CORIN

Not to be confused with Lipoprotein receptor-related protein 4, which is also abbreviated as LRP4.

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External IDs| GeneCards: [1]
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Species| Human| Mouse
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Corin, also called atrial natriuretic peptide-converting enzyme, is a protein that in humans is encoded by the CORIN gene.[1][2]

## Contents

* 1 Protein
* 2 Function
* 3 Variants and mutations
* 4 References
* 5 External links
* 6 Further reading

## Protein

[edit | edit source]

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]

## Function

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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 and mutations

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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]

## References

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1. ↑ 1.0 1.1 1.2 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): 14926–35. doi:10.1074/jbc.274.21.14926. PMID 10329693.
2. ↑ "Entrez Gene: CORIN corin, serine peptidase".
3. ↑ 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. PMID 11082206.
4. ↑ Chen S, Cao P, Dong N, Peng J, Zhang C, Wang H, Zhou T, Yang J, Zhang Y, Martelli EE, Naga Prasad SV, Miller RE, Malfait AM, Zhou Y, Wu Q (Sep 2015). "PCSK6-mediated corin activation is essential for normal blood pressure". Nature Medicine. 21 (9): 1048–53. doi:10.1038/nm.3920. PMC 4710517. PMID 26259032.
5. ↑ 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. PMID 14559895.
6. ↑ 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. PMID 17660514.
7. ↑ 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. PMID 18549807.
8. ↑ Wang H, Zhou T, Peng J, Xu P, Dong N, Chen S, Wu Q (Jan 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): 1654–63. doi:10.1074/jbc.M114.606442. PMC 4340409. PMID 25451932.
9. ↑ 9.0 9.1 Yan W, Wu F, Morser J, Wu Q (Jul 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): 8525–9. doi:10.1073/pnas.150149097. PMC 26981. PMID 10880574.
10. ↑ Chan JC, Knudson O, Wu F, Morser J, Dole WP, Wu Q (Jan 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): 785–90. doi:10.1073/pnas.0407234102. PMC 545541. PMID 15637153.
11. ↑ Wang W, Shen J, Cui Y, Jiang J, Chen S, Peng J, Wu Q (Jul 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.
12. ↑ Semenov AG, Tamm NN, Seferian KR, Postnikov AB, Karpova NS, Serebryanaya DV, Koshkina EV, Krasnoselsky MI, Katrukha AG (Jul 2010). "Processing of pro-B-type natriuretic peptide: furin and corin as candidate convertases". Clinical Chemistry. 56 (7): 1166–76. doi:10.1373/clinchem.2010.143883. PMID 20489134.
13. ↑ 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. PMC 4522930. PMID 24015598.
14. ↑ 14.0 14.1 14.2 Cui Y, Wang W, Dong N, Lou J, Srinivasan DK, Cheng W, Huang X, Liu M, Fang C, Peng J, Chen S, Wu S, Liu Z, Dong L, Zhou Y, Wu Q (Apr 2012). "Role of corin in trophoblast invasion and uterine spiral artery remodelling in pregnancy". Nature. 484 (7393): 246–50. doi:10.1038/nature10897. PMC 3578422. PMID 22437503.
15. ↑ 15.0 15.1 Dong N, Zhou T, Zhang Y, Liu M, Li H, Huang X, Liu Z, Wu Y, Fukuda K, Qin J, Wu Q (Jun 2014). "Corin mutations K317E and S472G from preeclamptic patients alter zymogen activation and cell surface targeting. [Corrected]". The Journal of Biological Chemistry. 289 (25): 17909–16. doi:10.1074/jbc.M114.551424. PMC 4067221. PMID 24828501.
16. ↑ Enshell-Seijffers D, Lindon C, Morgan BA (Jan 2008). "The serine protease Corin is a novel modifier of the Agouti pathway". Development. 135 (2): 217–25. doi:10.1242/dev.011031. PMC 2186067. PMID 18057101.
17. ↑ Qi X, Jiang J, Zhu M, Wu Q (Jun 2011). "Human corin isoforms with different cytoplasmic tails that alter cell surface targeting". The Journal of Biological Chemistry. 286 (23): 20963–9. doi:10.1074/jbc.M110.217570. PMC 3121476. PMID 21518754.
18. ↑ 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. PMID 16216958.
19. ↑ 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. PMID 17296875.
20. ↑ Wang W, Liao X, Fukuda K, Knappe S, Wu F, Dries DL, Qin J, Wu Q (Aug 2008). "Corin variant associated with hypertension and cardiac hypertrophy exhibits impaired zymogen activation and natriuretic peptide processing activity". Circulation Research. 103 (5): 502–8. doi:10.1161/CIRCRESAHA.108.177352. PMC 2652846. PMID 18669922.
21. ↑ Wang W, Cui Y, Shen J, Jiang J, Chen S, Peng J, Wu Q (Nov 2012). "Salt-sensitive hypertension and cardiac hypertrophy in transgenic mice expressing a corin variant identified in blacks". Hypertension. 60 (5): 1352–8. doi:10.1161/HYPERTENSIONAHA.112.201244. PMC 3475733. PMID 22987923.
22. ↑ Zhang Y, Li H, Zhou J, Wang A, Yang J, Wang C, Liu M, Zhou T, Zhu L, Zhang Y, Dong N, Wu Q (9 December 2014). "A corin variant identified in hypertensive patients that alters cytoplasmic tail and reduces cell surface expression and activity". Scientific Reports. 4: 7378. doi:10.1038/srep07378. PMC 4260221. PMID 25488193.
23. ↑ Dong N, Fang C, Jiang Y, Zhou T, Liu M, Zhou J, Shen J, Fukuda K, Qin J, Wu Q (Mar 2013). "Corin mutation R539C from hypertensive patients impairs zymogen activation and generates an inactive alternative ectodomain fragment". The Journal of Biological Chemistry. 288 (11): 7867–74. doi:10.1074/jbc.M112.411512. PMC 3597824. PMID 23372161.

## External links

[edit | edit source]

* Human CORIN genome location and CORIN gene details page in the UCSC Genome Browser.

## Further reading

[edit | edit source]

* Yan W, Wu F, Morser J, Wu Q (Jul 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): 8525–9. doi:10.1073/pnas.150149097. PMC 26981. PMID 10880574.
* 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. PMID 11082206.
* 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. PMID 11884416.
* 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. PMID 12154094.
* 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. PMID 14559895.
* 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. PMID 15192093.
* 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. PMID 16216958.
* 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. PMID 17296875.
* Wu Q (1 May 2007). "The serine protease corin in cardiovascular biology and disease". Frontiers in Bioscience. 12: 4179–90. doi:10.2741/2379. PMID 17485366.
* 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. PMID 17660514.
* Wu Q, Xu-Cai YO, Chen S, Wang W (Jan 2009). "Corin: new insights into the natriuretic peptide system". Kidney International. 75 (2): 142–6. doi:10.1038/ki.2008.418. PMC 2655200. PMID 18716601.
* 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. PMID 19751717.
* 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. PMID 21406676.
* Zhou Y, Wu Q (Feb 2013). "Role of corin and atrial natriuretic peptide in preeclampsia". Placenta. 34 (2): 89–94. doi:10.1016/j.placenta.2012.11.016. PMC 3563874. PMID 23211473.
* 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. PMID 24100222.
* Zhou Y, Wu Q (Feb 2014). "Corin in natriuretic peptide processing and hypertension". Current Hypertension Reports. 16 (2): 415. doi:10.1007/s11906-013-0415-7. PMC 3941447. PMID 24407448.