ID   CAN1_MACFA              Reviewed;         714 AA.
AC   Q9GLG2; Q4R593;
DT   19-JUL-2003, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2001, sequence version 1.
DT   10-JUN-2026, entry version 137.
DE   RecName: Full=Calpain-1 catalytic subunit;
DE            EC=3.4.22.52;
DE   AltName: Full=Calcium-activated neutral proteinase 1;
DE            Short=CANP 1;
DE   AltName: Full=Calpain mu-type;
DE   AltName: Full=Calpain-1 large subunit;
DE   AltName: Full=Micromolar-calpain;
DE            Short=muCANP;
GN   Name=CAPN1; Synonyms=CANPL1; ORFNames=QccE-12457;
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).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain cortex;
RG   International consortium for macaque cDNA sequencing and analysis;
RT   "DNA sequences of macaque genes expressed in brain or testis and its
RT   evolutionary implications.";
RL   Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Calcium-regulated non-lysosomal thiol-protease which catalyze
CC       limited proteolysis of substrates involved in cytoskeletal remodeling
CC       and signal transduction. Proteolytically cleaves CTBP1. Cleaves and
CC       activates caspase-7 (CASP7). {ECO:0000250|UniProtKB:P07384}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Broad endopeptidase specificity.; EC=3.4.22.52;
CC   -!- COFACTOR:
CC       Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000250};
CC       Note=Binds 4 Ca(2+) ions. {ECO:0000250};
CC   -!- ACTIVITY REGULATION: Activated by micromolar concentrations of calcium
CC       and inhibited by calpastatin. {ECO:0000250}.
CC   -!- SUBUNIT: Forms a heterodimer with a small (regulatory) subunit
CC       (CAPNS1).
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   -!- PTM: Undergoes calcium-induced successive autoproteolytic cleavages
CC       that generate a membrane-bound 78 kDa active form and an intracellular
CC       75 kDa active form. Calpastatin reduces with high efficiency the
CC       transition from 78 kDa to 75 kDa calpain forms (By similarity).
CC       {ECO:0000250}.
CC   -!- PTM: Ubiquitinated via 'Lys6'-, 'Lys27'-, 'Lys29'-, and 'Lys63'-linked
CC       chains by the E3 ubiquitin ligase complex at least composed of CUL3,
CC       KCTD7 and RBX1 to execute atypical, non-degradative ubiquitination.
CC       {ECO:0000250|UniProtKB:P07384}.
CC   -!- SIMILARITY: Belongs to the peptidase C2 family. {ECO:0000305}.
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DR   EMBL; AF284440; AAG22770.1; -; mRNA.
DR   EMBL; AB169651; BAE01732.1; -; mRNA.
DR   RefSeq; XP_005577362.2; XM_005577305.5.
DR   RefSeq; XP_005577364.1; XM_005577307.5.
DR   RefSeq; XP_005577365.3; XM_005577308.4.
DR   RefSeq; XP_015289608.1; XM_015434122.3.
DR   RefSeq; XP_015289609.1; XM_015434123.4.
DR   RefSeq; XP_045228059.1; XM_045372124.2.
DR   RefSeq; XP_065385481.1; XM_065529409.1.
DR   AlphaFoldDB; Q9GLG2; -.
DR   SMR; Q9GLG2; -.
DR   STRING; 9541.ENSMFAP00000003536; -.
DR   MEROPS; C02.001; -.
DR   GeneID; 101867512; -.
DR   KEGG; mcf:101867512; -.
DR   CTD; 823; -.
DR   VEuPathDB; HostDB:ENSMFAG00000001413; -.
DR   eggNOG; KOG0045; Eukaryota.
DR   BRENDA; 3.4.22.52; 1793.
DR   Proteomes; UP000233100; Chromosome 14.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
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:0008233; F:peptidase activity; ISS:UniProtKB.
DR   GO; GO:0006508; P:proteolysis; ISS:UniProtKB.
DR   CDD; cd00214; Calpain_III; 1.
DR   CDD; cd00044; CysPc; 1.
DR   CDD; cd16198; EFh_PEF_CAPN1; 1.
DR   FunFam; 1.10.238.10:FF:000124; Calpain-1 catalytic subunit; 1.
DR   FunFam; 2.60.120.380:FF:000001; Calpain-1 catalytic subunit; 1.
DR   FunFam; 3.90.70.10:FF:000001; Calpain-1 catalytic subunit; 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; IPR000169; Pept_cys_AS.
DR   InterPro; IPR001300; Peptidase_C2_calpain_cat.
DR   PANTHER; PTHR10183; CALPAIN; 1.
DR   PANTHER; PTHR10183:SF284; CALPAIN-1 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; 4.
DR   PROSITE; PS00139; THIOL_PROTEASE_CYS; 1.
PE   2: Evidence at transcript level;
KW   Autocatalytic cleavage; Calcium; Cell membrane; Cytoplasm; Hydrolase;
KW   Isopeptide bond; Membrane; Metal-binding; Phosphoprotein; Protease;
KW   Reference proteome; Repeat; Thiol protease; Ubl conjugation.
FT   CHAIN           1..714
FT                   /note="Calpain-1 catalytic subunit"
FT                   /id="PRO_0000207695"
FT   DOMAIN          55..354
FT                   /note="Calpain catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00239"
FT   DOMAIN          541..576
FT                   /note="EF-hand 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   DOMAIN          585..618
FT                   /note="EF-hand 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   DOMAIN          615..650
FT                   /note="EF-hand 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   DOMAIN          680..714
FT                   /note="EF-hand 4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   REGION          355..526
FT                   /note="Domain III"
FT   REGION          527..542
FT                   /note="Linker"
FT   REGION          543..713
FT                   /note="Domain IV"
FT   ACT_SITE        115
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        272
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        296
FT                   /evidence="ECO:0000250"
FT   BINDING         109
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000305"
FT   BINDING         114
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000305"
FT   BINDING         316
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000305"
FT   BINDING         318
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000305"
FT   BINDING         323
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000305"
FT   BINDING         598
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   BINDING         600
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   BINDING         602
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   BINDING         604
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   BINDING         609
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   BINDING         628
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   BINDING         630
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   BINDING         632
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   BINDING         634
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   BINDING         639
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   SITE            15..16
FT                   /note="Cleavage; for 78 kDa form"
FT                   /evidence="ECO:0000250"
FT   SITE            27..28
FT                   /note="Cleavage; for 75 kDa form"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         354
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:P07384"
SQ   SEQUENCE   714 AA;  81850 MW;  834690C214DE7AD8 CRC64;
     MAEEIITPVY CTGVSAQVQK QRAKELGLGR HENAIKYLGQ DYEQLRARCL QSGTLFRDEA
     FPPVPQSLGF KDLGPNSSKT YGIKWKRPTE LLSNPQFIVD GATRTDICQG ALGDCWLLAA
     IASLTLNDTL LHRVVPHGQS FQNGYAGIFH FQLWQFGEWV DVVVDDLLPI KDGKLVFVHS
     AEGNEFWSAL LEKAYAKVNG SYESLSGGST SEGFEDFTGG VTEWYELRKA PSDLYQIILK
     ALERGSLLGC SIDISSVLDM EAITFKKLVK GHAYSVTGAK QVNYRGQMVN LIRMRNPWGE
     VEWTGAWSDS SSEWNSVDPY EREQLRVKME DGEFWMSFRD FMREFTRLEI CNLTPDALKS
     RTIRKWNTTL YEGTWRRGST AGGCRNYPAT FWVNPQFKIR LDETDDPDDY GDRESGCSFV
     LALMQKHRRR ERRFGRDMET IGFAVYEVPP ELVGQPALHL KRDFFLANAS RARSEQFINL
     REVSTRFRLP PGEYVVVPST FEPNKEGDFV LRFFSEKSAG TAELDDQIQA NLPDEQVLSE
     EEIDENFKAL FRQLAGEDME ISVKELRTIL NRIISKHKDL RTKGFSLESC RSMVNLMDRD
     GNGKLGLVEF NILWNRIRNY LSIFRKFDLD KSGSMSAYEM RMAIESAGFK LNKKLYELII
     TRYSEPDLAV DFDNFVCCLV RLETMFRFFK TLDTDLDGVV TFDLFKWLQL TMFA
//