ID   CAN2_RABIT              Reviewed;         422 AA.
AC   P06814;
DT   01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT   01-JAN-1988, sequence version 1.
DT   08-NOV-2023, entry version 156.
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   Oryctolagus cuniculus (Rabbit).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX   NCBI_TaxID=9986;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=2424911; DOI=10.1016/s0021-9258(18)67679-3;
RA   Emori Y., Kawasaki H., Sugihara H., Imajoh S., Kawashima S., Suzuki K.;
RT   "Isolation and sequence analyses of cDNA clones for the large subunits of
RT   two isozymes of rabbit calcium-dependent protease.";
RL   J. Biol. Chem. 261:9465-9471(1986).
RN   [2]
RP   CALCIUM-BINDING DATA.
RX   PubMed=3038855; DOI=10.1093/oxfordjournals.jbchem.a121956;
RA   Minami Y., Emori Y., Kawasaki H., Suzuki K.;
RT   "E-F hand structure-domain of calcium-activated neutral protease (CANP) can
RT   bind Ca2+ ions.";
RL   J. Biochem. 101:889-895(1987).
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. Cell membrane. Note=Translocates to
CC       the plasma membrane upon Ca(2+) binding.
CC   -!- TISSUE SPECIFICITY: Ubiquitous.
CC   -!- SIMILARITY: Belongs to the peptidase C2 family. {ECO:0000305}.
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DR   EMBL; M13797; AAA31455.1; -; mRNA.
DR   PIR; B24815; B24815.
DR   AlphaFoldDB; P06814; -.
DR   SMR; P06814; -.
DR   STRING; 9986.ENSOCUP00000017627; -.
DR   MEROPS; C02.972; -.
DR   PaxDb; 9986-ENSOCUP00000017627; -.
DR   eggNOG; KOG0045; Eukaryota.
DR   InParanoid; P06814; -.
DR   BRENDA; 3.4.22.53; 1749.
DR   Proteomes; UP000001811; 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; 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; IPR038765; Papain-like_cys_pep_sf.
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; SM00054; EFh; 3.
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.
PE   1: Evidence at protein level;
KW   Calcium; Cell membrane; Cytoplasm; Hydrolase; Membrane; Metal-binding;
KW   Protease; Reference proteome; Repeat; Thiol protease.
FT   CHAIN           <1..422
FT                   /note="Calpain-2 catalytic subunit"
FT                   /id="PRO_0000207704"
FT   DOMAIN          <1..66
FT                   /note="Calpain catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00239"
FT   DOMAIN          294..327
FT                   /note="EF-hand 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   DOMAIN          324..359
FT                   /note="EF-hand 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   DOMAIN          389..422
FT                   /note="EF-hand 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   REGION          67..236
FT                   /note="Domain III"
FT   REGION          237..251
FT                   /note="Linker"
FT   REGION          252..422
FT                   /note="Domain IV"
FT   ACT_SITE        8
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00239,
FT                   ECO:0000255|PROSITE-ProRule:PRU10088, ECO:0000255|PROSITE-
FT                   ProRule:PRU10089, ECO:0000255|PROSITE-ProRule:PRU10090"
FT   BINDING         14
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="4"
FT                   /evidence="ECO:0000250"
FT   BINDING         21
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="4"
FT                   /evidence="ECO:0000250"
FT   BINDING         45
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="4"
FT                   /evidence="ECO:0000250"
FT   BINDING         264
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="5"
FT                   /evidence="ECO:0000250"
FT   BINDING         267
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="5"
FT                   /evidence="ECO:0000250"
FT   BINDING         269
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="5"
FT                   /evidence="ECO:0000250"
FT   BINDING         274
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="5"
FT                   /evidence="ECO:0000250"
FT   BINDING         307
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="6"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT                   ECO:0000269|PubMed:3038855"
FT   BINDING         309
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="6"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT                   ECO:0000269|PubMed:3038855"
FT   BINDING         311
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="6"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT                   ECO:0000269|PubMed:3038855"
FT   BINDING         313
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="6"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT                   ECO:0000269|PubMed:3038855"
FT   BINDING         318
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT                   ECO:0000269|PubMed:3038855"
FT   BINDING         337
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="7"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT                   ECO:0000269|PubMed:3038855"
FT   BINDING         339
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="7"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT                   ECO:0000269|PubMed:3038855"
FT   BINDING         341
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="7"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT                   ECO:0000269|PubMed:3038855"
FT   BINDING         343
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="7"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT                   ECO:0000269|PubMed:3038855"
FT   BINDING         348
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="7"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT                   ECO:0000269|PubMed:3038855"
FT   BINDING         380
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   BINDING         383
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   NON_TER         1
SQ   SEQUENCE   422 AA;  49494 MW;  AE4FA3C48A333C41 CRC64;
     QKLIRIRNPW GEVEWTGRWN DNCPNWNTVD PEVRERLAER HEDGEFWMSF SDFLRHYSRL
     EICNLTPDTL TSDTYKKWKL TKMDGNWRRG STAGGCRNYP NTFWMNPQYV IKLEEEDEDQ
     EDGESGCTFL VGLIQKHRRR QRKMGEDMHT IGFGIYEVPE ELRGQTNIHL GKNFFLTTRA
     RERSDTFINL REVLNRFKLP PGEYILVPST FEPNKNGDFC VRVFSEKKAD YQAVDDEIEA
     DLEEADVSED DIDDGFRRLF AQLAGEDAEI SAFELQNILR RVLAKRQDIK TDGLSIETCK
     IMVDMLDSDG TGKLGLKEFY VLWTKIQKYQ KIYREIDVDR SGTMNSYEMR KALEEAGFKL
     PCQLHEVIVA RFADDQLIID FDNFVRCLVR LETLFKIFKQ LDPDNTGMIQ LDLISWLCFS
     VL
//