Q9UNE0 (EDAR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Tumor necrosis factor receptor superfamily member EDAR

Alternative name(s):
Anhidrotic ectodysplasin receptor 1
Downless homolog
EDA-A1 receptor
Ectodermal dysplasia receptor
Ectodysplasin-A receptor

Gene names

Name:	EDAR
Synonyms:	DL

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	448 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Receptor for EDA isoform A1, but not for EDA isoform A2. Mediates the activation of NF-kappa-B and JNK. May promote caspase-independent cell death.
Subunit structure	Binds to EDARADD. Associates with TRAF1, TRAF2, TRAF3 and NIK. Ref.5 Ref.6
Subcellular location	Membrane; Single-pass type I membrane protein Probable.
Tissue specificity	Detected in fetal kidney, lung, skin and cultured neonatal epidermal keratinocytes. Not detected in lymphoblast and fibroblast cell lines.
Developmental stage	Found in craniofacial tissues from embryonic day 42-53. Expressed in fetal skin 11 and 15 weeks after gestation.
Polymorphism	Genetic variation in EDAR is associated with variations in head hair thickness and defines the hair morphology locus 1 (HRM1) [MIM:612630]. Besides skin color and facial features, hair morphology is one of the most distinctive traits among human populations, and classical classification of human population is based on such visible traits.
Involvement in disease	Defects in EDAR are a cause of ectodermal dysplasia anhidrotic (EDA) [MIM:224900]; also known ectodermal dysplasia hypohidrotic autosomal recessive (HED). Ectodermal dysplasia defines a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. EDA is characterized by sparse hair (atrichosis or hypotrichosis), abnormal or missing teeth and the inability to sweat due to the absence of sweat glands. Ref.1 Ref.5 Ref.7 Ref.13 Ref.14 Defects in EDAR are the cause of ectodermal dysplasia type 3 (ED3) [MIM:129490]; also known as ectodermal dysplasia hypohidrotic autosomal dominant or EDA3. ED3 is an autosomal dominant condition characterized by hypotrichosis, abnormal or missing teeth, and hypohidrosis due to the absence of sweat glands. Ref.1 Ref.10
Sequence similarities	Contains 1 death domain. Contains 3 TNFR-Cys repeats.

Ontologies

Keywords
Biological process	Apoptosis Differentiation
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation Ectodermal dysplasia
Domain	Repeat Signal Transmembrane Transmembrane helix
Molecular function	Developmental protein Receptor
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	integral to membrane Non-traceable author statement Ref.1. Source: UniProtKB
Molecular function	protein binding Inferred from physical interaction Ref.5. Source: HGNC transmembrane signaling receptor activity Non-traceable author statement Ref.1. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 26	26	Ref.4
	Chain	27 – 448	422	Tumor necrosis factor receptor superfamily member EDAR		PRO_0000034608
Regions
	Topological domain	27 – 187	161	Extracellular Potential
	Transmembrane	188 – 208	21	Helical; Potential
	Topological domain	209 – 448	240	Cytoplasmic Potential
	Repeat	30 – 71	42	TNFR-Cys 1
	Repeat	73 – 113	41	TNFR-Cys 2
	Repeat	115 – 148	34	TNFR-Cys 3
	Domain	358 – 431	74	Death
Amino acid modifications
	Modified residue	324	1	Phosphoserine By similarity
	Glycosylation	38	1	N-linked (GlcNAc...) Potential
	Disulfide bond	31 ↔ 44		By similarity
	Disulfide bond	47 ↔ 60		By similarity
	Disulfide bond	50 ↔ 71		By similarity
	Disulfide bond	74 ↔ 87		By similarity
	Disulfide bond	93 ↔ 113		By similarity
	Disulfide bond	135 ↔ 148		By similarity
Natural variations
	Natural variant	47	1	C → Y in EDA. Ref.9		VAR_054444
	Natural variant	87	1	C → R in EDA. Ref.1		VAR_013448
	Natural variant	89	1	R → H in EDA. Ref.1 Ref.9 Ref.10 Ref.14		VAR_013449
	Natural variant	98	1	R → Q in EDA. Ref.13		VAR_064830
	Natural variant	110	1	D → A in EDA. Ref.9 Ref.10		VAR_054445
	Natural variant	148	1	C → R in EDA. Ref.9		VAR_054446
	Natural variant	358	1	R → Q in EDA. Ref.13 Ref.14		VAR_064831
	Natural variant	370	1	V → A Associated with increase in hair thickness; results in decreased downstream activity of NFKB1 48 hours after transfection into cells. Ref.11 Ref.12 Corresponds to variant rs3827760 [ dbSNP | Ensembl ].		VAR_020011
	Natural variant	375	1	R → H in EDA; the mutant protein does not interact with EDARADD and is functionally inactive. Ref.7		VAR_054447
	Natural variant	377	1	L → F in EDA. Ref.9		VAR_054448
	Natural variant	382	1	G → S in EDA. Ref.8		VAR_054449
	Natural variant	396	1	Q → QQ in EDA. Ref.14		VAR_064832
	Natural variant	403	1	T → M in EDA. Ref.9 Ref.14		VAR_054450
	Natural variant	408	1	I → F in EDA. Ref.14		VAR_064833
	Natural variant	413	1	T → P in EDA. Ref.9		VAR_054451
	Natural variant	418	1	I → T in EDA. Ref.9		VAR_054452
	Natural variant	420	1	R → Q in EDA and ED3; abolishes NF-kappa-B activation and reduces JNK activation. Ref.1 Ref.6 Ref.9 Ref.10 Ref.14		VAR_013450
	Natural variant	434	1	W → C in EDA. Ref.9		VAR_054453
	Natural variant	434	1	W → R in EDA. Ref.13		VAR_064834
Experimental info
	Mutagenesis	379	1	E → K: Reduces activation of NF-kappa-B. Ref.6
	Sequence conflict	262	1	P → S in AAD50077. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q9UNE0 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: AC8D61249D608439	FASTA	448	48,582
	10 20 30 40 50 60 MAHVGDCTQT PWLPVLVVSL MCSARAEYSN CGENEYYNQT TGLCQECPPC GPGEEPYLSC 70 80 90 100 110 120 GYGTKDEDYG CVPCPAEKFS KGGYQICRRH KDCEGFFRAT VLTPGDMEND AECGPCLPGY 130 140 150 160 170 180 YMLENRPRNI YGMVCYSCLL APPNTKECVG ATSGASANFP GTSGSSTLSP FQHAHKELSG 190 200 210 220 230 240 QGHLATALII AMSTIFIMAI AIVLIIMFYI LKTKPSAPAC CTSHPGKSVE AQVSKDEEKK 250 260 270 280 290 300 EAPDNVVMFS EKDEFEKLTA TPAKPTKSEN DASSENEQLL SRSVDSDEEP APDKQGSPEL 310 320 330 340 350 360 CLLSLVHLAR EKSATSNKSA GIQSRRKKIL DVYANVCGVV EGLSPTELPF DCLEKTSRML 370 380 390 400 410 420 SSTYNSEKAV VKTWRHLAES FGLKRDEIGG MTDGMQLFDR ISTAGYSIPE LLTKLVQIER 430 440 LDAVESLCAD ILEWAGVVPP ASQPHAAS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Mutations in the human homologue of mouse dl cause autosomal recessive and dominant hypohidrotic ectodermal dysplasia." Monreal A.W., Ferguson B.M., Headon D.J., Street S.L., Overbeek P.A., Zonana J. Nat. Genet. 22:366-369(1999) [PubMed: 10431241] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], VARIANTS EDA ARG-87 AND HIS-89, VARIANT ED3 GLN-420. Tissue: Fetal heart and Skin.
[2]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Liver.
[4]	"Signal peptide prediction based on analysis of experimentally verified cleavage sites." Zhang Z., Henzel W.J. Protein Sci. 13:2819-2824(2004) [PubMed: 15340161] [Abstract] Cited for: PROTEIN SEQUENCE OF 27-41.
[5]	"Two-amino acid molecular switch in an epithelial morphogen that regulates binding to two distinct receptors." Yan M., Wang L.-C., Hymowitz S.G., Schilbach S., Lee J., Goddard A., de Vos A.M., Gao W.-Q., Dixit V.M. Science 290:523-527(2000) [PubMed: 11039935] [Abstract] Cited for: INTERACTION WITH EDA ISOFORM A1.
[6]	"The ectodermal dysplasia receptor activates the nuclear factor-kappaB, JNK, and cell death pathways and binds to ectodysplasin A." Kumar A., Eby M.T., Sinha S., Jasmin A., Chaudhary P.M. J. Biol. Chem. 276:2668-2677(2001) [PubMed: 11035039] [Abstract] Cited for: CHARACTERIZATION OF VARIANT GLN-420, MUTAGENESIS OF GLU-379, CHARACTERIZATION, INTERACTION WITH TRAF1 AND TRAF3.
[7]	"A rare case of hypohidrotic ectodermal dysplasia caused by compound heterozygous mutations in the EDAR gene." Shimomura Y., Sato N., Miyashita A., Hashimoto T., Ito M., Kuwano R. J. Invest. Dermatol. 123:649-655(2004) [PubMed: 15373768] [Abstract] Cited for: VARIANT EDA HIS-375, CHARACTERIZATION OF VARIANT EDA HIS-375.
[8]	"Novel mutations in the EDAR gene in two Pakistani consanguineous families with autosomal recessive hypohidrotic ectodermal dysplasia." Naeem M., Muhammad D., Ahmad W. Br. J. Dermatol. 153:46-50(2005) [PubMed: 16029325] [Abstract] Cited for: VARIANT HED SER-382.
[9]	"Mutations in EDAR account for one-quarter of non-ED1-related hypohidrotic ectodermal dysplasia." Chassaing N., Bourthoumieu S., Cossee M., Calvas P., Vincent M.-C. Hum. Mutat. 27:255-259(2006) [PubMed: 16435307] [Abstract] Cited for: VARIANTS HED TYR-47; HIS-89; ALA-110; ARG-148; PHE-377; MET-403; PRO-413; THR-418; GLN-420 AND CYS-434.
[10]	"Mutation screening of the ectodysplasin-A receptor gene EDAR in hypohidrotic ectodermal dysplasia." van der Hout A.H., Oudesluijs G.G., Venema A., Verheij J.B.G.M., Mol B.G.J., Rump P., Brunner H.G., Vos Y.J., van Essen A.J. Eur. J. Hum. Genet. 16:673-679(2008) [PubMed: 18231121] [Abstract] Cited for: VARIANTS HED HIS-89 AND ALA-110, VARIANT ED3 GLN-420.
[11]	"A scan for genetic determinants of human hair morphology: EDAR is associated with Asian hair thickness." Fujimoto A., Kimura R., Ohashi J., Omi K., Yuliwulandari R., Batubara L., Mustofa M.S., Samakkarn U., Settheetham-Ishida W., Ishida T., Morishita Y., Furusawa T., Nakazawa M., Ohtsuka R., Tokunaga K. Hum. Mol. Genet. 17:835-843(2008) [PubMed: 18065779] [Abstract] Cited for: VARIANT ALA-370, CHARACTERIZATION OF VARIANT ALA-370, ASSOCIATION WITH HAIR MORPHOLOGY TYPE 1.
[12]	"Enhanced ectodysplasin-A receptor (EDAR) signaling alters multiple fiber characteristics to produce the East Asian hair form." Mou C., Thomason H.A., Willan P.M., Clowes C., Harris W.E., Drew C.F., Dixon J., Dixon M.J., Headon D.J. Hum. Mutat. 29:1405-1411(2008) [PubMed: 18561327] [Abstract] Cited for: CHARACTERIZATION OF VARIANT ALA-370.
[13]	"Identification of mutations in the EDA and EDAR genes in Pakistani families with hypohidrotic ectodermal dysplasia." Shimomura Y., Wajid M., Weiser J., Kraemer L., Ishii Y., Lombillo V., Bale S.J., Christiano A.M. Clin. Genet. 75:582-584(2009) [PubMed: 19438931] [Abstract] Cited for: VARIANTS EDA GLN-98; GLN-358 AND ARG-434.
[14]	"Only four genes (EDA1, EDAR, EDARADD, and WNT10A) account for 90% of hypohidrotic/anhidrotic ectodermal dysplasia cases." Cluzeau C., Hadj-Rabia S., Jambou M., Mansour S., Guigue P., Masmoudi S., Bal E., Chassaing N., Vincent M.C., Viot G., Clauss F., Maniere M.C., Toupenay S., Le Merrer M., Lyonnet S., Cormier-Daire V., Amiel J., Faivre L. , de Prost Y., Munnich A., Bonnefont J.P., Bodemer C., Smahi A. Hum. Mutat. 32:70-72(2011) [PubMed: 20979233] [Abstract] Cited for: VARIANTS EDA HIS-89; GLN-358; GLN-396 INS; MET-403; PHE-408 AND GLN-420.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF130988 mRNA. Translation: AAD50076.1. AF130996 , AF130990, AF130991, AF130992, AF130993, AF130994, AF130995 Genomic DNA. Translation: AAD50077.1. CH471182 Genomic DNA. Translation: EAW53869.1. BC093870 mRNA. Translation: AAH93870.1. BC093872 mRNA. Translation: AAH93872.1.
IPI	IPI00007051.
RefSeq	NP_071731.1. NM_022336.3.
UniGene	Hs.171971.
3D structure databases
ProteinModelPortal	Q9UNE0.
SMR	Q9UNE0. Positions 30-126, 342-430.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9UNE0. 5 interactions.
STRING	Q9UNE0.
PTM databases
PhosphoSite	Q9UNE0.
Polymorphism databases
DMDM	21263572.
Proteomic databases
PRIDE	Q9UNE0.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000258443; ENSP00000258443; ENSG00000135960.
GeneID	10913.
KEGG	hsa:10913.
UCSC	uc002teq.2. human.
Organism-specific databases
CTD	10913.
GeneCards	GC02M109510.
H-InvDB	HIX0029820.
HGNC	HGNC:2895. EDAR.
HPA	HPA042292.
MIM	129490. phenotype. 224900. phenotype. 604095. gene. 612630. phenotype.
neXtProt	NX_Q9UNE0.
Orphanet	1810. Autosomal dominant hypohidrotic ectodermal dysplasia. 248. Autosomal recessive hypohidrotic ectodermal dysplasia.
PharmGKB	PA27602.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG17334.
GeneTree	ENSGT00530000063330.
HOVERGEN	HBG031530.
PhylomeDB	Q9UNE0.
Gene expression databases
ArrayExpress	Q9UNE0.
Bgee	Q9UNE0.
CleanEx	HS_EDAR.
Genevestigator	Q9UNE0.
GermOnline	ENSG00000135960. Homo sapiens.
Family and domain databases
InterPro	IPR000488. Death. IPR011029. DEATH-like. [Graphical view]
Gene3D	G3DSA:1.10.533.10. DEATH_like. 1 hit.
KO	K05162.
Pfam	PF00531. Death. 1 hit. [Graphical view]
SUPFAM	SSF47986. DEATH_like. 1 hit.
PROSITE	PS50017. DEATH_DOMAIN. False negative. PS00652. TNFR_NGFR_1. False negative. PS50050. TNFR_NGFR_2. False negative. [Graphical view]
ProtoNet	Search...
Other
NextBio	41449.
SOURCE	Search...

Entry information

Entry name

EDAR_HUMAN

Accession

Primary (citable) accession number: Q9UNE0
Secondary accession number(s): D3DX74, Q52LL5, Q9UND9

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 27, 2002
Last sequence update:	May 1, 2000
Last modified:	January 25, 2012
This is version 96 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.