ID TNR1A_HUMAN Reviewed; 455 AA. AC P19438; A8K4X3; B2RDE4; B3KPQ1; B4DQB7; B4E309; B5M0B5; D3DUR1; Q9UCA4; DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1991, sequence version 1. DT 02-SEP-2026, entry version 273. DE RecName: Full=Tumor necrosis factor receptor superfamily member 1A; DE AltName: Full=Tumor necrosis factor receptor 1; DE Short=TNF-R1; DE AltName: Full=Tumor necrosis factor receptor type I; DE Short=TNF-RI; DE Short=TNFR-I; DE AltName: Full=p55; DE AltName: Full=p60; DE AltName: CD_antigen=CD120a; DE Contains: DE RecName: Full=Tumor necrosis factor receptor superfamily member 1A, membrane form; DE Contains: DE RecName: Full=Tumor necrosis factor-binding protein 1; DE Short=TBPI; DE Flags: Precursor; GN Name=TNFRSF1A; Synonyms=TNFAR, TNFR1; 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), AND PROTEIN SEQUENCE OF 30-57 AND RP 252-264. RX PubMed=2158862; DOI=10.1016/0092-8674(90)90815-v; RA Loetscher H., Pan Y.-C.E., Lahm H.-W., Gentz R., Brockhaus M., Tabuchi H., RA Lesslauer W.; RT "Molecular cloning and expression of the human 55 kd tumor necrosis factor RT receptor."; RL Cell 61:351-359(1990). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Placenta; RX PubMed=2158863; DOI=10.1016/0092-8674(90)90816-w; RA Schall T.J., Lewis M., Koller K.J., Lee A., Rice G.C., Wong G.H.W., RA Getanaga T., Granger G.A., Lentz R., Raab H., Kohr W.J., Goeddel D.V.; RT "Molecular cloning and expression of a receptor for human tumor necrosis RT factor."; RL Cell 61:361-370(1990). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=1702293; DOI=10.1089/dna.1990.9.705; RA Himmler A., Maurer-Fogy I., Kroenke M., Scheurich P., Pfizenmaier K., RA Lantz M., Olsson I., Hauptmann R., Stratowa C., Adolf G.R.; RT "Molecular cloning and expression of human and rat tumor necrosis factor RT receptor chain (p60) and its soluble derivative, tumor necrosis factor- RT binding protein."; RL DNA Cell Biol. 9:705-715(1990). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND PROTEIN SEQUENCE OF 41-53; RP 110-124 AND 199-201 (ISOFORM 1). RX PubMed=1698610; DOI=10.1002/j.1460-2075.1990.tb07526.x; RA Nophar Y., Kemper O., Brakebusch C., Engelmann H., Zwang R., Aderka D., RA Holtmann H., Wallach D.; RT "Soluble forms of tumor necrosis factor receptors (TNF-Rs). The cDNA for RT the type I TNF-R, cloned using amino acid sequence data of its soluble RT form, encodes both the cell surface and a soluble form of the receptor."; RL EMBO J. 9:3269-3278(1990). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Placenta; RX PubMed=2170974; DOI=10.1073/pnas.87.19.7380; RA Gray P.W., Barrett K., Chantry D., Turner M., Feldman M.; RT "Cloning of human tumor necrosis factor (TNF) receptor cDNA and expression RT of recombinant soluble TNF-binding protein."; RL Proc. Natl. Acad. Sci. U.S.A. 87:7380-7384(1990). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=1315717; DOI=10.1016/0888-7543(92)90226-i; RA Fuchs P., Strehl S., Dworzak M., Himmler A., Ambros P.F.; RT "Structure of the human TNF receptor 1 (p60) gene (TNFR1) and localization RT to chromosome 12p13."; RL Genomics 13:219-224(1992). RN [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS LEU-75 AND GLN-121. RG SeattleSNPs variation discovery resource; RL Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3). RC TISSUE=Neutrophil, Teratocarcinoma, Tongue, and Uterus; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5). RX PubMed=19906316; DOI=10.1186/1471-2164-10-518; RA Wang P., Yu P., Gao P., Shi T., Ma D.; RT "Discovery of novel human transcript variants by analysis of intronic RT single-block EST with polyadenylation site."; RL BMC Genomics 10:518-518(2009). RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16541075; DOI=10.1038/nature04569; RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., RA Gibbs R.A.; RT "The finished DNA sequence of human chromosome 12."; RL Nature 440:346-351(2006). RN [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [12] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Muscle; 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 [13] RP PROTEIN SEQUENCE OF 41-57 (ISOFORM 1). RC TISSUE=Urine; RX PubMed=8015639; DOI=10.1159/000187851; RA Suzuki J., Tomizawa S., Arai H., Seki Y., Maruyama K., Kuroume T.; RT "Purification of two types of TNF inhibitors in the urine of the patient RT with chronic glomerulonephritis."; RL Nephron 66:386-390(1994). RN [14] RP PROTEIN SEQUENCE OF 41-45 (ISOFORM 1). RX PubMed=2153136; DOI=10.1016/s0021-9258(19)40049-5; RA Engelmann H., Novick D., Wallach D.; RT "Two tumor necrosis factor-binding proteins purified from human urine. RT Evidence for immunological cross-reactivity with cell surface tumor RT necrosis factor receptors."; RL J. Biol. Chem. 265:1531-1536(1990). RN [15] RP INTERACTION WITH MADD. RX PubMed=9115275; DOI=10.1074/jbc.272.18.12069; RA Schievella A.R., Chen J.H., Graham J.R., Lin L.-L.; RT "MADD, a novel death domain protein that interacts with the type 1 tumor RT necrosis factor receptor and activates mitogen-activated protein kinase."; RL J. Biol. Chem. 272:12069-12075(1997). RN [16] RP INTERACTION WITH HCV CORE PROTEIN (MICROBIAL INFECTION). RX PubMed=9557650; DOI=10.1128/jvi.72.5.3691-3697.1998; RA Zhu N., Khoshnan A., Schneider R., Matsumoto M., Dennert G., Ware C.F., RA Lai M.M.C.; RT "Hepatitis C virus core protein binds to the cytoplasmic domain of tumor RT necrosis factor (TNF) receptor 1 and enhances TNF-induced apoptosis."; RL J. Virol. 72:3691-3697(1998). RN [17] RP INTERACTION WITH RIPK1 AND SQSTM1. RX PubMed=10356400; DOI=10.1093/emboj/18.11.3044; RA Sanz L., Sanchez P., Lallena M.-J., Diaz-Meco M.T., Moscat J.; RT "The interaction of p62 with RIP links the atypical PKCs to NF-kappaB RT activation."; RL EMBO J. 18:3044-3053(1999). RN [18] RP INTERACTION WITH FEM1B. RX PubMed=10542291; DOI=10.1074/jbc.274.45.32461; RA Chan S.-L., Tan K.-O., Zhang L., Yee K.S.Y., Ronca F., Chan M.-Y., Yu V.C.; RT "F1Aalpha, a death receptor-binding protein homologous to the RT Caenorhabditis elegans sex-determining protein, FEM-1, is a caspase RT substrate that mediates apoptosis."; RL J. Biol. Chem. 274:32461-32468(1999). RN [19] RP INTERACTION WITH GRB2. RX PubMed=10359574; DOI=10.1084/jem.189.11.1707; RA Hildt E., Oess S.; RT "Identification of Grb2 as a novel binding partner of tumor necrosis factor RT (TNF) receptor I."; RL J. Exp. Med. 189:1707-1714(1999). RN [20] 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 [21] RP INTERACTION WITH BABAM2. RX PubMed=15465831; DOI=10.1074/jbc.m408678200; RA Li Q., Ching A.K.-K., Chan B.C.-L., Chow S.K.-Y., Lim P.-L., Ho T.C.-Y., RA Ip W.-K., Wong C.-K., Lam C.W.-K., Lee K.K.-H., Chan J.Y.-H., Chui Y.-L.; RT "A death receptor-associated anti-apoptotic protein, BRE, inhibits RT mitochondrial apoptotic pathway."; RL J. Biol. Chem. 279:52106-52116(2004). RN [22] RP INTERACTION WITH STAPHYLOCOCCUS AUREUS PROTEIN A (MICROBIAL INFECTION). RX PubMed=15247912; DOI=10.1038/nm1079; RA Gomez M.I., Lee A., Reddy B., Muir A., Soong G., Pitt A., Cheung A., RA Prince A.; RT "Staphylococcus aureus protein A induces airway epithelial inflammatory RT responses by activating TNFR1."; RL Nat. Med. 10:842-848(2004). RN [23] RP INTERACTION WITH STAPHYLOCOCCUS AUREUS PROTEIN A (MICROBIAL INFECTION). RX PubMed=16709567; DOI=10.1074/jbc.m601956200; RA Gomez M.I., O'Seaghdha M., Magargee M., Foster T.J., Prince A.S.; RT "Staphylococcus aureus protein A activates TNFR1 signaling through RT conserved IgG binding domains."; RL J. Biol. Chem. 281:20190-20196(2006). RN [24] RP INTERACTION WITH HHV-5 PROTEIN UL138 (MICROBIAL INFECTION). RX PubMed=21976655; DOI=10.1128/jvi.06005-11; RA Le V.T., Trilling M., Hengel H.; RT "The cytomegaloviral protein pUL138 acts as potentiator of tumor necrosis RT factor (TNF) receptor 1 surface density to enhance ULb'-encoded modulation RT of TNF-alpha signaling."; RL J. Virol. 85:13260-13270(2011). RN [25] RP INVOLVEMENT IN MS5, SUBCELLULAR LOCATION, AND ALTERNATIVE SPLICING (ISOFORM RP 4). RX PubMed=22801493; DOI=10.1038/nature11307; RA Gregory A.P., Dendrou C.A., Attfield K.E., Haghikia A., Xifara D.K., RA Butter F., Poschmann G., Kaur G., Lambert L., Leach O.A., Promel S., RA Punwani D., Felce J.H., Davis S.J., Gold R., Nielsen F.C., Siegel R.M., RA Mann M., Bell J.I., McVean G., Fugger L.; RT "TNF receptor 1 genetic risk mirrors outcome of anti-TNF therapy in RT multiple sclerosis."; RL Nature 488:508-511(2012). RN [26] RP GLYCOSYLATION AT ARG-376 (MICROBIAL INFECTION). RX PubMed=23955153; DOI=10.1038/nature12436; RA Li S., Zhang L., Yao Q., Li L., Dong N., Rong J., Gao W., Ding X., Sun L., RA Chen X., Chen S., Shao F.; RT "Pathogen blocks host death receptor signalling by arginine GlcNAcylation RT of death domains."; RL Nature 501:242-246(2013). RN [27] RP INTERACTION WITH SH3RF2; RIPK1 AND TRADD. RX PubMed=24130170; DOI=10.1093/carcin/bgt338; RA Kim T.W., Kang Y.K., Park Z.Y., Kim Y.H., Hong S.W., Oh S.J., Sohn H.A., RA Yang S.J., Jang Y.J., Lee D.C., Kim S.Y., Yoo H.S., Kim E., Yeom Y.I., RA Park K.C.; RT "SH3RF2 functions as an oncogene by mediating PAK4 protein stability."; RL Carcinogenesis 35:624-634(2014). RN [28] RP INTERACTION WITH PGLYRP1. RX PubMed=26183779; DOI=10.1074/jbc.m115.639732; RA Yashin D.V., Ivanova O.K., Soshnikova N.V., Sheludchenkov A.A., RA Romanova E.A., Dukhanina E.A., Tonevitsky A.G., Gnuchev N.V., Gabibov A.G., RA Georgiev G.P., Sashchenko L.P.; RT "Tag7 (PGLYRP1) in Complex with Hsp70 Induces Alternative Cytotoxic RT Processes in Tumor Cells via TNFR1 Receptor."; RL J. Biol. Chem. 290:21724-21731(2015). RN [29] RP INTERACTION WITH MUMPS VIRUS PROTEIN SH (MICROBIAL INFECTION). RX PubMed=28659487; DOI=10.1128/jvi.01037-17; RA Franz S., Rennert P., Woznik M., Gruetzke J., Luedde A., Arriero Pais E.M., RA Finsterbusch T., Geyer H., Mankertz A., Friedrich N.; RT "Mumps virus SH protein inhibits NF-kappaB activation by interacting with RT tumor necrosis factor receptor 1, interleukin-1 receptor 1, and Toll-like RT receptor 3 complexes."; RL J. Virol. 91:0-0(2017). RN [30] RP GLYCOSYLATION AT ARG-376 (MICROBIAL INFECTION), AND MUTAGENESIS OF ARG-376. 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). RN [31] RP GLYCOSYLATION (MICROBIAL INFECTION). RX PubMed=32766249; DOI=10.3389/fcell.2020.00641; RA Xue J., Hu S., Huang Y., Zhang Q., Yi X., Pan X., Li S.; RT "Arg-GlcNAcylation on TRADD by NleB and SseK1 is crucial for bacterial RT pathogenesis."; RL Front. Cell Dev. Biol. 8:641-641(2020). RN [32] RP X-RAY CRYSTALLOGRAPHY (2.85 ANGSTROMS) OF 30-211 IN COMPLEX WITH TNFB. RX PubMed=8387891; DOI=10.1016/0092-8674(93)90132-a; RA Banner D.W., D'Arcy A., Janes W., Gentz R., Schoenfeld H.-J., Broger C., RA Loetscher H., Lesslauer W.; RT "Crystal structure of the soluble human 55 kd TNF receptor-human TNF beta RT complex: implications for TNF receptor activation."; RL Cell 73:431-445(1993). RN [33] RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 41-202. RX PubMed=8939750; DOI=10.1016/s0969-2126(96)00134-7; RA Naismith J.H., Devine T.Q., Khono H., Sprang S.R.; RT "Structures of the extracellular domain of the type I tumor necrosis factor RT receptor."; RL Structure 4:1251-1262(1996). RN [34] RP VARIANTS FPF ARG-59; TYR-62; MET-79; PHE-81; ARG-117 AND TYR-117. RX PubMed=10199409; DOI=10.1016/s0092-8674(00)80721-7; RA McDermott M.F., Aksentijevich I., Galon J., McDermott E.M., RA Ogunkolade B.W., Centola M., Mansfield E., Gadina M., Karenko L., RA Pettersson T., McCarthy J., Frucht D.M., Aringer M., Torosyan Y., RA Teppo A.-M., Wilson M., Karaarslan H.M., Wan Y., Todd I., Wood G., RA Schlimgen R., Kumarajeewa T.R., Cooper S.M., Vella J.P., Amos C.I., RA Mulley J., Quane K.A., Molloy M.G., Rnaki A., Powell R.J., Hitman G.A., RA O'Shea J., Kastner D.L.; RT "Germline mutations in the extracellular domains of the 55 kDa TNF RT receptor, TNFR1, define a family of dominantly inherited autoinflammatory RT syndromes."; RL Cell 97:133-144(1999). RN [35] RP VARIANT FPF SER-59. RX PubMed=10902757; RX DOI=10.1002/1529-0131(200007)43:7<1535::aid-anr18>3.0.co;2-c; RA Dode C., Papo T., Fieschi C., Pecheux C., Dion E., Picard F., Godeau P., RA Bienvenu J., Piette J.-C., Delpech M., Grateau G.; RT "A novel missense mutation (C30S) in the gene encoding tumor necrosis RT factor receptor 1 linked to autosomal-dominant recurrent fever with RT localized myositis in a French family."; RL Arthritis Rheum. 43:1535-1542(2000). RN [36] RP VARIANTS FPF GLN-51; SER-59; GLY-62; LEU-75; GLY-115 AND GLN-121. RX PubMed=11443543; DOI=10.1086/321976; RA Aksentijevich I., Galon J., Soares M., Mansfield E., Hull K., Oh H.-H., RA Goldbach-Mansky R., Dean J., Athreya B., Reginato A.J., Henrickson M., RA Pons-Estel B., O'Shea J.J., Kastner D.L.; RT "The tumor-necrosis-factor receptor-associated periodic syndrome: new RT mutations in TNFRSF1A, ancestral origins, genotype-phenotype studies, and RT evidence for further genetic heterogeneity of periodic fevers."; RL Am. J. Hum. Genet. 69:301-314(2001). RN [37] RP VARIANTS FPF SER-99 AND PRO-121. RX PubMed=13130484; DOI=10.1002/art.11215; RA Aganna E., Hammond L., Hawkins P.N., Aldea A., McKee S.A., RA Ploos van Amstel H.K., Mischung C., Kusuhara K., Saulsbury F.T., RA Lachmann H.J., Bybee A., McDermott E.M., La Regina M., Arostegui J.I., RA Campistol J.M., Worthington S., High K.P., Molloy M.G., Baker N., RA Bidwell J.L., Castaner J.L., Whiteford M.L., Janssens-Korpola P.L., RA Manna R., Powell R.J., Woo P., Solis P., Minden K., Frenkel J., Yague J., RA Mirakian R.M., Hitman G.A., McDermott M.F.; RT "Heterogeneity among patients with tumor necrosis factor receptor- RT associated periodic syndrome phenotypes."; RL Arthritis Rheum. 48:2632-2644(2003). RN [38] RP VARIANT FPF SER-99. RX PubMed=14610673; DOI=10.1007/s00431-003-1338-0; RA Kusuhara K., Nomura A., Nakao F., Hara T.; RT "Tumour necrosis factor receptor-associated periodic syndrome with a novel RT mutation in the TNFRSF1A gene in a Japanese family."; RL Eur. J. Pediatr. 163:30-32(2004). CC -!- FUNCTION: Receptor for TNFSF2/TNF and homotrimeric TNFSF1/lymphotoxin- CC alpha. The adapter molecule FADD recruits caspase-8 to the activated CC receptor. The resulting death-inducing signaling complex (DISC) CC performs caspase-8 proteolytic activation which initiates the CC subsequent cascade of caspases (aspartate-specific cysteine proteases) CC mediating apoptosis. Contributes to the induction of non-cytocidal TNF CC effects including anti-viral state and activation of the acid CC sphingomyelinase. CC -!- SUBUNIT: Binding of TNF to the extracellular domain leads to CC homotrimerization. The aggregated death domains provide a novel CC molecular interface that interacts specifically with the death domain CC of TRADD. Various TRADD-interacting proteins such as TRAFS, RIPK1 and CC possibly FADD, are recruited to the complex by their association with CC TRADD. This complex activates at least two distinct signaling cascades, CC apoptosis and NF-kappa-B signaling. Interacts with BAG4, BABAM2, FEM1B, CC GRB2, SQSTM1 and TRPC4AP (PubMed:10356400, PubMed:10359574, CC PubMed:10542291, PubMed:15465831, PubMed:8387891, PubMed:9915703). CC Interacts directly with NOL3 (via CARD domain); inhibits TNF-signaling CC pathway (By similarity). Interacts with SH3RF2, TRADD and RIPK1. SH3RF2 CC facilitates the recruitment of RIPK1 and TRADD to TNFRSF1A in a TNF- CC dependent process (PubMed:24130170). Interacts with PGLYRP1; this CC interaction is important for cell death induction (PubMed:26183779). CC Interacts (via death domain) with MADD (via death domain) CC (PubMed:9115275). {ECO:0000250|UniProtKB:P25118, CC ECO:0000269|PubMed:10356400, ECO:0000269|PubMed:10359574, CC ECO:0000269|PubMed:10542291, ECO:0000269|PubMed:15465831, CC ECO:0000269|PubMed:24130170, ECO:0000269|PubMed:26183779, CC ECO:0000269|PubMed:8387891, ECO:0000269|PubMed:9115275, CC ECO:0000269|PubMed:9915703}. CC -!- SUBUNIT: (Microbial infection) Interacts with mumps virus protein SH; CC this interaction inhibits downstream NF-kappa-B pathway activation. CC {ECO:0000269|PubMed:28659487}. CC -!- SUBUNIT: (Microbial infection) Interacts with HCV core protein. CC {ECO:0000269|PubMed:9557650}. CC -!- SUBUNIT: (Microbial infection) Interacts with human CC cytomegalovirus/HHV-5 protein UL138. {ECO:0000269|PubMed:21976655}. CC -!- SUBUNIT: (Microbial infection) Interacts with host TNFRSF1A; this CC interaction leads to the stimulation of both surface expression and CC shedding of TNFRSF1A. {ECO:0000269|PubMed:15247912, CC ECO:0000269|PubMed:16709567}. CC -!- INTERACTION: CC P19438; P28799: GRN; NbExp=4; IntAct=EBI-299451, EBI-747754; CC P19438; Q969G6: RFK; NbExp=4; IntAct=EBI-299451, EBI-716872; CC P19438; Q13546: RIPK1; NbExp=7; IntAct=EBI-299451, EBI-358507; CC P19438; P01375: TNF; NbExp=32; IntAct=EBI-299451, EBI-359977; CC P19438; Q15628: TRADD; NbExp=14; IntAct=EBI-299451, EBI-359215; CC P19438-1; Q969G6: RFK; NbExp=2; IntAct=EBI-15795644, EBI-716872; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:22801493}; CC Single-pass type I membrane protein {ECO:0000269|PubMed:22801493}. CC Golgi apparatus membrane {ECO:0000269|PubMed:22801493}; Single-pass CC type I membrane protein {ECO:0000269|PubMed:22801493}. Secreted CC {ECO:0000269|PubMed:22801493}. Note=A secreted form is produced through CC proteolytic processing. CC -!- SUBCELLULAR LOCATION: [Isoform 4]: Secreted. Note=Lacks a Golgi- CC retention motif, is not membrane bound and therefore is secreted. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=5; CC Name=1; Synonyms=FL-TNFR1; CC IsoId=P19438-1; Sequence=Displayed; CC Name=2; CC IsoId=P19438-2; Sequence=VSP_037153; CC Name=4; Synonyms=Delta6-TNFR1; CC IsoId=P19438-4; Sequence=VSP_044949; CC Name=3; CC IsoId=P19438-3; Sequence=VSP_037154; CC Name=5; CC IsoId=P19438-5; Sequence=VSP_047613, VSP_047614; CC -!- DOMAIN: The domain that induces A-SMASE is probably identical to the CC death domain. The N-SMASE activation domain (NSD) is both necessary and CC sufficient for activation of N-SMASE. CC -!- DOMAIN: Both the cytoplasmic membrane-proximal region and the C- CC terminal region containing the death domain are involved in the CC interaction with TRPC4AP. {ECO:0000250}. CC -!- PTM: The soluble form is produced from the membrane form by proteolytic CC processing. CC -!- PTM: (Microbial infection) Glycosylated at Arg-376 by enteropathogenic CC E.coli protein NleB1 and S.typhimurium protein Ssek3: arginine CC GlcNAcylation prevents homotypic/heterotypic death domain interactions. CC {ECO:0000269|PubMed:32766249, ECO:0000305|PubMed:23955153}. CC -!- DISEASE: Periodic fever, familial, autosomal dominant (FPF) CC [MIM:142680]: A hereditary periodic fever syndrome characterized by CC recurrent fever, abdominal pain, localized tender skin lesions and CC myalgia. Reactive amyloidosis is the main complication and occurs in CC 25% of cases. {ECO:0000269|PubMed:10199409, CC ECO:0000269|PubMed:10902757, ECO:0000269|PubMed:11443543, CC ECO:0000269|PubMed:13130484, ECO:0000269|PubMed:14610673}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Multiple sclerosis 5 (MS5) [MIM:614810]: A multifactorial, CC inflammatory, demyelinating disease of the central nervous system. CC Sclerotic lesions are characterized by perivascular infiltration of CC monocytes and lymphocytes and appear as indurated areas in pathologic CC specimens (sclerosis in plaques). The pathological mechanism is CC regarded as an autoimmune attack of the myelin sheath, mediated by both CC cellular and humoral immunity. Clinical manifestations include visual CC loss, extra-ocular movement disorders, paresthesias, loss of sensation, CC weakness, dysarthria, spasticity, ataxia and bladder dysfunction. CC Genetic and environmental factors influence susceptibility to the CC disease. {ECO:0000269|PubMed:22801493}. Note=Disease susceptibility is CC associated with variants affecting the gene represented in this entry. CC An intronic mutation affecting alternative splicing and skipping of CC exon 6 directs increased expression of isoform 4 a transcript encoding CC a C-terminally truncated protein which is secreted and may function as CC a TNF antagonist. CC -!- MISCELLANEOUS: [Isoform 4]: Disease-associated isoform. Isoform 4 CC splicing pattern is driven by a variation in the exon 6/intron 6 CC boundary region that alters exon 6 splicing. Exon 6 skipping introduces CC a frameshift and the translation of a protein lacking the CC intracellular, the transmembrane and part of the extracellular domain. CC {ECO:0000305}. CC -!- WEB RESOURCE: Name=INFEVERS; Note=Repertory of FMF and hereditary CC autoinflammatory disorders mutations; CC URL="https://infevers.umai-montpellier.fr/web/search.php?n=22"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M58286; AAA36753.1; -; mRNA. DR EMBL; M33294; AAA03210.1; -; mRNA. DR EMBL; M63121; AAA36754.1; -; mRNA. DR EMBL; X55313; CAA39021.1; -; mRNA. DR EMBL; M60275; AAA36756.1; -; mRNA. DR EMBL; M75866; AAA61201.1; -; Genomic_DNA. DR EMBL; M75864; AAA61201.1; JOINED; Genomic_DNA. DR EMBL; M75865; AAA61201.1; JOINED; Genomic_DNA. DR EMBL; AY131997; AAM77802.1; -; Genomic_DNA. DR EMBL; AK056611; BAG51763.1; -; mRNA. DR EMBL; AK291088; BAF83777.1; -; mRNA. DR EMBL; AK298729; BAG60879.1; -; mRNA. DR EMBL; AK304517; BAG65321.1; -; mRNA. DR EMBL; AK315509; BAG37891.1; -; mRNA. DR EMBL; EU927389; ACH57451.1; -; mRNA. DR EMBL; AC006057; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471116; EAW88805.1; -; Genomic_DNA. DR EMBL; CH471116; EAW88806.1; -; Genomic_DNA. DR EMBL; BC010140; AAH10140.1; -; mRNA. DR CCDS; CCDS8542.1; -. [P19438-1] DR PIR; A38208; GQHUT1. DR RefSeq; NP_001056.1; NM_001065.4. [P19438-1] DR RefSeq; NP_001333020.1; NM_001346091.2. [P19438-2] DR RefSeq; NP_001333021.1; NM_001346092.2. DR PDB; 1EXT; X-ray; 1.85 A; A/B=41-201. DR PDB; 1FT4; X-ray; 2.90 A; A/B=41-201. DR PDB; 1ICH; NMR; -; A=345-455. DR PDB; 1NCF; X-ray; 2.25 A; A/B=41-201. DR PDB; 1TNR; X-ray; 2.85 A; R=44-182. DR PDB; 7K7A; NMR; -; A/B/C=209-238. DR PDB; 7KP7; X-ray; 2.65 A; D/E/F=42-184. DR PDB; 7KP8; X-ray; 3.15 A; E/F=43-184. DR PDB; 7KPB; X-ray; 3.00 A; E/F=42-184. DR PDB; 8P6Q; X-ray; 1.40 A; A=101-145. DR PDB; 8ZUI; EM; 2.56 A; D/E/F/J/K/L=30-211. DR PDB; 9V9C; EM; 2.62 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T=342-455. DR PDB; 9VIN; EM; 3.41 A; A/B/C/D/G/a/b/c/d/e/f/g/h=342-455. DR AlphaFoldDB; P19438; -. DR BMRB; P19438; -. DR EMDB; EMD-60484; -. DR EMDB; EMD-60489; -. DR EMDB; EMD-60490; -. DR EMDB; EMD-60491; -. DR EMDB; EMD-60494; -. DR EMDB; EMD-60497; -. DR EMDB; EMD-60549; -. DR EMDB; EMD-64869; -. DR EMDB; EMD-65094; -. DR SMR; P19438; -. DR BioGRID; 112986; 209. DR ComplexPortal; CPX-25723; sTNF-TNR1A receptor-ligand core complex, BIRC3 variant. DR ComplexPortal; CPX-25726; mTNF-TNR1A receptor-ligand core complex, BIRC3 variant. DR ComplexPortal; CPX-8828; sTNF-TNR1A receptor-ligand core complex, BIRC2 variant. DR ComplexPortal; CPX-8932; mTNF-TNR1A receptor-ligand core complex, BIRC2 variant. DR ComplexPortal; CPX-8945; Lymphotoxin-alpha-TNFRSF1A receptor complex. DR CORUM; P19438; -. DR DIP; DIP-407N; -. DR FunCoup; P19438; 1321. DR IntAct; P19438; 109. DR MINT; P19438; -. DR NDEx; IQUERY-CP-TNFRSF1A; 33 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000162749; -. DR BindingDB; P19438; -. DR ChEMBL; CHEMBL3378; -. DR DrugBank; DB03507; 6-[3-(4-Morpholinyl)Propyl]-2-(3-Nitrophenyl)-5-Thioxo-5,6,-Dihydro-7h-Thienol[2',3':4,5]Pyrrolo[1,2-C]Imidazol-7-One. DR DrugBank; DB11626; Tasonermin. DR DrugCentral; P19438; -. DR GlyConnect; P19438; 1 N-Linked glycan (1 site). DR GlyCosmos; P19438; 4 sites, No reported glycans. DR GlyGen; P19438; 5 sites, 2 N-linked glycans (1 site), 1 O-linked glycan (1 site). DR iPTMnet; P19438; -. DR PhosphoSitePlus; P19438; -. DR SwissPalm; P19438; -. DR BioMuta; TNFRSF1A; -. DR DMDM; 135959; -. DR jPOST; P19438; -. DR MassIVE; P19438; -. DR PaxDb; 9606-ENSP00000162749; -. DR PeptideAtlas; P19438; -. DR ProteomicsDB; 53659; -. [P19438-1] DR ProteomicsDB; 53660; -. [P19438-2] DR ProteomicsDB; 53661; -. [P19438-3] DR ProteomicsDB; 5939; -. DR ABCD; P19438; 189 sequenced antibodies. DR Antibodypedia; 1320; 1517 antibodies from 52 providers. DR DNASU; 7132; -. DR Ensembl; ENST00000162749.7; ENSP00000162749.2; ENSG00000067182.10. [P19438-1] DR Ensembl; ENST00000437813.8; ENSP00000513672.1; ENSG00000067182.10. [P19438-5] DR Ensembl; ENST00000698339.1; ENSP00000513670.1; ENSG00000067182.10. [P19438-5] DR Ensembl; ENST00000698340.1; ENSP00000513671.1; ENSG00000067182.10. [P19438-4] DR GeneID; 7132; -. DR KEGG; hsa:7132; -. DR MANE-Select; ENST00000162749.7; ENSP00000162749.2; NM_001065.4; NP_001056.1. DR UCSC; uc001qnu.4; human. [P19438-1] DR AGR; HGNC:11916; -. DR ClinPGx; PA36609; -. DR CTD; 7132; -. DR DisGeNET; 7132; -. DR GeneCards; TNFRSF1A; -. DR GeneReviews; TNFRSF1A; -. DR HGNC; HGNC:11916; TNFRSF1A. DR HPA; ENSG00000067182; Low tissue specificity. DR MalaCards; TNFRSF1A; -. DR MIM; 142680; phenotype. DR MIM; 191190; gene. DR MIM; 614810; phenotype. DR OpenTargets; ENSG00000067182; -. DR Orphanet; 329967; Intermittent hydrarthrosis. DR Orphanet; 32960; Tumor necrosis factor receptor 1 associated periodic syndrome. DR VEuPathDB; HostDB:ENSG00000067182; -. DR eggNOG; ENOG502S050; Eukaryota. DR GeneTree; ENSGT00940000159540; -. DR HOGENOM; CLU_050864_0_0_1; -. DR InParanoid; P19438; -. DR OMA; IVETPCT; -. DR OrthoDB; 9408020at2759; -. DR PAN-GO; P19438; 5 GO annotations based on evolutionary models. DR PhylomeDB; P19438; -. DR PathwayCommons; P19438; -. DR Reactome; R-HSA-5357786; TNFR1-induced proapoptotic signaling. DR Reactome; R-HSA-5357905; Regulation of TNFR1 signaling. DR Reactome; R-HSA-5357956; TNFR1-induced NF-kappa-B signaling pathway. DR Reactome; R-HSA-5626978; TNFR1-mediated ceramide production. DR Reactome; R-HSA-5669034; TNFs bind their physiological receptors. DR Reactome; R-HSA-6783783; Interleukin-10 signaling. DR Reactome; R-HSA-75893; TNF signaling. DR SignaLink; P19438; -. DR SIGNOR; P19438; -. DR Agora; ENSG00000067182; Agora Nominated Target for Alzheimer's Disease. DR BioGRID-ORCS; 7132; 29 hits in 1171 CRISPR screens. DR ChiTaRS; TNFRSF1A; human. DR EvolutionaryTrace; P19438; -. DR GeneWiki; TNFRSF1A; -. DR GenomeRNAi; 7132; -. DR Pharos; P19438; Tchem. DR PRO; PR:P19438; -. DR Proteomes; UP000005640; Chromosome 12. DR RNAct; P19438; protein. DR Bgee; ENSG00000067182; Expressed in tendon of biceps brachii and 200 other cell types or tissues. DR ExpressionAtlas; P19438; baseline and differential. DR GO; GO:0009986; C:cell surface; IDA:UniProt. DR GO; GO:0005576; C:extracellular region; IDA:BHF-UCL. DR GO; GO:0000139; C:Golgi membrane; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; TAS:ARUK-UCL. DR GO; GO:0045121; C:membrane raft; IDA:BHF-UCL. DR GO; GO:0005886; C:plasma membrane; IPI:ComplexPortal. DR GO; GO:0043235; C:signaling receptor complex; IDA:MGI. DR GO; GO:0002947; C:tumor necrosis factor receptor superfamily complex; IPI:ComplexPortal. DR GO; GO:0038023; F:signaling receptor activity; ISS:UniProt. DR GO; GO:0043120; F:tumor necrosis factor binding; IPI:ARUK-UCL. DR GO; GO:0005031; F:tumor necrosis factor receptor activity; IDA:UniProt. DR GO; GO:0007250; P:activation of NF-kappaB-inducing kinase activity; NAS:ComplexPortal. DR GO; GO:0003176; P:aortic valve development; ISS:BHF-UCL. DR GO; GO:0048143; P:astrocyte activation; IEA:Ensembl. DR GO; GO:0007259; P:cell surface receptor signaling pathway via JAK-STAT; IMP:BHF-UCL. DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEA:Ensembl. DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEP:UniProtKB. DR GO; GO:0019221; P:cytokine-mediated signaling pathway; ISS:UniProtKB. DR GO; GO:0060856; P:establishment of blood-brain barrier; IEA:Ensembl. DR GO; GO:0008625; P:extrinsic apoptotic signaling pathway via death domain receptors; TAS:BHF-UCL. DR GO; GO:0010467; P:gene expression; IEA:Ensembl. DR GO; GO:0006954; P:inflammatory response; ISS:UniProtKB. DR GO; GO:0010614; P:negative regulation of cardiac muscle hypertrophy; IEA:Ensembl. DR GO; GO:0003332; P:negative regulation of extracellular matrix constituent secretion; ISS:BHF-UCL. DR GO; GO:0050728; P:negative regulation of inflammatory response; IMP:BHF-UCL. DR GO; GO:1902339; P:positive regulation of apoptotic process involved in morphogenesis; ISS:BHF-UCL. DR GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; IEP:UniProtKB. DR GO; GO:1900119; P:positive regulation of execution phase of apoptosis; IEA:Ensembl. DR GO; GO:0050729; P:positive regulation of inflammatory response; ISS:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:BHF-UCL. DR GO; GO:0006693; P:prostaglandin metabolic process; IEA:InterPro. DR GO; GO:0072659; P:protein localization to plasma membrane; IMP:UniProtKB. DR GO; GO:0003177; P:pulmonary valve development; ISS:BHF-UCL. DR GO; GO:1903140; P:regulation of establishment of endothelial barrier; IMP:UniProtKB. DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IMP:UniProtKB. DR CDD; cd08313; Death_TNFR1; 1. DR CDD; cd10576; TNFRSF1A; 1. DR FunFam; 1.10.533.10:FF:000044; Tumor necrosis factor receptor superfamily member 1A; 1. DR FunFam; 2.10.50.10:FF:000020; Tumor necrosis factor receptor superfamily member 1A; 1. DR FunFam; 2.10.50.10:FF:000025; Tumor necrosis factor receptor superfamily member 1A; 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; 2. DR InterPro; IPR011029; DEATH-like_dom_sf. DR InterPro; IPR000488; Death_dom. DR InterPro; IPR001368; TNFR/NGFR_Cys_rich_reg. DR InterPro; IPR020419; TNFR_1A. DR InterPro; IPR052493; TNFRSF1A. DR InterPro; IPR033994; TNFRSF1A_death. DR InterPro; IPR033993; TNFRSF1A_N. DR PANTHER; PTHR46861; TUMOR NECROSIS FACTOR RECEPTOR SUPERFAMILY MEMBER 1A; 1. DR PANTHER; PTHR46861:SF1; TUMOR NECROSIS FACTOR RECEPTOR SUPERFAMILY MEMBER 1A; 1. DR Pfam; PF00531; Death; 1. DR Pfam; PF00020; TNFR_c6; 2. DR PRINTS; PR01918; TNFACTORR1A. DR SMART; SM00005; DEATH; 1. DR SMART; SM00208; TNFR; 4. DR SUPFAM; SSF47986; DEATH domain; 1. DR SUPFAM; SSF57586; TNF receptor-like; 3. DR PROSITE; PS50017; DEATH_DOMAIN; 1. DR PROSITE; PS00652; TNFR_NGFR_1; 3. DR PROSITE; PS50050; TNFR_NGFR_2; 3. DR PDBsum; 1EXT; -. DR PDBsum; 1FT4; -. DR PDBsum; 1ICH; -. DR PDBsum; 1NCF; -. DR PDBsum; 1TNR; -. DR PDBsum; 7K7A; -. DR PDBsum; 7KP7; -. DR PDBsum; 7KP8; -. DR PDBsum; 7KPB; -. DR PDBsum; 8P6Q; -. DR PDBsum; 8ZUI; -. DR PDBsum; 9V9C; -. DR PDBsum; 9VIN; -. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Amyloidosis; Apoptosis; Cell membrane; KW Cleavage on pair of basic residues; Direct protein sequencing; KW Disease variant; Disulfide bond; Glycoprotein; Golgi apparatus; KW Host-virus interaction; Membrane; Proteomics identification; Receptor; KW Reference proteome; Repeat; Secreted; Signal; Transmembrane; KW Transmembrane helix. FT SIGNAL 1..29 FT /evidence="ECO:0000269|PubMed:2158862" FT CHAIN 30..455 FT /note="Tumor necrosis factor receptor superfamily member FT 1A, membrane form" FT /id="PRO_0000034543" FT CHAIN 41..201 FT /note="Tumor necrosis factor-binding protein 1" FT /id="PRO_0000034544" FT TOPO_DOM 30..211 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 212..232 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 233..455 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT REPEAT 43..82 FT /note="TNFR-Cys 1" FT REPEAT 83..125 FT /note="TNFR-Cys 2" FT REPEAT 126..166 FT /note="TNFR-Cys 3" FT REPEAT 167..196 FT /note="TNFR-Cys 4" FT DOMAIN 356..441 FT /note="Death" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00064" FT REGION 254..273 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 338..348 FT /note="N-SMase activation domain (NSD)" FT CARBOHYD 54 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 145 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 151 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 376 FT /note="(Microbial infection) N-beta-linked (GlcNAc) FT arginine" FT /evidence="ECO:0000269|PubMed:30979585, FT ECO:0000305|PubMed:23955153" FT DISULFID 44..58 FT DISULFID 59..72 FT DISULFID 62..81 FT DISULFID 84..99 FT DISULFID 102..117 FT DISULFID 105..125 FT DISULFID 127..143 FT DISULFID 146..158 FT DISULFID 149..166 FT DISULFID 168..179 FT DISULFID 182..195 FT DISULFID 185..191 FT VAR_SEQ 1..232 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_037154" FT VAR_SEQ 1..108 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_037153" FT VAR_SEQ 184..455 FT /note="NCKKSLECTKLCLPQIENVKGTEDSGTTVLLPLVIFFGLCLLSLLFIGLMYR FT YQRWKSKLYSIVCGKSTPEKEGELEGTTTKPLAPNPSFSPTPGFTPTLGFSPVPSSTFT FT SSSTYTPGDCPNFAAPRREVAPPYQGADPILATALASDPIPNPLQKWEDSAHKPQSLDT FT DDPATLYAVVENVPPLRWKEFVRRLGLSDHEIDRLELQNGRCLREAQYSMLATWRRRTP FT RREATLELLGRVLRDMDLLGCLEDIEEALCGPAALPPAPSLLR -> KHHSAVAPGHFL FT WSLPFIPPLHWFNVSLPTVEVQALLHCLWEIDT (in isoform 4)" FT /evidence="ECO:0000305" FT /id="VSP_044949" FT VAR_SEQ 184..218 FT /note="NCKKSLECTKLCLPQIENVKGTEDSGTTVLLPLVI -> KVLLCRPGWNAVA FT RSRLTATSASQIQAILLLQPPK (in isoform 5)" FT /evidence="ECO:0000303|PubMed:19906316" FT /id="VSP_047613" FT VAR_SEQ 219..455 FT /note="Missing (in isoform 5)" FT /evidence="ECO:0000303|PubMed:19906316" FT /id="VSP_047614" FT VARIANT 51 FT /note="H -> Q (in FPF; dbSNP:rs104895254)" FT /evidence="ECO:0000269|PubMed:11443543" FT /id="VAR_019329" FT VARIANT 59 FT /note="C -> R (in FPF; dbSNP:rs104895217)" FT /evidence="ECO:0000269|PubMed:10199409" FT /id="VAR_013410" FT VARIANT 59 FT /note="C -> S (in FPF; dbSNP:rs104895223)" FT /evidence="ECO:0000269|PubMed:10902757, FT ECO:0000269|PubMed:11443543" FT /id="VAR_019302" FT VARIANT 62 FT /note="C -> G (in FPF; dbSNP:rs104895225)" FT /evidence="ECO:0000269|PubMed:11443543" FT /id="VAR_019303" FT VARIANT 62 FT /note="C -> Y (in FPF; dbSNP:rs104895218)" FT /evidence="ECO:0000269|PubMed:10199409" FT /id="VAR_013411" FT VARIANT 75 FT /note="P -> L (in FPF; benign; dbSNP:rs4149637)" FT /evidence="ECO:0000269|PubMed:11443543, ECO:0000269|Ref.7" FT /id="VAR_019330" FT VARIANT 79 FT /note="T -> M (in FPF; dbSNP:rs104895219)" FT /evidence="ECO:0000269|PubMed:10199409" FT /id="VAR_013412" FT VARIANT 81 FT /note="C -> F (in FPF; dbSNP:rs104895220)" FT /evidence="ECO:0000269|PubMed:10199409" FT /id="VAR_013413" FT VARIANT 99 FT /note="C -> S (in FPF; dbSNP:rs104895228)" FT /evidence="ECO:0000269|PubMed:13130484, FT ECO:0000269|PubMed:14610673" FT /id="VAR_019304" FT VARIANT 115 FT /note="S -> G (in FPF)" FT /evidence="ECO:0000269|PubMed:11443543" FT /id="VAR_019331" FT VARIANT 117 FT /note="C -> R (in FPF; dbSNP:rs104895221)" FT /evidence="ECO:0000269|PubMed:10199409" FT /id="VAR_013414" FT VARIANT 117 FT /note="C -> Y (in FPF; dbSNP:rs104895222)" FT /evidence="ECO:0000269|PubMed:10199409" FT /id="VAR_013415" FT VARIANT 121 FT /note="R -> P (in FPF; dbSNP:rs4149584)" FT /evidence="ECO:0000269|PubMed:13130484" FT /id="VAR_019305" FT VARIANT 121 FT /note="R -> Q (in FPF; uncertain significance; FT dbSNP:rs4149584)" FT /evidence="ECO:0000269|PubMed:11443543, ECO:0000269|Ref.7" FT /id="VAR_019332" FT VARIANT 305 FT /note="P -> T (in dbSNP:rs1804532)" FT /id="VAR_011813" FT MUTAGEN 376 FT /note="R->A: Abolished GlcNAcylation by E.coli NleB1." FT /evidence="ECO:0000269|PubMed:30979585" FT CONFLICT 13 FT /note="L -> LILPQ (in Ref. 8; BAG51763)" FT /evidence="ECO:0000305" FT CONFLICT 255 FT /note="K -> E (in Ref. 8; BAG37891)" FT /evidence="ECO:0000305" FT CONFLICT 286 FT /note="S -> G (in Ref. 8; BAG51763)" FT /evidence="ECO:0000305" FT CONFLICT 394 FT /note="R -> L (in Ref. 8; BAF83777)" FT /evidence="ECO:0000305" FT CONFLICT 412 FT /note="Missing (in Ref. 5; AAA36756)" FT /evidence="ECO:0000305" FT CONFLICT 443..446 FT /note="GPAA -> APP (in Ref. 5; AAA36756)" FT /evidence="ECO:0000305" FT STRAND 48..50 FT /evidence="ECO:0007829|PDB:1EXT" FT STRAND 52..54 FT /evidence="ECO:0007829|PDB:8ZUI" FT STRAND 58..60 FT /evidence="ECO:0007829|PDB:1EXT" FT STRAND 66..70 FT /evidence="ECO:0007829|PDB:1EXT" FT HELIX 77..79 FT /evidence="ECO:0007829|PDB:8ZUI" FT STRAND 80..83 FT /evidence="ECO:0007829|PDB:1EXT" FT STRAND 92..94 FT /evidence="ECO:0007829|PDB:1EXT" FT STRAND 97..101 FT /evidence="ECO:0007829|PDB:1TNR" FT HELIX 102..105 FT /evidence="ECO:0007829|PDB:1NCF" FT HELIX 107..109 FT /evidence="ECO:0007829|PDB:8P6Q" FT STRAND 112..115 FT /evidence="ECO:0007829|PDB:8P6Q" FT STRAND 119..121 FT /evidence="ECO:0007829|PDB:8P6Q" FT STRAND 124..126 FT /evidence="ECO:0007829|PDB:8P6Q" FT STRAND 132..139 FT /evidence="ECO:0007829|PDB:8P6Q" FT STRAND 141..144 FT /evidence="ECO:0007829|PDB:8P6Q" FT HELIX 146..148 FT /evidence="ECO:0007829|PDB:7KP8" FT STRAND 152..156 FT /evidence="ECO:0007829|PDB:1EXT" FT STRAND 160..162 FT /evidence="ECO:0007829|PDB:8ZUI" FT STRAND 165..168 FT /evidence="ECO:0007829|PDB:1EXT" FT STRAND 172..175 FT /evidence="ECO:0007829|PDB:1EXT" FT STRAND 178..181 FT /evidence="ECO:0007829|PDB:1EXT" FT HELIX 182..184 FT /evidence="ECO:0007829|PDB:1EXT" FT HELIX 192..195 FT /evidence="ECO:0007829|PDB:1EXT" FT HELIX 213..236 FT /evidence="ECO:0007829|PDB:7K7A" FT HELIX 357..365 FT /evidence="ECO:0007829|PDB:1ICH" FT HELIX 371..378 FT /evidence="ECO:0007829|PDB:1ICH" FT HELIX 382..391 FT /evidence="ECO:0007829|PDB:1ICH" FT HELIX 396..410 FT /evidence="ECO:0007829|PDB:1ICH" FT HELIX 417..427 FT /evidence="ECO:0007829|PDB:1ICH" FT HELIX 431..441 FT /evidence="ECO:0007829|PDB:1ICH" SQ SEQUENCE 455 AA; 50495 MW; 4CEFBA96D03B8225 CRC64; MGLSTVPDLL LPLVLLELLV GIYPSGVIGL VPHLGDREKR DSVCPQGKYI HPQNNSICCT KCHKGTYLYN DCPGPGQDTD CRECESGSFT ASENHLRHCL SCSKCRKEMG QVEISSCTVD RDTVCGCRKN QYRHYWSENL FQCFNCSLCL NGTVHLSCQE KQNTVCTCHA GFFLRENECV SCSNCKKSLE CTKLCLPQIE NVKGTEDSGT TVLLPLVIFF GLCLLSLLFI GLMYRYQRWK SKLYSIVCGK STPEKEGELE GTTTKPLAPN PSFSPTPGFT PTLGFSPVPS STFTSSSTYT PGDCPNFAAP RREVAPPYQG ADPILATALA SDPIPNPLQK WEDSAHKPQS LDTDDPATLY AVVENVPPLR WKEFVRRLGL SDHEIDRLEL QNGRCLREAQ YSMLATWRRR TPRREATLEL LGRVLRDMDL LGCLEDIEEA LCGPAALPPA PSLLR //