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Symbol CAPN1 contributors: mct/pgu - updated : 06-06-2016
HGNC name calpain 1, (mu/I) large subunit
HGNC id 1476
Corresponding disease
SPG76 spastic paraplegia 76
Location 11q13.1      Physical location : 64.949.342 - 64.979.476
Synonym name
  • Mu calpaîn
  • calpain, large polypeptide L1
  • Synonym symbol(s) CANP, CANPL1, muCANP, PIG30, CANP1, SPG76, muCL
    TYPE functioning gene
    STRUCTURE 30.79 kb     22 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Physical map
    HSMDPKIN 11q13 hypothetical protein FKSG44 EHD1 11q13 EH-domain containing 1 KIAA0404 11q13.3-q13.5 EH-domain containing 1 PPP2R5B 11q13 protein phosphatase 2, regulatory subunit B (B56), beta isoform GPHA2 11q13.1 glycoprotein hormone alpha 2 LOC283129 11q13.1 hypothetical protein LOC283129 LOC116071 11q13.1 hypothetical protein BC012330 SNX15 11q12 sorting nexin 15 ARL2 11q13 ADP-ribosylation factor-like 2 LOC390210 11 similar to Elongation factor 1-alpha 1 (EF-1-alpha-1) (Elongation factor 1 A-1) (eEF1A-1) (Elongation factor Tu) (EF-Tu) HSU79266 11q13.1 protein predicted by clone 23627 NAALADL1 11q12 N-acetylated alpha-linked acidic dipeptidase-like 1 LOC256676 11q13.1 hypothetical LOC256676 CDCA5 11q12.1 cell division cycle associated 5 ZFPL1 11q13 zinc finger protein-like 1 C11orf2 11q13 chromosome 11 open reading frame2 TM7SF2 11q13 transmembrane 7 superfamily member 2 C11orf5 11q13 chromosome 11 open reading frame 5 FAU 11q12-q13.1 Finkel-Biskis-Reilly murine sarcoma virus (FBR-MuSV) ubiquitously expressed (fox derived); ribosomal protein S30 MRPL49 11q13 mitochondrial ribosomal protein L49 HRD1 11q13 HRD1 protein LOC387778 11 similar to p33 ringo LOC387779 11 similar to Phosphoglycerate mutase 1 (Phosphoglycerate mutase isozyme B) (PGAM-B) (BPG-dependent PGAM 1) CAPN1 11q13 calpain 1, (mu/I) large subunit LOC387780 11 similar to solute carrier family 22 member 6; organic cationic transporter-like 1; solute carrier family 22 (organic anion transporter), member 6 POLA2 11q13.1 polymerase (DNA-directed), alpha (70kD) CDC42EP2 11q13 CDC42 effector protein (Rho GTPase binding) 2 DPF2 11q13 D4, zinc and double PHD fingers family 2 TIGD3 11q13.2 tigger transposable element derived 3 LOC283130 11q13.1 hypothetical protein LOC283130 FKSG44 11q13 hypothetical protein FKSG44 LOC387781 11 similar to UBIQUITIN-LIKE PROTEIN FUBI
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    22 - 3125 - 714 - 2016 27153400
    22 - 3094 - 714 - 2016 27153400
    22 - 3110 - 714 - 2016 27153400
    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
    at STAGE
  • 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