ID CAN1_RAT Reviewed; 713 AA. AC P97571; DT 18-OCT-2001, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-1997, sequence version 1. DT 02-SEP-2026, entry version 195. 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; 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|RGD:2267}; GN Synonyms=Cls1 {ECO:0000250|UniProtKB:P07384}; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=8950173; DOI=10.1016/s0167-4781(96)00135-2; RA Sorimachi H., Amano S., Ishiura S., Suzuki K.; RT "Primary sequences of rat mu-calpain large and small subunits are, RT respectively, moderately and highly similar to those of human."; RL Biochim. Biophys. Acta 1309:37-41(1996). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Prostate; 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 [3] RP X-RAY CRYSTALLOGRAPHY (2.07 ANGSTROMS) OF 27-356, AND CALCIUM-BINDING RP REGIONS. RX PubMed=11893336; DOI=10.1016/s0092-8674(02)00659-1; RA Moldoveanu T., Hosfield C.M., Lim D., Elce J.S., Jia Z., Davies P.L.; RT "A Ca(2+) switch aligns the active site of calpain."; RL Cell 108:649-660(2002). RN [4] RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 60-647. RX PubMed=14656436; DOI=10.1016/j.str.2003.11.007; RA Pal G.P., De Veyra T., Elce J.S., Jia Z.; RT "Crystal structure of a micro-like calpain reveals a partially activated RT conformation with low Ca2+ requirement."; RL Structure 11:1521-1526(2003). RN [5] RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 27-356 IN COMPLEX WITH INHIBITORS, RP SUBUNIT, AND CALCIUM-BINDING REGIONS. RX PubMed=15491615; DOI=10.1016/j.jmb.2004.09.016; RA Moldoveanu T., Campbell R.L., Cuerrier D., Davies P.L.; RT "Crystal structures of calpain-E64 and -leupeptin inhibitor complexes RT reveal mobile loops gating the active site."; RL J. Mol. Biol. 343:1313-1326(2004). 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-364', 'Gly-377' and 'His-399'. Cleaves and activates caspase-7 CC (CASP7). {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:0000269|PubMed:15491615}. 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 --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U53858; AAC53001.1; -; mRNA. DR EMBL; BC061880; AAH61880.1; -; mRNA. DR RefSeq; NP_062025.2; NM_019152.3. DR PDB; 1KXR; X-ray; 2.07 A; A/B=27-356. DR PDB; 1QXP; X-ray; 2.80 A; A/B=60-650. DR PDB; 1TL9; X-ray; 1.80 A; A=27-356. DR PDB; 1TLO; X-ray; 1.90 A; A=27-356. DR PDB; 2G8E; X-ray; 2.25 A; A=27-356. DR PDB; 2G8J; X-ray; 1.61 A; A=27-356. DR PDB; 2NQG; X-ray; 2.04 A; A=27-356. DR PDB; 2NQI; X-ray; 2.04 A; A=27-356. DR PDB; 2R9C; X-ray; 1.80 A; A=27-356. DR PDB; 2R9F; X-ray; 1.60 A; A=27-356. DR AlphaFoldDB; P97571; -. DR SMR; P97571; -. DR BioGRID; 247836; 3. DR FunCoup; P97571; 1432. DR IntAct; P97571; 1. DR STRING; 10116.ENSRNOP00000028431; -. DR BindingDB; P97571; -. DR ChEMBL; CHEMBL3747; -. DR MEROPS; C02.001; -. DR iPTMnet; P97571; -. DR PhosphoSitePlus; P97571; -. DR jPOST; P97571; -. DR PaxDb; 10116-ENSRNOP00000028431; -. DR Ensembl; ENSRNOT00055037693; ENSRNOP00055030736; ENSRNOG00055021953. DR Ensembl; ENSRNOT00060056241; ENSRNOP00060046447; ENSRNOG00060032465. DR Ensembl; ENSRNOT00065058236; ENSRNOP00065047913; ENSRNOG00065033912. DR GeneID; 29153; -. DR KEGG; rno:29153; -. DR UCSC; RGD:2267; rat. DR AGR; RGD:2267; -. DR CTD; 823; -. DR RGD; 2267; Capn1. DR eggNOG; KOG0045; Eukaryota. DR InParanoid; P97571; -. DR OrthoDB; 4764at9989; -. DR PhylomeDB; P97571; -. DR BRENDA; 3.4.22.52; 5301. DR Reactome; R-RNO-1474228; Degradation of the extracellular matrix. DR Reactome; R-RNO-6798695; Neutrophil degranulation. DR EvolutionaryTrace; P97571; -. DR PRO; PR:P97571; -. DR Proteomes; UP000002494; Unplaced. DR GO; GO:0001533; C:cornified envelope; ISO:RGD. DR GO; GO:0005737; C:cytoplasm; ISO:RGD. DR GO; GO:0005829; C:cytosol; ISS:UniProtKB. DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO. DR GO; GO:0005764; C:lysosome; ISO:RGD. DR GO; GO:0016020; C:membrane; ISO:RGD. DR GO; GO:0005739; C:mitochondrion; ISO:RGD. DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB. DR GO; GO:0098794; C:postsynapse; IDA:SynGO. DR GO; GO:0014069; C:postsynaptic density; IDA:SynGO. DR GO; GO:0098793; C:presynapse; IDA:SynGO. DR GO; GO:0005509; F:calcium ion binding; IMP:RGD. DR GO; GO:0004198; F:calcium-dependent cysteine-type endopeptidase activity; IDA:UniProtKB. DR GO; GO:0008092; F:cytoskeletal protein binding; IDA:RGD. DR GO; GO:0019899; F:enzyme binding; IPI:RGD. DR GO; GO:0008233; F:peptidase activity; ISO:RGD. DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IMP:RGD. DR GO; GO:0060056; P:mammary gland involution; ISO:RGD. DR GO; GO:0030837; P:negative regulation of actin filament polymerization; IMP:RGD. DR GO; GO:1901223; P:negative regulation of non-canonical NF-kappaB signal transduction; IMP:RGD. DR GO; GO:0010666; P:positive regulation of cardiac muscle cell apoptotic process; IMP:RGD. DR GO; GO:1903238; P:positive regulation of leukocyte tethering or rolling; IMP:RGD. DR GO; GO:0043117; P:positive regulation of vascular permeability; IMP:RGD. DR GO; GO:0016540; P:protein autoprocessing; IDA:RGD. DR GO; GO:0030163; P:protein catabolic process; IDA:RGD. DR GO; GO:0140249; P:protein catabolic process at postsynapse; IDA:SynGO. DR GO; GO:0006508; P:proteolysis; IDA:UniProtKB. DR GO; GO:0032801; P:receptor catabolic process; ISO:RGD. DR GO; GO:0050790; P:regulation of catalytic activity; ISS:UniProtKB. DR GO; GO:1990776; P:response to angiotensin; IMP:RGD. DR GO; GO:0046685; P:response to arsenic-containing substance; IEP:RGD. DR GO; GO:0097264; P:self proteolysis; ISS:UniProtKB. DR CDD; cd00214; Calpain_III; 1. DR CDD; cd00044; CysPc; 1. DR CDD; cd16198; EFh_PEF_CAPN1; 1. DR FunFam; 1.10.238.10:FF:000124; Calpain-1 catalytic subunit; 1. DR FunFam; 2.60.120.380:FF:000001; Calpain-1 catalytic subunit; 1. DR FunFam; 3.90.70.10:FF:000001; Calpain-1 catalytic subunit; 1. DR Gene3D; 2.60.120.380; -; 1. DR Gene3D; 3.90.70.10; Cysteine proteinases; 1. DR Gene3D; 1.10.238.10; EF-hand; 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; 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; CALPAIN; 1. DR PANTHER; PTHR10183:SF284; CALPAIN-1 CATALYTIC SUBUNIT; 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; SSF49758; Calpain large subunit, middle domain (domain III); 1. DR SUPFAM; SSF54001; Cysteine proteinases; 1. DR SUPFAM; SSF47473; EF-hand; 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. DR PDBsum; 1KXR; -. DR PDBsum; 1QXP; -. DR PDBsum; 1TL9; -. DR PDBsum; 1TLO; -. DR PDBsum; 2G8E; -. DR PDBsum; 2G8J; -. DR PDBsum; 2NQG; -. DR PDBsum; 2NQI; -. DR PDBsum; 2R9C; -. DR PDBsum; 2R9F; -. PE 1: Evidence at protein level; KW 3D-structure; Autocatalytic cleavage; Calcium; Cell membrane; Cytoplasm; KW Hydrolase; Membrane; Metal-binding; Phosphoprotein; Protease; KW Reference proteome; Repeat; Thiol protease. FT CHAIN 1..713 FT /note="Calpain-1 catalytic subunit" FT /id="PRO_0000207700" FT DOMAIN 55..354 FT /note="Calpain catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00239" FT DOMAIN 557..575 FT /note="EF-hand 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT DOMAIN 584..609 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 597 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 599 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 601 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 603 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 608 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 627 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 629 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 631 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 633 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 638 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" 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 HELIX 37..39 FT /evidence="ECO:0007829|PDB:2R9F" FT HELIX 42..51 FT /evidence="ECO:0007829|PDB:2R9F" FT HELIX 65..68 FT /evidence="ECO:0007829|PDB:2R9F" FT STRAND 70..76 FT /evidence="ECO:0007829|PDB:1QXP" FT HELIX 78..82 FT /evidence="ECO:0007829|PDB:2R9F" FT STRAND 84..86 FT /evidence="ECO:0007829|PDB:2R9F" FT HELIX 88..91 FT /evidence="ECO:0007829|PDB:2R9F" FT STRAND 99..102 FT /evidence="ECO:0007829|PDB:2G8J" FT HELIX 104..106 FT /evidence="ECO:0007829|PDB:2R9F" FT STRAND 111..113 FT /evidence="ECO:0007829|PDB:2R9F" FT HELIX 115..124 FT /evidence="ECO:0007829|PDB:2R9F" FT HELIX 128..134 FT /evidence="ECO:0007829|PDB:2R9F" FT STRAND 147..155 FT /evidence="ECO:0007829|PDB:2R9F" FT STRAND 158..166 FT /evidence="ECO:0007829|PDB:2R9F" FT STRAND 168..171 FT /evidence="ECO:0007829|PDB:2R9F" FT STRAND 174..177 FT /evidence="ECO:0007829|PDB:2R9F" FT STRAND 181..183 FT /evidence="ECO:0007829|PDB:1QXP" FT HELIX 187..199 FT /evidence="ECO:0007829|PDB:2R9F" FT STRAND 200..202 FT /evidence="ECO:0007829|PDB:1TL9" FT HELIX 203..205 FT /evidence="ECO:0007829|PDB:2R9F" FT STRAND 206..208 FT /evidence="ECO:0007829|PDB:1TL9" FT HELIX 210..216 FT /evidence="ECO:0007829|PDB:2R9F" FT STRAND 221..226 FT /evidence="ECO:0007829|PDB:2R9F" FT HELIX 227..229 FT /evidence="ECO:0007829|PDB:2R9F" FT HELIX 234..244 FT /evidence="ECO:0007829|PDB:2R9F" FT STRAND 247..251 FT /evidence="ECO:0007829|PDB:2R9F" FT STRAND 255..258 FT /evidence="ECO:0007829|PDB:2R9F" FT STRAND 261..263 FT /evidence="ECO:0007829|PDB:1KXR" FT STRAND 269..271 FT /evidence="ECO:0007829|PDB:2G8E" FT STRAND 274..284 FT /evidence="ECO:0007829|PDB:2R9F" FT STRAND 287..295 FT /evidence="ECO:0007829|PDB:2R9F" FT HELIX 312..316 FT /evidence="ECO:0007829|PDB:2R9F" FT HELIX 319..325 FT /evidence="ECO:0007829|PDB:2R9F" FT STRAND 331..337 FT /evidence="ECO:0007829|PDB:2R9F" FT HELIX 338..344 FT /evidence="ECO:0007829|PDB:2R9F" FT STRAND 347..352 FT /evidence="ECO:0007829|PDB:2R9F" FT STRAND 370..375 FT /evidence="ECO:0007829|PDB:1QXP" FT TURN 377..380 FT /evidence="ECO:0007829|PDB:1QXP" FT TURN 388..390 FT /evidence="ECO:0007829|PDB:1QXP" FT HELIX 391..393 FT /evidence="ECO:0007829|PDB:1QXP" FT STRAND 398..401 FT /evidence="ECO:0007829|PDB:1QXP" FT STRAND 418..425 FT /evidence="ECO:0007829|PDB:1QXP" FT STRAND 441..447 FT /evidence="ECO:0007829|PDB:1QXP" FT HELIX 461..464 FT /evidence="ECO:0007829|PDB:1QXP" FT STRAND 477..480 FT /evidence="ECO:0007829|PDB:1QXP" FT STRAND 482..487 FT /evidence="ECO:0007829|PDB:1QXP" FT STRAND 490..503 FT /evidence="ECO:0007829|PDB:1QXP" FT STRAND 506..516 FT /evidence="ECO:0007829|PDB:1QXP" FT STRAND 518..520 FT /evidence="ECO:0007829|PDB:1QXP" FT STRAND 528..530 FT /evidence="ECO:0007829|PDB:1QXP" FT STRAND 556..559 FT /evidence="ECO:0007829|PDB:1QXP" FT TURN 565..569 FT /evidence="ECO:0007829|PDB:1QXP" FT HELIX 586..596 FT /evidence="ECO:0007829|PDB:1QXP" FT STRAND 606..608 FT /evidence="ECO:0007829|PDB:1QXP" FT HELIX 609..623 FT /evidence="ECO:0007829|PDB:1QXP" FT HELIX 624..626 FT /evidence="ECO:0007829|PDB:1QXP" FT HELIX 636..645 FT /evidence="ECO:0007829|PDB:1QXP" SQ SEQUENCE 713 AA; 82119 MW; 6E664600B0EFAEBB CRC64; MAEELITPVY CTGVSAQVQK QRDKELGLGR HENAIKYLGQ DYENLRARCL QNGVLFQDDA FPPVSHSLGF KELGPNSSKT YGIKWKRPTE LLSNPQFIVD GATRTDICQG ALGDCWLLAA IASLTLNETI LHRVVPYGQS FQEGYAGIFH FQLWQFGEWV DVVVDDLLPT KDGKLVFVHS AQGNEFWSAL LEKAYAKVNG SYEALSGGCT SEAFEDFTGG VTEWYDLQKA PSDLYQIILK ALERGSLLGC SINISDIRDL EAITFKNLVR GHAYSVTDAK QVTYQGQRVN LIRMRNPWGE VEWKGPWSDN SYEWNKVDPY EREQLRVKME DGEFWMSFRD FIREFTKLEI CNLTPDALKS RTLRNWNTTF YEGTWRRGST AGGCRNYPAT FWVNPQFKIR LEEVDDADDY DSRESGCSFL 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 LETMFRFFKI LDTDLDGVVT FDLFKWLQLT MFA //