DYSF

The protein encoded by this gene belongs to the ferlin family and is a skeletal muscle protein found associated with the sarcolemma. It is involved in muscle contraction and contains C2 domains that play a role in calcium-mediated membrane fusion events, suggesting that it may be involved in membrane regeneration and repair. In addition, the protein encoded by this gene binds caveolin-3, a skeletal muscle membrane protein which is important in the formation of caveolae. Specific mutations in this gene have been shown to cause autosomal recessive limb girdle muscular dystrophy type 2B (LGMD2B) as well as Miyoshi myopathy. Alternative splicing results in multiple transcript variants.

Dysferlin

Key calcium ion sensor involved in the Ca2+-triggered synaptic vesicle-plasma membrane fusion. Plays a role in the sarcolemma repair mechanism of both skeletal muscle and cardiomyocytes that permits rapid resealing of membranes disrupted by mechanical stress (By similarity).

Macrophage activation involved in immune response Source: MGI
Membrane fusion Source: GO_Central
Monocyte activation involved in immune response Source: MGI
Negative regulation of phagocytosis Source: MGI
Plasma membrane organization Source: GO_Central
Plasma membrane repair Source: GO_Central
T-tubule organization Source: GO_Central
Vesicle fusion Source: GO_Central

Sarcolemma; Cell membrane; Cytoplasmic vesicle membrane. Colocalizes, during muscle differentiation, with BIN1 in the T-tubule system of myotubules and at the site of contact between two myotubes or a myoblast and a myotube. Wounding of myotubes led to its focal enrichment to the site of injury and to its relocalization in a Ca2+-dependent manner toward the plasma membrane. Colocalizes with AHNAK, AHNAK2 and PARVB at the sarcolemma of skeletal muscle. Detected on the apical plasma membrane of the syncytiotrophoblast. Reaches the plasmma membrane through a caveolin-independent mechanism. Retained by caveolin at the plasmma membrane (By similarity). Colocalizes, during muscle differentiation, with CACNA1S in the T-tubule system of myotubules (By similarity). Accumulates and colocalizes with fusion vesicles at the sarcolemma disruption sites (By similarity).

Muscular dystrophy, limb-girdle, autosomal recessive 2 (LGMDR2):
An autosomal recessive degenerative myopathy characterized by weakness and atrophy starting in the proximal pelvifemoral muscles, with onset in the late teens or later, massive elevation of serum creatine kinase levels and slow progression. Scapular muscle involvement is minor and not present at onset. Upper limb girdle involvement follows some years after the onset in lower limbs.
Miyoshi muscular dystrophy 1 (MMD1):
A late-onset muscular dystrophy involving the distal lower limb musculature. It is characterized by weakness that initially affects the gastrocnemius muscle during early adulthood.
Distal myopathy with anterior tibial onset (DMAT):
Onset of the disorder is between 14 and 28 years of age and the anterior tibial muscles are the first muscle group to be involved. Inheritance is autosomal recessive.

Cytoplasmic: 1-2046
Helical: 2047-2067
Extracellular: 2068-2080