ID   CAN2_BOVIN              Reviewed;         700 AA.
AC   Q27971; A4IFD3;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   05-FEB-2008, sequence version 2.
DT   24-JAN-2024, entry version 173.
DE   RecName: Full=Calpain-2 catalytic subunit;
DE            EC=3.4.22.53;
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   Bos taurus (Bovine).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Bovinae; Bos.
OX   NCBI_TaxID=9913;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Hereford; TISSUE=Ascending colon;
RG   NIH - Mammalian Gene Collection (MGC) project;
RL   Submitted (MAR-2007) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 377-585.
RC   TISSUE=Skeletal muscle;
RA   Sun W., Bidwell C.A., Ji S., Hancock D.L.;
RT   "Cloning the partial cDNA's for the calpain family of protease genes from
RT   bovine muscle.";
RL   Submitted (APR-1994) to the EMBL/GenBank/DDBJ databases.
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'. Proteolytically cleaves CPEB3 following neuronal stimulation
CC       which abolishes CPEB3 translational repressor activity, leading to
CC       translation of CPEB3 target mRNAs. {ECO:0000250|UniProtKB:O08529,
CC       ECO:0000250|UniProtKB:P17655}.
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
CC       (CAPNS1). Interacts with CPEB3; this leads to cleavage of CPEB3.
CC       {ECO:0000250|UniProtKB:O08529, ECO:0000250|UniProtKB:Q07009}.
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}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAA18455.1; Type=Frameshift; Evidence={ECO:0000305};
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DR   EMBL; BC134526; AAI34527.1; -; mRNA.
DR   EMBL; U07850; AAA18455.1; ALT_FRAME; mRNA.
DR   RefSeq; NP_001096556.1; NM_001103086.1.
DR   AlphaFoldDB; Q27971; -.
DR   SMR; Q27971; -.
DR   CORUM; Q27971; -.
DR   IntAct; Q27971; 3.
DR   MINT; Q27971; -.
DR   STRING; 9913.ENSBTAP00000059970; -.
DR   BindingDB; Q27971; -.
DR   ChEMBL; CHEMBL3612; -.
DR   MEROPS; C02.002; -.
DR   PaxDb; 9913-ENSBTAP00000044733; -.
DR   PeptideAtlas; Q27971; -.
DR   Ensembl; ENSBTAT00000047532.4; ENSBTAP00000044733.3; ENSBTAG00000012778.6.
DR   GeneID; 281662; -.
DR   KEGG; bta:281662; -.
DR   CTD; 824; -.
DR   VEuPathDB; HostDB:ENSBTAG00000012778; -.
DR   VGNC; VGNC:55037; CAPN2.
DR   eggNOG; KOG0045; Eukaryota.
DR   GeneTree; ENSGT00940000154784; -.
DR   HOGENOM; CLU_010982_0_1_1; -.
DR   InParanoid; Q27971; -.
DR   OMA; ELNLVNW; -.
DR   OrthoDB; 142935at2759; -.
DR   TreeFam; TF314748; -.
DR   Reactome; R-BTA-1474228; Degradation of the extracellular matrix.
DR   Proteomes; UP000009136; Chromosome 16.
DR   Bgee; ENSBTAG00000012778; Expressed in myometrium and 105 other cell types or tissues.
DR   ExpressionAtlas; Q27971; baseline.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0030425; C:dendrite; ISS:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR   GO; GO:0004198; F:calcium-dependent cysteine-type endopeptidase activity; ISS:UniProtKB.
DR   GO; GO:0071230; P:cellular response to amino acid stimulus; ISS:UniProtKB.
DR   GO; GO:0006508; P:proteolysis; ISS:UniProtKB.
DR   CDD; cd00214; Calpain_III; 1.
DR   CDD; cd00044; CysPc; 1.
DR   CDD; cd16199; EFh_PEF_CAPN2; 1.
DR   Gene3D; 2.60.120.380; -; 1.
DR   Gene3D; 3.90.70.10; Cysteine proteinases; 1.
DR   Gene3D; 1.10.238.10; EF-hand; 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; 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; CALPAIN; 1.
DR   PANTHER; PTHR10183:SF268; CALPAIN-2 CATALYTIC SUBUNIT; 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; SSF49758; Calpain large subunit, middle domain (domain III); 1.
DR   SUPFAM; SSF54001; Cysteine proteinases; 1.
DR   SUPFAM; SSF47473; EF-hand; 1.
DR   PROSITE; PS50203; CALPAIN_CAT; 1.
DR   PROSITE; PS00018; EF_HAND_1; 2.
DR   PROSITE; PS50222; EF_HAND_2; 3.
DR   PROSITE; PS00139; THIOL_PROTEASE_CYS; 1.
PE   2: Evidence at transcript 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_0000317423"
FT   CHAIN           20..700
FT                   /note="Calpain-2 catalytic subunit"
FT                   /id="PRO_0000207702"
FT   DOMAIN          45..344
FT                   /note="Calpain catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00239"
FT   DOMAIN          572..597
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   DOMAIN          652..672
FT                   /note="EF-hand 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   REGION          345..514
FT                   /note="Domain III"
FT                   /evidence="ECO:0000250"
FT   REGION          515..529
FT                   /note="Linker"
FT                   /evidence="ECO:0000250"
FT   REGION          530..700
FT                   /note="Domain IV"
FT                   /evidence="ECO:0000250"
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         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         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        417
FT                   /note="R -> Q (in Ref. 2; AAA18455)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        460..462
FT                   /note="ERS -> DV (in Ref. 2; AAA18455)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   700 AA;  79935 MW;  00FD932E9C6AB268 CRC64;
     MAGIAAKLAK DREAAEGLGS HERAVKYLNQ DYAALRDECL EAGALFQDPS FPALPSSLGF
     KELGPYSSKT RGIEWKRPTE ICDNPQFITG GATRTDICQG ALGDCWLLAA IASLTLNEEI
     LARVVPLDQS FQENYAGIFH FQFWQYGEWV EVVVDDRLPT KDGELLFVHS AEGSEFWSAL
     LEKAYAKING CYEALSGGAT TEGFEDFTGG IAEWYELRKA PPNLFRIIQK ALQKGSLLGC
     SIDITSAADS EAITFQKLVK GHAYSVTGAE EVESRGSLQK LIRIRNPWGE VEWTGQWNDN
     CPNWNTVDPE VRETLTRQHE DGEFWMSFND FLRHYSRLEI CNLTPDTLTS DSYKKWKLTK
     MDGNWRRGST AGGCRNYPNT FWMNPQYLIK LEEEDEDQED GESGCTFLVG LIQKHRRRQR
     KMGEDMHTIG FGIYEVPEEL TGQTNIHLSK KFFLTTRARE RSDTFINLRE VLNRFKLPPG
     EYIVVPSTFE PNKDGDFCIR VFSEKKADYQ VVDDEIEANI DEIDISEDDI DDGFRRLFAQ
     LAGEDAEISA FELQTILRRV LAKRQDIKSD GFSIETCKIM VDMLDSDGSG KLGLKEFYIL
     WTKIQKYQKI YREIDVDRSG TMNSYEMRKA LEEAGFKMPC QLHQVIVARF ADDDLIIDFD
     NFVRCLIRLE TLFRIFKQLD PENTGMIQLD LISWLSFSVL
//