CAN1_PIG
ID CAN1_PIG Reviewed; 714 AA.
AC P35750; Q29600; Q9N0M6;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2001, sequence version 3.
DT 03-AUG-2022, entry version 178.
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 {ECO:0000250|UniProtKB:P07384};
DE Short=muCANP {ECO:0000250|UniProtKB:P07384};
GN Name=CAPN1 {ECO:0000250|UniProtKB:P07384};
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 [MRNA].
RX PubMed=11219468; DOI=10.2527/2001.792552x;
RA Smith T.P.L., Simmen F.A., Zhao G., Vallet J.L.;
RT "Rapid communication: nucleotide sequences of two isoforms of porcine
RT micromolar calcium-activated neutral protease 1 cDNA.";
RL J. Anim. Sci. 79:552-553(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 326-415.
RC TISSUE=Small intestine;
RX PubMed=8672129; DOI=10.1007/s003359900153;
RA Winteroe A.K., Fredholm M., Davies W.;
RT "Evaluation and characterization of a porcine small intestine cDNA library:
RT analysis of 839 clones.";
RL Mamm. Genome 7:509-517(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 528-623.
RC TISSUE=Skeletal muscle;
RX PubMed=8312396; DOI=10.1016/0300-9084(93)90051-s;
RA Sun W., Ji S.Q., Ebert P.J., Bidwell C.A., Hancock D.L.;
RT "Cloning the partial cDNAs of mu-calpain and m-calpain from porcine
RT skeletal muscle.";
RL Biochimie 75:931-936(1993).
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.
CC {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; AF263610; AAF73444.1; -; mRNA.
DR EMBL; F14611; CAA23154.1; -; mRNA.
DR EMBL; U01180; AAA65125.1; -; mRNA.
DR RefSeq; NP_001335713.1; NM_001348784.1.
DR RefSeq; XP_005660759.1; XM_005660702.2.
DR AlphaFoldDB; P35750; -.
DR SMR; P35750; -.
DR STRING; 9823.ENSSSCP00000013824; -.
DR BindingDB; P35750; -.
DR ChEMBL; CHEMBL4062; -.
DR MEROPS; C02.001; -.
DR PaxDb; P35750; -.
DR PeptideAtlas; P35750; -.
DR PRIDE; P35750; -.
DR Ensembl; ENSSSCT00000067293; ENSSSCP00000067028; ENSSSCG00000012999.
DR Ensembl; ENSSSCT00030023973; ENSSSCP00030010752; ENSSSCG00030017341.
DR Ensembl; ENSSSCT00030023978; ENSSSCP00030010754; ENSSSCG00030017341.
DR Ensembl; ENSSSCT00035095488; ENSSSCP00035040163; ENSSSCG00035069457.
DR Ensembl; ENSSSCT00045028973; ENSSSCP00045020058; ENSSSCG00045016673.
DR Ensembl; ENSSSCT00055045028; ENSSSCP00055035871; ENSSSCG00055022554.
DR Ensembl; ENSSSCT00060079788; ENSSSCP00060034533; ENSSSCG00060058087.
DR Ensembl; ENSSSCT00060079791; ENSSSCP00060034536; ENSSSCG00060058087.
DR Ensembl; ENSSSCT00065043021; ENSSSCP00065018268; ENSSSCG00065031759.
DR Ensembl; ENSSSCT00070040541; ENSSSCP00070034011; ENSSSCG00070020405.
DR GeneID; 397027; -.
DR KEGG; ssc:397027; -.
DR CTD; 823; -.
DR VGNC; VGNC:86170; CAPN1.
DR eggNOG; KOG0045; Eukaryota.
DR GeneTree; ENSGT00940000159147; -.
DR HOGENOM; CLU_010982_0_1_1; -.
DR InParanoid; P35750; -.
DR OMA; TEWFDLR; -.
DR OrthoDB; 704215at2759; -.
DR TreeFam; TF314748; -.
DR BRENDA; 3.4.22.52; 6170.
DR Reactome; R-SSC-1474228; Degradation of the extracellular matrix.
DR Reactome; R-SSC-6798695; Neutrophil degranulation.
DR Reactome; R-SSC-6809371; Formation of the cornified envelope.
DR PRO; PR:P35750; -.
DR Proteomes; UP000008227; Chromosome 2.
DR Proteomes; UP000314985; Chromosome 2.
DR Bgee; ENSSSCG00000012999; Expressed in blood and 43 other tissues.
DR ExpressionAtlas; P35750; baseline and differential.
DR Genevisible; P35750; SS.
DR GO; GO:0005737; C:cytoplasm; IDA:CAFA.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
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:CAFA.
DR GO; GO:0006508; P:proteolysis; IDA:CAFA.
DR GO; GO:0050790; P:regulation of catalytic activity; 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; 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; 3.
DR PROSITE; PS00139; THIOL_PROTEASE_CYS; 1.
PE 2: Evidence at transcript level;
KW Autocatalytic cleavage; Calcium; Cell membrane; Cytoplasm; Hydrolase;
KW Membrane; Metal-binding; Phosphoprotein; Protease; Reference proteome;
KW Repeat; Thiol protease.
FT CHAIN 1..714
FT /note="Calpain-1 catalytic subunit"
FT /id="PRO_0000207697"
FT DOMAIN 55..354
FT /note="Calpain catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00239"
FT DOMAIN 585..618
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 615..650
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 680..714
FT /note="EF-hand 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REGION 355..526
FT /note="Domain III"
FT REGION 527..542
FT /note="Linker"
FT REGION 543..713
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 598
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 600
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 602
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 604
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 609
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 628
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 630
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 632
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 634
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 639
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 528
FT /note="V -> I (in Ref. 3; AAA65125)"
FT /evidence="ECO:0000305"
FT CONFLICT 531
FT /note="I -> N (in Ref. 3; AAA65125)"
FT /evidence="ECO:0000305"
FT CONFLICT 541
FT /note="E -> G (in Ref. 3; AAA65125)"
FT /evidence="ECO:0000305"
FT CONFLICT 622
FT /note="S -> A (in Ref. 3; AAA65125)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 714 AA; 81739 MW; 0BB31DE4FC56363A CRC64;
MAEEVITPVY CTGVSAQVQK LRAKELGLGR HENAIKYLGQ DYEQLRAHCL QSGSLFRDEA
FPPVPQSLGF KELGPNSSKT YGVKWKRPTE LFSNPQFIVD GATRTDICQG ALGDCWLLAA
IASLTLNDTL LHRVVPHGQS FQNGYAGIFH FQLWQFGEWV DVVVDDLLPT KDGKLVFVHS
AQGNEFWSAL LEKAYAKVNG SYEALSGGST SEGFEDFTGG VTEWYELRKA PSDLYSIILK
ALERGSLLGC SIDISSVLDM EAVTFKKLVK GHAYSVTGAK QVNYQGQMVN LIRMRNPWGE
VEWTGAWSDG SSEWNGVDPY QRDQLRVRME DGEFWMSFRD FLREFTRLEI CNLTPDALKS
QRVRNWNTTL YEGTWRRGST AGGCRNYPAT FWVNPQFKIR LEETDDPEDD YGGRESGCSF
VLALMQKHRR RERRFGRDME TIGFAVYEVP PELVGQPVHL KRDFFLANAS RARSEQFINL
REVSTRFRLP PGEYVVVPST FEPNKEGDFV LRFFSEKKAG TQELDDQVQA ILPDEQVLSE
EEIDENFKAL FRQLAGEDME ISVRELRTIL NRIISKHKDL RTKGFSLESC RSMVNLMDRD
GNGKLGLVEF NILWNRIRNY LSIFRKFDLD KSGSMSAYEM RMAIESAGFK LNKKLFELII
TRYSEPDLAV DFDNFVCCLV RLETMFRFFK TLDTDLDGVV TFDLFKWLQL TMFA
