EDA_MOUSE
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 03-AUG-2022, entry version 166.
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 GlyGen; O54693; 2 sites.
DR PhosphoSitePlus; O54693; -.
DR PaxDb; O54693; -.
DR PRIDE; O54693; -.
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; 560 antibodies from 36 providers.
DR DNASU; 13607; -.
DR Ensembl; ENSMUST00000113778; ENSMUSP00000109408; ENSMUSG00000059327. [O54693-3]
DR Ensembl; ENSMUST00000113779; ENSMUSP00000109409; ENSMUSG00000059327. [O54693-1]
DR Ensembl; ENSMUST00000113780; ENSMUSP00000109410; ENSMUSG00000059327. [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 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 PhylomeDB; O54693; -.
DR TreeFam; TF332099; -.
DR Reactome; R-MMU-5669034; TNFs bind their physiological receptors.
DR BioGRID-ORCS; 13607; 0 hits in 72 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 145 other tissues.
DR ExpressionAtlas; O54693; baseline and differential.
DR Genevisible; O54693; MM.
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:0005887; C:integral component of plasma membrane; IDA:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005811; C:lipid droplet; ISO: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:0048018; F:receptor ligand activity; IBA:GO_Central.
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: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:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IMP:MGI.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISO:MGI.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; IDA:MGI.
DR GO; GO:1901222; P:regulation of NIK/NF-kappaB signaling; 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 Pfam; PF00229; TNF; 1.
DR SUPFAM; SSF49842; SSF49842; 1.
DR PROSITE; PS50049; TNF_2; 1.
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
