Ectodysplasin A

Ectodysplasin A (EDA) is a protein that in humans is encoded by the EDA gene.

EDA
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1RJ7, 1RJ8
Identifiers
Aliases	EDA, ECTD1, ED1, ED1-A1, ED1-A2, EDA-A1, EDA-A2, EDA1, EDA2, HED, HED1, ODT1, STHAGX1, XHED, XLHED, TNLG7C, ectodysplasin A
External IDs	OMIM: 300451; MGI: 1195272; GeneCards: EDA; OMA:EDA - orthologs
Gene location (Human) Chr. X chromosome (human)[1] Band Xq13.1 Start 69,616,067 bp[1] End 70,039,472 bp[1]
Gene location (Mouse) Chr. X chromosome (mouse)[2] Band X C3|X 43.59 cM Start 99,019,212 bp[2] End 99,444,368 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in testicle oocyte right auricle left adrenal gland left adrenal cortex secondary oocyte right adrenal cortex gonad apex of heart buccal mucosa cell Top expressed in dental lamina saccule ectoderm otic vesicle otic placode outer enamel epithelium entorhinal cortex perirhinal cortex choroid plexus of fourth ventricle secondary oocyte More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding tumor necrosis factor receptor binding signaling receptor binding death receptor agonist activity death receptor binding Cellular component integral component of membrane collagen endoplasmic reticulum membrane membrane plasma membrane apical part of cell integral component of plasma membrane extracellular region cytoskeleton lipid droplet intracellular membrane-bounded organelle Biological process trachea gland development hair follicle placode formation hair follicle development cell differentiation gene expression positive regulation of canonical Wnt signaling pathway salivary gland cavitation tumor necrosis factor-mediated signaling pathway multicellular organism development positive regulation of gene expression positive regulation of NF-kappaB transcription factor activity immune response positive regulation of I-kappaB kinase/NF-kappaB signaling pigmentation cell-matrix adhesion skin development cytokine-mediated signaling pathway regulation of NIK/NF-kappaB signaling odontogenesis of dentin-containing tooth regulation of signaling receptor activity positive regulation of NIK/NF-kappaB signaling Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 1896 13607 Ensembl ENSG00000158813 ENSMUSG00000059327 UniProt Q92838 O54693 RefSeq (mRNA) NM_001005609 NM_001005610 NM_001005611 NM_001005612 NM_001005613 NM_001005614 NM_001399 NM_001177937 NM_001177938 NM_001177939 NM_001177940 NM_001177941 NM_001177942 NM_001177943 NM_001177944 NM_010099 RefSeq (protein) NP_001005609 NP_001005610 NP_001005612 NP_001005613 NP_001390 NP_001171408 NP_001171409 NP_001171410 NP_001171411 NP_001171412 NP_001171413 NP_001171414 NP_001171415 NP_034229 Location (UCSC) Chr X: 69.62 – 70.04 Mb Chr X: 99.02 – 99.44 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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.^[5][6] 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.^[7] 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.^[6] At least 61 disease-causing mutations in this gene have been discovered.^[8]

References

1. GRCh38: Ensembl release 89: ENSG00000158813 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000059327 – 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. 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 (Sep 1996). "X-linked anhidrotic (hypohidrotic) ectodermal dysplasia is caused by mutation in a novel transmembrane protein". Nat Genet. 13 (4): 409–16. doi:10.1038/ng0895-409. PMID 8696334. S2CID 25690815.
6. "Entrez Gene: EDA ectodysplasin A".
7. Barrow-McGee R, Kishi N, Joffre C, Ménard L, Hervieu A, Bakhouche BA, et al. (2016). "Beta 1-integrin-c-Met cooperation reveals an inside-in survival signalling on autophagy-related endomembranes". Nature Communications. 7: 11942. Bibcode:2016NatCo...711942B. doi:10.1038/ncomms11942. PMC 4931016. PMID 27336951.
8. Šimčíková D, Heneberg P (December 2019). "Refinement of evolutionary medicine predictions based on clinical evidence for the manifestations of Mendelian diseases". Scientific Reports. 9 (1): 18577. Bibcode:2019NatSR...918577S. doi:10.1038/s41598-019-54976-4. PMC 6901466. PMID 31819097.

Further reading

• Cui CY, Schlessinger D (2007). "EDA signaling and skin appendage development". Cell Cycle. 5 (21): 2477–83. doi:10.4161/cc.5.21.3403. PMC 2860309. PMID 17102627.
• Srivastava AK, Montonen O, Saarialho-Kere U, Chen E, Baybayan P, Pispa J, Limon J, Schlessinger D, Kere J (1996). "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. PMC 1914968. PMID 8554048.
• Montonen O, Ezer S, Saarialho-Kere UK, Herva R, Karjalainen-Lindsberg ML, Kaitila I, Schlessinger D, Srivastava AK, Thesleff I, Kere J (1998). "The gene defective in anhidrotic ectodermal dysplasia is expressed in the developing epithelium, neuroectoderm, thymus, and bone". J. Histochem. Cytochem. 46 (3): 281–9. doi:10.1177/002215549804600301. PMID 9487109.
• Ferguson BM, Thomas NS, Munoz F, Morgan D, Clarke A, Zonana J (1998). "Scarcity of mutations detected in families with X linked hypohidrotic ectodermal dysplasia: diagnostic implications". J. Med. Genet. 35 (2): 112–5. doi:10.1136/jmg.35.2.112. PMC 1051213. PMID 9507389.
• Hertz JM, Nørgaard Hansen K, Juncker I, Kjeldsen M, Gregersen N (1998). "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. doi:10.1111/j.1399-0004.1998.tb02678.x. PMID 9630076. S2CID 34921334.
• Monreal AW, Zonana J, Ferguson B (1998). "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. doi:10.1086/301984. PMC 1377324. PMID 9683615.
• Bayés M, Hartung AJ, Ezer S, Pispa J, Thesleff I, Srivastava AK, Kere J (1998). "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. doi:10.1093/hmg/7.11.1661. PMID 9736768.
• Martínez F, Millán JM, Orellana C, Prieto F (1999). "X-linked anhidrotic (hypohidrotic) ectodermal dysplasia caused by a novel mutation in EDA1 gene: 406T > G (Leu55Arg)". J. Invest. Dermatol. 113 (2): 285–6. doi:10.1046/j.1523-1747.1999.00656.x. PMID 10469321.
• Ezer S, Bayés M, Elomaa O, Schlessinger D, Kere J (1999). "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. doi:10.1093/hmg/8.11.2079. PMID 10484778.
• Yan M, Wang LC, Hymowitz SG, Schilbach S, Lee J, Goddard A, de Vos AM, Gao WQ, Dixit VM (2000). "Two-amino acid molecular switch in an epithelial morphogen that regulates binding to two distinct receptors". Science. 290 (5491): 523–7. Bibcode:2000Sci...290..523Y. doi:10.1126/science.290.5491.523. PMID 11039935.
• Drögemüller C, Distl O, Leeb T (2001). "Identification of a highly polymorphic microsatellite within the bovine ectodysplasin A (ED1) gene on BTA Xq22-24". Anim. Genet. 31 (6): 416. doi:10.1046/j.1365-2052.2000.00693.x. PMID 11167539.
• Elomaa O, Pulkkinen K, Hannelius U, Mikkola M, Saarialho-Kere U, Kere J (2001). "Ectodysplasin is released by proteolytic shedding and binds to the EDAR protein". Hum. Mol. Genet. 10 (9): 953–62. doi:10.1093/hmg/10.9.953. PMID 11309369.
• Vincent MC, Biancalana V, Ginisty D, Mandel JL, Calvas P (2001). "Mutational spectrum of the ED1 gene in X-linked hypohidrotic ectodermal dysplasia". Eur. J. Hum. Genet. 9 (5): 355–63. doi:10.1038/sj.ejhg.5200635. PMID 11378824.
• Chen Y, Molloy SS, Thomas L, Gambee J, Bächinger HP, Ferguson B, Zonana J, Thomas G, Morris NP (2001). "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. Bibcode:2001PNAS...98.7218C. doi:10.1073/pnas.131076098. PMC 34649. PMID 11416205.
• Sinha SK, Zachariah S, Quiñones HI, Shindo M, Chaudhary PM (2003). "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. doi:10.1074/jbc.M207923200. PMID 12270937.
• Kobielak A, Kobielak K, Biedziak B, Trzeciak WH (2003). "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. doi:10.18388/abp.2003_3734. PMID 12673367.
• Zhang XJ, Chen JJ, Song YX, Yang S, Xiong XY, Zhang AP, He PP, Gao M, Li YB, Lin D, Huang W (2004). "Mutation analysis of the ED1 gene in two Chinese Han families with X-linked hypohidrotic ectodermal dysplasia". Arch. Dermatol. Res. 295 (1): 38–42. doi:10.1007/s00403-003-0394-7. PMID 12682853. S2CID 26573351.
• Nishibu A, Hashiguchi T, Yotsumoto S, Takahashi M, Nakamura K, Kanzaki T, Kaneko F (2004). "A frameshift mutation of the ED1 gene in sibling cases with X-linked hypohidrotic ectodermal dysplasia". Dermatology. 207 (2): 178–81. doi:10.1159/000071790. PMID 12920369. S2CID 12792023.

External links

• GeneReview/NIH/UW entry on Hypohidrotic Ectodermal Dysplasia