{{Short description|Mammalian protein found in Homo sapiens}} {{For|the surname|Corin}} {{distinguish|text=Lipoprotein receptor-related protein 4, which is also abbreviated as LRP4}} {{cs1 config |name-list-style=vanc|display-authors=6}} {{Infobox_gene}} '''Corin''', also called '''atrial natriuretic peptide-converting enzyme''', is a protein that in humans is encoded by the ''CORIN'' gene.<ref name=YanW1999>{{cite journal | vauthors = Yan W, Sheng N, Seto M, Morser J, Wu Q | title = Corin, a mosaic transmembrane serine protease encoded by a novel cDNA from human heart | journal = The Journal of Biological Chemistry | volume = 274 | issue = 21 | pages = 14926–14935 | date = May 1999 | pmid = 10329693 | doi = 10.1074/jbc.274.21.14926 | doi-access = free }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: CORIN corin, serine peptidase| url = https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=10699| access-date = }}</ref>
== 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.<ref name="YanW1999"/><ref>{{cite journal | vauthors = Hooper JD, Scarman AL, Clarke BE, Normyle JF, Antalis TM | title = Localization of the mosaic transmembrane serine protease corin to heart myocytes | journal = European Journal of Biochemistry | volume = 267 | issue = 23 | pages = 6931–6937 | date = December 2000 | pmid = 11082206 | doi = 10.1046/j.1432-1033.2000.01806.x | doi-access = free }}</ref> Corin is synthesized as a zymogen that is activated by PCSK6.<ref>{{cite journal | vauthors = 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 | title = PCSK6-mediated corin activation is essential for normal blood pressure | journal = Nature Medicine | volume = 21 | issue = 9 | pages = 1048–1053 | date = September 2015 | pmid = 26259032 | pmc = 4710517 | doi = 10.1038/nm.3920 }}</ref>
Corin exhibits a trypsin-like catalytic activity favoring basic residues at the P1 position.<ref>{{cite journal | vauthors = Knappe S, Wu F, Masikat MR, Morser J, Wu Q | title = Functional analysis of the transmembrane domain and activation cleavage of human corin: design and characterization of a soluble corin | journal = The Journal of Biological Chemistry | volume = 278 | issue = 52 | pages = 52363–52370 | date = December 2003 | pmid = 14559895 | doi = 10.1074/jbc.M309991200 | doi-access = free }}</ref>
Human corin contains 19 ''N''-glycosylation sites.<ref name="YanW1999"/> ''N''-glycans promote corin expression on the cell surface and protect corin from metalloproteinase-mediated shedding.<ref>{{cite journal | vauthors = Liao X, Wang W, Chen S, Wu Q | title = Role of glycosylation in corin zymogen activation | journal = The Journal of Biological Chemistry | volume = 282 | issue = 38 | pages = 27728–27735 | date = September 2007 | pmid = 17660514 | doi = 10.1074/jbc.M703687200 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Gladysheva IP, King SM, Houng AK | title = N-glycosylation modulates the cell-surface expression and catalytic activity of corin | journal = Biochemical and Biophysical Research Communications | volume = 373 | issue = 1 | pages = 130–135 | date = August 2008 | pmid = 18549807 | doi = 10.1016/j.bbrc.2008.05.181 }}</ref><ref>{{cite journal | vauthors = Wang H, Zhou T, Peng J, Xu P, Dong N, Chen S, Wu Q | title = Distinct roles of N-glycosylation at different sites of corin in cell membrane targeting and ectodomain shedding | journal = The Journal of Biological Chemistry | volume = 290 | issue = 3 | pages = 1654–1663 | date = January 2015 | pmid = 25451932 | pmc = 4340409 | doi = 10.1074/jbc.M114.606442 | doi-access = free }}</ref>
== 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.<ref name=YanW2000>{{cite journal | vauthors = Yan W, Wu F, Morser J, Wu Q | title = Corin, a transmembrane cardiac serine protease, acts as a pro-atrial natriuretic peptide-converting enzyme | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 97 | issue = 15 | pages = 8525–8529 | date = July 2000 | pmid = 10880574 | pmc = 26981 | doi = 10.1073/pnas.150149097 | doi-access = free | bibcode = 2000PNAS...97.8525Y }}</ref> In mice, corin deficiency prevents pro-ANP processing and causes salt-sensitive hypertension.<ref name=ChanJ2005>{{cite journal | vauthors = Chan JC, Knudson O, Wu F, Morser J, Dole WP, Wu Q | title = Hypertension in mice lacking the proatrial natriuretic peptide convertase corin | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 102 | issue = 3 | pages = 785–790 | date = January 2005 | pmid = 15637153 | pmc = 545541 | doi = 10.1073/pnas.0407234102 | doi-access = free | bibcode = 2005PNAS..102..785C }}</ref><ref>{{cite journal | vauthors = Wang W, Shen J, Cui Y, Jiang J, Chen S, Peng J, Wu Q | title = Impaired sodium excretion and salt-sensitive hypertension in corin-deficient mice | journal = Kidney International | volume = 82 | issue = 1 | pages = 26–33 | date = July 2012 | pmid = 22418978 | pmc = 3376235 | doi = 10.1038/ki.2012.41 }}</ref>
Corin may also function as a pro-brain-type natriuretic peptide convertase.<ref name="YanW2000"/><ref>{{cite journal | vauthors = Semenov AG, Tamm NN, Seferian KR, Postnikov AB, Karpova NS, Serebryanaya DV, Koshkina EV, Krasnoselsky MI, Katrukha AG | title = Processing of pro-B-type natriuretic peptide: furin and corin as candidate convertases | journal = Clinical Chemistry | volume = 56 | issue = 7 | pages = 1166–1176 | date = July 2010 | pmid = 20489134 | doi = 10.1373/clinchem.2010.143883 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Ichiki T, Huntley BK, Burnett JC | title = BNP molecular forms and processing by the cardiac serine protease corin | journal = Advances in Clinical Chemistry | volume = 61 | pages = 1–31 | date = 2013 | pmid = 24015598 | pmc = 4522930 | doi = 10.1016/b978-0-12-407680-8.00001-4 | isbn = 9780124076808 }}</ref>
Corin-mediated ANP production in the pregnant uterus promotes spiral artery remodeling and trophoblast invasion.<ref name=CuiY2012>{{cite journal | vauthors = 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 | title = Role of corin in trophoblast invasion and uterine spiral artery remodelling in pregnancy | journal = Nature | volume = 484 | issue = 7393 | pages = 246–250 | date = March 2012 | pmid = 22437503 | pmc = 3578422 | doi = 10.1038/nature10897 | bibcode = 2012Natur.484..246C }}</ref> ''CORIN'' mutations have been reported in patients with preeclampsia.<ref name="CuiY2012"/><ref name=DongN2014>{{cite journal | vauthors = Dong N, Zhou T, Zhang Y, Liu M, Li H, Huang X, Liu Z, Wu Y, Fukuda K, Qin J, Wu Q | title = Corin mutations K317E and S472G from preeclamptic patients alter zymogen activation and cell surface targeting. [Corrected] | journal = The Journal of Biological Chemistry | volume = 289 | issue = 25 | pages = 17909–17916 | date = June 2014 | pmid = 24828501 | pmc = 4067221 | doi = 10.1074/jbc.M114.551424 | doi-access = free }}</ref>
In mice, corin functions in the dermal papilla to regulate coat color in an Agouti-dependent pathway.<ref>{{cite journal | vauthors = Enshell-Seijffers D, Lindon C, Morgan BA | title = The serine protease Corin is a novel modifier of the Agouti pathway | journal = Development | volume = 135 | issue = 2 | pages = 217–225 | date = January 2008 | pmid = 18057101 | pmc = 2186067 | doi = 10.1242/dev.011031 }}</ref>
== Variants and mutations == thumb|right|The golden-brown and pale-faced "sunshine" coat pattern in Siberian cats is due to a mutant corin allele interacting with a black fur color Variants encoded by alternative exons were reported in human and mouse corin.<ref>{{cite journal | vauthors = Qi X, Jiang J, Zhu M, Wu Q | title = Human corin isoforms with different cytoplasmic tails that alter cell surface targeting | journal = The Journal of Biological Chemistry | volume = 286 | issue = 23 | pages = 20963–20969 | date = June 2011 | pmid = 21518754 | pmc = 3121476 | doi = 10.1074/jbc.M110.217570 | doi-access = free }}</ref> A variant allele (T555I/Q568P) was found in African Americans with hypertension and cardiac hypertrophy.<ref>{{cite journal | vauthors = Dries DL, Victor RG, Rame JE, Cooper RS, Wu X, Zhu X, Leonard D, Ho SI, Wu Q, Post W, Drazner MH | title = Corin gene minor allele defined by 2 missense mutations is common in blacks and associated with high blood pressure and hypertension | journal = Circulation | volume = 112 | issue = 16 | pages = 2403–2410 | date = October 2005 | pmid = 16216958 | doi = 10.1161/CIRCULATIONAHA.105.568881 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Rame JE, Drazner MH, Post W, Peshock R, Lima J, Cooper RS, Dries DL | title = Corin I555(P568) allele is associated with enhanced cardiac hypertrophic response to increased systemic afterload | journal = Hypertension | volume = 49 | issue = 4 | pages = 857–864 | date = April 2007 | pmid = 17296875 | doi = 10.1161/01.HYP.0000258566.95867.9e | doi-access = free }}</ref> The amino acid substitutions impaired corin activity.<ref>{{cite journal | vauthors = Wang W, Liao X, Fukuda K, Knappe S, Wu F, Dries DL, Qin J, Wu Q | title = Corin variant associated with hypertension and cardiac hypertrophy exhibits impaired zymogen activation and natriuretic peptide processing activity | journal = Circulation Research | volume = 103 | issue = 5 | pages = 502–508 | date = August 2008 | pmid = 18669922 | pmc = 2652846 | doi = 10.1161/CIRCRESAHA.108.177352 }}</ref><ref>{{cite journal | vauthors = Wang W, Cui Y, Shen J, Jiang J, Chen S, Peng J, Wu Q | title = Salt-sensitive hypertension and cardiac hypertrophy in transgenic mice expressing a corin variant identified in blacks | journal = Hypertension | volume = 60 | issue = 5 | pages = 1352–1358 | date = November 2012 | pmid = 22987923 | pmc = 3475733 | doi = 10.1161/HYPERTENSIONAHA.112.201244 }}</ref> An insertion variant in exon 1 alters the cytoplasmic tail.<ref name=ZhangY2014>{{cite journal | vauthors = Zhang Y, Li H, Zhou J, Wang A, Yang J, Wang C, Liu M, Zhou T, Zhu L, Zhang Y, Dong N, Wu Q | title = A corin variant identified in hypertensive patients that alters cytoplasmic tail and reduces cell surface expression and activity | journal = Scientific Reports | volume = 4 | pages = 7378 | date = December 2014 | pmid = 25488193 | pmc = 4260221 | doi = 10.1038/srep07378 | bibcode = 2014NatSR...4E7378Z }}</ref> This variant appeared more frequently in hypertensive patients. ''CORIN'' mutations were found in patients with hypertension.<ref>{{cite journal | vauthors = Baris Feldman H, Chai Gadot C, Zahler D, Mory A, Aviram G, Elhanan E, Shefer G, Goldiner I, Amir Y, Kurolap A, Ablin JN | title = Corin and Left Atrial Cardiomyopathy, Hypertension, Arrhythmia, and Fibrosis | journal = The New England Journal of Medicine | volume = 389 | issue = 18 | pages = 1685–1692 | date = November 2023 | pmid = 37913506 | doi = 10.1056/NEJMoa2301908 | s2cid = 264931773 }}</ref><ref name="CuiY2012"/><ref name="DongN2014"/><ref>{{cite journal | vauthors = Dong N, Fang C, Jiang Y, Zhou T, Liu M, Zhou J, Shen J, Fukuda K, Qin J, Wu Q | title = Corin mutation R539C from hypertensive patients impairs zymogen activation and generates an inactive alternative ectodomain fragment | journal = The Journal of Biological Chemistry | volume = 288 | issue = 11 | pages = 7867–7874 | date = March 2013 | pmid = 23372161 | pmc = 3597824 | doi = 10.1074/jbc.M112.411512 | doi-access = free }}</ref>
In the cat family (Felidae), mutant alleles of the corin gene are responsible for "golden" or "metallic" fur, in particular the "sunshine" coloration (FIFé EMS Code "u") of the Siberian Forest Cat breed, but also in the British Shorthair and some other domestic cats (where EMS Code "y" is used to denote this coloration), as well as in golden tigers.<ref>{{Cite journal |last1=Beauvois |first1=H. |last2=Dufaure de Citres |first2=C. |last3=Gache |first3=V. |last4=Abitbol |first4=M. |date=10 May 2021 |title=Siberian cats help in solving part of the mystery surrounding golden cats |url=https://onlinelibrary.wiley.com/doi/10.1111/age.13076 |journal=Animal Genetics |volume=52 |issue=4 |pages=482–491 |doi=10.1111/age.13076 |pmid=33970502 |s2cid=234343679 |issn=0268-9146|url-access=subscription }}</ref>
== References == {{reflist|33em}}
== Further reading == {{refbegin|33em}} * {{cite journal | vauthors = Yan W, Wu F, Morser J, Wu Q | title = Corin, a transmembrane cardiac serine protease, acts as a pro-atrial natriuretic peptide-converting enzyme | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 97 | issue = 15 | pages = 8525–8529 | date = July 2000 | pmid = 10880574 | pmc = 26981 | doi = 10.1073/pnas.150149097 | doi-access = free | bibcode = 2000PNAS...97.8525Y }} * {{cite journal | vauthors = Hooper JD, Scarman AL, Clarke BE, Normyle JF, Antalis TM | title = Localization of the mosaic transmembrane serine protease corin to heart myocytes | journal = European Journal of Biochemistry | volume = 267 | issue = 23 | pages = 6931–6937 | date = December 2000 | pmid = 11082206 | doi = 10.1046/j.1432-1033.2000.01806.x | doi-access = free }} * {{cite journal | vauthors = Wu F, Yan W, Pan J, Morser J, Wu Q | title = Processing of pro-atrial natriuretic peptide by corin in cardiac myocytes | journal = The Journal of Biological Chemistry | volume = 277 | issue = 19 | pages = 16900–16905 | date = May 2002 | pmid = 11884416 | doi = 10.1074/jbc.M201503200 | doi-access = free }} * {{cite journal | vauthors = Pan J, Hinzmann B, Yan W, Wu F, Morser J, Wu Q | title = Genomic structures of the human and murine corin genes and functional GATA elements in their promoters | journal = The Journal of Biological Chemistry | volume = 277 | issue = 41 | pages = 38390–38398 | date = October 2002 | pmid = 12154094 | doi = 10.1074/jbc.M205686200 | doi-access = free }} * {{cite journal | vauthors = Knappe S, Wu F, Masikat MR, Morser J, Wu Q | title = Functional analysis of the transmembrane domain and activation cleavage of human corin: design and characterization of a soluble corin | journal = The Journal of Biological Chemistry | volume = 278 | issue = 52 | pages = 52363–52370 | date = December 2003 | pmid = 14559895 | doi = 10.1074/jbc.M309991200 | doi-access = free }} * {{cite journal | vauthors = Knappe S, Wu F, Madlansacay MR, Wu Q | title = Identification of domain structures in the propeptide of corin essential for the processing of proatrial natriuretic peptide | journal = The Journal of Biological Chemistry | volume = 279 | issue = 33 | pages = 34464–34471 | date = August 2004 | pmid = 15192093 | doi = 10.1074/jbc.M405041200 | doi-access = free }} * {{cite journal | vauthors = Dries DL, Victor RG, Rame JE, Cooper RS, Wu X, Zhu X, Leonard D, Ho SI, Wu Q, Post W, Drazner MH | title = Corin gene minor allele defined by 2 missense mutations is common in blacks and associated with high blood pressure and hypertension | journal = Circulation | volume = 112 | issue = 16 | pages = 2403–2410 | date = October 2005 | pmid = 16216958 | doi = 10.1161/CIRCULATIONAHA.105.568881 | doi-access = free }} * {{cite journal | vauthors = Rame JE, Drazner MH, Post W, Peshock R, Lima J, Cooper RS, Dries DL | title = Corin I555(P568) allele is associated with enhanced cardiac hypertrophic response to increased systemic afterload | journal = Hypertension | volume = 49 | issue = 4 | pages = 857–864 | date = April 2007 | pmid = 17296875 | doi = 10.1161/01.HYP.0000258566.95867.9e | doi-access = free }} * {{cite journal | vauthors = Wu Q | title = The serine protease corin in cardiovascular biology and disease | journal = Frontiers in Bioscience | volume = 12 | issue = 8–12 | pages = 4179–4190 | date = May 2007 | pmid = 17485366 | doi = 10.2741/2379 | doi-access = free }} * {{cite journal | vauthors = Liao X, Wang W, Chen S, Wu Q | title = Role of glycosylation in corin zymogen activation | journal = The Journal of Biological Chemistry | volume = 282 | issue = 38 | pages = 27728–27735 | date = September 2007 | pmid = 17660514 | doi = 10.1074/jbc.M703687200 | doi-access = free }} * {{cite journal | vauthors = Wu Q, Xu-Cai YO, Chen S, Wang W | title = Corin: new insights into the natriuretic peptide system | journal = Kidney International | volume = 75 | issue = 2 | pages = 142–146 | date = January 2009 | pmid = 18716601 | pmc = 2655200 | doi = 10.1038/ki.2008.418 }} * {{cite journal | vauthors = Peleg A, Jaffe AS, Hasin Y | title = Enzyme-linked immunoabsorbent assay for detection of human serine protease corin in blood | journal = Clinica Chimica Acta; International Journal of Clinical Chemistry | volume = 409 | issue = 1–2 | pages = 85–89 | date = November 2009 | pmid = 19751717 | doi = 10.1016/j.cca.2009.09.004 }} * {{cite journal | vauthors = Dries DL | title = Process matters: Emerging concepts underlying impaired natriuretic peptide system function in heart failure | journal = Circulation: Heart Failure | volume = 4 | issue = 2 | pages = 107–110 | date = March 2011 | pmid = 21406676 | doi = 10.1161/CIRCHEARTFAILURE.111.960948 | doi-access = free }} * {{cite journal | vauthors = Zhou Y, Wu Q | title = Role of corin and atrial natriuretic peptide in preeclampsia | journal = Placenta | volume = 34 | issue = 2 | pages = 89–94 | date = February 2013 | pmid = 23211473 | pmc = 3563874 | doi = 10.1016/j.placenta.2012.11.016 }} * {{cite journal | vauthors = Armaly Z, Assady S, Abassi Z | title = Corin: a new player in the regulation of salt-water balance and blood pressure | journal = Current Opinion in Nephrology and Hypertension | volume = 22 | issue = 6 | pages = 713–722 | date = November 2013 | pmid = 24100222 | doi = 10.1097/01.mnh.0000435609.35789.32 | s2cid = 34150725 }} * {{cite journal | vauthors = Zhou Y, Wu Q | title = Corin in natriuretic peptide processing and hypertension | journal = Current Hypertension Reports | volume = 16 | issue = 2 | pages = 415 | date = February 2014 | pmid = 24407448 | pmc = 3941447 | doi = 10.1007/s11906-013-0415-7 }} {{refend}}
== External links == * {{UCSC gene info|CORIN}}