CAPN3

Calpain, a heterodimer consisting of a large and a small subunit, is a major intracellular protease, although its function has not been well established. This gene encodes a muscle-specific member of the calpain large subunit family that specifically binds to titin. Mutations in this gene are associated with limb-girdle muscular dystrophies type 2A. Alternate promoters and alternative splicing result in multiple transcript variants encoding different isoforms and some variants are ubiquitously expressed.

Full Name

CALPAIN 3

Function

Calcium-regulated non-lysosomal thiol-protease. Proteolytically cleaves CTBP1 at 'His-409'. Mediates, with UTP25, the proteasome-independent degradation of p53/TP53 (PubMed:23357851, PubMed:27657329).

Biological Process

Apoptotic process Source: UniProtKB
Calcium-dependent self proteolysis Source: UniProtKB
Cellular response to calcium ion Source: UniProtKB
Cellular response to salt stress Source: UniProtKB
G1 to G0 transition involved in cell differentiation Source: Ensembl
Muscle cell cellular homeostasis Source: UniProtKB
Muscle organ development Source: UniProtKB
Muscle structure development Source: UniProtKB
Myofibril assembly Source: UniProtKB
Negative regulation of apoptotic process Source: UniProtKB
Negative regulation of protein sumoylation Source: UniProtKB
Negative regulation of transcription, DNA-templated Source: UniProtKB
Positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
Positive regulation of proteolysis Source: UniProtKB
Positive regulation of release of sequestered calcium ion into cytosol Source: UniProtKB
Positive regulation of satellite cell activation involved in skeletal muscle regeneration Source: UniProtKB
Positive regulation of transcription, DNA-templated Source: UniProtKB
Protein catabolic process Source: UniProtKB
Protein-containing complex assembly Source: UniProtKB
Protein destabilization Source: UniProtKB
Protein localization to membrane Source: UniProtKB
Proteolysis Source: UniProtKB
Regulation of catalytic activity Source: UniProtKB
Regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
Regulation of myoblast differentiation Source: Ensembl
Response to calcium ion Source: UniProtKB
Response to muscle activity Source: UniProtKB
Sarcomere organization Source: UniProtKB
Self proteolysis Source: UniProtKB

Cellular Location

Nucleolus; Cytoplasm

Involvement in disease

Muscular dystrophy, limb-girdle, autosomal recessive 1 (LGMDR1): An autosomal recessive degenerative myopathy characterized by progressive symmetrical atrophy and weakness of the proximal limb muscles and elevated serum creatine kinase. The symptoms usually begin during the first two decades of life, and the disease gradually worsens, often resulting in loss of walking ability 10 or 20 years after onset.
Muscular dystrophy, limb-girdle, autosomal dominant 4 (LGMDD4): A form of autosomal dominant limb-girdle muscular dystrophy, a myopathy characterized by proximal and/or distal muscle weakness and atrophy. The age at onset is variable and can range from the first to the sixth decade, although later onset is less common. LGMDD4 is characterized by onset of proximal muscle weakness in young adulthood, gait difficulties, increased serum creatine kinase, myalgia, and back pain. Some patients may have upper limb involvement. Disease severity and expressivity are highly variable.