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 27-MAR-2024, entry version 244. DE RecName: Full=Calpain-1 catalytic subunit {ECO:0000305}; DE EC=3.4.22.52 {ECO:0000269|PubMed:19617626, 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 FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=19617626; DOI=10.1074/jbc.m109.038174; RA Gafni J., Cong X., Chen S.F., Gibson B.W., Ellerby L.M.; RT "Calpain-1 cleaves and activates caspase-7."; RL J. Biol. Chem. 284:25441-25449(2009). RN [11] 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 [12] 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 [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=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 [14] 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 [15] 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 [16] 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 [17] 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 [18] 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 [19] 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:19617626, PubMed:21531719, CC PubMed:2400579). Proteolytically cleaves CTBP1 at 'Asn-375', 'Gly-387' CC and 'His-409' (PubMed:23707407). Cleaves and activates caspase-7 CC (CASP7) (PubMed:19617626). {ECO:0000269|PubMed:19617626, CC ECO:0000269|PubMed:21531719, ECO:0000269|PubMed:23707407, CC 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:19617626, CC 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=7; 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/"; 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; 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 PDB; 7W7O; X-ray; 1.59 A; A=27-360. DR PDB; 7X79; X-ray; 1.80 A; A=1-714. DR PDB; 8GX3; X-ray; 1.99 A; A=1-714. DR PDBsum; 1ZCM; -. DR PDBsum; 2ARY; -. DR PDBsum; 7W7O; -. DR PDBsum; 7X79; -. DR PDBsum; 8GX3; -. DR AlphaFoldDB; P07384; -. DR SMR; P07384; -. DR BioGRID; 107273; 182. DR ComplexPortal; CPX-4302; mu-Calpain complex. DR CORUM; P07384; -. DR IntAct; P07384; 56. 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; 9606-ENSP00000431984; -. DR PeptideAtlas; P07384; -. DR PRIDE; P07384; -. DR ProteomicsDB; 52001; -. DR Pumba; P07384; -. DR Antibodypedia; 1034; 691 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 AGR; HGNC:1476; -. 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; WNRIKNY; -. DR OrthoDB; 142935at2759; -. 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; 14 hits in 1156 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 178 other cell types or tissues. DR ExpressionAtlas; P07384; baseline and differential. DR GO; GO:0110158; C:calpain complex; ISS:ComplexPortal. 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 CDD; cd16198; EFh_PEF_CAPN1; 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 Genevisible; P07384; HS. 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 //