CORIN

Not to be confused with Lipoprotein receptor-related protein 4, which is also abbreviated as LRP4.
Corin, serine peptidase
Identifiers
Symbols CORIN ; ATC2; CRN; Lrp4; PEE5; TMPRSS10
External IDs OMIM: 605236 MGI: 1349451 HomoloGene: 4804 GeneCards: CORIN Gene
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez 10699 53419
Ensembl ENSG00000145244 ENSMUSG00000005220
UniProt Q9Y5Q5 Q9Z319
RefSeq (mRNA) NM_001278585 NM_001122756
RefSeq (protein) NP_001265514 NP_001116228
Location (UCSC) Chr 4:
47.59 – 47.84 Mb		 Chr 5:
72.3 – 72.5 Mb
PubMed search

Corin, also called atrial natriuretic peptide-converting enzyme, is a protein that in humans is encoded by the CORIN gene.[1][2]

Protein

The CORIN 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.

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

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

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

  1. 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): 14926–35. 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. 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. PMID 25451932.
  9. 1 2 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. 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. 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. PMID 24015598.
  14. 1 2 3 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. PMID 22437503.
  15. 1 2 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. 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. 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. 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. 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. 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. 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. PMID 23372161.

Further reading

  • 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. 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. 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. PMID 24407448. 
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