TNR27_HUMAN
ID TNR27_HUMAN Reviewed; 297 AA.
AC Q9HAV5; Q5VYX9; Q5VYY0; Q6UWM2; Q8IZA6;
DT 27-MAY-2002, integrated into UniProtKB/Swiss-Prot.
DT 30-NOV-2010, sequence version 2.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Tumor necrosis factor receptor superfamily member 27;
DE AltName: Full=X-linked ectodysplasin-A2 receptor;
DE Short=EDA-A2 receptor;
GN Name=EDA2R; Synonyms=TNFRSF27, XEDAR; ORFNames=UNQ2448/PRO5727/PRO34080;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), MUTAGENESIS OF GLU-256, AND VARIANT
RP ALA-129.
RC TISSUE=Fetal kidney;
RX PubMed=11039935; DOI=10.1126/science.290.5491.523;
RA Yan M., Wang L.-C., Hymowitz S.G., Schilbach S., Lee J., Goddard A.,
RA de Vos A.M., Gao W.-Q., Dixit V.M.;
RT "Two-amino acid molecular switch in an epithelial morphogen that regulates
RT binding to two distinct receptors.";
RL Science 290:523-527(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, AND VARIANT ALA-129.
RX PubMed=12270937; DOI=10.1074/jbc.m207923200;
RA Sinha S.K., Zachariah S., Quinones H.I., Shindo M., Chaudhary P.M.;
RT "Role of TRAF3 and -6 in the activation of the NF-kappa B and JNK pathways
RT by X-linked ectodermal dysplasia receptor.";
RL J. Biol. Chem. 277:44953-44961(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3), AND VARIANT
RP ALA-129.
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ALA-129.
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: Receptor for EDA isoform A2, but not for EDA isoform A1.
CC Mediates the activation of the NF-kappa-B and JNK pathways. Activation
CC seems to be mediated by binding to TRAF3 and TRAF6.
CC {ECO:0000269|PubMed:12270937}.
CC -!- SUBUNIT: Associates with TRAF1, TRAF3 and TRAF6.
CC -!- INTERACTION:
CC Q9HAV5; Q8TD06: AGR3; NbExp=3; IntAct=EBI-526033, EBI-3925742;
CC Q9HAV5; P27449: ATP6V0C; NbExp=3; IntAct=EBI-526033, EBI-721179;
CC Q9HAV5; Q96F15: GIMAP5; NbExp=3; IntAct=EBI-526033, EBI-6166686;
CC Q9HAV5; Q8N5M9: JAGN1; NbExp=3; IntAct=EBI-526033, EBI-10266796;
CC Q9HAV5; Q16617: NKG7; NbExp=3; IntAct=EBI-526033, EBI-3919611;
CC Q9HAV5; P60201-2: PLP1; NbExp=3; IntAct=EBI-526033, EBI-12188331;
CC Q9HAV5; O43765: SGTA; NbExp=3; IntAct=EBI-526033, EBI-347996;
CC Q9HAV5; P0DN84: STRIT1; NbExp=3; IntAct=EBI-526033, EBI-12200293;
CC Q9HAV5; E9PQX1: TMEM262; NbExp=3; IntAct=EBI-526033, EBI-17180389;
CC Q9HAV5; Q13114: TRAF3; NbExp=2; IntAct=EBI-526033, EBI-357631;
CC Q9HAV5; Q9Y4K3: TRAF6; NbExp=2; IntAct=EBI-526033, EBI-359276;
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type III membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9HAV5-1; Sequence=Displayed;
CC Name=2; Synonyms=Long;
CC IsoId=Q9HAV5-2; Sequence=VSP_011568;
CC Name=3;
CC IsoId=Q9HAV5-3; Sequence=VSP_011569;
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DR EMBL; AF298812; AAG28761.1; -; mRNA.
DR EMBL; AY152724; AAN73210.1; -; mRNA.
DR EMBL; AY358735; AAQ89952.1; -; mRNA.
DR EMBL; AY358736; AAQ89953.1; -; mRNA.
DR EMBL; AL353136; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC034919; AAH34919.1; -; mRNA.
DR CCDS; CCDS14386.1; -. [Q9HAV5-1]
DR CCDS; CCDS56603.1; -. [Q9HAV5-2]
DR RefSeq; NP_001186616.1; NM_001199687.2. [Q9HAV5-1]
DR RefSeq; NP_001229239.1; NM_001242310.1.
DR RefSeq; NP_001311130.1; NM_001324201.1.
DR RefSeq; NP_001311133.1; NM_001324204.1.
DR RefSeq; NP_001311134.1; NM_001324205.1.
DR RefSeq; NP_001311135.1; NM_001324206.1.
DR RefSeq; NP_068555.1; NM_021783.4. [Q9HAV5-1]
DR RefSeq; XP_011529302.1; XM_011531000.1. [Q9HAV5-2]
DR RefSeq; XP_011529303.1; XM_011531001.1. [Q9HAV5-2]
DR AlphaFoldDB; Q9HAV5; -.
DR BioGRID; 121904; 35.
DR IntAct; Q9HAV5; 23.
DR STRING; 9606.ENSP00000379365; -.
DR GlyGen; Q9HAV5; 1 site.
DR iPTMnet; Q9HAV5; -.
DR PhosphoSitePlus; Q9HAV5; -.
DR BioMuta; EDA2R; -.
DR DMDM; 313104030; -.
DR MassIVE; Q9HAV5; -.
DR PeptideAtlas; Q9HAV5; -.
DR PRIDE; Q9HAV5; -.
DR ProteomicsDB; 81446; -. [Q9HAV5-1]
DR ProteomicsDB; 81447; -. [Q9HAV5-2]
DR ProteomicsDB; 81448; -. [Q9HAV5-3]
DR Antibodypedia; 3374; 342 antibodies from 32 providers.
DR DNASU; 60401; -.
DR Ensembl; ENST00000253392.5; ENSP00000253392.5; ENSG00000131080.15. [Q9HAV5-2]
DR Ensembl; ENST00000374719.8; ENSP00000363851.3; ENSG00000131080.15. [Q9HAV5-1]
DR Ensembl; ENST00000396050.5; ENSP00000379365.2; ENSG00000131080.15. [Q9HAV5-2]
DR Ensembl; ENST00000451436.6; ENSP00000415242.3; ENSG00000131080.15. [Q9HAV5-1]
DR GeneID; 60401; -.
DR KEGG; hsa:60401; -.
DR MANE-Select; ENST00000374719.8; ENSP00000363851.3; NM_021783.5; NP_068555.2.
DR UCSC; uc004dwq.4; human. [Q9HAV5-1]
DR CTD; 60401; -.
DR DisGeNET; 60401; -.
DR GeneCards; EDA2R; -.
DR HGNC; HGNC:17756; EDA2R.
DR HPA; ENSG00000131080; Low tissue specificity.
DR MalaCards; EDA2R; -.
DR MIM; 300276; gene.
DR neXtProt; NX_Q9HAV5; -.
DR OpenTargets; ENSG00000131080; -.
DR Orphanet; 181; X-linked hypohidrotic ectodermal dysplasia.
DR PharmGKB; PA134974675; -.
DR VEuPathDB; HostDB:ENSG00000131080; -.
DR eggNOG; ENOG502S069; Eukaryota.
DR GeneTree; ENSGT00940000153259; -.
DR HOGENOM; CLU_041149_0_0_1; -.
DR InParanoid; Q9HAV5; -.
DR OMA; EVQCAFR; -.
DR OrthoDB; 672843at2759; -.
DR PhylomeDB; Q9HAV5; -.
DR TreeFam; TF331385; -.
DR PathwayCommons; Q9HAV5; -.
DR Reactome; R-HSA-5669034; TNFs bind their physiological receptors.
DR SignaLink; Q9HAV5; -.
DR SIGNOR; Q9HAV5; -.
DR BioGRID-ORCS; 60401; 7 hits in 694 CRISPR screens.
DR ChiTaRS; EDA2R; human.
DR GeneWiki; Ectodysplasin_A2_receptor; -.
DR GenomeRNAi; 60401; -.
DR Pharos; Q9HAV5; Tbio.
DR PRO; PR:Q9HAV5; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; Q9HAV5; protein.
DR Bgee; ENSG00000131080; Expressed in stromal cell of endometrium and 110 other tissues.
DR Genevisible; Q9HAV5; HS.
DR GO; GO:0016021; C:integral component of membrane; IC:HGNC-UCL.
DR GO; GO:0005887; C:integral component of plasma membrane; IEA:InterPro.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0038023; F:signaling receptor activity; IDA:HGNC-UCL.
DR GO; GO:0005031; F:tumor necrosis factor receptor activity; NAS:UniProtKB.
DR GO; GO:0010668; P:ectodermal cell differentiation; IC:BHF-UCL.
DR GO; GO:0008544; P:epidermis development; NAS:UniProtKB.
DR GO; GO:0072332; P:intrinsic apoptotic signaling pathway by p53 class mediator; IEA:Ensembl.
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; IDA:HGNC-UCL.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IDA:HGNC-UCL.
DR CDD; cd15838; TNFRSF27; 1.
DR InterPro; IPR001368; TNFR/NGFR_Cys_rich_reg.
DR InterPro; IPR022319; TNFR_27.
DR InterPro; IPR034060; TNFRSF27_N.
DR PANTHER; PTHR12120:SF8; PTHR12120:SF8; 2.
DR Pfam; PF00020; TNFR_c6; 2.
DR PRINTS; PR01973; TNFACTORR27.
DR SMART; SM00208; TNFR; 2.
DR PROSITE; PS00652; TNFR_NGFR_1; 2.
DR PROSITE; PS50050; TNFR_NGFR_2; 2.
PE 1: Evidence at protein level;
KW Alternative splicing; Developmental protein; Differentiation;
KW Disulfide bond; Glycoprotein; Membrane; Receptor; Reference proteome;
KW Repeat; Transmembrane; Transmembrane helix.
FT CHAIN 1..297
FT /note="Tumor necrosis factor receptor superfamily member
FT 27"
FT /id="PRO_0000058938"
FT TOPO_DOM 1..138
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 139..159
FT /note="Helical; Signal-anchor for type III membrane
FT protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 160..297
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 2..41
FT /note="TNFR-Cys 1"
FT REPEAT 43..83
FT /note="TNFR-Cys 2"
FT REPEAT 85..118
FT /note="TNFR-Cys 3"
FT REGION 272..297
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 74
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 3..15
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT DISULFID 18..31
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT DISULFID 21..41
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT DISULFID 44..58
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT DISULFID 61..75
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT DISULFID 64..83
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT DISULFID 86..104
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT DISULFID 107..118
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT VAR_SEQ 172
FT /note="R -> REKLIIFSDPVPASLNLIPEFA (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12270937"
FT /id="VSP_011568"
FT VAR_SEQ 172
FT /note="R -> RVT (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:12975309"
FT /id="VSP_011569"
FT VARIANT 57
FT /note="R -> K (in dbSNP:rs1385699)"
FT /id="VAR_044511"
FT VARIANT 129
FT /note="T -> A (in dbSNP:rs1385698)"
FT /evidence="ECO:0000269|PubMed:11039935,
FT ECO:0000269|PubMed:12270937, ECO:0000269|PubMed:12975309,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_044512"
FT MUTAGEN 256
FT /note="E->R: Abolishes TRAF6 association."
FT /evidence="ECO:0000269|PubMed:11039935"
FT CONFLICT 236
FT /note="M -> V (in Ref. 2; AAN73210)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 297 AA; 32759 MW; 05DBB377DC59350C CRC64;
MDCQENEYWD QWGRCVTCQR CGPGQELSKD CGYGEGGDAY CTACPPRRYK SSWGHHRCQS
CITCAVINRV QKVNCTATSN AVCGDCLPRF YRKTRIGGLQ DQECIPCTKQ TPTSEVQCAF
QLSLVEADTP TVPPQEATLV ALVSSLLVVF TLAFLGLFFL YCKQFFNRHC QRGGLLQFEA
DKTAKEESLF PVPPSKETSA ESQVSENIFQ TQPLNPILED DCSSTSGFPT QESFTMASCT
SESHSHWVHS PIECTELDLQ KFSSSASYTG AETLGGNTVE STGDRLELNV PFEVPSP
