CAN1_HUMAN
ID CAN1_HUMAN Reviewed; 714 AA.
AC P07384; Q2TTR0; Q6DHV4;
DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1988, sequence version 1.
DT 03-AUG-2022, entry version 235.
DE RecName: Full=Calpain-1 catalytic subunit {ECO:0000305};
DE EC=3.4.22.52 {ECO:0000269|PubMed:21531719};
DE AltName: Full=Calcium-activated neutral proteinase 1 {ECO:0000303|PubMed:3017764};
DE Short=CANP 1 {ECO:0000303|PubMed:3017764};
DE AltName: Full=Calpain mu-type {ECO:0000303|PubMed:2400579};
DE AltName: Full=Calpain-1 large subunit {ECO:0000303|PubMed:3017764};
DE AltName: Full=Cell proliferation-inducing gene 30 protein {ECO:0000303|Ref.3};
DE AltName: Full=Micromolar-calpain {ECO:0000303|PubMed:3017764};
DE Short=muCANP {ECO:0000303|PubMed:3017764};
GN Name=CAPN1 {ECO:0000312|HGNC:HGNC:1476}; Synonyms=CANPL1;
GN ORFNames=PIG30 {ECO:0000312|EMBL:AAT52221.1};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=3017764; DOI=10.1016/0014-5793(86)80919-x;
RA Aoki K., Imajoh S., Ohno S., Emori Y., Koike M., Kosaki G., Suzuki K.;
RT "Complete amino acid sequence of the large subunit of the low-Ca2+-
RT requiring form of human Ca2+-activated neutral protease (muCANP) deduced
RT from its cDNA sequence.";
RL FEBS Lett. 205:313-317(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=2400579;
RA Sorimachi H., Ohmi S., Emori Y., Kawasaki H., Saido T.C., Ohno S.,
RA Minami Y., Suzuki K.;
RT "A novel member of the calcium-dependent cysteine protease family.";
RL Biol. Chem. Hoppe-Seyler 371:171-176(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kim J.W.;
RT "Identification of a human cell proliferation inducing gene.";
RL Submitted (FEB-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ALA-103; PRO-433; ARG-492
RP AND ILE-676.
RG NIEHS SNPs program;
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT PRO-433.
RC TISSUE=Kidney, Pancreas, and Placenta;
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 [6]
RP ACTIVITY REGULATION, AUTOPROTEOLYTIC PROCESSING, COFACTOR, AND TISSUE
RP SPECIFICITY.
RX PubMed=8954105; DOI=10.1006/bbrc.1996.1779;
RA Melloni E., Michetti M., Salamino F., Minafra R., Pontremoli S.;
RT "Modulation of the calpain autoproteolysis by calpastatin and
RT phospholipids.";
RL Biochem. Biophys. Res. Commun. 229:193-197(1996).
RN [7]
RP AUTOPROTEOLYTIC PROCESSING, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=8769305; DOI=10.1016/0014-5793(96)00775-2;
RA Michetti M., Salamino F., Tedesco I., Averna M., Minafra R., Melloni E.,
RA Pontremoli S.;
RT "Autolysis of human erythrocyte calpain produces two active enzyme forms
RT with different cell localization.";
RL FEBS Lett. 392:11-15(1996).
RN [8]
RP ACTIVITY REGULATION, COFACTOR, CALCIUM-BINDING DATA, AND TISSUE
RP SPECIFICITY.
RX PubMed=9271093; DOI=10.1042/bj3250721;
RA Michetti M., Salamino F., Minafra R., Melloni E., Pontremoli S.;
RT "Calcium-binding properties of human erythrocyte calpain.";
RL Biochem. J. 325:721-726(1997).
RN [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [11]
RP CATALYTIC ACTIVITY, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=21531719; DOI=10.1074/jbc.m110.197400;
RA Hsu C.Y., Henry J., Raymond A.A., Mechin M.C., Pendaries V., Nassar D.,
RA Hansmann B., Balica S., Burlet-Schiltz O., Schmitt A.M., Takahara H.,
RA Paul C., Serre G., Simon M.;
RT "Deimination of human filaggrin-2 promotes its proteolysis by calpain 1.";
RL J. Biol. Chem. 286:23222-23233(2011).
RN [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [14]
RP FUNCTION.
RX PubMed=23707407; DOI=10.1016/j.jmb.2013.05.009;
RA Ono Y., Iemura S., Novak S.M., Doi N., Kitamura F., Natsume T.,
RA Gregorio C.C., Sorimachi H.;
RT "PLEIAD/SIMC1/C5orf25, a novel autolysis regulator for a skeletal-muscle-
RT specific calpain, CAPN3, scaffolds a CAPN3 substrate, CTBP1.";
RL J. Mol. Biol. 425:2955-2972(2013).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-354, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [17]
RP INVOLVEMENT IN SPG76, AND VARIANT SPG76 PRO-295.
RX PubMed=27153400; DOI=10.1016/j.ajhg.2016.04.002;
RA Gan-Or Z., Bouslam N., Birouk N., Lissouba A., Chambers D.B., Veriepe J.,
RA Androschuck A., Laurent S.B., Rochefort D., Spiegelman D.,
RA Dionne-Laporte A., Szuto A., Liao M., Figlewicz D.A., Bouhouche A.,
RA Benomar A., Yahyaoui M., Ouazzani R., Yoon G., Dupre N., Suchowersky O.,
RA Bolduc F.V., Parker J.A., Dion P.A., Drapeau P., Rouleau G.A.,
RA Bencheikh B.O.;
RT "Mutations in CAPN1 cause autosomal-recessive hereditary spastic
RT paraplegia.";
RL Am. J. Hum. Genet. 98:1038-1046(2016).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 33-353 OF MUTANT ALA-213,
RP CATALYTIC ACTIVITY, AND CALCIUM-BINDING REGIONS.
RX PubMed=16411745; DOI=10.1021/bi052077b;
RA Li Q., Hanzlik R.P., Weaver R.F., Schonbrunn E.;
RT "Molecular mode of action of a covalently inhibiting peptidomimetic on the
RT human calpain protease core.";
RL Biochemistry 45:701-708(2006).
CC -!- FUNCTION: Calcium-regulated non-lysosomal thiol-protease which
CC catalyzes limited proteolysis of substrates involved in cytoskeletal
CC remodeling and signal transduction (PubMed:21531719, PubMed:2400579).
CC Proteolytically cleaves CTBP1 at 'Asn-375', 'Gly-387' and 'His-409'
CC (PubMed:23707407). {ECO:0000269|PubMed:21531719,
CC ECO:0000269|PubMed:23707407, ECO:0000269|PubMed:2400579}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Broad endopeptidase specificity.; EC=3.4.22.52;
CC Evidence={ECO:0000269|PubMed:16411745, ECO:0000269|PubMed:21531719};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000269|PubMed:8954105, ECO:0000269|PubMed:9271093};
CC Note=Binds 4 Ca(2+) ions. {ECO:0000269|PubMed:9271093};
CC -!- ACTIVITY REGULATION: Activated by micromolar concentrations of calcium
CC and inhibited by calpastatin. {ECO:0000269|PubMed:8954105,
CC ECO:0000269|PubMed:9271093}.
CC -!- SUBUNIT: Forms a heterodimer with a small (regulatory) subunit CAPNS1.
CC {ECO:0000250|UniProtKB:P97571}.
CC -!- INTERACTION:
CC P07384; P05067: APP; NbExp=3; IntAct=EBI-1542113, EBI-77613;
CC P07384; Q92934: BAD; NbExp=3; IntAct=EBI-1542113, EBI-700771;
CC P07384; P13569: CFTR; NbExp=3; IntAct=EBI-1542113, EBI-349854;
CC P07384; P30085-3: CMPK1; NbExp=3; IntAct=EBI-1542113, EBI-23373346;
CC P07384; P15311: EZR; NbExp=2; IntAct=EBI-1542113, EBI-1056902;
CC P07384; Q96CV9: OPTN; NbExp=3; IntAct=EBI-1542113, EBI-748974;
CC P07384; P18031: PTPN1; NbExp=4; IntAct=EBI-1542113, EBI-968788;
CC P07384; P40763: STAT3; NbExp=2; IntAct=EBI-1542113, EBI-518675;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:21531719,
CC ECO:0000269|PubMed:8769305}. Cell membrane
CC {ECO:0000269|PubMed:8769305}. Note=Translocates to the plasma membrane
CC upon Ca(2+) binding. In granular keratinocytes and in lower
CC corneocytes, colocalizes with FLG and FLG2 (PubMed:21531719).
CC {ECO:0000269|PubMed:21531719}.
CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:2400579,
CC ECO:0000269|PubMed:3017764, ECO:0000269|PubMed:8769305,
CC ECO:0000269|PubMed:8954105, ECO:0000269|PubMed:9271093}.
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.
CC {ECO:0000269|PubMed:8769305, ECO:0000269|PubMed:8954105}.
CC -!- DISEASE: Spastic paraplegia 76, autosomal recessive (SPG76)
CC [MIM:616907]: A form of spastic paraplegia, a neurodegenerative
CC disorder characterized by a slow, gradual, progressive weakness and
CC spasticity of the lower limbs. Rate of progression and the severity of
CC symptoms are quite variable. Initial symptoms may include difficulty
CC with balance, weakness and stiffness in the legs, muscle spasms, and
CC dragging the toes when walking. In some forms of the disorder, bladder
CC symptoms (such as incontinence) may appear, or the weakness and
CC stiffness may spread to other parts of the body.
CC {ECO:0000269|PubMed:27153400}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the peptidase C2 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=CaBP; Note=Calpain;
CC URL="http://structbio.vanderbilt.edu/cabp_database/general/prot_pages/calpain.html";
CC -!- WEB RESOURCE: Name=Calpains homepage;
CC URL="https://cals.arizona.edu/calpains/";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/capn1/";
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DR EMBL; X04366; CAA27881.1; -; mRNA.
DR EMBL; AY550975; AAT52221.1; -; mRNA.
DR EMBL; AY796340; AAV41878.1; -; Genomic_DNA.
DR EMBL; BC008751; AAH08751.1; -; mRNA.
DR EMBL; BC017200; AAH17200.1; -; mRNA.
DR EMBL; BC075862; AAH75862.1; -; mRNA.
DR CCDS; CCDS44644.1; -.
DR PIR; A26213; CIHUH.
DR RefSeq; NP_001185797.1; NM_001198868.1.
DR RefSeq; NP_001185798.1; NM_001198869.1.
DR RefSeq; NP_005177.2; NM_005186.3.
DR RefSeq; XP_006718761.1; XM_006718698.1.
DR RefSeq; XP_011543594.1; XM_011545292.1.
DR PDB; 1ZCM; X-ray; 2.00 A; A=33-353.
DR PDB; 2ARY; X-ray; 2.40 A; A/B=29-360.
DR PDBsum; 1ZCM; -.
DR PDBsum; 2ARY; -.
DR AlphaFoldDB; P07384; -.
DR SMR; P07384; -.
DR BioGRID; 107273; 147.
DR ComplexPortal; CPX-4302; mu-Calpain complex.
DR CORUM; P07384; -.
DR IntAct; P07384; 55.
DR MINT; P07384; -.
DR STRING; 9606.ENSP00000431984; -.
DR BindingDB; P07384; -.
DR ChEMBL; CHEMBL3891; -.
DR DrugBank; DB07627; (2S)-4-METHYL-2-(3-PHENYLTHIOUREIDO)-N-((3S)-TETRAHYDRO-2-HYDROXY-3-FURANYL)PENTANAMIDE.
DR DrugBank; DB04276; 4-[[(2S)-2-[[(2S)-3-Carboxy-2-hydroxypropanoyl]amino]-4-methylpentanoyl]amino]butyl-(diaminomethylidene)azanium.
DR DrugBank; DB04653; N-[(benzyloxy)carbonyl]-L-leucyl-N-[(1S)-3-fluoro-1-(4-hydroxybenzyl)-2-oxopropyl]-L-leucinamide.
DR GuidetoPHARMACOLOGY; 2336; -.
DR MEROPS; C02.001; -.
DR GlyGen; P07384; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P07384; -.
DR MetOSite; P07384; -.
DR PhosphoSitePlus; P07384; -.
DR SwissPalm; P07384; -.
DR BioMuta; CAPN1; -.
DR DMDM; 115574; -.
DR CPTAC; CPTAC-35; -.
DR CPTAC; CPTAC-36; -.
DR EPD; P07384; -.
DR jPOST; P07384; -.
DR MassIVE; P07384; -.
DR MaxQB; P07384; -.
DR PaxDb; P07384; -.
DR PeptideAtlas; P07384; -.
DR PRIDE; P07384; -.
DR ProteomicsDB; 52001; -.
DR Antibodypedia; 1034; 580 antibodies from 44 providers.
DR DNASU; 823; -.
DR Ensembl; ENST00000279247.11; ENSP00000279247.7; ENSG00000014216.16.
DR Ensembl; ENST00000524773.5; ENSP00000434176.1; ENSG00000014216.16.
DR Ensembl; ENST00000527323.5; ENSP00000431984.1; ENSG00000014216.16.
DR Ensembl; ENST00000533129.5; ENSP00000431686.1; ENSG00000014216.16.
DR Ensembl; ENST00000533820.5; ENSP00000435272.1; ENSG00000014216.16.
DR GeneID; 823; -.
DR KEGG; hsa:823; -.
DR MANE-Select; ENST00000279247.11; ENSP00000279247.7; NM_005186.4; NP_005177.2.
DR UCSC; uc001odf.3; human.
DR CTD; 823; -.
DR DisGeNET; 823; -.
DR GeneCards; CAPN1; -.
DR HGNC; HGNC:1476; CAPN1.
DR HPA; ENSG00000014216; Tissue enhanced (esophagus).
DR MalaCards; CAPN1; -.
DR MIM; 114220; gene.
DR MIM; 616907; phenotype.
DR neXtProt; NX_P07384; -.
DR OpenTargets; ENSG00000014216; -.
DR Orphanet; 488594; Autosomal recessive spastic paraplegia type 76.
DR PharmGKB; PA26057; -.
DR VEuPathDB; HostDB:ENSG00000014216; -.
DR eggNOG; KOG0045; Eukaryota.
DR GeneTree; ENSGT00940000159147; -.
DR HOGENOM; CLU_010982_0_1_1; -.
DR InParanoid; P07384; -.
DR OMA; TEWFDLR; -.
DR OrthoDB; 704215at2759; -.
DR PhylomeDB; P07384; -.
DR TreeFam; TF314748; -.
DR BRENDA; 3.4.22.52; 2681.
DR BRENDA; 3.4.22.53; 2681.
DR PathwayCommons; P07384; -.
DR Reactome; R-HSA-1474228; Degradation of the extracellular matrix.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR Reactome; R-HSA-6809371; Formation of the cornified envelope.
DR Reactome; R-HSA-8862803; Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models.
DR SignaLink; P07384; -.
DR SIGNOR; P07384; -.
DR BioGRID-ORCS; 823; 10 hits in 1079 CRISPR screens.
DR ChiTaRS; CAPN1; human.
DR EvolutionaryTrace; P07384; -.
DR GeneWiki; CAPN1; -.
DR GenomeRNAi; 823; -.
DR Pharos; P07384; Tchem.
DR PRO; PR:P07384; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; P07384; protein.
DR Bgee; ENSG00000014216; Expressed in lower esophagus mucosa and 176 other tissues.
DR ExpressionAtlas; P07384; baseline and differential.
DR Genevisible; P07384; HS.
DR GO; GO:0001533; C:cornified envelope; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:1904813; C:ficolin-1-rich granule lumen; TAS:Reactome.
DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB.
DR GO; GO:0005764; C:lysosome; IEA:Ensembl.
DR GO; GO:0016020; C:membrane; IDA:BHF-UCL.
DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0004198; F:calcium-dependent cysteine-type endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0008233; F:peptidase activity; IDA:UniProtKB.
DR GO; GO:0060056; P:mammary gland involution; IEA:Ensembl.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; TAS:ProtInc.
DR GO; GO:0006508; P:proteolysis; IDA:UniProtKB.
DR GO; GO:0032801; P:receptor catabolic process; IEA:Ensembl.
DR GO; GO:0050790; P:regulation of catalytic activity; IDA:UniProtKB.
DR GO; GO:0016241; P:regulation of macroautophagy; NAS:ParkinsonsUK-UCL.
DR GO; GO:2000310; P:regulation of NMDA receptor activity; TAS:ARUK-UCL.
DR GO; GO:0097264; P:self proteolysis; IDA: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; Acetylation; Autocatalytic cleavage; Calcium; Cell membrane;
KW Cytoplasm; Disease variant; Hereditary spastic paraplegia; Hydrolase;
KW Membrane; Metal-binding; Neurodegeneration; Phosphoprotein; Protease;
KW Reference proteome; Repeat; Thiol protease.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378"
FT CHAIN 2..714
FT /note="Calpain-1 catalytic subunit"
FT /id="PRO_0000207694"
FT DOMAIN 55..354
FT /note="Calpain catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00239"
FT DOMAIN 541..576
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 585..618
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 615..650
FT /note="EF-hand 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 680..714
FT /note="EF-hand 4"
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 316
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
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 SITE 27..28
FT /note="Cleavage; for 75 kDa form"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378"
FT MOD_RES 354
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VARIANT 103
FT /note="T -> A (in dbSNP:rs17885718)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_021085"
FT VARIANT 295
FT /note="R -> P (in SPG76; dbSNP:rs756205995)"
FT /evidence="ECO:0000269|PubMed:27153400"
FT /id="VAR_077899"
FT VARIANT 433
FT /note="R -> P (in dbSNP:rs10895991)"
FT /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.4"
FT /id="VAR_021086"
FT VARIANT 492
FT /note="G -> R (in dbSNP:rs17883283)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_021087"
FT VARIANT 676
FT /note="V -> I (in dbSNP:rs17884773)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_021088"
FT CONFLICT 548
FT /note="K -> N (in Ref. 5; AAH08751)"
FT /evidence="ECO:0000305"
FT HELIX 37..39
FT /evidence="ECO:0007829|PDB:1ZCM"
FT HELIX 42..51
FT /evidence="ECO:0007829|PDB:1ZCM"
FT HELIX 65..68
FT /evidence="ECO:0007829|PDB:1ZCM"
FT HELIX 78..80
FT /evidence="ECO:0007829|PDB:1ZCM"
FT STRAND 84..86
FT /evidence="ECO:0007829|PDB:1ZCM"
FT HELIX 88..91
FT /evidence="ECO:0007829|PDB:1ZCM"
FT STRAND 99..102
FT /evidence="ECO:0007829|PDB:1ZCM"
FT HELIX 104..106
FT /evidence="ECO:0007829|PDB:1ZCM"
FT STRAND 111..113
FT /evidence="ECO:0007829|PDB:1ZCM"
FT HELIX 115..124
FT /evidence="ECO:0007829|PDB:1ZCM"
FT HELIX 128..134
FT /evidence="ECO:0007829|PDB:1ZCM"
FT STRAND 147..155
FT /evidence="ECO:0007829|PDB:1ZCM"
FT STRAND 158..166
FT /evidence="ECO:0007829|PDB:1ZCM"
FT STRAND 168..171
FT /evidence="ECO:0007829|PDB:1ZCM"
FT STRAND 174..177
FT /evidence="ECO:0007829|PDB:1ZCM"
FT HELIX 187..198
FT /evidence="ECO:0007829|PDB:1ZCM"
FT HELIX 203..205
FT /evidence="ECO:0007829|PDB:1ZCM"
FT HELIX 210..216
FT /evidence="ECO:0007829|PDB:1ZCM"
FT STRAND 217..220
FT /evidence="ECO:0007829|PDB:2ARY"
FT STRAND 221..226
FT /evidence="ECO:0007829|PDB:1ZCM"
FT HELIX 227..229
FT /evidence="ECO:0007829|PDB:1ZCM"
FT HELIX 234..244
FT /evidence="ECO:0007829|PDB:1ZCM"
FT STRAND 247..251
FT /evidence="ECO:0007829|PDB:1ZCM"
FT STRAND 256..258
FT /evidence="ECO:0007829|PDB:1ZCM"
FT STRAND 274..284
FT /evidence="ECO:0007829|PDB:1ZCM"
FT STRAND 287..295
FT /evidence="ECO:0007829|PDB:1ZCM"
FT HELIX 312..316
FT /evidence="ECO:0007829|PDB:1ZCM"
FT HELIX 319..325
FT /evidence="ECO:0007829|PDB:1ZCM"
FT STRAND 331..337
FT /evidence="ECO:0007829|PDB:1ZCM"
FT HELIX 338..344
FT /evidence="ECO:0007829|PDB:1ZCM"
FT STRAND 347..352
FT /evidence="ECO:0007829|PDB:1ZCM"
SQ SEQUENCE 714 AA; 81890 MW; 1CB6D7C56D063498 CRC64;
MSEEIITPVY CTGVSAQVQK QRARELGLGR HENAIKYLGQ DYEQLRVRCL QSGTLFRDEA
FPPVPQSLGY KDLGPNSSKT YGIKWKRPTE LLSNPQFIVD GATRTDICQG ALGDCWLLAA
IASLTLNDTL LHRVVPHGQS FQNGYAGIFH FQLWQFGEWV DVVVDDLLPI KDGKLVFVHS
AEGNEFWSAL LEKAYAKVNG SYEALSGGST SEGFEDFTGG VTEWYELRKA PSDLYQIILK
ALERGSLLGC SIDISSVLDM EAITFKKLVK GHAYSVTGAK QVNYRGQVVS LIRMRNPWGE
VEWTGAWSDS SSEWNNVDPY ERDQLRVKME DGEFWMSFRD FMREFTRLEI CNLTPDALKS
RTIRKWNTTL YEGTWRRGST AGGCRNYPAT FWVNPQFKIR LDETDDPDDY GDRESGCSFV
LALMQKHRRR ERRFGRDMET IGFAVYEVPP ELVGQPAVHL KRDFFLANAS RARSEQFINL
REVSTRFRLP PGEYVVVPST FEPNKEGDFV LRFFSEKSAG TVELDDQIQA NLPDEQVLSE
EEIDENFKAL FRQLAGEDME ISVKELRTIL NRIISKHKDL RTKGFSLESC RSMVNLMDRD
GNGKLGLVEF NILWNRIRNY LSIFRKFDLD KSGSMSAYEM RMAIESAGFK LNKKLYELII
TRYSEPDLAV DFDNFVCCLV RLETMFRFFK TLDTDLDGVV TFDLFKWLQL TMFA
