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Symbol CAPN1 contributors: mct/pgu - updated : 06-06-2016
HGNC name calpain 1, (mu/I) large subunit
HGNC id 1476
Type ubiquitous
   expressed in (based on citations)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestiveintestinelarge intestinecolon moderately
 mouth   predominantly
Lymphoid/Immunespleen   moderately
 thymus   highly
 tonsils   highly
Nervousbrain   highly Homo sapiens
Respiratoryrespiratory tractlarynx  highly
Urinarybladder   moderately
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Nervouscentral  highly Homo sapiens
SystemCellPubmedSpeciesStageRna symbol
Blood/Hematopoieticplatelet Homo sapiensAdult
cell lineage
cell lines
fluid/secretion blood, lymph
  • a N terminal regulatory domain processed after activation (I), an amphipathic -helical domain and a mitochondrial targeting sequence
  • a cysteine protease domain (II)
  • a linker domain (III)
  • a calcium binding domain
  • five calmodulin-like EF hand motifs (IV)
  • mono polymer heteromer , dimer
    interspecies homolog to rattus Capn1 (89.34 pc)
    homolog to murine Capn1 (89.34 pc)
  • peptidase C2 family, papain superfamily
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     plasma membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
  • translocated to the plasma membrane upon Ca2+ binding
  • imported into mitochondria
  • normally localizes to the interphase nuclei and chromatin
  • basic FUNCTION
  • calcium dependent neutral cysteine proteinase (non lysosomal) catalyzing limited proteolysis of substrates involved in cytoskeletal remodelling and signal transduction
  • regulating cell migration by proteolysing filamin and talin
  • involved in positive regulation of cell proliferation
  • may play a role in mitochondrial apoptotic signalling
  • CAPN1, and CAPN2 facilitates actin reorganization during glucose-stimulated insulin secretion
  • plays an important role in controlling the levels of autophagy in normal living cells by regulating the levels of a key signaling molecule, ATG12-ATG5 conjugate
  • CASP1-proteasome-dependent NFKBIA polymer degradation may contribute to cancer progression through constitutive NF-kappaB activation
  • involved in physiological platelet activation, and in diabetes-associated platelet hyperactivation
  • CAPN1 and CAPN2 are critical modulator for regulation of CDKN1B in cells of the osteoblast lineage
  • CAPN1 and CAPN2 at least in part share similar functions under the control of calpastatin (CAST)
  • intracellular, non-lysosomal cytoplasmic cysteine endopeptidase
  • calcium regulated cysteine proteases that have been described in a wide range of cellular processes, including apoptosis, migration and cell cycle regulation
  • role for calpain 1 in repressing differentiation, thus maintaining a proliferative neural stem cell pool
  • CAPN1- regulation of MMP2 activity in vascular smooth muscle cells facilitates age-associated aortic wall calcification and fibrosis
  • CAPN1 is identified as a novel regulator in IgE-mediated mast cell activation 7)
  • critical role of CAPN1 in the early phase and during progression of amyotrophic lateral sclerosis (ALS)
  • CAPN1 induces ER stress and MAPK8/MAPK9 activation, thereby mediating apoptosis in cardiomyocytes
  • its activation plays critical role in vascular calcification caused by oxLDL, which might be mediated by inorganic pyrophosphate (PPi)metabolism disorder
  • is involved in synaptic plasticity, synaptic restructuring, and axon maturation and maintenance
  • CELLULAR PROCESS cell life, proliferation/growth
    cell organization/biogenesis
    cell migration & motility
    signaling signal transduction
    a component
  • heterodimerizing with the small subunit CAPNS1
    small molecule metal binding,
    calcium Ca2+
  • CAPN1-activated form of CASP7 has unique enzymatic activity, localization, and binding affinity when compared with the caspase-activated form
  • is essential for the proteolytic processing of FLG2 and the deimination accelerates this process
  • RAD21 cleavage by CAPN1 promotes separation of chromosome arms, which coincides with a calcium-induced partial loss of cohesin at several chromosomal loci
  • is a RAD21 peptidase (cleaves RAD21 at L192, in a calcium-dependent manner)
  • CAPN1 and CAPN2 cleave and functionally activate TRPC5
  • phosphorylation of ZFHX3 was an important regulatory mechanism protecting it from digestion by CAPN1
  • ATXN3 is a substrate of CAPN1 and CAPN2 and these proteases present promising targets for therapeutic intervention
  • overactivation of CAPN1 caused by calcium overload proteolyses CREB1, resulting in a reduction of SLC2A3 expression and consequently impairing glucose uptake and metabolism in AD brain
  • CAST inhibit CAPN1 activity and thus prevent cell death
  • dual role for CAPN1 in the weaned gland after the pregnancy/lactation cycle, controlling programmed cell death and participating in the epigenetic programme during adipocyte differentiation
  • interacts with CDK5 and NR2B to control NMDA-receptor degradation and synaptic plasticity
  • OLR1 is, at least in part, responsible for the inhibitory effect of oxidized low-density lipoprotein (ox-LDL) on macrophage migration and this process involves CAPN1 and CAPN2
  • cell & other
    activated by micromolar concentrations of calcium
    inhibited by calpastatin CAST
    corresponding disease(s) SPG76
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in higher grading of the ovarian carcinoma
    constitutional     --over  
    associated with an increase in mitochondrial ROS generation and oxidative damage and a reduction in ATP synthase alpha(ATP5A1) protein and ATP synthase activity
    Variant & Polymorphism
    Candidate gene
  • is a novel molecular candidate to retard age-associated extracellular matrix remodeling and its attendant risk for hypertension and atherosclerosis
  • Marker
    Therapy target
    potential therapeutic target for the management of allergic inflammation
  • Capn1 knock-out mice may serve as a useful model system for neuronal protection and apoptosis in traumatic brain injury and other neurodegenerative disorders in which oxidative stress plays a role
  • Calpain-1 protein and activity in mitochondria were elevated in diabetic mouse hearts