EDAR_HUMAN
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 03-AUG-2022, entry version 177.
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 Q9UNE0-2; 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.
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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_022336.3. [Q9UNE0-1]
DR RefSeq; XP_006712267.1; XM_006712204.1. [Q9UNE0-2]
DR AlphaFoldDB; Q9UNE0; -.
DR BioGRID; 116118; 73.
DR IntAct; Q9UNE0; 8.
DR STRING; 9606.ENSP00000258443; -.
DR ChEMBL; CHEMBL1250376; -.
DR GlyGen; Q9UNE0; 1 site.
DR iPTMnet; Q9UNE0; -.
DR PhosphoSitePlus; Q9UNE0; -.
DR BioMuta; EDAR; -.
DR DMDM; 21263572; -.
DR jPOST; Q9UNE0; -.
DR MassIVE; Q9UNE0; -.
DR PaxDb; Q9UNE0; -.
DR PeptideAtlas; Q9UNE0; -.
DR PRIDE; Q9UNE0; -.
DR ProteomicsDB; 19402; -.
DR ProteomicsDB; 85279; -. [Q9UNE0-1]
DR ABCD; Q9UNE0; 14 sequenced antibodies.
DR Antibodypedia; 33144; 335 antibodies from 33 providers.
DR DNASU; 10913; -.
DR Ensembl; ENST00000258443.7; ENSP00000258443.2; ENSG00000135960.10. [Q9UNE0-1]
DR Ensembl; ENST00000376651.1; ENSP00000365839.1; ENSG00000135960.10. [Q9UNE0-2]
DR Ensembl; ENST00000409271.5; ENSP00000386371.1; ENSG00000135960.10. [Q9UNE0-2]
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 GeneCards; EDAR; -.
DR GeneReviews; EDAR; -.
DR HGNC; HGNC:2895; EDAR.
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 neXtProt; NX_Q9UNE0; -.
DR OpenTargets; ENSG00000135960; -.
DR Orphanet; 1810; Autosomal dominant hypohidrotic ectodermal dysplasia.
DR Orphanet; 248; Autosomal recessive hypohidrotic ectodermal dysplasia.
DR PharmGKB; PA27602; -.
DR VEuPathDB; HostDB:ENSG00000135960; -.
DR eggNOG; ENOG502QRV5; Eukaryota.
DR GeneTree; ENSGT00940000153259; -.
DR HOGENOM; CLU_039634_0_0_1; -.
DR InParanoid; Q9UNE0; -.
DR OMA; CGENEYH; -.
DR OrthoDB; 672843at2759; -.
DR PhylomeDB; Q9UNE0; -.
DR TreeFam; TF331385; -.
DR PathwayCommons; Q9UNE0; -.
DR Reactome; R-HSA-5669034; TNFs bind their physiological receptors.
DR SignaLink; Q9UNE0; -.
DR SIGNOR; Q9UNE0; -.
DR BioGRID-ORCS; 10913; 97 hits in 1071 CRISPR screens.
DR GeneWiki; EDAR; -.
DR GenomeRNAi; 10913; -.
DR Pharos; Q9UNE0; Tbio.
DR PRO; PR:Q9UNE0; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q9UNE0; protein.
DR Bgee; ENSG00000135960; Expressed in secondary oocyte and 77 other tissues.
DR Genevisible; Q9UNE0; HS.
DR GO; GO:0045177; C:apical part of cell; IEA:Ensembl.
DR GO; GO:0016021; C:integral component of membrane; NAS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0038023; F:signaling receptor activity; IBA:GO_Central.
DR GO; GO:0004888; F:transmembrane signaling receptor activity; IDA:HGNC-UCL.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0008544; P:epidermis development; TAS:HGNC-UCL.
DR GO; GO:0001942; P:hair follicle development; IEA:Ensembl.
DR GO; GO:0042475; P:odontogenesis of dentin-containing tooth; IEA:Ensembl.
DR GO; GO:0043473; P:pigmentation; IEA:Ensembl.
DR GO; GO:0010628; P:positive regulation of gene expression; IEA:Ensembl.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IBA:GO_Central.
DR GO; GO:0046330; P:positive regulation of JNK cascade; IBA:GO_Central.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; IEA:Ensembl.
DR GO; GO:0060662; P:salivary gland cavitation; IEA:Ensembl.
DR CDD; cd13421; TNFRSF_EDAR; 1.
DR Gene3D; 1.10.533.10; -; 1.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR034052; EDAR_N.
DR SUPFAM; SSF47986; SSF47986; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Apoptosis; Developmental protein; Differentiation;
KW Direct protein sequencing; Disease variant; Disulfide bond;
KW Ectodermal dysplasia; Glycoprotein; Membrane; Receptor; Reference proteome;
KW Repeat; Signal; 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 230..260
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 263..280
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)"
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)"
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)"
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 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
