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Reviewed, UniProtKB/Swiss-Prot Q9UNE0 (EDAR_HUMAN)

Last modified January 19, 2010. Version 79. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Tumor necrosis factor receptor superfamily member EDAR
Alternative name(s):
    Anhidrotic ectodysplasin receptor 1
    Ectodysplasin-A receptor
    EDA-A1 receptor
    Ectodermal dysplasia receptor
    Downless homolog
Gene names
Name: EDAR
Synonyms: DL
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length448 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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.4 Ref.5

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 hair morphology type 1 (HRM1) [MIM:612630]; also called variation in hair thickness. 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.4 Ref.1

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.9

Sequence similarities

Contains 1 death domain.

Contains 3 TNFR-Cys repeats.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

EDAQ928381EBI-529289,EBI-529425
MAP3K14Q995581EBI-529289,EBI-358011
Traf1P394281EBI-529289,EBI-520123From a different organism.
Traf2P394291EBI-529289,EBI-520016From a different organism.
TRAF3Q131141EBI-529289,EBI-357631

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2626 Ref.3
Chain27 – 448422Tumor necrosis factor receptor superfamily member EDAR
PRO_0000034608

Regions

Topological domain27 – 187161Extracellular Potential
Transmembrane188 – 20821 Potential
Topological domain209 – 448240Cytoplasmic Potential
Repeat30 – 7142TNFR-Cys 1
Repeat73 – 11341TNFR-Cys 2
Repeat115 – 14834TNFR-Cys 3
Domain358 – 43174Death

Amino acid modifications

Modified residue3241Phosphoserine By similarity
Glycosylation381N-linked (GlcNAc...) Potential
Disulfide bond31 ↔ 44 By similarity
Disulfide bond47 ↔ 60 By similarity
Disulfide bond50 ↔ 71 By similarity
Disulfide bond74 ↔ 87 By similarity
Disulfide bond93 ↔ 113 By similarity
Disulfide bond135 ↔ 148 By similarity

Natural variations

Natural variant471C → Y in HED. Ref.8
VAR_054444
Natural variant871C → R in EDA. Ref.1
VAR_013448
Natural variant891R → H in EDA; also in autosomal recessive HED. Ref.1 Ref.9 Ref.8
VAR_013449
Natural variant1101D → A in HED. Ref.9 Ref.8
VAR_054445
Natural variant1481C → R in HED. Ref.8
VAR_054446
Natural variant3701V → A Associated with hair morphology; results in decreased downstream activity of NFKB1 48 hours after transfection into cells. dbSNP rs3827760. Ref.10
VAR_020011
Natural variant3751R → H in HED; the mutant protein does not interact with EDARADD and is functionally inactive. Ref.6
VAR_054447
Natural variant3771L → F in HED. Ref.8
VAR_054448
Natural variant3821G → S in HED. Ref.7
VAR_054449
Natural variant4031T → M in HED. Ref.8
VAR_054450
Natural variant4131T → P in HED. Ref.8
VAR_054451
Natural variant4181I → T in HED. Ref.8
VAR_054452
Natural variant4201R → Q in ED3; abolishes NF-kappa-B activation and reduces JNK activation. Ref.5 Ref.1 Ref.9 Ref.8
VAR_013450
Natural variant4341W → C in HED. Ref.8
VAR_054453

Experimental info

Mutagenesis3791E → K: Reduces activation of NF-kappa-B. Ref.5
Sequence conflict2621P → S in AAD50077. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q9UNE0-1 [UniParc].

Last modified May 1, 2000. Version 1.
Checksum: AC8D61249D608439

FASTA44848,582
        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 

« Hide

References

« Hide '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]"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.
[3]"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.
[4]"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.
[5]"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.
[6]"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 HED HIS-375, CHARACTERIZATION OF VARIANT HED HIS-375.
[7]"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.
[8]"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.
[9]"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.
[10]"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.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF130988 mRNA. Translation: AAD50076.1.
AF130996 expand/collapse EMBL AC list , AF130990, AF130991, AF130992, AF130993, AF130994, AF130995 Genomic DNA. Translation: AAD50077.1.
BC093870 mRNA. Translation: AAH93870.1.
BC093872 mRNA. Translation: AAH93872.1.
IPIIPI00007051.
RefSeqNP_071731.1.
UniGeneHs.171971

3D structure databases

SMRQ9UNE0. Positions 30-167, 346-430.
ModBaseSearch...

Protein-protein interaction databases

IntActQ9UNE0. 5 interactions.
STRINGQ9UNE0.

PTM databases

PhosphoSiteQ9UNE0.

Proteomic databases

PRIDEQ9UNE0.

Genome annotation databases

EnsemblENST00000258443; ENSP00000258443; ENSG00000135960; Homo sapiens. [Genome view]
GeneID10913.
KEGGhsa:10913.
UCSCuc002teq.2. human.

Organism-specific databases

CTD10913.
GeneCardsGC02M108969.
H-InvDBHIX0029820.
HGNCHGNC:2895. EDAR.
MIM129490. phenotype.
224900. phenotype.
604095. gene.
612630. phenotype.
Orphanet1810. Autosomal dominant hypohidrotic ectodermal dysplasia.
181. Christ-Siemens-Touraine syndrome.
248. Ectodermal dysplasia, hypohidrotic, autosomal recessive.
PharmGKBPA27602.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG17334.
HOVERGENQ9UNE0.
PhylomeDBQ9UNE0.

Gene expression databases

ArrayExpressQ9UNE0.
BgeeQ9UNE0.
CleanExHS_EDAR.
GenevestigatorQ9UNE0.
GermOnlineENSG00000135960. Homo sapiens.

Family and domain databases

InterProIPR000488. Death.
IPR011029. DEATH-like.
[Graphical view]
PfamPF00531. Death. 1 hit.
[Graphical view]
PROSITEPS50017. DEATH_DOMAIN. False negative.
PS00652. TNFR_NGFR_1. False negative.
PS50050. TNFR_NGFR_2. False negative.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio41449.
SOURCESearch...

Entry information

Entry nameEDAR_HUMAN
AccessionPrimary (citable) accession number: Q9UNE0
Secondary accession number(s): Q52LL5, Q9UND9
Entry history
Integrated into UniProtKB/Swiss-Prot: May 27, 2002
Last sequence update: May 1, 2000
Last modified: January 19, 2010
This is version 79 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
DisclaimerAny 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.

Relevant documents

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents