| CORIN | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Aliases | CORIN , ATC2, CRN, Lrp4, PEE5, TMPRSS10, corin, serine peptidase | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 605236; MGI: 1349451; HomoloGene: 4804; GeneCards: CORIN; OMA:CORIN - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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| Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Corin, also called atrial natriuretic peptide-converting enzyme, is a protein that in humans is encoded by the CORIN gene. [5] [6]
Human corin, a polypeptide of 1042 amino acids, consists of an N-terminal cytoplasmic domain, a transmembrane domain and an extracellular region with two frizzled-like domains, eight LDL receptor-like domains, a scavenger receptor-like domain and a C-terminal trypsin-like serine protease domain. [5] [7] Corin is synthesized as a zymogen that is activated by PCSK6. [8]
Corin exhibits a trypsin-like catalytic activity favoring basic residues at the P1 position. [9]
Human corin contains 19 N-glycosylation sites. [5] N-glycans promote corin expression on the cell surface and protect corin from metalloproteinase-mediated shedding. [10] [11] [12]
Corin converts the atrial natriuretic peptide (ANP) precursor, pro-ANP, to mature ANP, a cardiac hormone that regulates salt-water balance and blood pressure. [13] In mice, corin deficiency prevents pro-ANP processing and causes salt-sensitive hypertension. [14] [15]
Corin may also function as a pro-brain-type natriuretic peptide convertase. [13] [16] [17]
Corin-mediated ANP production in the pregnant uterus promotes spiral artery remodeling and trophoblast invasion. [18] CORIN mutations have been reported in patients with preeclampsia. [18] [19]
In mice, corin functions in the dermal papilla to regulate coat color in an Agouti-dependent pathway. [20]
Variants encoded by alternative exons were reported in human and mouse corin. [21] A variant allele (T555I/Q568P) was found in African Americans with hypertension and cardiac hypertrophy. [22] [23] The amino acid substitutions impaired corin activity. [24] [25] An insertion variant in exon 1 alters the cytoplasmic tail. [26] This variant appeared more frequently in hypertensive patients. CORIN mutations were found in patients with hypertension. [27] [18] [19] [28]
Atrial Natriuretic Peptide (ANP) or atrial natriuretic factor (ANF) is a natriuretic peptide hormone secreted from the cardiac atria that in humans is encoded by the NPPA gene. Natriuretic peptides are a family of hormone/paracrine factors that are structurally related. The main function of ANP is causing a reduction in expanded extracellular fluid (ECF) volume by increasing renal sodium excretion. ANP is synthesized and secreted by cardiac muscle cells in the walls of the atria in the heart. These cells contain volume receptors which respond to increased stretching of the atrial wall due to increased atrial blood volume.
Enteropeptidase is an enzyme produced by cells of the duodenum and is involved in digestion in humans and other animals. Enteropeptidase converts trypsinogen into its active form trypsin, resulting in the subsequent activation of pancreatic digestive enzymes. Absence of enteropeptidase results in intestinal digestion impairment.
A catalytic triad is a set of three coordinated amino acids that can be found in the active site of some enzymes. Catalytic triads are most commonly found in hydrolase and transferase enzymes. An acid-base-nucleophile triad is a common motif for generating a nucleophilic residue for covalent catalysis. The residues form a charge-relay network to polarise and activate the nucleophile, which attacks the substrate, forming a covalent intermediate which is then hydrolysed to release the product and regenerate free enzyme. The nucleophile is most commonly a serine or cysteine amino acid, but occasionally threonine or even selenocysteine. The 3D structure of the enzyme brings together the triad residues in a precise orientation, even though they may be far apart in the sequence.
Caveolin-3 is a protein that in humans is encoded by the CAV3 gene. Alternative splicing has been identified for this locus, with inclusion or exclusion of a differentially spliced intron. In addition, transcripts utilize multiple polyA sites and contain two potential translation initiation sites.
Caspase-9 is an enzyme that in humans is encoded by the CASP9 gene. It is an initiator caspase, critical to the apoptotic pathway found in many tissues. Caspase-9 homologs have been identified in all mammals for which they are known to exist, such as Mus musculus and Pan troglodytes.
Proteinase-activated receptor 1 (PAR1) also known as protease-activated receptor 1, coagulation factor II receptor and thrombin receptor is a protein that in humans is encoded by the F2R gene. PAR1 is a G protein-coupled receptor and one of four protease-activated receptors involved in the regulation of thrombotic response. Highly expressed in platelets and endothelial cells, PAR1 plays a key role in mediating the interplay between coagulation and inflammation, which is important in the pathogenesis of inflammatory and fibrotic lung diseases. It is also involved both in disruption and maintenance of endothelial barrier integrity, through interaction with either thrombin or activated protein C, respectively.
Natriuretic peptide precursor C, also known as NPPC, is a protein that in humans is encoded by the NPPC gene. The precursor NPPC protein is cleaved to the 22 amino acid peptide C-type natriuretic peptide (CNP).
Natriuretic peptide receptor B (NPR2), also known as atrionatriuretic peptide receptor B and formerly as guanylate cyclase B, is an atrial natriuretic peptide receptor which in humans is encoded by the NPR2 gene.
Natriuretic peptide receptor C/guanylate cyclase C , also known as NPR3, is an atrial natriuretic peptide receptor. In humans it is encoded by the NPR3 gene.
Suppressor of tumorigenicity 14 protein, also known as matriptase, is a protein that in humans is encoded by the ST14 gene. ST14 orthologs have been identified in most mammals for which complete genome data are available.
Kallikrein-6 is a protein that in humans is encoded by the KLK6 gene. Kallikrein-6 is also referred to as neurosin, protease M, hK6, or zyme. It is a 223 amino acid sequence, derived from its 244 original form, which contains a 16 residue presignal and 5 residue activation peptide.
Fibroblast activation protein alpha (FAP-alpha) also known as prolyl endopeptidase FAP is an enzyme that in humans is encoded by the FAP gene.
Kunitz-type protease inhibitor 1 is an enzyme that in humans is encoded by the SPINT1 gene.
Kallikrein-related peptidase 7 (KLK7) is a serine protease that in humans is encoded by the KLK7 gene. KLK7 was initially purified from the epidermis and characterised as stratum corneum chymotryptic enzyme (SCCE). It was later identified as the seventh member of the human kallikrein family, which includes fifteen homologous serine proteases located on chromosome 19 (19q13).
Hepatocyte growth factor activator is a protein that in humans is encoded by the HGFAC gene.
Kallikrein-14 is a protein that in humans is encoded by the KLK14 gene.
Prostasin is a protein that in humans is encoded by the PRSS8 gene.
Serine protease hepsin is an enzyme that in humans is encoded by the HPN gene.
Glutamyl endopeptidase is an extracellular bacterial serine protease of the glutamyl endopeptidase I family that was initially isolated from the Staphylococcus aureus strain V8. The protease is, hence, commonly referred to as "V8 protease", or alternatively SspA from its corresponding gene.
Brain natriuretic peptide 32 (BNP), also known as B-type natriuretic peptide, is a hormone secreted by cardiomyocytes in the heart ventricles in response to stretching caused by increased ventricular blood volume. BNP is one of the three natriuretic peptides, in addition to ANP and CNP.
