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FLASH GENE
Symbol DAG1 contributors: mct/shn - updated : 12/01/2013
HGNC name dystroglycan 1 (dystrophin-associated glycoprotein 1)
HGNC id 2666
Corresponding disease
DEL3P21 chromosome 3p21 microdeletion
SCARMD4 severe childhood muscular dystrophy 4
Location 3p21.31      Physical location : 49.506.145 - 49.573.046
Synonym name
  • dystrophin-associated glycoprotein 1, cleaved into the following 2 chains
  • dystrophin-associated glycoprotein-1
  • alpha-dystroglycan
  • beta-dystroglycan
  • Synonym symbol(s) 156DAG, A3a, AGRNR, DAG, MDDGC7
    DNA
    TYPE functioning gene
    STRUCTURE 65.49 kb     3 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Map pter - D3S1581 - D3S2384 - DAG1 - D3S3629 - D3S2456 - cen
    Physical map
    ARIH2 3p21.2-p21.3 ariadne homolog 2 (Drosophila) PH-4 3p21.31 hypoxia-inducible factor prolyl 4-hydroxylase WDR6 15q21 WD repeat domain 6 FLJ10496 3p21.31 hypothetical protein FLJ10496 DKFZP564J0123 3p21.31 nuclear protein E3-3 IMPDH2 3p21.2 IMP (inosine monophosphate) dehydrogenase 2 FLJ20259 3p21.31 FLJ20259 protein QARS 3p21.3-p21.2 glutaminyl-tRNA synthetase USP19 3p21.3-p14.2 ubiquitin specific protease 19 LAMB2 3p21.3-p21.2 laminin, beta 2 (laminin S) FLJ12800 3p21.31 hypothetical protein FLJ12800 MGC35097 3p21.31 hypothetical protein MGC35097 LOC339834 3p21.31 hypothetical protein LOC339834 FLJ43654 3p21.31 FLJ43654 protein USP4 3p21.31 ubiquitin specific protease 4 (proto-oncogene) GPX1 3p21.2 glutathione peroxidase 1 ARHA 3p21.2 ras homolog gene family, member A TCTA 3p21 T-cell leukemia translocation altered gene AMT 3p21.2 aminomethyltransferase (glycine cleavage system protein T) NICN1 3p21.31 nicolin 1 DAG1 3p21.2-p21.1 dystroglycan 1 (dystrophin-associated glycoprotein 1) BSN 3p21.31 bassoon (presynaptic cytomatrix protein) APEH 3p21.3-p21.2 N-acylaminoacyl-peptide hydrolase MST1 3p21.31 macrophage stimulating 1 (hepatocyte growth factor-like) RNF123 3p24.3 ring finger protein 123 GMPPB 3p21.31 GDP-mannose pyrophosphorylase B IHPK1 3p21.31 inositol hexaphosphate kinase 1 LOC389117 3 similar to mouse fat 1 cadherin LOC389118 3 similar to VLLR9392 LOC389119 3 similar to RIKEN cDNA 6530418L21 UBE1L 3p21.2 ubiquitin-activating enzyme E1-like TRIP 3p21.31 TRAF interacting protein MGC8407 3p21.31 hypothetical protein MGC8407 LOC389120 3 similar to RIKEN cDNA 4921517D21 LOC285405 3p21.31 similar to RIKEN cDNA 4921517D21 MST1R 3p21.3 macrophage stimulating 1 receptor (c-met-related tyrosine kinase)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    3 splicing 5543 - 895 - -
  • preproprotein
  • 5 splicing 5904 - 895 - -
  • preproprotein
  • 3 splicing 5594 - 895 - -
    4 splicing 5663 - 895 - -
    5 splicing 5825 - 895 - -
    4 splicing 5436 - 895 - -
    6 splicing 5847 - 895 - -
    3 splicing 5683 - 895 - -
    4 splicing 5595 - 895 - -
    4 splicing 5690 - 895 - -
    4 splicing 5600 - 895 - -
    4 splicing 5384 - 895 - -
    4 splicing 5694 - 895 - -
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart    
    Nervousbrain   highly
    Reproductivemale systemprostate  highly
    Urinarykidney   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelial    
    Muscularstriatumcardiac  
    Muscularstriatumskeletal  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousepithelial cell
    Skin/Tegumentmelanocyte
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • dystroglycan-type cadherin-like domain
  • one peptidase S72 domain
  • conjugated GlycoP
    isoforms Precursor T precursor of the 43kDa DYS associated transmembrane glycoprotein DAG beta (dystroglycan beta)
    HOMOLOGY
    interspecies ortholog to DAG1, pan troglodytes
    ortholog to Dag1, Mus musculus
    ortholog to Dag1, Rattus norvegicus
    ortholog to dag1, danio rerio
    Homologene
    FAMILY
    CATEGORY receptor
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
        intracellular
    intracellular,cytoplasm,cytoskeleton
    text
  • alpha DG is secreted whereas beta-DG is localized at the cytoskeleton
  • localized at costameres and neuromuscular junctions in the sarcolemma of skeletal muscle (Ayalon 2008)
  • basic FUNCTION
  • required for the development of Reichert's membrane
  • required for the formation of a basement membrane in embryoid bodies
  • necessary for myofibre survival and synapse differentiation or stability
  • acting as a Schwann cell receptor for mycobacterium leprae, in the presence of the G domain of LAMA2
  • major organizer of extracellular matrix proteins, of the neuromuscular function and of synaptic components
  • playing a role in the regulation of the actin cytoskeleton, transduction of signals from the extracellular matrix to the cytoskeleton and regulation of the cell morphology
  • a key signaling component in the Notch pathway
  • necessary for Laminin enhancement of filopodial formation, process outgrowth, and process branching in differentiating oligodendroglia
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • a 156kDa extracellular component DAG alpha (dystroglycan alpha) membrane associated through a non covalent interaction with the extracellular domain of DAG beta
  • bound to laminin 2 (alpha 2,beta 1,gamma 1) and to agrin and perlecan, multifunctional protein critical in the formation of extracellular matrix in cells contacting basement membranes
  • connecting the intracellular cytoskeleton to ECM and protecting muscle from mechanical injury
  • receptor for lymphocytic choriomeningitis virus and Lassa fever virus
  • INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • ions Ca2+ binding
  • protein
  • agrin
  • laminin A/B1/B2 and merosin M/B1/B2
  • laminin-1
  • dystrophin
  • Biglycan
  • utrophin
  • growth factor receptor 2, Grb2
  • Caveolin-3
  • rapsyn RING-H2 domain
  • AGR2 and AGR3
  • AGR
  • DAG1 function requires xylosyl- and glucuronyltransferase activities of LARGE to bind laminin-G domain-containing ECM ligands
  • CHST10 suppressed the glycosylation and reduced the ligand binding activity of DAG1
  • sulfate transfer induced by CHST10 plays a regulatory role in the formation of functional glycans DAG1
  • GYLTL1B regulates functional DAG1 glycosylation in prostate cancer cell lines
  • POMGNT2 might encode O-GlcNAc transferase that specifically glycosylates DAG1
  • interacts with DAG1 and controls motility and mechanical properties of Schwann cells
  • POMGNT1 stem region modulates O-mannosylation sites of DAG1, by its carbohydrate-binding domain
  • cell & other
    REGULATION
    activated by activated MUSK binding dystroglycan is regulated by alternative mRNA splicing of agrin
    Other precursor of the 43kDa DYS associated transmembrane glycoprotein DAG beta (dystroglycan beta)
    O-mannosyl phosphorylation is required for laminin binding, and when defective, may have a role in congenital muscular dystrophy (Yoshida-Moriguchi 2010)
    ASSOCIATED DISORDERS
    corresponding disease(s) SCARMD4 , DEL3P21
    Susceptibility
    Variant & Polymorphism
    Candidate gene
  • defect of dystroglycan glycosylation may be a factor in cancer progression (de Bernabé 2009)
  • candidate gene for the site of mutation in autosomal recessive muscular dystrophies
  • Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Heterozygous Dag1neo2 mice are viable and fertile but homozygous Dag1neo2 embryos exhibit gross developmental abnormalities beginning around 6.5 days of gestation that is due to a disruption of Reichert's membrane
  • chimaeric mice generated with ES cells targeted for both dystroglycan alleles have skeletal muscles essentially devoid of dystroglycans and develop a progressive muscle pathology with many disrupted neuromuscular junctions
  • brain-selective deletion of dystroglycan in mice is sufficient to cause congenital muscular dystrophie-like brain malformations, including disarray of cerebral cortical layering, fusion of cerebral hemispheres and cerebellar folia, and aberrant migration of granule cells
  • striated muscle-specific disruption of the mouse Dag1 gene results in loss of the dystrophin-glycoprotein complex in differentiated muscle and a remarkably mild muscular dystrophy with hypertrophy and without tissue fibrosis
  • mouse harboring the Dag1 Thr192Met mutation display muscular dystrophy and cognitive impairment
  • Dg morpholino knockdown leads to disruption of epidermal differentiation by affecting the intercalation of multiciliated cells, deposition of laminin, and organization of fibronectin in the extracellular matrix
  • disruption of dystroglycan-Laminin interactions result in decreased filopodial number and length, decreased process length, and decreased numbers of primary and secondary processes