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FLASH GENE
Symbol DMD contributors: mct/pgu - updated : 04-03-2015
HGNC name dystrophin
HGNC id 2928
Corresponding disease
BMD muscular dystrophy, progressive, Becker type (dystrophin defect)
CMD3B cardiomyopathy, dilated 3B
DELXP21 chromosome Xp21 microdeletion syndrome
DMD muscular dystrophy, Duchenne or type
OED blindness, night, congenital, stationary 2,
Location Xp21.1      Physical location : 31.137.344 - 33.357.726
Synonym name
  • dystrophin (muscular dystrophy, Duchenne and Becker types)
  • ORF (Dmd gene)(AA 1-61)
  • Duchenne muscular dystrophy protein
  • Synonym symbol(s) DYS, DP71, DXS142, DXS164, DXS206, DXS230, DXS239, DXS268, DXS269, DXS270, DXS272
    DNA
    TYPE functioning gene
    STRUCTURE 2220.38 kb     79 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    alternative promoter
    Binding site   enhancer
    text structure
  • alternative promoters of the muscle, brain, cerebellar Purkinje enhancer : dystrophin muscle enhancer 1 (DME1)
  • muscle-specific enhancer 2 (DME2), within intron1 (activity may be restricted to later stages of cardiac muscle development )
  • MAPPING cloned Y linked N status confirmed
    Physical map
    LOC139420 Xp22.11 similar to KIAA1387 protein RDXP2 Xp22.12 radixin pseudogene 2 FLJ32742 Xp22.11 hypothetical protein FLJ32742 LOC347442 Xp22.11 similar to H326 FLJ32965 Xp22.11 hypothetical protein FLJ32965 LOC392434 X similar to melanoma antigen LOC392435 X similar to melanoma antigen LOC392436 X similar to melanoma antigen MAGE LOC340569 Xp22.11 pseudogene of origin recognition complex, subunit 1-like LOC139425 Xp22.11 similar to H326 IL1RAPL1 Xp22.1-p21.3 interleukin 1 receptor accessory protein-like 1 MAGEB2 Xp21.3 melanoma antigen, family B, 2 MAGEB3 Xp21.3 melanoma antigen, family B, 3 MAGEB4 Xp21.3 melanoma antigen, family B, 4 MAGEB1 Xp21.3 melanoma antigen, family B, 1 NR0B1 Xp21.3 nuclear receptor subfamily 0, group B, member 1 FLJ11577 Xp21.3 hypothetical protein FLJ11577 LOC392437 X similar to hypothetical protein GK Xp22.3-p21.3 glycerol kinase TAB3 Xp21.3 TAK1-binding protein 3 FTHL17 Xp21 ferritin, heavy polypeptide-like 17 DMD Xp21.3-p21.2 dystrophin (muscular dystrophy, Duchenne and Becker types) LOC392438 X hypothetical gene supported by NM_004607 LOC158724 Xp21.1 similar to hypothetical protein FLJ35782 LOC389843 X similar to hypothetical protein FLJ35782 LOC139431 Xp21.1 similar to ferritin heavy chain - chicken LOC392439 X similar to PR264/SC35 TM4SF10 Xp11.4 transmembrane 4 superfamily member 10 FLJ35782 Xp21.1 hypothetical protein FLJ35782 LOC392440 X similar to hypothetical protein MGC33889
    RNA
    TRANSCRIPTS type messenger
    text contains at least seven internal promoters that produce different tissue-specific dystrophins, named according with their molecular weights as Dp427, Dp260, Dp116, Dp140, and Dp71
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    79 - 13993 427 3685 - 1992 1307251
  • also called DYS, DP427m
  • specific promoter, unique N terminus
  • large, rod-like cytoskeletal protein at found at the inner surface of muscle fibers.
  • 51 initiation site 9771 260 2344 retina outer plexiform layer 1992 1307251
  • also called DP260-1
  • promoter/exon 1 in intron 29, exons 30-79
  • impairment related to dystrophin isoform Dp260 leads to red-green color defect
  • 36 splicing 7410 140 1225 central nervous system, kidney 1992 1307251
  • also called DP140
  • may be involved in cognitive development, promoter/exon 1 in intron 44, exons 45-79
  • strong association between the risk of cognitive disability and deltion of this isoform (PMID: 20098710)
  • 25 splicing 5623 116 956 peripheral nerve 1992 1307251
  • also called DP116
  • anchored with utrophin in a sarcoglycan complex, promoter/exon 1 in intron 55, exons 56-79
  • - initiation site 1571 40 340 - 1988 3180845
  • also called DP40
  • same start site than DP71, exons 63-710
  • 17 splicing initiation site 4584 71 604 microsomes, nuclear variant 1992 1307251
  • also called DP71a/DP71d or Dp71a
  • start site for a new coding sequence, exons 63-79, lacking exon 71
  • associates with the nuclear matrix
  • dynamic component of nuclear matrix that might participate in the nuclear modeling occurring during neuronal differentiation
  • 33 splicing initiation site 7048 140 1133 - 1992 1307251
  • also called DP140bc
  • promoter/exon 1 in intron 44, exons 45-79, start site in exon 51, lacking exons 71-4 and 78
  • 17 splicing initiation site 4591 71 635 mitochondria, cytoplasmic variant 1992 1307251
  • also called DP71b/DP71f or Dp71b
  • start site for a new coding sequence, exons 63-79, lacking exon 78
  • 79 initiation site 14082 - 3562 - 1992 1307251
  • also called DP427p2
  • insertion of 82 nucleotides after exon 1
  • 82 initiation site 14069 - 3677 neurons, cortex, hippocampus 1992 1307251
  • also called DP427c
  • promoter upstream DP427m, unique N terminus
  • 35 - 7378 140 1243 - 1992 1307251
  • also called DP140b
  • promoter/exon 1 in intron 44, exons 45-79, start site exon 51, lacking exon 78
  • 51 initiation site 9914 260 2341 - 1992 1307251
  • also called DP260-2
  • promoter/exon 1 in intron 29, exons 30-79
  • 34 splicing initiation site 7339 140 1230 - 1992 1307251
  • also called DP140ab
  • promoter/exon 1 in intron 44, exons 45-79, start site exon 51, lacking exons 71 and 78
  • 33 splicing initiation site 7050 140 1105 - 1992 1307251
  • also called DP140c
  • promoter/exon 1 in intron 44, exons 45-79, start site exon 51, lacking exon 71-74
  • 18 - 4623 71 617 most abundant dystrophin product in the brain 2009 19602481
  • also called DP71
  • start site for a novel coding sequence, exons 63-79 including exons 71 and 78, most abundant product
  • has its promoter region and specific first exon between exons 62 and 63 (7 kb upstream to exon 63)
  • required for development of cognitive functions and provide insights into the understanding of molecular mechanisms underlying cognitive impairment associated with DMD and BMD phenotype
  • down-regulation of the Dp71 promoter activity down-regulated during myogenesis, in differentiated cells, and efficient promoter activity was restored in differentiated muscle cells by exogenous expression of Sp1 and Sp3
  • 15 - 4552 11 622 microsomes 1992 1307251
  • also called DP71ab
  • start site for a new coding sequence, exons 63-79 lacking exon 71, 78
  • EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart    
    Hearing/Equilibriumearinnercochlea highly
    Nervousbrain    
     nerve   highly
    Visualeyeretina   
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Visualrod photoreceptor
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    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