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FLASH GENE
Symbol ACTN3 contributors: mct - updated : 09-01-2012
HGNC name actinin, alpha 3
HGNC id 165
Corresponding disease
ACTN3D alpha-actinin-3 deficiency
Location 11q13.2      Physical location : 66.314.390 - 66.330.797
Synonym name
  • alpha-actinin skeletal muscle isoform 3
  • F-actin cross-linking protein
  • Synonym symbol(s) MGC117002, MGC117005
    DNA
    TYPE functioning gene
    STRUCTURE 16.41 kb     21 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked   status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    21 - 2858 103.3 901 - 2003 15221860
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal   Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Skeletonosteoblast Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • one actin-binding domain
  • two ch (calponin-homology) domains
  • two ef-hand calcium-binding domains
  • four spectrin repeats
  • mono polymer homomer , dimer
    HOMOLOGY
    interspecies ortholog to rattus Actn3
    Homologene
    FAMILY
    CATEGORY motor/contractile
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    text localized to the Z-disc and analogous dense bodies, where it helps to anchor the myofibrillar actin filaments
    basic FUNCTION
  • one of many genes contributing to genetic variation in muscle performance and adaptation to exercise
  • potentially participating with ACTN2 in sequestering parafibromin (HRPT2) in the cytoplasmic compartment
  • potentially regulates PYGM activity by altering its level of phosphorylation
  • presence of ACTN3 protein is associated with improved sprint/power performance in athletes and the general population
  • major component of the Z-disk in skeletal muscle, where they crosslink actin and other structural proteins to maintain an ordered myofibrillar array
  • potentially necessary for optimal forceful repetitive muscle contractions
  • is an integral part of the Z line of the sarcomere
  • role of ACTN3 in contractile properties of human single muscle fibers
  • play a role in the regulation of calcineurin signaling
  • ACTN3 influences likely sarcomeric composition in a dose-dependent fashion in skeletal muscle, which translates directly to function
  • role in modulating muscle metabolism with altered fatiguability
  • play a role in regulating fiber size and muscle growth during embryonic muscle development
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule metal binding,
    Ca2+
    protein
    cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) ACTN3D
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional        
    changes the overall protein composition of fast fiber Z-disks and alters their elastic properties, providing a mechanistic explanation for the loss of force generation and increased susceptibility to eccentric damage in ACTN3-deficient individuals
    constitutional       loss of function
    reduces the activity of glycogen phosphorylase and results in a fundamental shift toward more oxidative pathways of energy utilization
    constitutional       loss of function
    is underrepresented in elite sprint/power athletes and has been associated with reduced muscle mass and strength in humans
    Susceptibility
  • to passive muscle stiffness
  • Variant & Polymorphism other
  • R577X associated to elite athlete status (overrepresentation of the 577XX genotype among elite endurance athletes)
  • R577X polymorphism of the ACTN3 has been associated
  • with passive muscle stiffness
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Actn3 KO mice showing reductions in muscle strength, increased endurance capacity, reduced fast fiber size, shifts in fast fiber metabolism toward oxidative metabolism
  • Actn3(-/-) mouse displays significantly reduced bone mass, with reduced cortical bone volume (-14p100) and trabecular number (-61p100) seen by microCT