CAN3_PIG
ID CAN3_PIG Reviewed; 821 AA.
AC P43368; O46596; Q28961;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 16-JUN-2003, sequence version 2.
DT 03-AUG-2022, entry version 148.
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 Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE.
RA Sun W., Muir M.W., Hancock D.L., Stuart J.J.;
RT "Cloning the full length cDNA of pig skeletal muscle specific calpain by
RT Polymerase Chain Reaction.";
RL Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE OF 277-651.
RC TISSUE=Skeletal muscle;
RA Ji S.Q., Hancock D.L., Bidwell C.A., Anderson D.B.;
RL Submitted (JAN-1994) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 372-509.
RC TISSUE=Blood;
RX PubMed=8833248; DOI=10.1007/s003359900062;
RA Briley G.P., Riggs P.K., Womack J.E., Hancock D.L., Bidwell C.A.;
RT "Chromosomal localization of the porcine skeletal muscle calpain gene.";
RL Mamm. Genome 7:226-228(1996).
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; AF043295; AAB99847.1; -; mRNA.
DR EMBL; U05678; AAA17032.1; -; mRNA.
DR EMBL; U23954; AAA67685.1; -; Genomic_DNA.
DR RefSeq; NP_999336.1; NM_214171.1.
DR AlphaFoldDB; P43368; -.
DR SMR; P43368; -.
DR STRING; 9823.ENSSSCP00000005095; -.
DR MEROPS; C02.004; -.
DR PaxDb; P43368; -.
DR PeptideAtlas; P43368; -.
DR PRIDE; P43368; -.
DR GeneID; 397349; -.
DR KEGG; ssc:397349; -.
DR CTD; 825; -.
DR eggNOG; KOG0045; Eukaryota.
DR InParanoid; P43368; -.
DR OrthoDB; 704215at2759; -.
DR BRENDA; 3.4.22.54; 6170.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; 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..821
FT /note="Calpain-3"
FT /id="PRO_0000207709"
FT DOMAIN 73..417
FT /note="Calpain catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00239"
FT DOMAIN 649..683
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 692..725
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 722..757
FT /note="EF-hand 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 787..821
FT /note="EF-hand 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REGION 1..34
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 418..586
FT /note="Domain III"
FT REGION 587..649
FT /note="Linker"
FT REGION 603..652
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 650..821
FT /note="Domain IV"
FT COMPBIAS 9..24
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 613..645
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 128
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00239"
FT ACT_SITE 334
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00239"
FT ACT_SITE 358
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00239"
FT BINDING 662
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P20807"
FT BINDING 665
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P20807"
FT BINDING 667
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P20807"
FT BINDING 672
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P20807"
FT BINDING 705
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 707
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 709
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 711
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 716
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 735
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 737
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 739
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 741
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 746
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 800
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P20807"
FT BINDING 802
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P20807"
FT BINDING 804
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P20807"
FT BINDING 806
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P20807"
FT CONFLICT 281
FT /note="K -> N (in Ref. 2; AAA17032)"
FT /evidence="ECO:0000305"
FT CONFLICT 307..308
FT /note="GC -> V (in Ref. 2; AAA17032)"
FT /evidence="ECO:0000305"
FT CONFLICT 446..447
FT /note="GC -> TG (in Ref. 2; AAA17032)"
FT /evidence="ECO:0000305"
FT CONFLICT 446
FT /note="G -> A (in Ref. 3; AAA67685)"
FT /evidence="ECO:0000305"
FT CONFLICT 487
FT /note="K -> R (in Ref. 2; AAA17032)"
FT /evidence="ECO:0000305"
FT CONFLICT 570
FT /note="I -> M (in Ref. 2; AAA17032)"
FT /evidence="ECO:0000305"
FT CONFLICT 579
FT /note="N -> K (in Ref. 2; AAA17032)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 821 AA; 94551 MW; 868E2769AD3AAFDF CRC64;
MPTVISASMA PRTGASQVPR TMPQAAQGKG TEAGVGNPGG KYSAIISRNF PIIGVKEKTF
EQLHKKCLEK KVLYLDPEFP PDETSLFYSQ KFPIQFVWKR PPEICENPRF IIGGANRTDI
CQGDLGDCWF LAAIACLTLN KRLLFRVIPH DQSFTENYAG IFHFQFWRYG DWVDVVIDDC
LPTYNNQLVF TKSNHRNEFW SALLEKAYAK LHGSYEALKG GNTTEAMEDF TGGVTEFFEI
KDAPRDMYKI MKKAIERGSL MGCSIDDGTN MTYGTSPSGL KMGDLIARMV RNMDESRLRD
SDLIPEGCSD DRPTRTIVPV QFETRMACGL VKGHAYSVTG LEEALFKGEK VKLVRLRNPW
GQVEWNGSWS DSWKDWSFVD KDEKARLQHQ VTEDGEFWMS YDDFIYHFTK LEICNLTADA
LESDKLQTWT VSVNEGRWVR GCSAGGCRNF PDTFWTNPQY RLKLLEEDDD PDDSEVICSF
LVALMQKNRR KDRKLGANLF TIGFAIYEVP KEMHGNKQHL QKDFFLYNAS KARSRTYINM
REVSERFRLP PSEYVIVPST YEPHQEGEFI LRVFSEKRNL SEEVENTISV DRPVRKKKTK
PIIFVSDRAN SNKELGVDQE SEEGQDKTSP DKQEKSPKPE PSNTDQESEE QQQFRNIFRQ
IAGDDMEICA DELKNVLNRV VNKHKDLKTE GFTLESCRSM IALMDTDGSG RLNLQEFHHL
WKKIKSWQKI FKHYDTDQSG TINSYEMRNA VNDAGFHLNN QLYDIITMRY ADKYMNIDFD
SFICCFVRLE GMFRAFNAFD KDGDGIIKLN VLEWLQLTMY A
