CAN1_RAT
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 03-AUG-2022, entry version 182.
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'. {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}.
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DR EMBL; U53858; AAC53001.1; -; mRNA.
DR EMBL; BC061880; AAH61880.1; -; mRNA.
DR RefSeq; NP_062025.1; NM_019152.2.
DR PDB; 1KXR; X-ray; 2.07 A; A/B=27-356.
DR PDB; 1QXP; X-ray; 2.80 A; A/B=60-647.
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 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; -.
DR AlphaFoldDB; P97571; -.
DR SMR; P97571; -.
DR BioGRID; 247836; 3.
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; P97571; -.
DR PRIDE; P97571; -.
DR GeneID; 29153; -.
DR KEGG; rno:29153; -.
DR UCSC; RGD:2267; rat.
DR CTD; 823; -.
DR RGD; 2267; Capn1.
DR eggNOG; KOG0045; Eukaryota.
DR InParanoid; P97571; -.
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; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0005764; C:lysosome; ISO:RGD.
DR GO; GO:0016020; C:membrane; IDA:RGD.
DR GO; GO:0005739; C:mitochondrion; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
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:0007568; P:aging; IEP:RGD.
DR GO; GO:0007420; P:brain development; IEP: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 NIK/NF-kappaB signaling; 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: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 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 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..379
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
