title: Two-amino acid molecular switch in an epithelial morphogen that regulates binding to two distinct receptors.
abstract: Ectodysplasin, a member of the tumor necrosis factor family, is encoded by the anhidrotic ectodermal dysplasia (EDA) gene. Mutations in EDA give rise to a clinical syndrome characterized by loss of hair, sweat glands, and teeth. EDA-A1 and EDA-A2 are two isoforms of ectodysplasin that differ only by an insertion of two amino acids. This insertion functions to determine receptor binding specificity, such that EDA-A1 binds only the receptor EDAR, whereas EDA-A2 binds only the related, but distinct, X-linked ectodysplasin-A2 receptor (XEDAR). In situ binding and organ culture studies indicate that EDA-A1 and EDA-A2 are differentially expressed and play a role in epidermal morphogenesis.
authors.affiliation: Department of Molecular Oncology, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.
authors.forename: M
authors.initials: M
authors.lastname: Yan
authors.forename: L C
authors.initials: LC
authors.lastname: Wang
authors.forename: S G
authors.initials: SG
authors.lastname: Hymowitz
authors.forename: S
authors.initials: S
authors.lastname: Schilbach
authors.forename: J
authors.initials: J
authors.lastname: Lee
authors.forename: A
authors.initials: A
authors.lastname: Goddard
authors.forename: A M
authors.initials: AM
authors.lastname: de Vos
authors.forename: W Q
authors.initials: WQ
authors.lastname: Gao
authors.forename: V M
authors.initials: VM
authors.lastname: Dixit
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism; D004476:Ectodermal Dysplasia / Q000235:genetics; D053331:Ectodysplasins; D004817:Epidermis / Q000196:embryology / Q000378:metabolism*; D006801:Humans; D020672:I-kappa B Proteins; D017403:In Situ Hybridization; D008024:Ligands; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism*; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009024:Morphogenesis; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D017354:Point Mutation; D011487:Protein Conformation; D011506:Proteins / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D048029:TNF Receptor-Associated Factor 6; D014162:Transfection
chemical_list: D004268:DNA-Binding Proteins; C506018:EDA protein, human; D053331:Ectodysplasins; C506019:Eda protein, mouse; D020672:I-kappa B Proteins; D008024:Ligands; D008565:Membrane Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; C000606205:Nfkbia protein, mouse; D011506:Proteins; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; D048029:TNF Receptor-Associated Factor 6; D000072000:NF-KappaB Inhibitor alpha