CAN1_MACFA
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 03-AUG-2022, entry version 126.
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.
CC {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 -!- 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; NP_001272270.1; NM_001285341.1.
DR RefSeq; XP_005577362.2; XM_005577305.2.
DR RefSeq; XP_005577364.1; XM_005577307.2.
DR RefSeq; XP_015289607.1; XM_015434121.1.
DR RefSeq; XP_015289608.1; XM_015434122.1.
DR RefSeq; XP_015289609.1; XM_015434123.1.
DR AlphaFoldDB; Q9GLG2; -.
DR SMR; Q9GLG2; -.
DR STRING; 9541.XP_005577359.1; -.
DR MEROPS; C02.001; -.
DR PRIDE; Q9GLG2; -.
DR GeneID; 101867512; -.
DR KEGG; mcf:101867512; -.
DR CTD; 823; -.
DR VEuPathDB; HostDB:ENSMFAG00000001413; -.
DR eggNOG; KOG0045; Eukaryota.
DR OrthoDB; 704215at2759; -.
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 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; IPR029643; CAPN1.
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:SF284; PTHR10183:SF284; 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; SSF47473; SSF47473; 1.
DR SUPFAM; SSF49758; SSF49758; 1.
DR SUPFAM; SSF54001; SSF54001; 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 Membrane; Metal-binding; Phosphoprotein; Protease; Reference proteome;
KW Repeat; Thiol protease.
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
