CORIN

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

Not to be confused with Lipoprotein receptor-related protein 4, which is also abbreviated as LRP4.
CORIN
Identifiers
AliasesCORIN, ATC2, CRN, Lrp4, PEE5, TMPRSS10, corin, serine peptidase
External IDsOMIM: 605236 MGI: 1349451 HomoloGene: 4804 GeneCards: CORIN
Gene location (Human)
Chr.Chromosome 4 (human)[1]
Band4p12Start47,593,999 bp[1]
End47,838,106 bp[1]
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

10699

53419

Ensembl

ENSG00000145244

ENSMUSG00000005220

UniProt

Q9Y5Q5

Q9Z319

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 MbChr 5: 72.3 – 72.5 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.[18][19][27]

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References
  1. GRCh38: Ensembl release 89: ENSG00000145244 - Ensembl, May 2017
  2. 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. 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.
  6. "Entrez Gene: CORIN corin, serine peptidase".
  7. 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.
  8. 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.
  9. 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.
  10. 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.
  11. 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.
  12. 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.
  13. 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.
  14. 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.
  15. 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.
  16. 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.
  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. PMC 4522930. PMID 24015598.
  18. 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.
  19. 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.
  20. 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.
  21. 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.
  22. 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.
  23. 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.
  24. 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.
  25. 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.
  26. 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.
  27. 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.

Further reading
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