Endothelin 2

Endothelin 2, also known as ET-2, is a protein that in humans is encoded by the EDN2 gene.[5]

EDN2
Identifiers
Aliases	EDN2, ET2, PPET2, ET-2, endothelin 2
External IDs	OMIM: 131241 MGI: 95284 HomoloGene: 1477 GeneCards: EDN2
Gene location (Human) Chr. Chromosome 1 (human)[1] Band 1p34.2 Start 41,478,775 bp[1] End 41,484,683 bp[1]
Gene location (Mouse) Chr. Chromosome 4 (mouse)[2] Band 4|4 D2.1 Start 120,161,206 bp[2] End 120,167,360 bp[2]
Gene ontology Molecular function • hormone activity • endothelin B receptor binding Cellular component • extracellular region • intracellular • cell • extracellular Biological process • positive regulation of prostaglandin-endoperoxide synthase activity • hormonal regulation of the force of heart contraction • regulation of systemic arterial blood pressure by endothelin • vasoconstriction • cytokine-mediated signaling pathway • positive regulation of cytosolic calcium ion concentration • neutrophil chemotaxis • positive regulation of heart rate • positive regulation of leukocyte chemotaxis • cell surface receptor signaling pathway • vein smooth muscle contraction • macrophage chemotaxis • regulation of vasoconstriction • positive regulation of cell proliferation • artery smooth muscle contraction • energy homeostasis • macrophage activation • prostaglandin biosynthetic process • lung alveolus development • temperature homeostasis • positive regulation of the force of heart contraction by chemical signal • inositol phosphate-mediated signaling • positive regulation of smooth muscle contraction • calcium-mediated signaling • regulation of receptor activity • G-protein coupled receptor signaling pathway Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	1907	13615
Ensembl	ENSG00000127129	ENSMUSG00000028635
UniProt	P20800	P22389
RefSeq (mRNA)	NM_001956 NM_001302269	NM_007902
RefSeq (protein)	NP_001289198 NP_001947	NP_031928
Location (UCSC)	Chr 1: 41.48 – 41.48 Mb	Chr 4: 120.16 – 120.17 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

Endothelin 2 is a member of the endothelin protein family of secretory vasoconstrictive peptides. The preproprotein is processed to a short mature form which functions as a ligand for the endothelin receptors that initiate intracellular signaling events. This gene product is involved in a wide range of biological processes, such as hypertension and ovulation.[5]

Endothelin 2 (ET-2) expression is mainly localized to the granulosa cells within the follicle, as observed in bovine, murine, and human ovarian tissue. Endothelin 2 has functions within the ovarian follicle related to ovulation. ET-2 causes strong contractions in smooth muscle cells of ovarian tissue, and ET-2 production is highest just before ovulation.[6][7][8][9]

References

1. GRCh38: Ensembl release 89: ENSG00000127129 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000028635 - 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. "Entrez Gene: endothelin 2".
6. Klipper, E., A. Levit, Y. Mastich, B. Berisha, D. Schams, and R. Meidan. 2010. Induction of Endothelin-2 Expression by Luteinizing Hormone and Hypoxia: Possible Role in Bovine Corpus Luteum Formation. Endocrinology. 151:1914–1922.
7. Ko, C., M.C. Gieske, L. Al-Alem, Y. Hahn, W. Su, M.C. Gong, M. Iglarz, and Y. Koo. 2006. Endothelin-2 in Ovarian Follicular Rupture. Endocrinology. 147:1770–1779.
8. Na, G., P.J. Bridges, Y. Koo, C. Ko. 2008. Role of hypoxia in the regulation of periovulatory EDN2 expression in the mouse. Canadian Journal of Physiology and Pharmacology. 86:310-319.
9. Imbar, T., E. Klipper, C. Greenfield, A. Hurwitz, R. Haimov-Kochman, R. Meidan. 2012. Altered endothelin expression in granulosa-lutein cells of women with polycystic ovary syndrome. Life Sciences. 91:703–709.

Further reading

• Arjomand-Nahad F, Landt O, Stangl K, Diefenbach K, Roots I (2006). "Fifteen polymorphisms in endothelin-1, endothelin-2 and endothelin-receptor-A genotyped by four duplex assays and seven simple assays on a LightCycler using hybridization probes". Clinical Chemistry and Laboratory Medicine. 44 (8): 929–32. doi:10.1515/CCLM.2006.180. PMID 16879056.
• Ryckman KK, Morken NH, White MJ, Velez DR, Menon R, Fortunato SJ, Magnus P, Williams SM, Jacobsson B (2010). "Maternal and fetal genetic associations of PTGER3 and PON1 with preterm birth". PLoS One. 5 (2): e9040. doi:10.1371/journal.pone.0009040. PMC 2815792. PMID 20140262.
• Dimoulios P, Kolios G, Notas G, Matrella E, Xidakis C, Koulentaki M, Tsagarakis N, Kouroumalis A, Kouroumalis E (February 2005). "Ursodeoxycholic acid reduces increased circulating endothelin 2 in primary biliary cirrhosis". Alimentary Pharmacology & Therapeutics. 21 (3): 227–34. doi:10.1111/j.1365-2036.2005.02307.x. PMID 15691296.
• Menon R, Pearce B, Velez DR, Merialdi M, Williams SM, Fortunato SJ, Thorsen P (2009). "Racial disparity in pathophysiologic pathways of preterm birth based on genetic variants". Reproductive Biology and Endocrinology. 7: 62. doi:10.1186/1477-7827-7-62. PMC 2714850. PMID 19527514.
• Kotake-Nara E, Saida K (2006). "Endothelin-2/vasoactive intestinal contractor: regulation of expression via reactive oxygen species induced by CoCl2, and Biological activities including neurite outgrowth in PC12 cells". TheScientificWorldJournal. 6: 176–86. doi:10.1100/tsw.2006.37. PMC 5917238. PMID 16493522.
• Paulino EC, Steil AA, Jancar S (July 2006). "Effect of endothelins on human neutrophil activation by immune complexes". International Immunopharmacology. 6 (7): 1119–25. doi:10.1016/j.intimp.2006.01.022. PMID 16714215.
• Velez DR, Fortunato SJ, Thorsen P, Lombardi SJ, Williams SM, Menon R (2008). "Preterm birth in Caucasians is associated with coagulation and inflammation pathway gene variants". PLoS One. 3 (9): e3283. doi:10.1371/journal.pone.0003283. PMC 2553267. PMID 18818748.
• Dagle JM, Lepp NT, Cooper ME, Schaa KL, Kelsey KJ, Orr KL, Caprau D, Zimmerman CR, Steffen KM, Johnson KJ, Marazita ML, Murray JC (April 2009). "Determination of genetic predisposition to patent ductus arteriosus in preterm infants". Pediatrics. 123 (4): 1116–23. doi:10.1542/peds.2008-0313. PMC 2734952. PMID 19336370.
• Wiesmann F, Veeck J, Galm O, Hartmann A, Esteller M, Knüchel R, Dahl E (2009). "Frequent loss of endothelin-3 (EDN3) expression due to epigenetic inactivation in human breast cancer". Breast Cancer Research. 11 (3): R34. doi:10.1186/bcr2319. PMC 2716502. PMID 19527488.
• Meidan R, Levy N (December 2007). "The ovarian endothelin network: an evolving story". Trends in Endocrinology and Metabolism. 18 (10): 379–85. doi:10.1016/j.tem.2007.09.002. PMID 17997104.
• Talmud PJ, Drenos F, Shah S, Shah T, Palmen J, Verzilli C, Gaunt TR, Pallas J, Lovering R, Li K, Casas JP, Sofat R, Kumari M, Rodriguez S, Johnson T, Newhouse SJ, Dominiczak A, Samani NJ, Caulfield M, Sever P, Stanton A, Shields DC, Padmanabhan S, Melander O, Hastie C, Delles C, Ebrahim S, Marmot MG, Smith GD, Lawlor DA, Munroe PB, Day IN, Kivimaki M, Whittaker J, Humphries SE, Hingorani AD (November 2009). "Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip". American Journal of Human Genetics. 85 (5): 628–42. doi:10.1016/j.ajhg.2009.10.014. PMC 2775832. PMID 19913121.
• Rebourcet R, Mignot TM, Robert B, Ferré F (2004). "Endothelin-2 down-regulation occurs in parallel with the anti-proliferative effect of dimethylsulfoxide in BeWO human choriocarcinoma cell line". Cellular and Molecular Biology. 50 Online Pub: OL701-12. PMID 15619356.
• Nagai T, Ogimoto A, Okayama H, Ohtsuka T, Shigematsu Y, Hamada M, Miki T, Higaki J (December 2007). "A985G polymorphism of the endothelin-2 gene and atrial fibrillation in patients with hypertrophic cardiomyopathy". Circulation Journal. 71 (12): 1932–6. doi:10.1253/circj.71.1932. PMID 18037749.
• Velez DR, Fortunato S, Thorsen P, Lombardi SJ, Williams SM, Menon R (February 2009). "Spontaneous preterm birth in African Americans is associated with infection and inflammatory response gene variants". American Journal of Obstetrics and Gynecology. 200 (2): 209.e1-27. doi:10.1016/j.ajog.2008.08.051. PMC 4829203. PMID 19019335.
• Grimshaw MJ, Hagemann T, Ayhan A, Gillett CE, Binder C, Balkwill FR (April 2004). "A role for endothelin-2 and its receptors in breast tumor cell invasion". Cancer Research. 64 (7): 2461–8. doi:10.1158/0008-5472.can-03-1069. PMID 15059899.
• Dowal L, Provitera P, Scarlata S (August 2006). "Stable association between G alpha(q) and phospholipase C beta 1 in living cells". The Journal of Biological Chemistry. 281 (33): 23999–4014. doi:10.1074/jbc.M512330200. PMID 16754659.
• Sun DJ, Liu Y, Lu DC, Kim W, Lee JH, Maynard J, Deisseroth A (July 2007). "Endothelin-3 growth factor levels decreased in cervical cancer compared with normal cervical epithelial cells". Human Pathology. 38 (7): 1047–56. doi:10.1016/j.humpath.2006.12.015. PMID 17445867.
• Darrah R, McKone E, O'Connor C, Rodgers C, Genatossio A, McNamara S, Gibson R, Stuart Elborn J, Ennis M, Gallagher CG, Kalsheker N, Aitken M, Wiese D, Dunn J, Smith P, Pace R, Londono D, Goddard KA, Knowles MR, Drumm ML (March 2010). "EDNRA variants associate with smooth muscle mRNA levels, cell proliferation rates, and cystic fibrosis pulmonary disease severity". Physiological Genomics. 41 (1): 71–7. doi:10.1152/physiolgenomics.00185.2009. PMC 2841492. PMID 20028935.
• Bailey SD, Xie C, Do R, Montpetit A, Diaz R, Mohan V, Keavney B, Yusuf S, Gerstein HC, Engert JC, Anand S (October 2010). "Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study". Diabetes Care. 33 (10): 2250–3. doi:10.2337/dc10-0452. PMC 2945168. PMID 20628086.
• Davenport AP, Hyndman KA, Dhaun N, Southan C, Kohan DE, Pollock JS, Pollock DM, Webb DJ, Maguire JJ (April 2016). "Endothelin". Pharmacological Reviews. 68 (2): 357–418. doi:10.1124/pr.115.011833. PMC 4815360. PMID 26956245.