CAN2_MOUSE
ID CAN2_MOUSE Reviewed; 700 AA.
AC O08529; O35518; O54843;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 03-AUG-2022, entry version 201.
DE RecName: Full=Calpain-2 catalytic subunit;
DE EC=3.4.22.53;
DE AltName: Full=80 kDa M-calpain subunit;
DE Short=CALP80;
DE AltName: Full=Calcium-activated neutral proteinase 2;
DE Short=CANP 2;
DE AltName: Full=Calpain M-type;
DE AltName: Full=Calpain-2 large subunit;
DE AltName: Full=Millimolar-calpain;
DE Short=M-calpain;
DE Flags: Precursor;
GN Name=Capn2;
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].
RC STRAIN=BALB/cJ;
RX PubMed=9339374; DOI=10.1006/geno.1997.4870;
RA Dear T.N., Matena K., Vingron M., Boehm T.;
RT "A new subfamily of vertebrate calpains lacking a calmodulin-like domain:
RT implications for calpain regulation and evolution.";
RL Genomics 45:175-184(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ;
RA Ozaki Y.;
RL Submitted (OCT-1997) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=CNS;
RX PubMed=9669314;
RX DOI=10.1002/(sici)1097-4547(19980615)52:6<653::aid-jnr4>3.0.co;2-7;
RA Glass J.D., Nash N.R., Dry I., Culver D., Levey A.I., Wesselingh S.;
RT "Cloning of m-calpain 80 kD subunit from the axonal degeneration-resistant
RT WLD(S) mouse mutant.";
RL J. Neurosci. Res. 52:653-660(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP FUNCTION, AND INTERACTION WITH CPEB3.
RX PubMed=22711986; DOI=10.1128/mcb.00296-12;
RA Wang C.F., Huang Y.S.;
RT "Calpain 2 activated through N-methyl-D-aspartic acid receptor signaling
RT cleaves CPEB3 and abrogates CPEB3-repressed translation in neurons.";
RL Mol. Cell. Biol. 32:3321-3332(2012).
CC -!- FUNCTION: Calcium-regulated non-lysosomal thiol-protease which
CC catalyzes limited proteolysis of substrates involved in cytoskeletal
CC remodeling and signal transduction. Proteolytically cleaves MYOC at
CC 'Arg-226' (By similarity). Proteolytically cleaves CPEB3 following
CC neuronal stimulation which abolishes CPEB3 translational repressor
CC activity, leading to translation of CPEB3 target mRNAs
CC (PubMed:22711986). {ECO:0000250|UniProtKB:P17655,
CC ECO:0000269|PubMed:22711986}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Broad endopeptidase specificity.; EC=3.4.22.53;
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000250};
CC Note=Binds 7 Ca(2+) ions. {ECO:0000250};
CC -!- ACTIVITY REGULATION: Activated by 200-1000 micromolar concentrations of
CC calcium and inhibited by calpastatin.
CC -!- SUBUNIT: Forms a heterodimer with a small (regulatory) subunit (CAPNS1)
CC (By similarity). Interacts with CPEB3; this leads to cleavage of CPEB3
CC (PubMed:22711986). {ECO:0000250|UniProtKB:Q07009,
CC ECO:0000269|PubMed:22711986}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cell membrane
CC {ECO:0000250}. Note=Translocates to the plasma membrane upon Ca(2+)
CC binding. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- SIMILARITY: Belongs to the peptidase C2 family. {ECO:0000305}.
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DR EMBL; Y10139; CAA71227.1; -; mRNA.
DR EMBL; D38117; BAA22964.1; -; mRNA.
DR EMBL; AF015038; AAB94029.1; -; mRNA.
DR EMBL; BC054726; AAH54726.1; -; mRNA.
DR CCDS; CCDS35813.1; -.
DR RefSeq; NP_033924.2; NM_009794.3.
DR AlphaFoldDB; O08529; -.
DR SMR; O08529; -.
DR BioGRID; 198471; 24.
DR ComplexPortal; CPX-4301; M-Calpain complex.
DR IntAct; O08529; 4.
DR MINT; O08529; -.
DR STRING; 10090.ENSMUSP00000068895; -.
DR MEROPS; C02.002; -.
DR iPTMnet; O08529; -.
DR PhosphoSitePlus; O08529; -.
DR SwissPalm; O08529; -.
DR EPD; O08529; -.
DR jPOST; O08529; -.
DR MaxQB; O08529; -.
DR PaxDb; O08529; -.
DR PeptideAtlas; O08529; -.
DR PRIDE; O08529; -.
DR ProteomicsDB; 273831; -.
DR Antibodypedia; 20748; 449 antibodies from 39 providers.
DR DNASU; 12334; -.
DR Ensembl; ENSMUST00000068505; ENSMUSP00000068895; ENSMUSG00000026509.
DR GeneID; 12334; -.
DR KEGG; mmu:12334; -.
DR UCSC; uc007dye.2; mouse.
DR CTD; 824; -.
DR MGI; MGI:88264; Capn2.
DR VEuPathDB; HostDB:ENSMUSG00000026509; -.
DR eggNOG; KOG0045; Eukaryota.
DR GeneTree; ENSGT00940000154784; -.
DR HOGENOM; CLU_010982_0_1_1; -.
DR InParanoid; O08529; -.
DR OMA; CLETRNT; -.
DR OrthoDB; 704215at2759; -.
DR PhylomeDB; O08529; -.
DR TreeFam; TF314748; -.
DR BRENDA; 3.4.22.53; 3474.
DR Reactome; R-MMU-1474228; Degradation of the extracellular matrix.
DR BioGRID-ORCS; 12334; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Capn2; mouse.
DR PRO; PR:O08529; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; O08529; protein.
DR Bgee; ENSMUSG00000026509; Expressed in endothelial cell of lymphatic vessel and 262 other tissues.
DR Genevisible; O08529; MM.
DR GO; GO:0110158; C:calpain complex; ISO:MGI.
DR GO; GO:0042995; C:cell projection; ISO:MGI.
DR GO; GO:0000785; C:chromatin; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0030425; C:dendrite; ISO:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0009897; C:external side of plasma membrane; ISO:MGI.
DR GO; GO:0005925; C:focal adhesion; ISO:MGI.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0005764; C:lysosome; IDA:MGI.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0045121; C:membrane raft; ISO:MGI.
DR GO; GO:0005758; C:mitochondrial intermembrane space; ISO:MGI.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0097038; C:perinuclear endoplasmic reticulum; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISS:BHF-UCL.
DR GO; GO:0031143; C:pseudopodium; ISO:MGI.
DR GO; GO:0005509; F:calcium ion binding; ISO:MGI.
DR GO; GO:0004198; F:calcium-dependent cysteine-type endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0008092; F:cytoskeletal protein binding; ISO:MGI.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0008233; F:peptidase activity; IDA:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0048266; P:behavioral response to pain; ISO:MGI.
DR GO; GO:0001824; P:blastocyst development; IMP:MGI.
DR GO; GO:0071230; P:cellular response to amino acid stimulus; IDA:UniProtKB.
DR GO; GO:0035458; P:cellular response to interferon-beta; IEA:Ensembl.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEA:Ensembl.
DR GO; GO:0007565; P:female pregnancy; IEA:Ensembl.
DR GO; GO:0007520; P:myoblast fusion; IMP:MGI.
DR GO; GO:0010666; P:positive regulation of cardiac muscle cell apoptotic process; ISO:MGI.
DR GO; GO:1901741; P:positive regulation of myoblast fusion; ISO:MGI.
DR GO; GO:1901216; P:positive regulation of neuron death; ISO:MGI.
DR GO; GO:2001247; P:positive regulation of phosphatidylcholine biosynthetic process; ISO:MGI.
DR GO; GO:0016540; P:protein autoprocessing; ISO:MGI.
DR GO; GO:0030163; P:protein catabolic process; ISO:MGI.
DR GO; GO:0006508; P:proteolysis; IDA:UniProtKB.
DR GO; GO:0051603; P:proteolysis involved in protein catabolic process; ISO:MGI.
DR GO; GO:0051493; P:regulation of cytoskeleton organization; IEA:InterPro.
DR GO; GO:0032675; P:regulation of interleukin-6 production; ISO:MGI.
DR GO; GO:0042542; P:response to hydrogen peroxide; IEA:Ensembl.
DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl.
DR GO; GO:0009612; P:response to mechanical stimulus; IEA:Ensembl.
DR CDD; cd00214; Calpain_III; 1.
DR CDD; cd00044; CysPc; 1.
DR CDD; cd16199; EFh_PEF_CAPN2; 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; IPR029539; CAPN2.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR042736; EFh_PEF_CAPN2.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR000169; Pept_cys_AS.
DR InterPro; IPR001300; Peptidase_C2_calpain_cat.
DR PANTHER; PTHR10183:SF268; PTHR10183:SF268; 1.
DR Pfam; PF01067; Calpain_III; 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 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; 2.
DR PROSITE; PS00139; THIOL_PROTEASE_CYS; 1.
PE 1: Evidence at protein level;
KW Acetylation; Calcium; Cell membrane; Cytoplasm; Hydrolase; Membrane;
KW Metal-binding; Protease; Reference proteome; Repeat; Thiol protease.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P17655"
FT PROPEP 2..19
FT /note="Anchors to the small subunit"
FT /evidence="ECO:0000255"
FT /id="PRO_0000026491"
FT CHAIN 20..700
FT /note="Calpain-2 catalytic subunit"
FT /id="PRO_0000026492"
FT DOMAIN 45..344
FT /note="Calpain catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00239"
FT DOMAIN 572..605
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 602..637
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REGION 345..514
FT /note="Domain III"
FT REGION 515..529
FT /note="Linker"
FT REGION 530..700
FT /note="Domain IV"
FT ACT_SITE 105
FT /evidence="ECO:0000250"
FT ACT_SITE 262
FT /evidence="ECO:0000250"
FT ACT_SITE 286
FT /evidence="ECO:0000250"
FT BINDING 89
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 91
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 96
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 175
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 229
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 230
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 292
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT BINDING 299
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT BINDING 319
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT BINDING 323
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT BINDING 542
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000250"
FT BINDING 545
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000250"
FT BINDING 547
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000250"
FT BINDING 552
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000250"
FT BINDING 585
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 587
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 589
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 591
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 596
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 615
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 617
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 619
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 621
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 626
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 658
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 661
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:P17655"
FT CONFLICT 194
FT /note="A -> T (in Ref. 1; CAA71227)"
FT /evidence="ECO:0000305"
FT CONFLICT 212
FT /note="A -> G (in Ref. 2; BAA22964)"
FT /evidence="ECO:0000305"
FT CONFLICT 402
FT /note="E -> G (in Ref. 1; CAA71227)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 700 AA; 79872 MW; 682146B290968316 CRC64;
MAGIAIKLAK DREAAEGLGS HERAIKYLNQ DYETLRNECL EAGALFQDPS FPALPSSLGY
KELGPYSSKT RGIEWKRPTE ICADPQFIIG GATRTDICQG ALGDCWLLAA IASLTLNEEI
LARVVPPDQS FQENYAGIFH FQFWQYGEWV EVVVDDRLPT KDGELLFVHS AEGSEFWSAL
LEKAYAKING CYEALSGGAT TEGFEDFTGG IAEWYELRKP PPNLFKIIQK ALEKGSLLGC
SIDITSAADS EAVTYQKLVK GHAYSVTGAE EVESSGSLQK LIRIRNPWGQ VEWTGKWNDN
CPSWNTVDPE VRANLTERQE DGEFWMSFSD FLRHYSRLEI CNLTPDTLTC DSYKKWKLTK
MDGNWRRGST AGGCRNYPNT FWMNPQYLIK LEEEDEDEED GERGCTFLVG LIQKHRRRQR
KMGEDMHTIG FGIYEVPEEL TGQTNIHLGK NFFLTTRARE RSDTFINLRE VLNRFKLPPG
EYVLVPSTFE PHKDGDFCIR VFSEKKADYQ AVDDEIEANI EEIDANEEDI DDGFRRLFVQ
LAGEDAEISA FELQTILRRV LAKRQDIKSD GFSIETCKIM VDMLDEDGSG KLGLKEFYIL
WTKIQKYQKI YREIDVDRSG TMNSYEMRKA LEEAGFKLPC QLHQVIVARF ADDELIIDFD
NFVRCLVRLE TLFKIFKQLD PENTGTIQLN LASWLSFSVL
