PGAM5
PGAM5 is a mitochondrial serine/threonine protein phosphatase that dephosphorylates a range of substrates to influence senescence, mitophagy and cell death. It is also known as MGC5352 or BXLBv68, and was previously named phosphoglycerate mutase family member 5. Browse Assay Genie's current range of PGAM5 research reagents below, or read on for the biology behind the target.
PGAM5 is a mitochondrial serine/threonine phosphatase that dephosphorylates several substrates and so takes part in different biological processes, including cellular senescence and mitophagy. It modulates senescence by regulating mitochondrial dynamics. It participates in mitochondrial fission by dephosphorylating DNM1L (DRP1), and it dephosphorylates MFN2 in a stress-sensitive manner, which protects MFN2 from ubiquitination and degradation and promotes formation of the mitochondrial network.
The enzyme also regulates mitophagy independently of PARKIN, by interacting with and dephosphorylating FUNDC1, which in turn interacts with LC3. In the anti-oxidative response, PGAM5 forms a tertiary complex with KEAP1 and NRF2. In necroptosis, it acts as a RIPK3 target and recruits the RIPK1-RIPK3-MLKL necrosis 'attack' complex to mitochondria. The NCBI Gene summary describes it as enabling protein serine/threonine phosphatase activity and predicts roles in positive regulation of mitochondrial fission and negative regulation of cold-induced thermogenesis.
The PGAM5 gene encodes a protein found at the mitochondrial outer and inner membranes. HGNC places it in the serine/threonine phosphatases and the phosphoglycerate mutases gene groups, and UniProt assigns it to the BPG-dependent PGAM subfamily of the phosphoglycerate mutase family, which is reflected in its original name. Orthologues are annotated in both mouse and rat as Pgam5, so the protein can be studied in common rodent models.
PGAM5 dephosphorylates FUNDC1 to regulate mitophagy independently of PARKIN, making it a focus for studies of mitochondrial quality control.
By dephosphorylating DNM1L (DRP1) and MFN2, PGAM5 links fission and network formation to cellular stress responses.
PGAM5 is a RIPK3 target that recruits the RIPK1-RIPK3-MLKL complex to mitochondria, relevant to programmed necrosis studies.
PGAM5 forms a complex with KEAP1 and NRF2 and so regulates the anti-oxidative response.
PGAM5 is a mitochondrial serine/threonine phosphatase. It dephosphorylates DNM1L (DRP1), MFN2 and FUNDC1 to influence mitochondrial fission, network formation and mitophagy. It also forms a complex with KEAP1 and NRF2 and recruits the necroptosis complex to mitochondria via RIPK3.
HGNC lists the full name as PGAM family member 5, mitochondrial serine/threonine protein phosphatase. Aliases include MGC5352 and BXLBv68, and earlier names were phosphoglycerate mutase family member 5 and PGAM family member 5, serine/threonine protein phosphatase, mitochondrial.
Mouse and rat both have a Pgam5 orthologue. PGAM5 belongs to the phosphoglycerate mutase family, the BPG-dependent PGAM subfamily, but acts as a protein phosphatase. Check the datasheet of any product for its validated reactivity.
Other phosphoglycerate mutase family members with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q96HS1; product specifications from Assay Genie datasheets.