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FLASH GENE
Symbol DYSF contributors: mct/npt/pgu - updated : 23-02-2013
HGNC name dysferlin, limb girdle muscular dystrophy 2B (autosomal recessive)
HGNC id 3097
Corresponding disease
DMAT myopathy, distal with anterior tibial onset
LGMD2B limb girdle muscular dystrophy 2B
MMD1 Miyoshi myopathy 1
Location 2p13.2      Physical location : 71.680.752 - 71.913.892
Synonym name
  • dystrophy-associated fer-1-like 1
  • Fer-1-like protein 1
  • dystrophy-associated fer-1-like protein
  • Synonym symbol(s) FER1L1, LGMD2B, FLJ00175, FLJ90168
    DNA
    TYPE functioning gene
    STRUCTURE 233.14 kb     55 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence cytosine-phosphate-guanine/HTF
    Binding site   silencer
    MAPPING cloned Y linked N status confirmed
    Map see LGMD2B
    Physical map
    ADD2 2p14-p13 adducin 2 (beta) CLECSF13 2p13.3 likely ortholog of mouse C-type (calcium dependent, carbohydrate recognition domain) lectin, superfamily member 13 CD207 2p13 CD207 antigen, langerin VAX2 2p13.3 ventral anterior homeobox 2 ATP6V1B1 2p13 ATPase, H+ transporting, lysosomal 56/58kDa, V1 subunit B, isoform 1 (Renal tubular acidosis with deafness) FLJ12056 2p13.2 hypothetical protein FLJ12056 TEX261 2p13.2 testis expressed gene 261 LOC115131 2p13.2 similar to POSSIBLE GUSTATORY RECEPTOR CLONE PTE01 OR7E91P 2p12 olfactory receptor, family 7, subfamily E, member 91 pseudogene OR7E62P 2p12 olfactory receptor, family 7, subfamily E, member 62 pseudogene NAGK 2p13 N-acetylglucosamine kinase MCEE 2p12 methylmalonyl CoA epimerase MPHOSPH10 2p12 M-phase phosphoprotein 10 (U3 small nucleolar ribonucleoprotein) LOC391386 2 similar to KIAA1155 protein NP220 2p13 similar to KIAA1155 protein DYSF 2p13.3-p13.1 dysferlin, limb girdle muscular dystrophy 2B (autosomal recessive) P450RAI-2 SEC15L2 2p13.2 SEC15-like 2 (S. cerevisiae)
    RNA
    TRANSCRIPTS type messenger
    text
  • fourteen dysferlin transcripts (PMID: 19221801)
  • alternative splicing involving exons 5a and 40a, in addition to previously reported alternative splicing of exon 17 (PMID: 19221801)
  • identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    55 - 6772 - 2119 - 2009 19221801
    56 - 6682 230 2081 skeletal muscle, heart, placenta, brain, spleen, kidney, intestine, and lung tissues 2009 19221801
    retains phylogenic conservancy and shows similar expression pattern as the currently known human dysferlin
    55 - 6914 - 2080 - 2009 19221801
    - - 6616 - 2067 - 2009 19221801
    - - 6709 - 2098 - 2009 19221801
    - - 6679 - 2088 - 2009 19221801
    - - 6721 - 2102 - 2009 19221801
    - - 6775 - 2112 - 2009 19221801
    56 - 7004 - 2118 - 2009 19221801
    55 - 6941 - 2097 - 2009 19221801
    56 - 6983 - 2111 - 2009 19221801
    56 - 6953 - 2101 - 2009 19221801
    55 - 6911 237 2087 - 2009 19221801
    54 - 6848 - 2066 - 2009 19221801
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularvessel   highly Homo sapiensAdult
    Lymphoid/Immunespleen   highly
    Nervousbrain   moderately
    Reproductivefemale systemplacenta  highly
    Urinarykidney   moderately
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal   Homo sapiensAdult
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticmonocyte Homo sapiensAdult
    Cardiovascularendothelial cell Homo sapiensAdult
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period pregnancy
    Text placenta, in mononuclear cytotrophoblasts and the syncytiotrophoblast
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • seven calcium-dependent C2 binding domains, which are required to promote fusion of intracellular membrane vesicles
  • a C2A domain binding to AHNAK
  • several nuclear membrane targeting sequences, a single transmembrane segment
  • two highly conserved DYSF domains, namely DYSF N in the N-terminus and DYSF C in the C-terminus, with unknown function
  • a short C terminal extracellular tail, that is an apparent binding site for affixin
  • mono polymer dimer
    HOMOLOGY
    interspecies homolog to C.elegans spermatogenesis factor fer-1
    Homologene
    FAMILY
  • dysferlin family
  • CATEGORY structural protein
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,cytosolic,vesicle
    text
  • in normal skeletal muscle, dysferlin and AHNAK colocalize at the sarcolemmal membrane and T-tubules
  • abundant dysferlin expression in the Golgi apparatus, around the perinuclear region and to a lesser extent in the nucleus of endothelial cells
  • basic FUNCTION
  • involved in muscle contraction and contains C2 domains that play a role in calcium-mediated membrane fusion events
  • involved in membrane regeneration and repair (first member of the membrane repair machinery in skeletal muscle)
  • implicated in calcium-dependent membrane repair
  • participates in the recruitment and stabilization of AHNAK to the sarcolemma
  • involved in efficient and active membrane repair system to overcome the rigours of frequent contraction of the muscles
  • is necessary for correct T-tubule formation, and dysferlin-deficient skeletal muscle is characterized by abnormally configured T-tubules
  • role for the muscle repair protein dysferlin in endothelial cell adhesion and angiogenesis
  • ferlins are calcium-sensing proteins and are candidate mediators of vesicle-plasma membrane fusion during myoblast fusion
  • membrane-anchored protein known to facilitate membrane repair in skeletal muscles following mechanical injury
  • not only mediates membrane repair but also trafficking of client proteins, ultimately, help bridging dysferlinopathies to aberrant membrane signaling
  • indirectly regulates the membrane expression of proteins by trafficking the lipid patches/vesicles that contain membrane proteins, rather than binding directly the cargo proteins
  • multi-C2 domain transmembrane protein involved in skeletal muscle membrane repair, but also in myogenesis, cellular adhesion and intercellular calcium signaling
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • CAPN3/DYSF
  • DYSF dimerization is mediated by its transmembrane domain and by multiple C2 domains
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • CAPN3
  • CAV3 (putative low affinity process)and CAV1 (caveolins are essential for dysferlin association with the plasma membrane)
  • interacting with other dysferlin molecules and annexins A1 and A2 at the sarcolemma
  • interacting with PARVB
  • interacts with alpha-tubulin and microtubules in muscle cells
  • ferlins and EHBP1 may compete for EHD binding to regulate the complex process of exit from the endocytic recycling compartment, translocation to the plasma membrane, and reorganization of the actin cytoskeleton to facilitate the fusion of exocytosed vesicles to the membrane
  • HDAC6 is a novel dysferlin-binding partner(DYSF prevents HDAC6 from deacetylating alpha-tubulin by physically binding to both the enzyme, via its C2D domain, and to the substrate, alpha-tubulin, via its C2A and C2B domains)
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) DMAT , LGMD2B , MMD1
    related resource Limb-Girdle Muscular Dystrophy ,type 2B
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    neuromuscularmyopathy 
    enhancement of the neutrophil response is a potential therapeutic avenue in the dysferlinopathies
    ANIMAL & CELL MODELS
  • deleted in SJL mice
  • overexpression of dysferlin in mice resulted in a striking phenotype of kyphosis, irregular gait, and reduced muscle mass and strength