Corin

Corin
Properties of human protein
Mass / length primary structure	1042 amino acids
Secondary to quaternary structure	single pass type II membrane protein
Identifier
Gene name	CORIN
External IDs	OMIM : 605236 ; UniProt : Q9Y5Q5 ;
Enzyme classification
EC, category	3.4.21. , Serine protease
MEROPS	S01.019
Response type	hydrolysis
Substrate	Pro-ANP
Products	ANP
Occurrence
Homology family	ANP-converting enzyme
Parent taxon	Euteleostomi
	Orthologue

Corin is an enzyme found in most vertebrate animals .

It is a membrane-bound serine protease of the heart , which activates the peptide hormone atrial natriuretic peptide (ANP) . Corin is involved in blood pressure regulation. Corin deficiency can potentially lead to arterial high blood pressure and thus to pressure-related heart disease .

The Natriuretic Peptide System

The natriuretic peptide system is an endocrine system that is involved in the regulation of the electrolyte and fluid balance . The system consists of three members of similar structure: Atrial Natriuretic Peptide ( ANP) , Brain Natriuretic Peptide (BNP) and C-Type Natriuretic Peptide (CNP) . ANP and BNP are mainly synthesized in the heart, while CNP is synthesized in the brain , kidneys , bones and blood vessels , among others . ANP and BNP regulate blood volume and pressure . With increased blood volume or blood pressure, ANP and BNP are released into the bloodstream and lead to an increased excretion of sodium ( natriuresis ) and water ( diuresis ) in the kidneys and blood vessels , to an expansion of the blood vessels ( vasodilation ), and to an inhibition of the release of Renin and endothelin , thus lowering blood volume and blood pressure. CNP inhibits cell growth of smooth muscle cells and inhibits in animal studies , a narrowing of the coronary arteries .

The natriuretic peptides are synthesized as inactive prohormones . By a signal peptidase is the respective pre-pro peptide initially the signal peptide cleaved, there arises the propeptide . The propeptide is cleaved into the inactive N-terminal peptide and the biologically active C-terminal peptide by a propeptide convertase .

Corin specifically splits Pro-ANP to ANP and, to a lesser extent, is also able to split Pro-BNP.

The cardiac serine protease Corin

Corin is a membrane-bound serine protease that is expressed in heart muscle cells .

Corin consists of an N-terminal transmembrane domain , two frizzled-like domains , eight LDL receptor repetitions, a scavenger receptor domain and a trypsin- like protease domain. Corin consists of 1042 amino acids and is a particularly large protein. Corin has a molecular mass of approx. 150–200 kDa and has 19 glycosylation sites. The human CORIN gene is one of the largest known protease genes . It is located on chromonsome 4p12-13 with 22 exons and an extension of over 200 kilobases .

Corin is mainly formed in the myocardial cells, the expression of Corin m-RNA is stronger in the muscles of the atria than in the heart chambers . Small amounts of Corin m-RNA have also been found in kidneys , bones and hair follicles . In other muscle-rich tissues such as stomach , small intestine , urinary bladder , skeletal muscles and non-pregnant uterus , however, Corin m-RNA was not detected.

Corin splits Pro-ANP into ANP. Knockout mice lacking the CORIN gene produce pro-ANP but no ANP in the heart muscle tissue. If Corin is fed to the knockout mice, they are able to convert pro-ANP into ANP. Corin can also split pro-BNP, albeit less efficiently than pro-ANP. In contrast, Pro-CNP is not split by Corin. The activation pathway of Pro-CNP differs from the activation of ANP and BNP in that CNP is activated in the cell ( intracellular ), whereas ANP and BNP are activated on the cell membrane ( extracellular ).

Animal data

CORIN knockout mice develop high blood pressure , especially when they have an increased intake of table salt . Corin m-RNA is not detectable in the non-pregnant uterus, whereas large amounts of Corin can be detected in the pregnant uterus. Pregnant CORIN knockout mice develop gestational hypertension and proteinuria , a condition that resembles preeclampsia .

Corin variants in humans

So far, two variants of the CORIN gene ( single nucleotide polymorphisms (SNP) ) have been described, which are more common in Americans of black African descent (approx. 12%) than in whites (<0.2%).

Carriers of the gene variant CORIN gene variant I555 / P568 have an increased risk of developing arterial high blood pressure and heart enlargement (concentric cardiac hypertrophy) .

swell

Qingyu Wu, Ye Olivia Xu-Cai, Shenghan Chen, Wei Wang: Corin: new insights into the natriuretic peptide system . In: Kidney International . 75, No. 2, January 2009, pp. 142-146. doi : 10.1038 / ki.2008.418 . PMID 18716601 .