EDA_HUMAN
ID EDA_HUMAN Reviewed; 391 AA.
AC Q92838; A0AUZ2; A2A337; B7ZLU2; B7ZLU4; O75910; Q5JS00; Q5JUM7; Q9UP77;
AC Q9Y6L0; Q9Y6L1; Q9Y6L2; Q9Y6L3; Q9Y6L4;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1999, sequence version 2.
DT 03-AUG-2022, entry version 209.
DE RecName: Full=Ectodysplasin-A;
DE AltName: Full=Ectodermal dysplasia protein;
DE Short=EDA protein;
DE Contains:
DE RecName: Full=Ectodysplasin-A, membrane form;
DE Contains:
DE RecName: Full=Ectodysplasin-A, secreted form;
GN Name=EDA; Synonyms=ED1, EDA2;
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 [MRNA] (ISOFORM 2), NUCLEOTIDE SEQUENCE [GENOMIC DNA]
RP OF 1-132, VARIANTS XHED HIS-61 AND LEU-69, AND FUNCTION.
RC TISSUE=Sweat gland;
RX PubMed=8696334; DOI=10.1038/ng0895-409;
RA Kere J., Srivastava A.K., Montonen O., Zonana J., Thomas N.S.T.,
RA Ferguson B.M., Munoz F., Morgan D., Clarke A., Baybayan P., Chen E.Y.,
RA Ezer S., Saarialho-Kere U., la Chapelle A., Schlessinger D.;
RT "X-linked anhidrotic (hypohidrotic) ectodermal dysplasia is caused by
RT mutation in a novel transmembrane protein.";
RL Nat. Genet. 13:409-416(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE [GENOMIC DNA]
RP OF 133-391, AND VARIANTS XHED.
RC TISSUE=Fetal liver;
RX PubMed=9683615; DOI=10.1086/301984;
RA Monreal A.W., Zonana J., Ferguson B.M.;
RT "Identification of a new splice form of the EDA1 gene permits detection of
RT nearly all X-linked hypohidrotic ectodermal dysplasia mutations.";
RL Am. J. Hum. Genet. 63:380-389(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 3; 4; 5; 6 AND 7), AND VARIANTS
RP XHED.
RX PubMed=9736768; DOI=10.1093/hmg/7.11.1661;
RA Bayes M., Hartung A.J., Ezer S., Pispa J., Thesleff I., Srivastava A.K.,
RA Kere J.;
RT "The anhidrotic ectodermal dysplasia gene (EDA) undergoes alternative
RT splicing and encodes ectodysplasin-A with deletion mutations in collagenous
RT repeats.";
RL Hum. Mol. Genet. 7:1661-1669(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 3 AND 8).
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 TISSUE SPECIFICITY, AND ALTERNATIVE SPLICING.
RA Kobielak K., Kobielak A., Trzciak W.H.;
RT "Expression of a novel transcript isoform of the EDA gene in human
RT umbilical cord.";
RL Eur. J. Hum. Genet. Suppl. 7:104-104(1999).
RN [7]
RP FUNCTION, AND RECEPTOR INTERACTION (ISOFORMS 1 AND 3).
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 PROTEOLYTIC PROCESSING, CHARACTERIZATION OF VARIANT XHED CYS-153, AND
RP CHARACTERIZATION OF VARIANT HIS-156.
RX PubMed=11309369; DOI=10.1093/hmg/10.9.953;
RA Elomaa O., Pulkkinen K., Hannelius U., Mikkola M., Saarialho-Kere U.,
RA Kere J.;
RT "Ectodysplasin is released by proteolytic shedding and binds to the EDAR
RT protein.";
RL Hum. Mol. Genet. 10:953-962(2001).
RN [9]
RP CHARACTERIZATION OF VARIANTS XHED CYS-153; CYS-155; CYS-156; HIS-156 AND
RP ASN-158, MUTAGENESIS OF ARG-159, AND CLEAVAGE SITE.
RX PubMed=11416205; DOI=10.1073/pnas.131076098;
RA Chen Y., Molloy S.S., Thomas L., Gambee J., Baechinger H.P., Ferguson B.M.,
RA Zonana J., Thomas G., Morris N.P.;
RT "Mutations within a furin consensus sequence block proteolytic release of
RT ectodysplasin-A and cause X-linked hypohidrotic ectodermal dysplasia.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:7218-7223(2001).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 230-391, AND SUBUNIT.
RX PubMed=14656435; DOI=10.1016/j.str.2003.11.009;
RA Hymowitz S.G., Compaan D.M., Yan M., Wallweber H.J., Dixit V.M.,
RA Starovasnik M.A., de Vos A.M.;
RT "The crystal structures of EDA-A1 and EDA-A2: splice variants with distinct
RT receptor specificity.";
RL Structure 11:1513-1520(2003).
RN [11]
RP VARIANT XHED TYR-54.
RX PubMed=9630076; DOI=10.1111/j.1399-0004.1998.tb02678.x;
RA Hertz J.M., Noergaard Hansen K., Juncker I., Kjeldsen M., Gregersen N.;
RT "A novel missense mutation (402C-->T) in exon 1 in the EDA gene in a family
RT with X-linked hypohidrotic ectodermal dysplasia.";
RL Clin. Genet. 53:205-209(1998).
RN [12]
RP VARIANT XHED LYS-63.
RX PubMed=9507389; DOI=10.1136/jmg.35.2.112;
RA Ferguson B.M., Thomas N.S.T., Munoz F., Morgan D., Clarke A., Zonana J.;
RT "Scarcity of mutations detected in families with X linked hypohidrotic
RT ectodermal dysplasia: diagnostic implications.";
RL J. Med. Genet. 35:112-115(1998).
RN [13]
RP VARIANT XHED ARG-55.
RX PubMed=10469321; DOI=10.1046/j.1523-1747.1999.00656.x;
RA Martinez F., Millan J.M., Orellana C., Prieto F.;
RT "X-linked anhidrotic (hypohidrotic) ectodermal dysplasia caused by a novel
RT mutation in EDA1 gene: 406T > G (Leu55Arg).";
RL J. Invest. Dermatol. 113:285-286(1999).
RN [14]
RP VARIANT XHED SER-156.
RX PubMed=10951256; DOI=10.1046/j.1523-1747.2000.00065-1.x;
RA Aoki N., Ito K., Tachibana T., Ito M.;
RT "A novel arginine-->Serine mutation in EDA1 in a Japanese family with X-
RT linked anhidrotic ectodermal dysplasia.";
RL J. Invest. Dermatol. 115:329-330(2000).
RN [15]
RP VARIANTS XHED THR-349 AND ASN-360.
RX PubMed=11343303; DOI=10.1002/ajmg.1225;
RA Kobielak K., Kobielak A., Roszkiewicz J., Wierzba J., Limon J.,
RA Trzeciak W.H.;
RT "Mutations in the EDA gene in three unrelated families reveal no apparent
RT correlation between phenotype and genotype in the patients with an X-linked
RT anhidrotic ectodermal dysplasia.";
RL Am. J. Med. Genet. 100:191-197(2001).
RN [16]
RP VARIANTS XHED ARG-60; TYR-252; VAL-269; SER-302 AND MET-378.
RX PubMed=11378824; DOI=10.1038/sj.ejhg.5200635;
RA Vincent M.-C., Biancalana V., Ginisty D., Mandel J.-L., Calvas P.;
RT "Mutational spectrum of the ED1 gene in X-linked hypohidrotic ectodermal
RT dysplasia.";
RL Eur. J. Hum. Genet. 9:355-363(2001).
RN [17]
RP VARIANTS XHED CYS-156; HIS-156; CYS-255; ASP-255; GLY-274; TYR-332 AND
RP THR-349.
RX PubMed=11295832; DOI=10.1002/humu.33;
RA Paeaekkoenen K., Cambiaghi S., Novelli G., Ouzts L.V., Penttinen M.,
RA Kere J., Srivastava A.K.;
RT "The mutation spectrum of the EDA gene in X-linked anhidrotic ectodermal
RT dysplasia.";
RL Hum. Mutat. 17:349-349(2001).
RN [18]
RP VARIANTS XHED CYS-153; CYS-155; CYS-156; HIS-156; ASN-158; 183-GLY--PRO-194
RP DEL; 185-ASN--PRO-196 DEL; GLU-189; 191-PRO--PRO-196 DEL; ARG-207; ASP-218;
RP 218-GLY--PRO-223 DEL; ARG-291; SER-299; CYS-320; CYS-343; ARG-374; PRO-378
RP AND MET-378.
RX PubMed=11279189; DOI=10.1074/jbc.m101280200;
RA Schneider P., Street S.L., Gaide O., Hertig S., Tardivel A., Tschopp J.,
RA Runkel L., Alevizopoulos K., Ferguson B.M., Zonana J.;
RT "Mutations leading to X-linked hypohidrotic ectodermal dysplasia affect
RT three major functional domains in the tumor necrosis factor family member
RT ectodysplasin-A.";
RL J. Biol. Chem. 276:18819-18827(2001).
RN [19]
RP VARIANTS XHED ALA-198 AND MET-378.
RX PubMed=12225002; DOI=10.1001/archderm.138.9.1256;
RA Vincent M.-C., Cossee M., Vabres P., Stewart F., Bonneau D., Calvas P.;
RT "Pitfalls in clinical diagnosis of female carriers of X-linked hypohidrotic
RT ectodermal dysplasia.";
RL Arch. Dermatol. 138:1256-1258(2002).
RN [20]
RP VARIANT XHED HIS-306.
RX PubMed=12932274; DOI=10.1046/j.1365-2133.2003.05480.x;
RA Hsu M.M.L., Chao S.C., Lu A.C.H.;
RT "A novel missense mutation (Gln306His) in exon 7 of the ED1 gene causing
RT anhidrotic ectodermal dysplasia with prominent milia-like facial sebaceous
RT papules.";
RL Br. J. Dermatol. 149:443-445(2003).
RN [21]
RP INVOLVEMENT IN STHAGX1, AND VARIANT STHAGX1 GLY-65.
RX PubMed=16583127; DOI=10.1007/s10038-006-0389-2;
RA Tao R., Jin B., Guo S.Z., Qing W., Feng G.Y., Brooks D.G., Liu L., Xu J.,
RA Li T., Yan Y., He L.;
RT "A novel missense mutation of the EDA gene in a Mongolian family with
RT congenital hypodontia.";
RL J. Hum. Genet. 51:498-502(2006).
RN [22]
RP VARIANT [LARGE SCALE ANALYSIS] LEU-118.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [23]
RP VARIANT XHED GLU-358.
RX PubMed=17256800; DOI=10.1002/ajmg.a.31567;
RA Tarpey P., Pemberton T.J., Stockton D.W., Das P., Ninis V., Edkins S.,
RA Andrew Futreal P., Wooster R., Kamath S., Nayak R., Stratton M.R.,
RA Patel P.I.;
RT "A novel Gln358Glu mutation in ectodysplasin A associated with X-linked
RT dominant incisor hypodontia.";
RL Am. J. Med. Genet. A 143:390-394(2007).
RN [24]
RP VARIANTS XHED CYS-155; CYS-156; HIS-156; 183-GLY--PRO-194 DEL;
RP 184-PRO--GLY-189 DEL; 185-ASN--PRO-196 DEL; ARG-291; TYR-298; GLY-307;
RP ASP-372 AND ILE-373.
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 [25]
RP VARIANT STHAGX1 MET-338.
RX PubMed=18657636; DOI=10.1016/j.ejmg.2008.06.002;
RA Han D., Gong Y., Wu H., Zhang X., Yan M., Wang X., Qu H., Feng H., Song S.;
RT "Novel EDA mutation resulting in X-linked non-syndromic hypodontia and the
RT pattern of EDA-associated isolated tooth agenesis.";
RL Eur. J. Med. Genet. 51:536-546(2008).
RN [26]
RP VARIANTS XHED CYS-153; CYS-155 AND THR-349.
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 [27]
RP VARIANTS STHAGX1 GLU-259; CYS-289 AND HIS-334.
RX PubMed=19278982; DOI=10.1177/0022034508328627;
RA Song S., Han D., Qu H., Gong Y., Wu H., Zhang X., Zhong N., Feng H.;
RT "EDA gene mutations underlie non-syndromic oligodontia.";
RL J. Dent. Res. 88:126-131(2009).
RN [28]
RP VARIANT XHED ARG-381.
RX PubMed=19127222; DOI=10.1203/pdr.0b013e3181991229;
RA Gunadi X., Miura K., Ohta M., Sugano A., Lee M.J., Sato Y., Matsunaga A.,
RA Hayashi K., Horikawa T., Miki K., Wataya-Kaneda M., Katayama I.,
RA Nishigori C., Matsuo M., Takaoka Y., Nishio H.;
RT "Two novel mutations in the ED1 gene in Japanese families with X-linked
RT hypohidrotic ectodermal dysplasia.";
RL Pediatr. Res. 65:453-457(2009).
RN [29]
RP VARIANT XHED CYS-155.
RX PubMed=20486090; DOI=10.4238/vol9-2gmr810;
RA Khabour O.F., Mesmar F.S., Al-Tamimi F., Al-Batayneh O.B., Owais A.I.;
RT "Missense mutation of the EDA gene in a Jordanian family with X-linked
RT hypohidrotic ectodermal dysplasia: phenotypic appearance and speech
RT problems.";
RL Genet. Mol. Res. 9:941-948(2010).
RN [30]
RP VARIANTS XHED GLY-156; 192-GLY--GLN-197 DEL; VAL-207; ARG-211; ARG-266;
RP ARG-274; PRO-293; VAL-296; ASP-299; GLY-323; TYR-346 AND VAL-356.
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 [31]
RP VARIANT XHED PRO-354.
RX PubMed=22008666; DOI=10.1016/j.gene.2011.10.009;
RA Liu Y., Yu X., Wang L., Li C., Archacki S., Huang C., Liu J.Y., Wang Q.,
RA Liu M., Tang Z.;
RT "Mutation p.Leu354Pro in EDA causes severe hypohidrotic ectodermal
RT dysplasia in a Chinese family.";
RL Gene 491:246-250(2012).
RN [32]
RP VARIANT XHED ARG-319.
RX PubMed=22350046;
RA Piccione M., Serra G., Sanfilippo C., Andreucci E., Sani I., Corsello G.;
RT "A new mutation in EDA gene in X-linked hypohidrotic ectodermal dysplasia
RT associated with keratoconus.";
RL Minerva Pediatr. 64:59-64(2012).
RN [33]
RP VARIANT STHAGX1 SER-260.
RX PubMed=23625373; DOI=10.1177/0022034513487557;
RA Yang Y., Luo L., Xu J., Zhu P., Xue W., Wang J., Li W., Wang M., Cheng K.,
RA Liu S., Tang Z., Ring B.Z., Su L.;
RT "Novel EDA p.Ile260Ser mutation linked to non-syndromic hypodontia.";
RL J. Dent. Res. 92:500-506(2013).
RN [34]
RP INVOLVEMENT IN STHAGX1.
RX PubMed=23603338; DOI=10.1177/0022034513487210;
RA Nikopensius T., Annilo T., Jagomaegi T., Gilissen C., Kals M.,
RA Krjutskov K., Maegi R., Eelmets M., Gerst-Talas U., Remm M., Saag M.,
RA Hoischen A., Metspalu A.;
RT "Non-syndromic tooth agenesis associated with a nonsense mutation in
RT ectodysplasin-A (EDA).";
RL J. Dent. Res. 92:507-511(2013).
RN [35]
RP VARIANTS STHAGX1 LEU-289 AND VAL-379.
RX PubMed=24487376; DOI=10.1177/0022034514522059;
RA Lee K.E., Ko J., Shin T.J., Hyun H.K., Lee S.H., Kim J.W.;
RT "Oligodontia and curly hair occur with ectodysplasin-a mutations.";
RL J. Dent. Res. 93:371-375(2014).
RN [36]
RP VARIANTS XHED GLN-51; CYS-125; PRO-132; HIS-153; CYS-155; HIS-156;
RP 183-GLY--PRO-194 DEL; 185-ASN--PRO-196 DEL; 191-PRO--PRO-196 DEL;
RP 193-PRO--GLY-201 DEL; 219-PRO--GLY-230 DEL; GLY-274; ARG-291; SER-299;
RP HIS-304; GLU-316; ARG-319; SER-319 DEL; PHE-332; ASP-350; HIS-358 AND
RP VAL-381.
RX PubMed=24724966; DOI=10.1111/cge.12404;
RA Guazzarotti L., Tadini G., Mancini G.E., Giglio S., Willoughby C.E.,
RA Callea M., Sani I., Nannini P., Mameli C., Tenconi A.A., Mauri S.,
RA Bottero A., Caimi A., Morelli M., Zuccotti G.V.;
RT "Phenotypic heterogeneity and mutational spectrum in a cohort of 45 Italian
RT males subjects with X-linked ectodermal dysplasia.";
RL Clin. Genet. 87:338-342(2015).
RN [37]
RP VARIANTS XHED CYS-155; ASP-221; SER-299 AND MET-338.
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).
RN [38]
RP CHARACTERIZATION OF VARIANTS XHED LEU-252; CYS-343 AND ARG-374,
RP CHARACTERIZATION OF VARIANTS STHAGX1 GLU-259; CYS-289; HIS-334; CYS-343 AND
RP ARG-374, AND FUNCTION.
RX PubMed=27144394; DOI=10.1371/journal.pone.0154884;
RA Shen W., Wang Y., Liu Y., Liu H., Zhao H., Zhang G., Snead M.L., Han D.,
RA Feng H.;
RT "Functional study of ectodysplasin-a mutations causing non-syndromic tooth
RT agenesis.";
RL PLoS ONE 11:E0154884-E0154884(2016).
RN [39]
RP VARIANTS XHED PRO-289; CYS-290 AND SER-379, CHARACTERIZATION OF VARIANTS
RP XHED PRO-289; CYS-290 AND SER-379, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=34582123; DOI=10.1002/mgg3.1824;
RA Yu K., Shen Y., Jiang C.L., Huang W., Wang F., Wu Y.Q.;
RT "Two novel ectodysplasin A gene mutations and prenatal diagnosis of X-
RT linked hypohidrotic ectodermal dysplasia.";
RL Mol. Genet. Genomic Med. 0:0-0(2021).
CC -!- FUNCTION: Cytokine which is involved in epithelial-mesenchymal
CC signaling during morphogenesis of ectodermal organs. Functions as a
CC ligand activating the DEATH-domain containing receptors EDAR and EDA2R
CC (PubMed:8696334, PubMed:11039935, PubMed:27144394, PubMed:34582123).
CC May also play a role in cell adhesion (By similarity).
CC {ECO:0000250|UniProtKB:O54693, ECO:0000269|PubMed:11039935,
CC ECO:0000269|PubMed:27144394, ECO:0000269|PubMed:34582123,
CC ECO:0000269|PubMed:8696334}.
CC -!- FUNCTION: [Isoform 1]: Binds only to the receptor EDAR, while isoform 3
CC binds exclusively to the receptor EDA2R. {ECO:0000269|PubMed:11039935,
CC ECO:0000269|PubMed:27144394}.
CC -!- FUNCTION: [Isoform 3]: Binds only to the receptor EDA2R.
CC {ECO:0000269|PubMed:11039935, ECO:0000269|PubMed:27144394}.
CC -!- SUBUNIT: Homotrimer. The homotrimers may then dimerize and form higher-
CC order oligomers. {ECO:0000269|PubMed:14656435}.
CC -!- INTERACTION:
CC Q92838; P27449: ATP6V0C; NbExp=4; IntAct=EBI-529425, EBI-721179;
CC Q92838; Q4LDR2: CTXN3; NbExp=3; IntAct=EBI-529425, EBI-12019274;
CC Q92838; P49447: CYB561; NbExp=6; IntAct=EBI-529425, EBI-8646596;
CC Q92838; Q9UPQ8: DOLK; NbExp=6; IntAct=EBI-529425, EBI-8645574;
CC Q92838; P54849: EMP1; NbExp=3; IntAct=EBI-529425, EBI-4319440;
CC Q92838; P54852: EMP3; NbExp=7; IntAct=EBI-529425, EBI-3907816;
CC Q92838; Q96F15: GIMAP5; NbExp=6; IntAct=EBI-529425, EBI-6166686;
CC Q92838; O95214: LEPROTL1; NbExp=4; IntAct=EBI-529425, EBI-750776;
CC Q92838; Q6FHL7: LEPROTL1; NbExp=3; IntAct=EBI-529425, EBI-10249700;
CC Q92838; Q9UBY5: LPAR3; NbExp=3; IntAct=EBI-529425, EBI-12033434;
CC Q92838; P21145: MAL; NbExp=7; IntAct=EBI-529425, EBI-3932027;
CC Q92838; Q5J8X5: MS4A13; NbExp=3; IntAct=EBI-529425, EBI-12070086;
CC Q92838; Q6P499: NIPAL3; NbExp=8; IntAct=EBI-529425, EBI-10252783;
CC Q92838; Q9NRP0: OSTC; NbExp=3; IntAct=EBI-529425, EBI-1044658;
CC Q92838; Q8TBU1: OSTCL; NbExp=3; IntAct=EBI-529425, EBI-10273677;
CC Q92838; P26678: PLN; NbExp=11; IntAct=EBI-529425, EBI-692836;
CC Q92838; Q01453: PMP22; NbExp=3; IntAct=EBI-529425, EBI-2845982;
CC Q92838; Q96IW7: SEC22A; NbExp=7; IntAct=EBI-529425, EBI-8652744;
CC Q92838; Q9NVC3: SLC38A7; NbExp=3; IntAct=EBI-529425, EBI-10314552;
CC Q92838; Q69YG0: TMEM42; NbExp=3; IntAct=EBI-529425, EBI-12038591;
CC Q92838; P56557: TMEM50B; NbExp=3; IntAct=EBI-529425, EBI-12366453;
CC Q92838; Q9H2L4: TMEM60; NbExp=3; IntAct=EBI-529425, EBI-2852148;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:O54693};
CC Single-pass type II membrane protein {ECO:0000250|UniProtKB:O54693}.
CC -!- SUBCELLULAR LOCATION: [Ectodysplasin-A, secreted form]: Secreted
CC {ECO:0000269|PubMed:11309369, ECO:0000269|PubMed:34582123}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=8;
CC Comment=Additional isoforms seem to exist.;
CC Name=1; Synonyms=A1, II, EDA1 {ECO:0000303|PubMed:27144394};
CC IsoId=Q92838-1; Sequence=Displayed;
CC Name=2; Synonyms=I;
CC IsoId=Q92838-2; Sequence=VSP_006454, VSP_006455;
CC Name=3; Synonyms=A2, EDA2 {ECO:0000303|PubMed:27144394};
CC IsoId=Q92838-3; Sequence=VSP_006464;
CC Name=4; Synonyms=C;
CC IsoId=Q92838-5; Sequence=VSP_006458, VSP_006461;
CC Name=5; Synonyms=D;
CC IsoId=Q92838-6; Sequence=VSP_006456, VSP_006457;
CC Name=6; Synonyms=E;
CC IsoId=Q92838-7; Sequence=VSP_006459, VSP_006461;
CC Name=7; Synonyms=F;
CC IsoId=Q92838-8; Sequence=VSP_006460, VSP_006461;
CC Name=8;
CC IsoId=Q92838-9; Sequence=VSP_038402, VSP_006464;
CC -!- TISSUE SPECIFICITY: Not abundant; expressed in specific cell types of
CC ectodermal (but not mesodermal) origin of keratinocytes, hair
CC follicles, sweat glands. Also in adult heart, liver, muscle, pancreas,
CC prostate, fetal liver, uterus, small intestine and umbilical chord.
CC {ECO:0000269|Ref.6}.
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:O54693}.
CC -!- PTM: Processing by furin produces a secreted form.
CC {ECO:0000269|PubMed:11416205}.
CC -!- DISEASE: Ectodermal dysplasia 1, hypohidrotic, X-linked (XHED)
CC [MIM:305100]: A form of ectodermal dysplasia, a heterogeneous group of
CC disorders due to abnormal development of two or more ectodermal
CC structures. Characterized by sparse hair (atrichosis or hypotrichosis),
CC abnormal or missing teeth and the inability to sweat due to the absence
CC of sweat glands. It is the most common form of over 150 clinically
CC distinct ectodermal dysplasias. {ECO:0000269|PubMed:10469321,
CC ECO:0000269|PubMed:10951256, ECO:0000269|PubMed:11279189,
CC ECO:0000269|PubMed:11295832, ECO:0000269|PubMed:11309369,
CC ECO:0000269|PubMed:11343303, ECO:0000269|PubMed:11378824,
CC ECO:0000269|PubMed:11416205, ECO:0000269|PubMed:12225002,
CC ECO:0000269|PubMed:12932274, ECO:0000269|PubMed:17256800,
CC ECO:0000269|PubMed:18231121, ECO:0000269|PubMed:19127222,
CC ECO:0000269|PubMed:19438931, ECO:0000269|PubMed:20486090,
CC ECO:0000269|PubMed:20979233, ECO:0000269|PubMed:22008666,
CC ECO:0000269|PubMed:22350046, ECO:0000269|PubMed:24724966,
CC ECO:0000269|PubMed:27144394, ECO:0000269|PubMed:27657131,
CC ECO:0000269|PubMed:34582123, ECO:0000269|PubMed:8696334,
CC ECO:0000269|PubMed:9507389, ECO:0000269|PubMed:9630076,
CC ECO:0000269|PubMed:9683615, ECO:0000269|PubMed:9736768}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Tooth agenesis, selective, X-linked, 1 (STHAGX1) [MIM:313500]:
CC A form of selective tooth agenesis, a common anomaly characterized by
CC the congenital absence of one or more teeth. Selective tooth agenesis
CC without associated systemic disorders has sometimes been divided into 2
CC types: oligodontia, defined as agenesis of 6 or more permanent teeth,
CC and hypodontia, defined as agenesis of less than 6 teeth. The number in
CC both cases does not include absence of third molars (wisdom teeth).
CC {ECO:0000269|PubMed:16583127, ECO:0000269|PubMed:18657636,
CC ECO:0000269|PubMed:19278982, ECO:0000269|PubMed:23603338,
CC ECO:0000269|PubMed:23625373, ECO:0000269|PubMed:24487376,
CC ECO:0000269|PubMed:27144394}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: [Isoform 5]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the tumor necrosis factor family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC77372.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305};
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DR EMBL; U59227; AAC50678.1; -; Genomic_DNA.
DR EMBL; U59228; AAC50679.1; -; mRNA.
DR EMBL; AH006445; AAC36303.1; -; Genomic_DNA.
DR EMBL; AF060999; AAC36302.1; -; mRNA.
DR EMBL; AF040628; AAC77363.1; -; mRNA.
DR EMBL; AF061189; AAC77371.1; -; mRNA.
DR EMBL; AF061190; AAC77372.1; ALT_SEQ; mRNA.
DR EMBL; AF061191; AAC77373.1; -; mRNA.
DR EMBL; AF061192; AAC77374.1; -; mRNA.
DR EMBL; AF061193; AAC77375.1; -; mRNA.
DR EMBL; AF061194; AAC77376.1; -; mRNA.
DR EMBL; AL158069; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL158141; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; FO393403; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC126143; AAI26144.1; -; mRNA.
DR EMBL; BC144049; AAI44050.1; -; mRNA.
DR EMBL; BC144051; AAI44052.1; -; mRNA.
DR CCDS; CCDS14394.1; -. [Q92838-1]
DR CCDS; CCDS35318.2; -. [Q92838-2]
DR CCDS; CCDS35319.2; -. [Q92838-9]
DR CCDS; CCDS43966.1; -. [Q92838-3]
DR CCDS; CCDS55436.1; -. [Q92838-7]
DR RefSeq; NP_001005609.1; NM_001005609.1. [Q92838-3]
DR RefSeq; NP_001005610.2; NM_001005610.3. [Q92838-2]
DR RefSeq; NP_001005612.2; NM_001005612.2. [Q92838-9]
DR RefSeq; NP_001005613.1; NM_001005613.3. [Q92838-7]
DR RefSeq; NP_001390.1; NM_001399.4. [Q92838-1]
DR PDB; 1RJ7; X-ray; 2.30 A; A/B/D/E/F/G/H/I/J/K/L/M=233-391.
DR PDB; 1RJ8; X-ray; 2.23 A; A/B/D/E/F/G=230-389.
DR PDBsum; 1RJ7; -.
DR PDBsum; 1RJ8; -.
DR AlphaFoldDB; Q92838; -.
DR SMR; Q92838; -.
DR BioGRID; 108224; 110.
DR IntAct; Q92838; 71.
DR STRING; 9606.ENSP00000363680; -.
DR GlyGen; Q92838; 2 sites.
DR iPTMnet; Q92838; -.
DR PhosphoSitePlus; Q92838; -.
DR BioMuta; EDA; -.
DR DMDM; 6166135; -.
DR MassIVE; Q92838; -.
DR PaxDb; Q92838; -.
DR PeptideAtlas; Q92838; -.
DR PRIDE; Q92838; -.
DR ProteomicsDB; 75522; -. [Q92838-1]
DR ProteomicsDB; 75524; -. [Q92838-3]
DR ProteomicsDB; 75529; -. [Q92838-9]
DR ABCD; Q92838; 3 sequenced antibodies.
DR Antibodypedia; 27342; 560 antibodies from 36 providers.
DR DNASU; 1896; -.
DR Ensembl; ENST00000338901.4; ENSP00000340611.4; ENSG00000158813.18. [Q92838-5]
DR Ensembl; ENST00000374552.9; ENSP00000363680.4; ENSG00000158813.18. [Q92838-1]
DR Ensembl; ENST00000374553.6; ENSP00000363681.2; ENSG00000158813.18. [Q92838-3]
DR Ensembl; ENST00000524573.5; ENSP00000432585.1; ENSG00000158813.18. [Q92838-9]
DR Ensembl; ENST00000525810.5; ENSP00000434195.1; ENSG00000158813.18. [Q92838-2]
DR Ensembl; ENST00000527388.5; ENSP00000434861.1; ENSG00000158813.18. [Q92838-7]
DR GeneID; 1896; -.
DR KEGG; hsa:1896; -.
DR MANE-Select; ENST00000374552.9; ENSP00000363680.4; NM_001399.5; NP_001390.1.
DR UCSC; uc004dxm.2; human. [Q92838-1]
DR CTD; 1896; -.
DR DisGeNET; 1896; -.
DR GeneCards; EDA; -.
DR GeneReviews; EDA; -.
DR HGNC; HGNC:3157; EDA.
DR HPA; ENSG00000158813; Low tissue specificity.
DR MalaCards; EDA; -.
DR MIM; 300451; gene.
DR MIM; 305100; phenotype.
DR MIM; 313500; phenotype.
DR neXtProt; NX_Q92838; -.
DR OpenTargets; ENSG00000158813; -.
DR Orphanet; 2227; NON RARE IN EUROPE: Hypodontia.
DR Orphanet; 99798; Oligodontia.
DR Orphanet; 181; X-linked hypohidrotic ectodermal dysplasia.
DR PharmGKB; PA27601; -.
DR VEuPathDB; HostDB:ENSG00000158813; -.
DR eggNOG; ENOG502QUAV; Eukaryota.
DR GeneTree; ENSGT00730000111220; -.
DR HOGENOM; CLU_1880065_0_0_1; -.
DR InParanoid; Q92838; -.
DR OMA; REITHQK; -.
DR OrthoDB; 1183050at2759; -.
DR PhylomeDB; Q92838; -.
DR TreeFam; TF332099; -.
DR PathwayCommons; Q92838; -.
DR Reactome; R-HSA-5669034; TNFs bind their physiological receptors. [Q92838-3]
DR SignaLink; Q92838; -.
DR SIGNOR; Q92838; -.
DR BioGRID-ORCS; 1896; 10 hits in 707 CRISPR screens.
DR ChiTaRS; EDA; human.
DR EvolutionaryTrace; Q92838; -.
DR GeneWiki; EDA_(gene); -.
DR GenomeRNAi; 1896; -.
DR Pharos; Q92838; Tbio.
DR PRO; PR:Q92838; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; Q92838; protein.
DR Bgee; ENSG00000158813; Expressed in oocyte and 128 other tissues.
DR ExpressionAtlas; Q92838; baseline and differential.
DR Genevisible; Q92838; HS.
DR GO; GO:0045177; C:apical part of cell; IEA:Ensembl.
DR GO; GO:0005581; C:collagen trimer; IEA:UniProtKB-KW.
DR GO; GO:0005856; C:cytoskeleton; TAS:ProtInc.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:Ensembl.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; TAS:ProtInc.
DR GO; GO:0005887; C:integral component of plasma membrane; IEA:Ensembl.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005811; C:lipid droplet; IDA:HPA.
DR GO; GO:0016020; C:membrane; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0038177; F:death receptor agonist activity; IMP:UniProtKB.
DR GO; GO:0005123; F:death receptor binding; IDA:UniProtKB.
DR GO; GO:0048018; F:receptor ligand activity; IBA:GO_Central.
DR GO; GO:0005102; F:signaling receptor binding; IDA:HGNC-UCL.
DR GO; GO:0005164; F:tumor necrosis factor receptor binding; IEA:InterPro.
DR GO; GO:0048513; P:animal organ development; IBA:GO_Central.
DR GO; GO:0060070; P:canonical Wnt signaling pathway; IEA:Ensembl.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0007160; P:cell-matrix adhesion; IEA:Ensembl.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IMP:UniProtKB.
DR GO; GO:0010467; P:gene expression; IEA:Ensembl.
DR GO; GO:0060789; P:hair follicle placode formation; IEA:Ensembl.
DR GO; GO:0006955; P:immune response; IEA:InterPro.
DR GO; GO:0042475; P:odontogenesis of dentin-containing tooth; IMP:UniProtKB.
DR GO; GO:0043473; P:pigmentation; IEA:Ensembl.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; 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; IEA:Ensembl.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IDA:HGNC-UCL.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; IEA:Ensembl.
DR GO; GO:1901222; P:regulation of NIK/NF-kappaB signaling; IMP:UniProtKB.
DR GO; GO:0060662; P:salivary gland cavitation; IEA:Ensembl.
DR GO; GO:0061153; P:trachea gland development; IEA:Ensembl.
DR Gene3D; 2.60.120.40; -; 1.
DR InterPro; IPR006052; TNF_dom.
DR InterPro; IPR008983; Tumour_necrosis_fac-like_dom.
DR Pfam; PF00229; TNF; 1.
DR SUPFAM; SSF49842; SSF49842; 1.
DR PROSITE; PS50049; TNF_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane;
KW Cleavage on pair of basic residues; Collagen; Developmental protein;
KW Differentiation; Disease variant; Ectodermal dysplasia; Glycoprotein;
KW Membrane; Reference proteome; Secreted; Signal-anchor; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..391
FT /note="Ectodysplasin-A, membrane form"
FT /id="PRO_0000034538"
FT CHAIN 160..391
FT /note="Ectodysplasin-A, secreted form"
FT /evidence="ECO:0000305|PubMed:11416205"
FT /id="PRO_0000034539"
FT TOPO_DOM 1..41
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 42..62
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 63..391
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT DOMAIN 180..229
FT /note="Collagen-like"
FT REGION 73..127
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 146..245
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 80..111
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 146..174
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 181..230
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 159..160
FT /note="Cleavage; by furin"
FT /evidence="ECO:0000269|PubMed:11416205"
FT CARBOHYD 313
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 372
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 133..147
FT /note="MALLNFFFPDEKPYS -> VSHLVGAAAAPSPRG (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:9736768"
FT /id="VSP_006458"
FT VAR_SEQ 133..147
FT /note="MALLNFFFPDEKPYS -> DFDYIISFSYGLQGFC (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:9736768"
FT /id="VSP_006459"
FT VAR_SEQ 133..147
FT /note="MALLNFFFPDEKPYS -> LHVSFSLRKKKAGHQ (in isoform 7)"
FT /evidence="ECO:0000303|PubMed:9736768"
FT /id="VSP_006460"
FT VAR_SEQ 133..142
FT /note="MALLNFFFPD -> ACFPQVLLSL (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:9736768"
FT /id="VSP_006456"
FT VAR_SEQ 133..135
FT /note="MAL -> GHQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:8696334"
FT /id="VSP_006454"
FT VAR_SEQ 136..391
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:8696334"
FT /id="VSP_006455"
FT VAR_SEQ 143..391
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:9736768"
FT /id="VSP_006457"
FT VAR_SEQ 148..391
FT /note="Missing (in isoform 4, isoform 6 and isoform 7)"
FT /evidence="ECO:0000303|PubMed:9736768"
FT /id="VSP_006461"
FT VAR_SEQ 265..267
FT /note="Missing (in isoform 8)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_038402"
FT VAR_SEQ 307..308
FT /note="Missing (in isoform 3 and isoform 8)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:9736768"
FT /id="VSP_006464"
FT VARIANT 51
FT /note="L -> Q (in XHED; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:24724966"
FT /id="VAR_075310"
FT VARIANT 54
FT /note="H -> Y (in XHED)"
FT /evidence="ECO:0000269|PubMed:9630076"
FT /id="VAR_010611"
FT VARIANT 55
FT /note="L -> R (in XHED)"
FT /evidence="ECO:0000269|PubMed:10469321"
FT /id="VAR_010612"
FT VARIANT 60
FT /note="C -> R (in XHED)"
FT /evidence="ECO:0000269|PubMed:11378824"
FT /id="VAR_013484"
FT VARIANT 61
FT /note="Y -> H (in XHED; dbSNP:rs132630308)"
FT /evidence="ECO:0000269|PubMed:8696334"
FT /id="VAR_005179"
FT VARIANT 63
FT /note="E -> K (in XHED; dbSNP:rs132630311)"
FT /evidence="ECO:0000269|PubMed:9507389"
FT /id="VAR_005180"
FT VARIANT 65
FT /note="R -> G (in STHAGX1; dbSNP:rs132630319)"
FT /evidence="ECO:0000269|PubMed:16583127"
FT /id="VAR_029534"
FT VARIANT 69
FT /note="R -> L (in XHED; dbSNP:rs132630309)"
FT /evidence="ECO:0000269|PubMed:8696334"
FT /id="VAR_005181"
FT VARIANT 118
FT /note="P -> L (in a colorectal cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036590"
FT VARIANT 125
FT /note="S -> C (in XHED; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:24724966"
FT /id="VAR_075311"
FT VARIANT 132
FT /note="Q -> P (in XHED; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:24724966"
FT /id="VAR_075312"
FT VARIANT 153
FT /note="R -> C (in XHED; abolishes proteolytic processing;
FT dbSNP:rs397516662)"
FT /evidence="ECO:0000269|PubMed:11279189,
FT ECO:0000269|PubMed:11309369, ECO:0000269|PubMed:11416205,
FT ECO:0000269|PubMed:19438931"
FT /id="VAR_054454"
FT VARIANT 153
FT /note="R -> H (in XHED; unknown pathological significance;
FT dbSNP:rs140642493)"
FT /evidence="ECO:0000269|PubMed:24724966"
FT /id="VAR_075313"
FT VARIANT 155
FT /note="R -> C (in XHED; abolishes proteolytic processing;
FT dbSNP:rs132630312)"
FT /evidence="ECO:0000269|PubMed:11279189,
FT ECO:0000269|PubMed:11416205, ECO:0000269|PubMed:18231121,
FT ECO:0000269|PubMed:19438931, ECO:0000269|PubMed:20486090,
FT ECO:0000269|PubMed:24724966, ECO:0000269|PubMed:27657131,
FT ECO:0000269|PubMed:9683615"
FT /id="VAR_005182"
FT VARIANT 156
FT /note="R -> C (in XHED; abolishes proteolytic processing;
FT dbSNP:rs132630313)"
FT /evidence="ECO:0000269|PubMed:11279189,
FT ECO:0000269|PubMed:11295832, ECO:0000269|PubMed:11416205,
FT ECO:0000269|PubMed:18231121, ECO:0000269|PubMed:9683615,
FT ECO:0000269|PubMed:9736768"
FT /id="VAR_005183"
FT VARIANT 156
FT /note="R -> G (in XHED)"
FT /evidence="ECO:0000269|PubMed:20979233"
FT /id="VAR_064858"
FT VARIANT 156
FT /note="R -> H (in XHED; abolishes proteolytic processing;
FT dbSNP:rs132630314)"
FT /evidence="ECO:0000269|PubMed:11279189,
FT ECO:0000269|PubMed:11295832, ECO:0000269|PubMed:11309369,
FT ECO:0000269|PubMed:11416205, ECO:0000269|PubMed:18231121,
FT ECO:0000269|PubMed:24724966, ECO:0000269|PubMed:9683615"
FT /id="VAR_005184"
FT VARIANT 156
FT /note="R -> S (in XHED)"
FT /evidence="ECO:0000269|PubMed:10951256"
FT /id="VAR_054455"
FT VARIANT 158
FT /note="K -> N (in XHED; abolishes proteolytic processing;
FT dbSNP:rs727504649)"
FT /evidence="ECO:0000269|PubMed:11279189,
FT ECO:0000269|PubMed:11416205"
FT /id="VAR_054456"
FT VARIANT 183..194
FT /note="Missing (in XHED)"
FT /evidence="ECO:0000269|PubMed:11279189,
FT ECO:0000269|PubMed:18231121, ECO:0000269|PubMed:24724966"
FT /id="VAR_054457"
FT VARIANT 184..189
FT /note="Missing (in XHED)"
FT /evidence="ECO:0000269|PubMed:18231121"
FT /id="VAR_054458"
FT VARIANT 185..196
FT /note="Missing (in XHED)"
FT /evidence="ECO:0000269|PubMed:11279189,
FT ECO:0000269|PubMed:18231121, ECO:0000269|PubMed:24724966"
FT /id="VAR_054459"
FT VARIANT 189
FT /note="G -> E (in XHED)"
FT /evidence="ECO:0000269|PubMed:11279189"
FT /id="VAR_054460"
FT VARIANT 191..196
FT /note="Missing (in XHED)"
FT /evidence="ECO:0000269|PubMed:11279189,
FT ECO:0000269|PubMed:24724966"
FT /id="VAR_054461"
FT VARIANT 192..197
FT /note="Missing (in XHED)"
FT /evidence="ECO:0000269|PubMed:20979233"
FT /id="VAR_064859"
FT VARIANT 193..201
FT /note="Missing (in XHED; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:24724966"
FT /id="VAR_075314"
FT VARIANT 198
FT /note="G -> A (in XHED)"
FT /evidence="ECO:0000269|PubMed:12225002"
FT /id="VAR_054462"
FT VARIANT 207
FT /note="G -> R (in XHED)"
FT /evidence="ECO:0000269|PubMed:11279189"
FT /id="VAR_054463"
FT VARIANT 207
FT /note="G -> V (in XHED)"
FT /evidence="ECO:0000269|PubMed:20979233"
FT /id="VAR_064860"
FT VARIANT 209
FT /note="P -> L (in XHED; dbSNP:rs132630315)"
FT /evidence="ECO:0000269|PubMed:9683615"
FT /id="VAR_005185"
FT VARIANT 211
FT /note="T -> R (in XHED)"
FT /evidence="ECO:0000269|PubMed:20979233"
FT /id="VAR_064861"
FT VARIANT 218..223
FT /note="Missing (in XHED)"
FT /evidence="ECO:0000269|PubMed:11279189"
FT /id="VAR_054465"
FT VARIANT 218
FT /note="G -> D (in XHED)"
FT /evidence="ECO:0000269|PubMed:11279189"
FT /id="VAR_054464"
FT VARIANT 219..230
FT /note="Missing (in XHED; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:24724966"
FT /id="VAR_075315"
FT VARIANT 221
FT /note="G -> D (in XHED; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:27657131"
FT /id="VAR_077561"
FT VARIANT 224
FT /note="G -> A (in XHED; dbSNP:rs132630316)"
FT /evidence="ECO:0000269|PubMed:9683615"
FT /id="VAR_005186"
FT VARIANT 252
FT /note="H -> L (in XHED; loss of interaction with EDAR for
FT isoform 1; decreased interaction with EDA2R for isoform 3;
FT changed downstream signaling; dbSNP:rs879255552)"
FT /evidence="ECO:0000269|PubMed:9683615"
FT /id="VAR_005187"
FT VARIANT 252
FT /note="H -> Y (in XHED)"
FT /evidence="ECO:0000269|PubMed:11378824"
FT /id="VAR_013485"
FT VARIANT 255
FT /note="G -> C (in XHED)"
FT /evidence="ECO:0000269|PubMed:11295832"
FT /id="VAR_011077"
FT VARIANT 255
FT /note="G -> D (in XHED; mild; dbSNP:rs1064793105)"
FT /evidence="ECO:0000269|PubMed:11295832"
FT /id="VAR_011078"
FT VARIANT 259
FT /note="A -> E (in STHAGX1; decreased interaction with EDAR
FT for isoform 1; decreased interaction with EDA2R for isoform
FT 3; changed downstream signaling; dbSNP:rs879255611)"
FT /evidence="ECO:0000269|PubMed:19278982"
FT /id="VAR_071454"
FT VARIANT 260
FT /note="I -> S (in STHAGX1)"
FT /evidence="ECO:0000269|PubMed:23625373"
FT /id="VAR_071455"
FT VARIANT 266
FT /note="L -> R (in XHED)"
FT /evidence="ECO:0000269|PubMed:20979233"
FT /id="VAR_064862"
FT VARIANT 269
FT /note="G -> V (in XHED)"
FT /evidence="ECO:0000269|PubMed:11378824"
FT /id="VAR_013486"
FT VARIANT 274
FT /note="W -> G (in XHED)"
FT /evidence="ECO:0000269|PubMed:11295832,
FT ECO:0000269|PubMed:24724966"
FT /id="VAR_011079"
FT VARIANT 274
FT /note="W -> R (in XHED)"
FT /evidence="ECO:0000269|PubMed:20979233"
FT /id="VAR_064863"
FT VARIANT 289
FT /note="R -> C (in STHAGX1; decreased interaction with EDAR
FT for isoform 1; decreased interaction with EDA2R for isoform
FT 3; changed downstream signaling; dbSNP:rs879255551)"
FT /evidence="ECO:0000269|PubMed:19278982"
FT /id="VAR_071456"
FT VARIANT 289
FT /note="R -> L (in STHAGX1)"
FT /evidence="ECO:0000269|PubMed:24487376"
FT /id="VAR_071457"
FT VARIANT 289
FT /note="R -> P (in XHED; when associated in cis with C-290;
FT loss of function in EDAR-mediated signaling when associated
FT in cis with C-290; not secreted when associated in cis with
FT C-290)"
FT /evidence="ECO:0000269|PubMed:34582123"
FT /id="VAR_085684"
FT VARIANT 290
FT /note="S -> C (in XHED; when associated in cis with P-289;
FT loss of function in EDAR-mediated signaling when associated
FT in cis with P-289; not secreted when associated in cis with
FT P-289)"
FT /evidence="ECO:0000269|PubMed:34582123"
FT /id="VAR_085685"
FT VARIANT 291
FT /note="G -> R (in XHED; dbSNP:rs397516677)"
FT /evidence="ECO:0000269|PubMed:11279189,
FT ECO:0000269|PubMed:18231121, ECO:0000269|PubMed:24724966,
FT ECO:0000269|PubMed:9736768"
FT /id="VAR_010613"
FT VARIANT 291
FT /note="G -> W (in XHED)"
FT /evidence="ECO:0000269|PubMed:9736768"
FT /id="VAR_010614"
FT VARIANT 293
FT /note="L -> P (in XHED)"
FT /evidence="ECO:0000269|PubMed:20979233"
FT /id="VAR_064864"
FT VARIANT 296
FT /note="L -> V (in XHED)"
FT /evidence="ECO:0000269|PubMed:20979233"
FT /id="VAR_064865"
FT VARIANT 298
FT /note="D -> H (in XHED)"
FT /evidence="ECO:0000269|PubMed:9736768"
FT /id="VAR_010615"
FT VARIANT 298
FT /note="D -> Y (in XHED)"
FT /evidence="ECO:0000269|PubMed:18231121"
FT /id="VAR_054466"
FT VARIANT 299
FT /note="G -> D (in XHED)"
FT /evidence="ECO:0000269|PubMed:20979233"
FT /id="VAR_064866"
FT VARIANT 299
FT /note="G -> S (in XHED; dbSNP:rs397516679)"
FT /evidence="ECO:0000269|PubMed:11279189,
FT ECO:0000269|PubMed:24724966, ECO:0000269|PubMed:27657131,
FT ECO:0000269|PubMed:9683615, ECO:0000269|PubMed:9736768"
FT /id="VAR_005188"
FT VARIANT 302
FT /note="F -> S (in XHED)"
FT /evidence="ECO:0000269|PubMed:11378824"
FT /id="VAR_013487"
FT VARIANT 304
FT /note="Y -> H (in XHED; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:24724966"
FT /id="VAR_075316"
FT VARIANT 306
FT /note="Q -> H (in XHED)"
FT /evidence="ECO:0000269|PubMed:12932274"
FT /id="VAR_054467"
FT VARIANT 307
FT /note="V -> G (in XHED)"
FT /evidence="ECO:0000269|PubMed:18231121"
FT /id="VAR_054468"
FT VARIANT 316
FT /note="D -> E (in XHED; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:24724966"
FT /id="VAR_075317"
FT VARIANT 319
FT /note="S -> R (in XHED)"
FT /evidence="ECO:0000269|PubMed:22350046,
FT ECO:0000269|PubMed:24724966"
FT /id="VAR_067319"
FT VARIANT 320
FT /note="Y -> C (in XHED)"
FT /evidence="ECO:0000269|PubMed:11279189"
FT /id="VAR_054469"
FT VARIANT 323
FT /note="V -> G (in XHED)"
FT /evidence="ECO:0000269|PubMed:20979233"
FT /id="VAR_064867"
FT VARIANT 332
FT /note="C -> F (in XHED; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:24724966"
FT /id="VAR_075318"
FT VARIANT 332
FT /note="C -> Y (in XHED; dbSNP:rs1602624745)"
FT /evidence="ECO:0000269|PubMed:11295832"
FT /id="VAR_011080"
FT VARIANT 334
FT /note="R -> H (in STHAGX1; decreased interaction with EDAR
FT for isoform 1; decreased interaction with EDA2R for isoform
FT 3; changed downstream signaling; dbSNP:rs142948132)"
FT /evidence="ECO:0000269|PubMed:19278982"
FT /id="VAR_071458"
FT VARIANT 338
FT /note="T -> M (in STHAGX1 and XHED; dbSNP:rs132630321)"
FT /evidence="ECO:0000269|PubMed:18657636,
FT ECO:0000269|PubMed:27657131"
FT /id="VAR_064868"
FT VARIANT 343
FT /note="Y -> C (in XHED; loss of interaction with EDAR for
FT isoform 1; decreased interaction with EDA2R for isoform 3;
FT changed downstream signaling)"
FT /evidence="ECO:0000269|PubMed:11279189"
FT /id="VAR_054470"
FT VARIANT 346
FT /note="C -> Y (in XHED)"
FT /evidence="ECO:0000269|PubMed:20979233"
FT /id="VAR_064869"
FT VARIANT 349
FT /note="A -> T (in XHED; dbSNP:rs132630317)"
FT /evidence="ECO:0000269|PubMed:11295832,
FT ECO:0000269|PubMed:11343303, ECO:0000269|PubMed:19438931,
FT ECO:0000269|PubMed:9683615"
FT /id="VAR_005189"
FT VARIANT 350
FT /note="G -> D (in XHED; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:24724966"
FT /id="VAR_075319"
FT VARIANT 354
FT /note="L -> P (in XHED)"
FT /evidence="ECO:0000269|PubMed:22008666"
FT /id="VAR_067250"
FT VARIANT 356
FT /note="A -> D (in XHED)"
FT /evidence="ECO:0000269|PubMed:9683615"
FT /id="VAR_005190"
FT VARIANT 356
FT /note="A -> V (in XHED; dbSNP:rs876657639)"
FT /evidence="ECO:0000269|PubMed:20979233"
FT /id="VAR_064870"
FT VARIANT 357
FT /note="R -> P (in XHED; dbSNP:rs61747506)"
FT /evidence="ECO:0000269|PubMed:9683615"
FT /id="VAR_005191"
FT VARIANT 358
FT /note="Q -> E (in XHED; dbSNP:rs132630320)"
FT /evidence="ECO:0000269|PubMed:17256800"
FT /id="VAR_054471"
FT VARIANT 358
FT /note="Q -> H (in XHED; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:24724966"
FT /id="VAR_075320"
FT VARIANT 360
FT /note="I -> N (in XHED)"
FT /evidence="ECO:0000269|PubMed:11343303"
FT /id="VAR_054472"
FT VARIANT 372
FT /note="N -> D (in XHED)"
FT /evidence="ECO:0000269|PubMed:18231121"
FT /id="VAR_054473"
FT VARIANT 373
FT /note="M -> I (in XHED)"
FT /evidence="ECO:0000269|PubMed:18231121"
FT /id="VAR_054474"
FT VARIANT 374
FT /note="S -> R (in XHED; decreased interaction with EDAR for
FT isoform 1; decreased interaction with EDA2R for isoform 3;
FT changed downstream signaling)"
FT /evidence="ECO:0000269|PubMed:11279189"
FT /id="VAR_054475"
FT VARIANT 378
FT /note="T -> M (in XHED; dbSNP:rs1569407346)"
FT /evidence="ECO:0000269|PubMed:11279189,
FT ECO:0000269|PubMed:11378824, ECO:0000269|PubMed:12225002"
FT /id="VAR_013488"
FT VARIANT 378
FT /note="T -> P (in XHED)"
FT /evidence="ECO:0000269|PubMed:11279189"
FT /id="VAR_054476"
FT VARIANT 379
FT /note="F -> S (in XHED; loss of function in EDAR-mediated
FT signaling; not secreted)"
FT /evidence="ECO:0000269|PubMed:34582123"
FT /id="VAR_085686"
FT VARIANT 379
FT /note="F -> V (in STHAGX1)"
FT /evidence="ECO:0000269|PubMed:24487376"
FT /id="VAR_071459"
FT VARIANT 381
FT /note="G -> R (in XHED)"
FT /evidence="ECO:0000269|PubMed:19127222"
FT /id="VAR_064871"
FT VARIANT 381
FT /note="G -> V (in XHED; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:24724966"
FT /id="VAR_075321"
FT MUTAGEN 159
FT /note="R->A: Abolishes proteolytic processing."
FT /evidence="ECO:0000269|PubMed:11416205"
FT STRAND 249..254
FT /evidence="ECO:0007829|PDB:1RJ8"
FT STRAND 257..261
FT /evidence="ECO:0007829|PDB:1RJ8"
FT HELIX 262..264
FT /evidence="ECO:0007829|PDB:1RJ8"
FT HELIX 266..269
FT /evidence="ECO:0007829|PDB:1RJ8"
FT STRAND 275..279
FT /evidence="ECO:0007829|PDB:1RJ8"
FT TURN 281..283
FT /evidence="ECO:0007829|PDB:1RJ8"
FT STRAND 284..286
FT /evidence="ECO:0007829|PDB:1RJ8"
FT TURN 288..290
FT /evidence="ECO:0007829|PDB:1RJ8"
FT STRAND 293..295
FT /evidence="ECO:0007829|PDB:1RJ8"
FT STRAND 299..307
FT /evidence="ECO:0007829|PDB:1RJ8"
FT STRAND 310..316
FT /evidence="ECO:0007829|PDB:1RJ8"
FT STRAND 318..324
FT /evidence="ECO:0007829|PDB:1RJ8"
FT STRAND 327..336
FT /evidence="ECO:0007829|PDB:1RJ8"
FT STRAND 338..340
FT /evidence="ECO:0007829|PDB:1RJ7"
FT STRAND 342..354
FT /evidence="ECO:0007829|PDB:1RJ8"
FT STRAND 359..364
FT /evidence="ECO:0007829|PDB:1RJ8"
FT STRAND 370..372
FT /evidence="ECO:0007829|PDB:1RJ8"
FT TURN 375..377
FT /evidence="ECO:0007829|PDB:1RJ8"
FT STRAND 378..386
FT /evidence="ECO:0007829|PDB:1RJ8"
SQ SEQUENCE 391 AA; 41294 MW; 15DB3F5053293CBA CRC64;
MGYPEVERRE LLPAAAPRER GSQGCGCGGA PARAGEGNSC LLFLGFFGLS LALHLLTLCC
YLELRSELRR ERGAESRLGG SGTPGTSGTL SSLGGLDPDS PITSHLGQPS PKQQPLEPGE
AALHSDSQDG HQMALLNFFF PDEKPYSEEE SRRVRRNKRS KSNEGADGPV KNKKKGKKAG
PPGPNGPPGP PGPPGPQGPP GIPGIPGIPG TTVMGPPGPP GPPGPQGPPG LQGPSGAADK
AGTRENQPAV VHLQGQGSAI QVKNDLSGGV LNDWSRITMN PKVFKLHPRS GELEVLVDGT
YFIYSQVEVY YINFTDFASY EVVVDEKPFL QCTRSIETGK TNYNTCYTAG VCLLKARQKI
AVKMVHADIS INMSKHTTFF GAIRLGEAPA S
