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FLASH GENE
Symbol AFG3L2 contributors: mct - updated : 01-09-2015
HGNC name AFG3 ATPase family gene 3-like 2 (S. cerevisiae)
HGNC id 315
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • an ATP-binding/ATPase domain (AAA domain), the structural hallmark of the AAA-protease subfamily
  • a zinc-dependent metalloprotease domain in a single polypeptide
    • conjugated MetalloP
    HOMOLOGY
    interspecies homolog to yeast mitochondrial proteins, Yta10p (Afg3p) (Di Bella 2010)
    intraspecies homolog to paraplegin SPG7
    Homologene
    FAMILY
  • AAA ATPase family (in the N terminal)
  • peptidase M41 family (in the C terminal)
    • CATEGORY chaperone/stress , enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria,inner
    intracellular,cytoplasm,organelle,membrane
    basic FUNCTION
  • turn over of mistranslated and misfolded mt DNA encoded polypeptides
  • crucial role by linking mitochondrial metabolism and axonal development
  • important role of the homo-oligomeric AFG3L2 m-AAA complex in neuronal degeneration
  • unexpectedly essential role in protecting the cerebellum from neurodegeneration and expand the spectrum of molecular mechanisms underlying the overlapping features of hereditary ataxias
  • is linked to mitochondrial Ca2+ buffering
  • cell-autonomous requirement of AFG3L2 for survival of Purkinje cell
  • SPG7 assembles with AFG3L2 into the mAAA protease at the inner membrane of mitochondria, degrades damaged proteins, and regulates the synthesis of mitochondrial ribosomes
    • CELLULAR PROCESS protein, degradation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • component of the m-AAA protease, a high molecular weight complex in the inner mitochondrial membrane evolutionary conserved from yeast to mammals (exists in a hetero-oligomeric form, composed of paraplegin and AFG3L2)
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • assembles with the homologous protein paraplegin to form a supracomplex in charge of the essential protein quality control within mitochondria
  • mitochondrial processing peptidase PMPCB generates an intermediate form of AFG3L2 that is matured autocatalytically
  • AFG3L1, AFG3L2 are also required for maturation of newly imported paraplegin subunits after their cleavage by PMPCB
  • SPG7 is cleaved and activated by AFG3L2 upon assembly
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) SCA28 , SPAX5
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       loss of function
    causes a marked reduction in mitochondrial Ca2+ buffering
    Susceptibility
    Variant & Polymorphism
    Candidate gene excellent candidate for motoneuron and cerebellar diseases with early onset unknown etiology
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • loss of Afg3l2 in mouse embryonic fibroblasts (MEFs) reduces mitochondrial Ca2+ uptake capacity
  • Afg3l2-/- mice resemble patients carrying homozygous mutations, showing a severe neurological syndrome that leads to lethality at P16