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.[1][3] Corin is synthesized as a zymogen that is activated by PCSK6.[4]
Corin exhibits a trypsin-like catalytic activity favoring basic residues at the P1 position.[5]
Human corin contains 19 N-glycosylation sites.[1]N-glycans promote corin expression on the cell surface and protect corin from metalloproteinase-mediated shedding.[6][7][8]
Corin converts the atrial natriuretic peptide (ANP) precursor, pro-ANP, to mature ANP, a cardiac hormone that regulates salt-water balance and blood pressure.[9] In mice, corin deficiency prevents pro-ANP processing and causes salt-sensitive hypertension.[10][11]
Corin may also function as a pro-brain-type natriuretic peptide convertase.[9][12][13]
Corin-mediated ANP production in the pregnant uterus promotes spiral artery remodeling and trophoblast invasion.[14]CORIN mutations have been reported in patients with preeclampsia.[14][15]
In mice, corin functions in the dermal papilla to regulate coat color in an Agouti-dependent pathway.[16]
Variants encoded by alternative exons were reported in human and mouse corin.[17] A variant allele (T555I/Q568P) was found in African Americans with hypertension and cardiac hypertrophy.[18][19] The amino acid substitutions impaired corin activity.[20][21] An insertion variant in exon 1 alters the cytoplasmic tail.[22] This variant appeared more frequently in hypertensive patients. CORIN mutations were found in patients with hypertension.[14][15][23]
↑ 1.01.11.2Yan 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): 14926–35. doi:10.1074/jbc.274.21.14926. PMID10329693.
↑Knappe S, Wu F, Masikat MR, Morser J, Wu Q (Dec 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): 52363–70. doi:10.1074/jbc.M309991200. PMID14559895.
↑Liao X, Wang W, Chen S, Wu Q (Sep 2007). "Role of glycosylation in corin zymogen activation". The Journal of Biological Chemistry. 282 (38): 27728–35. doi:10.1074/jbc.M703687200. PMID17660514.
↑Gladysheva IP, King SM, Houng AK (Aug 2008). "N-glycosylation modulates the cell-surface expression and catalytic activity of corin". Biochemical and Biophysical Research Communications. 373 (1): 130–5. doi:10.1016/j.bbrc.2008.05.181. PMID18549807.
↑Dries DL, Victor RG, Rame JE, Cooper RS, Wu X, Zhu X, Leonard D, Ho SI, Wu Q, Post W, Drazner MH (Oct 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): 2403–10. doi:10.1161/CIRCULATIONAHA.105.568881. PMID16216958.
↑Rame JE, Drazner MH, Post W, Peshock R, Lima J, Cooper RS, Dries DL (Apr 2007). "Corin I555(P568) allele is associated with enhanced cardiac hypertrophic response to increased systemic afterload". Hypertension. 49 (4): 857–64. doi:10.1161/01.HYP.0000258566.95867.9e. PMID17296875.
Hooper JD, Scarman AL, Clarke BE, Normyle JF, Antalis TM (Dec 2000). "Localization of the mosaic transmembrane serine protease corin to heart myocytes". European Journal of Biochemistry / FEBS. 267 (23): 6931–7. doi:10.1046/j.1432-1033.2000.01806.x. PMID11082206.
Wu F, Yan W, Pan J, Morser J, Wu Q (May 2002). "Processing of pro-atrial natriuretic peptide by corin in cardiac myocytes". The Journal of Biological Chemistry. 277 (19): 16900–5. doi:10.1074/jbc.M201503200. PMID11884416.
Pan J, Hinzmann B, Yan W, Wu F, Morser J, Wu Q (Oct 2002). "Genomic structures of the human and murine corin genes and functional GATA elements in their promoters". The Journal of Biological Chemistry. 277 (41): 38390–8. doi:10.1074/jbc.M205686200. PMID12154094.
Knappe S, Wu F, Masikat MR, Morser J, Wu Q (Dec 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): 52363–70. doi:10.1074/jbc.M309991200. PMID14559895.
Knappe S, Wu F, Madlansacay MR, Wu Q (Aug 2004). "Identification of domain structures in the propeptide of corin essential for the processing of proatrial natriuretic peptide". The Journal of Biological Chemistry. 279 (33): 34464–71. doi:10.1074/jbc.M405041200. PMID15192093.
Dries DL, Victor RG, Rame JE, Cooper RS, Wu X, Zhu X, Leonard D, Ho SI, Wu Q, Post W, Drazner MH (Oct 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): 2403–10. doi:10.1161/CIRCULATIONAHA.105.568881. PMID16216958.
Rame JE, Drazner MH, Post W, Peshock R, Lima J, Cooper RS, Dries DL (Apr 2007). "Corin I555(P568) allele is associated with enhanced cardiac hypertrophic response to increased systemic afterload". Hypertension. 49 (4): 857–64. doi:10.1161/01.HYP.0000258566.95867.9e. PMID17296875.
Wu Q (1 May 2007). "The serine protease corin in cardiovascular biology and disease". Frontiers in Bioscience. 12: 4179–90. doi:10.2741/2379. PMID17485366.
Liao X, Wang W, Chen S, Wu Q (Sep 2007). "Role of glycosylation in corin zymogen activation". The Journal of Biological Chemistry. 282 (38): 27728–35. doi:10.1074/jbc.M703687200. PMID17660514.
Peleg A, Jaffe AS, Hasin Y (Nov 2009). "Enzyme-linked immunoabsorbent assay for detection of human serine protease corin in blood". Clinica Chimica Acta; International Journal of Clinical Chemistry. 409 (1–2): 85–9. doi:10.1016/j.cca.2009.09.004. PMID19751717.
Dries DL (Mar 2011). "Process matters: Emerging concepts underlying impaired natriuretic peptide system function in heart failure". Circulation: Heart Failure. 4 (2): 107–10. doi:10.1161/CIRCHEARTFAILURE.111.960948. PMID21406676.
Armaly Z, Assady S, Abassi Z (Nov 2013). "Corin: a new player in the regulation of salt-water balance and blood pressure". Current Opinion in Nephrology and Hypertension. 22 (6): 713–22. doi:10.1097/01.mnh.0000435609.35789.32. PMID24100222.
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