EDAR_MOUSE
ID EDAR_MOUSE Reviewed; 448 AA.
AC Q9R187; Q9DC43;
DT 27-MAY-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=Tumor necrosis factor receptor superfamily member EDAR;
DE AltName: Full=Anhidrotic ectodysplasin receptor 1;
DE AltName: Full=Downless;
DE AltName: Full=Ectodermal dysplasia receptor;
DE AltName: Full=Ectodysplasin-A receptor;
DE Flags: Precursor;
GN Name=Edar; Synonyms=Dl;
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 [MRNA], AND VARIANT LYS-379.
RC TISSUE=Embryonic foot, Embryonic skin, and Embryonic tail;
RX PubMed=10431242; DOI=10.1038/11943;
RA Headon D.J., Overbeek P.A.;
RT "Involvement of a novel Tnf receptor homologue in hair follicle
RT induction.";
RL Nat. Genet. 22:370-374(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 205-448.
RC STRAIN=C57BL/6J; TISSUE=Lung;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP INDUCTION BY ACTIVIN A.
RX PubMed=11203701; DOI=10.1006/dbio.2000.9955;
RA Laurikkala J., Mikkola M.L., Mustonen T., Aaberg T., Koppinen P., Pispa J.,
RA Nieminen P., Galceran J., Grosschedl R., Thesleff I.;
RT "TNF signaling via the ligand-receptor pair ectodysplasin and edar controls
RT the function of epithelial signaling centers and is regulated by Wnt and
RT activin during tooth organogenesis.";
RL Dev. Biol. 229:443-455(2001).
CC -!- FUNCTION: Receptor for EDA isoform TAA, but not for EDA isoform TA-2
CC (By similarity). May mediate the activation of NF-kappa-B and JNK. May
CC promote caspase-independent cell death. {ECO:0000250}.
CC -!- SUBUNIT: Binds to EDARADD. Associates with TRAF1, TRAF2, TRAF3 and NIK.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass type I
CC membrane protein {ECO:0000305}.
CC -!- DEVELOPMENTAL STAGE: Transcripts are not detectable in the branchial
CC arch epithelium before morphological tooth formation (10 dpc), but are
CC highly expressed during the initiation of tooth development (11 dpc).
CC Starting 12 dpc, expression is high and limited to the budding cells,
CC and remains high in the fully developed enamel knot at 14 dpc, whereas
CC all other dental cells were completely negative. During 15 dpc the
CC enamel knot disappears largely through apoptosis, and no transcripts
CC were detected in the tooth germs of newborns. In skin, uniformly
CC distributed in the basal cells of the epidermis before follicle
CC initiation. Expression becomes focally elevated before placodes become
CC distinguishable. By 17 dpc transcripts are almost exclusively confined
CC to maturing follicles and the recently initiated placodes.
CC -!- INDUCTION: By activin A in 12 dpc dental epithelium.
CC {ECO:0000269|PubMed:11203701}.
CC -!- DISEASE: Note=Defects in Edar are a cause of the downless 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 -!- SEQUENCE CAUTION:
CC Sequence=BAB23385.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF160502; AAD50425.1; -; mRNA.
DR EMBL; AK004576; BAB23385.1; ALT_INIT; mRNA.
DR CCDS; CCDS23862.1; -.
DR RefSeq; NP_034230.1; NM_010100.3.
DR AlphaFoldDB; Q9R187; -.
DR STRING; 10090.ENSMUSP00000003312; -.
DR GlyGen; Q9R187; 1 site.
DR iPTMnet; Q9R187; -.
DR PhosphoSitePlus; Q9R187; -.
DR PaxDb; Q9R187; -.
DR PRIDE; Q9R187; -.
DR ProteomicsDB; 275437; -.
DR ABCD; Q9R187; 14 sequenced antibodies.
DR Antibodypedia; 33144; 335 antibodies from 33 providers.
DR DNASU; 13608; -.
DR Ensembl; ENSMUST00000003312; ENSMUSP00000003312; ENSMUSG00000003227.
DR GeneID; 13608; -.
DR KEGG; mmu:13608; -.
DR UCSC; uc007fdh.2; mouse.
DR CTD; 10913; -.
DR MGI; MGI:1343498; Edar.
DR VEuPathDB; HostDB:ENSMUSG00000003227; -.
DR eggNOG; ENOG502QRV5; Eukaryota.
DR GeneTree; ENSGT00940000153259; -.
DR HOGENOM; CLU_039634_0_0_1; -.
DR InParanoid; Q9R187; -.
DR OMA; CGENEYH; -.
DR OrthoDB; 672843at2759; -.
DR PhylomeDB; Q9R187; -.
DR TreeFam; TF331385; -.
DR Reactome; R-MMU-5669034; TNFs bind their physiological receptors.
DR BioGRID-ORCS; 13608; 0 hits in 73 CRISPR screens.
DR ChiTaRS; Edar; mouse.
DR PRO; PR:Q9R187; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q9R187; protein.
DR Bgee; ENSMUSG00000003227; Expressed in prostate bud and 73 other tissues.
DR Genevisible; Q9R187; MM.
DR GO; GO:0045177; C:apical part of cell; IDA:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0038023; F:signaling receptor activity; IBA:GO_Central.
DR GO; GO:0004888; F:transmembrane signaling receptor activity; ISO:MGI.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0001942; P:hair follicle development; IMP:MGI.
DR GO; GO:0042475; P:odontogenesis of dentin-containing tooth; IMP:MGI.
DR GO; GO:0043473; P:pigmentation; 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; IBA:GO_Central.
DR GO; GO:0046330; P:positive regulation of JNK cascade; IBA:GO_Central.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; IDA:MGI.
DR GO; GO:0060662; P:salivary gland cavitation; IDA:MGI.
DR CDD; cd13421; TNFRSF_EDAR; 1.
DR Gene3D; 1.10.533.10; -; 1.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR034052; EDAR_N.
DR SUPFAM; SSF47986; SSF47986; 1.
PE 1: Evidence at protein level;
KW Apoptosis; Developmental protein; Differentiation; Disease variant;
KW Disulfide bond; Glycoprotein; Membrane; Receptor; Reference proteome;
KW Repeat; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..26
FT /evidence="ECO:0000255"
FT CHAIN 27..448
FT /note="Tumor necrosis factor receptor superfamily member
FT EDAR"
FT /id="PRO_0000034609"
FT TOPO_DOM 27..187
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 188..208
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 209..448
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 30..71
FT /note="TNFR-Cys 1"
FT REPEAT 73..113
FT /note="TNFR-Cys 2"
FT REPEAT 115..150
FT /note="TNFR-Cys 3"
FT DOMAIN 358..431
FT /note="Death"
FT REGION 220..297
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 252..280
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 38
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 31..44
FT /evidence="ECO:0000250"
FT DISULFID 47..60
FT /evidence="ECO:0000250"
FT DISULFID 50..71
FT /evidence="ECO:0000250"
FT DISULFID 74..87
FT /evidence="ECO:0000250"
FT DISULFID 93..113
FT /evidence="ECO:0000250"
FT DISULFID 135..148
FT /evidence="ECO:0000255"
FT VARIANT 379
FT /note="E -> K (in recessive downless Jackson)"
FT /evidence="ECO:0000269|PubMed:10431242"
SQ SEQUENCE 448 AA; 48434 MW; FCCAF38F3D6BB971 CRC64;
MAHVGDCKWM SWLPVLVVSL MCSAKAEDSN CGENEYHNQT TGLCQQCPPC RPGEEPYMSC
GYGTKDDDYG CVPCPAEKFS KGGYQICRRH KDCEGFFRAT VLTPGDMEND AECGPCLPGY
YMLENRPRNI YGMVCYSCLL APPNTKECVG ATSGVSAHSS STSGGSTLSP FQHAHKELSG
QGHLATALII AMSTIFIMAI AIVLIIMFYI MKTKPSAPAC CSSPPGKSAE APANTHEEKK
EAPDSVVTFP ENGEFQKLTA TPTKTPKSEN DASSENEQLL SRSVDSDEEP APDKQGSPEL
CLLSLVHLAR EKSVTSNKSA GIQSRRKKIL DVYANVCGVV EGLSPTELPF DCLEKTSRML
SSTYNSEKAV VKTWRHLAES FGLKRDEIGG MTDGMQLFDR ISTAGYSIPE LLTKLVQIER
LDAVESLCAD ILEWAGVVPP ASPPPAAS
