ID   WGN_DROME               Reviewed;         343 AA.
AC   Q9VWS4; Q7Z1X1;
DT   09-DEC-2015, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2002, sequence version 2.
DT   04-NOV-2026, entry version 167.
DE   RecName: Full=Tumor necrosis factor receptor superfamily member wgn {ECO:0000303|PubMed:12084706};
DE   AltName: Full=Protein wengen {ECO:0000312|FlyBase:FBgn0030941};
DE   Flags: Precursor;
GN   Name=wgn {ECO:0000312|FlyBase:FBgn0030941};
GN   Synonyms=Vader {ECO:0000312|EMBL:AAM48414.1};
GN   ORFNames=CG6531 {ECO:0000312|FlyBase:FBgn0030941};
OS   Drosophila melanogaster (Fruit fly).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Altocrustacea; Allotriocarida;
OC   Hexapoda; Insecta; Pterygota; Neoptera; Eumetabola; Endopterygota;
OC   Aparaglossata; Panorpida; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC   Drosophilidae; Drosophila; Sophophora.
OX   NCBI_TaxID=7227 {ECO:0000312|Proteomes:UP000000803};
RN   [1] {ECO:0000312|EMBL:BAC01264.1}
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH EGR, SUBCELLULAR
RP   LOCATION, AND DEVELOPMENTAL STAGE.
RX   PubMed=12084706; DOI=10.1074/jbc.c200324200;
RA   Kanda H., Igaki T., Kanuka H., Yagi T., Miura M.;
RT   "Wengen, a member of the Drosophila tumor necrosis factor receptor
RT   superfamily, is required for Eiger signaling.";
RL   J. Biol. Chem. 277:28372-28375(2002).
RN   [2] {ECO:0000312|Proteomes:UP000000803}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
RX   PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA   Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA   Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA   George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA   Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA   Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA   Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA   An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA   Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA   Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA   Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA   Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA   Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA   Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA   Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA   Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA   Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA   Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA   Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA   Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA   Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA   Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA   McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA   Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA   Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA   Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA   Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA   Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA   Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA   Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA   Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA   Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA   Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA   Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA   Venter J.C.;
RT   "The genome sequence of Drosophila melanogaster.";
RL   Science 287:2185-2195(2000).
RN   [3] {ECO:0000312|Proteomes:UP000000803}
RP   GENOME REANNOTATION.
RC   STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
RX   PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA   Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA   Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA   Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA   Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA   Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA   Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT   "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT   review.";
RL   Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN   [4] {ECO:0000312|EMBL:AAM48414.1}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Berkeley {ECO:0000312|EMBL:AAM48414.1};
RC   TISSUE=Embryo {ECO:0000312|EMBL:AAM48414.1};
RX   PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA   Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA   Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA   Celniker S.E.;
RT   "A Drosophila full-length cDNA resource.";
RL   Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN   [5] {ECO:0000312|EMBL:AAM66764.1}
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 14-343, FUNCTION, INTERACTION WITH TRAF6, AND
RP   DEVELOPMENTAL STAGE.
RX   PubMed=12894227; DOI=10.1038/sj.onc.1206715;
RA   Kauppila S., Maaty W.S., Chen P., Tomar R.S., Eby M.T., Chapo J., Chew S.,
RA   Rathore N., Zachariah S., Sinha S.K., Abrams J.M., Chaudhary P.M.;
RT   "Eiger and its receptor, Wengen, comprise a TNF-like system in
RT   Drosophila.";
RL   Oncogene 22:4860-4867(2003).
RN   [6] {ECO:0000305}
RP   FUNCTION.
RX   PubMed=19289090; DOI=10.1016/j.devcel.2009.01.002;
RA   Igaki T., Pastor-Pareja J.C., Aonuma H., Miura M., Xu T.;
RT   "Intrinsic tumor suppression and epithelial maintenance by endocytic
RT   activation of Eiger/TNF signaling in Drosophila.";
RL   Dev. Cell 16:458-465(2009).
RN   [7] {ECO:0000305}
RP   FUNCTION.
RX   PubMed=19375319; DOI=10.1016/j.cub.2009.03.062;
RA   Babcock D.T., Landry C., Galko M.J.;
RT   "Cytokine signaling mediates UV-induced nociceptive sensitization in
RT   Drosophila larvae.";
RL   Curr. Biol. 19:799-806(2009).
RN   [8] {ECO:0000305}
RP   FUNCTION, INTERACTION WITH MOE, AND DEVELOPMENTAL STAGE.
RX   PubMed=23544124; DOI=10.1371/journal.pone.0060091;
RA   Ruan W., Unsain N., Desbarats J., Fon E.A., Barker P.A.;
RT   "Wengen, the sole tumour necrosis factor receptor in Drosophila,
RT   collaborates with moesin to control photoreceptor axon targeting during
RT   development.";
RL   PLoS ONE 8:E60091-E60091(2013).
RN   [9]
RP   FUNCTION, INTERACTION WITH EGR, AND SUBCELLULAR LOCATION.
RX   PubMed=33824334; DOI=10.1038/s41467-021-22080-9;
RA   Palmerini V., Monzani S., Laurichesse Q., Loudhaief R., Mari S.,
RA   Cecatiello V., Olieric V., Pasqualato S., Colombani J., Andersen D.S.,
RA   Mapelli M.;
RT   "Drosophila TNFRs Grindelwald and Wengen bind Eiger with different
RT   affinities and promote distinct cellular functions.";
RL   Nat. Commun. 12:2070-2070(2021).
RN   [10]
RP   TISSUE SPECIFICITY, INDUCTION BY BACTERIAL INFECTION, AND DISRUPTION
RP   PHENOTYPE.
RX   PubMed=38944657; DOI=10.1038/s41467-024-49786-w;
RA   Zhang P., Pronovost S.M., Marchetti M., Zhang C., Kang X., Kandelouei T.,
RA   Li C., Edgar B.A.;
RT   "Inter-cell type interactions that control JNK signaling in the Drosophila
RT   intestine.";
RL   Nat. Commun. 15:5493-5493(2024).
CC   -!- FUNCTION: Receptor for egr (PubMed:12084706, PubMed:12894227,
CC       PubMed:33824334). Involved in induction of apoptosis by triggering JNK
CC       signaling (PubMed:12894227). Mediates the tumor suppressor activity of
CC       egr which eliminates oncogenic cells from epithelia, thereby
CC       maintaining epithelial integrity (PubMed:19289090). Following UV-
CC       induced epidermal damage, binds to egr released from apoptotic
CC       epidermal cells and plays a role in development of thermal allodynia, a
CC       responsiveness to subthreshold thermal stimuli which are not normally
CC       perceived as noxious (PubMed:19375319). Together with Moe, involved in
CC       control of axon targeting of R8 and R2-R5 photoreceptors, independent
CC       of egr (PubMed:23544124). {ECO:0000269|PubMed:12084706,
CC       ECO:0000269|PubMed:12894227, ECO:0000269|PubMed:19289090,
CC       ECO:0000269|PubMed:19375319, ECO:0000269|PubMed:23544124,
CC       ECO:0000269|PubMed:33824334}.
CC   -!- SUBUNIT: Monomer (PubMed:33824334). Interacts (via extracellular
CC       cystein-rich domain) with egr (via secreted TNF-homology soluble form);
CC       forms heterohexamers when 3 copies associate with egr trimers
CC       (PubMed:12084706, PubMed:33824334). Interacts with Traf6
CC       (PubMed:12894227). Interacts with Moe (PubMed:23544124).
CC       {ECO:0000269|PubMed:12084706, ECO:0000269|PubMed:12894227,
CC       ECO:0000269|PubMed:23544124, ECO:0000269|PubMed:33824334}.
CC   -!- INTERACTION:
CC       Q9VWS4; Q8MUJ1: egr; NbExp=3; IntAct=EBI-161953, EBI-108054;
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12084706};
CC       Single-pass type I membrane protein {ECO:0000305}. Cytoplasmic vesicle
CC       membrane {ECO:0000269|PubMed:33824334}; Single-pass type I membrane
CC       protein {ECO:0000305}.
CC   -!- TISSUE SPECIFICITY: Expressed in the adult midgut; under normal
CC       conditions expressed at higher levels than the other TNF receptor grnd.
CC       {ECO:0000269|PubMed:12894227, ECO:0000269|PubMed:23544124,
CC       ECO:0000269|PubMed:38944657}.
CC   -!- DEVELOPMENTAL STAGE: Present at all stages of development with
CC       expression detected in embryo, larva, pupa and adult (PubMed:12084706).
CC       In third instar larvae, detected in photoreceptor neurons, including R8
CC       photoreceptors, and also in adult head (at protein level)
CC       (PubMed:23544124). Expression appears to be very low or undetectable in
CC       pregastrulating embryos. During gastrulation, detected in the inner
CC       layer of embryonic tissue corresponding to the presumptive mesoderm. At
CC       germ band extended stages, continues to accumulate in the mesodermal
CC       segments of the embryo. In later-staged embryos (stages 15/16),
CC       detected in subsets of cells within the condensing nerve cord
CC       (PubMed:12894227). {ECO:0000269|PubMed:12084706}.
CC   -!- INDUCTION: Down-regulated by bacterial infection in the gut.
CC       {ECO:0000269|PubMed:38944657}.
CC   -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown in gut progenitor cells,
CC       enterocytes or cells of the enteroblast-enterocyte lineage does not
CC       affect stress-induced intestinal stem cell proliferation.
CC   -!- MISCELLANEOUS: 'wengen' is named after a village at the foot of the
CC       Eiger mountain after which the TNF gene egr is named.
CC       {ECO:0000303|PubMed:12084706}.
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DR   EMBL; AB085747; BAC01264.1; -; mRNA.
DR   EMBL; AE014298; AAF48864.2; -; Genomic_DNA.
DR   EMBL; AY118385; AAM48414.1; -; mRNA.
DR   EMBL; AY115552; AAM66764.1; -; mRNA.
DR   RefSeq; NP_728186.1; NM_167626.2.
DR   AlphaFoldDB; Q9VWS4; -.
DR   FunCoup; Q9VWS4; 164.
DR   IntAct; Q9VWS4; 2.
DR   STRING; 7227.FBpp0074388; -.
DR   PaxDb; 7227-FBpp0074388; -.
DR   PeptideAtlas; Q9VWS4; -.
DR   DNASU; 32849; -.
DR   EnsemblMetazoa; FBtr0074617; FBpp0074388; FBgn0030941.
DR   GeneID; 32849; -.
DR   KEGG; dme:Dmel_CG6531; -.
DR   UCSC; CG6531-RA; d. melanogaster.
DR   AGR; FB:FBgn0030941; -.
DR   CTD; 32849; -.
DR   FlyBase; FBgn0030941; wgn.
DR   VEuPathDB; VectorBase:FBgn0030941; -.
DR   eggNOG; ENOG502SCIN; Eukaryota.
DR   HOGENOM; CLU_069708_0_0_1; -.
DR   InParanoid; Q9VWS4; -.
DR   OMA; AAWVLDW; -.
DR   OrthoDB; 6126731at2759; -.
DR   PhylomeDB; Q9VWS4; -.
DR   BioGRID-ORCS; 32849; 0 hits in 1 CRISPR screen.
DR   GenomeRNAi; 32849; -.
DR   PRO; PR:Q9VWS4; -.
DR   Proteomes; UP000000803; Chromosome X.
DR   Bgee; FBgn0030941; Expressed in crop (Drosophila) and 109 other cell types or tissues.
DR   ExpressionAtlas; Q9VWS4; baseline and differential.
DR   GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR   GO; GO:0030659; C:cytoplasmic vesicle membrane; EXP:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; IDA:FlyBase.
DR   GO; GO:0005031; F:tumor necrosis factor receptor activity; IDA:FlyBase.
DR   GO; GO:0006915; P:apoptotic process; IDA:UniProtKB.
DR   GO; GO:1900074; P:negative regulation of neuromuscular synaptic transmission; IGI:FlyBase.
DR   GO; GO:0070050; P:neuron cellular homeostasis; IGI:FlyBase.
DR   GO; GO:0072499; P:photoreceptor cell axon guidance; IMP:FlyBase.
DR   GO; GO:1904801; P:positive regulation of neuron remodeling; IGI:FlyBase.
DR   GO; GO:0043068; P:positive regulation of programmed cell death; IGI:FlyBase.
DR   GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IGI:FlyBase.
DR   Gene3D; 2.10.50.10; Tumor Necrosis Factor Receptor, subunit A, domain 2; 1.
DR   InterPro; IPR001368; TNFR/NGFR_Cys_rich_reg.
DR   Pfam; PF00020; TNFR_c6; 1.
DR   SMART; SM00208; TNFR; 1.
DR   PROSITE; PS50050; TNFR_NGFR_2; 1.
PE   1: Evidence at protein level;
KW   Apoptosis; Cell membrane; Coiled coil; Cytoplasmic vesicle; Disulfide bond;
KW   Membrane; Neurogenesis; Receptor; Reference proteome; Signal;
KW   Transmembrane; Transmembrane helix.
FT   SIGNAL          1..76
FT                   /evidence="ECO:0000255"
FT   CHAIN           77..343
FT                   /note="Tumor necrosis factor receptor superfamily member
FT                   wgn"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000434983"
FT   TOPO_DOM        77..201
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        202..222
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        223..343
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   REPEAT          99..137
FT                   /note="TNFR-Cys"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT   REGION          1..44
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          74..96
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          225..257
FT                   /evidence="ECO:0000255"
FT   COMPBIAS        13..24
FT                   /note="Low complexity"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        29..39
FT                   /note="Basic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   DISULFID        100..113
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT   DISULFID        116..129
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT   DISULFID        119..137
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
SQ   SEQUENCE   343 AA;  37829 MW;  BD5E6F5318A82170 CRC64;
     MMPPRLPGGH GGAMRSRSSS SGHHLNTTFH KRRRRRQQHH IGGSHISISH GSYLALLLLS
     TTCSLVATSA SSSSSAANTD IAPPDPPPVS QVSIASSSPC APQHWWDSQR DRCTPCTRCQ
     GEMIPLRPCQ LHTDTICGSI YDLKIDWVVL AKTEPNWKER RKSSEYEHFE HNAPLQHLTH
     EQLQQLHEEA AAAWVLDWQT GVLYVAVLTC LVFFSVAACI LIHHMRQWRR MERRLDQDVE
     ELSTKLMAKL AEVQSLDGGT FFIGNADALR GLPASAATTH PATTQSGIFQ PQHVLLPEKR
     GKHQERRILK TLQPGNVYIE ESNAGLGGMG VGLGVRGCSG LKG
//