TNR1A_HUMAN
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 03-AUG-2022, entry version 254.
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-alpha and homotrimeric
CC TNFSF1/lymphotoxin-alpha. The adapter molecule FADD recruits caspase-8
CC to the activated receptor. The resulting death-inducing signaling
CC complex (DISC) performs caspase-8 proteolytic activation which
CC initiates the subsequent cascade of caspases (aspartate-specific
CC cysteine proteases) mediating apoptosis. Contributes to the induction
CC of non-cytocidal TNF effects including anti-viral state and activation
CC of the acid 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 alpha-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=6; IntAct=EBI-299451, EBI-358507;
CC P19438; P01375: TNF; NbExp=15; IntAct=EBI-299451, EBI-359977;
CC P19438; Q15628: TRADD; NbExp=13; 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 -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/tnfrsf1a/";
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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_001065.3. [P19438-1]
DR RefSeq; NP_001333020.1; NM_001346091.1. [P19438-2]
DR RefSeq; NP_001333021.1; NM_001346092.1.
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 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 AlphaFoldDB; P19438; -.
DR BMRB; P19438; -.
DR SMR; P19438; -.
DR BioGRID; 112986; 202.
DR CORUM; P19438; -.
DR DIP; DIP-407N; -.
DR IntAct; P19438; 98.
DR MINT; P19438; -.
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 GlyGen; P19438; 3 sites.
DR iPTMnet; P19438; -.
DR PhosphoSitePlus; P19438; -.
DR SwissPalm; P19438; -.
DR BioMuta; TNFRSF1A; -.
DR DMDM; 135959; -.
DR EPD; P19438; -.
DR jPOST; P19438; -.
DR MassIVE; P19438; -.
DR MaxQB; P19438; -.
DR PaxDb; P19438; -.
DR PeptideAtlas; P19438; -.
DR PRIDE; P19438; -.
DR ProteomicsDB; 53659; -. [P19438-1]
DR ProteomicsDB; 53660; -. [P19438-2]
DR ProteomicsDB; 53661; -. [P19438-3]
DR ProteomicsDB; 5939; -.
DR ABCD; P19438; 8 sequenced antibodies.
DR Antibodypedia; 1320; 1478 antibodies from 51 providers.
DR DNASU; 7132; -.
DR Ensembl; ENST00000162749.7; ENSP00000162749.2; ENSG00000067182.8. [P19438-1]
DR Ensembl; ENST00000366159.8; ENSP00000380389.3; ENSG00000067182.8. [P19438-5]
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 CTD; 7132; -.
DR DisGeNET; 7132; -.
DR GeneCards; 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 neXtProt; NX_P19438; -.
DR OpenTargets; ENSG00000067182; -.
DR Orphanet; 329967; Intermittent hydrarthrosis.
DR Orphanet; 802; NON RARE IN EUROPE: Multiple sclerosis.
DR Orphanet; 32960; Tumor necrosis factor receptor 1 associated periodic syndrome.
DR PharmGKB; PA36609; -.
DR VEuPathDB; HostDB:ENSG00000067182; -.
DR eggNOG; ENOG502S050; Eukaryota.
DR GeneTree; ENSGT00940000159540; -.
DR HOGENOM; CLU_050864_0_0_1; -.
DR InParanoid; P19438; -.
DR OMA; ICRCKPQ; -.
DR OrthoDB; 976094at2759; -.
DR PhylomeDB; P19438; -.
DR TreeFam; TF333916; -.
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 NFkappaB 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 BioGRID-ORCS; 7132; 16 hits in 1084 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 198 other tissues.
DR ExpressionAtlas; P19438; baseline and differential.
DR Genevisible; P19438; HS.
DR GO; GO:0009986; C:cell surface; IEA:Ensembl.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
DR GO; GO:0000139; C:Golgi membrane; IDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0016020; C:membrane; TAS:ARUK-UCL.
DR GO; GO:0045121; C:membrane raft; IDA:BHF-UCL.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0043235; C:receptor complex; IDA:MGI.
DR GO; GO:0002947; C:tumor necrosis factor receptor superfamily complex; TAS:ARUK-UCL.
DR GO; GO:0043120; F:tumor necrosis factor binding; IPI:ARUK-UCL.
DR GO; GO:0005031; F:tumor necrosis factor receptor activity; IBA:GO_Central.
DR GO; GO:0003176; P:aortic valve development; ISS:BHF-UCL.
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:0042742; P:defense response to bacterium; IEA:Ensembl.
DR GO; GO:0008625; P:extrinsic apoptotic signaling pathway via death domain receptors; TAS:BHF-UCL.
DR GO; GO:0006954; P:inflammatory response; ISS:UniProtKB.
DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IEA:Ensembl.
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 I-kappaB kinase/NF-kappaB signaling; IEP:UniProtKB.
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:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; 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:0010803; P:regulation of tumor necrosis factor-mediated signaling pathway; IEA:Ensembl.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IEA:Ensembl.
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 Gene3D; 1.10.533.10; -; 1.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR000488; Death_domain.
DR InterPro; IPR001368; TNFR/NGFR_Cys_rich_reg.
DR InterPro; IPR020419; TNFR_1A.
DR InterPro; IPR033994; TNFRSF1A_death.
DR InterPro; IPR033993; TNFRSF1A_N.
DR Pfam; PF00531; Death; 1.
DR Pfam; PF00020; TNFR_c6; 3.
DR PRINTS; PR01918; TNFACTORR1A.
DR SMART; SM00005; DEATH; 1.
DR SMART; SM00208; TNFR; 4.
DR SUPFAM; SSF47986; SSF47986; 1.
DR PROSITE; PS50017; DEATH_DOMAIN; 1.
DR PROSITE; PS00652; TNFR_NGFR_1; 3.
DR PROSITE; PS50050; TNFR_NGFR_2; 3.
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; Receptor; Reference proteome; Repeat;
KW Secreted; Signal; Transmembrane; 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 variant; 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; unknown pathological 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:1FT4"
FT STRAND 58..60
FT /evidence="ECO:0007829|PDB:1EXT"
FT STRAND 66..70
FT /evidence="ECO:0007829|PDB:1EXT"
FT STRAND 73..77
FT /evidence="ECO:0007829|PDB:7KP8"
FT STRAND 80..83
FT /evidence="ECO:0007829|PDB:1EXT"
FT STRAND 92..94
FT /evidence="ECO:0007829|PDB:1EXT"
FT HELIX 107..109
FT /evidence="ECO:0007829|PDB:1EXT"
FT STRAND 112..115
FT /evidence="ECO:0007829|PDB:1EXT"
FT STRAND 124..126
FT /evidence="ECO:0007829|PDB:1EXT"
FT STRAND 131..137
FT /evidence="ECO:0007829|PDB:1EXT"
FT STRAND 140..145
FT /evidence="ECO:0007829|PDB:1EXT"
FT STRAND 152..156
FT /evidence="ECO:0007829|PDB:1EXT"
FT STRAND 160..162
FT /evidence="ECO:0007829|PDB:1TNR"
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
