ID EDAR_HUMAN Reviewed; 448 AA. AC Q9UNE0; B2R9H2; B4DLC5; D3DX74; E9PC98; Q52LL5; Q9UND9; DT 27-MAY-2002, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-2000, sequence version 1. DT 04-NOV-2026, entry version 197. DE RecName: Full=Tumor necrosis factor receptor superfamily member EDAR; DE AltName: Full=Anhidrotic ectodysplasin receptor 1; DE AltName: Full=Downless homolog; DE AltName: Full=EDA-A1 receptor; DE AltName: Full=Ectodermal dysplasia receptor; DE AltName: Full=Ectodysplasin-A receptor; DE Flags: Precursor; GN Name=EDAR; Synonyms=DL; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), VARIANTS ECTD10B RP ARG-87 AND HIS-89, AND VARIANT ECTD10A GLN-420. RC TISSUE=Fetal heart, and Skin; RX PubMed=10431241; DOI=10.1038/11937; RA Monreal A.W., Ferguson B.M., Headon D.J., Street S.L., Overbeek P.A., RA Zonana J.; RT "Mutations in the human homologue of mouse dl cause autosomal recessive and RT dominant hypohidrotic ectodermal dysplasia."; RL Nat. Genet. 22:366-369(1999). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT RP ALA-370. RC TISSUE=Tongue; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Liver; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP PROTEIN SEQUENCE OF 27-41. RX PubMed=15340161; DOI=10.1110/ps.04682504; RA Zhang Z., Henzel W.J.; RT "Signal peptide prediction based on analysis of experimentally verified RT cleavage sites."; RL Protein Sci. 13:2819-2824(2004). RN [7] RP INTERACTION WITH EDA ISOFORM A1. RX PubMed=11039935; DOI=10.1126/science.290.5491.523; RA Yan M., Wang L.-C., Hymowitz S.G., Schilbach S., Lee J., Goddard A., RA de Vos A.M., Gao W.-Q., Dixit V.M.; RT "Two-amino acid molecular switch in an epithelial morphogen that regulates RT binding to two distinct receptors."; RL Science 290:523-527(2000). RN [8] RP CHARACTERIZATION OF VARIANT GLN-420, MUTAGENESIS OF GLU-379, RP CHARACTERIZATION, AND INTERACTION WITH TRAF1 AND TRAF3. RX PubMed=11035039; DOI=10.1074/jbc.m008356200; RA Kumar A., Eby M.T., Sinha S., Jasmin A., Chaudhary P.M.; RT "The ectodermal dysplasia receptor activates the nuclear factor-kappaB, RT JNK, and cell death pathways and binds to ectodysplasin A."; RL J. Biol. Chem. 276:2668-2677(2001). RN [9] RP VARIANT ECTD10B HIS-375, AND CHARACTERIZATION OF VARIANT ECTD10B HIS-375. RX PubMed=15373768; DOI=10.1111/j.0022-202x.2004.23405.x; RA Shimomura Y., Sato N., Miyashita A., Hashimoto T., Ito M., Kuwano R.; RT "A rare case of hypohidrotic ectodermal dysplasia caused by compound RT heterozygous mutations in the EDAR gene."; RL J. Invest. Dermatol. 123:649-655(2004). RN [10] RP VARIANT ECTD10B SER-382. RX PubMed=16029325; DOI=10.1111/j.1365-2133.2005.06642.x; RA Naeem M., Muhammad D., Ahmad W.; RT "Novel mutations in the EDAR gene in two Pakistani consanguineous families RT with autosomal recessive hypohidrotic ectodermal dysplasia."; RL Br. J. Dermatol. 153:46-50(2005). RN [11] RP VARIANTS ECTD10B TYR-47; HIS-89; ALA-110; ARG-148; PHE-377; MET-403; RP PRO-413; THR-418; GLN-420 AND CYS-434. RX PubMed=16435307; DOI=10.1002/humu.20295; RA Chassaing N., Bourthoumieu S., Cossee M., Calvas P., Vincent M.-C.; RT "Mutations in EDAR account for one-quarter of non-ED1-related hypohidrotic RT ectodermal dysplasia."; RL Hum. Mutat. 27:255-259(2006). RN [12] RP VARIANTS ECTD10B HIS-89 AND ALA-110, AND VARIANT ECTD10A GLN-420. RX PubMed=18231121; DOI=10.1038/sj.ejhg.5202012; RA van der Hout A.H., Oudesluijs G.G., Venema A., Verheij J.B.G.M., RA Mol B.G.J., Rump P., Brunner H.G., Vos Y.J., van Essen A.J.; RT "Mutation screening of the ectodysplasin-A receptor gene EDAR in RT hypohidrotic ectodermal dysplasia."; RL Eur. J. Hum. Genet. 16:673-679(2008). RN [13] RP VARIANT ALA-370, CHARACTERIZATION OF VARIANT ALA-370, AND ASSOCIATION WITH RP HAIR MORPHOLOGY TYPE 1. RX PubMed=18065779; DOI=10.1093/hmg/ddm355; RA Fujimoto A., Kimura R., Ohashi J., Omi K., Yuliwulandari R., Batubara L., RA Mustofa M.S., Samakkarn U., Settheetham-Ishida W., Ishida T., Morishita Y., RA Furusawa T., Nakazawa M., Ohtsuka R., Tokunaga K.; RT "A scan for genetic determinants of human hair morphology: EDAR is RT associated with Asian hair thickness."; RL Hum. Mol. Genet. 17:835-843(2008). RN [14] RP CHARACTERIZATION OF VARIANT ALA-370. RX PubMed=18561327; DOI=10.1002/humu.20795; RA Mou C., Thomason H.A., Willan P.M., Clowes C., Harris W.E., Drew C.F., RA Dixon J., Dixon M.J., Headon D.J.; RT "Enhanced ectodysplasin-A receptor (EDAR) signaling alters multiple fiber RT characteristics to produce the East Asian hair form."; RL Hum. Mutat. 29:1405-1411(2008). RN [15] RP VARIANTS ECTD10B GLN-98; GLN-358 AND ARG-434. RX PubMed=19438931; DOI=10.1111/j.1399-0004.2009.01178.x; RA Shimomura Y., Wajid M., Weiser J., Kraemer L., Ishii Y., Lombillo V., RA Bale S.J., Christiano A.M.; RT "Identification of mutations in the EDA and EDAR genes in Pakistani RT families with hypohidrotic ectodermal dysplasia."; RL Clin. Genet. 75:582-584(2009). RN [16] RP VARIANTS ECTD10B HIS-89; GLN-358; GLN-396 INS; MET-403; PHE-408 AND RP GLN-420. RX PubMed=20979233; DOI=10.1002/humu.21384; RA Cluzeau C., Hadj-Rabia S., Jambou M., Mansour S., Guigue P., Masmoudi S., RA Bal E., Chassaing N., Vincent M.C., Viot G., Clauss F., Maniere M.C., RA Toupenay S., Le Merrer M., Lyonnet S., Cormier-Daire V., Amiel J., RA Faivre L., de Prost Y., Munnich A., Bonnefont J.P., Bodemer C., Smahi A.; RT "Only four genes (EDA1, EDAR, EDARADD, and WNT10A) account for 90% of RT hypohidrotic/anhidrotic ectodermal dysplasia cases."; RL Hum. Mutat. 32:70-72(2011). RN [17] RP VARIANT ECTD10B GLN-420, AND VARIANT LEU-370. RX PubMed=27657131; DOI=10.3390/genes7090065; RA Zeng B., Xiao X., Li S., Lu H., Lu J., Zhu L., Yu D., Zhao W.; RT "Eight mutations of three genes (EDA, EDAR, and WNT10A) identified in seven RT hypohidrotic ectodermal dysplasia patients."; RL Genes (Basel) 7:0-0(2016). CC -!- FUNCTION: Receptor for EDA isoform A1, but not for EDA isoform A2. CC Mediates the activation of NF-kappa-B and JNK. May promote caspase- CC independent cell death. CC -!- SUBUNIT: Binds to EDARADD. Associates with TRAF1, TRAF2, TRAF3 and NIK. CC -!- INTERACTION: CC Q9UNE0; Q92838: EDA; NbExp=3; IntAct=EBI-529289, EBI-529425; CC Q9UNE0; Q8NHL6: LILRB1; NbExp=2; IntAct=EBI-529289, EBI-2805262; CC Q9UNE0-2; O43765: SGTA; NbExp=3; IntAct=EBI-12964110, EBI-347996; CC Q9UNE0-2; O75841: UPK1B; NbExp=3; IntAct=EBI-12964110, EBI-12237619; CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass type I CC membrane protein {ECO:0000305}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9UNE0-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9UNE0-2; Sequence=VSP_054187; CC -!- TISSUE SPECIFICITY: Detected in fetal kidney, lung, skin and cultured CC neonatal epidermal keratinocytes. Not detected in lymphoblast and CC fibroblast cell lines. CC -!- DEVELOPMENTAL STAGE: Found in craniofacial tissues from embryonic day CC 42-53. Expressed in fetal skin 11 and 15 weeks after gestation. CC -!- POLYMORPHISM: Genetic variation in EDAR is associated with variations CC in head hair thickness and defines the hair morphology locus 1 (HRM1) CC [MIM:612630]. Besides skin color and facial features, hair morphology CC is one of the most distinctive traits among human populations, and CC classical classification of human population is based on such visible CC traits. CC -!- DISEASE: Ectodermal dysplasia 10A, hypohidrotic/hair/nail type, CC autosomal dominant (ECTD10A) [MIM:129490]: A form of ectodermal CC dysplasia, a heterogeneous group of disorders due to abnormal CC development of two or more ectodermal structures. It is an autosomal CC dominant condition characterized by hypotrichosis, abnormal or missing CC teeth, and hypohidrosis due to the absence of sweat glands. CC {ECO:0000269|PubMed:10431241, ECO:0000269|PubMed:18231121}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Ectodermal dysplasia 10B, hypohidrotic/hair/tooth type, CC autosomal recessive (ECTD10B) [MIM:224900]: A disorder due to abnormal CC development of two or more ectodermal structures, and characterized by CC sparse hair (atrichosis or hypotrichosis), abnormal or missing teeth CC and the inability to sweat due to the absence of sweat glands. CC {ECO:0000269|PubMed:10431241, ECO:0000269|PubMed:15373768, CC ECO:0000269|PubMed:16029325, ECO:0000269|PubMed:16435307, CC ECO:0000269|PubMed:18231121, ECO:0000269|PubMed:19438931, CC ECO:0000269|PubMed:20979233, ECO:0000269|PubMed:27657131}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF130988; AAD50076.1; -; mRNA. DR EMBL; AF130996; AAD50077.1; -; Genomic_DNA. DR EMBL; AF130990; AAD50077.1; JOINED; Genomic_DNA. DR EMBL; AF130991; AAD50077.1; JOINED; Genomic_DNA. DR EMBL; AF130992; AAD50077.1; JOINED; Genomic_DNA. DR EMBL; AF130993; AAD50077.1; JOINED; Genomic_DNA. DR EMBL; AF130994; AAD50077.1; JOINED; Genomic_DNA. DR EMBL; AF130995; AAD50077.1; JOINED; Genomic_DNA. DR EMBL; AK296936; BAG59487.1; -; mRNA. DR EMBL; AK313781; BAG36519.1; -; mRNA. DR EMBL; AC073415; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC092160; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC133784; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471182; EAW53869.1; -; Genomic_DNA. DR EMBL; BC093870; AAH93870.1; -; mRNA. DR EMBL; BC093872; AAH93872.1; -; mRNA. DR CCDS; CCDS2081.1; -. [Q9UNE0-1] DR RefSeq; NP_071731.1; NM_022336.4. [Q9UNE0-1] DR RefSeq; XP_006712267.1; XM_006712204.2. [Q9UNE0-2] DR PDB; 7X9G; X-ray; 2.80 A; C=28-150. DR SMR; Q9UNE0; -. DR BioGRID; 116118; 74. DR IntAct; Q9UNE0; 61. DR STRING; 9606.ENSP00000258443; -. DR NDEx; IQUERY-CP-EDAR; 3 NDEx IQuery Curated Pathways. DR ChEMBL; CHEMBL1250376; -. DR GlyCosmos; Q9UNE0; 2 sites, 1 glycan. DR GlyGen; Q9UNE0; 2 sites, 1 O-linked glycan (1 site). DR iPTMnet; Q9UNE0; -. DR PhosphoSitePlus; Q9UNE0; -. DR BioMuta; EDAR; -. DR DMDM; 21263572; -. DR PaxDb; 9606-ENSP00000258443; -. DR PeptideAtlas; Q9UNE0; -. DR ProteomicsDB; 19402; -. DR ProteomicsDB; 85279; -. [Q9UNE0-1] DR jPOST; Q9UNE0; -. DR MassIVE; Q9UNE0; -. DR DNASU; 10913; -. DR Ensembl; ENST00000258443.7; ENSP00000258443.2; ENSG00000135960.11. [Q9UNE0-1] DR Ensembl; ENST00000376651.1; ENSP00000365839.1; ENSG00000135960.11. [Q9UNE0-2] DR Ensembl; ENST00000409271.5; ENSP00000386371.1; ENSG00000135960.11. [Q9UNE0-2] DR Ensembl; ENST00000970167.1; ENSP00000640226.1; ENSG00000135960.11. [Q9UNE0-1] DR GeneID; 10913; -. DR KEGG; hsa:10913; -. DR MANE-Select; ENST00000258443.7; ENSP00000258443.2; NM_022336.4; NP_071731.1. DR UCSC; uc002teq.4; human. [Q9UNE0-1] DR CTD; 10913; -. DR DisGeNET; 10913; -. DR VEuPathDB; HostDB:ENSG00000135960; -. DR GeneCards; EDAR; -. DR GeneReviews; EDAR; -. DR HGNC; HGNC:2895; EDAR. DR AGR; HGNC:2895; -. DR HPA; ENSG00000135960; Tissue enhanced (esophagus). DR MalaCards; EDAR; -. DR MIM; 129490; phenotype. DR MIM; 224900; phenotype. DR MIM; 604095; gene. DR MIM; 612630; phenotype. DR OpenTargets; ENSG00000135960; -. DR Orphanet; 1810; Autosomal dominant hypohidrotic ectodermal dysplasia. DR Orphanet; 248; Autosomal recessive hypohidrotic ectodermal dysplasia. DR ClinPGx; PA27602; -. DR eggNOG; ENOG502QRV5; Eukaryota. DR GeneTree; ENSGT00940000153259; -. DR HOGENOM; CLU_039634_0_0_1; -. DR InParanoid; Q9UNE0; -. DR OMA; ACCAGQV; -. DR OrthoDB; 9903718at2759; -. DR PhylomeDB; Q9UNE0; -. DR Reactome; R-HSA-5669034; TNFs bind their physiological receptors. DR SignaLink; Q9UNE0; -. DR SIGNOR; Q9UNE0; -. DR Agora; ENSG00000135960; Agora Nominated Target for Alzheimer's Disease. DR GeneWiki; EDAR; -. DR GenomeRNAi; 10913; -. DR PRO; PR:Q9UNE0; -. DR Bgee; ENSG00000135960; Expressed in secondary oocyte and 78 other cell types or tissues. DR CDD; cd13421; TNFRSF_EDAR; 1. DR FunFam; 2.10.50.10:FF:000023; Ectodysplasin A receptor; 1. DR FunFam; 1.10.533.10:FF:000006; Tumor necrosis factor receptor superfamily member EDAR; 1. DR Gene3D; 1.10.533.10; Death Domain, Fas; 1. DR Gene3D; 2.10.50.10; Tumor Necrosis Factor Receptor, subunit A, domain 2; 1. DR InterPro; IPR011029; DEATH-like_dom_sf. DR InterPro; IPR056762; Death_EDAR. DR InterPro; IPR034052; EDAR_N. DR InterPro; IPR047526; TNR19/27/EDAR. DR PANTHER; PTHR12120; TNFR-CYS DOMAIN-CONTAINING PROTEIN; 1. DR PANTHER; PTHR12120:SF9; TUMOR NECROSIS FACTOR RECEPTOR SUPERFAMILY MEMBER EDAR; 1. DR Pfam; PF24979; Death_EDAR; 1. DR SUPFAM; SSF47986; DEATH domain; 1. DR GO; GO:0016020; C:membrane; NAS:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0004888; F:transmembrane signaling receptor activity; IDA:HGNC-UCL. DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IDA:ARUK-UCL. DR GO; GO:0008544; P:epidermis development; TAS:HGNC-UCL. DR GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; IEA:InterPro. DR GO; GO:0046330; P:positive regulation of JNK cascade; IEA:InterPro. DR Proteomes; UP000005640; Chromosome 2. DR PathwayCommons; Q9UNE0; -. DR Pharos; Q9UNE0; Tbio. DR ABCD; Q9UNE0; 14 sequenced antibodies. DR Antibodypedia; 33144; 405 antibodies from 35 providers. DR RNAct; Q9UNE0; protein. DR BioGRID-ORCS; 10913; 98 hits in 1150 CRISPR screens. DR AlphaFoldDB; Q9UNE0; -. DR FunCoup; Q9UNE0; 953. DR PAN-GO; Q9UNE0; 4 GO annotations based on evolutionary models. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Apoptosis; Developmental protein; KW Differentiation; Direct protein sequencing; Disease variant; KW Disulfide bond; Ectodermal dysplasia; Glycoprotein; Membrane; KW Proteomics identification; Receptor; Reference proteome; Repeat; Signal; KW Transmembrane; Transmembrane helix. FT SIGNAL 1..26 FT /evidence="ECO:0000269|PubMed:15340161" FT CHAIN 27..448 FT /note="Tumor necrosis factor receptor superfamily member FT EDAR" FT /id="PRO_0000034608" FT TOPO_DOM 27..187 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 188..208 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 209..448 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT REPEAT 30..71 FT /note="TNFR-Cys 1" FT REPEAT 73..113 FT /note="TNFR-Cys 2" FT REPEAT 115..148 FT /note="TNFR-Cys 3" FT DOMAIN 358..431 FT /note="Death" FT REGION 220..297 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 233..243 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 271..283 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT CARBOHYD 38 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 31..44 FT /evidence="ECO:0000250" FT DISULFID 47..60 FT /evidence="ECO:0000250" FT DISULFID 50..71 FT /evidence="ECO:0000250" FT DISULFID 74..87 FT /evidence="ECO:0000250" FT DISULFID 93..113 FT /evidence="ECO:0000250" FT DISULFID 135..148 FT /evidence="ECO:0000250" FT VAR_SEQ 219 FT /note="A -> GDGPHAPVPCFLDSPSTPPVGEPGCSLPPLSPA (in isoform FT 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_054187" FT VARIANT 47 FT /note="C -> Y (in ECTD10B; dbSNP:rs778903951)" FT /evidence="ECO:0000269|PubMed:16435307" FT /id="VAR_054444" FT VARIANT 87 FT /note="C -> R (in ECTD10B; dbSNP:rs121908451)" FT /evidence="ECO:0000269|PubMed:10431241" FT /id="VAR_013448" FT VARIANT 89 FT /note="R -> H (in ECTD10B; dbSNP:rs121908450)" FT /evidence="ECO:0000269|PubMed:10431241, FT ECO:0000269|PubMed:16435307, ECO:0000269|PubMed:18231121, FT ECO:0000269|PubMed:20979233" FT /id="VAR_013449" FT VARIANT 98 FT /note="R -> Q (in ECTD10B; dbSNP:rs144473052)" FT /evidence="ECO:0000269|PubMed:19438931" FT /id="VAR_064830" FT VARIANT 110 FT /note="D -> A (in ECTD10B; dbSNP:rs121908455)" FT /evidence="ECO:0000269|PubMed:16435307, FT ECO:0000269|PubMed:18231121" FT /id="VAR_054445" FT VARIANT 148 FT /note="C -> R (in ECTD10B; dbSNP:rs1181378221)" FT /evidence="ECO:0000269|PubMed:16435307" FT /id="VAR_054446" FT VARIANT 358 FT /note="R -> Q (in ECTD10B; dbSNP:rs886039564)" FT /evidence="ECO:0000269|PubMed:19438931, FT ECO:0000269|PubMed:20979233" FT /id="VAR_064831" FT VARIANT 370 FT /note="V -> A (associated with increase in hair thickness; FT results in decreased downstream activity of NFKB1 48 hours FT after transfection into cells; dbSNP:rs3827760)" FT /evidence="ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:18065779, ECO:0000269|PubMed:18561327" FT /id="VAR_020011" FT VARIANT 370 FT /note="V -> L (in dbSNP:rs1267372612)" FT /evidence="ECO:0000269|PubMed:27657131" FT /id="VAR_077562" FT VARIANT 375 FT /note="R -> H (in ECTD10B; the mutant protein does not FT interact with EDARADD and is functionally inactive; FT dbSNP:rs121908454)" FT /evidence="ECO:0000269|PubMed:15373768" FT /id="VAR_054447" FT VARIANT 377 FT /note="L -> F (in ECTD10B)" FT /evidence="ECO:0000269|PubMed:16435307" FT /id="VAR_054448" FT VARIANT 382 FT /note="G -> S (in ECTD10B; dbSNP:rs747806672)" FT /evidence="ECO:0000269|PubMed:16029325" FT /id="VAR_054449" FT VARIANT 396 FT /note="Q -> QQ (in ECTD10B)" FT /evidence="ECO:0000269|PubMed:20979233" FT /id="VAR_064832" FT VARIANT 403 FT /note="T -> M (in ECTD10B; dbSNP:rs1696610832)" FT /evidence="ECO:0000269|PubMed:16435307, FT ECO:0000269|PubMed:20979233" FT /id="VAR_054450" FT VARIANT 408 FT /note="I -> F (in ECTD10B)" FT /evidence="ECO:0000269|PubMed:20979233" FT /id="VAR_064833" FT VARIANT 413 FT /note="T -> P (in ECTD10B)" FT /evidence="ECO:0000269|PubMed:16435307" FT /id="VAR_054451" FT VARIANT 418 FT /note="I -> T (in ECTD10B; dbSNP:rs1696609870)" FT /evidence="ECO:0000269|PubMed:16435307" FT /id="VAR_054452" FT VARIANT 420 FT /note="R -> Q (in ECTD10A and ECTD10B; abolishes NF-kappa-B FT activation and reduces JNK activation; dbSNP:rs121908453)" FT /evidence="ECO:0000269|PubMed:10431241, FT ECO:0000269|PubMed:11035039, ECO:0000269|PubMed:16435307, FT ECO:0000269|PubMed:18231121, ECO:0000269|PubMed:20979233, FT ECO:0000269|PubMed:27657131" FT /id="VAR_013450" FT VARIANT 434 FT /note="W -> C (in ECTD10B; dbSNP:rs528478080)" FT /evidence="ECO:0000269|PubMed:16435307" FT /id="VAR_054453" FT VARIANT 434 FT /note="W -> R (in ECTD10B; dbSNP:rs773885029)" FT /evidence="ECO:0000269|PubMed:19438931" FT /id="VAR_064834" FT MUTAGEN 379 FT /note="E->K: Reduces activation of NF-kappa-B." FT /evidence="ECO:0000269|PubMed:11035039" FT CONFLICT 156 FT /note="S -> P (in Ref. 2; BAG36519)" FT /evidence="ECO:0000305" FT CONFLICT 262 FT /note="P -> S (in Ref. 1; AAD50077)" FT /evidence="ECO:0000305" FT STRAND 54..57 FT /evidence="ECO:0007829|PDB:7X9G" FT STRAND 70..73 FT /evidence="ECO:0007829|PDB:7X9G" FT HELIX 93..96 FT /evidence="ECO:0007829|PDB:7X9G" FT STRAND 100..102 FT /evidence="ECO:0007829|PDB:7X9G" FT STRAND 106..108 FT /evidence="ECO:0007829|PDB:7X9G" FT STRAND 132..134 FT /evidence="ECO:0007829|PDB:7X9G" FT CONFLICT Q9UNE0-2:229 FT /note="F -> L (in Ref. 2; BAG59487)" FT /evidence="ECO:0000305" SQ SEQUENCE 448 AA; 48582 MW; AC8D61249D608439 CRC64; MAHVGDCTQT PWLPVLVVSL MCSARAEYSN CGENEYYNQT TGLCQECPPC GPGEEPYLSC GYGTKDEDYG CVPCPAEKFS KGGYQICRRH KDCEGFFRAT VLTPGDMEND AECGPCLPGY YMLENRPRNI YGMVCYSCLL APPNTKECVG ATSGASANFP GTSGSSTLSP FQHAHKELSG QGHLATALII AMSTIFIMAI AIVLIIMFYI LKTKPSAPAC CTSHPGKSVE AQVSKDEEKK EAPDNVVMFS EKDEFEKLTA TPAKPTKSEN DASSENEQLL SRSVDSDEEP APDKQGSPEL CLLSLVHLAR EKSATSNKSA GIQSRRKKIL DVYANVCGVV EGLSPTELPF DCLEKTSRML SSTYNSEKAV VKTWRHLAES FGLKRDEIGG MTDGMQLFDR ISTAGYSIPE LLTKLVQIER LDAVESLCAD ILEWAGVVPP ASQPHAAS //