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FLASH GENE

Symbol

CORIN

contributors: mct/npt - updated : 10-01-2015

HGNC name	corin, serine protease
HGNC id	19012

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	244.11 kb     22 Exon(s)

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_006587 22 - 4942 NP_006578 - 1042 - Pan (2002) NM_001278585 20 - 4703 NP_001265514 - 938 - - NM_001278586 14 - 2442 NP_001265515 - 734 - -

EXPRESSION

Type

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart       highly Homo sapiens Reproductive female system placenta       Homo sapiens Urinary kidney       highly Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular striatum cardiac

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic progenitor cell Homo sapiens Muscular myocyte not specific chondrocyte 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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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)