CAN1_BOVIN
ID CAN1_BOVIN Reviewed; 716 AA.
AC Q27970; Q9N0U3; Q9N0V6; Q9N185;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 12-DEC-2006, sequence version 3.
DT 03-AUG-2022, entry version 169.
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 {ECO:0000250|UniProtKB:P07384};
DE AltName: Full=Micromolar-calpain {ECO:0000250|UniProtKB:P07384};
DE Short=muCANP {ECO:0000250|UniProtKB:P07384};
GN Name=CAPN1 {ECO:0000250|UniProtKB:P07384, ECO:0000303|PubMed:11048924};
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=11048924; DOI=10.2527/2000.78102589x;
RA Smith T.P.L., Casas E., Rexroad C.E. III, Kappes S.M., Keele J.W.;
RT "Bovine CAPN1 maps to a region of BTA29 containing a quantitative trait
RT locus for meat tenderness.";
RL J. Anim. Sci. 78:2589-2594(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Smith T.P.L., Casas E., Rexroad C.E., Kappes S.M., Keele J.W.;
RT "Bovine CAPN1 maps to a region containing a QTL for meat tenderness.";
RL Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Fetal muscle;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (SEP-2006) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 530-625.
RC TISSUE=Skeletal muscle;
RA Sun W., Bidwell C.A., Ji S., Hancock D.L.;
RL Submitted (APR-1994) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP PROTEIN SEQUENCE OF 16-41.
RX PubMed=2065086; DOI=10.1016/0167-4838(91)99009-h;
RA Zimmerman U.J., Schlaepfer W.W.;
RT "Two-stage autolysis of the catalytic subunit initiates activation of
RT calpain I.";
RL Biochim. Biophys. Acta 1078:192-198(1991).
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 {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}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA18454.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF248054; AAF64504.2; -; Genomic_DNA.
DR EMBL; AF252504; AAF64504.2; JOINED; Genomic_DNA.
DR EMBL; AF221129; AAF32364.1; -; mRNA.
DR EMBL; BC123635; AAI23636.1; -; mRNA.
DR EMBL; U07849; AAA18454.1; ALT_FRAME; mRNA.
DR PIR; S16181; S16181.
DR RefSeq; NP_776684.1; NM_174259.2.
DR AlphaFoldDB; Q27970; -.
DR SMR; Q27970; -.
DR IntAct; Q27970; 1.
DR MINT; Q27970; -.
DR STRING; 9913.ENSBTAP00000011678; -.
DR MEROPS; C02.001; -.
DR PaxDb; Q27970; -.
DR PeptideAtlas; Q27970; -.
DR PRIDE; Q27970; -.
DR GeneID; 281661; -.
DR KEGG; bta:281661; -.
DR CTD; 823; -.
DR eggNOG; KOG0045; Eukaryota.
DR HOGENOM; CLU_010982_0_1_1; -.
DR InParanoid; Q27970; -.
DR OrthoDB; 704215at2759; -.
DR TreeFam; TF314748; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
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 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 1: Evidence at protein level;
KW Autocatalytic cleavage; Calcium; Cell membrane; Cytoplasm;
KW Direct protein sequencing; Hydrolase; Membrane; Metal-binding;
KW Phosphoprotein; Protease; Reference proteome; Repeat; Thiol protease.
FT CHAIN 1..716
FT /note="Calpain-1 catalytic subunit"
FT /id="PRO_0000207693"
FT DOMAIN 55..354
FT /note="Calpain catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00239"
FT DOMAIN 543..578
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 587..620
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 617..652
FT /note="EF-hand 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 682..716
FT /note="EF-hand 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REGION 355..528
FT /note="Domain III"
FT REGION 529..544
FT /note="Linker"
FT REGION 545..715
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 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 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 606
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 611
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
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 636
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 641
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"
FT CONFLICT 21
FT /note="Q -> T (in Ref. 5; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 316
FT /note="G -> A (in Ref. 1; AAF64504)"
FT /evidence="ECO:0000305"
FT CONFLICT 381
FT /note="A -> V (in Ref. 1; AAF64504)"
FT /evidence="ECO:0000305"
FT CONFLICT 530
FT /note="V -> I (in Ref. 4; AAA18454)"
FT /evidence="ECO:0000305"
FT CONFLICT 624
FT /note="S -> A (in Ref. 4; AAA18454)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 716 AA; 82207 MW; A7F55C197BD5DF23 CRC64;
MAEEFITPVY CTGVSAQVQK QRAKELGLGR HENAIKYLGQ DYEQLRVHCL QRGALFRDEA
FPPVPQSLGF KELGPNSSKT YGIKWKRPTE LFSNPQFIVD GATRTDICQG ALGDCWLLAA
IASLTLNDTL LHRVVPHGQS FQDGYAGIFH FQLWQFGEWV DVVVDDLLPT KDGKLVFVHS
AQGNEFWSAL LEKAYAKVNG SYEALSGGST SEGFEDFTGG VTEWYELRKA PSDLYNIILK
ALERGSLLGC SIDISSILDM EAVTFKKLVK GHAYSVTGAK QVNYQGQMVN LIRMRNPWGE
VEWTGAWSDG SSEWNGVDPY MREQLRVKME DGEFWMSFRD FMREFTRLEI CNLTPDALKS
QRFRNWNTTL YEGTWRRGST AGGCRNYPAT FWVNPQFKIR LEETDDPDPD DYGGRESGCS
FLLALMQKHR RRERRFGRDM ETIGFAVYEV PPELMGQPAV HLKRDFFLSN ASRARSEQFI
NLREVSTRFR LPPGEYVVVP STFEPNKEGD FVLRFFSEKS AGTQELDDQV QANLPDEQVL
SEEEIDENFK SLFRQLAGED MEISVKELRT ILNRIISKHK DLRTTGFSLE SCRSMVNLMD
RDGNGKLGLV EFNILWNRIR NYLSIFRKFD LDKSGSMSAY EMRMAIEFAG FKLNKKLYEL
IITRYSEPDL AVDFDNFVCC LVRLETMFRF FKTLDTDLDG VVTFDLFKWL QLTMFA
