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dysferlin; dystrophy-associated fer-1-like protein; fer-1-like protein 1 (DYSF, FER1L1)

Function: - key Ca+2 sensor involved in the Ca+2-triggered synaptic vesicle - plasma membrane fusion - role in the sarcolemma repair mechanism of both skeletal muscle & cardiomyocytes that permits rapid resealing of membranes disrupted by mechanical stress (putative) - interacts with CACNA1S - interacts with ANXA1 & ANXA2; (Ca+2 & injury state dependent) - interacts with CACNA1S & PARVB - interacts with TRIM72/MG53; interaction is required for transport to sites of cell injury during repair patch formation (putative) - interacts with CAV3 & PARVB - interacts with AHNAK (Ca+2-independent) - interacts with AHNAK2 (Ca+2-independent) Structure: - C2 domain 1 associates with lipid membranes (Ca+2-dependent) - belongs to the ferlin family - contains 5 C2 domains - homologous to C. elegans spermatogenesis factor fer-1; fer-1 spermatozoa show defective mobility Compartment: - single-pass type 2 membrane protein - cell membrane, sarcolemma - cytoplasmic vesicle membrane - colocalizes, during muscle differentiation, with BIN1 in the T-tubule system of myotubules & at the site of contact between two myotubes or a myoblast & a myotube - wounding of myotubes leads to its focal enrichment to the site of injury & to its relocalization (Ca+2-dependent) toward the plasma membrane - colocalizes with AHNAK, AHNAK2 & PARVB at the sarcolemma of skeletal muscle - detected on apical plasma membrane of syncytiotrophoblast - reaches the plasma membrane through a caveolin-independent mechanism - retained by caveolin at the plasma membrane - colocalizes, during muscle differentiation, with CACNA1S in the T-tubule system of myotubules (putative) - accumulates & colocalizes with fusion vesicles at the sarcolemma disruption sites (putative) Alternative - splicing: named isoforms=15 Expression: - expressed in skeletal muscle, myoblast, myotube & in the syncytiotrophoblast of the placenta (at protein level) - highly expressed in skeletal muscle - also found in heart, brain, spleen, intestine, placenta & at lower levels in liver, lung, kidney & pancreas - expression in limb tissue from 5-6 weeks embryos; persists throughout development Pathology: - defects in DYSF are the cause of a) limb-girdle muscular dystrophy type 2B b) Miyoshi myopathy c) distal myopathy with anterior tibial onset Laboratory: - dysferlin in leukocytes

Related

MM/LGMD2B or dysferlin gene

General

membrane protein phosphoprotein

Properties

SIZE: entity length = 2080 aa MW = 237 kD COMPARTMENT: cytoplasm cellular membrane MOTIF: C2 domain {1-85} MOTIF: binding site FOR-BINDING-OF: phospholipid Ca+2-binding site C2 domain {207-302} MOTIF: binding site FOR-BINDING-OF: phospholipid Ca+2-binding site C2 domain {366-479} MOTIF: binding site FOR-BINDING-OF: phospholipid Ca+2-binding site Thr phosphorylation site {T437} arginine-rich region {1038-1097} MOTIF: arginine residue (SEVERAL) C2 domain {1139-1244} MOTIF: binding site FOR-BINDING-OF: phospholipid Ca+2-binding site C2 domain {1565-1663} MOTIF: binding site FOR-BINDING-OF: phospholipid Ca+2-binding site transmembrane domain {2047-2067}

Database Correlations

OMIM correlations MORBIDMAP 603009 UniProt O75923 PFAM correlations Entrez Gene 8291 Kegg hsa:8291

References

  1. Liu J et al Dysferlin, a novel skeletal muscle gene, is mutated in Miyoshi myopathy and limb girdle muscular dystrophy. Nature Genetics 20:31-6, 1998 PMID: 9731526
  2. Bashir R et al A gene related to Caenorhabditis elegans spermatogenesis factor fer-1 is mutated in limb-girdle muscular dystrophy type 2B. Nature Genetics 20:37-42, 1998 PMID: 9731527
  3. UniProt :accession O75923
  4. Leiden muscular Dystrophy pages: Dysferlin http://www.dmd.nl/dysf_home.html
  5. GeneReviews http://www.ncbi.nlm.nih.gov/sites/genetests/lab/gene/DYSF
  6. Wikipedia: Dysferlin http://en.wikipedia.org/wiki/Dysferlin