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FLASH GENE
Symbol CAPN3 contributors: mct - updated : 11-04-2014
HGNC name calpain 3, (p94)
HGNC id 1480
Corresponding disease
LGMD2A limb girdle muscular dystrophy 2A
Location 15q15.1      Physical location : 42.640.300 - 42.704.515
Synonym name
  • calpain,large polypeptide L3
  • calcium activated neutral protease 3, muscle specific
  • muscle-specific calcium-activated neutral protease 3
  • calpain, large polypeptide L3
  • new calpain 1
  • Synonym symbol(s) CANP3, LGMD2, LGMD2A, nCL-1, CANPL3, p94, MGC10767, MGC11121, MGC4403
    EC.number 3.4.22.54
    DNA
    TYPE functioning gene
    STRUCTURE 64.22 kb     28 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Physical map
    OIP5 15q14 Opa-interacting protein 5 NUSAP1 15q14 nucleolar and spindle associated protein 1 CIA30 KIAA0252 15q14 nucleolar and spindle associated protein 1 ITPKA 15q14-q21 inositol 1,4,5-trisphosphate 3-kinase A LTK 15q15.1-q15.2 leukocyte tyrosine kinase DKFZP727M111 15q14 DKFZP727M111 protein LOC283747 15q14 similar to elongation factor SIII p15 subunit TYRO3 15q15.1-q21.1 TYRO3 protein tyrosine kinase MGA 15q15 MAX gene associated MAPKBP1 15q14 likely ortholog of mouse mitogen activated protein kinase binding proten 1 PLA2G4B 15q11.2-q21.3 phospholipase A2, group IVB (cytosolic) SPTBN5 15q21 spectrin, beta, non-erythrocytic 5 EHD4 15q11.1-q15 EH-domain containing 4 FLJ45651 15q14 FLJ45651 protein LOC388117 15 LOC388117 cPLA2delta LOC255189 15q14 hypothetical protein LOC255189 VPS39 15q14-q15 vacuolar protein sorting 39 (yeast) DKFZP564G2022 15q14 DKFZP564G2022 protein GANC 15q15.1-q15.2 glucosidase, alpha; neutral C CAPN3 15q15.1-q15.3 calpain 3, (p94) ZFP106 15q14 zinc finger protein 106 homolog (mouse) SNAP23 15q14-q15.1 synaptosomal-associated protein, 23kDa FLJ36812 15q14 hypothetical protein FLJ36812 FLJ10460 15q14 hypothetical protein FLJ10460 LOC390579 15 similar to myosin regulatory light chain-like LOC388118 15 similar to kinesin-like protein STARD9 15q14 START domain containing 9 CDAN1 15q14-q15 congenital dyserythropoietic anemia, type I TTBK2 15q14 tau tubulin kinase 2 LOC390580 15 similar to Ac2-125 UBR1 15q15-q21.1 ubiquitin protein ligase E3 component n-recognin 1 LOC146053 15q14 similar to ribosomal protein S3a; 40S ribosomal protein S3a; v-fos transformation effector protein 1 LOC255320 15q15.1 similar to Microsomal signal peptidase 25 kDa subunit (SPase 25 kDa subunit) (SPC25) FLJ23375 15q15.1 hypothetical protein FLJ23375 CCNDBP1 15q14-q15 cyclin D-type binding-protein 1 EPB42 15q15 erythrocyte membrane protein band 4.2 TGM5 15q15.2 transglutaminase 5 LOC390581 15 similar to ATP synthase, H+ transporting, mitochondrial F0 complex, subunit d; ATP synthase, H+ transporting, mitochondrial F1F0, subunit d TGM7 15q15.2 similar to ATP synthase, H+ transporting, mitochondrial F0 complex, subunit d; ATP synthase, H+ transporting, mitochondrial F1F0, subunit d LCMT2 15q14 leucine carboxyl methyltransferase 2 LOC161823 15q15.1 similar to Adenosine deaminase CG11994-PA
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    24 - 3316 94 821 - 1999 10330145
    23 splicing 3298 93.3 815 - 1999 10330145
    inclusion of intronic sequence between exons 16, 17
    21 splicing 3040 83.5 729 lens specific 1999 10330145
    alternative specific first exon, hydrolyzing substrates such as crystallins during lens cataract formation
    13 - 1661 - 309 - 2006 16627476
    9 - 1291 - 156 - 2006 16627476
    10 - 1309 - 156 - 2006 16627476
    differs in the 5' UTR and uses a downstream start codon
    - - 3901 - 426 - 2006 16627476
  • has an alternate 5' sequence and lacks an exon in the 3' region
  • has a shorter and distinct N-terminus and a truncated C-terminus
  • 27 - 3223 - 728 - -
    - - 3521 - 107 - 2006 16627476
  • has an alternate 5' sequence and an additional middle exon
  • lacks a 3' exon
  • EXPRESSION
    Rna function mRNA is expressed at high levels in muscle and appears to have some role in developmental processes
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart    
    Digestivemouthtongue  highly
     pharynx   highly
    Hearing/Equilibriumearinnercochlea highly
    Nervousnervecranial nerve   
    Reproductivefemale systembreastmammary gland  
     female systemuterus   
    Skin/Tegumentskin   highly
    Visualeyelens  moderately Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal highly Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Muscularmyocyte
    Visuallens fibers Homo sapiens
    cell lineage
    cell lines
    fluid/secretion blood
    at STAGE
    physiological period embryo
    Text heart
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a N terminal regulatory domain processed after activation (I)
  • a cysteine protease domain (II)
  • a linker domain (III)
  • specific IS2 segment between domains III and IV, important functional site that may regulate the transient activation and limited proteolysis of CAPN3
  • a calcium binding domain with four calmodulin-like EF hand motifs (IV)
  • two nuclear localization signals (NLS)
  • mono polymer heteromer , dimer
    HOMOLOGY
    interspecies ortholog to rattus capn3
    ortholog to murine Capn3
    Homologene
    FAMILY
  • papain superfamily
  • calpain cysteine protease (C2) family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    text localized in the N2 region of myofibrils
    basic FUNCTION
  • calcium dependent neutral cysteine proteinase (non lysosomal)
  • possessing a proteolytic activity against a potential substrate
  • involved in cytoskeleton remodeling
  • participating in sarcomere remodeling by acting upstream of the ubiquitin-proteasome pathway
  • playing a physiological role in regulating the dysferlin protein complex
  • is a critical but unstable enigmatic skeletal muscle protease
  • has many attributes that make it ideally suited as a sensor of sarcomeric integrity and function, involved in its repair and maintenance
  • is uniquely activated during lens fiber differentiation
  • is an intracellular Na+-dependent protease, and Na+ regulate contribution of CAPN3 as a structural component in muscle cells
  • is needed for the regenerative process probably during sarcomere remodeling
  • having different cellular functions depending on the subcellular compartment in which it is located
  • localizes to triads, where it plays an important role as a structural component and not as a protease
  • CELLULAR PROCESS cell organization/biogenesis
    PHYSIOLOGICAL PROCESS development
    text cytoskeletal remodeling
    PATHWAY
    metabolism
    signaling signal transduction
    a component
  • heterodimerizing with a small subunit
  • INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • Ca2+
  • protein
  • dysferlin, DYSF
  • interacting with TTN
  • inhibition of NACA gene expression leads to enhanced, and overexpression of NACA gene to repressed, activity of CAPN1 and, to a lesser extent, CAPN3 in myoblasts
  • SIMC1 is a CAPN3-binding protein, and suppresses the protease activity of CAPN3
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) LGMD2A
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    reduced expression associated with increased in body fat, obesity and insulin resistance
    Susceptibility to idiopathic eosinophilic myositis
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Capn3-deficient muscle in mice
  • Rbfox1 downregulation and altered Capn3 splicing by Frg1 in a mouse model of Facioscapulohumeral muscular dystrophy (FSHD)