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    CAPN3 calpain 3 [ Homo sapiens (human) ]

    Gene ID: 825, updated on 7-Apr-2024

    Summary

    Official Symbol
    CAPN3provided by HGNC
    Official Full Name
    calpain 3provided by HGNC
    Primary source
    HGNC:HGNC:1480
    See related
    Ensembl:ENSG00000092529 MIM:114240; AllianceGenome:HGNC:1480
    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; LGMDD4; LGMDR1
    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
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See CAPN3 in Genome Data Viewer
    Location:
    15q15.1
    Exon count:
    26
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 15 NC_000015.10 (42359501..42412317)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 15 NC_060939.1 (40165536..40218365)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 15 NC_000015.9 (42651699..42704515)

    Chromosome 15 - NC_000015.10Genomic Context describing neighboring genes Neighboring gene VPS39 divergent transcript Neighboring gene transmembrane protein 87A Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9297 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9298 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr15:42565593-42566792 Neighboring gene glucosidase alpha, neutral C Neighboring gene BCL2 interacting protein 3 pseudogene 5 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:42652107-42652607 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr15:42655654-42656620 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr15:42676684-42677239 Neighboring gene uncharacterized LOC105370794 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr15:42677734-42678933 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9299 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9300 Neighboring gene zinc finger protein 106 Neighboring gene RNA, U6 small nuclear 188, pseudogene Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr15:42749529-42750361 Neighboring gene H3K27ac hESC enhancer GRCh37_chr15:42750362-42751193 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9301 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9302 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9303 Neighboring gene H3K27ac hESC enhancer GRCh37_chr15:42787505-42788048 Neighboring gene H3K27ac hESC enhancer GRCh37_chr15:42788049-42788592 Neighboring gene MPRA-validated peak2311 silencer 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 Apr 4 07:08:55 2018

    Bibliography

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    Phenotypes

    EBI GWAS Catalog

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

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Potential readthrough

    Included gene: GANC

    Clone Names

    • MGC4403, MGC10767, MGC11121, MGC14344

    Gene Ontology Provided by GOA

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

    NEW Try the new Transcript table

    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
      16399..69215
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_849

    mRNA and Protein(s)

    1. NM_000070.3NP_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)
      AC012651
      Consensus CDS
      CCDS45245.1
      UniProtKB/Swiss-Prot
      A6H8K6, P20807, Q7L4R0, Q9BQC8, Q9BTU4, Q9Y5S6, Q9Y5S7
      UniProtKB/TrEMBL
      F8W8F5
      Related
      ENSP00000380349.3, ENST00000397163.8
      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_024344.2NP_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)
      AC012651
      Consensus CDS
      CCDS32207.1
      UniProtKB/TrEMBL
      F8W8F5
      Related
      ENSP00000350181.3, ENST00000357568.8
      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_173087.2NP_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)
      AC012651
      Consensus CDS
      CCDS10085.1
      UniProtKB/TrEMBL
      F8W8F5
      Related
      ENSP00000183936.4, ENST00000349748.8
      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_173088.2NP_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)
      AC012651
      Consensus CDS
      CCDS45246.1
      UniProtKB/TrEMBL
      A0A0S2Z3E1, H3BMH1
      Related
      ENSP00000380384.4, ENST00000397200.8
      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_173089.2NP_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)
      AC012651
      Consensus CDS
      CCDS10086.1
      UniProtKB/TrEMBL
      Q496N2
      Related
      ENSP00000501303.1, ENST00000674093.1
      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_173090.2NP_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)
      AC012651
      Consensus CDS
      CCDS10086.1
      UniProtKB/TrEMBL
      Q496N2
      Related
      ENSP00000380387.4, ENST00000397204.9
      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: GCF_000001405.40-RS_2023_10

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000015.10 Reference GRCh38.p14 Primary Assembly

      Range
      42359501..42412317
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060939.1 Alternate T2T-CHM13v2.0

      Range
      40165536..40218365
      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.