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Cast calpastatin [ Mus musculus (house mouse) ]

Gene ID: 12380, updated on 5-Mar-2024

Summary

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Official Symbol
Castprovided by MGI
Official Full Name
calpastatinprovided by MGI
Primary source
MGI:MGI:1098236
See related
Ensembl:ENSMUSG00000021585 AllianceGenome:MGI:1098236
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Mus musculus
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Summary
This gene encodes an inhibitor of the calcium-dependent cysteine protease, calpain. This protein plays roles in multiple processes, including apoptosis, cell cycle regulation, and membrane fusion. Multiple protein isoforms exist which contain unique N-terminal domains, and multiple inhibitory domains that share homology with each other. Some isoforms may be tissue-specific. Two different pseudogenes of this gene are found on chromosome 19. [provided by RefSeq, Jul 2014]
Expression
Broad expression in bladder adult (RPKM 25.7), placenta adult (RPKM 10.2) and 17 other tissues See more
Orthologs
human all
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Genomic context

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Location:
13 C1; 13 40.52 cM
Exon count:
35
Annotation release Status Assembly Chr Location
RS_2024_02 current GRCm39 (GCF_000001635.27) 13 NC_000079.7 (74840485..74956993, complement)
108.20200622 previous assembly GRCm38.p6 (GCF_000001635.26) 13 NC_000079.6 (74692366..74808874, complement)

Chromosome 13 - NC_000079.7Genomic Context describing neighboring genes Neighboring gene STARR-seq mESC enhancer starr_35022 Neighboring gene predicted gene, 57808 Neighboring gene predicted gene, 57809 Neighboring gene STARR-seq mESC enhancer starr_35023 Neighboring gene predicted gene, 46430 Neighboring gene STARR-positive B cell enhancer ABC_E10801 Neighboring gene endoplasmic reticulum aminopeptidase 1 Neighboring gene STARR-positive B cell enhancer ABC_E5406 Neighboring gene heterogeneous nuclear ribonucleoprotein A1 pseudogene Neighboring gene STARR-seq mESC enhancer starr_35025 Neighboring gene heterogeneous nuclear ribonucleoprotein A1-like 2, pseudogene Neighboring gene STARR-seq mESC enhancer starr_35028 Neighboring gene STARR-seq mESC enhancer starr_35029 Neighboring gene predicted gene, 30867

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: Mouse ENCODE transcriptome data
  • Description: RNA profiling data sets generated by the Mouse ENCODE project.
  • BioProject: PRJNA66167
  • Publication: PMID 25409824
  • Analysis date: n/a

Bibliography

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Related articles in PubMed

  1. Skeletal muscle-specific calpastatin overexpression mitigates muscle weakness in aging and extends life span. Schroder EA, et al. J Appl Physiol (1985), 2021 Aug 1. PMID 34197232, Free PMC Article
  2. Endothelial calpain systems orchestrate myofibroblast differentiation during wound healing. Miyazaki T, et al. FASEB J, 2019 Feb. PMID 30199285
  3. Calpain Inhibition Attenuates Adipose Tissue Inflammation and Fibrosis in Diet-induced Obese Mice. Muniappan L, et al. Sci Rep, 2017 Oct 31. PMID 29089532, Free PMC Article
  4. Calpastatin Overexpression Preserves Cognitive Function Following Seizures, While Maintaining Post-Injury Neurogenesis. Machado VM, et al. Front Mol Neurosci, 2017. PMID 28386216, Free PMC Article
  5. Targeting host calpain proteases decreases influenza A virus infection. Blanc F, et al. Am J Physiol Lung Cell Mol Physiol, 2016 Apr 1. PMID 26747784

See all (82) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Osteocyte-Derived CaMKK2 Regulates Osteoclasts and Bone Mass in a Sex-Dependent Manner through Secreted Calpastatin.
    Title: Osteocyte-Derived CaMKK2 Regulates Osteoclasts and Bone Mass in a Sex-Dependent Manner through Secreted Calpastatin.
  2. Critical Roles of Calpastatin in Ischemia/Reperfusion Injury in Aged Livers.
    Title: Critical Roles of Calpastatin in Ischemia/Reperfusion Injury in Aged Livers.
  3. Small-molecule suppression of calpastatin degradation reduces neuropathology in models of Huntington's disease.
    Title: Small-molecule suppression of calpastatin degradation reduces neuropathology in models of Huntington's disease.
  4. Skeletal muscle-specific calpastatin overexpression mitigates muscle weakness in aging and extends life span.
    Title: Skeletal muscle-specific calpastatin overexpression mitigates muscle weakness in aging and extends life span.
  5. Impaired experience-dependent maternal care in presynaptic active zone protein CAST-deficient dams.
    Title: Impaired experience-dependent maternal care in presynaptic active zone protein CAST-deficient dams.
  6. These data identify distinct roles for CAST/ELKS as positive regulators of CaV2.1 channel density.
    Title: CAST/ELKS Proteins Control Voltage-Gated Ca(2+) Channel Density and Synaptic Release Probability at a Mammalian Central Synapse.
  7. These results suggest that CAST and ELKS work in concert to promote retinal synapse formation, transmission, and maintenance.
    Title: Cytomatrix proteins CAST and ELKS regulate retinal photoreceptor development and maintenance.
  8. mice that were either wild type (WT) or overexpressing calpastatin (CAST Tg), the endogenous inhibitor of calpains were fed with high (60% kcal) fat diet for 16 weeks. CAST overexpression significantly reduced adipocyte apoptosis, adipose tissue collagen and macrophage accumulation; and significantly attenuated obesity-induced inflammatory responses in adipose tissue.
    Title: Calpain Inhibition Attenuates Adipose Tissue Inflammation and Fibrosis in Diet-induced Obese Mice.
  9. The knockdown of CAST in mutant huntingtin-expressing cells and the knockout of the Cast gene in a knock-in mouse model of HD resulted in a worsening of the molecular HD-related hallmarks including elevated formation of huntingtin fragments and increased amount of respective aggregates
    Title: Calpastatin ablation aggravates the molecular phenotype in cell and animal models of Huntington disease.
  10. calpains and calpastatin in patients with idiopathic pulmonary arterial hypertension (PAH) and mice with hypoxic or spontaneous (SM22-5HTT(+) strain) PH, were investigated.
    Title: Extracellular Calpain/Calpastatin Balance Is Involved in the Progression of Pulmonary Hypertension.
Submit: New GeneRIF Correction See all GeneRIFs (35)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics  (MGI)
  • Targeted (3)  1 citation
  • Endonuclease-mediated (2) 

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by MGI

Function Evidence Code Pubs
enables calcium-dependent cysteine-type endopeptidase inhibitor activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables calcium-dependent cysteine-type endopeptidase inhibitor activity ISO
Inferred from Sequence Orthology
more info
  
enables cysteine-type endopeptidase inhibitor activity IEA
Inferred from Electronic Annotation
more info
  
enables peptidase inhibitor activity IEA
Inferred from Electronic Annotation
more info
  
enables protease binding ISO
Inferred from Sequence Orthology
more info
  
Process Evidence Code Pubs
involved_in egg activation ISO
Inferred from Sequence Orthology
more info
  
involved_in inhibition of cysteine-type endopeptidase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in inhibition of cysteine-type endopeptidase activity ISO
Inferred from Sequence Orthology
more info
  
acts_upstream_of_or_within negative regulation of peptidase activity IGI
Inferred from Genetic Interaction
more info
 PubMed 
involved_in negative regulation of type B pancreatic cell apoptotic process ISO
Inferred from Sequence Orthology
more info
  
acts_upstream_of_or_within protein catabolic process ISA
Inferred from Sequence Alignment
more info
 PubMed 
Component Evidence Code Pubs
is_active_in cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytosol ISO
Inferred from Sequence Orthology
more info
  
located_in endoplasmic reticulum ISO
Inferred from Sequence Orthology
more info
  
located_in membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in membrane ISO
Inferred from Sequence Orthology
more info
  
located_in postsynaptic density ISO
Inferred from Sequence Orthology
more info
  

General protein information

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Preferred Names
calpastatin
Names
calpain inhibitor
calpastatin type III

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.

mRNA and Protein(s)

  1. NM_001301153.1 → NP_001288082.1  calpastatin isoform 1

    See identical proteins and their annotated locations for NP_001288082.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
    Source sequence(s)
    AA033475, AK036576, AK037098, AK083395, BY771015, CF164079, CN529927
    Consensus CDS
    CCDS88491.1
    UniProtKB/Swiss-Prot
    P51125, Q9EQV4, Q9EQV5, Q9QXQ3, Q9QXQ4, Q9R0N1
    UniProtKB/TrEMBL
    Q8CB83
    Related
    ENSMUSP00000152174.2, ENSMUST00000223206.2
    Conserved Domains (1) summary
    pfam00748
    Location:591 → 715
    Calpain_inhib; Calpain inhibitor

  2. NM_001301155.1 → NP_001288084.1  calpastatin isoform 3

    See identical proteins and their annotated locations for NP_001288084.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) represents use of an alternate promoter and therefore differs in the 5' UTR and 5' coding region, compared to variant 1. These differences cause translation initiation at a downstream start codon and result in an isoform (3) with a shorter N-terminus. This variant (3) also uses an alternate in-frame splice site in the coding region, compared to variant 1. The resulting protein (isoform 3) has a shorter N-terminus and is shorter than isoform 1.
    Source sequence(s)
    AK029293, AK037098, AK083395, CJ072297
    Consensus CDS
    CCDS88490.1
    UniProtKB/TrEMBL
    Q8CB83, Q8CE04
    Related
    ENSMUSP00000152118.2, ENSMUST00000223033.2
    Conserved Domains (1) summary
    pfam00748
    Location:231 → 355
    Calpain_inhib; Calpain inhibitor

  3. NM_001301156.1 → NP_001288085.1  calpastatin isoform 4

    See identical proteins and their annotated locations for NP_001288085.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) represents use of an alternate promoter and therefore differs in the 5' UTR and 5' coding region, compared to variant 1. These differences cause translation initiation at a downstream start codon and result in an isoform (4) with a shorter N-terminus. This variant (4) also lacks an internal exon in the coding region. The resulting protein (isoform 4) has a shorter N-terminus and is shorter than isoform 1.
    Source sequence(s)
    AK029293, AK037098, AK083310, AK083395, CJ072297
    Consensus CDS
    CCDS88489.1
    UniProtKB/TrEMBL
    Q8C281, Q8CB83
    Related
    ENSMUSP00000152306.2, ENSMUST00000222588.2
    Conserved Domains (1) summary
    pfam00748
    Location:489 → 613
    Calpain_inhib; Calpain inhibitor

  4. NM_001301157.1 → NP_001288086.1  calpastatin isoform 5

    See identical proteins and their annotated locations for NP_001288086.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) represents use of an alternate promoter and therefore differs in the 5' UTR and 5' coding region, compared to variant 1. These differences cause translation initiation at a downstream start codon and result in an isoform (5) with a shorter N-terminus. This variant also lacks two internal exons relative to variant 1. The resulting protein (isoform 5) has a shorter N-terminus and is shorter than isoform 1.
    Source sequence(s)
    AK037098, AK083395, BC010603, CJ072297
    Consensus CDS
    CCDS88488.1
    UniProtKB/TrEMBL
    Q8CB83, Q921U7
    Related
    ENSMUSP00000152550.2, ENSMUST00000223126.2
    Conserved Domains (1) summary
    pfam00748
    Location:212 → 336
    Calpain_inhib; Calpain inhibitor

  5. NM_001301158.1 → NP_001288087.1  calpastatin isoform 6

    See identical proteins and their annotated locations for NP_001288087.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (6) represents use of an alternate promoter and therefore differs in the 5' UTR and 5' coding region, compared to variant 1. These differences cause translation initiation at an alternate start codon and result in an isoform (6) with a shorter and distinct N-terminus. This variant (6) also uses an alternate in-frame splice site in the coding region, compared to variant 1. The resulting protein (isoform 6) has a distinct N-terminus and is shorter than isoform 1.
    Source sequence(s)
    AK006253, AK029293, AK037098, AK083395, BY086784
    Consensus CDS
    CCDS88486.1
    UniProtKB/TrEMBL
    A0A1Y7VJN8
    Related
    ENSMUSP00000152504.2, ENSMUST00000220738.2
    Conserved Domains (1) summary
    pfam00748
    Location:249 → 372
    Calpain_inhib; Calpain inhibitor

  6. NM_001301160.1 → NP_001288089.1  calpastatin isoform 7

    See identical proteins and their annotated locations for NP_001288089.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (7) represents use of an alternate promoter and therefore differs in the 5' UTR and 5' coding region, compared to variant 1. These differences cause translation initiation at an alternate start codon and result in an isoform (7) with a shorter N-terminus. The resulting protein (isoform 7) has a shorter and distinct N-terminus and is shorter than isoform 1.
    Source sequence(s)
    AK006253, AK029293, AK037098, AK083395, AK161284
    Consensus CDS
    CCDS88487.1
    UniProtKB/TrEMBL
    Q3TTN2
    Related
    ENSMUSP00000152657.2, ENSMUST00000223309.2
    Conserved Domains (1) summary
    pfam00748
    Location:234 → 358
    Calpain_inhib; Calpain inhibitor

  7. NM_001301181.1 → NP_001288110.1  calpastatin isoform 8

    See identical proteins and their annotated locations for NP_001288110.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (8) represents use of an alternate promoter and therefore differs in the 5' UTR and 5' coding region, compared to variant 1. These differences cause translation initiation at an alternate start codon and result in an isoform (8) with a shorter and distinct N-terminus. The resulting protein (isoform 8) has a distinct and shorter N-terminus and is shorter than isoform 1.
    Source sequence(s)
    AK006253, AK037098, AK083395, AK161284, BY086784
    UniProtKB/Swiss-Prot
    P51125
    UniProtKB/TrEMBL
    Q3TTN2
    Conserved Domains (1) summary
    pfam00748
    Location:249 → 373
    Calpain_inhib; Calpain inhibitor

  8. NM_009817.4 → NP_033947.1  calpastatin isoform 2

    See identical proteins and their annotated locations for NP_033947.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) represents use of an alternate promoter and therefore differs in the 5' UTR and 5' coding region, compared to variant 1. These differences cause translation initiation at an alternate start codon and result in an isoform (2) with a shorter and distinct N-terminus. This variant also lacks one internal exons relative to variant 1. The resulting protein (isoform 2) has a distinct N-terminus and is shorter than isoform 1.
    Source sequence(s)
    AK028843, AK037098, AK083395, CD550676
    Consensus CDS
    CCDS26648.1
    UniProtKB/TrEMBL
    Q8CB83, Q8CE80
    Related
    ENSMUSP00000065275.5, ENSMUST00000065629.6
    Conserved Domains (1) summary
    pfam00748
    Location:557 → 681
    Calpain_inhib; Calpain inhibitor

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

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

Reference GRCm39 C57BL/6J

Genomic

  1. NC_000079.7 Reference GRCm39 C57BL/6J

    Range
    74840485..74956993 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_006517059.1 → XP_006517122.1  calpastatin isoform X3

    UniProtKB/TrEMBL
    Q8CB83
    Conserved Domains (1) summary
    pfam00748
    Location:295 → 419
    Calpain_inhib; Calpain inhibitor

  2. XM_006517056.2 → XP_006517119.1  calpastatin isoform X1

    UniProtKB/TrEMBL
    Q8CB83
    Conserved Domains (1) summary
    pfam00748
    Location:314 → 438
    Calpain_inhib; Calpain inhibitor

  3. XM_011244466.4 → XP_011242768.1  calpastatin isoform X2

    See identical proteins and their annotated locations for XP_011242768.1

    UniProtKB/TrEMBL
    Q8CB83
    Conserved Domains (2) summary
    PTZ00449
    Location:23 → 217
    PTZ00449; 104 kDa microneme/rhoptry antigen; Provisional
    pfam00748
    Location:299 → 423
    Calpain_inhib; Calpain inhibitor

  4. XM_017315374.1 → XP_017170863.1  calpastatin isoform X5

    UniProtKB/TrEMBL
    Q8CB83
    Conserved Domains (1) summary
    pfam00748
    Location:212 → 336
    Calpain_inhib; Calpain inhibitor

  5. XM_011244467.4 → XP_011242769.1  calpastatin isoform X4

    See identical proteins and their annotated locations for XP_011242769.1

    UniProtKB/TrEMBL
    Q8CB83
    Conserved Domains (1) summary
    pfam00748
    Location:231 → 355
    Calpain_inhib; Calpain inhibitor

  6. XM_011244469.4 → XP_011242771.1  calpastatin isoform X6

    Conserved Domains (1) summary
    pfam00748
    Location:234 → 357
    Calpain_inhib; Calpain inhibitor
Nucleotide Protein Strain
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P51125.2 GenPept UniProtKB/Swiss-Prot:P51125

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