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

• GeneReview/NIH/UW entry on Hypohidrotic Ectodermal Dysplasia

Notes and References

1. 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 .
2. Web site: Entrez Gene: EDA ectodysplasin A.
3. 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 .
4. 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 .