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FLASH GENE
Symbol DMD contributors: mct/pgu - updated : 04-03-2015
HGNC name dystrophin
HGNC id 2928
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N-terminal part of dystrophin is reported as a globular actin binding domain 1 (N-ABD), and WW domain
  • one actin-binding domain
  • a central rod domain with 24 weakly repeating units of 110 AAs similar to the coiled-coil repeats of spectrin, and disrupted by
    • four potential hinges that may ensure flexibility (critical role for the rod domain in different aspects of dystrophin function, in particular a reduced stability of the R23 repeat)
  • two calponin homology (CH) domains within the actin-binding domain
  • C terminal ZZ type zinc binding domain required for the binding of dystrophin and utrophin to beta dystroglycan, a cysteine-rich zinc-finger domain near the dystrophin C-terminus, implicated in forming a stable interaction between dystrophin and beta-dystroglycan
    • secondary structure homologous sequence motifs have been proposed to form domains with a triple-helical bundle-type structure
    HOMOLOGY
    interspecies homolog to murine Dmd
    Homologene
    FAMILY
    CATEGORY structural protein
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton
    intracellular,nucleus,nucleoplasm
    text inner surface of striated muscles, beneath the sarcolemma
    basic FUNCTION
  • involved in muscle development and vision (anchoring the cytoskeleton to the plasma membrane)
  • stabilizes the cell membrane of muscle cells against the mechanical forces associated with muscle contraction and stretch
  • muscle scaffolding protein that establishes a structural link between the cytoskeleton and the extracellular matrix
  • with utrophin have distinct effects on the structural dynamics of actin
  • in addition to its protective role, may act as a signaling molecule in cell signaling pathways such as muscle cell growth, cytoskeleton organization, muscle homeostasis, and atrophy/hypertrophy
  • recruits neuronal nitric oxide synthase (NOS1) to the sarcolemma, but not UTRN
  • acts as a link between the sarcolemma transmembrane glycoprotein complex and actin fibers, protecting actin filaments against depolymerization
  • DMD and UTRN are highly similar proteins that both link cortical actin filaments with a complex of sarcolemmal glycoproteins, yet localize to different subcellular domains within normal muscle cells
  • DMD binds microtubules with high affinity and pauses microtubule polymerization, whereas utrophin has no activity in either assay
  • is a tumor suppressor and likely anti-metastatic factor
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling sensory transduction/vision
    a component
  • part of the dystrophin-glycoprotein complex (DGC), which bridges the inner cytoskeleton (F-actin) and the extra-cellular matrix
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding ANK2, ANK3 (require ANK3 for retention at costameres but not delivery to the sarcolemma)
  • associating with the dystroglycan complex
  • interacting with SYNM, an important IF protein in muscle cells that helps fortify the linkage between the peripheral layer of cellular myofibrils and the costameric regions located along the sarcolemma
  • with UTRN, bind to actin with similar affinities, and both stabilize actin filaments against depolymerization, but dystrophin and utrophin differ in their effects on the extent of lateral association with actin and in the ionic strength dependence of actin binding
  • ANK2 binds to dystrophin, DCTN4, and microtubules and is required for sarcolemmal association of these proteins as well as dystroglycan
  • UTRN and DMD interact with actin through their N-terminal actin-binding domain (N-ABD)
  • SSPN is a necessary component of DMD and UTRN function
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) BMD , CMD3B , DMD , OED , DELXP21
    related resource Becker
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional   deletion    
    disruption to the amino terminus in end stage cardiomyopathy
    constitutional     --low  
    lack of dystrophin leads to a general dysregulation of vesicle trafficking
    Susceptibility to viral (enterovirus) heart disease and increased risk of cardiomyopathy
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    neuromuscularmyopathydegenerative
    suramin, a transforming growth factor-beta 1 (TGF-beta1) blocker, might be a useful therapeutic alternative for the treatment of dystrophinopathies (DMD and other myopathy)
    ANIMAL & CELL MODELS
  • increased levels of matrix metalloproteinase-9 (Mmp-9) protein causes myopathy in dystrophin-deficient mdx mice
  • suramin decreased creatine kinase in mdx mice and attenuated fibrosis in all muscles studied, except for cardiac muscle
  • severe muscle phenotype observed in mdx/mTRG2 animals is caused by defects in muscle stem cells function (MUSC), demonstrating that progressive loss of MUSC reserve plays a major role in determining the severity of the dystrophic phenotype
  • mice lacking utrophin and dystrophin (mdx/utrn -/-) are severely affected and die prematurely
  • altered acetylcholine release in the hippocampus of dystrophin-deficient mice