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}.
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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
//
