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Q9UNE0 (EDAR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 115. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference 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.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

Ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant (ECTD10A) [MIM:129490]: A form of ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. It is an autosomal dominant condition characterized by hypotrichosis, abnormal or missing teeth, and hypohidrosis due to the absence of sweat glands.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.10

Ectodermal dysplasia 10B, hypohidrotic/hair/tooth type, autosomal recessive (ECTD10B) [MIM:224900]: A disorder due to abnormal development of two or more ectodermal structures, and characterized by sparse hair (atrichosis or hypotrichosis), abnormal or missing teeth and the inability to sweat due to the absence of sweat glands.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.7 Ref.8 Ref.9 Ref.10 Ref.13 Ref.14

Sequence similarities

Contains 1 death domain.

Contains 3 TNFR-Cys repeats.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2626 Ref.4
Chain27 – 448422Tumor necrosis factor receptor superfamily member EDAR
PRO_0000034608

Regions

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

Amino acid modifications

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 ECTD10B. Ref.9
VAR_054444
Natural variant871C → R in ECTD10B. Ref.1
VAR_013448
Natural variant891R → H in ECTD10B. Ref.1 Ref.9 Ref.10 Ref.14
VAR_013449
Natural variant981R → Q in ECTD10B. Ref.13
VAR_064830
Natural variant1101D → A in ECTD10B. Ref.9 Ref.10
VAR_054445
Natural variant1481C → R in ECTD10B. Ref.9
VAR_054446
Natural variant3581R → Q in ECTD10B. Ref.13 Ref.14
VAR_064831
Natural variant3701V → 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 variant3751R → H in ECTD10B; the mutant protein does not interact with EDARADD and is functionally inactive. Ref.7
VAR_054447
Natural variant3771L → F in ECTD10B. Ref.9
VAR_054448
Natural variant3821G → S in ECTD10B. Ref.8
VAR_054449
Natural variant3961Q → QQ in ECTD10B. Ref.14
VAR_064832
Natural variant4031T → M in ECTD10B. Ref.9 Ref.14
VAR_054450
Natural variant4081I → F in ECTD10B. Ref.14
VAR_064833
Natural variant4131T → P in ECTD10B. Ref.9
VAR_054451
Natural variant4181I → T in ECTD10B. Ref.9
VAR_054452
Natural variant4201R → Q in ECTD10A and ECTD10B; abolishes NF-kappa-B activation and reduces JNK activation. Ref.1 Ref.6 Ref.9 Ref.10 Ref.14
VAR_013450
Natural variant4341W → C in ECTD10B. Ref.9
VAR_054453
Natural variant4341W → R in ECTD10B. Ref.13
VAR_064834

Experimental info

Mutagenesis3791E → K: Reduces activation of NF-kappa-B. Ref.6
Sequence conflict2621P → S in AAD50077. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q9UNE0 [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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], VARIANTS ECTD10B ARG-87 AND HIS-89, VARIANT ECTD10A 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. expand/collapse author list , 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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: VARIANT ECTD10B HIS-375, CHARACTERIZATION OF VARIANT ECTD10B 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] [Europe PMC] [Abstract]
Cited for: VARIANT ECTD10B 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] [Europe PMC] [Abstract]
Cited for: VARIANTS ECTD10B 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] [Europe PMC] [Abstract]
Cited for: VARIANTS ECTD10B HIS-89 AND ALA-110, VARIANT ECTD10A 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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: VARIANTS ECTD10B 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. expand/collapse author list , de Prost Y., Munnich A., Bonnefont J.P., Bodemer C., Smahi A.
Hum. Mutat. 32:70-72(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ECTD10B HIS-89; GLN-358; GLN-396 INS; MET-403; PHE-408 AND GLN-420.
+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.
CH471182 Genomic DNA. Translation: EAW53869.1.
BC093870 mRNA. Translation: AAH93870.1.
BC093872 mRNA. Translation: AAH93872.1.
RefSeqNP_071731.1. NM_022336.3.
UniGeneHs.171971.

3D structure databases

ProteinModelPortalQ9UNE0.
SMRQ9UNE0. Positions 21-168, 346-436.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid116118. 7 interactions.
IntActQ9UNE0. 5 interactions.
STRING9606.ENSP00000258443.

Chemistry

ChEMBLCHEMBL1250376.
GuidetoPHARMACOLOGY2325.

PTM databases

PhosphoSiteQ9UNE0.

Polymorphism databases

DMDM21263572.

Proteomic databases

PaxDbQ9UNE0.
PRIDEQ9UNE0.

Protocols and materials databases

DNASU10913.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000258443; ENSP00000258443; ENSG00000135960.
GeneID10913.
KEGGhsa:10913.
UCSCuc002teq.4. human.

Organism-specific databases

CTD10913.
GeneCardsGC02M109510.
HGNCHGNC:2895. EDAR.
HPAHPA042292.
MIM129490. phenotype.
224900. phenotype.
604095. gene.
612630. phenotype.
neXtProtNX_Q9UNE0.
Orphanet1810. Autosomal dominant hypohidrotic ectodermal dysplasia.
248. Autosomal recessive hypohidrotic ectodermal dysplasia.
PharmGKBPA27602.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG43402.
HOGENOMHOG000112327.
HOVERGENHBG031530.
KOK05162.
OrthoDBEOG780RMB.
PhylomeDBQ9UNE0.
TreeFamTF331385.

Gene expression databases

ArrayExpressQ9UNE0.
BgeeQ9UNE0.
CleanExHS_EDAR.
GenevestigatorQ9UNE0.

Family and domain databases

Gene3D1.10.533.10. 1 hit.
InterProIPR011029. DEATH-like_dom.
IPR000488. Death_domain.
[Graphical view]
PfamPF00531. Death. 1 hit.
[Graphical view]
SUPFAMSSF47986. SSF47986. 1 hit.
ProtoNetSearch...

Other

GeneWikiEDAR.
GenomeRNAi10913.
NextBio41449.
PROQ9UNE0.
SOURCESearch...

Entry information

Entry nameEDAR_HUMAN
AccessionPrimary (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: March 19, 2014
This is version 115 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
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

SIMILARITY comments

Index of protein domains and families

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

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