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FLASH GENE
Symbol ATG12 contributors: np/mct - updated : 15-01-2015
HGNC name ATG12 autophagy related 12 homolog (S. cerevisiae)
HGNC id 588
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
HOMOLOGY
interspecies homolog to Drosophila Cgi0861
Homologene
FAMILY
  • ATG12 family
  • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    basic FUNCTION
  • with ATG2B, ATG5, ATG9B, are autophagy-related genes, having mononucleotide repeats with seven or more nucleotides
  • two ubiquitin-like conjugation systems, ATG12 and GABARAPL2 systems, which are tightly associated with expansion of autophagosomal membrane are required for autophagosome formation
  • ATG12-ATG5 conjugate has a novel E3-like activity for protein lipidation in autophagy
  • ATG5-ATG12 conjugate, a key regulator of the autophagic process, plays an important role in innate antiviral immune responses
  • ubiquitin-like modifier required for macroautophagy, has a single known conjugation target, another autophagy regulator called ATG5
  • role for ATG12-ATG3 in mitochondrial homeostasis and implicate the ATG12 conjugation system in cellular functions distinct from the early steps of autophagosome formation
  • ATG12 conjugation system directs cellular functions distinct from the early steps of autophagosome formation
  • like ubiquitin and SUMO, may serve as a broad-based ubiquitin-like protein conjugation with far-reaching implications in biology and human disease
  • essential autophagy protein that is a positive mediator of mitochondrial apoptosis
  • MAP1LC3B, ATG5 and ATG12 are involved in mitochondrial quality control after oxidative damage, and to cellular longevity.
  • CELLULAR PROCESS cell life, cell death/apoptosis
    protein, degradation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • covalently linked to APG5L component of conjugation system leading to protein degradation
  • part of ATG12-ATG3 complex
  • is a key component of an E3-like ATG12-ATG5-ATG16L1 protein complex that catalyzes conjugation of the MAP1LC3 protein to lipids, thus controlling autophagic vesicle formation and expansion
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding to APG5L
  • ATG10 interacts with ATG7 to receive an ubiquitin-like protein ATG12, recognizes both ATG12 and ATG5 directly and catalyzes their conjugation reaction
  • directly regulates the apoptotic pathway by binding and inactivating prosurvival BCL2 family members, including BCL2 and MCL1
  • interaction between ATG12 and BCL2 family members may thus constitute an important point of convergence between autophagy and apoptosis in response to specific signals
  • concerted interactions among TECPR1, ATG12-ATG5, and PtdIns(3)P provide the fusion specificity between autophagosomes and lysosomes and the assembly of this complex initiates the autophagosome maturation process
  • autophagic E2 enzymes, ATG10, interacts with ATG7 to receive ATG12, a ubiquitin-like molecule, and is also involved in the ATG12-ATG5 conjugation reaction
  • during process of induced autophagy, the ATG12-ATG5 conjugate requires 2 different binding partners, ATG16L1 for autophagosome elongation and TECPR1 for lysosomal fusion
  • cell & other
    REGULATION
    induced by mitochondrial DNA deletions and chloramphenicol treatment
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   deletion    
    frequently deleted in lung cancers
    tumoral somatic mutation      
    in gastric and colorectal cancers with microsatellite instability
    Susceptibility to development of hepatocellular carcinoma (HCC)
    Variant & Polymorphism other
  • ATG12 rs26537 significantly associated with HCC risk
  • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS