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Protein

Ectodysplasin-A

Gene

Eda

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Cytokine which is involved in epithelial-mesenchymal signaling during morphogenesis of ectodermal organs. Functions as a ligand activating the DEATH-domain containing receptors EDAR and EDA2R. Isoform TAA binds only to the receptor EDAR, while isoform TA-A2 binds exclusively to the receptor EDA2R (By similarity). May also play a role in cell adhesion (PubMed:10534613).By similarity1 Publication
Isoform TAA binds only to the receptor EDAR, while isoform TA-A2 binds exclusively to the receptor EDA2R.By similarity
Isoform TA-A2 binds exclusively to the receptor EDA2R.By similarity

GO - Molecular functioni

GO - Biological processi

  • cell differentiation Source: UniProtKB-KW
  • cell-matrix adhesion Source: MGI
  • cytokine-mediated signaling pathway Source: UniProtKB
  • gene expression Source: MGI
  • hair follicle development Source: MGI
  • hair follicle placode formation Source: MGI
  • immune response Source: InterPro
  • odontogenesis of dentin-containing tooth Source: MGI
  • pigmentation Source: MGI
  • positive regulation of canonical Wnt signaling pathway Source: MGI
  • positive regulation of gene expression Source: MGI
  • positive regulation of I-kappaB kinase/NF-kappaB signaling Source: MGI
  • positive regulation of NF-kappaB import into nucleus Source: MGI
  • positive regulation of NF-kappaB transcription factor activity Source: Ensembl
  • regulation of NIK/NF-kappaB signaling Source: UniProtKB
  • salivary gland cavitation Source: MGI
  • skin development Source: MGI
  • trachea gland development Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Differentiation

Enzyme and pathway databases

ReactomeiR-MMU-5669034. TNFs bind their physiological receptors.

Names & Taxonomyi

Protein namesi
Recommended name:
Ectodysplasin-A
Alternative name(s):
EDA protein homolog
Tabby protein
Cleaved into the following 2 chains:
Gene namesi
Name:Eda
Synonyms:Ed1, Ta
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome X

Organism-specific databases

MGIiMGI:1195272. Eda.

Subcellular locationi

Ectodysplasin-A, secreted form :
  • Secreted By similarity

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 41CytoplasmicSequence analysisAdd BLAST41
Transmembranei42 – 62Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST21
Topological domaini63 – 391ExtracellularSequence analysisAdd BLAST329

GO - Cellular componenti

  • apical part of cell Source: MGI
  • collagen trimer Source: UniProtKB-KW
  • endoplasmic reticulum membrane Source: MGI
  • extracellular region Source: UniProtKB-SubCell
  • integral component of plasma membrane Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Involvement in diseasei

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.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000345401 – 391Ectodysplasin-A, membrane formAdd BLAST391
ChainiPRO_0000034541160 – 391Ectodysplasin-A, secreted formBy similarityAdd BLAST232

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi313N-linked (GlcNAc...)Sequence analysis1
Glycosylationi372N-linked (GlcNAc...)Sequence analysis1

Post-translational modificationi

N-glycosylated.1 Publication
Processing by furin produces a secreted form.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei159 – 160Cleavage; by furinBy similarity2

Keywords - PTMi

Cleavage on pair of basic residues, Glycoprotein

Proteomic databases

PaxDbiO54693.
PRIDEiO54693.

PTM databases

PhosphoSitePlusiO54693.

Expressioni

Gene expression databases

BgeeiENSMUSG00000059327.
CleanExiMM_EDA.
ExpressionAtlasiO54693. baseline and differential.
GenevisibleiO54693. MM.

Interactioni

Subunit structurei

Homotrimer. The homotrimers may then dimerize and form higher-order oligomers.1 Publication

GO - Molecular functioni

Protein-protein interaction databases

BioGridi199371. 1 interactor.
STRINGi10090.ENSMUSP00000109409.

Structurei

3D structure databases

ProteinModelPortaliO54693.
SMRiO54693.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini180 – 229Collagen-likeAdd BLAST50

Sequence similaritiesi

Belongs to the tumor necrosis factor family.Curated
Contains 1 collagen-like domain.Curated

Keywords - Domaini

Collagen, Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IH6U. Eukaryota.
ENOG41121ZD. LUCA.
GeneTreeiENSGT00730000111220.
HOGENOMiHOG000231318.
HOVERGENiHBG005564.
InParanoidiO54693.
KOiK05480.
OMAiDEKPYSE.
OrthoDBiEOG091G0GBQ.
PhylomeDBiO54693.
TreeFamiTF332099.

Family and domain databases

Gene3Di2.60.120.40. 1 hit.
InterProiIPR006052. TNF_dom.
IPR008983. Tumour_necrosis_fac-like_dom.
[Graphical view]
PfamiPF00229. TNF. 1 hit.
[Graphical view]
SUPFAMiSSF49842. SSF49842. 1 hit.
PROSITEiPS50049. TNF_2. 1 hit.
[Graphical view]

Sequences (6)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 6 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist.
Isoform TAA (identifier: O54693-1) [UniParc]FASTAAdd to basket
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.

« Hide

        10         20         30         40         50
MGYPEVERRE PLPAAAPRER GSQGCGCRGA PARAGEGNSC RLFLGFFGLS
60 70 80 90 100
LALHLLTLCC YLELRSELRR ERGTESRLGG PGAPGTSGTL SSPGSLDPVG
110 120 130 140 150
PITRHLGQPS FQQQPLEPGE DPLPPDSQDR HQMALLNFFF PDEKAYSEEE
160 170 180 190 200
SRRVRRNKRS KSGEGADGPV KNKKKGKKAG PPGPNGPPGP PGPPGPQGPP
210 220 230 240 250
GIPGIPGIPG TTVMGPPGPP GPPGPQGPPG LQGPSGAADK TGTRENQPAV
260 270 280 290 300
VHLQGQGSAI QVKNDLSGGV LNDWSRITMN PKVFKLHPRS GELEVLVDGT
310 320 330 340 350
YFIYSQVEVY YINFTDFASY EVVVDEKPFL QCTRSIETGK TNYNTCYTAG
360 370 380 390
VCLLKARQKI AVKMVHADIS INMSKHTTFF GAIRLGEAPA S
Length:391
Mass (Da):41,603
Last modified:July 15, 1999 - v2
Checksum:iE5ECEDA5BD60DEFF
GO
Isoform TA-A2 (identifier: O54693-2) [UniParc]FASTAAdd to basket

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

Show »
Length:389
Mass (Da):41,375
Checksum:iA07C1D59AE9D82AE
GO
Isoform TA-A3 (identifier: O54693-3) [UniParc]FASTAAdd to basket

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

Show »
Length:386
Mass (Da):41,060
Checksum:i1D7ADCB916E4A3F7
GO
Isoform TAB (identifier: O54693-4) [UniParc]FASTAAdd to basket

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

Show »
Length:177
Mass (Da):19,297
Checksum:iD7728EFFEC6C6BF3
GO
Isoform TAC (identifier: O54693-5) [UniParc]FASTAAdd to basket

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

Show »
Length:220
Mass (Da):23,008
Checksum:iBB7A04B54D3BC159
GO
Isoform TAD (identifier: O54693-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     295-308: Missing.

Show »
Length:377
Mass (Da):39,988
Checksum:iE9FB3C2A253881AD
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti126D → E in AAB88121 (PubMed:9285798).Curated1
Sequence conflicti126D → E in AAB88122 (PubMed:9285798).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_006465133 – 238MALLN…PSGAA → VSHLGGAAALEAPSPARLGG GLGLRAQGTLPLRAKFQGRS WEWAGVLGRGCPGQVVLGSC LGSSRPSPVPWSWKAQPARA APGEVWAA in isoform TAC. 1 PublicationAdd BLAST106
Alternative sequenceiVSP_006466169 – 177PVKNKKKGK → KSTQVIFFP in isoform TAB. 1 Publication9
Alternative sequenceiVSP_006467178 – 391Missing in isoform TAB. 1 PublicationAdd BLAST214
Alternative sequenceiVSP_006468239 – 391Missing in isoform TAC. 1 PublicationAdd BLAST153
Alternative sequenceiVSP_006469265 – 267Missing in isoform TA-A3. 1 Publication3
Alternative sequenceiVSP_006470295 – 308Missing in isoform TAD. 1 PublicationAdd BLAST14
Alternative sequenceiVSP_006471307 – 308Missing in isoform TA-A2 and isoform TA-A3. 2 Publications2

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
BC144791 mRNA. Translation: AAI44792.1.
CCDSiCCDS30299.1. [O54693-1]
CCDS53141.1. [O54693-6]
CCDS53143.1. [O54693-3]
RefSeqiNP_001171408.1. NM_001177937.1. [O54693-2]
NP_001171410.1. NM_001177939.1. [O54693-3]
NP_001171413.1. NM_001177942.1. [O54693-6]
NP_034229.1. NM_010099.2. [O54693-1]
UniGeneiMm.328086.

Genome annotation databases

EnsembliENSMUST00000113778; ENSMUSP00000109408; ENSMUSG00000059327. [O54693-3]
ENSMUST00000113779; ENSMUSP00000109409; ENSMUSG00000059327. [O54693-1]
ENSMUST00000113780; ENSMUSP00000109410; ENSMUSG00000059327. [O54693-6]
GeneIDi13607.
KEGGimmu:13607.
UCSCiuc009tvo.1. mouse. [O54693-5]
uc009tvp.1. mouse. [O54693-4]
uc009tvq.1. mouse. [O54693-1]
uc009tvs.1. mouse. [O54693-3]
uc009tvu.1. mouse. [O54693-2]
uc012hmq.1. mouse. [O54693-6]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
BC144791 mRNA. Translation: AAI44792.1.
CCDSiCCDS30299.1. [O54693-1]
CCDS53141.1. [O54693-6]
CCDS53143.1. [O54693-3]
RefSeqiNP_001171408.1. NM_001177937.1. [O54693-2]
NP_001171410.1. NM_001177939.1. [O54693-3]
NP_001171413.1. NM_001177942.1. [O54693-6]
NP_034229.1. NM_010099.2. [O54693-1]
UniGeneiMm.328086.

3D structure databases

ProteinModelPortaliO54693.
SMRiO54693.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi199371. 1 interactor.
STRINGi10090.ENSMUSP00000109409.

PTM databases

PhosphoSitePlusiO54693.

Proteomic databases

PaxDbiO54693.
PRIDEiO54693.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000113778; ENSMUSP00000109408; ENSMUSG00000059327. [O54693-3]
ENSMUST00000113779; ENSMUSP00000109409; ENSMUSG00000059327. [O54693-1]
ENSMUST00000113780; ENSMUSP00000109410; ENSMUSG00000059327. [O54693-6]
GeneIDi13607.
KEGGimmu:13607.
UCSCiuc009tvo.1. mouse. [O54693-5]
uc009tvp.1. mouse. [O54693-4]
uc009tvq.1. mouse. [O54693-1]
uc009tvs.1. mouse. [O54693-3]
uc009tvu.1. mouse. [O54693-2]
uc012hmq.1. mouse. [O54693-6]

Organism-specific databases

CTDi1896.
MGIiMGI:1195272. Eda.

Phylogenomic databases

eggNOGiENOG410IH6U. Eukaryota.
ENOG41121ZD. LUCA.
GeneTreeiENSGT00730000111220.
HOGENOMiHOG000231318.
HOVERGENiHBG005564.
InParanoidiO54693.
KOiK05480.
OMAiDEKPYSE.
OrthoDBiEOG091G0GBQ.
PhylomeDBiO54693.
TreeFamiTF332099.

Enzyme and pathway databases

ReactomeiR-MMU-5669034. TNFs bind their physiological receptors.

Miscellaneous databases

PROiO54693.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000059327.
CleanExiMM_EDA.
ExpressionAtlasiO54693. baseline and differential.
GenevisibleiO54693. MM.

Family and domain databases

Gene3Di2.60.120.40. 1 hit.
InterProiIPR006052. TNF_dom.
IPR008983. Tumour_necrosis_fac-like_dom.
[Graphical view]
PfamiPF00229. TNF. 1 hit.
[Graphical view]
SUPFAMiSSF49842. SSF49842. 1 hit.
PROSITEiPS50049. TNF_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiEDA_MOUSE
AccessioniPrimary (citable) accession number: O54693
Secondary accession number(s): B7ZMT7
, O35705, Q9QWJ8, Q9QZ01, Q9QZ02
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: July 15, 1999
Last modified: November 2, 2016
This is version 138 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.