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FLASH GENE
Symbol CORIN contributors: mct/npt - updated : 10-01-2015
HGNC name corin, serine protease
HGNC id 19012
Location 4p12      Physical location : 47.596.019 - 47.840.059
Synonym name
  • corin
  • pro-ANP-converting enzyme
  • heart specific serine proteinase
  • atrial natriuteric peptide-converting enzyme
  • transmembrane protease, serine 10
    • Synonym symbol(s) ATC2, CRN, PRSC, TMPRSS10, Lrp4
    EC.number 3.4.21.-
    DNA
    TYPE functioning gene
    STRUCTURE 244.11 kb     22 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    22 - 4942 - 1042 - Pan (2002)
    20 - 4703 - 938 - -
    14 - 2442 - 734 - -
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly Homo sapiens
    Reproductivefemale systemplacenta    Homo sapiens
    Urinarykidney   highly Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumcardiac  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticprogenitor cell Homo sapiens
    Muscularmyocyte
    not specificchondrocyte Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text bone, kidney
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • short N terminal cytoplasmic domain and transmembrane sequence
  • 19 predicted N-glycosylation sites in its extracellular domains
  • two frizzled-like cysteine-rich motifs
  • eight LDL-receptor domains,a macrophage scavenger receptor domain
  • a C terminal trypsin-like protease domain
  • a sequence in the cytoplasmic tail plays an important role in corin cell surface targeting and zymogen activation
    • HOMOLOGY
    Homologene
    FAMILY
  • peptidase S1 family
    • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
    text type 2 membrane protein
    basic FUNCTION
  • converting pro-atrial natriuretic peptide to biologically active atrial natriuretic peptide, a cardiac hormone that regulates blood volume and pressure
  • may also function as a pro-brain-type natriuretic peptide convertase
  • may also contribute to the regulation of the natriuretic peptide system,, and might be an attractive target for treatment of cardiovascular diseases (Gladysheva 2008)
  • native corin is a glycosylated protease that is localized on the cell surface of pro-NPPA-expressing cardiomyocytes in both zymogen and catalytically active forms (Gladysheva 2008)
  • important in maintaining normal blood pressure and corin deficiency may contribute to hypertension and heart disease in patients (Wu 2009)
  • new function of corin and NPPA in promoting trophoblast invasion and spiral artery remodelling
  • CORIN and NPPA are essential for physiological changes at the maternal-fetal interface, suggesting that defects in CORIN and NPPA function may contribute to pre-eclampsia
  • has potentially an important role in a new adaptive mechanism of the response to variations of salt in the diet
  • plays a role in cardiomyopathy by modulating myocardial fibrosis, cardiac function, heart failure, and survival
  • plays a critical role in trophoblast migration and spiral artery remodeling during early pregnancy in humans
  • cardiac protease that activates the natriuretic peptides
  • mediates an essential step in the cascade of natriuretic peptide biosynthesis and eventually their action
  • membrane-bound protease essential for activating natriuretic peptides and regulating blood pressure
  • serine protease which activates pro-atrial natriuretic peptide, has recently been shown to be involved in the pathophysiology of preeclampsia
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS cardiovascular , development
    text
  • embryogenesis
  • blood pressure
    • PATHWAY
    metabolism lipid/lipoprotein
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding to GATA4 essential for cardiac expression
  • ADAM10-mediated shedding and CORIN autocleavage are important mechanisms regulating CORIN function and preventing excessive, potentially hazardous, proteolytic activities in the heart
  • activates atrial natriuretic peptide (NPPA), a cardiac hormone that is important in regulating blood pressure
  • N-glycans are required for corin cell surface expression and zymogen activation
    • cell & other
    REGULATION
    activated by N-linked oligosaccharides that play an important role in corin activation (Liao 2007)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    in heart failure, plasma corin levels were significantly lower compared with that of healthy controls, but not in those with acute myocardial infarction (Dong 2010)
    constitutional       loss of function
    with inhibition of natriuretic peptides following exposure to IR may contribute to the development of Radiation-induced heart disease (RIHD) through the acceleration of cellular senescence
    constitutional     --low  
    in patients with osteoporosis and the reduction was associated with high rates of bone turnover
    constitutional     --low  
    reduced corin levels in the kidney may reflect the underlying pathology in CKD (chronic kidney disease)
    Susceptibility
  • to heart failure
  • to preeclampsia
    • Variant & Polymorphism other
  • corin I555(P568) allele is associated with an increased risk for death or heart failure (Rame 2009)
  • two minor alleles (C for rs2271036 and G for rs2271037) were significantly associated to preeclampsia (
    • Candidate gene
  • plasma corin may be used as a biomarker in the diagnosis of heart failure (Dong 2010)
  • promising biomarker of cardiomyopathy and heart failure
    • Marker
  • low serum corin levels may reflect impaired bone homeostasis in patients with osteoporosis
    • Therapy target
    ANIMAL & CELL MODELS
  • mice deficient in either Corin or ANP displayed poor trophoblast invasion, impaired spiral artery remodeling and phenocopied human pre-eclampsia
  • corin overexpression significantly prolonged life in mice with dilated cardiomyopathy
  • pregnant corin- or Nppa-deficient mice developed high blood pressure and proteinuria, characteristics of pre-eclampsia (pMID: 22437503)