CORIN

This gene encodes a member of the type II transmembrane serine protease class of the trypsin superfamily. Members of this family are composed of multiple structurally distinct domains. The encoded protein converts pro-atrial natriuretic peptide to biologically active atrial natriuretic peptide, a cardiac hormone that regulates blood volume and pressure. This protein may also function as a pro-brain-type natriuretic peptide convertase. [provided by RefSeq]

Full Name

corin, serine peptidase

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).

Isoform 2:
has weaker endopeptidase activity compared to isoform 1.

Biological Process

Female pregnancy Source: UniProtKB
Peptide hormone processing Source: UniProtKB
Regulation of blood pressure Source: UniProtKB
Regulation of cardiac conduction Source: Reactome
Regulation of renal sodium excretion Source: UniProtKB
Regulation of systemic arterial blood pressure by atrial natriuretic peptide Source: UniProtKB

Cellular Location

Cell membrane. May easily detached from the endothelial cell membrane.
Isoform 2: Cell membrane. Less efficiently targeted to the cell membrane compared to isoform 1.
Atrial natriuretic peptide-converting enzyme, 180 kDa soluble fragment: Secreted. Soluble form produced following cleavage by ADAM10.
Atrial natriuretic peptide-converting enzyme, 160 kDa soluble fragment: Secreted. Soluble form produced following autocatalytic cleavage.
Atrial natriuretic peptide-converting enzyme, 100 kDa soluble fragment: Secreted. Soluble form produced following autocatalytic cleavage.

Involvement in disease

Pre-eclampsia/eclampsia 5 (PEE5):
A hypertensive disorder of pregnancy characterized by new hypertension (blood pressure 140/90 or greater) presenting after 20 weeks' gestation with clinically relevant proteinuria. It impacts 2 individuals, the mother and her child, both of whom can be severely affected. Preeclampsia is one of the causes of maternal mortality and morbidity worldwide.

Topology

Cytoplasmic: 1-45
Helical: 46-66
Extracellular: 67-1042

PTM

N-glycosylated; required for processing and activation.
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.
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).