CORIN

Last updated
CORIN
Identifiers
Aliases CORIN , ATC2, CRN, Lrp4, PEE5, TMPRSS10, corin, serine peptidase
External IDs OMIM: 605236 MGI: 1349451 HomoloGene: 4804 GeneCards: CORIN
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_006587
NM_001278585
NM_001278586

NM_001122756
NM_016869

RefSeq (protein)

NP_001265514
NP_001265515
NP_006578

NP_001116228
NP_058565

Location (UCSC) Chr 4: 47.59 – 47.84 Mb Chr 5: 72.46 – 72.66 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Corin, also called atrial natriuretic peptide-converting enzyme, is a protein that in humans is encoded by the CORIN gene. [5] [6]

Contents

Protein

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]

Function

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 and mutations

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]

Related Research Articles

<span class="mw-page-title-main">Atrial natriuretic peptide</span> Cardiac hormone which increases renal sodium excretion

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.

<span class="mw-page-title-main">Enteropeptidase</span> Class of enzymes

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.

Adenosine A<sub>1</sub> receptor Cell surface receptor found in humans

The adenosine A1 receptor (A1AR) is one member of the adenosine receptor group of G protein-coupled receptors with adenosine as endogenous ligand.

<span class="mw-page-title-main">Caspase-9</span> Protein-coding gene in the species Homo sapiens

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.

<span class="mw-page-title-main">Coagulation factor II receptor</span> Mammalian protein found in humans

Proteinase-activated receptor 1 (PAR1) also known as protease-activated receptor 1 or coagulation factor II (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.

<span class="mw-page-title-main">Natriuretic peptide precursor C</span> Protein-coding gene in the species Homo sapiens

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).

<span class="mw-page-title-main">NPR2</span> Protein-coding gene in Homo sapiens

Natriuretic peptide receptor B/guanylate cyclase B , also known as NPR2, is an atrial natriuretic peptide receptor. In humans it is encoded by the NPR2 gene.

<span class="mw-page-title-main">NPR3</span> Protein-coding gene in humans

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.

<span class="mw-page-title-main">ST14</span> Protein-coding gene in the species Homo sapiens

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.

<span class="mw-page-title-main">KLK6</span> Protein-coding gene in the species Homo sapiens

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.

<span class="mw-page-title-main">Fibroblast activation protein, alpha</span>

Fibroblast activation protein alpha (FAP-alpha) also known as prolyl endopeptidase FAP is an enzyme that in humans is encoded by the FAP gene.

<span class="mw-page-title-main">SPINT1</span> Protein-coding gene in the species Homo sapiens

Kunitz-type protease inhibitor 1 is an enzyme that in humans is encoded by the SPINT1 gene.

<span class="mw-page-title-main">KLK7</span> Protein-coding gene in the species Homo sapiens

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).

<span class="mw-page-title-main">HGFAC</span> Protein-coding gene in humans

Hepatocyte growth factor activator is a protein that in humans is encoded by the HGFAC gene.

<span class="mw-page-title-main">PRSS8</span> Protein-coding gene in the species Homo sapiens

Prostasin is a protein that in humans is encoded by the PRSS8 gene.

<span class="mw-page-title-main">HPN (gene)</span> Protein-coding gene in humans

Serine protease hepsin is an enzyme that in humans is encoded by the HPN gene.

<span class="mw-page-title-main">MYL7</span> Protein-coding gene in the species Homo sapiens

Atrial Light Chain-2 (ALC-2) also known as Myosin regulatory light chain 2, atrial isoform (MLC2a) is a protein that in humans is encoded by the MYL7 gene. ALC-2 expression is restricted to cardiac muscle atria in healthy individuals, where it functions to modulate cardiac development and contractility. In human diseases, including hypertrophic cardiomyopathy, dilated cardiomyopathy, ischemic cardiomyopathy and others, ALC-2 expression is altered.

Cenderitide is a natriuretic peptide developed by the Mayo Clinic as a potential treatment for heart failure. Cenderitide is created by the fusion of the 15 amino acid C-terminus of the snake venom dendroaspis natriuretic peptide (DNP) with the full C-type natriuretic peptide (CNP) structure. This peptide chimera is a dual activator of the natriuretic peptide receptors NPR-A and NPR-B and therefore exhibits the natriuretic and diuretic properties of DNP, as well as the antiproliferative and antifibrotic properties of CNP.

<span class="mw-page-title-main">Glutamyl endopeptidase GluV8</span>

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.

<span class="mw-page-title-main">Brain natriuretic peptide 32</span> Hormone secreted in the heart

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.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000145244 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000005220 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 1 2 3 Yan W, Sheng N, Seto M, Morser J, Wu Q (May 1999). "Corin, a mosaic transmembrane serine protease encoded by a novel cDNA from human heart". The Journal of Biological Chemistry. 274 (21): 14926–14935. doi: 10.1074/jbc.274.21.14926 . PMID   10329693.
  6. "Entrez Gene: CORIN corin, serine peptidase".
  7. Hooper JD, Scarman AL, Clarke BE, Normyle JF, Antalis TM (December 2000). "Localization of the mosaic transmembrane serine protease corin to heart myocytes". European Journal of Biochemistry. 267 (23): 6931–6937. doi: 10.1046/j.1432-1033.2000.01806.x . PMID   11082206.
  8. Chen S, Cao P, Dong N, Peng J, Zhang C, Wang H, et al. (September 2015). "PCSK6-mediated corin activation is essential for normal blood pressure". Nature Medicine. 21 (9): 1048–1053. doi:10.1038/nm.3920. PMC   4710517 . PMID   26259032.
  9. Knappe S, Wu F, Masikat MR, Morser J, Wu Q (December 2003). "Functional analysis of the transmembrane domain and activation cleavage of human corin: design and characterization of a soluble corin". The Journal of Biological Chemistry. 278 (52): 52363–52370. doi: 10.1074/jbc.M309991200 . PMID   14559895.
  10. Liao X, Wang W, Chen S, Wu Q (September 2007). "Role of glycosylation in corin zymogen activation". The Journal of Biological Chemistry. 282 (38): 27728–27735. doi: 10.1074/jbc.M703687200 . PMID   17660514.
  11. Gladysheva IP, King SM, Houng AK (August 2008). "N-glycosylation modulates the cell-surface expression and catalytic activity of corin". Biochemical and Biophysical Research Communications. 373 (1): 130–135. doi:10.1016/j.bbrc.2008.05.181. PMID   18549807.
  12. Wang H, Zhou T, Peng J, Xu P, Dong N, Chen S, et al. (January 2015). "Distinct roles of N-glycosylation at different sites of corin in cell membrane targeting and ectodomain shedding". The Journal of Biological Chemistry. 290 (3): 1654–1663. doi: 10.1074/jbc.M114.606442 . PMC   4340409 . PMID   25451932.
  13. 1 2 Yan W, Wu F, Morser J, Wu Q (July 2000). "Corin, a transmembrane cardiac serine protease, acts as a pro-atrial natriuretic peptide-converting enzyme". Proceedings of the National Academy of Sciences of the United States of America. 97 (15): 8525–8529. Bibcode:2000PNAS...97.8525Y. doi: 10.1073/pnas.150149097 . PMC   26981 . PMID   10880574.
  14. Chan JC, Knudson O, Wu F, Morser J, Dole WP, Wu Q (January 2005). "Hypertension in mice lacking the proatrial natriuretic peptide convertase corin". Proceedings of the National Academy of Sciences of the United States of America. 102 (3): 785–790. Bibcode:2005PNAS..102..785C. doi: 10.1073/pnas.0407234102 . PMC   545541 . PMID   15637153.
  15. Wang W, Shen J, Cui Y, Jiang J, Chen S, Peng J, et al. (July 2012). "Impaired sodium excretion and salt-sensitive hypertension in corin-deficient mice". Kidney International. 82 (1): 26–33. doi:10.1038/ki.2012.41. PMC   3376235 . PMID   22418978.
  16. Semenov AG, Tamm NN, Seferian KR, Postnikov AB, Karpova NS, Serebryanaya DV, et al. (July 2010). "Processing of pro-B-type natriuretic peptide: furin and corin as candidate convertases". Clinical Chemistry. 56 (7): 1166–1176. doi: 10.1373/clinchem.2010.143883 . PMID   20489134.
  17. Ichiki T, Huntley BK, Burnett JC (2013). "BNP molecular forms and processing by the cardiac serine protease corin". Advances in Clinical Chemistry. 61: 1–31. doi:10.1016/b978-0-12-407680-8.00001-4. ISBN   9780124076808. PMC   4522930 . PMID   24015598.
  18. 1 2 3 Cui Y, Wang W, Dong N, Lou J, Srinivasan DK, Cheng W, et al. (March 2012). "Role of corin in trophoblast invasion and uterine spiral artery remodelling in pregnancy". Nature. 484 (7393): 246–250. Bibcode:2012Natur.484..246C. doi:10.1038/nature10897. PMC   3578422 . PMID   22437503.
  19. 1 2 Dong N, Zhou T, Zhang Y, Liu M, Li H, Huang X, et al. (June 2014). "Corin mutations K317E and S472G from preeclamptic patients alter zymogen activation and cell surface targeting. [Corrected]". The Journal of Biological Chemistry. 289 (25): 17909–17916. doi: 10.1074/jbc.M114.551424 . PMC   4067221 . PMID   24828501.
  20. Enshell-Seijffers D, Lindon C, Morgan BA (January 2008). "The serine protease Corin is a novel modifier of the Agouti pathway". Development. 135 (2): 217–225. doi:10.1242/dev.011031. PMC   2186067 . PMID   18057101.
  21. Qi X, Jiang J, Zhu M, Wu Q (June 2011). "Human corin isoforms with different cytoplasmic tails that alter cell surface targeting". The Journal of Biological Chemistry. 286 (23): 20963–20969. doi: 10.1074/jbc.M110.217570 . PMC   3121476 . PMID   21518754.
  22. Dries DL, Victor RG, Rame JE, Cooper RS, Wu X, Zhu X, et al. (October 2005). "Corin gene minor allele defined by 2 missense mutations is common in blacks and associated with high blood pressure and hypertension". Circulation. 112 (16): 2403–2410. doi: 10.1161/CIRCULATIONAHA.105.568881 . PMID   16216958.
  23. Rame JE, Drazner MH, Post W, Peshock R, Lima J, Cooper RS, et al. (April 2007). "Corin I555(P568) allele is associated with enhanced cardiac hypertrophic response to increased systemic afterload". Hypertension. 49 (4): 857–864. doi: 10.1161/01.HYP.0000258566.95867.9e . PMID   17296875.
  24. Wang W, Liao X, Fukuda K, Knappe S, Wu F, Dries DL, et al. (August 2008). "Corin variant associated with hypertension and cardiac hypertrophy exhibits impaired zymogen activation and natriuretic peptide processing activity". Circulation Research. 103 (5): 502–508. doi:10.1161/CIRCRESAHA.108.177352. PMC   2652846 . PMID   18669922.
  25. Wang W, Cui Y, Shen J, Jiang J, Chen S, Peng J, et al. (November 2012). "Salt-sensitive hypertension and cardiac hypertrophy in transgenic mice expressing a corin variant identified in blacks". Hypertension. 60 (5): 1352–1358. doi:10.1161/HYPERTENSIONAHA.112.201244. PMC   3475733 . PMID   22987923.
  26. Zhang Y, Li H, Zhou J, Wang A, Yang J, Wang C, et al. (December 2014). "A corin variant identified in hypertensive patients that alters cytoplasmic tail and reduces cell surface expression and activity". Scientific Reports. 4: 7378. Bibcode:2014NatSR...4E7378Z. doi:10.1038/srep07378. PMC   4260221 . PMID   25488193.
  27. Baris Feldman H, Chai Gadot C, Zahler D, Mory A, Aviram G, Elhanan E, et al. (November 2023). "Corin and Left Atrial Cardiomyopathy, Hypertension, Arrhythmia, and Fibrosis". The New England Journal of Medicine. 389 (18): 1685–1692. doi:10.1056/NEJMoa2301908. PMID   37913506. S2CID   264931773.
  28. Dong N, Fang C, Jiang Y, Zhou T, Liu M, Zhou J, et al. (March 2013). "Corin mutation R539C from hypertensive patients impairs zymogen activation and generates an inactive alternative ectodomain fragment". The Journal of Biological Chemistry. 288 (11): 7867–7874. doi: 10.1074/jbc.M112.411512 . PMC   3597824 . PMID   23372161.

Further reading