CAN1_MOUSE
ID CAN1_MOUSE Reviewed; 713 AA.
AC O35350; O88666;
DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 197.
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;
DE Short=muCANP {ECO:0000250|UniProtKB:P07384};
GN Name=Capn1 {ECO:0000312|MGI:MGI:88263};
GN Synonyms=Canp1, Capa1 {ECO:0000250|UniProtKB:P07384};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=CF-1;
RA Poirier C., Poussard S., Faust D.M., Imaizumi-Sherrer T., Weiss M.C.,
RA Ducastaing A., Montarras D., Pinset C., Guenet J.-L.;
RL Submitted (AUG-1997) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=129;
RA Sahr K.E., Andrabi S., Peters L.L., Chishti A.H.;
RT "Cloning and characterization of the cDNA and gene encoding the mouse mu-
RT calpain large subunit protein.";
RL Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Colon;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=16452087; DOI=10.1074/mcp.t500041-mcp200;
RA Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L.;
RT "Comprehensive identification of phosphorylation sites in postsynaptic
RT density preparations.";
RL Mol. Cell. Proteomics 5:914-922(2006).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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 at
CC 'Asn-375', 'Gly-388' and 'His-410'. {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; AF021847; AAB72222.1; -; mRNA.
DR EMBL; AF084459; AAC33134.1; -; mRNA.
DR EMBL; BC026138; AAH26138.1; -; mRNA.
DR CCDS; CCDS37893.1; -.
DR RefSeq; NP_001103974.1; NM_001110504.1.
DR RefSeq; NP_031626.1; NM_007600.3.
DR AlphaFoldDB; O35350; -.
DR SMR; O35350; -.
DR BioGRID; 198470; 31.
DR ComplexPortal; CPX-4304; mu-Calpain complex.
DR DIP; DIP-60303N; -.
DR IntAct; O35350; 4.
DR STRING; 10090.ENSMUSP00000025891; -.
DR MEROPS; C02.001; -.
DR iPTMnet; O35350; -.
DR PhosphoSitePlus; O35350; -.
DR SwissPalm; O35350; -.
DR EPD; O35350; -.
DR jPOST; O35350; -.
DR PaxDb; O35350; -.
DR PeptideAtlas; O35350; -.
DR PRIDE; O35350; -.
DR ProteomicsDB; 265432; -.
DR Antibodypedia; 1034; 580 antibodies from 44 providers.
DR DNASU; 12333; -.
DR Ensembl; ENSMUST00000025891; ENSMUSP00000025891; ENSMUSG00000024942.
DR Ensembl; ENSMUST00000164843; ENSMUSP00000127498; ENSMUSG00000024942.
DR GeneID; 12333; -.
DR KEGG; mmu:12333; -.
DR UCSC; uc008ggj.2; mouse.
DR CTD; 823; -.
DR MGI; MGI:88263; Capn1.
DR VEuPathDB; HostDB:ENSMUSG00000024942; -.
DR eggNOG; KOG0045; Eukaryota.
DR GeneTree; ENSGT00940000159147; -.
DR HOGENOM; CLU_010982_0_1_1; -.
DR InParanoid; O35350; -.
DR OMA; TEWFDLR; -.
DR OrthoDB; 704215at2759; -.
DR PhylomeDB; O35350; -.
DR TreeFam; TF314748; -.
DR BRENDA; 3.4.22.52; 3474.
DR Reactome; R-MMU-1474228; Degradation of the extracellular matrix.
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR BioGRID-ORCS; 12333; 3 hits in 73 CRISPR screens.
DR ChiTaRS; Capn1; mouse.
DR PRO; PR:O35350; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; O35350; protein.
DR Bgee; ENSMUSG00000024942; Expressed in granulocyte and 136 other tissues.
DR ExpressionAtlas; O35350; baseline and differential.
DR Genevisible; O35350; MM.
DR GO; GO:0110158; C:calpain complex; IC:ComplexPortal.
DR GO; GO:0001533; C:cornified envelope; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0005764; C:lysosome; IDA:MGI.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; IDA:MGI.
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; IDA:MGI.
DR GO; GO:0008092; F:cytoskeletal protein binding; ISO:MGI.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0008233; F:peptidase activity; ISO:MGI.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; ISO:MGI.
DR GO; GO:0060056; P:mammary gland involution; IMP:MGI.
DR GO; GO:0030837; P:negative regulation of actin filament polymerization; ISO:MGI.
DR GO; GO:1901223; P:negative regulation of NIK/NF-kappaB signaling; ISO:MGI.
DR GO; GO:0010666; P:positive regulation of cardiac muscle cell apoptotic process; ISO:MGI.
DR GO; GO:1903238; P:positive regulation of leukocyte tethering or rolling; ISO:MGI.
DR GO; GO:0043117; P:positive regulation of vascular permeability; ISO:MGI.
DR GO; GO:0016540; P:protein autoprocessing; ISO:MGI.
DR GO; GO:0030163; P:protein catabolic process; ISO:MGI.
DR GO; GO:0006508; P:proteolysis; IMP:MGI.
DR GO; GO:0032801; P:receptor catabolic process; IDA:MGI.
DR GO; GO:0050790; P:regulation of catalytic activity; ISS:UniProtKB.
DR GO; GO:1990776; P:response to angiotensin; ISO:MGI.
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; Hydrolase;
KW Membrane; Metal-binding; Phosphoprotein; Protease; Reference proteome;
KW Repeat; Thiol protease.
FT CHAIN 1..713
FT /note="Calpain-1 catalytic subunit"
FT /id="PRO_0000207696"
FT DOMAIN 55..354
FT /note="Calpain catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00239"
FT DOMAIN 540..575
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 584..617
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 614..649
FT /note="EF-hand 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 679..713
FT /note="EF-hand 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REGION 355..525
FT /note="Domain III"
FT REGION 526..541
FT /note="Linker"
FT REGION 542..712
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 597
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 599
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 601
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 603
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 608
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 627
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 629
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 631
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 633
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 638
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 488
FT /note="L -> P (in Ref. 2; AAC33134)"
FT /evidence="ECO:0000305"
FT CONFLICT 696
FT /note="D -> N (in Ref. 2; AAC33134)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 713 AA; 82106 MW; 3E1E26C95802B864 CRC64;
MTEELITPVY CTGVSAQVQK KRDKELGLGR HENAIKYLGQ DYETLRARCL QSGVLFQDEA
FPPVSHSLGF KELGPHSSKT YGIKWKRPTE LMSNPQFIVD GATRTDICQG ALGDCWLLAA
IASLTLNETI LHRVVPYGQS FQDGYAGIFH FQLWQFGEWV DVVIDDLLPT KDGKLVFVHS
AQGNEFWSAL LEKAYAKVNG SYEALSGGCT SEAFEDFTGG VTEWYDLQKA PSDLYQIILK
ALERGSLLGC SINISDIRDL EAITFKNLVR GHAYSVTGAK QVTYQGQRVN LIRMRNPWGE
VEWKGPWSDS SYEWNKVDPY EREQLRVKME DGEFWMSFRD FIREFTKLEI CNLTPDALKS
RTLRNWNTTF YEGTWRRGST AGGCRNYPAT FWVNPQFKIR LEEVDDADDY DNRESGCSFL
LALMQKHRRR ERRFGRDMET IGFAVYQVPR ELAGQPVHLK RDFFLANASR AQSEHFINLR
EVSNRIRLPP GEYIVVPSTF EPNKEGDFLL RFFSEKKAGT QELDDQIQAN LPDEKVLSEE
EIDDNFKTLF SKLAGDDMEI SVKELQTILN RIISKHKDLR TNGFSLESCR SMVNLMDRDG
NGKLGLVEFN ILWNRIRNYL TIFRKFDLDK SGSMSAYEMR MAIEAAGFKL NKKLHELIIT
RYSEPDLAVD FDNFVCCLVR LETMFRFFKL LDTDLDGVVT FDLFKWLQLT MFA
