ID CAN2_PIG Reviewed; 324 AA. AC P43367; DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1997, sequence version 2. DT 08-NOV-2023, entry version 150. 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: Fragment; GN Name=CAPN2; OS Sus scrofa (Pig). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus. OX NCBI_TaxID=9823; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-209. RC TISSUE=Skeletal muscle; RX PubMed=8312396; DOI=10.1016/0300-9084(93)90051-s; RA Sun W., Ji S.Q., Ebert P.J., Bidwell C.A., Hancock D.L.; RT "Cloning the partial cDNAs of mu-calpain and m-calpain from porcine RT skeletal muscle."; RL Biochimie 75:931-936(1993). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] OF 122-324. RC TISSUE=Pulmonary artery; RX PubMed=9728040; DOI=10.1152/ajplung.1998.275.3.l461; RA Zhang J.L., Patel J.M., Block E.R.; RT "Hypoxia-specific upregulation of calpain activity and gene expression in RT pulmonary artery endothelial cells."; RL Am. J. Physiol. 275:L461-L468(1998). 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 --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U01181; AAC48401.1; -; mRNA. DR EMBL; U71320; AAB17381.1; -; mRNA. DR AlphaFoldDB; P43367; -. DR SMR; P43367; -. DR STRING; 9823.ENSSSCP00000026311; -. DR BindingDB; P43367; -. DR ChEMBL; CHEMBL4143; -. DR MEROPS; C95.001; -. DR PaxDb; 9823-ENSSSCP00000026311; -. DR PeptideAtlas; P43367; -. DR eggNOG; KOG0045; Eukaryota. DR InParanoid; P43367; -. DR BRENDA; 3.4.22.53; 6170. DR Proteomes; UP000008227; Unplaced. DR Proteomes; UP000314985; Unplaced. DR Proteomes; UP000694570; Unplaced. DR Proteomes; UP000694571; Unplaced. DR Proteomes; UP000694720; Unplaced. DR Proteomes; UP000694722; Unplaced. DR Proteomes; UP000694723; Unplaced. DR Proteomes; UP000694724; Unplaced. DR Proteomes; UP000694725; Unplaced. DR Proteomes; UP000694726; Unplaced. DR Proteomes; UP000694727; Unplaced. DR Proteomes; UP000694728; Unplaced. 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 Gene3D; 2.60.120.380; -; 1. DR Gene3D; 1.10.238.10; EF-hand; 1. DR InterPro; IPR033883; C2_III. 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 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 SMART; SM00720; calpain_III; 1. DR SUPFAM; SSF49758; Calpain large subunit, middle domain (domain III); 1. DR SUPFAM; SSF47473; EF-hand; 1. DR PROSITE; PS00018; EF_HAND_1; 1. DR PROSITE; PS50222; EF_HAND_2; 1. PE 2: Evidence at transcript level; KW Calcium; Cell membrane; Cytoplasm; Hydrolase; Membrane; Metal-binding; KW Protease; Reference proteome; Repeat; Thiol protease. FT CHAIN <1..324 FT /note="Calpain-2 catalytic subunit" FT /id="PRO_0000207703" FT DOMAIN 190..224 FT /note="EF-hand 1" FT /evidence="ECO:0000305" FT DOMAIN 226..261 FT /note="EF-hand 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT REGION <1..138 FT /note="Domain III" FT REGION 139..153 FT /note="Linker" FT REGION 158..324 FT /note="Domain IV" FT BINDING 166 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="5" FT /evidence="ECO:0000250" FT BINDING 169 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="5" FT /evidence="ECO:0000250" FT BINDING 171 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="5" FT /evidence="ECO:0000250" FT BINDING 176 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="5" FT /evidence="ECO:0000250" FT BINDING 209 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="6" FT /evidence="ECO:0000250" FT BINDING 211 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="6" FT /evidence="ECO:0000250" FT BINDING 213 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="6" FT /evidence="ECO:0000250" FT BINDING 215 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="6" FT /evidence="ECO:0000250" FT BINDING 220 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="6" FT /evidence="ECO:0000250" FT BINDING 239 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="7" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 241 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="7" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 243 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="7" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 245 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="7" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 250 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="7" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 282 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250" FT BINDING 285 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250" FT CONFLICT 202 FT /note="R -> K (in Ref. 2; AAB17381)" FT /evidence="ECO:0000305" FT NON_TER 1 SQ SEQUENCE 324 AA; 37809 MW; 3929553239E123CF CRC64; YPNTFWMNPQ YLIKLEEEDE DQEDGESGCT FLVGLIQKHR RRQRKMGEDM HTIGFGIYEV PEELTGQTNI HLSKNFFLTH RARERSDTFI NLREVLNRFK LPPGEYILVP STFEPNKDGD FCIRVFSEKK ADYQVVDDEI EADLEENDAS EDDIDDGFRR LFAQLAGEDA EISAFELQTI LRRVLAKRQD IKSDGFSIET CRIMVDMLDS DGSAKLGLKE FYILWTKIQK YQKIYREIDV DRSGTMNSYE MRKALEEAGF KLPCQLHQVI VARFADDQLI IDFDNFVRCL VRLETLFRIS KQLDSENTGT IELDLISWLC FSVL //