Ectodysplasin A receptor
Ectodysplasin A receptor (EDAR) is a protein that in humans is encoded by the EDAR gene. EDAR is a cell surface receptor for ectodysplasin A which plays an important role in the development of ectodermal tissues such as the skin.[1][2][3] It is structurally related to members of the TNF receptor superfamily.[4]
Function
EDAR and other genes provide instructions for making proteins that work together during embryonic development. These proteins form part of a signaling pathway that is critical for the interaction between two cell layers, the ectoderm and the mesoderm. In the early embryo, these cell layers form the basis for many of the body's organs and tissues. Ectoderm-mesoderm interactions are essential for the proper formation of several structures that arise from the ectoderm, including the skin, hair, nails, teeth, and sweat glands.[3]
Clinical significance
Mutation in this gene have been associated with hypohidrotic ectodermal dysplasia, a disorder characterized by a lower density of sweat glands.[3]
East Asian characteristics
A point mutation in EDAR, 370A, found in most East Asians but not common in African or European populations, is thought to be responsible for a number of differences between these populations, including the thicker hair, more numerous sweat glands, smaller breasts, and dentition characteristic of East Asians.[5] The difference in dentition was not visible in mice due to the radically different structure of mice from human teeth, but it is considered reasonable that that difference also is due to the mutation.[6] The 370A mutation arose in humans approximately 30,000 years ago, and now is found in 93% of Han Chinese and in the majority of people in nearby Asian populations.
See also
References
- ↑ Monreal AW, Ferguson BM, Headon DJ, Street SL, Overbeek PA, Zonana J (Aug 1999). "Mutations in the human homologue of mouse dl cause autosomal recessive and dominant hypohidrotic ectodermal dysplasia". Nature Genetics 22 (4): 366–9. doi:10.1038/11937. PMID 10431241.
- ↑ Aswegan AL, Josephson KD, Mowbray R, Pauli RM, Spritz RA, Williams MS (Nov 1997). "Autosomal dominant hypohidrotic ectodermal dysplasia in a large family". American Journal of Medical Genetics 72 (4): 462–7. doi:10.1002/(SICI)1096-8628(19971112)72:4<462::AID-AJMG17>3.0.CO;2-P. PMID 9375732.
- 1 2 3 "Entrez Gene: EDAR ectodysplasin A receptor".
- ↑ Online 'Mendelian Inheritance in Man' (OMIM) 604095
- ↑ Kamberov YG, Wang S, Tan J, Gerbault P, Wark A, Tan L, Yang Y, Li S, Tang K, Chen H, Powell A, Itan Y, Fuller D, Lohmueller J, Mao J, Schachar A, Paymer M, Hostetter E, Byrne E, Burnett M, McMahon AP, Thomas MG, Lieberman DE, Jin L, Tabin CJ, Morgan BA, Sabeti PC (Feb 2013). "Modeling recent human evolution in mice by expression of a selected EDAR variant". Cell 152 (4): 691–702. doi:10.1016/j.cell.2013.01.016. PMC 3575602. PMID 23415220.
- ↑ Nicholas Wade (February 14, 2013). "East Asian Physical Traits Linked to 35,000-Year-Old Mutation". The New York Times. Retrieved February 15, 2013.
Further reading
- Thesleff I, Mikkola ML (May 2002). "Death receptor signaling giving life to ectodermal organs". Science's STKE 2002 (131): PE22. doi:10.1126/stke.2002.131.pe22. PMID 11997580.
- Ho L, Williams MS, Spritz RA (May 1998). "A gene for autosomal dominant hypohidrotic ectodermal dysplasia (EDA3) maps to chromosome 2q11-q13". American Journal of Human Genetics 62 (5): 1102–6. doi:10.1086/301839. PMC 1377096. PMID 9545409.
- Kumar A, Eby MT, Sinha S, Jasmin A, Chaudhary PM (Jan 2001). "The ectodermal dysplasia receptor activates the nuclear factor-kappaB, JNK, and cell death pathways and binds to ectodysplasin A". The Journal of Biological Chemistry 276 (4): 2668–77. doi:10.1074/jbc.M008356200. PMID 11035039.
- Yan M, Wang LC, Hymowitz SG, Schilbach S, Lee J, Goddard A, de Vos AM, Gao WQ, Dixit VM (Oct 2000). "Two-amino acid molecular switch in an epithelial morphogen that regulates binding to two distinct receptors". Science 290 (5491): 523–7. doi:10.1126/science.290.5491.523. PMID 11039935.
- Elomaa O, Pulkkinen K, Hannelius U, Mikkola M, Saarialho-Kere U, Kere J (Apr 2001). "Ectodysplasin is released by proteolytic shedding and binds to the EDAR protein". Human Molecular Genetics 10 (9): 953–62. doi:10.1093/hmg/10.9.953. PMID 11309369.
- Koppinen P, Pispa J, Laurikkala J, Thesleff I, Mikkola ML (Oct 2001). "Signaling and subcellular localization of the TNF receptor Edar". Experimental Cell Research 269 (2): 180–92. doi:10.1006/excr.2001.5331. PMID 11570810.
- Headon DJ, Emmal SA, Ferguson BM, Tucker AS, Justice MJ, Sharpe PT, Zonana J, Overbeek PA (2002). "Gene defect in ectodermal dysplasia implicates a death domain adapter in development". Nature 414 (6866): 913–6. doi:10.1038/414913a. PMID 11780064.
- Yan M, Zhang Z, Brady JR, Schilbach S, Fairbrother WJ, Dixit VM (Mar 2002). "Identification of a novel death domain-containing adaptor molecule for ectodysplasin-A receptor that is mutated in crinkled mice". Current Biology 12 (5): 409–13. doi:10.1016/S0960-9822(02)00687-5. PMID 11882293.
- Sinha SK, Zachariah S, Quiñones HI, Shindo M, Chaudhary PM (Nov 2002). "Role of TRAF3 and -6 in the activation of the NF-kappa B and JNK pathways by X-linked ectodermal dysplasia receptor". The Journal of Biological Chemistry 277 (47): 44953–61. doi:10.1074/jbc.M207923200. PMID 12270937.
- Shu H, Chen S, Bi Q, Mumby M, Brekken DL (Mar 2004). "Identification of phosphoproteins and their phosphorylation sites in the WEHI-231 B lymphoma cell line". Molecular & Cellular Proteomics 3 (3): 279–86. doi:10.1074/mcp.D300003-MCP200. PMID 14729942.
- Zhang Z, Henzel WJ (Oct 2004). "Signal peptide prediction based on analysis of experimentally verified cleavage sites". Protein Science 13 (10): 2819–24. doi:10.1110/ps.04682504. PMC 2286551. PMID 15340161.
- Hashimoto T, Cui CY, Schlessinger D (Apr 2006). "Repertoire of mouse ectodysplasin-A (EDA-A) isoforms". Gene 371 (1): 42–51. doi:10.1016/j.gene.2005.11.003. PMID 16423472.
- Chassaing N, Bourthoumieu S, Cossee M, Calvas P, Vincent MC (Mar 2006). "Mutations in EDAR account for one-quarter of non-ED1-related hypohidrotic ectodermal dysplasia". Human Mutation 27 (3): 255–9. doi:10.1002/humu.20295. PMID 16435307.
- Tariq M, Wasif N, Ahmad W (Jul 2007). "A novel deletion mutation in the EDAR gene in a Pakistani family with autosomal recessive hypohidrotic ectodermal dysplasia". The British Journal of Dermatology 157 (1): 207–9. doi:10.1111/j.1365-2133.2007.07949.x. PMID 17501952.
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