Ectodysplasin A Explained
Ectodysplasin A (EDA) is a protein that in humans is encoded by the EDA gene.
Ectodysplasin A is a transmembrane protein of the TNF family which plays an important role in the development of ectodermal tissues such as skin in humans.[1] [2] It is recognized by the ectodysplasin A receptor.
Function
The protein encoded by this gene is a type II membrane protein that can be cleaved by furin to produce a secreted form. The encoded protein, which belongs to the tumor necrosis factor family, acts as a homotrimer and may be involved in cell-cell signaling during the development of ectodermal organs. Along with c-Met, it has been shown to be involved in the differentiation of anatomical placodes, precursors of scales, feathers and hair follicles in vertebrates.[3] Defects in this gene are a cause of ectodermal dysplasia, anhidrotic, which is also known as X-linked hypohidrotic ectodermal dysplasia. Several transcript variants encoding many different isoforms have been found for this gene.[2] At least 61 disease-causing mutations in this gene have been discovered.[4]
References
Further reading
- Cui CY, Schlessinger D . EDA signaling and skin appendage development . Cell Cycle . 5 . 21 . 2477–83 . 2007 . 17102627 . 2860309 . 10.4161/cc.5.21.3403 .
- Srivastava AK, Montonen O, Saarialho-Kere U, Chen E, Baybayan P, Pispa J, Limon J, Schlessinger D, Kere J . Fine mapping of the EDA gene: a translocation breakpoint is associated with a CpG island that is transcribed . Am. J. Hum. Genet. . 58 . 1 . 126–32 . 1996 . 8554048 . 1914968 .
- Montonen O, Ezer S, Saarialho-Kere UK, Herva R, Karjalainen-Lindsberg ML, Kaitila I, Schlessinger D, Srivastava AK, Thesleff I, Kere J . The gene defective in anhidrotic ectodermal dysplasia is expressed in the developing epithelium, neuroectoderm, thymus, and bone . J. Histochem. Cytochem. . 46 . 3 . 281–9 . 1998 . 9487109 . 10.1177/002215549804600301 . free .
- Ferguson BM, Thomas NS, Munoz F, Morgan D, Clarke A, Zonana J . Scarcity of mutations detected in families with X linked hypohidrotic ectodermal dysplasia: diagnostic implications . J. Med. Genet. . 35 . 2 . 112–5 . 1998 . 9507389 . 1051213 . 10.1136/jmg.35.2.112 .
- Hertz JM, Nørgaard Hansen K, Juncker I, Kjeldsen M, Gregersen N . A novel missense mutation (402C→T) in exon 1 in the EDA gene in a family with X-linked hypohidrotic ectodermal dysplasia . Clin. Genet. . 53 . 3 . 205–9 . 1998 . 9630076 . 10.1111/j.1399-0004.1998.tb02678.x . 34921334 .
- Monreal AW, Zonana J, Ferguson B . Identification of a new splice form of the EDA1 gene permits detection of nearly all X-linked hypohidrotic ectodermal dysplasia mutations . Am. J. Hum. Genet. . 63 . 2 . 380–9 . 1998 . 9683615 . 1377324 . 10.1086/301984 .
- Bayés M, Hartung AJ, Ezer S, Pispa J, Thesleff I, Srivastava AK, Kere J . The anhidrotic ectodermal dysplasia gene (EDA) undergoes alternative splicing and encodes ectodysplasin-A with deletion mutations in collagenous repeats . Hum. Mol. Genet. . 7 . 11 . 1661–9 . 1998 . 9736768 . 10.1093/hmg/7.11.1661 . free .
- Martínez F, Millán JM, Orellana C, Prieto F . X-linked anhidrotic (hypohidrotic) ectodermal dysplasia caused by a novel mutation in EDA1 gene: 406T > G (Leu55Arg) . J. Invest. Dermatol. . 113 . 2 . 285–6 . 1999 . 10469321 . 10.1046/j.1523-1747.1999.00656.x . free .
- Ezer S, Bayés M, Elomaa O, Schlessinger D, Kere J . Ectodysplasin is a collagenous trimeric type II membrane protein with a tumor necrosis factor-like domain and co-localizes with cytoskeletal structures at lateral and apical surfaces of cells . Hum. Mol. Genet. . 8 . 11 . 2079–86 . 1999 . 10484778 . 10.1093/hmg/8.11.2079 . free .
- Yan M, Wang LC, Hymowitz SG, Schilbach S, Lee J, Goddard A, de Vos AM, Gao WQ, Dixit VM . Two-amino acid molecular switch in an epithelial morphogen that regulates binding to two distinct receptors . Science . 290 . 5491 . 523–7 . 2000 . 11039935 . 10.1126/science.290.5491.523 . 2000Sci...290..523Y .
- Drögemüller C, Distl O, Leeb T . Identification of a highly polymorphic microsatellite within the bovine ectodysplasin A (ED1) gene on BTA Xq22-24 . Anim. Genet. . 31 . 6 . 416 . 2001 . 11167539 . 10.1046/j.1365-2052.2000.00693.x .
- Elomaa O, Pulkkinen K, Hannelius U, Mikkola M, Saarialho-Kere U, Kere J . Ectodysplasin is released by proteolytic shedding and binds to the EDAR protein . Hum. Mol. Genet. . 10 . 9 . 953–62 . 2001 . 11309369 . 10.1093/hmg/10.9.953 . free .
- Vincent MC, Biancalana V, Ginisty D, Mandel JL, Calvas P . Mutational spectrum of the ED1 gene in X-linked hypohidrotic ectodermal dysplasia . Eur. J. Hum. Genet. . 9 . 5 . 355–63 . 2001 . 11378824 . 10.1038/sj.ejhg.5200635 . free .
- Chen Y, Molloy SS, Thomas L, Gambee J, Bächinger HP, Ferguson B, Zonana J, Thomas G, Morris NP . Mutations within a furin consensus sequence block proteolytic release of ectodysplasin-A and cause X-linked hypohidrotic ectodermal dysplasia . Proc. Natl. Acad. Sci. U.S.A. . 98 . 13 . 7218–23 . 2001 . 11416205 . 34649 . 10.1073/pnas.131076098 . 2001PNAS...98.7218C . free .
- Sinha SK, Zachariah S, Quiñones HI, Shindo M, Chaudhary PM . Role of TRAF3 and -6 in the activation of the NF-kappa B and JNK pathways by X-linked ectodermal dysplasia receptor . J. Biol. Chem. . 277 . 47 . 44953–61 . 2003 . 12270937 . 10.1074/jbc.M207923200 . free .
- Kobielak A, Kobielak K, Biedziak B, Trzeciak WH . A novel mutation A1270G of the EDA1 gene causing Tyr343Cys substitution in ectodysplasin-A in a family with anhidrotic ectodermal dysplasia . Acta Biochim. Pol. . 50 . 1 . 255–8 . 2003 . 10.18388/abp.2003_3734 . 12673367 . free .
- Zhang XJ, Chen JJ, Song YX, Yang S, Xiong XY, Zhang AP, He PP, Gao M, Li YB, Lin D, Huang W . Mutation analysis of the ED1 gene in two Chinese Han families with X-linked hypohidrotic ectodermal dysplasia . Arch. Dermatol. Res. . 295 . 1 . 38–42 . 2004 . 12682853 . 10.1007/s00403-003-0394-7 . 26573351 .
- Nishibu A, Hashiguchi T, Yotsumoto S, Takahashi M, Nakamura K, Kanzaki T, Kaneko F . A frameshift mutation of the ED1 gene in sibling cases with X-linked hypohidrotic ectodermal dysplasia . Dermatology . 207 . 2 . 178–81 . 2004 . 12920369 . 10.1159/000071790 . 12792023 .
External links
Notes and References
- Kere J, Srivastava AK, Montonen O, Zonana J, Thomas N, Ferguson B, Munoz F, Morgan D, Clarke A, Baybayan P, Chen EY, Ezer S, Saarialho-Kere U, de la Chapelle A, Schlessinger D . X-linked anhidrotic (hypohidrotic) ectodermal dysplasia is caused by mutation in a novel transmembrane protein . Nat Genet . 13 . 4 . 409–16 . Sep 1996 . 8696334 . 10.1038/ng0895-409 . 25690815 .
- Web site: Entrez Gene: EDA ectodysplasin A.
- Barrow-McGee R, Kishi N, Joffre C, Ménard L, Hervieu A, Bakhouche BA, Noval AJ, Mai A, Guzmán C, Robert-Masson L, Iturrioz X, Hulit J, Brennan CH, Hart IR, Parker PJ, Ivaska J, Kermorgant S . 6 . Beta 1-integrin-c-Met cooperation reveals an inside-in survival signalling on autophagy-related endomembranes . Nature Communications . 7 . 11942 . 2016 . 27336951 . 10.1038/ncomms11942 . 4931016. 2016NatCo...711942B .
- Šimčíková D, Heneberg P . Refinement of evolutionary medicine predictions based on clinical evidence for the manifestations of Mendelian diseases . Scientific Reports . 9 . 1 . 18577 . December 2019 . 31819097 . 6901466 . 10.1038/s41598-019-54976-4. 2019NatSR...918577S .