CAPN1
The calpains, calcium-activated neutral proteases, are nonlysosomal, intracellular cysteine proteases. The mammalian calpains include ubiquitous, stomach-specific, and muscle-specific proteins. The ubiquitous enzymes consist of heterodimers with distinct large, catalytic subunits associated with a common small, regulatory subunit. This gene encodes the large subunit of the ubiquitous enzyme, calpain 1. Several transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Nov 2010]
Function
Calcium-regulated non-lysosomal thiol-protease which catalyzes limited proteolysis of substrates involved in cytoskeletal remodeling and signal transduction (PubMed:21531719, PubMed:2400579).
Proteolytically cleaves CTBP1 at 'Asn-375', 'Gly-387' and 'His-409' (PubMed:23707407).
Biological Process
Cornification Source: Reactome
Extracellular matrix disassembly Source: Reactome
Mammary gland involution Source: Ensembl
Neutrophil degranulation Source: Reactome
Positive regulation of cell population proliferation Source: ProtInc
Proteolysis Source: UniProtKB
Receptor catabolic process Source: Ensembl
Regulation of catalytic activity Source: UniProtKB
Regulation of macroautophagy Source: ParkinsonsUK-UCL
Regulation of NMDA receptor activity Source: ARUK-UCL
Self proteolysis Source: UniProtKB
Cellular Location
Cell membrane; Cytoplasm. Translocates to the plasma membrane upon Ca2+ binding. In granular keratinocytes and in lower corneocytes, colocalizes with FLG and FLG2 (PubMed:21531719).
Involvement in disease
Spastic paraplegia 76, autosomal recessive (SPG76): A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body.
PTM
Undergoes calcium-induced successive autoproteolytic cleavages that generate a membrane-bound 78 kDa active form and an intracellular 75 kDa active form. Calpastatin reduces with high efficiency the transition from 78 kDa to 75 kDa calpain forms.