ID   TNR25_HUMAN             Reviewed;         417 AA.
AC   Q93038; B1ALX2; B1ALX3; B7ZLL7; O00275; O00276; O00277; O00278; O00279;
AC   O00280; O14865; O14866; P78507; P78515; Q17RU4; Q92983; Q93036; Q93037;
AC   Q99722; Q99830; Q99831; Q9BY86; Q9UME0; Q9UME1; Q9UME5;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1997, sequence version 2.
DT   24-JAN-2024, entry version 208.
DE   RecName: Full=Tumor necrosis factor receptor superfamily member 25;
DE   AltName: Full=Apo-3;
DE   AltName: Full=Apoptosis-inducing receptor AIR;
DE   AltName: Full=Apoptosis-mediating receptor DR3;
DE   AltName: Full=Apoptosis-mediating receptor TRAMP;
DE   AltName: Full=Death receptor 3;
DE   AltName: Full=Lymphocyte-associated receptor of death;
DE            Short=LARD;
DE   AltName: Full=Protein WSL;
DE   AltName: Full=Protein WSL-1;
DE   Flags: Precursor;
GN   Name=TNFRSF25; Synonyms=APO3, DDR3, DR3, TNFRSF12, WSL, WSL1;
GN   ORFNames=UNQ455/PRO779;
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] (ISOFORMS 1; 3 AND 4), AND MUTAGENESIS.
RC   TISSUE=Lymphoid tissue;
RX   PubMed=8934525; DOI=10.1038/384372a0;
RA   Kitson J., Raven T., Jiang Y.-P., Goeddel D.V., Giles K.M., Pun K.-T.,
RA   Grinham C.J., Brown R., Farrow S.N.;
RT   "A death-domain-containing receptor that mediates apoptosis.";
RL   Nature 384:372-375(1996).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND FUNCTION.
RC   TISSUE=Umbilical vein endothelial cell;
RX   PubMed=8875942; DOI=10.1126/science.274.5289.990;
RA   Chinnaiyan A.M., O'Rourke K., Yu G.-L., Lyons R.H., Garg M., Duan D.R.,
RA   Xing L., Gentz R., Ni J., Dixit V.M.;
RT   "Signal transduction by DR3, a death domain-containing receptor related to
RT   TNFR-1 and CD95.";
RL   Science 274:990-992(1996).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RA   Degli-Esposti M.A., Din W.S., Cosman D., Smith C.A., Goodwin R.G.;
RL   Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND FUNCTION.
RC   TISSUE=Heart;
RX   PubMed=8994832; DOI=10.1016/s0960-9822(02)70791-4;
RA   Marsters S.A., Sheridan J.P., Donahue C.J., Pitti R.M., Gray C.L.,
RA   Goddard A.D., Bauer K.D., Ashkenazi A.;
RT   "Apo-3, a new member of the tumor necrosis factor receptor family, contains
RT   a death domain and activates apoptosis and NF-kappa-B.";
RL   Curr. Biol. 6:1669-1676(1996).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3; 4; 5; 6; 7; 8; 9 AND 10).
RX   PubMed=9114039; DOI=10.1073/pnas.94.9.4615;
RA   Screaton G.R., Xu X.-N., Olsen A.L., Cowper A.E., Tan R., McMichael A.J.,
RA   Bell J.I.;
RT   "LARD: a new lymphoid-specific death domain containing receptor regulated
RT   by alternative pre-mRNA splicing.";
RL   Proc. Natl. Acad. Sci. U.S.A. 94:4615-4619(1997).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 11 AND 12).
RX   PubMed=9446802; DOI=10.1006/bbrc.1997.7948;
RA   Warzocha K., Ribeiro P., Charlot C., Renard N., Coiffier B., Salles G.;
RT   "A new death receptor 3 isoform: expression in human lymphoid cell lines
RT   and non-Hodgkin's lymphomas.";
RL   Biochem. Biophys. Res. Commun. 242:376-379(1998).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), AND VARIANT GLY-159.
RA   Shiozawa S., Konishi Y., Murayama K., Mukae N., Yamamoto E., Hayashi S.,
RA   Sato M., Shiozawa K., Tsukamoto Y.;
RL   Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases.
RN   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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   [9]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GLN-23; GLY-159 AND
RP   ARG-254.
RG   NIEHS SNPs program;
RL   Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases.
RN   [10]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16710414; DOI=10.1038/nature04727;
RA   Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA   Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA   Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA   Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA   Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA   Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA   Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA   Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA   Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA   Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA   Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA   Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA   Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA   Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA   Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA   Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA   Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA   Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA   McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA   Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA   Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA   Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA   Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA   Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA   White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA   Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA   Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA   Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT   "The DNA sequence and biological annotation of human chromosome 1.";
RL   Nature 441:315-321(2006).
RN   [11]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 10).
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).
RN   [12]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 4-417, AND FUNCTION.
RC   TISSUE=Brain, and Fetal lung;
RX   PubMed=9052839; DOI=10.1016/s1074-7613(00)80244-7;
RA   Bodmer J.-L., Burns K., Schneider P., Hofmann K., Steiner V., Thome M.,
RA   Bornand T., Hahne M., Schroeter M., Wilson A., French L.E., Browning J.L.,
RA   Macdonald H.R., Tschopp J.;
RT   "TRAMP, a novel apoptosis-mediating receptor with sequence homology to
RT   tumor necrosis factor receptor 1 and Fas(Apo-1/CD95).";
RL   Immunity 6:79-88(1997).
RN   [13]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 7-417.
RC   TISSUE=Brain;
RA   Chaudhary P.M., Hood L.E.;
RL   Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases.
RN   [14]
RP   INTERACTION WITH BAG4.
RX   PubMed=9915703; DOI=10.1126/science.283.5401.543;
RA   Jiang Y., Woronicz J.D., Liu W., Goeddel D.V.;
RT   "Prevention of constitutive TNF receptor 1 signaling by silencer of death
RT   domains.";
RL   Science 283:543-546(1999).
RN   [15]
RP   SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
RX   PubMed=14759258; DOI=10.1186/gb-2004-5-2-r8;
RA   Hillman R.T., Green R.E., Brenner S.E.;
RT   "An unappreciated role for RNA surveillance.";
RL   Genome Biol. 5:R8.1-R8.16(2004).
RN   [16]
RP   GLYCOSYLATION AT ARG-352 (MICROBIAL INFECTION), AND MUTAGENESIS OF ARG-250.
RX   PubMed=30979585; DOI=10.1016/j.molcel.2019.03.028;
RA   Ding J., Pan X., Du L., Yao Q., Xue J., Yao H., Wang D.C., Li S., Shao F.;
RT   "Structural and functional insights into host death domains inactivation by
RT   the bacterial arginine GlcNAcyltransferase effector.";
RL   Mol. Cell 74:922-935(2019).
CC   -!- FUNCTION: Receptor for TNFSF12/APO3L/TWEAK. Interacts directly with the
CC       adapter TRADD. Mediates activation of NF-kappa-B and induces apoptosis.
CC       May play a role in regulating lymphocyte homeostasis.
CC       {ECO:0000269|PubMed:8875942, ECO:0000269|PubMed:8994832,
CC       ECO:0000269|PubMed:9052839}.
CC   -!- SUBUNIT: Homodimer. Interacts strongly via the death domains with
CC       TNFRSF1 and TRADD to activate at least two distinct signaling cascades,
CC       apoptosis and NF-kappa-B signaling. Interacts with BAG4.
CC       {ECO:0000269|PubMed:9915703}.
CC   -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane; Single-pass type I
CC       membrane protein.
CC   -!- SUBCELLULAR LOCATION: [Isoform 2]: Cell membrane; Single-pass type I
CC       membrane protein.
CC   -!- SUBCELLULAR LOCATION: [Isoform 9]: Cell membrane; Single-pass type I
CC       membrane protein.
CC   -!- SUBCELLULAR LOCATION: [Isoform 11]: Cell membrane; Single-pass type I
CC       membrane protein.
CC   -!- SUBCELLULAR LOCATION: [Isoform 3]: Secreted.
CC   -!- SUBCELLULAR LOCATION: [Isoform 4]: Secreted.
CC   -!- SUBCELLULAR LOCATION: [Isoform 5]: Secreted.
CC   -!- SUBCELLULAR LOCATION: [Isoform 6]: Secreted.
CC   -!- SUBCELLULAR LOCATION: [Isoform 7]: Secreted.
CC   -!- SUBCELLULAR LOCATION: [Isoform 8]: Secreted.
CC   -!- SUBCELLULAR LOCATION: [Isoform 10]: Secreted.
CC   -!- SUBCELLULAR LOCATION: [Isoform 12]: Secreted.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=12;
CC       Name=1; Synonyms=WSL-1, LARD-1A;
CC         IsoId=Q93038-1; Sequence=Displayed;
CC       Name=2; Synonyms=LARD-1B;
CC         IsoId=Q93038-2; Sequence=VSP_006504;
CC       Name=3; Synonyms=WSL-S1, LARD-3;
CC         IsoId=Q93038-3; Sequence=VSP_006497, VSP_006498;
CC       Name=4; Synonyms=WSL-S2, LARD-2;
CC         IsoId=Q93038-4; Sequence=VSP_006501, VSP_006502;
CC       Name=5; Synonyms=LARD-4, LARD-11;
CC         IsoId=Q93038-5; Sequence=VSP_006495;
CC       Name=6; Synonyms=LARD-5;
CC         IsoId=Q93038-6; Sequence=VSP_006491, VSP_006495;
CC       Name=7; Synonyms=LARD-6;
CC         IsoId=Q93038-7; Sequence=VSP_006491, VSP_006493, VSP_006494;
CC       Name=8; Synonyms=LARD-7;
CC         IsoId=Q93038-8; Sequence=VSP_006492;
CC       Name=9; Synonyms=LARD-8;
CC         IsoId=Q93038-9; Sequence=VSP_006491;
CC       Name=10; Synonyms=LARD-9;
CC         IsoId=Q93038-10; Sequence=VSP_006503;
CC       Name=11; Synonyms=Beta;
CC         IsoId=Q93038-11; Sequence=VSP_006496;
CC       Name=12; Synonyms=Beta soluble;
CC         IsoId=Q93038-12; Sequence=VSP_006499, VSP_006500;
CC   -!- TISSUE SPECIFICITY: Abundantly expressed in thymocytes and lymphocytes.
CC       Detected in lymphocyte-rich tissues such as thymus, colon, intestine,
CC       and spleen. Also found in the prostate.
CC   -!- PTM: (Microbial infection) Glycosylated at Arg-352 by enteropathogenic
CC       E.coli protein NleB1. {ECO:0000305|PubMed:30979585}.
CC   -!- PTM: Glycosylated. {ECO:0000305}.
CC   -!- MISCELLANEOUS: [Isoform 3]: May be produced at very low levels due to a
CC       premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC       decay. {ECO:0000305}.
CC   -!- MISCELLANEOUS: [Isoform 4]: May be produced at very low levels due to a
CC       premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC       decay. {ECO:0000305}.
CC   -!- MISCELLANEOUS: [Isoform 5]: May be produced at very low levels due to a
CC       premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC       decay. {ECO:0000305}.
CC   -!- MISCELLANEOUS: [Isoform 6]: May be produced at very low levels due to a
CC       premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC       decay. {ECO:0000305}.
CC   -!- MISCELLANEOUS: [Isoform 7]: May be produced at very low levels due to a
CC       premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC       decay. {ECO:0000305}.
CC   -!- MISCELLANEOUS: [Isoform 12]: May be produced at very low levels due to
CC       a premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC       decay. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC       URL="http://egp.gs.washington.edu/data/tnfrsf25/";
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DR   EMBL; Y09392; CAA70561.1; -; mRNA.
DR   EMBL; Y09392; CAA70559.1; -; mRNA.
DR   EMBL; Y09392; CAA70560.1; -; mRNA.
DR   EMBL; U72763; AAC50819.1; -; mRNA.
DR   EMBL; U83599; AAB41434.1; -; Genomic_DNA.
DR   EMBL; U83600; AAB41435.1; -; Genomic_DNA.
DR   EMBL; U78029; AAB40918.1; -; mRNA.
DR   EMBL; U74611; AAB39714.1; -; mRNA.
DR   EMBL; U94501; AAC51306.1; -; mRNA.
DR   EMBL; U94504; AAC51309.1; -; mRNA.
DR   EMBL; U94502; AAC51307.1; -; mRNA.
DR   EMBL; U94503; AAC51308.1; -; mRNA.
DR   EMBL; U94505; AAC51310.1; -; mRNA.
DR   EMBL; U94506; AAC51311.1; -; mRNA.
DR   EMBL; U94507; AAC51312.1; -; mRNA.
DR   EMBL; U94508; AAC51313.1; -; mRNA.
DR   EMBL; U94509; AAC51314.1; -; mRNA.
DR   EMBL; U94510; AAC51315.1; -; mRNA.
DR   EMBL; U94512; AAC51316.1; -; mRNA.
DR   EMBL; U83598; AAB41433.1; -; mRNA.
DR   EMBL; AF026070; AAC39556.1; -; mRNA.
DR   EMBL; AF026071; AAB82288.1; -; mRNA.
DR   EMBL; AB051850; BAB40662.1; -; Genomic_DNA.
DR   EMBL; AB051851; BAB40663.1; -; Genomic_DNA.
DR   EMBL; AY358309; AAQ88676.1; -; mRNA.
DR   EMBL; AY254324; AAO63495.1; -; Genomic_DNA.
DR   EMBL; U75380; AAC51192.1; -; mRNA.
DR   EMBL; AL158217; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC117189; AAI17190.1; -; mRNA.
DR   EMBL; BC143886; AAI43887.1; -; mRNA.
DR   EMBL; U75381; AAC51193.1; -; mRNA.
DR   EMBL; U83597; AAB41432.1; -; mRNA.
DR   CCDS; CCDS71.1; -. [Q93038-1]
DR   CCDS; CCDS72.1; -. [Q93038-11]
DR   CCDS; CCDS73.1; -. [Q93038-10]
DR   CCDS; CCDS74.1; -. [Q93038-9]
DR   CCDS; CCDS75.1; -. [Q93038-8]
DR   RefSeq; NP_001034753.1; NM_001039664.1. [Q93038-5]
DR   RefSeq; NP_003781.1; NM_003790.2. [Q93038-1]
DR   RefSeq; NP_683866.1; NM_148965.1. [Q93038-11]
DR   RefSeq; NP_683867.1; NM_148966.1. [Q93038-10]
DR   RefSeq; NP_683868.1; NM_148967.1. [Q93038-9]
DR   RefSeq; NP_683871.1; NM_148970.1. [Q93038-8]
DR   PDB; 5YGP; X-ray; 2.09 A; A/B/C/D=328-415.
DR   PDB; 5YGS; X-ray; 2.69 A; A/B/C/D=328-415.
DR   PDBsum; 5YGP; -.
DR   PDBsum; 5YGS; -.
DR   AlphaFoldDB; Q93038; -.
DR   SMR; Q93038; -.
DR   BioGRID; 114258; 13.
DR   DIP; DIP-59563N; -.
DR   IntAct; Q93038; 2.
DR   STRING; 9606.ENSP00000367013; -.
DR   GlyCosmos; Q93038; 5 sites, 1 glycan.
DR   GlyGen; Q93038; 4 sites, 1 O-linked glycan (2 sites).
DR   iPTMnet; Q93038; -.
DR   BioMuta; TNFRSF25; -.
DR   DMDM; 2501233; -.
DR   MassIVE; Q93038; -.
DR   PaxDb; 9606-ENSP00000367013; -.
DR   PeptideAtlas; Q93038; -.
DR   ProteomicsDB; 75674; -. [Q93038-1]
DR   ProteomicsDB; 75675; -. [Q93038-10]
DR   ProteomicsDB; 75678; -. [Q93038-2]
DR   ProteomicsDB; 75680; -. [Q93038-4]
DR   ProteomicsDB; 75685; -. [Q93038-9]
DR   Antibodypedia; 13011; 796 antibodies from 42 providers.
DR   DNASU; 8718; -.
DR   Ensembl; ENST00000348333.7; ENSP00000314451.3; ENSG00000215788.11. [Q93038-9]
DR   Ensembl; ENST00000351748.7; ENSP00000326762.3; ENSG00000215788.11. [Q93038-8]
DR   Ensembl; ENST00000351959.9; ENSP00000337713.5; ENSG00000215788.11. [Q93038-10]
DR   Ensembl; ENST00000356876.8; ENSP00000349341.3; ENSG00000215788.11. [Q93038-1]
DR   Ensembl; ENST00000377782.7; ENSP00000367013.3; ENSG00000215788.11. [Q93038-11]
DR   Ensembl; ENST00000414040.6; ENSP00000404274.2; ENSG00000215788.11. [Q93038-3]
DR   Ensembl; ENST00000485036.5; ENSP00000431554.1; ENSG00000215788.11. [Q93038-12]
DR   Ensembl; ENST00000502588.5; ENSP00000423121.1; ENSG00000215788.11. [Q93038-6]
DR   Ensembl; ENST00000502730.5; ENSP00000421976.1; ENSG00000215788.11. [Q93038-7]
DR   Ensembl; ENST00000510563.5; ENSP00000424071.1; ENSG00000215788.11. [Q93038-5]
DR   GeneID; 8718; -.
DR   KEGG; hsa:8718; -.
DR   MANE-Select; ENST00000356876.8; ENSP00000349341.3; NM_003790.3; NP_003781.1.
DR   UCSC; uc001ana.4; human. [Q93038-1]
DR   AGR; HGNC:11910; -.
DR   CTD; 8718; -.
DR   DisGeNET; 8718; -.
DR   GeneCards; TNFRSF25; -.
DR   HGNC; HGNC:11910; TNFRSF25.
DR   HPA; ENSG00000215788; Tissue enhanced (brain, lymphoid tissue, pituitary gland).
DR   MIM; 603366; gene.
DR   neXtProt; NX_Q93038; -.
DR   OpenTargets; ENSG00000215788; -.
DR   PharmGKB; PA36603; -.
DR   VEuPathDB; HostDB:ENSG00000215788; -.
DR   eggNOG; ENOG502S19V; Eukaryota.
DR   GeneTree; ENSGT00940000161888; -.
DR   HOGENOM; CLU_053353_0_0_1; -.
DR   InParanoid; Q93038; -.
DR   OMA; GVFWVQV; -.
DR   OrthoDB; 5343799at2759; -.
DR   PhylomeDB; Q93038; -.
DR   TreeFam; TF333916; -.
DR   PathwayCommons; Q93038; -.
DR   Reactome; R-HSA-5669034; TNFs bind their physiological receptors.
DR   SignaLink; Q93038; -.
DR   SIGNOR; Q93038; -.
DR   BioGRID-ORCS; 8718; 12 hits in 1151 CRISPR screens.
DR   ChiTaRS; TNFRSF25; human.
DR   GeneWiki; TNFRSF25; -.
DR   GenomeRNAi; 8718; -.
DR   Pharos; Q93038; Tbio.
DR   PRO; PR:Q93038; -.
DR   Proteomes; UP000005640; Chromosome 1.
DR   RNAct; Q93038; Protein.
DR   Bgee; ENSG00000215788; Expressed in right hemisphere of cerebellum and 130 other cell types or tissues.
DR   ExpressionAtlas; Q93038; baseline and differential.
DR   GO; GO:0005829; C:cytosol; NAS:UniProtKB.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR   GO; GO:0038023; F:signaling receptor activity; NAS:UniProtKB.
DR   GO; GO:0005031; F:tumor necrosis factor receptor activity; TAS:ProtInc.
DR   GO; GO:0006915; P:apoptotic process; TAS:ProtInc.
DR   GO; GO:0097190; P:apoptotic signaling pathway; TAS:ProtInc.
DR   GO; GO:0007166; P:cell surface receptor signaling pathway; TAS:ProtInc.
DR   GO; GO:0042981; P:regulation of apoptotic process; NAS:UniProtKB.
DR   GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR   CDD; cd08815; Death_TNFRSF25_DR3; 1.
DR   CDD; cd13420; TNFRSF25; 1.
DR   Gene3D; 1.10.533.10; Death Domain, Fas; 1.
DR   Gene3D; 2.10.50.10; Tumor Necrosis Factor Receptor, subunit A, domain 2; 1.
DR   InterPro; IPR011029; DEATH-like_dom_sf.
DR   InterPro; IPR000488; Death_domain.
DR   InterPro; IPR001368; TNFR/NGFR_Cys_rich_reg.
DR   InterPro; IPR022329; TNFR_25.
DR   InterPro; IPR034050; TNFRSF25_N.
DR   PANTHER; PTHR47220; TUMOR NECROSIS FACTOR RECEPTOR SUPERFAMILY MEMBER 25; 1.
DR   PANTHER; PTHR47220:SF1; TUMOR NECROSIS FACTOR RECEPTOR SUPERFAMILY MEMBER 25; 1.
DR   Pfam; PF00531; Death; 1.
DR   Pfam; PF00020; TNFR_c6; 1.
DR   PRINTS; PR01972; TNFACTORR25.
DR   SMART; SM00005; DEATH; 1.
DR   SMART; SM00208; TNFR; 2.
DR   SUPFAM; SSF47986; DEATH domain; 1.
DR   SUPFAM; SSF57586; TNF receptor-like; 2.
DR   PROSITE; PS50017; DEATH_DOMAIN; 1.
DR   PROSITE; PS00652; TNFR_NGFR_1; 2.
DR   PROSITE; PS50050; TNFR_NGFR_2; 1.
DR   Genevisible; Q93038; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Apoptosis; Cell membrane;
KW   Disulfide bond; Glycoprotein; Membrane; Receptor; Reference proteome;
KW   Repeat; Secreted; Signal; Transmembrane; Transmembrane helix.
FT   SIGNAL          1..24
FT                   /evidence="ECO:0000255"
FT   CHAIN           25..417
FT                   /note="Tumor necrosis factor receptor superfamily member
FT                   25"
FT                   /id="PRO_0000034606"
FT   TOPO_DOM        25..199
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        200..220
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        221..417
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   REPEAT          34..71
FT                   /note="TNFR-Cys 1"
FT   REPEAT          72..115
FT                   /note="TNFR-Cys 2"
FT   REPEAT          116..163
FT                   /note="TNFR-Cys 3"
FT   REPEAT          164..192
FT                   /note="TNFR-Cys 4"
FT   DOMAIN          332..413
FT                   /note="Death"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00064"
FT   CARBOHYD        67
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        106
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        352
FT                   /note="(Microbial infection) N-beta-linked (GlcNAc)
FT                   arginine"
FT                   /evidence="ECO:0000305|PubMed:30979585"
FT   DISULFID        35..47
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT   DISULFID        48..61
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT   DISULFID        51..70
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT   DISULFID        73..89
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT   DISULFID        92..107
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT   DISULFID        95..115
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT   DISULFID        117..130
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT   DISULFID        138..155
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT   DISULFID        141..162
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT   DISULFID        165..176
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT   DISULFID        179..191
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT   DISULFID        187..195
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT   VAR_SEQ         54..236
FT                   /note="Missing (in isoform 8)"
FT                   /evidence="ECO:0000303|PubMed:9114039"
FT                   /id="VSP_006492"
FT   VAR_SEQ         54..98
FT                   /note="Missing (in isoform 6, isoform 7 and isoform 9)"
FT                   /evidence="ECO:0000303|PubMed:9114039"
FT                   /id="VSP_006491"
FT   VAR_SEQ         156..171
FT                   /note="SRRDTDCGTCLPGFYE -> HPSVTLGQRPHPSSTS (in isoform 7)"
FT                   /evidence="ECO:0000303|PubMed:9114039"
FT                   /id="VSP_006493"
FT   VAR_SEQ         172..417
FT                   /note="Missing (in isoform 7)"
FT                   /evidence="ECO:0000303|PubMed:9114039"
FT                   /id="VSP_006494"
FT   VAR_SEQ         182..417
FT                   /note="Missing (in isoform 5 and isoform 6)"
FT                   /evidence="ECO:0000303|PubMed:9114039"
FT                   /id="VSP_006495"
FT   VAR_SEQ         182..277
FT                   /note="STLGSCPERCAAVCGWRQMFWVQVLLAGLVVPLLLGATLTYTYRHCWPHKPL
FT                   VTADEAGMEALTPPPATHLSPLDSAHTLLAPPDSSEKICTVQLV -> PPPSLAGAPWG
FT                   AVQSAVPLSVAGGRVGGVLGMRVGELGWTEGRRVRRGATTQHPPAAFSVLGPGAPGWPC
FT                   GPPPAWGHPDLHIPPLLASQAPGYCR (in isoform 12)"
FT                   /evidence="ECO:0000303|PubMed:9446802"
FT                   /id="VSP_006499"
FT   VAR_SEQ         182..218
FT                   /note="STLGSCPERCAAVCGWRQMFWVQVLLAGLVVPLLLGA -> VLGPGAPGWPC
FT                   GPPPAWGHPDLHIPPLLASQAPGYCR (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:8934525,
FT                   ECO:0000303|PubMed:9114039"
FT                   /id="VSP_006497"
FT   VAR_SEQ         182..200
FT                   /note="STLGSCPERCAAVCGWRQM -> PPPSLAGAPWGAVQSAVPLSVAGGRVGV
FT                   (in isoform 11)"
FT                   /evidence="ECO:0000303|PubMed:9446802"
FT                   /id="VSP_006496"
FT   VAR_SEQ         200..253
FT                   /note="MFWVQVLLAGLVVPLLLGATLTYTYRHCWPHKPLVTADEAGMEALTPPPATH
FT                   LS -> SRWCAGNARGRTGMDRGEAGEEGGNHPTPTSCFQCSGSRCSWLALWSPSCLGP
FT                   P (in isoform 4)"
FT                   /evidence="ECO:0000303|PubMed:8934525,
FT                   ECO:0000303|PubMed:9114039"
FT                   /id="VSP_006501"
FT   VAR_SEQ         200..237
FT                   /note="MFWVQVLLAGLVVPLLLGATLTYTYRHCWPHKPLVTAD -> N (in
FT                   isoform 10)"
FT                   /evidence="ECO:0000303|PubMed:15489334,
FT                   ECO:0000303|PubMed:9114039"
FT                   /id="VSP_006503"
FT   VAR_SEQ         219..417
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:8934525,
FT                   ECO:0000303|PubMed:9114039"
FT                   /id="VSP_006498"
FT   VAR_SEQ         236
FT                   /note="A -> AA (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:9114039"
FT                   /id="VSP_006504"
FT   VAR_SEQ         254..417
FT                   /note="Missing (in isoform 4)"
FT                   /evidence="ECO:0000303|PubMed:8934525,
FT                   ECO:0000303|PubMed:9114039"
FT                   /id="VSP_006502"
FT   VAR_SEQ         278..417
FT                   /note="Missing (in isoform 12)"
FT                   /evidence="ECO:0000303|PubMed:9446802"
FT                   /id="VSP_006500"
FT   VARIANT         23
FT                   /note="R -> Q (in dbSNP:rs35771371)"
FT                   /evidence="ECO:0000269|Ref.9"
FT                   /id="VAR_018826"
FT   VARIANT         159
FT                   /note="D -> G (in dbSNP:rs11800462)"
FT                   /evidence="ECO:0000269|Ref.7, ECO:0000269|Ref.9"
FT                   /id="VAR_018827"
FT   VARIANT         254
FT                   /note="P -> R (in dbSNP:rs34529016)"
FT                   /evidence="ECO:0000269|Ref.9"
FT                   /id="VAR_018828"
FT   VARIANT         370
FT                   /note="R -> L (in dbSNP:rs1064590)"
FT                   /id="VAR_011814"
FT   VARIANT         381
FT                   /note="R -> H (in dbSNP:rs1059333)"
FT                   /id="VAR_011815"
FT   MUTAGEN         354
FT                   /note="L->A: Suppresses homodimerization, TNFR1
FT                   interaction, and apoptosis induction."
FT                   /evidence="ECO:0000269|PubMed:8934525"
FT   MUTAGEN         356
FT                   /note="L->A: Suppresses homodimerization, and TNFR1
FT                   interaction."
FT                   /evidence="ECO:0000269|PubMed:8934525"
FT   MUTAGEN         373
FT                   /note="D->A: Suppresses homodimerization, and TNFR1
FT                   interaction."
FT                   /evidence="ECO:0000269|PubMed:8934525"
FT   CONFLICT        4..6
FT                   /note="RPR -> AAA (in Ref. 12; AAC51192/AAC51193)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        60
FT                   /note="P -> H (in Ref. 13; AAB41435)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        167
FT                   /note="P -> L (in Ref. 12 and 13)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        312
FT                   /note="A -> R (in Ref. 1 and 6)"
FT                   /evidence="ECO:0000305"
FT   HELIX           328..333
FT                   /evidence="ECO:0007829|PDB:5YGP"
FT   HELIX           334..338
FT                   /evidence="ECO:0007829|PDB:5YGP"
FT   TURN            339..341
FT                   /evidence="ECO:0007829|PDB:5YGP"
FT   HELIX           347..354
FT                   /evidence="ECO:0007829|PDB:5YGP"
FT   HELIX           359..382
FT                   /evidence="ECO:0007829|PDB:5YGP"
FT   TURN            383..385
FT                   /evidence="ECO:0007829|PDB:5YGP"
FT   HELIX           390..397
FT                   /evidence="ECO:0007829|PDB:5YGP"
FT   HELIX           401..414
FT                   /evidence="ECO:0007829|PDB:5YGP"
SQ   SEQUENCE   417 AA;  45385 MW;  5226319DFDB46706 CRC64;
     MEQRPRGCAA VAAALLLVLL GARAQGGTRS PRCDCAGDFH KKIGLFCCRG CPAGHYLKAP
     CTEPCGNSTC LVCPQDTFLA WENHHNSECA RCQACDEQAS QVALENCSAV ADTRCGCKPG
     WFVECQVSQC VSSSPFYCQP CLDCGALHRH TRLLCSRRDT DCGTCLPGFY EHGDGCVSCP
     TSTLGSCPER CAAVCGWRQM FWVQVLLAGL VVPLLLGATL TYTYRHCWPH KPLVTADEAG
     MEALTPPPAT HLSPLDSAHT LLAPPDSSEK ICTVQLVGNS WTPGYPETQE ALCPQVTWSW
     DQLPSRALGP AAAPTLSPES PAGSPAMMLQ PGPQLYDVMD AVPARRWKEF VRTLGLREAE
     IEAVEVEIGR FRDQQYEMLK RWRQQQPAGL GAVYAALERM GLDGCVEDLR SRLQRGP
//