Q8WWZ3 (EDAD_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ectodysplasin-A receptor-associated adapter protein

Alternative name(s):
EDAR-associated death domain protein
Protein crinkled homolog

Gene names

Name:

EDARADD

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	215 AA.
Sequence status	Complete.
Protein existence	Evidence 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	Defects in EDARADD 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.7 Ref.9 Ref.10
Sequence similarities	Contains 1 death domain.

Ontologies

Keywords
Biological process	Differentiation
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation Ectodermal dysplasia
Molecular function	Developmental protein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW signal transduction Inferred from electronic annotation. Source: InterPro
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 215	215	Ectodysplasin-A receptor-associated adapter protein		PRO_0000086928
Regions
	Domain	123 – 202	80	Death
Natural variations
	Alternative sequence	1 – 20	20	MGLRT…PGHQE → MASPDDPLRA in isoform B.		VSP_003861
	Natural variant	9	1	M → I. Ref.3 Ref.4 Ref.6 Corresponds to variant rs966365 [ dbSNP | Ensembl ].		VAR_050963
	Natural variant	103	1	S → F. Ref.8		VAR_054509
	Natural variant	114	1	D → Y in EDA. Ref.10		VAR_064835
	Natural variant	122	1	L → R in EDA; severely impairs NF-kappa-B activation and acted in a dominant-negative manner. Ref.7		VAR_054510
	Natural variant	135 – 136	2	Missing in EDA; impairs the interaction with EDAR and severely inhibits NF-kappa-B activity.		VAR_064836
	Natural variant	152	1	E → K in EDA; may reduce binding to EDAR; impairs NF-kappa-B activation by about 50%. Ref.1 Ref.7		VAR_013482

Sequences

	Sequence		Length	Mass (Da)
	Isoform A [UniParc]. Last modified November 4, 2008. Version 3. Checksum: 25C198E3CA1F68F2	FASTA	215	24,802
	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
	Isoform B [UniParc]. Checksum: A83CCC3E4F3115CF	FASTA	205	23,690
	10 20 30 40 50 60 MASPDDPLRA DHMVKEPVED TDPSTLSFNM SDKYPIQDTE LPKAEECDTI TLNCPRNSDM 70 80 90 100 110 120 KNQGEENGFP DSTGDPLPEI SKDNSCKENC TCSSCLLRAP TISDLLNDQD LLDVIRIKLD 130 140 150 160 170 180 PCHPTVKNWR NFASKWGMSY DELCFLEQRP QSPTLEFLLR NSQRTVGQLM ELCRLYHRAD 190 200 VEKVLRRWVD EEWPKRERGD PSRHF

References

	« Hide 'large scale' referencesShow '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: 11780064] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B), VARIANT EDA 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: 11882293] [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. , 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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A), VARIANT ILE-9. Tissue: Mammary gland.
[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. , 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: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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] (ISOFORM A), VARIANT ILE-9.
[7]	"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: 17354266] [Abstract] Cited for: VARIANT EDA ARG-122, CHARACTERIZATION OF VARIANTS EDA ARG-122 AND LYS-152.
[8]	"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: VARIANT PHE-103.
[9]	"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: 20222921] [Abstract] Cited for: VARIANT EDA 135-THR-VAL-136 DEL, CHARACTERIZATION OF VARIANT EDA 135-THR-VAL-136 DEL.
[10]	"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: VARIANT EDA TYR-114.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY028914 mRNA. Translation: AAK40288.1. AY071862 mRNA. Translation: AAL60590.1. AY028912 , AY028906, AY028908, AY028909, AY028910, AY028911 Genomic DNA. Translation: AAK40285.1. AY028912 , AY028907, AY028908, AY028909, AY028910, AY028911 Genomic DNA. Translation: AAK40286.1. AY028913 mRNA. Translation: AAK40287.1. AK290862 mRNA. Translation: BAF83551.1. 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. BC128082 mRNA. Translation: AAI28083.1.
IPI	IPI00103484. IPI00152912.
RefSeq	NP_542776.1. NM_080738.3. NP_665860.2. NM_145861.2.
UniGene	Hs.352224.
3D structure databases
ProteinModelPortal	Q8WWZ3.
SMR	Q8WWZ3. Positions 119-205.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q8WWZ3. 2 interactions.
STRING	Q8WWZ3.
Polymorphism databases
DMDM	212276512.
Proteomic databases
PRIDE	Q8WWZ3.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000334232; ENSP00000335076; ENSG00000186197.
GeneID	128178.
KEGG	hsa:128178.
UCSC	uc001hxv.1. human.
Organism-specific databases
CTD	128178.
GeneCards	GC01P236511.
HGNC	HGNC:14341. EDARADD.
HPA	HPA018836.
MIM	224900. phenotype. 606603. gene.
neXtProt	NX_Q8WWZ3.
Orphanet	1810. Autosomal dominant hypohidrotic ectodermal dysplasia. 248. Autosomal recessive hypohidrotic ectodermal dysplasia.
GenAtlas	Search...
Phylogenomic databases
GeneTree	ENSGT00390000001136.
HOGENOM	HBG403026.
HOVERGEN	HBG018567.
InParanoid	Q8WWZ3.
OMA	YHRADVE.
Gene expression databases
ArrayExpress	Q8WWZ3.
Bgee	Q8WWZ3.
CleanEx	HS_EDARADD.
Genevestigator	Q8WWZ3.
GermOnline	ENSG00000186197. Homo sapiens.
Family and domain databases
InterPro	IPR000488. Death. IPR011029. DEATH-like. [Graphical view]
Gene3D	G3DSA:1.10.533.10. DEATH_like. 1 hit.
Pfam	PF00531. Death. 1 hit. [Graphical view]
SUPFAM	SSF47986. DEATH_like. 1 hit.
PROSITE	PS50017. DEATH_DOMAIN. False negative. [Graphical view]
ProtoNet	Search...
Other
NextBio	82231.
SOURCE	Search...

Entry information

Entry name

EDAD_HUMAN

Accession

Primary (citable) accession number: Q8WWZ3
Secondary accession number(s): A2VCK5, B1AL54, Q5VYJ7

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 6, 2002
Last sequence update:	November 4, 2008
Last modified:	January 25, 2012
This is version 88 of the entry and version 3 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.