Reviewed, UniProtKB/Swiss-Prot O54693 (EDA_MOUSE)

Names and origin

Protein names

Recommended name:
    Ectodysplasin-A
Alternative name(s):
    EDA protein homolog
    Tabby protein
Cleaved into the following 2 chains:
    1- Recommended name:
            Ectodysplasin-A, membrane form
    2- Recommended name:
            Ectodysplasin-A, secreted form

Gene names

Name:	Eda
Synonyms:	Ed1, Ta

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

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 transcript level.

General annotation (Comments)

Function	Involved in epithelial-mesenchymal signaling during morphogenesis of ectodermal organs. Isoform TAA binds only to the receptor EDAR, while isoform TA-A2 binds exclusively to the receptor XEDAR.
Subunit structure	Homotrimer By similarity.
Subcellular location	Cell membrane; Single-pass type II membrane protein By similarity. Ectodysplasin-A, secreted form: Secreted By similarity.
Post-translational modification	N-glycosylated By similarity. Processing by furin produces a secreted form By similarity.
Involvement in disease	Defects in Eda are the cause of the tabby phenotype in mice (the equivalent of anhidrotic ectodermal dysplasia in humans). The disease is characterized by sparse hair (atrichosis or hypotrichosis), abnormal or missing teeth and the inability to sweat due to the absence of sweat glands.
Sequence similarities	Belongs to the tumor necrosis factor family. Contains 1 collagen-like domain.

Ontologies

Keywords
Biological process	Differentiation
Cellular component	Cell membrane Membrane Secreted
Coding sequence diversity	Alternative splicing
Domain	Collagen Signal-anchor Transmembrane
Molecular function	Developmental protein
PTM	Cleavage on pair of basic residues Glycoprotein
Gene Ontology (GO)
Biological process	cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW cell-matrix adhesion Ref.3 Inferred from direct assay. Source: MGI gene expression Inferred from mutant phenotype. Source: MGI hair follicle development Inferred from mutant phenotype. Source: MGI immune response Inferred from electronic annotation. Source: InterPro odontogenesis of dentine-containing tooth Inferred from mutant phenotype. Source: MGI pigmentation Inferred from mutant phenotype. Source: MGI positive regulation of NF-kappaB import into nucleus Inferred from direct assay. Source: MGI salivary gland development Inferred from direct assay. Source: MGI skin development Inferred from mutant phenotype. Source: MGI
Cellular component	apical part of cell Inferred from direct assay. Source: MGI endoplasmic reticulum membrane Ref.3 Inferred from direct assay. Source: MGI extracellular region Inferred from electronic annotation. Source: UniProtKB-KW integral to plasma membrane Ref.3 Inferred from direct assay. Source: MGI
Molecular function	tumor necrosis factor receptor binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 6 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.

Isoform TAA (identifier: O54693-1)

Also known as: A1;

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 TA-A2 (identifier: O54693-2)

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

Isoform TA-A3 (identifier: O54693-3)

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

Isoform TAB (identifier: O54693-4)

The sequence of this isoform differs from the canonical sequence as follows:
     169-177: PVKNKKKGK → KSTQVIFFP
     178-391: Missing.

Isoform TAC (identifier: O54693-5)

The sequence of this isoform differs from the canonical sequence as follows:
     133-238: MALLNFFFPD...PGLQGPSGAA → VSHLGGAAAL...RAAPGEVWAA
     239-391: Missing.

Isoform TAD (identifier: O54693-6)

The sequence of this isoform differs from the canonical sequence as follows:
     295-308: 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_0000034540
	Chain	160 – 391	232	Ectodysplasin-A, secreted form By similarity		PRO_0000034541
Regions
	Topological domain	1 – 41	41	Cytoplasmic Potential
	Transmembrane	42 – 62	21	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 By similarity
Amino acid modifications
	Glycosylation	313	1	N-linked (GlcNAc...) Potential
	Glycosylation	372	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	133 – 238	106	MALLN…PSGAA → VSHLGGAAALEAPSPARLGG GLGLRAQGTLPLRAKFQGRS WEWAGVLGRGCPGQVVLGSC LGSSRPSPVPWSWKAQPARA APGEVWAA in isoform TAC.		VSP_006465
	Alternative sequence	169 – 177	9	PVKNKKKGK → KSTQVIFFP in isoform TAB.		VSP_006466
	Alternative sequence	178 – 391	214	Missing in isoform TAB.		VSP_006467
	Alternative sequence	239 – 391	153	Missing in isoform TAC.		VSP_006468
	Alternative sequence	265 – 267	3	Missing in isoform TA-A3.		VSP_006469
	Alternative sequence	295 – 308	14	Missing in isoform TAD.		VSP_006470
	Alternative sequence	307 – 308	2	Missing in isoform TA-A2 and isoform TA-A3.		VSP_006471
Experimental info
	Sequence conflict	126	1	D → E in AAB88121. Ref.2
	Sequence conflict	126	1	D → E in AAB88122. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform TAA (A1) [UniParc]. Last modified July 15, 1999. Version 2. Checksum: E5ECEDA5BD60DEFF	FASTA	391	41,603
	10 20 30 40 50 60 MGYPEVERRE PLPAAAPRER GSQGCGCRGA PARAGEGNSC RLFLGFFGLS LALHLLTLCC 70 80 90 100 110 120 YLELRSELRR ERGTESRLGG PGAPGTSGTL SSPGSLDPVG PITRHLGQPS FQQQPLEPGE 130 140 150 160 170 180 DPLPPDSQDR HQMALLNFFF PDEKAYSEEE SRRVRRNKRS KSGEGADGPV KNKKKGKKAG 190 200 210 220 230 240 PPGPNGPPGP PGPPGPQGPP GIPGIPGIPG TTVMGPPGPP GPPGPQGPPG LQGPSGAADK 250 260 270 280 290 300 TGTRENQPAV 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 TA-A2. Checksum: A07C1D59AE9D82AE	FASTA	389	41,375
	10 20 30 40 50 60 MGYPEVERRE PLPAAAPRER GSQGCGCRGA PARAGEGNSC RLFLGFFGLS LALHLLTLCC 70 80 90 100 110 120 YLELRSELRR ERGTESRLGG PGAPGTSGTL SSPGSLDPVG PITRHLGQPS FQQQPLEPGE 130 140 150 160 170 180 DPLPPDSQDR HQMALLNFFF PDEKAYSEEE SRRVRRNKRS KSGEGADGPV KNKKKGKKAG 190 200 210 220 230 240 PPGPNGPPGP PGPPGPQGPP GIPGIPGIPG TTVMGPPGPP GPPGPQGPPG LQGPSGAADK 250 260 270 280 290 300 TGTRENQPAV VHLQGQGSAI QVKNDLSGGV LNDWSRITMN PKVFKLHPRS GELEVLVDGT 310 320 330 340 350 360 YFIYSQVYYI NFTDFASYEV VVDEKPFLQC TRSIETGKTN YNTCYTAGVC LLKARQKIAV 370 380 KMVHADISIN MSKHTTFFGA IRLGEAPAS
	Isoform TA-A3. Checksum: 1D7ADCB916E4A3F7	FASTA	386	41,060
	10 20 30 40 50 60 MGYPEVERRE PLPAAAPRER GSQGCGCRGA PARAGEGNSC RLFLGFFGLS LALHLLTLCC 70 80 90 100 110 120 YLELRSELRR ERGTESRLGG PGAPGTSGTL SSPGSLDPVG PITRHLGQPS FQQQPLEPGE 130 140 150 160 170 180 DPLPPDSQDR HQMALLNFFF PDEKAYSEEE SRRVRRNKRS KSGEGADGPV KNKKKGKKAG 190 200 210 220 230 240 PPGPNGPPGP PGPPGPQGPP GIPGIPGIPG TTVMGPPGPP GPPGPQGPPG LQGPSGAADK 250 260 270 280 290 300 TGTRENQPAV VHLQGQGSAI QVKNGGVLND WSRITMNPKV FKLHPRSGEL EVLVDGTYFI 310 320 330 340 350 360 YSQVYYINFT DFASYEVVVD EKPFLQCTRS IETGKTNYNT CYTAGVCLLK ARQKIAVKMV 370 380 HADISINMSK HTTFFGAIRL GEAPAS
	Isoform TAB. Checksum: D7728EFFEC6C6BF3	FASTA	177	19,297
	10 20 30 40 50 60 MGYPEVERRE PLPAAAPRER GSQGCGCRGA PARAGEGNSC RLFLGFFGLS LALHLLTLCC 70 80 90 100 110 120 YLELRSELRR ERGTESRLGG PGAPGTSGTL SSPGSLDPVG PITRHLGQPS FQQQPLEPGE 130 140 150 160 170 DPLPPDSQDR HQMALLNFFF PDEKAYSEEE SRRVRRNKRS KSGEGADGKS TQVIFFP
	Isoform TAC. Checksum: BB7A04B54D3BC159	FASTA	220	23,008
	10 20 30 40 50 60 MGYPEVERRE PLPAAAPRER GSQGCGCRGA PARAGEGNSC RLFLGFFGLS LALHLLTLCC 70 80 90 100 110 120 YLELRSELRR ERGTESRLGG PGAPGTSGTL SSPGSLDPVG PITRHLGQPS FQQQPLEPGE 130 140 150 160 170 180 DPLPPDSQDR HQVSHLGGAA ALEAPSPARL GGGLGLRAQG TLPLRAKFQG RSWEWAGVLG 190 200 210 220 RGCPGQVVLG SCLGSSRPSP VPWSWKAQPA RAAPGEVWAA
	Isoform TAD. Checksum: E9FB3C2A253881AD	FASTA	377	39,988
	10 20 30 40 50 60 MGYPEVERRE PLPAAAPRER GSQGCGCRGA PARAGEGNSC RLFLGFFGLS LALHLLTLCC 70 80 90 100 110 120 YLELRSELRR ERGTESRLGG PGAPGTSGTL SSPGSLDPVG PITRHLGQPS FQQQPLEPGE 130 140 150 160 170 180 DPLPPDSQDR HQMALLNFFF PDEKAYSEEE SRRVRRNKRS KSGEGADGPV KNKKKGKKAG 190 200 210 220 230 240 PPGPNGPPGP PGPPGPQGPP GIPGIPGIPG TTVMGPPGPP GPPGPQGPPG LQGPSGAADK 250 260 270 280 290 300 TGTRENQPAV VHLQGQGSAI QVKNDLSGGV LNDWSRITMN PKVFKLHPRS GELEVYYINF 310 320 330 340 350 360 TDFASYEVVV DEKPFLQCTR SIETGKTNYN TCYTAGVCLL KARQKIAVKM VHADISINMS 370 KHTTFFGAIR LGEAPAS

References

[1]	"The Tabby phenotype is caused by mutation in a mouse homologue of the EDA gene that reveals novel mouse and human exons and encodes a protein (ectodysplasin-A) with collagenous domains." Srivastava A.K., Pispa J., Hartung A.J., Du Y., Ezer S., Jenks T., Shimada T., Pekkanen M., Mikkola M.L., Ko M.S.H., Thesleff I., Kere J., Schlessinger D. Proc. Natl. Acad. Sci. U.S.A. 94:13069-13074(1997) [PubMed: 9371801] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS TAA; TAB AND TAC). Strain: 129/Sv.
[2]	"Cloning of Tabby, the murine homolog of the human EDA gene: evidence for a membrane-associated protein with a short collagenous domain." Ferguson B.M., Brockdorff N., Formstone E., Ngyuen T., Kronmiller J.E., Zonana J. Hum. Mol. Genet. 6:1589-1594(1997) [PubMed: 9285798] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM TAD).
[3]	"Ectodysplasin, a protein required for epithelial morphogenesis, is a novel TNF homologue and promotes cell-matrix adhesion." Mikkola M.L., Pispa J., Pekkanen M., Paulin L., Nieminen P., Kere J., Thesleff I. Mech. Dev. 88:133-146(1999) [PubMed: 10534613] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS TA-A2 AND TA-A3). Tissue: Embryo.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF016627 mRNA. Translation: AAB95202.1. AF016628 mRNA. Translation: AAB95203.1. AF016629 mRNA. Translation: AAB95204.1. AF016630 mRNA. Translation: AAB95205.1. AF016631 mRNA. Translation: AAB95206.1. AF004434 Genomic DNA. Translation: AAB88121.1. AF004435 mRNA. Translation: AAB88122.1. Y13438 Genomic DNA. Translation: CAA73849.1. AJ243657 mRNA. Translation: CAB52696.1. AJ243658 mRNA. Translation: CAB52697.1.
IPI	IPI00117049. IPI00230269. IPI00230270. IPI00230272. IPI00230273. IPI00230274.
RefSeq	NP_034229.1.
UniGene	Mm.328086
3D structure databases
SMR	O54693. Positions 242-390.
ModBase	Search...
Genome annotation databases
Ensembl	ENSMUSG00000059327. Mus musculus. [Contig view]
GeneID	13607.
KEGG	mmu:13607.
Organism-specific databases
MGI	MGI:1195272. Eda.
Phylogenomic databases
HOGENOM	O54693.
HOVERGEN	O54693.
OMA	O54693. TLPPDSQ.
Gene expression databases
ArrayExpress	O54693.
Bgee	O54693.
CleanEx	MM_EDA.
GermOnline	ENSMUSG00000059327. Mus musculus.
Family and domain databases
InterPro	IPR008160. Collagen. IPR006052. TNF_family. IPR008983. Tumour_necrosis_fac-like. [Graphical view]
Gene3D	G3DSA:2.60.120.40. Tumour_necrosis_fac-like. 1 hit.
Pfam	PF01391. Collagen. 1 hit. PF00229. TNF. 1 hit. [Graphical view]
SMART	SM00207. TNF. 1 hit. [Graphical view]
PROSITE	PS00251. TNF_1. False negative. PS50049. TNF_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	284246.
SOURCE	Search...

Entry information

Entry name

EDA_MOUSE

Accession

Primary (citable) accession number: O54693
Secondary accession number(s): O35705 , Q9QWJ8, Q9QZ01, Q9QZ02

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	July 15, 1999
Last modified:	June 16, 2009
This is version 78 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)