mitochondrion outer membrane (Single-pass membrane protein); Mitochondrion inner membrane (Single-pass membrane protein)

Subunit

Dimer. Forms a ternary complex with NFE2L2 and KEAP1. Interacts with BCL2L1 and MAP3K5. Upon TNF-induced necrosis, forms in complex with RIPK1, RIPK3 and MLKL; the formation of this complex leads to PGAM5 phosphorylation. Isoform 2, but not isoform 1, interacts with DNM1L; this interaction leads to DNM1L dephosphorylation and activation and eventually to mitochondria fragmentation

• Lo S.-C. et al. PGAM5, a Bcl-XL-interacting protein, is a novel substrate for the redox-regulated Keap1-dependent ubiquitin ligase complex. — J. Biol. Chem. (2006)
• Scherer S.E. et al. The finished DNA sequence of human chromosome 12. — Nature (2006)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Hammond P.W. et al. In vitro selection and characterization of Bcl-X(L)-binding proteins from a mix of tissue-specific mRNA display libraries. — J. Biol. Chem. (2001)
• Sekine S. et al. Rhomboid protease PARL mediates the mitochondrial membrane potential loss-induced cleavage of PGAM5. — J. Biol. Chem. (2012)
• Lo S.-C. et al. PGAM5 tethers a ternary complex containing Keap1 and Nrf2 to mitochondria. — Exp. Cell Res. (2008)
• Takeda K. et al. Mitochondrial phosphoglycerate mutase 5 uses alternate catalytic activity as a protein serine/threonine phosphatase to activate ASK1. — Proc. Natl. Acad. Sci. U.S.A. (2009)
• Choudhary C. et al. Lysine acetylation targets protein complexes and co-regulates major cellular functions. — Science (2009)