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Q8WWZ3 (EDAD_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 109. 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·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Ectodysplasin-A receptor-associated adapter protein
Alternative name(s):
EDAR-associated death domain protein
Protein crinkled homolog
Gene names
Name:EDARADD
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length215 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Adapter protein that interacts with EDAR DEATH domain and couples the receptor to EDA signaling pathway during morphogenesis of ectodermal organs. Mediates the activation of NF-kappa-B. Ref.2

Subunit structure

Self-associates and binds EDAR, TRAF1, TRAF2 and TRAF3.

Subcellular location

Cytoplasm Probable.

Tissue specificity

Detected in adult pancreas, placenta and fetal skin, and at lower levels in lung, thymus, prostate and testis.

Involvement in disease

Ectodermal dysplasia 11A, hypohidrotic/hair/nail type, autosomal dominant (ECTD11A) [MIM:614940]: 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.8 Ref.11

Ectodermal dysplasia 11B, hypohidrotic/hair/tooth type, autosomal recessive (ECTD11B) [MIM:614941]: 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.8 Ref.10

Sequence similarities

Contains 1 death domain.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform A (identifier: Q8WWZ3-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform B (identifier: Q8WWZ3-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-20: MGLRTTKQMGRGTKAPGHQE → MASPDDPLRA

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 215215Ectodysplasin-A receptor-associated adapter protein
PRO_0000086928

Regions

Domain123 – 20280Death

Natural variations

Alternative sequence1 – 2020MGLRT…PGHQE → MASPDDPLRA in isoform B.
VSP_003861
Natural variant91M → I. Ref.3 Ref.4 Ref.7
Corresponds to variant rs966365 [ dbSNP | Ensembl ].
VAR_050963
Natural variant1031S → F. Ref.9
Corresponds to variant rs114632254 [ dbSNP | Ensembl ].
VAR_054509
Natural variant1141D → Y in ECTD11A. Ref.11
VAR_064835
Natural variant1221L → R in ECTD11A; severely impairs NF-kappa-B activation and acted in a dominant-negative manner. Ref.8
VAR_054510
Natural variant135 – 1362Missing in ECTD11B; impairs the interaction with EDAR and severely inhibits NF-kappa-B activity.
VAR_064836
Natural variant1521E → K in ECTD11B; may reduce binding to EDAR; impairs NF-kappa-B activation by about 50%. Ref.1 Ref.8
VAR_013482

Sequences

Sequence LengthMass (Da)Tools
Isoform A [UniParc].

Last modified November 4, 2008. Version 3.
Checksum: 25C198E3CA1F68F2

FASTA21524,802
        10         20         30         40         50         60 
MGLRTTKQMG RGTKAPGHQE DHMVKEPVED TDPSTLSFNM SDKYPIQDTE LPKAEECDTI 

        70         80         90        100        110        120 
TLNCPRNSDM KNQGEENGFP DSTGDPLPEI SKDNSCKENC TCSSCLLRAP TISDLLNDQD 

       130        140        150        160        170        180 
LLDVIRIKLD PCHPTVKNWR NFASKWGMSY DELCFLEQRP QSPTLEFLLR NSQRTVGQLM 

       190        200        210 
ELCRLYHRAD VEKVLRRWVD EEWPKRERGD PSRHF 

« Hide

Isoform B [UniParc].

Checksum: A83CCC3E4F3115CF
Show »

FASTA20523,690

References

« Hide 'large scale' references
[1]"Gene defect in ectodermal dysplasia implicates a DEATH domain adapter in development."
Headon D.J., Emmal S.A., Ferguson B.M., Tucker A.S., Justice M.J., Sharpe P.T., Zonana J., Overbeek P.A.
Nature 414:913-916(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B), VARIANT ECTD11B LYS-152.
[2]"Identification of a novel DEATH domain-containing adaptor molecule for ectodysplasin-A receptor that is mutated in crinkled mice."
Yan M., Zhang Z., Brady J.R., Schilbach S., Fairbrother W.J., Dixit V.M.
Curr. Biol. 12:409-413(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B), FUNCTION.
Tissue: Skin.
[3]"A novel death domain adapter required for ectodermal development."
Emmal S.A., Ferguson B.M., Zonana J.
Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ILE-9.
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS A AND B), VARIANT ILE-9.
Tissue: Mammary gland and Placenta.
[5]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]Mural R.J., Istrail S., Sutton 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"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] (ISOFORM A), VARIANT ILE-9.
[8]"Autosomal dominant anhidrotic ectodermal dysplasias at the EDARADD locus."
Bal E., Baala L., Cluzeau C., El Kerch F., Ouldim K., Hadj-Rabia S., Bodemer C., Munnich A., Courtois G., Sefiani A., Smahi A.
Hum. Mutat. 28:703-709(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ECTD11A ARG-122, CHARACTERIZATION OF VARIANT ECTD11A ARG-122, CHARACTERIZATION OF VARIANT ECTD11B LYS-152.
[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] [Europe PMC] [Abstract]
Cited for: VARIANT PHE-103.
[10]"Mutations in EDARADD account for a small proportion of hypohidrotic ectodermal dysplasia cases."
Chassaing N., Cluzeau C., Bal E., Guigue P., Vincent M.C., Viot G., Ginisty D., Munnich A., Smahi A., Calvas P.
Br. J. Dermatol. 162:1044-1048(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ECTD11B 135-THR-VAL-136 DEL, CHARACTERIZATION OF VARIANT ECTD11B 135-THR-VAL-136 DEL.
[11]"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: VARIANT ECTD11A TYR-114.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY028914 mRNA. Translation: AAK40288.1.
AY071862 mRNA. Translation: AAL60590.1.
AY028912 expand/collapse EMBL AC list , AY028906, AY028908, AY028909, AY028910, AY028911 Genomic DNA. Translation: AAK40285.1.
AY028912 expand/collapse EMBL AC list , AY028907, AY028908, AY028909, AY028910, AY028911 Genomic DNA. Translation: AAK40286.1.
AY028913 mRNA. Translation: AAK40287.1.
AK290862 mRNA. Translation: BAF83551.1.
AK291930 mRNA. Translation: BAF84619.1.
AK314634 mRNA. Translation: BAG37197.1.
AL354693, AL136105 Genomic DNA. Translation: CAH70608.1.
AL354693, AL136105 Genomic DNA. Translation: CAH70609.1.
AL136105, AL354693 Genomic DNA. Translation: CAI22302.1.
AL136105, AL354693 Genomic DNA. Translation: CAI22303.1.
CH471098 Genomic DNA. Translation: EAW70052.1.
BC128082 mRNA. Translation: AAI28083.1.
RefSeqNP_542776.1. NM_080738.3.
NP_665860.2. NM_145861.2.
UniGeneHs.352224.

3D structure databases

ProteinModelPortalQ8WWZ3.
SMRQ8WWZ3. Positions 120-204.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid126096. 5 interactions.
IntActQ8WWZ3. 3 interactions.
STRING9606.ENSP00000335076.

Polymorphism databases

DMDM212276512.

Proteomic databases

PaxDbQ8WWZ3.
PRIDEQ8WWZ3.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000334232; ENSP00000335076; ENSG00000186197. [Q8WWZ3-1]
ENST00000359362; ENSP00000352320; ENSG00000186197. [Q8WWZ3-2]
GeneID128178.
KEGGhsa:128178.
UCSCuc001hxu.1. human. [Q8WWZ3-1]
uc001hxv.1. human. [Q8WWZ3-2]

Organism-specific databases

CTD128178.
GeneCardsGC01P236511.
HGNCHGNC:14341. EDARADD.
HPAHPA018836.
MIM606603. gene.
614940. phenotype.
614941. phenotype.
neXtProtNX_Q8WWZ3.
Orphanet1810. Autosomal dominant hypohidrotic ectodermal dysplasia.
248. Autosomal recessive hypohidrotic ectodermal dysplasia.
99798. Oligodontia.
PharmGKBPA27603.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG46533.
HOGENOMHOG000013132.
HOVERGENHBG018567.
InParanoidQ8WWZ3.
OMADHMAKEP.
PhylomeDBQ8WWZ3.
TreeFamTF335658.

Gene expression databases

ArrayExpressQ8WWZ3.
BgeeQ8WWZ3.
CleanExHS_EDARADD.
GenevestigatorQ8WWZ3.

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

GeneWikiEDARADD.
GenomeRNAi128178.
NextBio82231.
PROQ8WWZ3.
SOURCESearch...

Entry information

Entry nameEDAD_HUMAN
AccessionPrimary (citable) accession number: Q8WWZ3
Secondary accession number(s): A2VCK5 expand/collapse secondary AC list , A8K7B5, B1AL54, B9ZVW5, Q5VYJ7
Entry history
Integrated into UniProtKB/Swiss-Prot: June 6, 2002
Last sequence update: November 4, 2008
Last modified: April 16, 2014
This is version 109 of the entry and version 3 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 1

Human chromosome 1: entries, gene names and cross-references to MIM