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CAPN3 calpain 3 [ Homo sapiens (human) ]

Gene ID: 825, updated on 12-Aug-2018

Summary

Official Symbol
CAPN3provided by HGNC
Official Full Name
calpain 3provided by HGNC
Primary source
HGNC:HGNC:1480
See related
Ensembl:ENSG00000092529 MIM:114240; Vega:OTTHUMG00000130619
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
p94; CANP3; LGMD2; nCL-1; CANPL3; LGMD2A
Summary
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. [provided by RefSeq, Jul 2008]
Expression
Broad expression in bone marrow (RPKM 19.1), kidney (RPKM 13.9) and 24 other tissues See more
Orthologs

Genomic context

See CAPN3 in Genome Data Viewer
Location:
15q15.1
Exon count:
26
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 15 NC_000015.10 (42359500..42412317)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 15 NC_000015.9 (42646545..42704515)

Chromosome 15 - NC_000015.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105370795 Neighboring gene transmembrane protein 87A Neighboring gene glucosidase alpha, neutral C Neighboring gene BCL2 interacting protein 3 pseudogene 5 Neighboring gene uncharacterized LOC105370794 Neighboring gene zinc finger protein 106 Neighboring gene RNA, U6 small nuclear 188, pseudogene Neighboring gene synaptosome associated protein 23 Neighboring gene leucine rich repeat containing 57

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Jun 15 11:32:44 2016

Bibliography

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Phenotypes

NHGRI GWAS Catalog

Description
Biological, clinical and population relevance of 95 loci for blood lipids.
NHGRI GWA Catalog
Discovery and refinement of loci associated with lipid levels.
NHGRI GWA Catalog

HIV-1 interactions

Replication interactions

Interaction Pubs
Knockdown of calpain 3 (CAPN3; p94) by shRNA library screening inhibits HIV-1 replication in cultured Jurkat T-cells PubMed

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env Activation of the Ca(2+)-dependent protease, calpain, is involved in cytotoxic effects mediated by HIV-1 gp120 in neuroblastoma cultures PubMed

Go to the HIV-1, Human Interaction Database

Pathways from BioSystems

  • Degradation of the extracellular matrix, organism-specific biosystem (from REACTOME)
    Degradation of the extracellular matrix, organism-specific biosystemMatrix metalloproteinases (MMPs), previously referred to as matrixins because of their role in degradation of the extracellular matrix (ECM), are zinc and calcium dependent proteases belonging to the...
  • Extracellular matrix organization, organism-specific biosystem (from REACTOME)
    Extracellular matrix organization, organism-specific biosystemThe extracellular matrix is a component of all mammalian tissues, a network consisting largely of the fibrous proteins collagen, elastin and associated-microfibrils, fibronectin and laminins embedded...
  • Integrin-mediated Cell Adhesion, organism-specific biosystem (from WikiPathways)
    Integrin-mediated Cell Adhesion, organism-specific biosystemIntegrins are receptors that mediate attachment between a cell and the tissues surrounding it, which may be other cells or the extracellular matrix (ECM). They also play a role in cell signaling and ...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Potential readthrough

Included gene: GANC

Homology

Clone Names

  • MGC4403, MGC10767, MGC11121, MGC14344

Gene Ontology Provided by GOA

Function Evidence Code Pubs
calcium ion binding ISS
Inferred from Sequence or Structural Similarity
more info
 
calcium-dependent cysteine-type endopeptidase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
calcium-dependent cysteine-type endopeptidase activity ISS
Inferred from Sequence or Structural Similarity
more info
 
calcium-dependent cysteine-type endopeptidase activity TAS
Traceable Author Statement
more info
PubMed 
catalytic activity IDA
Inferred from Direct Assay
more info
PubMed 
cysteine-type peptidase activity TAS
Traceable Author Statement
more info
PubMed 
ligase regulator activity IDA
Inferred from Direct Assay
more info
PubMed 
peptidase activity IDA
Inferred from Direct Assay
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein-containing complex scaffold activity ISS
Inferred from Sequence or Structural Similarity
more info
 
sodium ion binding ISS
Inferred from Sequence or Structural Similarity
more info
 
structural constituent of muscle ISS
Inferred from Sequence or Structural Similarity
more info
 
titin binding IPI
Inferred from Physical Interaction
more info
PubMed 
Process Evidence Code Pubs
G1 to G0 transition involved in cell differentiation IEA
Inferred from Electronic Annotation
more info
 
apoptotic process TAS
Traceable Author Statement
more info
PubMed 
cellular response to calcium ion ISS
Inferred from Sequence or Structural Similarity
more info
 
cellular response to salt stress ISS
Inferred from Sequence or Structural Similarity
more info
 
muscle cell cellular homeostasis TAS
Traceable Author Statement
more info
PubMed 
muscle organ development TAS
Traceable Author Statement
more info
PubMed 
muscle structure development ISS
Inferred from Sequence or Structural Similarity
more info
 
myofibril assembly ISS
Inferred from Sequence or Structural Similarity
more info
 
myofibril assembly TAS
Traceable Author Statement
more info
PubMed 
negative regulation of apoptotic process IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
negative regulation of apoptotic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of protein sumoylation IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of skeletal muscle cell differentiation IEA
Inferred from Electronic Annotation
more info
 
negative regulation of transcription, DNA-templated ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of NF-kappaB transcription factor activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of proteolysis ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of release of sequestered calcium ion into cytosol ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of satellite cell activation involved in skeletal muscle regeneration ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of transcription, DNA-templated IMP
Inferred from Mutant Phenotype
more info
PubMed 
protein catabolic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
protein destabilization IMP
Inferred from Mutant Phenotype
more info
PubMed 
protein localization to membrane ISS
Inferred from Sequence or Structural Similarity
more info
 
protein-containing complex assembly ISS
Inferred from Sequence or Structural Similarity
more info
 
proteolysis IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
proteolysis IDA
Inferred from Direct Assay
more info
PubMed 
regulation of I-kappaB kinase/NF-kappaB signaling IMP
Inferred from Mutant Phenotype
more info
PubMed 
regulation of catalytic activity IDA
Inferred from Direct Assay
more info
PubMed 
regulation of myoblast differentiation IEA
Inferred from Electronic Annotation
more info
 
response to calcium ion ISS
Inferred from Sequence or Structural Similarity
more info
 
response to muscle activity ISS
Inferred from Sequence or Structural Similarity
more info
 
sarcomere organization ISS
Inferred from Sequence or Structural Similarity
more info
 
self proteolysis IDA
Inferred from Direct Assay
more info
PubMed 
Component Evidence Code Pubs
T-tubule ISS
Inferred from Sequence or Structural Similarity
more info
 
Z disc ISS
Inferred from Sequence or Structural Similarity
more info
 
cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
cytoplasm IDA
Inferred from Direct Assay
more info
PubMed 
cytosol ISS
Inferred from Sequence or Structural Similarity
more info
 
intracellular TAS
Traceable Author Statement
more info
PubMed 
myofibril ISS
Inferred from Sequence or Structural Similarity
more info
 
nucleus IDA
Inferred from Direct Assay
more info
PubMed 
plasma membrane ISS
Inferred from Sequence or Structural Similarity
more info
 
protein-containing complex ISS
Inferred from Sequence or Structural Similarity
more info
 

General protein information

Preferred Names
calpain-3
Names
calpain p94, large [catalytic] subunit
calpain, large polypeptide L3
muscle-specific calcium-activated neutral protease 3 large subunit
new calpain 1
NP_000061.1
NP_077320.1
NP_775110.1
NP_775111.1
NP_775112.1
NP_775113.1

NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_008660.1 RefSeqGene

    Range
    16398..69215
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_000070.2NP_000061.1  calpain-3 isoform a

    See identical proteins and their annotated locations for NP_000061.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longest isoform (a).
    Source sequence(s)
    AF209502, BC003169
    Consensus CDS
    CCDS45245.1
    UniProtKB/Swiss-Prot
    P20807
    Related
    ENSP00000380349.3, OTTHUMP00000249592, ENST00000397163.7, OTTHUMT00000421075
    Conserved Domains (6) summary
    cd00051
    Location:697751
    EFh; EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to ...
    pfam00648
    Location:75415
    Peptidase_C2; Calpain family cysteine protease
    pfam01067
    Location:429579
    Calpain_III; Calpain large subunit, domain III
    pfam13499
    Location:728784
    EF-hand_7; EF-hand domain pair
    pfam16648
    Location:583653
    Calpain_u2; Unstructured region on Calpain-3
    cl08302
    Location:728817
    EFh; EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to ...
  2. NM_024344.1NP_077320.1  calpain-3 isoform b

    See identical proteins and their annotated locations for NP_077320.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an in-frame exon in the coding region, compared to variant 1. It encodes isoform b, which is slightly shorter than isoform a.
    Source sequence(s)
    AF127764, AF209502
    Consensus CDS
    CCDS32207.1
    UniProtKB/Swiss-Prot
    P20807
    Related
    ENSP00000350181.3, OTTHUMP00000249591, ENST00000357568.7, OTTHUMT00000421074
    Conserved Domains (6) summary
    cd00051
    Location:691745
    EFh; EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to ...
    pfam00648
    Location:75415
    Peptidase_C2; Calpain family cysteine protease
    pfam01067
    Location:429579
    Calpain_III; Calpain large subunit, domain III
    pfam13499
    Location:722778
    EF-hand_7; EF-hand domain pair
    pfam16648
    Location:583647
    Calpain_u2; Unstructured region on Calpain-3
    cl08302
    Location:722811
    EFh; EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to ...
  3. NM_173087.1NP_775110.1  calpain-3 isoform c

    See identical proteins and their annotated locations for NP_775110.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) lacks three in-frame exons in the coding region, compared to variant 1. It encodes isoform c, which is shorter than isoform a.
    Source sequence(s)
    AF127765, AF209502
    Consensus CDS
    CCDS10085.1
    UniProtKB/Swiss-Prot
    P20807
    Related
    ENSP00000183936.4, OTTHUMP00000161195, ENST00000349748.7, OTTHUMT00000253102
    Conserved Domains (4) summary
    cd00051
    Location:605659
    EFh; EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to ...
    pfam00648
    Location:75367
    Peptidase_C2; Calpain family cysteine protease
    pfam01067
    Location:381531
    Calpain_III; Calpain large subunit, domain III
    pfam13499
    Location:636692
    EF-hand_7; EF-hand domain pair
  4. NM_173088.1NP_775111.1  calpain-3 isoform d

    See identical proteins and their annotated locations for NP_775111.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) differs in the 5' UTR and 5' coding region, and uses a downstream start codon, compared to variant 1. It encodes isoform d, which has a shorter N-terminus compared to isoform a.
    Source sequence(s)
    BC003169
    Consensus CDS
    CCDS45246.1
    UniProtKB/Swiss-Prot
    P20807
    UniProtKB/TrEMBL
    A0A0S2Z3E1
    Related
    ENSP00000380384.4, OTTHUMP00000249593, ENST00000397200.8, OTTHUMT00000257740
    Conserved Domains (3) summary
    pfam01067
    Location:167
    Calpain_III; Calpain large subunit, domain III
    pfam16648
    Location:71141
    Calpain_u2; Unstructured region on Calpain-3
    cd16190
    Location:141309
    EFh_PEF_CAPN3; Calcium-activated neutral
  5. NM_173089.1NP_775112.1  calpain-3 isoform e

    See identical proteins and their annotated locations for NP_775112.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) differs in the 5' UTR and uses a downstream start codon, compared to variant 1. It encodes isoform e, which has a shorter N-terminus compared to isoform a.
    Source sequence(s)
    BC003169, BC004883
    Consensus CDS
    CCDS10086.1
    UniProtKB/Swiss-Prot
    P20807
    Related
    ENSP00000336840.4, OTTHUMP00000161196, ENST00000337571.8, OTTHUMT00000253103
    Conserved Domains (2) summary
    cd15897
    Location:3160
    EFh_PEF; EF-hand motif [structural motif]
    cl25352
    Location:1156
    EFh_PEF; The penta-EF hand (PEF) family
  6. NM_173090.1NP_775113.1  calpain-3 isoform e

    See identical proteins and their annotated locations for NP_775113.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (6) differs in the 5' UTR and uses a downstream start codon, compared to variant 1. It encodes isoform e, which has a shorter N-terminus compared to isoform a.
    Source sequence(s)
    BC003169, BC007810
    Consensus CDS
    CCDS10086.1
    UniProtKB/Swiss-Prot
    P20807
    Related
    ENSP00000380387.4, OTTHUMP00000249594, ENST00000397204.8, OTTHUMT00000421081
    Conserved Domains (2) summary
    cd15897
    Location:3160
    EFh_PEF; EF-hand motif [structural motif]
    cl25352
    Location:1156
    EFh_PEF; The penta-EF hand (PEF) family

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...Open this link in a new tab

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000015.10 Reference GRCh38.p12 Primary Assembly

    Range
    42359500..42412317
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_212465.2: Suppressed sequence

    Description
    NM_212465.2: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.
  2. NR_027911.1: Suppressed sequence

    Description
    NR_027911.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.
  3. NR_027912.1: Suppressed sequence

    Description
    NR_027912.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.
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