ID   EDA_MOUSE               Reviewed;         391 AA.
AC   O54693; B7ZMT7; O35705; Q9QWJ8; Q9QZ01; Q9QZ02;
DT   15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT   15-JUL-1999, sequence version 2.
DT   24-JAN-2024, entry version 174.
DE   RecName: Full=Ectodysplasin-A;
DE   AltName: Full=EDA protein homolog;
DE   AltName: Full=Tabby protein;
DE   Contains:
DE     RecName: Full=Ectodysplasin-A, membrane form;
DE   Contains:
DE     RecName: Full=Ectodysplasin-A, secreted form;
GN   Name=Eda; Synonyms=Ed1, Ta;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS TAA; TAB AND TAC).
RC   STRAIN=129/Sv;
RX   PubMed=9371801; DOI=10.1073/pnas.94.24.13069;
RA   Srivastava A.K., Pispa J., Hartung A.J., Du Y., Ezer S., Jenks T.,
RA   Shimada T., Pekkanen M., Mikkola M.L., Ko M.S.H., Thesleff I., Kere J.,
RA   Schlessinger D.;
RT   "The Tabby phenotype is caused by mutation in a mouse homologue of the EDA
RT   gene that reveals novel mouse and human exons and encodes a protein
RT   (ectodysplasin-A) with collagenous domains.";
RL   Proc. Natl. Acad. Sci. U.S.A. 94:13069-13074(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM TAD).
RX   PubMed=9285798; DOI=10.1093/hmg/6.9.1589;
RA   Ferguson B.M., Brockdorff N., Formstone E., Ngyuen T., Kronmiller J.E.,
RA   Zonana J.;
RT   "Cloning of Tabby, the murine homolog of the human EDA gene: evidence for a
RT   membrane-associated protein with a short collagenous domain.";
RL   Hum. Mol. Genet. 6:1589-1594(1997).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS TA-A2 AND TA-A3), FUNCTION,
RP   SUBCELLULAR LOCATION, TOPOLOGY, GLYCOSYLATION, AND SUBUNIT.
RC   TISSUE=Embryo;
RX   PubMed=10534613; DOI=10.1016/s0925-4773(99)00180-x;
RA   Mikkola M.L., Pispa J., Pekkanen M., Paulin L., Nieminen P., Kere J.,
RA   Thesleff I.;
RT   "Ectodysplasin, a protein required for epithelial morphogenesis, is a novel
RT   TNF homologue and promotes cell-matrix adhesion.";
RL   Mech. Dev. 88:133-146(1999).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM TA-A2).
RC   TISSUE=Brain;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
CC   -!- FUNCTION: Cytokine which is involved in epithelial-mesenchymal
CC       signaling during morphogenesis of ectodermal organs. Functions as a
CC       ligand activating the DEATH-domain containing receptors EDAR and EDA2R.
CC       Isoform TAA binds only to the receptor EDAR, while isoform TA-A2 binds
CC       exclusively to the receptor EDA2R (By similarity). May also play a role
CC       in cell adhesion (PubMed:10534613). {ECO:0000250|UniProtKB:Q92838,
CC       ECO:0000269|PubMed:10534613}.
CC   -!- FUNCTION: Isoform TAA binds only to the receptor EDAR, while isoform
CC       TA-A2 binds exclusively to the receptor EDA2R.
CC       {ECO:0000250|UniProtKB:Q92838}.
CC   -!- FUNCTION: Isoform TA-A2 binds exclusively to the receptor EDA2R.
CC       {ECO:0000250|UniProtKB:Q92838}.
CC   -!- SUBUNIT: Homotrimer. The homotrimers may then dimerize and form higher-
CC       order oligomers. {ECO:0000269|PubMed:10534613}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10534613};
CC       Single-pass type II membrane protein {ECO:0000269|PubMed:10534613}.
CC   -!- SUBCELLULAR LOCATION: [Ectodysplasin-A, secreted form]: Secreted
CC       {ECO:0000250|UniProtKB:Q92838}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=6;
CC         Comment=Additional isoforms seem to exist.;
CC       Name=TAA; Synonyms=A1;
CC         IsoId=O54693-1; Sequence=Displayed;
CC       Name=TA-A2;
CC         IsoId=O54693-2; Sequence=VSP_006471;
CC       Name=TA-A3;
CC         IsoId=O54693-3; Sequence=VSP_006469, VSP_006471;
CC       Name=TAB;
CC         IsoId=O54693-4; Sequence=VSP_006466, VSP_006467;
CC       Name=TAC;
CC         IsoId=O54693-5; Sequence=VSP_006465, VSP_006468;
CC       Name=TAD;
CC         IsoId=O54693-6; Sequence=VSP_006470;
CC   -!- PTM: N-glycosylated. {ECO:0000269|PubMed:10534613}.
CC   -!- PTM: Processing by furin produces a secreted form.
CC       {ECO:0000250|UniProtKB:Q92838}.
CC   -!- DISEASE: Note=Defects in Eda are the cause of the tabby phenotype in
CC       mice (the equivalent of anhidrotic ectodermal dysplasia in humans). The
CC       disease is characterized by sparse hair (atrichosis or hypotrichosis),
CC       abnormal or missing teeth and the inability to sweat due to the absence
CC       of sweat glands.
CC   -!- SIMILARITY: Belongs to the tumor necrosis factor family. {ECO:0000305}.
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DR   EMBL; AF016627; AAB95202.1; -; mRNA.
DR   EMBL; AF016628; AAB95203.1; -; mRNA.
DR   EMBL; AF016629; AAB95204.1; -; mRNA.
DR   EMBL; AF016630; AAB95205.1; -; mRNA.
DR   EMBL; AF016631; AAB95206.1; -; mRNA.
DR   EMBL; AF004434; AAB88121.1; -; Genomic_DNA.
DR   EMBL; AF004435; AAB88122.1; -; mRNA.
DR   EMBL; Y13438; CAA73849.1; -; Genomic_DNA.
DR   EMBL; AJ243657; CAB52696.1; -; mRNA.
DR   EMBL; AJ243658; CAB52697.1; -; mRNA.
DR   EMBL; BC144791; AAI44792.1; -; mRNA.
DR   CCDS; CCDS30299.1; -. [O54693-1]
DR   CCDS; CCDS53141.1; -. [O54693-6]
DR   CCDS; CCDS53143.1; -. [O54693-3]
DR   RefSeq; NP_001171408.1; NM_001177937.1. [O54693-2]
DR   RefSeq; NP_001171410.1; NM_001177939.1. [O54693-3]
DR   RefSeq; NP_001171413.1; NM_001177942.1. [O54693-6]
DR   RefSeq; NP_034229.1; NM_010099.2. [O54693-1]
DR   AlphaFoldDB; O54693; -.
DR   SMR; O54693; -.
DR   BioGRID; 199371; 1.
DR   STRING; 10090.ENSMUSP00000109409; -.
DR   GlyCosmos; O54693; 2 sites, No reported glycans.
DR   GlyGen; O54693; 2 sites.
DR   PhosphoSitePlus; O54693; -.
DR   PaxDb; 10090-ENSMUSP00000109409; -.
DR   ProteomicsDB; 277670; -. [O54693-1]
DR   ProteomicsDB; 277671; -. [O54693-2]
DR   ProteomicsDB; 277672; -. [O54693-3]
DR   ProteomicsDB; 277675; -. [O54693-6]
DR   ABCD; O54693; 3 sequenced antibodies.
DR   Antibodypedia; 27342; 607 antibodies from 37 providers.
DR   DNASU; 13607; -.
DR   Ensembl; ENSMUST00000113778.8; ENSMUSP00000109408.2; ENSMUSG00000059327.10. [O54693-3]
DR   Ensembl; ENSMUST00000113779.8; ENSMUSP00000109409.2; ENSMUSG00000059327.10. [O54693-1]
DR   Ensembl; ENSMUST00000113780.8; ENSMUSP00000109410.2; ENSMUSG00000059327.10. [O54693-6]
DR   GeneID; 13607; -.
DR   KEGG; mmu:13607; -.
DR   UCSC; uc009tvo.1; mouse. [O54693-5]
DR   UCSC; uc009tvp.1; mouse. [O54693-4]
DR   UCSC; uc009tvq.1; mouse. [O54693-1]
DR   UCSC; uc009tvs.1; mouse. [O54693-3]
DR   UCSC; uc009tvu.1; mouse. [O54693-2]
DR   UCSC; uc012hmq.1; mouse. [O54693-6]
DR   AGR; MGI:1195272; -.
DR   CTD; 1896; -.
DR   MGI; MGI:1195272; Eda.
DR   VEuPathDB; HostDB:ENSMUSG00000059327; -.
DR   eggNOG; ENOG502QUAV; Eukaryota.
DR   GeneTree; ENSGT00730000111220; -.
DR   HOGENOM; CLU_062448_0_0_1; -.
DR   InParanoid; O54693; -.
DR   OMA; REITHQK; -.
DR   OrthoDB; 5361136at2759; -.
DR   PhylomeDB; O54693; -.
DR   TreeFam; TF332099; -.
DR   Reactome; R-MMU-5669034; TNFs bind their physiological receptors.
DR   BioGRID-ORCS; 13607; 0 hits in 77 CRISPR screens.
DR   ChiTaRS; Eda; mouse.
DR   PRO; PR:O54693; -.
DR   Proteomes; UP000000589; Chromosome X.
DR   RNAct; O54693; Protein.
DR   Bgee; ENSMUSG00000059327; Expressed in dental lamina and 149 other cell types or tissues.
DR   ExpressionAtlas; O54693; baseline and differential.
DR   GO; GO:0045177; C:apical part of cell; IDA:MGI.
DR   GO; GO:0005581; C:collagen trimer; IEA:UniProtKB-KW.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:MGI.
DR   GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR   GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR   GO; GO:0005811; C:lipid droplet; ISO:MGI.
DR   GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR   GO; GO:0038177; F:death receptor agonist activity; ISS:UniProtKB.
DR   GO; GO:0005123; F:death receptor binding; ISS:UniProtKB.
DR   GO; GO:0005102; F:signaling receptor binding; ISO:MGI.
DR   GO; GO:0005164; F:tumor necrosis factor receptor binding; IEA:InterPro.
DR   GO; GO:0048513; P:animal organ development; IBA:GO_Central.
DR   GO; GO:0060070; P:canonical Wnt signaling pathway; IMP:MGI.
DR   GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR   GO; GO:0007160; P:cell-matrix adhesion; IDA:MGI.
DR   GO; GO:0019221; P:cytokine-mediated signaling pathway; ISS:UniProtKB.
DR   GO; GO:0010467; P:gene expression; IMP:MGI.
DR   GO; GO:0001942; P:hair follicle development; IMP:MGI.
DR   GO; GO:0060789; P:hair follicle placode formation; IGI:MGI.
DR   GO; GO:0006955; P:immune response; IEA:InterPro.
DR   GO; GO:0042475; P:odontogenesis of dentin-containing tooth; IMP:MGI.
DR   GO; GO:0043473; P:pigmentation; IMP:MGI.
DR   GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; IMP:MGI.
DR   GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IMP:MGI.
DR   GO; GO:0010628; P:positive regulation of gene expression; IDA:MGI.
DR   GO; GO:1901224; P:positive regulation of non-canonical NF-kappaB signal transduction; IDA:MGI.
DR   GO; GO:1901222; P:regulation of non-canonical NF-kappaB signal transduction; ISS:UniProtKB.
DR   GO; GO:0060662; P:salivary gland cavitation; IDA:MGI.
DR   GO; GO:0043588; P:skin development; IMP:MGI.
DR   GO; GO:0061153; P:trachea gland development; IMP:MGI.
DR   CDD; cd00184; TNF; 1.
DR   Gene3D; 2.60.120.40; -; 1.
DR   InterPro; IPR006052; TNF_dom.
DR   InterPro; IPR008983; Tumour_necrosis_fac-like_dom.
DR   PANTHER; PTHR15151:SF13; ECTODYSPLASIN-A; 1.
DR   PANTHER; PTHR15151; PROTEIN EIGER; 1.
DR   Pfam; PF00229; TNF; 1.
DR   SUPFAM; SSF49842; TNF-like; 1.
DR   PROSITE; PS50049; TNF_2; 1.
DR   Genevisible; O54693; MM.
PE   1: Evidence at protein level;
KW   Alternative splicing; Cell membrane; Cleavage on pair of basic residues;
KW   Collagen; Developmental protein; Differentiation; Glycoprotein; Membrane;
KW   Reference proteome; Secreted; Signal-anchor; Transmembrane;
KW   Transmembrane helix.
FT   CHAIN           1..391
FT                   /note="Ectodysplasin-A, membrane form"
FT                   /id="PRO_0000034540"
FT   CHAIN           160..391
FT                   /note="Ectodysplasin-A, secreted form"
FT                   /evidence="ECO:0000250|UniProtKB:Q92838"
FT                   /id="PRO_0000034541"
FT   TOPO_DOM        1..41
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        42..62
FT                   /note="Helical; Signal-anchor for type II membrane protein"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        63..391
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          180..229
FT                   /note="Collagen-like"
FT   REGION          1..28
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          72..129
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          146..244
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        146..174
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        181..230
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   SITE            159..160
FT                   /note="Cleavage; by furin"
FT                   /evidence="ECO:0000250|UniProtKB:Q92838"
FT   CARBOHYD        313
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        372
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   VAR_SEQ         133..238
FT                   /note="MALLNFFFPDEKAYSEEESRRVRRNKRSKSGEGADGPVKNKKKGKKAGPPGP
FT                   NGPPGPPGPPGPQGPPGIPGIPGIPGTTVMGPPGPPGPPGPQGPPGLQGPSGAA -> V
FT                   SHLGGAAALEAPSPARLGGGLGLRAQGTLPLRAKFQGRSWEWAGVLGRGCPGQVVLGSC
FT                   LGSSRPSPVPWSWKAQPARAAPGEVWAA (in isoform TAC)"
FT                   /evidence="ECO:0000303|PubMed:9371801"
FT                   /id="VSP_006465"
FT   VAR_SEQ         169..177
FT                   /note="PVKNKKKGK -> KSTQVIFFP (in isoform TAB)"
FT                   /evidence="ECO:0000303|PubMed:9371801"
FT                   /id="VSP_006466"
FT   VAR_SEQ         178..391
FT                   /note="Missing (in isoform TAB)"
FT                   /evidence="ECO:0000303|PubMed:9371801"
FT                   /id="VSP_006467"
FT   VAR_SEQ         239..391
FT                   /note="Missing (in isoform TAC)"
FT                   /evidence="ECO:0000303|PubMed:9371801"
FT                   /id="VSP_006468"
FT   VAR_SEQ         265..267
FT                   /note="Missing (in isoform TA-A3)"
FT                   /evidence="ECO:0000303|PubMed:10534613"
FT                   /id="VSP_006469"
FT   VAR_SEQ         295..308
FT                   /note="Missing (in isoform TAD)"
FT                   /evidence="ECO:0000303|PubMed:9285798"
FT                   /id="VSP_006470"
FT   VAR_SEQ         307..308
FT                   /note="Missing (in isoform TA-A2 and isoform TA-A3)"
FT                   /evidence="ECO:0000303|PubMed:10534613,
FT                   ECO:0000303|PubMed:15489334"
FT                   /id="VSP_006471"
FT   CONFLICT        126
FT                   /note="D -> E (in Ref. 2; AAB88121/AAB88122)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   391 AA;  41603 MW;  E5ECEDA5BD60DEFF CRC64;
     MGYPEVERRE PLPAAAPRER GSQGCGCRGA PARAGEGNSC RLFLGFFGLS LALHLLTLCC
     YLELRSELRR ERGTESRLGG PGAPGTSGTL SSPGSLDPVG PITRHLGQPS FQQQPLEPGE
     DPLPPDSQDR HQMALLNFFF PDEKAYSEEE SRRVRRNKRS KSGEGADGPV KNKKKGKKAG
     PPGPNGPPGP PGPPGPQGPP GIPGIPGIPG TTVMGPPGPP GPPGPQGPPG LQGPSGAADK
     TGTRENQPAV VHLQGQGSAI QVKNDLSGGV LNDWSRITMN PKVFKLHPRS GELEVLVDGT
     YFIYSQVEVY YINFTDFASY EVVVDEKPFL QCTRSIETGK TNYNTCYTAG VCLLKARQKI
     AVKMVHADIS INMSKHTTFF GAIRLGEAPA S
//