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FLASH GENE
Symbol PGAM5 contributors: mct - updated : 02-10-2017
HGNC name phosphoglycerate mutase family member 5
HGNC id 28763
Location 12q24.33      Physical location : 133.287.392 - 133.299.322
Synonym name
  • Bcl-XL-binding protein v68
  • serine/threonine-protein phosphatase PGAM5, mitochondrial
  • Synonym symbol(s) BXLBV68, MGC5352
    EC.number 3.1.3.16
    DNA
    TYPE functioning gene
    STRUCTURE 11.94 kb     6 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    6 - 1194 28 255 - 2008 18387606
  • PGAM5S
  • addition of 16 hydrophobic AAS at the C terminus that potentially rendered the short form of PGAM5, PGAM5S, more hydrophobic than PGAM5L
  • 6 - 2851 - 289 - 2008 18387606
  • PGAM5L
  • is a Kinase Substrate of RIPK1/RIPK3
  • 6 - 2848 - 288 - 2008 18387606
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N terminus containing a conserved NXESGE motif that binds to the substrate binding pocket in the Kelch domain, and catalytically important N-terminal WDPNWD motif acts as a structural integrator assembling PGAM5 into a dodecamer, allosterically activating the phosphatase by promoting an ordering of the catalytic loop (
  • conserved E(S/T)GE motifs
  • C-terminal PGAM domain binds BCL2L1, and facing the cytoplasm
  • HOMOLOGY
    Homologene
    FAMILY
  • PGAM family
  • CATEGORY receptor serine/threonine phosphatase
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,mitochondria,outer
    intracellular,cytoplasm,organelle,membrane
    text
  • anchored in the mitochondrial membrane
  • targeted to the outer membrane of mitochondria by an N-terminal mitochondrial-localization sequence
  • basic FUNCTION
  • KEAP1-dependent ubiquitination of PGAM5 results in proteasome-dependent degradation of PGAM5
  • enzyme of intermediary metabolism that converts 3-phosphoglycerate to 2-phosphoglycerate in glycolysis
  • is the convergent point for multiple necrosis pathways
  • mitochondrial phosphatase that functions in programmed necrosis (necroptosis)
  • is the convergent point for multiple necrosis pathways
  • is an atypical mitochondrial Ser/Thr phosphatase that modulates mitochondrial dynamics and participates in both apoptotic and necrotic cell death
  • protects cells from necroptosis by independently promoting mitophagy
  • is a mitochondrial protein phosphatase that has been reported to be involved in various stress responses from mitochondrial quality control to cell death
  • is involved in the whole-body metabolism in response to stresses that impose metabolic challenges on mitochondria
  • PGAM5 controls cardiomyocyte apoptosis induced by myocardial ischemia/reperfusion injury(MIRI) through regulating KEAP1-mediated BCL2L1 degradation
  • is a mitochondrial membrane protein that functions as an atypical Ser/Thr phosphatase and is a regulator of oxidative stress response, necroptosis, and autophagy
  • is a mitochondrial protein that plays crucial roles in apoptosis and necroptosis
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • forms a ternary complex containing both KEAP1 and NFE2L2, in which the dimeric KEAP1 protein simultaneously binds both PGAM5 and NFE2L2 through their conserved E(S/T)GE motifs
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • lacking PGAM activity and instead associates with the MAP kinase kinase kinase MAP3K5 and acting as a specific protein Ser/Thr phosphatase that activates MAP3K5 by dephosphorylation of inhibitory sites
  • dephosphorylates and activates mitochondrial fission protein DNM1L
  • PARL mediates the mitochondrial membrane potential loss-induced cleavage of PGAM5
  • PARL mediates likely differential cleavage of PINK1 and PGAM5 depending on the health status of mitochondria
  • signaling pathway linking mitochondria-damaging signals to the dephosphorylation of FUNDC1 by PGAM5, which ultimately induces mitophagy
  • BCL2L1, interacts with and inhibits PGAM5, a mitochondrially localized phosphatase, to prevent the dephosphorylation of FUNDC1 at serine 13 (Ser13), which activates hypoxia-induced mitophagy
  • is a mitochondrial phosphatase that has been reported to function downstream of RIPK3 to promote necroptosis and IL1B secretion
  • PGAM5 is indispensable for the process of PINK1 dependent mitophagy which antagonizes necroptosis
  • functions as a phosphohistidine phosphatase that specifically associates with and dephosphorylates the catalytic histidine on NME2
  • by dephosphorylating NME2, PGAM5 negatively regulates CD4(+) T cells by inhibiting NME2-mediated histidine phosphorylation and activation of the KCNN4
  • PGAM5 might participate in the degradation of BCL2L1 mediated by KEAP1
  • depletion of NFE2L2 or PGAM5, but not KEAP1, inhibits mitochondrial retrograde trafficking induced by proteasome inhibition
  • PGAM5 regulates PINK1-PRKN-mediated mitophagy, which can exert a neuroprotective effect against carbonyl cyanide m-chlorophenylhydrazone (CCCP)-induced apoptosis
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    digestiveliver 
    PGAM5-DNM1L axis is a potential therapeutic target for acute immune-mediated liver injury
    cardiovascularatheroma 
    may represent a therapeutic target for stroke, myocardial infarction and other diseases caused by oxidative damage and necroptosis
    ANIMAL & CELL MODELS
  • Pgam5-deficient mice are resistant to several metabolic insults