Capn3 calpain 3 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Capn3provided by MGI
Official Full Name: calpain 3provided by MGI
Primary source: MGI:MGI:107437
See related: Ensembl:ENSMUSG00000079110 AllianceGenome:MGI:107437
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: p94; Lp82; Capa3; Capa-3
Summary: Enables calcium-dependent cysteine-type endopeptidase activity; metal ion binding activity; and molecular adaptor activity. A structural constituent of muscle. Involved in several processes, including G1 to G0 transition involved in cell differentiation; positive regulation of release of sequestered calcium ion into cytosol; and regulation of transcription, DNA-templated. Acts upstream of or within negative regulation of skeletal muscle cell differentiation; proteolysis; and sarcomere organization. Located in cytosol and plasma membrane. Part of protein-containing complex. Is expressed in several structures, including brain; eye; heart; and musculature. Used to study autosomal recessive limb-girdle muscular dystrophy type 2A. Human ortholog(s) of this gene implicated in autosomal dominant limb-girdle muscular dystrophy; autosomal recessive limb-girdle muscular dystrophy type 2A; and muscular dystrophy. Orthologous to human CAPN3 (calpain 3). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Biased expression in thymus adult (RPKM 10.1), genital fat pad adult (RPKM 5.2) and 12 other tissues See more
Orthologs: human all
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Genomic context

Location:: 2 E5; 2 60.31 cM

Exon count:: 25

Annotation release	Status	Assembly	Chr	Location
109	current	GRCm39 (GCF_000001635.27)	2	NC_000068.8 (120294074..120335400)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	2	NC_000068.7 (120463593..120504919)

Chromosome 2 - NC_000068.8 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

A Small-Molecule Approach to Restore a Slow-Oxidative Phenotype and Defective CaMKIIbeta Signaling in Limb Girdle Muscular Dystrophy.
Title: A Small-Molecule Approach to Restore a Slow-Oxidative Phenotype and Defective CaMKIIβ Signaling in Limb Girdle Muscular Dystrophy.
Mitochondrial dysfunction and consequences in calpain-3-deficient muscle.
Title: Mitochondrial dysfunction and consequences in calpain-3-deficient muscle.
Frizzled related protein deficiency impairs muscle strength, gait and calpain 3 levels.
Title: Frizzled related protein deficiency impairs muscle strength, gait and calpain 3 levels.
Study shows that impaired skeletal muscle regeneration in calpain-3 null muscle is associated with perturbations in mTORC1 signaling and defective mitochondrial biogenesis.
Title: Impaired regeneration in calpain-3 null muscle is associated with perturbations in mTORC1 signaling and defective mitochondrial biogenesis.
Destabilization of PGC1a is attributable to decreased p38 MAPK activation via diminished CaMKII signaling. Thus, we elucidate a pathway downstream of Ca(2+)-mediated CaMKII activation that is dysfunctional in C3KO(Capn3 knock-out mice ) mice, leading to reduced transcription of genes involved in muscle adaptation
Title: Failure to up-regulate transcription of genes necessary for muscle adaptation underlies limb girdle muscular dystrophy 2A (calpainopathy).
CAPN3 deficiency leads to degradation of SERCA proteins and Ca2+ dysregulation in the skeletal muscle.
Title: Calpain 3 deficiency affects SERCA expression and function in the skeletal muscle.
Cleavage of C-terminal titin by CAPN3 is associated with limb-girdle muscular dystrophy 2A and tibial muscular dystrophy.
Title: CAPN3-mediated processing of C-terminal titin replaced by pathological cleavage in titinopathy.
these studies reveal a novel interaction between CAPN3 and CaM and identify CaM as the first positive regulator of CAPN3 activity.
Title: Autolytic activation of calpain 3 proteinase is facilitated by calmodulin protein.
data suggest that skNAC controls myoblast migration and sarcomere architecture in a calpain-dependent manner
Title: skNAC depletion stimulates myoblast migration and perturbs sarcomerogenesis by enhancing calpain 1 and 3 activity.
our results suggest that a component of FSHD pathogenesis may arise by over-expression of FRG1, reducing Rbfox1 levels and leading to aberrant expression of an altered Calpain 3 protein through dysregulated splicing
Title: Rbfox1 downregulation and altered calpain 3 splicing by FRG1 in a mouse model of Facioscapulohumeral muscular dystrophy (FSHD).

Submit: New GeneRIF Correction See all GeneRIFs (32)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Gene trapped (1) 1 citation
Targeted (3) 1 citation
Endonuclease-mediated (5)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

AI323605 (e-PCR)
- UniSTS:178692

PMC104364P1 (e-PCR)
- UniSTS:270108

AF091998 (e-PCR)
- UniSTS:159011

Capn3 (e-PCR), detects polymorphism
- UniSTS:507941

Capn3 (e-PCR), detects polymorphism
- UniSTS:507942

GDB:595526 (e-PCR)
- UniSTS:158024

RH126773 (e-PCR)
- UniSTS:209737

NoName (e-PCR)
- UniSTS:489038

Capn3 (e-PCR), detects polymorphism
- UniSTS:141224

Capn3 (e-PCR), detects polymorphism
- UniSTS:141225

CANP3SKM (e-PCR)
- UniSTS:253914

SKM-CALPOV (e-PCR)
- UniSTS:251621

G36400 (e-PCR)
- UniSTS:80614

Homology

Homologs of the Capn3 gene: The Capn3 gene is conserved in human, Rhesus monkey, dog, cow, rat, chicken, zebrafish, and frog.
Orthologs from Annotation Pipeline: 486 organisms have orthologs with human gene Capn3
Orthologs

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables calcium ion binding	IDA Inferred from Direct Assay more info	PubMed
enables calcium-dependent cysteine-type endopeptidase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
enables calcium-dependent cysteine-type endopeptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables calcium-dependent cysteine-type endopeptidase activity	ISO Inferred from Sequence Orthology more info
enables catalytic activity	ISO Inferred from Sequence Orthology more info
enables cysteine-type peptidase activity	IEA Inferred from Electronic Annotation more info
enables enzyme binding	ISO Inferred from Sequence Orthology more info
enables hydrolase activity	IEA Inferred from Electronic Annotation more info
enables identical protein binding	ISO Inferred from Sequence Orthology more info
enables ligase regulator activity	ISO Inferred from Sequence Orthology more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables molecular adaptor activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables peptidase activity	ISO Inferred from Sequence Orthology more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables signaling receptor binding	ISO Inferred from Sequence Orthology more info
enables sodium ion binding	IDA Inferred from Direct Assay more info	PubMed
enables structural constituent of muscle	IMP Inferred from Mutant Phenotype more info	PubMed
enables titin binding	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in G1 to G0 transition involved in cell differentiation	IDA Inferred from Direct Assay more info	PubMed
involved_in calcium-dependent self proteolysis	ISO Inferred from Sequence Orthology more info
involved_in cellular response to calcium ion	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to salt stress	IDA Inferred from Direct Assay more info	PubMed
involved_in muscle structure development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within myofibril assembly	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of DNA-templated transcription	IDA Inferred from Direct Assay 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 apoptotic process	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of protein sumoylation	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of DNA-templated transcription	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of DNA-templated transcription	ISO Inferred from Sequence Orthology 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 NF-kappaB transcription factor activity	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of proteolysis	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of release of sequestered calcium ion into cytosol	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of satellite cell activation involved in skeletal muscle regeneration	IDA Inferred from Direct Assay more info	PubMed
involved_in programmed cell death	IDA Inferred from Direct Assay more info	PubMed
involved_in protein catabolic process	ISO Inferred from Sequence Orthology more info
involved_in protein destabilization	ISO Inferred from Sequence Orthology more info
involved_in protein localization to membrane	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein-containing complex assembly	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in proteolysis	IBA Inferred from Biological aspect of Ancestor more info	PubMed
acts_upstream_of_or_within proteolysis	IDA Inferred from Direct Assay more info	PubMed
involved_in proteolysis	IDA Inferred from Direct Assay more info	PubMed
involved_in proteolysis	ISO Inferred from Sequence Orthology more info
involved_in regulation of I-kappaB kinase/NF-kappaB signaling	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of I-kappaB kinase/NF-kappaB signaling	ISO Inferred from Sequence Orthology more info
involved_in regulation of catalytic activity	ISO Inferred from Sequence Orthology more info
involved_in regulation of myoblast differentiation	IDA Inferred from Direct Assay more info	PubMed
involved_in response to calcium ion	ISO Inferred from Sequence Orthology more info
involved_in response to muscle activity	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within sarcomere organization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in self proteolysis	ISO Inferred from Sequence Orthology more info
involved_in sodium-dependent self proteolysis	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
located_in T-tubule	ISO Inferred from Sequence Orthology more info
located_in Z disc	ISO Inferred from Sequence Orthology 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 cytoplasm	ISO Inferred from Sequence Orthology more info
located_in cytosol	IDA Inferred from Direct Assay more info	PubMed
located_in myofibril	ISO Inferred from Sequence Orthology more info
located_in nucleolus	ISO Inferred from Sequence Orthology more info
located_in nucleus	ISO Inferred from Sequence Orthology more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	ISO Inferred from Sequence Orthology more info
part_of protein-containing complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: calpain-3

Names: CANP 3; calcium-activated neutral proteinase 3; calpain L3; calpain p94; muscle-specific calcium-activated neutral protease 3; skeletal muscle specific calpain p94

NP_001103231.1

EC 3.4.22.54

NP_001171270.1

EC 3.4.22.54

NP_031627.2

EC 3.4.22.54

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)

NM_001109761.2 → NP_001103231.1 calpain-3 isoform b

See identical proteins and their annotated locations for NP_001103231.1

Status: VALIDATED

Description

Transcript Variant: This variant (b) has multiple differences, compared to variant a. The resulting protein (isoform b) is shorter and has a distinct N-terminus when it is compared to isoform a.

Source sequence(s)

BB202194, BC090661

Consensus CDS

CCDS50680.1

UniProtKB/TrEMBL

Q0VGP9

Related

ENSMUSP00000028748.7, ENSMUST00000028748.14

Conserved Domains (5) summary

cd00051
Location:585 → 639

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:51 → 347

Peptidase_C2; Calpain family cysteine protease

pfam01067
Location:361 → 511

Calpain_III; Calpain large subunit, domain III

pfam13499
Location:616 → 672

EF-hand_7; EF-hand domain pair

cl08302
Location:616 → 705

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 ...
NM_001177799.1 → NP_001171270.1 calpain-3 isoform c

Status: VALIDATED

Description

Transcript Variant: This variant (c) lacks several alternate, in-frame coding exons, compared to variant a. The resulting protein (isoform c) is shorter when it is compared to isoform a.

Source sequence(s)

AF127766, BB202194, BC090661, BC139790, BY142198, CN664345

Consensus CDS

CCDS50679.1

UniProtKB/Swiss-Prot

Q64691

UniProtKB/TrEMBL

A4QPE6, Q0VGP9

Related

ENSMUSP00000106349.2, ENSMUST00000110721.9

Conserved Domains (5) summary

cd00051
Location:605 → 659

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:77 → 367

Peptidase_C2; Calpain family cysteine protease

pfam01067
Location:381 → 531

Calpain_III; Calpain large subunit, domain III

pfam13499
Location:636 → 692

EF-hand_7; EF-hand domain pair

cl08302
Location:636 → 725

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 ...
NM_007601.3 → NP_031627.2 calpain-3 isoform a

See identical proteins and their annotated locations for NP_031627.2

Status: VALIDATED

Description

Transcript Variant: This variant (a) is the longest transcript and it encodes the longest protein (isoform a).

Source sequence(s)

AL935121, BB202194, BC090661, BC139790, BY142198, CN664345

Consensus CDS

CCDS16620.1

UniProtKB/Swiss-Prot

Q64691, Q9WUC5

UniProtKB/TrEMBL

A4QPE6, Q0VGP9

Related

ENSMUSP00000028749.8, ENSMUST00000028749.15

Conserved Domains (6) summary

cd00051
Location:697 → 751

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:77 → 415

Peptidase_C2; Calpain family cysteine protease

pfam01067
Location:429 → 579

Calpain_III; Calpain large subunit, domain III

pfam13499
Location:728 → 784

EF-hand_7; EF-hand domain pair

pfam16648
Location:583 → 653

Calpain_u2; Unstructured region on Calpain-3

cl08302
Location:728 → 817

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 ...