Q92838 (EDA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ectodysplasin-A

Alternative name(s):
Ectodermal dysplasia protein
Short name=EDA protein

Cleaved into the following 2 chains:

1. Ectodysplasin-A, membrane form
2. Ectodysplasin-A, secreted form

Gene names

Name:	EDA
Synonyms:	ED1, EDA2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	391 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	Seems to be involved in epithelial-mesenchymal signaling during morphogenesis of ectodermal organs. Isoform 1 binds only to the receptor EDAR, while isoform 3 binds exclusively to the receptor XEDAR.
Subunit structure	Homotrimer. The homotrimers may then dimerize and form higher-order oligomers. Ref.10
Subcellular location	Cell membrane; Single-pass type II membrane protein. Ectodysplasin-A, secreted form: Secreted.
Tissue specificity	Not abundant; expressed in specific cell types of ectodermal (but not mesodermal) origin of keratinocytes, hair follicles, sweat glands. Also in adult heart, liver, muscle, pancreas, prostate, fetal liver, uterus, small intestine and umbilical chord. Ref.6
Post-translational modification	N-glycosylated. Processing by furin produces a secreted form.
Involvement in disease	Ectodermal dysplasia 1, hypohidrotic, X-linked (XHED) [MIM:305100]: A form of ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. Characterized by sparse hair (atrichosis or hypotrichosis), abnormal or missing teeth and the inability to sweat due to the absence of sweat glands. It is the most common form of over 150 clinically distinct ectodermal dysplasias. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.2 Ref.3 Ref.8 Ref.9 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.23 Ref.24 Ref.26 Ref.27 Ref.28 Ref.29 Ref.30 Ref.31 Tooth agenesis selective X-linked 1 (STHAGX1) [MIM:313500]: A form of selective tooth agenesis, a common anomaly characterized by the congenital absence of one or more teeth. Selective tooth agenesis without associated systemic disorders has sometimes been divided into 2 types: oligodontia, defined as agenesis of 6 or more permanent teeth, and hypodontia, defined as agenesis of less than 6 teeth. The number in both cases does not include absence of third molars (wisdom teeth). Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.21 Ref.25
Sequence similarities	Belongs to the tumor necrosis factor family. Contains 1 collagen-like domain.
Sequence caution	The sequence AAC77372.1 differs from that shown. Reason: Intron retention. The sequence CAI39805.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence CAI41611.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Biological process	Differentiation
Cellular component	Cell membrane Membrane Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation Ectodermal dysplasia
Domain	Collagen Signal-anchor Transmembrane Transmembrane helix
Molecular function	Developmental protein
PTM	Cleavage on pair of basic residues Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW cell-matrix adhesion Inferred from electronic annotation. Source: Compara ectoderm development Traceable author statement Ref.1. Source: ProtInc gene expression Inferred from electronic annotation. Source: Compara hair follicle placode formation Inferred from electronic annotation. Source: Compara immune response Inferred from electronic annotation. Source: InterPro odontogenesis of dentin-containing tooth Inferred from electronic annotation. Source: Compara pigmentation Inferred from electronic annotation. Source: Compara positive regulation of I-kappaB kinase/NF-kappaB cascade Inferred from electronic annotation. Source: Compara positive regulation of NF-kappaB import into nucleus Inferred from electronic annotation. Source: Compara positive regulation of NF-kappaB transcription factor activity Inferred from direct assay Ref.7. Source: HGNC positive regulation of canonical Wnt receptor signaling pathway Inferred from electronic annotation. Source: Compara salivary gland cavitation Inferred from electronic annotation. Source: Compara signal transduction Traceable author statement Ref.1. Source: ProtInc skin development Inferred from electronic annotation. Source: Compara trachea gland development Inferred from electronic annotation. Source: Compara
Cellular_component	apical part of cell Inferred from electronic annotation. Source: Compara collagen Inferred from electronic annotation. Source: UniProtKB-KW cytoskeleton Traceable author statement PubMed 10484778. Source: ProtInc endoplasmic reticulum membrane Inferred from electronic annotation. Source: Compara integral to membrane Traceable author statement Ref.1. Source: ProtInc integral to plasma membrane Inferred from electronic annotation. Source: Compara plasma membrane Traceable author statement PubMed 10484778Ref.3. Source: ProtInc
Molecular_function	receptor binding Inferred from direct assay Ref.7. Source: HGNC
Complete GO annotation...

Alternative products

This entry describes 8 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.

Isoform 1 (identifier: Q92838-1)

Also known as: A1; II;

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 2 (identifier: Q92838-2)

Also known as: I;

The sequence of this isoform differs from the canonical sequence as follows:
     133-135: MAL → GHQ
     136-391: Missing.

Isoform 3 (identifier: Q92838-3)

Also known as: A2;

The sequence of this isoform differs from the canonical sequence as follows:
     307-308: Missing.

Isoform 4 (identifier: Q92838-5)

Also known as: C;

The sequence of this isoform differs from the canonical sequence as follows:
     133-147: MALLNFFFPDEKPYS → VSHLVGAAAAPSPRG
     148-391: Missing.

Isoform 5 (identifier: Q92838-6)

Also known as: D;

The sequence of this isoform differs from the canonical sequence as follows:
     133-142: MALLNFFFPD → ACFPQVLLSL
     143-391: Missing.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Isoform 6 (identifier: Q92838-7)

Also known as: E;

The sequence of this isoform differs from the canonical sequence as follows:
     133-147: MALLNFFFPDEKPYS → DFDYIISFSYGLQGFC
     148-391: Missing.

Isoform 7 (identifier: Q92838-8)

Also known as: F;

The sequence of this isoform differs from the canonical sequence as follows:
     133-147: MALLNFFFPDEKPYS → LHVSFSLRKKKAGHQ
     148-391: Missing.

Isoform 8 (identifier: Q92838-9)

The sequence of this isoform differs from the canonical sequence as follows:
     265-267: Missing.
     307-308: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 391

391

Ectodysplasin-A, membrane form

PRO_0000034538

Chain

160 – 391

232

Ectodysplasin-A, secreted form

PRO_0000034539

Regions

Topological domain

1 – 41

41

Cytoplasmic Potential

Transmembrane

42 – 62

21

Helical; Signal-anchor for type II membrane protein; Potential

Topological domain

63 – 391

329

Extracellular Potential

Domain

180 – 229

50

Collagen-like

Sites

Site

159 – 160

2

Cleavage; by furin

Amino acid modifications

Glycosylation

313

1

N-linked (GlcNAc...) Potential

Glycosylation

372

1

N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence

133 – 147

15

MALLN…EKPYS → VSHLVGAAAAPSPRG in isoform 4.

VSP_006458

Alternative sequence

133 – 147

15

MALLN…EKPYS → DFDYIISFSYGLQGFC in isoform 6.

VSP_006459

Alternative sequence

133 – 147

15

MALLN…EKPYS → LHVSFSLRKKKAGHQ in isoform 7.

VSP_006460

Alternative sequence

133 – 142

10

MALLNFFFPD → ACFPQVLLSL in isoform 5.

VSP_006456

Alternative sequence

133 – 135

3

MAL → GHQ in isoform 2.

VSP_006454

Alternative sequence

136 – 391

256

Missing in isoform 2.

VSP_006455

Alternative sequence

143 – 391

249

Missing in isoform 5.

VSP_006457

Alternative sequence

148 – 391

244

Missing in isoform 4, isoform 6 and isoform 7.

VSP_006461

Alternative sequence

265 – 267

3

Missing in isoform 8.

VSP_038402

Alternative sequence

307 – 308

2

Missing in isoform 3 and isoform 8.

VSP_006464

Natural variant

54

1

H → Y in XHED. Ref.11

VAR_010611

Natural variant

55

1

L → R in XHED. Ref.13

VAR_010612

Natural variant

60

1

C → R in XHED. Ref.16

VAR_013484

Natural variant

61

1

Y → H in XHED. Ref.1

VAR_005179

Natural variant

63

1

E → K in XHED. Ref.12

VAR_005180

Natural variant

65

1

R → G in STHAGX1. Ref.21

VAR_029534

Natural variant

69

1

R → L in XHED. Ref.1

VAR_005181

Natural variant

118

1

P → L in a colorectal cancer sample; somatic mutation. Ref.22

VAR_036590

Natural variant

153

1

R → C in XHED; abolishes proteolytic processing. Ref.8 Ref.9 Ref.18 Ref.26

VAR_054454

Natural variant

155

1

R → C in XHED; abolishes proteolytic processing. Ref.9 Ref.18 Ref.24 Ref.26 Ref.28

VAR_005182

Natural variant

156

1

R → C in XHED; abolishes proteolytic processing. Ref.9 Ref.17 Ref.18 Ref.24

VAR_005183

Natural variant

156

1

R → G in XHED. Ref.29

VAR_064858

Natural variant

156

1

R → H in XHED; abolishes proteolytic processing. Ref.8 Ref.9 Ref.17 Ref.18 Ref.24

VAR_005184

Natural variant

156

1

R → S in XHED. Ref.14

VAR_054455

Natural variant

158

1

K → N in XHED; abolishes proteolytic processing. Ref.9 Ref.18

VAR_054456

Natural variant

183 – 194

12

Missing in XHED.

VAR_054457

Natural variant

184 – 189

6

Missing in XHED.

VAR_054458

Natural variant

185 – 196

12

Missing in XHED.

VAR_054459

Natural variant

189

1

G → E in XHED. Ref.18

VAR_054460

Natural variant

191 – 196

6

Missing in XHED.

VAR_054461

Natural variant

192 – 197

6

Missing in XHED.

VAR_064859

Natural variant

198

1

G → A in XHED. Ref.19

VAR_054462

Natural variant

207

1

G → R in XHED. Ref.18

VAR_054463

Natural variant

207

1

G → V in XHED. Ref.29

VAR_064860

Natural variant

209

1

P → L in XHED.

VAR_005185

Natural variant

211

1

T → R in XHED. Ref.29

VAR_064861

Natural variant

218 – 223

6

Missing in XHED.

VAR_054465

Natural variant

218

1

G → D in XHED. Ref.18

VAR_054464

Natural variant

224

1

G → A in XHED.

VAR_005186

Natural variant

252

1

H → L in XHED.

VAR_005187

Natural variant

252

1

H → Y in XHED. Ref.16

VAR_013485

Natural variant

255

1

G → C in XHED. Ref.17

VAR_011077

Natural variant

255

1

G → D in XHED; mild. Ref.17

VAR_011078

Natural variant

266

1

L → R in XHED. Ref.29

VAR_064862

Natural variant

269

1

G → V in XHED. Ref.16

VAR_013486

Natural variant

274

1

W → G in XHED. Ref.17

VAR_011079

Natural variant

274

1

W → R in XHED. Ref.29

VAR_064863

Natural variant

291

1

G → R in XHED. Ref.18 Ref.24

VAR_010613

Natural variant

291

1

G → W in XHED.

VAR_010614

Natural variant

293

1

L → P in XHED. Ref.29

VAR_064864

Natural variant

296

1

L → V in XHED. Ref.29

VAR_064865

Natural variant

298

1

D → H in XHED.

VAR_010615

Natural variant

298

1

D → Y in XHED. Ref.24

VAR_054466

Natural variant

299

1

G → D in XHED. Ref.29

VAR_064866

Natural variant

299

1

G → S in XHED. Ref.18

VAR_005188

Natural variant

302

1

F → S in XHED. Ref.16

VAR_013487

Natural variant

306

1

Q → H in XHED. Ref.20

VAR_054467

Natural variant

307

1

V → G in XHED. Ref.24

VAR_054468

Natural variant

319

1

S → R in XHED. Ref.31

VAR_067319

Natural variant

320

1

Y → C in XHED. Ref.18

VAR_054469

Natural variant

323

1

V → G in XHED. Ref.29

VAR_064867

Natural variant

332

1

C → Y in XHED. Ref.17

VAR_011080

Natural variant

338

1

T → M in STHAGX1. Ref.25

VAR_064868

Natural variant

343

1

Y → C in XHED. Ref.18

VAR_054470

Natural variant

346

1

C → Y in XHED. Ref.29

VAR_064869

Natural variant

349

1

A → T in XHED. Ref.15 Ref.17 Ref.26

VAR_005189

Natural variant

354

1

L → P in XHED. Ref.30

VAR_067250

Natural variant

356

1

A → D in XHED.

VAR_005190

Natural variant

356

1

A → V in XHED. Ref.29

VAR_064870

Natural variant

357

1

R → P in XHED.

VAR_005191

Natural variant

358

1

Q → E in XHED. Ref.23

VAR_054471

Natural variant

360

1

I → N in XHED. Ref.15

VAR_054472

Natural variant

372

1

N → D in XHED. Ref.24

VAR_054473

Natural variant

373

1

M → I in XHED. Ref.24

VAR_054474

Natural variant

374

1

S → R in XHED. Ref.18

VAR_054475

Natural variant

378

1

T → M in XHED. Ref.16 Ref.18 Ref.19

VAR_013488

Natural variant

378

1

T → P in XHED. Ref.18

VAR_054476

Natural variant

381

1

G → R in XHED. Ref.27

VAR_064871

Experimental info

Mutagenesis

159

1

R → A: Abolishes proteolytic processing. Ref.9

Secondary structure

1

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391

Helix Strand Turn

Details...

Beta strand

249 – 254

6

Beta strand

257 – 261

5

Helix

262 – 264

3

Helix

266 – 269

4

Beta strand

275 – 279

5

Turn

281 – 283

3

Beta strand

284 – 286

3

Turn

288 – 290

3

Beta strand

293 – 295

3

Beta strand

299 – 306

8

Beta strand

309 – 316

8

Beta strand

318 – 324

7

Beta strand

327 – 336

10

Beta strand

338 – 340

3

Beta strand

342 – 354

13

Beta strand

359 – 364

6

Beta strand

370 – 372

3

Turn

375 – 377

3

Beta strand

378 – 386

9

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (A1) (II) [UniParc]. Last modified July 15, 1999. Version 2. Checksum: 15DB3F5053293CBA	FASTA	391	41,294
	10 20 30 40 50 60 MGYPEVERRE LLPAAAPRER GSQGCGCGGA PARAGEGNSC LLFLGFFGLS LALHLLTLCC 70 80 90 100 110 120 YLELRSELRR ERGAESRLGG SGTPGTSGTL SSLGGLDPDS PITSHLGQPS PKQQPLEPGE 130 140 150 160 170 180 AALHSDSQDG HQMALLNFFF PDEKPYSEEE SRRVRRNKRS KSNEGADGPV KNKKKGKKAG 190 200 210 220 230 240 PPGPNGPPGP PGPPGPQGPP GIPGIPGIPG TTVMGPPGPP GPPGPQGPPG LQGPSGAADK 250 260 270 280 290 300 AGTRENQPAV VHLQGQGSAI QVKNDLSGGV LNDWSRITMN PKVFKLHPRS GELEVLVDGT 310 320 330 340 350 360 YFIYSQVEVY YINFTDFASY EVVVDEKPFL QCTRSIETGK TNYNTCYTAG VCLLKARQKI 370 380 390 AVKMVHADIS INMSKHTTFF GAIRLGEAPA S
	Isoform 2 (I) [UniParc]. Checksum: 90C19D0674EC540D	FASTA	135	14,048
	10 20 30 40 50 60 MGYPEVERRE LLPAAAPRER GSQGCGCGGA PARAGEGNSC LLFLGFFGLS LALHLLTLCC 70 80 90 100 110 120 YLELRSELRR ERGAESRLGG SGTPGTSGTL SSLGGLDPDS PITSHLGQPS PKQQPLEPGE 130 AALHSDSQDG HQGHQ
	Isoform 3 (A2) [UniParc]. Checksum: 9289F3104CD83454	FASTA	389	41,065
	10 20 30 40 50 60 MGYPEVERRE LLPAAAPRER GSQGCGCGGA PARAGEGNSC LLFLGFFGLS LALHLLTLCC 70 80 90 100 110 120 YLELRSELRR ERGAESRLGG SGTPGTSGTL SSLGGLDPDS PITSHLGQPS PKQQPLEPGE 130 140 150 160 170 180 AALHSDSQDG HQMALLNFFF PDEKPYSEEE SRRVRRNKRS KSNEGADGPV KNKKKGKKAG 190 200 210 220 230 240 PPGPNGPPGP PGPPGPQGPP GIPGIPGIPG TTVMGPPGPP GPPGPQGPPG LQGPSGAADK 250 260 270 280 290 300 AGTRENQPAV VHLQGQGSAI QVKNDLSGGV LNDWSRITMN PKVFKLHPRS GELEVLVDGT 310 320 330 340 350 360 YFIYSQVYYI NFTDFASYEV VVDEKPFLQC TRSIETGKTN YNTCYTAGVC LLKARQKIAV 370 380 KMVHADISIN MSKHTTFFGA IRLGEAPAS
	Isoform 4 (C) [UniParc]. Checksum: 4B46D2AF7EF8063D	FASTA	147	15,097
	10 20 30 40 50 60 MGYPEVERRE LLPAAAPRER GSQGCGCGGA PARAGEGNSC LLFLGFFGLS LALHLLTLCC 70 80 90 100 110 120 YLELRSELRR ERGAESRLGG SGTPGTSGTL SSLGGLDPDS PITSHLGQPS PKQQPLEPGE 130 140 AALHSDSQDG HQVSHLVGAA AAPSPRG
	Isoform 5 (D) [UniParc]. Checksum: C0ACDCC07BE70D7F	FASTA	142	14,798
	10 20 30 40 50 60 MGYPEVERRE LLPAAAPRER GSQGCGCGGA PARAGEGNSC LLFLGFFGLS LALHLLTLCC 70 80 90 100 110 120 YLELRSELRR ERGAESRLGG SGTPGTSGTL SSLGGLDPDS PITSHLGQPS PKQQPLEPGE 130 140 AALHSDSQDG HQACFPQVLL SL
	Isoform 6 (E) [UniParc]. Checksum: B4473D0DBEFFD289	FASTA	148	15,582
	10 20 30 40 50 60 MGYPEVERRE LLPAAAPRER GSQGCGCGGA PARAGEGNSC LLFLGFFGLS LALHLLTLCC 70 80 90 100 110 120 YLELRSELRR ERGAESRLGG SGTPGTSGTL SSLGGLDPDS PITSHLGQPS PKQQPLEPGE 130 140 AALHSDSQDG HQDFDYIISF SYGLQGFC
	Isoform 7 (F) [UniParc]. Checksum: F49B7DEFB05D4336	FASTA	147	15,443
	10 20 30 40 50 60 MGYPEVERRE LLPAAAPRER GSQGCGCGGA PARAGEGNSC LLFLGFFGLS LALHLLTLCC 70 80 90 100 110 120 YLELRSELRR ERGAESRLGG SGTPGTSGTL SSLGGLDPDS PITSHLGQPS PKQQPLEPGE 130 140 AALHSDSQDG HQLHVSFSLR KKKAGHQ
	Isoform 8 [UniParc]. Checksum: E498990FECC30F26	FASTA	386	40,750
	10 20 30 40 50 60 MGYPEVERRE LLPAAAPRER GSQGCGCGGA PARAGEGNSC LLFLGFFGLS LALHLLTLCC 70 80 90 100 110 120 YLELRSELRR ERGAESRLGG SGTPGTSGTL SSLGGLDPDS PITSHLGQPS PKQQPLEPGE 130 140 150 160 170 180 AALHSDSQDG HQMALLNFFF PDEKPYSEEE SRRVRRNKRS KSNEGADGPV KNKKKGKKAG 190 200 210 220 230 240 PPGPNGPPGP PGPPGPQGPP GIPGIPGIPG TTVMGPPGPP GPPGPQGPPG LQGPSGAADK 250 260 270 280 290 300 AGTRENQPAV VHLQGQGSAI QVKNGGVLND WSRITMNPKV FKLHPRSGEL EVLVDGTYFI 310 320 330 340 350 360 YSQVYYINFT DFASYEVVVD EKPFLQCTRS IETGKTNYNT CYTAGVCLLK ARQKIAVKMV 370 380 HADISINMSK HTTFFGAIRL GEAPAS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"X-linked anhidrotic (hypohidrotic) ectodermal dysplasia is caused by mutation in a novel transmembrane protein." Kere J., Srivastava A.K., Montonen O., Zonana J., Thomas N.S.T., Ferguson B.M., Munoz F., Morgan D., Clarke A., Baybayan P., Chen E.Y., Ezer S., Saarialho-Kere U., la Chapelle A., Schlessinger D. Nat. Genet. 13:409-416(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-132, VARIANTS XHED HIS-61 AND LEU-69. Tissue: Sweat gland.
[2]	"Identification of a new splice form of the EDA1 gene permits detection of nearly all X-linked hypohidrotic ectodermal dysplasia mutations." Monreal A.W., Zonana J., Ferguson B.M. Am. J. Hum. Genet. 63:380-389(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 133-391, VARIANTS XHED. Tissue: Fetal liver.
[3]	"The anhidrotic ectodermal dysplasia gene (EDA) undergoes alternative splicing and encodes ectodysplasin-A with deletion mutations in collagenous repeats." Bayes M., Hartung A.J., Ezer S., Pispa J., Thesleff I., Srivastava A.K., Kere J. Hum. Mol. Genet. 7:1661-1669(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 3; 4; 5; 6 AND 7), VARIANTS XHED.
[4]	"The DNA sequence of the human X chromosome." Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R. Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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] (ISOFORMS 1; 3 AND 8).
[6]	"Expression of a novel transcript isoform of the EDA gene in human umbilical cord." Kobielak K., Kobielak A., Trzciak W.H. Eur. J. Hum. Genet. Suppl. 7:104-104(1999) Cited for: TISSUE SPECIFICITY, ALTERNATIVE SPLICING.
[7]	"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: RECEPTOR INTERACTION (ISOFORMS 1 AND 3).
[8]	"Ectodysplasin is released by proteolytic shedding and binds to the EDAR protein." Elomaa O., Pulkkinen K., Hannelius U., Mikkola M., Saarialho-Kere U., Kere J. Hum. Mol. Genet. 10:953-962(2001) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEOLYTIC PROCESSING, CHARACTERIZATION OF VARIANT XHED CYS-153, CHARACTERIZATION OF VARIANT HIS-156.
[9]	"Mutations within a furin consensus sequence block proteolytic release of ectodysplasin-A and cause X-linked hypohidrotic ectodermal dysplasia." Chen Y., Molloy S.S., Thomas L., Gambee J., Baechinger H.P., Ferguson B.M., Zonana J., Thomas G., Morris N.P. Proc. Natl. Acad. Sci. U.S.A. 98:7218-7223(2001) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS XHED CYS-153; CYS-155; CYS-156; HIS-156 AND ASN-158, MUTAGENESIS OF ARG-159, CLEAVAGE SITE.
[10]	"The crystal structures of EDA-A1 and EDA-A2: splice variants with distinct receptor specificity." Hymowitz S.G., Compaan D.M., Yan M., Wallweber H.J., Dixit V.M., Starovasnik M.A., de Vos A.M. Structure 11:1513-1520(2003) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 230-391, SUBUNIT.
[11]	"A novel missense mutation (402C-->T) in exon 1 in the EDA gene in a family with X-linked hypohidrotic ectodermal dysplasia." Hertz J.M., Noergaard Hansen K., Juncker I., Kjeldsen M., Gregersen N. Clin. Genet. 53:205-209(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT XHED TYR-54.
[12]	"Scarcity of mutations detected in families with X linked hypohidrotic ectodermal dysplasia: diagnostic implications." Ferguson B.M., Thomas N.S.T., Munoz F., Morgan D., Clarke A., Zonana J. J. Med. Genet. 35:112-115(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT XHED LYS-63.
[13]	"X-linked anhidrotic (hypohidrotic) ectodermal dysplasia caused by a novel mutation in EDA1 gene: 406T > G (Leu55Arg)." Martinez F., Millan J.M., Orellana C., Prieto F. J. Invest. Dermatol. 113:285-286(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT XHED ARG-55.
[14]	"A novel arginine-->Serine mutation in EDA1 in a Japanese family with X-linked anhidrotic ectodermal dysplasia." Aoki N., Ito K., Tachibana T., Ito M. J. Invest. Dermatol. 115:329-330(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT XHED SER-156.
[15]	"Mutations in the EDA gene in three unrelated families reveal no apparent correlation between phenotype and genotype in the patients with an X-linked anhidrotic ectodermal dysplasia." Kobielak K., Kobielak A., Roszkiewicz J., Wierzba J., Limon J., Trzeciak W.H. Am. J. Med. Genet. 100:191-197(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS XHED THR-349 AND ASN-360.
[16]	"Mutational spectrum of the ED1 gene in X-linked hypohidrotic ectodermal dysplasia." Vincent M.-C., Biancalana V., Ginisty D., Mandel J.-L., Calvas P. Eur. J. Hum. Genet. 9:355-363(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS XHED ARG-60; TYR-252; VAL-269; SER-302 AND MET-378.
[17]	"The mutation spectrum of the EDA gene in X-linked anhidrotic ectodermal dysplasia." Paeaekkoenen K., Cambiaghi S., Novelli G., Ouzts L.V., Penttinen M., Kere J., Srivastava A.K. Hum. Mutat. 17:349-349(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS XHED CYS-156; HIS-156; CYS-255; ASP-255; GLY-274; TYR-332 AND THR-349.
[18]	"Mutations leading to X-linked hypohidrotic ectodermal dysplasia affect three major functional domains in the tumor necrosis factor family member ectodysplasin-A." Schneider P., Street S.L., Gaide O., Hertig S., Tardivel A., Tschopp J., Runkel L., Alevizopoulos K., Ferguson B.M., Zonana J. J. Biol. Chem. 276:18819-18827(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS XHED CYS-153; CYS-155; CYS-156; HIS-156; ASN-158; 183-GLY--PRO-194 DEL; 185-ASN--PRO-196 DEL; GLU-189; 191-PRO--PRO-196 DEL; ARG-207; ASP-218; 218-GLY--PRO-223 DEL; ARG-291; SER-299; CYS-320; CYS-343; ARG-374; PRO-378 AND MET-378.
[19]	"Pitfalls in clinical diagnosis of female carriers of X-linked hypohidrotic ectodermal dysplasia." Vincent M.-C., Cossee M., Vabres P., Stewart F., Bonneau D., Calvas P. Arch. Dermatol. 138:1256-1258(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS XHED ALA-198 AND MET-378.
[20]	"A novel missense mutation (Gln306His) in exon 7 of the ED1 gene causing anhidrotic ectodermal dysplasia with prominent milia-like facial sebaceous papules." Hsu M.M.L., Chao S.C., Lu A.C.H. Br. J. Dermatol. 149:443-445(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT XHED HIS-306.
[21]	"A novel missense mutation of the EDA gene in a Mongolian family with congenital hypodontia." Tao R., Jin B., Guo S.Z., Qing W., Feng G.Y., Brooks D.G., Liu L., Xu J., Li T., Yan Y., He L. J. Hum. Genet. 51:498-502(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT STHAGX1 GLY-65.
[22]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] LEU-118.
[23]	"A novel Gln358Glu mutation in ectodysplasin A associated with X-linked dominant incisor hypodontia." Tarpey P., Pemberton T.J., Stockton D.W., Das P., Ninis V., Edkins S., Andrew Futreal P., Wooster R., Kamath S., Nayak R., Stratton M.R., Patel P.I. Am. J. Med. Genet. A 143:390-394(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT XHED GLU-358.
[24]	"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 XHED CYS-155; CYS-156; HIS-156; 183-GLY--PRO-194 DEL; 184-PRO--GLY-189 DEL; 185-ASN--PRO-196 DEL; ARG-291; TYR-298; GLY-307; ASP-372 AND ILE-373.
[25]	"Novel EDA mutation resulting in X-linked non-syndromic hypodontia and the pattern of EDA-associated isolated tooth agenesis." Han D., Gong Y., Wu H., Zhang X., Yan M., Wang X., Qu H., Feng H., Song S. Eur. J. Med. Genet. 51:536-546(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT STHAGX1 MET-338.
[26]	"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 XHED CYS-153; CYS-155 AND THR-349.
[27]	"Two novel mutations in the ED1 gene in Japanese families with X-linked hypohidrotic ectodermal dysplasia." Gunadi X., Miura K., Ohta M., Sugano A., Lee M.J., Sato Y., Matsunaga A., Hayashi K., Horikawa T., Miki K., Wataya-Kaneda M., Katayama I., Nishigori C., Matsuo M., Takaoka Y., Nishio H. Pediatr. Res. 65:453-457(2009) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT XHED ARG-381.
[28]	"Missense mutation of the EDA gene in a Jordanian family with X-linked hypohidrotic ectodermal dysplasia: phenotypic appearance and speech problems." Khabour O.F., Mesmar F.S., Al-Tamimi F., Al-Batayneh O.B., Owais A.I. Genet. Mol. Res. 9:941-948(2010) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT XHED CYS-155.
[29]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS XHED GLY-156; 192-GLY--GLN-197 DEL; VAL-207; ARG-211; ARG-266; ARG-274; PRO-293; VAL-296; ASP-299; GLY-323; TYR-346 AND VAL-356.
[30]	"Mutation p.Leu354Pro in EDA causes severe hypohidrotic ectodermal dysplasia in a Chinese family." Liu Y., Yu X., Wang L., Li C., Archacki S., Huang C., Liu J.Y., Wang Q., Liu M., Tang Z. Gene 491:246-250(2012) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT XHED PRO-354.
[31]	"A new mutation in EDA gene in X-linked hypohidrotic ectodermal dysplasia associated with keratoconus." Piccione M., Serra G., Sanfilippo C., Andreucci E., Sani I., Corsello G. Minerva Pediatr. 64:59-64(2012) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT XHED ARG-319.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U59227 Genomic DNA. Translation: AAC50678.1.
U59228 mRNA. Translation: AAC50679.1.
AH006445 Genomic DNA. Translation: AAC36303.1.
AF060999 mRNA. Translation: AAC36302.1.
AF040628 mRNA. Translation: AAC77363.1.
AF061189 mRNA. Translation: AAC77371.1.
AF061190 mRNA. Translation: AAC77372.1. Sequence problems.
AF061191 mRNA. Translation: AAC77373.1.
AF061192 mRNA. Translation: AAC77374.1.
AF061193 mRNA. Translation: AAC77375.1.
AF061194 mRNA. Translation: AAC77376.1.
AL158069, AL450449 Genomic DNA. Translation: CAI41611.1. Sequence problems.
AL158069, AL158141, AL450449 Genomic DNA. Translation: CAI41612.2.
AL158069, AL158141, AL450449 Genomic DNA. Translation: CAM24742.1.
AL158141, AL450449, AL158069 Genomic DNA. Translation: CAI40385.2.
AL158141, AL158069, AL450449 Genomic DNA. Translation: CAM17680.1.
AL450449, AL158069 Genomic DNA. Translation: CAI39805.1. Sequence problems.
AL450449, AL158069, AL158141 Genomic DNA. Translation: CAI39806.2.
AL450449, AL158069, AL158141 Genomic DNA. Translation: CAM14498.1.
BC126143 mRNA. Translation: AAI26144.1.
BC144049 mRNA. Translation: AAI44050.1.
BC144051 mRNA. Translation: AAI44052.1.

IPI

IPI00023765.
IPI00216145.
IPI00216147.
IPI00216148.
IPI00216149.
IPI00216150.
IPI00954278.
IPI00975907.

RefSeq

NP_001005609.1. NM_001005609.1.
NP_001005610.2. NM_001005610.2.
NP_001005612.2. NM_001005612.2.
NP_001005613.1. NM_001005613.2.
NP_001390.1. NM_001399.4.

UniGene

Hs.105407.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1RJ7	X-ray	2.30	A/B/D/E/F/G/H/I/J/K/L/M	233-391	[»]
1RJ8	X-ray	2.23	A/B/D/E/F/G	230-391	[»]

DisProt

DP00460.

ProteinModelPortal

Q92838.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q92838. 1 interaction.

PTM databases

PhosphoSite

Q92838.

Polymorphism databases

DMDM

6166135.

Proteomic databases

PaxDb

Q92838.

PRIDE

Q92838.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000338901; ENSP00000340611; ENSG00000158813.
ENST00000374552; ENSP00000363680; ENSG00000158813.
ENST00000374553; ENSP00000363681; ENSG00000158813.
ENST00000524573; ENSP00000432585; ENSG00000158813.
ENST00000525810; ENSP00000434195; ENSG00000158813.
ENST00000527388; ENSP00000434861; ENSG00000158813.

GeneID

1896.

KEGG

hsa:1896.

UCSC

uc004dxm.1. human.
uc004dxn.1. human.
uc004dxp.1. human.
uc004dxr.3. human.
uc004dxs.3. human.
uc011mpj.2. human.

Organism-specific databases

CTD

1896.

GeneCards

GC0XP068752.

HGNC

HGNC:3157. EDA.

HPA

CAB012644.

MIM

300451. gene.
305100. phenotype.
313500. phenotype.

neXtProt

NX_Q92838.

Orphanet

181. Christ-Siemens-Touraine syndrome.
2227. Hypodontia.

PharmGKB

PA27601.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG82078.

HOVERGEN

HBG005564.

InParanoid

Q92838.

KO

K05480.

OMA

DEKPYSE.

OrthoDB

EOG4Q2DGH.

PhylomeDB

Q92838.

Gene expression databases

ArrayExpress

Q92838.

Bgee

Q92838.

Genevestigator

Q92838.

GermOnline

ENSG00000158813. Homo sapiens.

Family and domain databases

Gene3D

2.60.120.40. 1 hit.

InterPro

IPR008160. Collagen.
IPR006052. TNF.
IPR008983. Tumour_necrosis_fac-like_dom.
[Graphical view]

Pfam

PF01391. Collagen. 1 hit.
PF00229. TNF. 1 hit.
[Graphical view]

SMART

SM00207. TNF. 1 hit.
[Graphical view]

SUPFAM

SSF49842. TNF_like. 1 hit.

PROSITE

PS00251. TNF_1. False negative.
PS50049. TNF_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q92838.

GenomeRNAi

1896.

NextBio

7729.

PMAP-CutDB

Q92838.

SOURCE

Search...

Entry information

Entry name

EDA_HUMAN

Accession

Primary (citable) accession number: Q92838
Secondary accession number(s): A0AUZ2 , A2A337, B7ZLU2, B7ZLU4, O75910, Q5JS00, Q5JUM7, Q9UP77, Q9Y6L0, Q9Y6L1, Q9Y6L2, Q9Y6L3, Q9Y6L4

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	July 15, 1999
Last modified:	May 1, 2013
This is version 137 of the entry and version 2 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.