ID   CAN1_PONAB              Reviewed;         714 AA.
AC   Q5NVS7;
DT   24-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT   04-JAN-2005, sequence version 1.
DT   22-FEB-2023, entry version 109.
DE   RecName: Full=Calpain-1 catalytic subunit {ECO:0000305};
DE            EC=3.4.22.52 {ECO:0000250|UniProtKB:P07384};
DE   AltName: Full=Calcium-activated neutral proteinase 1 {ECO:0000250|UniProtKB:P07384};
DE            Short=CANP 1 {ECO:0000250|UniProtKB:P07384};
DE   AltName: Full=Calpain mu-type {ECO:0000250|UniProtKB:P07384};
DE   AltName: Full=Calpain-1 large subunit;
DE   AltName: Full=Micromolar-calpain {ECO:0000250|UniProtKB:P07384};
DE            Short=muCANP {ECO:0000250|UniProtKB:P07384};
GN   Name=CAPN1 {ECO:0000250|UniProtKB:P07384};
OS   Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Pongo.
OX   NCBI_TaxID=9601;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain cortex;
RG   The German cDNA consortium;
RL   Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
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 CTBP1.
CC       Cleaves and activates caspase-7 (CASP7).
CC       {ECO:0000250|UniProtKB:P07384}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Broad endopeptidase specificity.; EC=3.4.22.52;
CC         Evidence={ECO:0000250|UniProtKB:P07384};
CC   -!- COFACTOR:
CC       Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC         Evidence={ECO:0000250|UniProtKB:P07384};
CC       Note=Binds 4 Ca(2+) ions. {ECO:0000250|UniProtKB:P07384};
CC   -!- ACTIVITY REGULATION: Activated by micromolar concentrations of calcium
CC       and inhibited by calpastatin. {ECO:0000250|UniProtKB:P07384}.
CC   -!- SUBUNIT: Forms a heterodimer with a small (regulatory) subunit CAPNS1.
CC       {ECO:0000250|UniProtKB:P97571}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P07384}. Cell
CC       membrane {ECO:0000250|UniProtKB:P07384}. Note=Translocates to the
CC       plasma membrane upon Ca(2+) binding. {ECO:0000250|UniProtKB:P07384}.
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|UniProtKB:P07384}.
CC   -!- SIMILARITY: Belongs to the peptidase C2 family. {ECO:0000305}.
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DR   EMBL; CR925924; CAI29586.1; -; mRNA.
DR   RefSeq; NP_001127061.1; NM_001133589.1.
DR   AlphaFoldDB; Q5NVS7; -.
DR   SMR; Q5NVS7; -.
DR   STRING; 9601.ENSPPYP00000003556; -.
DR   MEROPS; C02.001; -.
DR   GeneID; 100174090; -.
DR   KEGG; pon:100174090; -.
DR   CTD; 823; -.
DR   eggNOG; KOG0045; Eukaryota.
DR   InParanoid; Q5NVS7; -.
DR   OrthoDB; 142935at2759; -.
DR   Proteomes; UP000001595; Unplaced.
DR   GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR   GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
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   GO; GO:0050790; P:regulation of catalytic activity; ISS:UniProtKB.
DR   GO; GO:0097264; P:self proteolysis; ISS:UniProtKB.
DR   CDD; cd00214; Calpain_III; 1.
DR   CDD; cd00044; CysPc; 1.
DR   CDD; cd16198; EFh_PEF_CAPN1; 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; 3.
DR   PROSITE; PS00139; THIOL_PROTEASE_CYS; 1.
PE   2: Evidence at transcript level;
KW   Autocatalytic cleavage; Calcium; Cell membrane; Cytoplasm; Hydrolase;
KW   Membrane; Metal-binding; Phosphoprotein; Protease; Reference proteome;
KW   Repeat; Thiol protease.
FT   CHAIN           1..714
FT                   /note="Calpain-1 catalytic subunit"
FT                   /id="PRO_0000207698"
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:0000305"
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;  81854 MW;  40613EBE7FBD7D3A CRC64;
     MSEEIITPVY CTGVSAQVQK QRARELGLGR HENAIKYLGQ DYEQLRVRCL QSGTLFRDEA
     FPPVPQSLGY KDLGPNSSKT YGIKWKRPTE LLSNPQFIVD GATRTDICQG ALGDCWLLAA
     IASLTLNDTL LHRVVPHGQS FQNGYAGIFH FQLWQFGEWV DVVVDDLLPI KDGKLVFVHS
     AEGNEFWSAL LEKAYAKVNG SYEALSGGST SEGFEDFTGG VTEWYELRKA PSDLYQIILK
     ALERGSLLGC SIDISSVLDM EAITFKKLVK GHAYSVTGAK QVNYRGQMVS LIRMRNPWGE
     VEWTGAWSDS SSEWNNVDPY ERDQLRVKME DGEFWMSFRD FMREFTRLEI CNLTPDALKS
     RTIRKWNTTL YEGTWRRGST AGGCRNYPAT FWVNPQFKIR LDETDDPDDY GDRESGCSFV
     LALMQKHRRR ERRFGRDMET IGFAVYEVPP ELAGQPAVHL KRDFFLANAS RARSEQFINL
     REVSTRFRLP PGEYVVVPST FEPNKEGDFV LRFFSEKSAG TAELDDQIQA NLPDEQVLSE
     EEIDENFKAL FRQLAGEDME TSVKELRTIL NRIISKHKDL RTKGFSLESC RSMVNLMDRD
     GNGKLGLVEF NILWNRIRNY LSIFRKFDLD KSGSMSAYEM RMAIESAGFK LNKKLYELII
     TRYSEPDLAV DFDNFVCCLV RLETMFRFFK TLDTDLDGVV TFDLFKWLQL TMFA
//