ID CAN2_MACFA Reviewed; 700 AA.
AC Q9GLG1;
DT 19-JUL-2003, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 24-JAN-2024, entry version 142.
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 Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9541;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Retina;
RX PubMed=11406271; DOI=10.1016/s0167-4781(01)00212-3;
RA Nakajima T., Fukiage C., Azuma M., Ma H., Shearer T.R.;
RT "Different expression patterns for ubiquitous calpains and Capn3 splice
RT variants in monkey ocular tissues.";
RL Biochim. Biophys. Acta 1519:55-64(2001).
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 -!- 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; AF284441; AAG22771.1; -; mRNA.
DR RefSeq; NP_001274615.1; NM_001287686.1.
DR AlphaFoldDB; Q9GLG1; -.
DR SMR; Q9GLG1; -.
DR STRING; 9541.ENSMFAP00000033269; -.
DR MEROPS; C02.002; -.
DR VEuPathDB; HostDB:ENSMFAG00000003091; -.
DR eggNOG; KOG0045; Eukaryota.
DR OMA; ELNLVNW; -.
DR OrthoDB; 142935at2759; -.
DR BRENDA; 3.4.22.53; 1793.
DR Proteomes; UP000233100; Chromosome 1.
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_0000026489"
FT CHAIN 20..700
FT /note="Calpain-2 catalytic subunit"
FT /id="PRO_0000026490"
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 DOMAIN 667..700
FT /note="EF-hand 3"
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 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"
SQ SEQUENCE 700 AA; 80026 MW; DCEE16214F05057C CRC64;
MAGIAAKLVK DREAAEGLGS HERAIKYLNQ DYEALRNECL EAGTLFQDPS FPAIPSALGF
KELGPYSSKT RGIEWKRPTE ICADPQFIIG GATRTDICQG ALGDCWLLAA IASLTLNEEI
LARVVPLNQS FQENYAGIFH FQFWQYGEWV EVVVDDRLPT KDGELLFVHS AEGSEFWSAL
LEKAYAKING CYEALSGGAT TEGFEDFTGG IAEWYELKKP PPNLFKIIQK ALQKGSLLGC
SIDITSAADS EAITYQKLVK GHAYSVTGAE EVESSGSLQK LIRIRNPWGE VEWTGRWNDN
CPSWNTIDPE ERERLTRRHE DGEFWMSFSD FLRHYSRLEI CNLTPDTLTS DTYKKWKLTK
MDGNWRRGST AGGCRNYPNT FWMNPQYLIK LEEEDEDEED GESGCTFLVG LIQKHRRRQR
KMGEDMHTIG FGIYEVPEEL SGQTNIHLSK NFFLTNRARE RSDTFINLRE VLNRFKLPPG
EYILVPSTFE PNKDGDFCIR VFSEKKADYQ AVDDEIEANL EEFDISEDDI DDGFRRLFAQ
LAGEDAEISA FELQTILRRV LAKRQDIKSD GFSIETCKIM VDMLDSDGSG KLGLKEFYIL
WTKIQKYQKI YREIDVDRSG TMNSYEMRKA LEEAGFKMPC QLHQVIVARF ADDQLIIDFD
NFVRCLVRLE TLFKIFKQLD PENTGTIELD LISWLCFSVL
//
