The tumor necrosis factor receptor (TNFR) superfamily represents a growing family of type I transmembrane glycoproteins that are involved in various cellular functions, including proliferation, differentiation and programmed cell death. These proteins share homology for cysteine-rich repeats in the extracellular ligand binding domain and an intracellular death domain. Members of the TNFR superfamily transmit signals through protein-protein interactions, and these signals can lead to the activation of either the caspase and Jun kinase pathways, which promote cell death, or the NFκB pathway, which results in cell survival. The ectodermal dysplasia receptor (EDAR) promotes all three of these pathways and mediates ectodermal differentiation. EDAR is encoded by the downless gene and is mutated in ectodermal dysplasia syndromes, which are characterized by impaired hair, teeth and sweat gland development. Ectodysplasin A (EDA) is a type II membrane protein that is encoded by the Tabby gene and produces many splice variants, the longest of which, EDA-A1, serves as the ligand for EDAR. EDA-A2, which differs from EDA-A1 by the deletion of two amino acids, binds only the X-linked ectodysplasin-A2 receptor (XEDAR). Both EDAR and XEDAR exhibit homology with TROY.
Function:
Receptor for EDA isoform A1, but not for EDA isoform A2. Mediates the activation of NF-kappa-B and JNK. May promote caspase-independent cell death.
Subunit:
Binds to EDARADD. Associates with TRAF1, TRAF2, TRAF3 and NIK.
Subcellular Location:
Membrane; Single-pass type I membrane protein (Probable).
Tissue Specificity:
Detected in fetal kidney, lung, skin and cultured neonatal epidermal keratinocytes. Not detected in lymphoblast and fibroblast cell lines.
DISEASE:
Defects in EDAR are a cause of ectodermal dysplasia anhidrotic (EDA) [MIM:22980]; also known ectodermal dysplasia hypohidrotic autosomal recessive (HED). Ectodermal dysplasia defines a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. EDA is characterized by sparse hair (atrichosis or hypotrichosis), abnormal or missing teeth and the inability to sweat due to the absence of sweat glands.
Defects in EDAR are the cause of ectodermal dysplasia type 3 (ED3) [MIM:129490]; also known as ectodermal dysplasia hypohidrotic autosomal dominant or EDA3. ED3 is an autosomal dominant condition characterized by hypotrichosis, abnormal or missing teeth, and hypohidrosis due to the absence of sweat glands.
Similarity:
Contains 1 death domain.
Contains 3 TNFR-Cys repeats.
SWISS:
Q9UNE0
Gene ID:
10913
Database links:
Entrez Gene: 10913 Human
Entrez Gene: 1728 Mouse
Entrez Gene: 365581 Rat
Omim: 604095 Human
SwissProt: Q9UNE0 Human
SwissProt: Q9R187 Mouse
Unigene: 171971 Human
Unigene: 174523 Mouse
Unigene: 133578 Rat
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