CAN3_BOVIN
ID CAN3_BOVIN Reviewed; 822 AA.
AC P51186; O97700; Q9TTH9;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 16-JUN-2003, sequence version 2.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Calpain-3;
DE EC=3.4.22.54;
DE AltName: Full=Calcium-activated neutral proteinase 3;
DE Short=CANP 3;
DE AltName: Full=Calpain L3;
DE AltName: Full=Calpain p94;
DE AltName: Full=Muscle-specific calcium-activated neutral protease 3;
DE AltName: Full=New calpain 1;
DE Short=nCL-1;
GN Name=CAPN3; Synonyms=NCL1;
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 [MRNA].
RC TISSUE=Skeletal muscle;
RX PubMed=10612236; DOI=10.1046/j.1365-2052.1999.00550.x;
RA Nonneman D., Koohmaraie M.;
RT "Molecular cloning and mapping of the bovine and ovine skeletal muscle-
RT specific calpains.";
RL Anim. Genet. 30:456-458(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 278-394.
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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 288-604.
RX PubMed=11204692; DOI=10.2527/2001.791122x;
RA Ilian M.A., Morton J.D., Kent M.P., Le Couteur C.E., Hickford J.,
RA Cowley R., Bickerstaffe R.;
RT "Intermuscular variation in tenderness: association with the ubiquitous and
RT muscle-specific calpains.";
RL J. Anim. Sci. 79:122-132(2001).
CC -!- FUNCTION: Calcium-regulated non-lysosomal thiol-protease.
CC Proteolytically cleaves CTBP1. Mediates, with UTP25, the proteasome-
CC independent degradation of p53/TP53. {ECO:0000250|UniProtKB:P20807}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Broad endopeptidase activity.; EC=3.4.22.54;
CC -!- ACTIVITY REGULATION: Activated by micromolar concentrations of calcium
CC and inhibited by calpastatin.
CC -!- SUBUNIT: Homodimer; via EF-hand domain 4. Interacts with TTN/titin.
CC Interacts with CMYA5; this interaction, which results in CMYA5
CC proteolysis, may protect CAPN3 from autolysis. Interacts with SIMC1.
CC Interacts with UTP25; the interaction is required for CAPN3
CC translocation to the nucleolus. {ECO:0000250|UniProtKB:P20807}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P20807}.
CC Nucleus, nucleolus {ECO:0000250|UniProtKB:P20807}.
CC -!- TISSUE SPECIFICITY: Skeletal muscle.
CC -!- SIMILARITY: Belongs to the peptidase C2 family. {ECO:0000305}.
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DR EMBL; AF087569; AAF23261.1; -; mRNA.
DR EMBL; U07858; AAC24459.1; -; mRNA.
DR EMBL; AF115744; AAD05333.1; -; mRNA.
DR RefSeq; NP_776685.1; NM_174260.2.
DR AlphaFoldDB; P51186; -.
DR SMR; P51186; -.
DR STRING; 9913.ENSBTAP00000011677; -.
DR MEROPS; C02.004; -.
DR PaxDb; P51186; -.
DR PRIDE; P51186; -.
DR GeneID; 281663; -.
DR KEGG; bta:281663; -.
DR CTD; 825; -.
DR eggNOG; KOG0045; Eukaryota.
DR InParanoid; P51186; -.
DR OrthoDB; 704215at2759; -.
DR BRENDA; 3.4.22.54; 908.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0030016; C:myofibril; ISS:UniProtKB.
DR GO; GO:0005730; C:nucleolus; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; ISS:UniProtKB.
DR GO; GO:0030315; C:T-tubule; ISS:UniProtKB.
DR GO; GO:0030018; C:Z disc; 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:0003824; F:catalytic activity; ISS:UniProtKB.
DR GO; GO:0055103; F:ligase regulator activity; ISS:UniProtKB.
DR GO; GO:0060090; F:molecular adaptor activity; ISS:UniProtKB.
DR GO; GO:0008233; F:peptidase activity; ISS:UniProtKB.
DR GO; GO:0031402; F:sodium ion binding; ISS:UniProtKB.
DR GO; GO:0008307; F:structural constituent of muscle; ISS:UniProtKB.
DR GO; GO:0031432; F:titin binding; ISS:UniProtKB.
DR GO; GO:1990092; P:calcium-dependent self proteolysis; ISS:UniProtKB.
DR GO; GO:0071277; P:cellular response to calcium ion; ISS:UniProtKB.
DR GO; GO:0071472; P:cellular response to salt stress; ISS:UniProtKB.
DR GO; GO:0061061; P:muscle structure development; ISS:UniProtKB.
DR GO; GO:0030239; P:myofibril assembly; ISS:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0033234; P:negative regulation of protein sumoylation; ISS:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISS:UniProtKB.
DR GO; GO:0045862; P:positive regulation of proteolysis; ISS:UniProtKB.
DR GO; GO:0051281; P:positive regulation of release of sequestered calcium ion into cytosol; ISS:UniProtKB.
DR GO; GO:0014718; P:positive regulation of satellite cell activation involved in skeletal muscle regeneration; ISS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0030163; P:protein catabolic process; ISS:UniProtKB.
DR GO; GO:0072657; P:protein localization to membrane; ISS:UniProtKB.
DR GO; GO:0065003; P:protein-containing complex assembly; ISS:UniProtKB.
DR GO; GO:0006508; P:proteolysis; ISS:UniProtKB.
DR GO; GO:0050790; P:regulation of catalytic activity; ISS:UniProtKB.
DR GO; GO:0043122; P:regulation of I-kappaB kinase/NF-kappaB signaling; ISS:UniProtKB.
DR GO; GO:0051592; P:response to calcium ion; ISS:UniProtKB.
DR GO; GO:0014850; P:response to muscle activity; ISS:UniProtKB.
DR GO; GO:0045214; P:sarcomere organization; 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; IPR029531; CAPN3.
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:SF329; PTHR10183:SF329; 1.
DR Pfam; PF01067; Calpain_III; 1.
DR Pfam; PF13202; EF-hand_5; 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 SMART; SM00054; EFh; 3.
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 Calcium; Cytoplasm; Hydrolase; Metal-binding; Nucleus; Protease;
KW Reference proteome; Repeat; Thiol protease.
FT CHAIN 1..822
FT /note="Calpain-3"
FT /id="PRO_0000207705"
FT DOMAIN 74..418
FT /note="Calpain catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00239"
FT DOMAIN 650..684
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 693..726
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 723..758
FT /note="EF-hand 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 788..822
FT /note="EF-hand 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REGION 1..36
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 419..587
FT /note="Domain III"
FT REGION 588..650
FT /note="Linker"
FT REGION 604..652
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 651..822
FT /note="Domain IV"
FT COMPBIAS 614..631
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 129
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00239"
FT ACT_SITE 335
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00239"
FT ACT_SITE 359
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00239"
FT BINDING 663
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P20807"
FT BINDING 666
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P20807"
FT BINDING 668
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P20807"
FT BINDING 673
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P20807"
FT BINDING 706
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 708
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 710
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 712
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 717
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 736
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 738
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 740
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 742
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 747
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 801
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P20807"
FT BINDING 803
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P20807"
FT BINDING 805
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P20807"
FT BINDING 807
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P20807"
FT CONFLICT 282
FT /note="K -> N (in Ref. 2; AAC24459)"
FT /evidence="ECO:0000305"
FT CONFLICT 308..309
FT /note="GC -> V (in Ref. 2; AAC24459)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 822 AA; 94603 MW; AEDE66F67508D743 CRC64;
MPTVISASVA PRTGAEPMSP GPIAQAAQDK GTEAGGGNPS GIYSAIISRN FPIIGVKEKT
FEQLHKKCLE KKVLFVDPEF PPDETSLFYS QKFPIQFVWK RPPEICENPR FIVGGANRTD
ICQGDLGDCW FLAAIACLTL NKRLLFRVIP HDQSFTENYA GIFHFQFWRY GDWVDVVIDD
CLPTYNNQLV FTKSNHRNEF WNALLEKAYA KLHGSYEALK GGNTTEAMED FTGGVTEFFE
IKDAPRDMYK IMKKAIERGS LMGCSIDDGT NMTYGTSPSG LKMGELIERM VRNMDNSRLR
DSDLIPEGCS DDRPTRMIVP VQFETRMACG LVKGHAYSVT GLEEALYKGE KVKLVRLRNP
WGQVEWNGSW SDSWKDWSYV DKDEKARLQH QVTEDGEFWM SYDDFIYHFT KLEICNLTAD
ALESDKLQTW TVSVNEGRWV RGCSAGGCRN FPDTFWTNPQ YRLKLLEEDD DPDDSEVICS
FLVALMQKNR RKDRKLGANL FTIGFAIYEV PKEMHGNKQH LQKDFFLYNA SKARSRTYIN
MREVSERFRL PPSEYVIVPS TYEPHQEGEF ILRVFSEKRN LSEEVENTIS VDRPVKKKKN
KPIIFVSDRA NSNKELGVDQ ETEEGKDNTS PDKQAKSPQL EPGNTDQESE EQRQFRNIFR
QIAGDDMEIC ADELKNVLNR VVNKHKDLKT QGFTLESCRS MIALMDTDGS GRLNLQEFHH
LWKKIKTWQK IFKHYDTDQS GTINSYEMRN AVKDAGFHLN NQLYDIITMR YADKYMNIDF
DSFICCFVRL EGMFRAFNAF DKDGDGIIKL NVLEWLQLTM YA
