| IED ID | IndEnz0002019145 |
| Enzyme Type ID | protease019145 |
| Protein Name |
Calpain-1 catalytic subunit EC 3.4.22.52 Calcium-activated neutral proteinase 1 CANP 1 Calpain mu-type Calpain-1 large subunit Cell proliferation-inducing gene 30 protein Micromolar-calpain muCANP |
| Gene Name | CAPN1 CANPL1 PIG30 |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MSEEIITPVYCTGVSAQVQKQRARELGLGRHENAIKYLGQDYEQLRVRCLQSGTLFRDEAFPPVPQSLGYKDLGPNSSKTYGIKWKRPTELLSNPQFIVDGATRTDICQGALGDCWLLAAIASLTLNDTLLHRVVPHGQSFQNGYAGIFHFQLWQFGEWVDVVVDDLLPIKDGKLVFVHSAEGNEFWSALLEKAYAKVNGSYEALSGGSTSEGFEDFTGGVTEWYELRKAPSDLYQIILKALERGSLLGCSIDISSVLDMEAITFKKLVKGHAYSVTGAKQVNYRGQVVSLIRMRNPWGEVEWTGAWSDSSSEWNNVDPYERDQLRVKMEDGEFWMSFRDFMREFTRLEICNLTPDALKSRTIRKWNTTLYEGTWRRGSTAGGCRNYPATFWVNPQFKIRLDETDDPDDYGDRESGCSFVLALMQKHRRRERRFGRDMETIGFAVYEVPPELVGQPAVHLKRDFFLANASRARSEQFINLREVSTRFRLPPGEYVVVPSTFEPNKEGDFVLRFFSEKSAGTVELDDQIQANLPDEQVLSEEEIDENFKALFRQLAGEDMEISVKELRTILNRIISKHKDLRTKGFSLESCRSMVNLMDRDGNGKLGLVEFNILWNRIRNYLSIFRKFDLDKSGSMSAYEMRMAIESAGFKLNKKLYELIITRYSEPDLAVDFDNFVCCLVRLETMFRFFKTLDTDLDGVVTFDLFKWLQLTMFA |
| Enzyme Length | 714 |
| Uniprot Accession Number | P07384 |
| Absorption | |
| Active Site | ACT_SITE 115; /evidence=ECO:0000250; ACT_SITE 272; /evidence=ECO:0000250; ACT_SITE 296; /evidence=ECO:0000250 |
| Activity Regulation | ACTIVITY REGULATION: Activated by micromolar concentrations of calcium and inhibited by calpastatin. {ECO:0000269|PubMed:8954105, ECO:0000269|PubMed:9271093}. |
| Binding Site | |
| Calcium Binding | CA_BIND 99..106; /note=1; CA_BIND 302..333; /note=2; CA_BIND 598..609; /note=3; CA_BIND 628..639; /note=4 |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=Broad endopeptidase specificity.; EC=3.4.22.52; Evidence={ECO:0000269|PubMed:16411745, ECO:0000269|PubMed:21531719}; |
| DNA Binding | |
| EC Number | 3.4.22.52 |
| Enzyme Function | FUNCTION: Calcium-regulated non-lysosomal thiol-protease which catalyzes limited proteolysis of substrates involved in cytoskeletal remodeling and signal transduction (PubMed:21531719, PubMed:2400579). Proteolytically cleaves CTBP1 at 'Asn-375', 'Gly-387' and 'His-409' (PubMed:23707407). {ECO:0000269|PubMed:21531719, ECO:0000269|PubMed:23707407, ECO:0000269|PubMed:2400579}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (3); Beta strand (15); Calcium binding (4); Chain (1); Domain (5); Helix (16); Initiator methionine (1); Modified residue (2); Natural variant (5); Region (3); Sequence conflict (1); Site (2) |
| Keywords | 3D-structure;Acetylation;Autocatalytic cleavage;Calcium;Cell membrane;Cytoplasm;Disease variant;Hereditary spastic paraplegia;Hydrolase;Membrane;Metal-binding;Neurodegeneration;Phosphoprotein;Protease;Reference proteome;Repeat;Thiol protease |
| Interact With | P05067; Q92934; P13569; P30085-3; P15311; Q96CV9; P18031; P40763 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:21531719, ECO:0000269|PubMed:8769305}. Cell membrane {ECO:0000269|PubMed:8769305}. Note=Translocates to the plasma membrane upon Ca(2+) binding. In granular keratinocytes and in lower corneocytes, colocalizes with FLG and FLG2 (PubMed:21531719). {ECO:0000269|PubMed:21531719}. |
| Modified Residue | MOD_RES 2; /note="N-acetylserine"; /evidence="ECO:0007744|PubMed:19413330, ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378"; MOD_RES 354; /note="Phosphothreonine"; /evidence="ECO:0007744|PubMed:23186163" |
| Post Translational Modification | PTM: Undergoes calcium-induced successive autoproteolytic cleavages that generate a membrane-bound 78 kDa active form and an intracellular 75 kDa active form. Calpastatin reduces with high efficiency the transition from 78 kDa to 75 kDa calpain forms. {ECO:0000269|PubMed:8769305, ECO:0000269|PubMed:8954105}. |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (2) |
| Cross Reference PDB | 1ZCM; 2ARY; |
| Mapped Pubmed ID | 10639123; 10830966; 11076937; 11853546; 11861304; 12000759; 12121992; 12200134; 12393869; 12843408; 14612448; 14980313; 15131115; 15302874; 15471877; 15488707; 15590628; 15663601; 15809056; 15935327; 15948206; 15950654; 15975558; 16107503; 16150694; 16361262; 16598790; 16697376; 16740134; 16908521; 17121855; 17157313; 17359359; 17515931; 17608959; 17620599; 17690304; 17716656; 17765980; 17908236; 17977825; 18032503; 18070881; 18071073; 18085799; 18165173; 18468730; 18498295; 18624398; 18624772; 18726991; 18793761; 18806756; 18823990; 19457105; 19617626; 19712109; 19901552; 19946330; 20034566; 20041182; 20179351; 20398180; 20514436; 20518497; 20557290; 20659425; 20933204; 21030783; 21209906; 21268016; 21305563; 21315622; 21374734; 21442128; 21494752; 21516125; 21555338; 21670566; 21808066; 21825064; 21839844; 21864727; 21876002; 21880013; 21988832; 21997417; 22190034; 22335024; 22449977; 22477191; 22480599; 22623428; 22805611; 23023391; 23035980; 23289183; 23400779; 23408424; 23515028; 23629652; 23650620; 23707532; 23733271; 23919677; 24413738; 24416790; 24670325; 24691096; 25086406; 25241761; 25309925; 25336645; 25476568; 25918155; 26063807; 26172506; 26284543; 26317226; 26496610; 26496999; 26638075; 26974309; 26974350; 27036949; 27320912; 27349634; 27456359; 27742573; 28192161; 28498452; 28536704; 28686728; 29047085; 29572388; 29614685; 29993134; 30177525; 30177812; 30425303; 30572172; 30796192; 30959065; 31023339; 31262726; 31395734; 31878359; 31982778; 32332747; 32395869; 32544313; 32852077; 32860341; 33078830; 33258989; 33486633; 33729106; 34148878; 34440793; 34728688; 7592818; 7698360; 8993318; 9228946; 9407132; 9989581; |
| Motif | |
| Gene Encoded By | |
| Mass | 81,890 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda | 3.4.22.52;3.4.22.53; |