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CAPN3 calpain 3 [ Homo sapiens (human) ]

Gene ID: 825, updated on 23-Oct-2021

Summary

Official Symbol
CAPN3provided by HGNC
Official Full Name
calpain 3provided by HGNC
Primary source
HGNC:HGNC:1480
See related
Ensembl:ENSG00000092529 MIM:114240
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
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Genomic context

See CAPN3 in Genome Data Viewer
Location:
15q15.1
Exon count:
26
Annotation release Status Assembly Chr Location
109.20210514 current GRCh38.p13 (GCF_000001405.39) 15 NC_000015.10 (42359501..42412317)
105.20201022 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 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 Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Phenotypes

Associated conditions

Description Tests
Biological, clinical and population relevance of 95 loci for blood lipids.
GeneReviews: Not available
Discovery and refinement of loci associated with lipid levels.
GeneReviews: Not available
Limb-girdle muscular dystrophy, type 2A
MedGen: C1869123 OMIM: 253600 GeneReviews: Calpainopathy
Compare labs
Muscular dystrophy, limb-girdle, autosomal dominant 4
MedGen: C4748295 OMIM: 618129 GeneReviews: Not available
Compare labs

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

Homology

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
PubMed 
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 apoptotic process IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
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 negative regulation of transcription, DNA-templated ISS
Inferred from Sequence or Structural Similarity
more info
 
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 positive regulation of transcription, DNA-templated IMP
Inferred from Mutant Phenotype
more info
PubMed 
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
PubMed 
involved_in proteolysis IDA
Inferred from Direct Assay
more info
PubMed 
involved_in regulation of I-kappaB kinase/NF-kappaB signaling 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
PubMed 
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 intracellular anatomical structure TAS
Traceable Author Statement
more info
PubMed 
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)

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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
    P20807
    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/Swiss-Prot
    P20807
    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/Swiss-Prot
    P20807
    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/Swiss-Prot
    P20807
    UniProtKB/TrEMBL
    A0A0S2Z3E1
    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/Swiss-Prot
    P20807
    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/Swiss-Prot
    P20807
    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: Homo sapiens Updated Annotation Release 109.20210514

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

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000015.10 Reference GRCh38.p13 Primary Assembly

    Range
    42359501..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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