| IED ID | IndEnz0002015873 |
| Enzyme Type ID | protease015873 |
| Protein Name |
Atrial natriuretic peptide-converting enzyme EC 3.4.21.- Corin Heart-specific serine proteinase ATC2 Pro-ANP-converting enzyme Transmembrane protease serine 10 Cleaved into: Atrial natriuretic peptide-converting enzyme, N-terminal propeptide; Atrial natriuretic peptide-converting enzyme, activated protease fragment; Atrial natriuretic peptide-converting enzyme, 180 kDa soluble fragment; Atrial natriuretic peptide-converting enzyme, 160 kDa soluble fragment; Atrial natriuretic peptide-converting enzyme, 100 kDa soluble fragment |
| Gene Name | CORIN CRN TMPRSS10 |
| 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 | MKQSPALAPEERCRRAGSPKPVLRADDNNMGNGCSQKLATANLLRFLLLVLIPCICALVLLLVILLSYVGTLQKVYFKSNGSEPLVTDGEIQGSDVILTNTIYNQSTVVSTAHPDQHVPAWTTDASLPGDQSHRNTSACMNITHSQCQMLPYHATLTPLLSVVRNMEMEKFLKFFTYLHRLSCYQHIMLFGCTLAFPECIIDGDDSHGLLPCRSFCEAAKEGCESVLGMVNYSWPDFLRCSQFRNQTESSNVSRICFSPQQENGKQLLCGRGENFLCASGICIPGKLQCNGYNDCDDWSDEAHCNCSENLFHCHTGKCLNYSLVCDGYDDCGDLSDEQNCDCNPTTEHRCGDGRCIAMEWVCDGDHDCVDKSDEVNCSCHSQGLVECRNGQCIPSTFQCDGDEDCKDGSDEENCSVIQTSCQEGDQRCLYNPCLDSCGGSSLCDPNNSLNNCSQCEPITLELCMNLPYNSTSYPNYFGHRTQKEASISWESSLFPALVQTNCYKYLMFFSCTILVPKCDVNTGEHIPPCRALCEHSKERCESVLGIVGLQWPEDTDCSQFPEENSDNQTCLMPDEYVEECSPSHFKCRSGQCVLASRRCDGQADCDDDSDEENCGCKERDLWECPSNKQCLKHTVICDGFPDCPDYMDEKNCSFCQDDELECANHACVSRDLWCDGEADCSDSSDEWDCVTLSINVNSSSFLMVHRAATEHHVCADGWQEILSQLACKQMGLGEPSVTKLIQEQEKEPRWLTLHSNWESLNGTTLHELLVNGQSCESRSKISLLCTKQDCGRRPAARMNKRILGGRTSRPGRWPWQCSLQSEPSGHICGCVLIAKKWVLTVAHCFEGRENAAVWKVVLGINNLDHPSVFMQTRFVKTIILHPRYSRAVVDYDISIVELSEDISETGYVRPVCLPNPEQWLEPDTYCYITGWGHMGNKMPFKLQEGEVRIISLEHCQSYFDMKTITTRMICAGYESGTVDSCMGDSGGPLVCEKPGGRWTLFGLTSWGSVCFSKVLGPGVYSNVSYFVEWIKRQIYIQTFLLN |
| Enzyme Length | 1042 |
| Uniprot Accession Number | Q9Y5Q5 |
| Absorption | |
| Active Site | ACT_SITE 843; /note=Charge relay system; /evidence=ECO:0000250; ACT_SITE 892; /note=Charge relay system; /evidence=ECO:0000250; ACT_SITE 985; /note=Charge relay system |
| Activity Regulation | ACTIVITY REGULATION: Inhibited in a dose-dependent manner by non-specific trypsin-like serine protease inhibitors including benzamidine. |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | 3.4.21.- |
| Enzyme Function | FUNCTION: Serine-type endopeptidase involved in atrial natriuretic peptide (NPPA) and brain natriuretic peptide (NPPB) processing (PubMed:10880574, PubMed:21288900, PubMed:20489134, PubMed:21763278). Converts through proteolytic cleavage the non-functional propeptides NPPA and NPPB into their active hormones, ANP and BNP(1-32) respectively, thereby regulating blood pressure in the heart and promoting natriuresis, diuresis and vasodilation (PubMed:10880574, PubMed:21288900, PubMed:20489134, PubMed:21763278). Proteolytic cleavage of pro-NPPA also plays a role in female pregnancy by promoting trophoblast invasion and spiral artery remodeling in uterus (PubMed:22437503). Also acts as a regulator of sodium reabsorption in kidney (By similarity). {ECO:0000250|UniProtKB:Q9Z319, ECO:0000269|PubMed:10880574, ECO:0000269|PubMed:20489134, ECO:0000269|PubMed:21288900, ECO:0000269|PubMed:21763278, ECO:0000269|PubMed:22437503}.; FUNCTION: [Isoform 2]: Has weaker endopeptidase activity compared to isoform 1. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (3); Alternative sequence (1); Chain (6); Compositional bias (1); Disulfide bond (36); Domain (11); Glycosylation (19); Motif (1); Mutagenesis (11); Natural variant (5); Region (1); Sequence conflict (2); Site (3); Topological domain (2); Transmembrane (1) |
| Keywords | Alternative splicing;Autocatalytic cleavage;Cell membrane;Disulfide bond;Glycoprotein;Hydrolase;Membrane;Protease;Reference proteome;Repeat;Secreted;Serine protease;Signal-anchor;Transmembrane;Transmembrane helix;Zymogen |
| Interact With | Q13520; O00501; P54849; Q8TED1 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:19751717, ECO:0000269|PubMed:21288900, ECO:0000269|PubMed:21518754}; Single-pass type II membrane protein {ECO:0000269|PubMed:19751717, ECO:0000269|PubMed:21288900, ECO:0000269|PubMed:21518754}. Note=May easily detached from the endothelial cell membrane.; SUBCELLULAR LOCATION: [Isoform 2]: Cell membrane; Single-pass type II membrane protein. Note=Less efficiently targeted to the cell membrane compared to isoform 1.; SUBCELLULAR LOCATION: [Atrial natriuretic peptide-converting enzyme, 180 kDa soluble fragment]: Secreted. Note=Soluble form produced following cleavage by ADAM10.; SUBCELLULAR LOCATION: [Atrial natriuretic peptide-converting enzyme, 160 kDa soluble fragment]: Secreted. Note=Soluble form produced following autocatalytic cleavage.; SUBCELLULAR LOCATION: [Atrial natriuretic peptide-converting enzyme, 100 kDa soluble fragment]: Secreted. Note=Soluble form produced following autocatalytic cleavage. |
| Modified Residue | |
| Post Translational Modification | PTM: N-glycosylated; required for processing and activation. {ECO:0000269|PubMed:17660514, ECO:0000269|PubMed:21518754}.; PTM: Activated through proteolytic processing by a trypsin-like protease; cleaved into a N-terminal propeptide and an activated corin protease fragment. Different soluble forms are produced by cleavage and autocatalytic cleavage: Atrial natriuretic peptide-converting enzyme, 180 kDa soluble fragment is produced by cleavage by ADAM10, while 160 kDa and 100 kDa soluble fragments are produced by autocatalytic cleavage. Cleavage by ADAM10 to produce soluble 180 kDa soluble fragment takes place after the transmembrane region and before FZ 1.; PTM: A disulfide bond links the activated corin protease fragment and the N-terminal propeptide. The disulfide bond also links the activated corin protease fragment with soluble fragments (100 kDa, 160 kDa and 180 kDa fragments). |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 11884416; 12154094; 15192093; 16216958; 17296875; 17890485; 18669922; 19326473; 19913121; 19919978; 20613715; 20628086; 20670840; 20802129; 21216831; 22093942; 22987923; 23327554; 23372161; 23434834; 24015598; 24100222; 24828501; 25451932; 25474356; 25488193; 25516437; 25649697; 25663063; 25981578; 26022632; 26048191; 26086065; 26259032; 26344336; 26488448; 26577631; 27343265; 27871468; 27898523; 28005267; 28714548; 28861913; 29180304; 29370493; 29391274; 29523263; 30195494; 30352487; 30580684; 30765878; 31856714; 32719113; 32828311; 33125488; 34369881; 34846782; |
| Motif | MOTIF 26..29; /note=DDNN motif |
| Gene Encoded By | |
| Mass | 116,486 |
| Kinetics | BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=1.28 mM for pyroGlu-Phe-Lys-pNA.HCl {ECO:0000269|PubMed:14559895}; KM=3.52 mM for pyroGlu-Pro-Arg-pNA.HCl {ECO:0000269|PubMed:14559895}; KM=2.95 mM for H-D-Pro-Phe-Arg-pNA.2HCl {ECO:0000269|PubMed:14559895}; KM=1.92 mM for Bz-Ile-Glu-(gamma-OR)-Gly-Arg-pNA.HCl {ECO:0000269|PubMed:14559895}; KM=16 mM for pyroGlu-Gly-Arg-pNA.HCl {ECO:0000269|PubMed:14559895}; |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |