CAN3_MOUSE
ID CAN3_MOUSE Reviewed; 821 AA.
AC Q64691; A2AVV3; Q9WUC5;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 187.
DE RecName: Full=Calpain-3;
DE EC=3.4.22.54;
DE AltName: Full=Calcium-activated neutral proteinase 3;
DE Short=CANP 3;
DE AltName: Full=Calpain L3;
DE AltName: Full=Calpain p94;
DE AltName: Full=Muscle-specific calcium-activated neutral protease 3;
GN Name=Capn3;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG).
RX PubMed=8661728; DOI=10.1007/s003359900108;
RA Richard I., Beckmann J.S.;
RT "Molecular cloning of mouse canp3, the gene associated with limb-girdle
RT muscular dystrophy 2A in human.";
RL Mamm. Genome 7:377-379(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT).
RA Dickson J.M.J., Love D., Evans C.W.E.;
RT "Alternatively exon-spliced calpain 3 isoform expressed in mouse thymus.";
RL Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP SEQUENCE REVISION TO 638-640.
RA Dickson J.M.J., Love D., Evans C.W.E.;
RL Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
CC -!- FUNCTION: Calcium-regulated non-lysosomal thiol-protease.
CC Proteolytically cleaves CTBP1 at 'His-410'. Mediates, with UTP25, the
CC proteasome-independent degradation of p53/TP53.
CC {ECO:0000250|UniProtKB:P20807}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Broad endopeptidase activity.; EC=3.4.22.54;
CC -!- ACTIVITY REGULATION: Activated by micromolar concentrations of calcium
CC and inhibited by calpastatin.
CC -!- SUBUNIT: Homodimer; via EF-hand domain 4. Interacts with TTN/titin.
CC Interacts with CMYA5; this interaction, which results in CMYA5
CC proteolysis, may protect CAPN3 from autolysis. Interacts with SIMC1.
CC Interacts with UTP25; the interaction is required for CAPN3
CC translocation to the nucleolus. {ECO:0000250|UniProtKB:P20807}.
CC -!- INTERACTION:
CC Q64691; Q9ES46: Parvb; NbExp=3; IntAct=EBI-21927513, EBI-6914996;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P20807}.
CC Nucleus, nucleolus {ECO:0000250|UniProtKB:P20807}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Long;
CC IsoId=Q64691-1; Sequence=Displayed;
CC Name=Short;
CC IsoId=Q64691-2; Sequence=VSP_005230, VSP_005231;
CC -!- SIMILARITY: Belongs to the peptidase C2 family. {ECO:0000305}.
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DR EMBL; X92523; CAA63301.1; -; mRNA.
DR EMBL; AF127766; AAD28255.2; -; mRNA.
DR EMBL; AL935121; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS16620.1; -. [Q64691-1]
DR CCDS; CCDS50679.1; -. [Q64691-2]
DR RefSeq; NP_001171270.1; NM_001177799.1. [Q64691-2]
DR RefSeq; NP_031627.2; NM_007601.3. [Q64691-1]
DR AlphaFoldDB; Q64691; -.
DR SMR; Q64691; -.
DR BioGRID; 198472; 10.
DR IntAct; Q64691; 1.
DR STRING; 10090.ENSMUSP00000028749; -.
DR MEROPS; C02.004; -.
DR iPTMnet; Q64691; -.
DR PhosphoSitePlus; Q64691; -.
DR MaxQB; Q64691; -.
DR PaxDb; Q64691; -.
DR PRIDE; Q64691; -.
DR ProteomicsDB; 281763; -. [Q64691-1]
DR ProteomicsDB; 281764; -. [Q64691-2]
DR Antibodypedia; 10719; 198 antibodies from 29 providers.
DR DNASU; 12335; -.
DR Ensembl; ENSMUST00000028749; ENSMUSP00000028749; ENSMUSG00000079110. [Q64691-1]
DR Ensembl; ENSMUST00000110721; ENSMUSP00000106349; ENSMUSG00000079110. [Q64691-2]
DR GeneID; 12335; -.
DR KEGG; mmu:12335; -.
DR UCSC; uc008lvz.2; mouse. [Q64691-1]
DR UCSC; uc008lwa.2; mouse. [Q64691-2]
DR CTD; 825; -.
DR MGI; MGI:107437; Capn3.
DR VEuPathDB; HostDB:ENSMUSG00000079110; -.
DR eggNOG; KOG0045; Eukaryota.
DR GeneTree; ENSGT00940000156092; -.
DR InParanoid; Q64691; -.
DR PhylomeDB; Q64691; -.
DR TreeFam; TF314748; -.
DR BRENDA; 3.4.22.54; 3474.
DR Reactome; R-MMU-1474228; Degradation of the extracellular matrix.
DR BioGRID-ORCS; 12335; 1 hit in 72 CRISPR screens.
DR PRO; PR:Q64691; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q64691; protein.
DR Bgee; ENSMUSG00000079110; Expressed in lens of camera-type eye and 62 other tissues.
DR ExpressionAtlas; Q64691; baseline and differential.
DR Genevisible; Q64691; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0030016; C:myofibril; ISS:UniProtKB.
DR GO; GO:0005730; C:nucleolus; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0030315; C:T-tubule; ISS:UniProtKB.
DR GO; GO:0030018; C:Z disc; ISS:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0004198; F:calcium-dependent cysteine-type endopeptidase activity; IDA:MGI.
DR GO; GO:0003824; F:catalytic activity; ISS:UniProtKB.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0055103; F:ligase regulator activity; ISS:UniProtKB.
DR GO; GO:0060090; F:molecular adaptor activity; IMP:UniProtKB.
DR GO; GO:0008233; F:peptidase activity; ISS:UniProtKB.
DR GO; GO:0005102; F:signaling receptor binding; ISO:MGI.
DR GO; GO:0031402; F:sodium ion binding; IDA:UniProtKB.
DR GO; GO:0008307; F:structural constituent of muscle; IMP:UniProtKB.
DR GO; GO:0031432; F:titin binding; ISS:UniProtKB.
DR GO; GO:1990092; P:calcium-dependent self proteolysis; ISS:UniProtKB.
DR GO; GO:0071277; P:cellular response to calcium ion; IDA:UniProtKB.
DR GO; GO:0071472; P:cellular response to salt stress; IDA:UniProtKB.
DR GO; GO:0070315; P:G1 to G0 transition involved in cell differentiation; IDA:UniProtKB.
DR GO; GO:0061061; P:muscle structure development; IMP:UniProtKB.
DR GO; GO:0030239; P:myofibril assembly; IMP:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0033234; P:negative regulation of protein sumoylation; ISS:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IMP:UniProtKB.
DR GO; GO:0045862; P:positive regulation of proteolysis; IDA:UniProtKB.
DR GO; GO:0051281; P:positive regulation of release of sequestered calcium ion into cytosol; IMP:UniProtKB.
DR GO; GO:0014718; P:positive regulation of satellite cell activation involved in skeletal muscle regeneration; IDA:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0012501; P:programmed cell death; IDA:UniProtKB.
DR GO; GO:0030163; P:protein catabolic process; ISS:UniProtKB.
DR GO; GO:0031648; P:protein destabilization; ISO:MGI.
DR GO; GO:0072657; P:protein localization to membrane; IMP:UniProtKB.
DR GO; GO:0065003; P:protein-containing complex assembly; IMP:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IDA:UniProtKB.
DR GO; GO:0050790; P:regulation of catalytic activity; ISS:UniProtKB.
DR GO; GO:0043122; P:regulation of I-kappaB kinase/NF-kappaB signaling; IMP:UniProtKB.
DR GO; GO:0045661; P:regulation of myoblast differentiation; IDA:UniProtKB.
DR GO; GO:0051592; P:response to calcium ion; ISS:UniProtKB.
DR GO; GO:0014850; P:response to muscle activity; ISS:UniProtKB.
DR GO; GO:0045214; P:sarcomere organization; IMP:MGI.
DR GO; GO:0097264; P:self proteolysis; ISS:UniProtKB.
DR GO; GO:1990091; P:sodium-dependent self proteolysis; ISO:MGI.
DR CDD; cd00214; Calpain_III; 1.
DR CDD; cd00044; CysPc; 1.
DR InterPro; IPR033883; C2_III.
DR InterPro; IPR022684; Calpain_cysteine_protease.
DR InterPro; IPR022682; Calpain_domain_III.
DR InterPro; IPR022683; Calpain_III.
DR InterPro; IPR036213; Calpain_III_sf.
DR InterPro; IPR029531; CAPN3.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR000169; Pept_cys_AS.
DR InterPro; IPR001300; Peptidase_C2_calpain_cat.
DR PANTHER; PTHR10183:SF329; PTHR10183:SF329; 1.
DR Pfam; PF01067; Calpain_III; 1.
DR Pfam; PF13202; EF-hand_5; 1.
DR Pfam; PF13833; EF-hand_8; 1.
DR Pfam; PF00648; Peptidase_C2; 1.
DR PRINTS; PR00704; CALPAIN.
DR SMART; SM00720; calpain_III; 1.
DR SMART; SM00230; CysPc; 1.
DR SMART; SM00054; EFh; 3.
DR SUPFAM; SSF47473; SSF47473; 1.
DR SUPFAM; SSF49758; SSF49758; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR PROSITE; PS50203; CALPAIN_CAT; 1.
DR PROSITE; PS00018; EF_HAND_1; 2.
DR PROSITE; PS50222; EF_HAND_2; 4.
DR PROSITE; PS00139; THIOL_PROTEASE_CYS; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Calcium; Cytoplasm; Hydrolase; Metal-binding;
KW Nucleus; Protease; Reference proteome; Repeat; Thiol protease.
FT CHAIN 1..821
FT /note="Calpain-3"
FT /id="PRO_0000207708"
FT DOMAIN 74..417
FT /note="Calpain catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00239"
FT DOMAIN 649..683
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 692..725
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 722..757
FT /note="EF-hand 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 787..821
FT /note="EF-hand 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REGION 1..37
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 418..586
FT /note="Domain III"
FT REGION 587..649
FT /note="Linker"
FT REGION 603..651
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 650..820
FT /note="Domain IV"
FT COMPBIAS 613..651
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 129
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00239"
FT ACT_SITE 334
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00239"
FT ACT_SITE 358
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00239"
FT BINDING 662
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P20807"
FT BINDING 665
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P20807"
FT BINDING 667
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P20807"
FT BINDING 672
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P20807"
FT BINDING 705
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 707
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 709
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 711
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 716
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 735
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 737
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 739
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 741
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 746
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 800
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P20807"
FT BINDING 802
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P20807"
FT BINDING 804
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P20807"
FT BINDING 806
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P20807"
FT VAR_SEQ 268..315
FT /note="Missing (in isoform Short)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_005230"
FT VAR_SEQ 595..638
FT /note="Missing (in isoform Short)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_005231"
FT CONFLICT 66
FT /note="R -> K (in Ref. 1; CAA63301 and 2; AAD28255)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 821 AA; 94242 MW; C7FC94E31E1084C9 CRC64;
MPTVISPTVA PRTGAEPRSP GPVPHPAQGK TTEAGGGHPS GIYSAIISRN FPIIGVKEKT
FEQLRRKCLE KKVLYLDPEF PPDETSLFYS QKFPIQFVWK RPPEICENPR FIIGGANRTD
ICQGDLGDCW FLAAIACLTL NERLLFRVIP HDQSFTENYA GIFHFQFWRY GDWVDVVIDD
CLPTYNNQLV FTKSNHRNEF WSALLEKAYA KLHGSYEALK GGNTTEAMED FTGGVTEFFE
IKDAPSDMYK IMRKAIERGS LMGCSIDDGT NMTYGTSPSG LNMGELIARM VRNMDNSLLR
DSDLDPRGSD DRPSRTIVPV QYETRMACGL VKGHAYSVTG LEEALFKGEK VKLVRLRNPW
GQVEWNGSWS DGWKDWSFVD KDEKARLQHQ VTEDGEFWMS YDDFVYHFTK LEICNLTADA
LESDKLQTWT VSVNEGRWVR GCSAGGCRNF PDTFWTNPQY RLKLLEEDDD PEDSEVICSF
LVALMQKNRR KDRKLGANLF TIGFAIYEVP KEMHGNKQHL QKDFFLYNAS KARSKTYINM
REVSQRFRLP PSEYVIVPST YEPHQEGEFI LRVFSEKRNL SEEAENTISV DRPVKKKKNK
PIIFVSDRAN SNKELGVDQE AEEGKDKAGP EKRGETPQPR PGHTDQESEE QQQFRNIFRQ
IAGDDMEICA DELKNVLNTV VNKHKDLKTQ GFTLESCRSM IALMDTDGSG RLNLQEFHHL
WKKIKAWQKI FKHYDTDHSG TINSYEMRNA VNDAGFHLNS QLYDIITMRY ADKHMNIDFD
SFICCFVRLE GMFRAFNAFD KDGDGIIKLN VLEWLQLTMY A
