TRADD_HUMAN
ID TRADD_HUMAN Reviewed; 312 AA.
AC Q15628; B2RDS3; B3KQZ9; Q52NZ1;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1999, sequence version 2.
DT 03-AUG-2022, entry version 207.
DE RecName: Full=Tumor necrosis factor receptor type 1-associated DEATH domain protein {ECO:0000305};
DE Short=TNFR1-associated DEATH domain protein {ECO:0000303|PubMed:7758105};
DE AltName: Full=TNFRSF1A-associated via death domain {ECO:0000303|PubMed:7758105};
GN Name=TRADD {ECO:0000303|PubMed:7758105, ECO:0000312|HGNC:HGNC:12030};
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), FUNCTION, IDENTIFICATION IN COMPLEX
RP I, TISSUE SPECIFICITY, AND INTERACTION WITH TNFRSF1A.
RX PubMed=7758105; DOI=10.1016/0092-8674(95)90070-5;
RA Hsu H., Xiong J., Goeddel D.V.;
RT "The TNF receptor 1-associated protein TRADD signals cell death and NF-
RT kappa B activation.";
RL Cell 81:495-504(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Scheuerpflug C.G., Dechant M., Fellenberg J., Ewerbeck V., Debatin K.M.;
RT "Sequence, genomic organisation, and mutation analysis of the human TRADD
RT gene in childhood B- and T-lineage acute lymphoblastic leukemia and ALPS.";
RL Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Kaiser C., Kohstall B., Kieser A.;
RT "Cloning of the human TRADD gene locus.";
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG SeattleSNPs variation discovery resource;
RL Submitted (MAR-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Cerebellum, and Mammary gland;
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [8]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Pancreas;
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 [10]
RP FUNCTION, IDENTIFICATION IN COMPLEX I, AND INTERACTION WITH RIPK1.
RX PubMed=8612133; DOI=10.1016/s1074-7613(00)80252-6;
RA Hsu H., Huang J., Shu H.-B., Baichwal V.R., Goeddel D.V.;
RT "TNF-dependent recruitment of the protein kinase RIP to the TNF receptor-1
RT signaling complex.";
RL Immunity 4:387-396(1996).
RN [11]
RP INTERACTION WITH 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 [12]
RP INTERACTION WITH HIPK2.
RX PubMed=11032752; DOI=10.1006/bbrc.2000.3700;
RA Li X., Wang Y., Debatin K.-M., Hug H.;
RT "The serine/threonine kinase HIPK2 interacts with TRADD, but not with CD95
RT or TNF-R1 in 293T cells.";
RL Biochem. Biophys. Res. Commun. 277:513-517(2000).
RN [13]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH KRT14 AND KRT18.
RX PubMed=11684708; DOI=10.1083/jcb.200103078;
RA Inada H., Izawa I., Nishizawa M., Fujita E., Kiyono T., Takahashi T.,
RA Momoi T., Inagaki M.;
RT "Keratin attenuates tumor necrosis factor-induced cytotoxicity through
RT association with TRADD.";
RL J. Cell Biol. 155:415-426(2001).
RN [14]
RP IDENTIFICATION IN COMPLEX I WITH CHUCK; IKBKB AND IKBKG, AND INTERACTION
RP WITH TRPC4AP.
RX PubMed=14585990; DOI=10.1128/mcb.23.22.8334-8344.2003;
RA Soond S.M., Terry J.L., Colbert J.D., Riches D.W.H.;
RT "TRUSS, a novel tumor necrosis factor receptor 1 scaffolding protein that
RT mediates activation of the transcription factor NF-kappaB.";
RL Mol. Cell. Biol. 23:8334-8344(2003).
RN [15]
RP INTERACTION WITH DAB2IP.
RX PubMed=15310755; DOI=10.1074/jbc.m407617200;
RA Zhang H., Zhang R., Luo Y., D'Alessio A., Pober J.S., Min W.;
RT "AIP1/DAB2IP, a novel member of the Ras-GAP family, transduces TRAF2-
RT induced ASK1-JNK activation.";
RL J. Biol. Chem. 279:44955-44965(2004).
RN [16]
RP INTERACTION WITH TOMM70.
RX PubMed=20628368; DOI=10.1038/cr.2010.103;
RA Liu X.Y., Wei B., Shi H.X., Shan Y.F., Wang C.;
RT "Tom70 mediates activation of interferon regulatory factor 3 on
RT mitochondria.";
RL Cell Res. 20:994-1011(2010).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [18]
RP IDENTIFICATION IN APOPTOTIC COMPLEX I.
RX PubMed=21307340; DOI=10.1091/mbc.e10-10-0827;
RA Huang Y., Chen L., Zhou Y., Liu H., Yang J., Liu Z., Wang C.;
RT "UXT-V1 protects cells against TNF-induced apoptosis through modulating
RT complex II formation.";
RL Mol. Biol. Cell 22:1389-1397(2011).
RN [19]
RP FUNCTION, GLYCOSYLATION AT ARG-235 (MICROBIAL INFECTION), AND MUTAGENESIS
RP OF ARG-235.
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 [20]
RP INTERACTION WITH TNFRSF1A.
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 [21]
RP GLYCOSYLATION (MICROBIAL INFECTION).
RX PubMed=28069818; DOI=10.1128/iai.00010-17;
RA Guenster R.A., Matthews S.A., Holden D.W., Thurston T.L.M.;
RT "SseK1 and SseK3 type III secretion system effectors inhibit NF-kappaB
RT signaling and necroptotic cell death in salmonella-infected macrophages.";
RL Infect. Immun. 85:0-0(2017).
RN [22]
RP GLYCOSYLATION (MICROBIAL INFECTION).
RX PubMed=29449376; DOI=10.1074/jbc.ra118.001796;
RA Esposito D., Gunster R.A., Martino L., El Omari K., Wagner A.,
RA Thurston T.L.M., Rittinger K.;
RT "Structural basis for the glycosyltransferase activity of the Salmonella
RT effector SseK3.";
RL J. Biol. Chem. 293:5064-5078(2018).
RN [23]
RP GLYCOSYLATION (MICROBIAL INFECTION).
RX PubMed=30902834; DOI=10.1074/mcp.ra118.001093;
RA Newson J.P.M., Scott N.E., Yeuk Wah Chung I., Wong Fok Lung T., Giogha C.,
RA Gan J., Wang N., Strugnell R.A., Brown N.F., Cygler M., Pearson J.S.,
RA Hartland E.L.;
RT "Salmonella effectors SseK1 and SseK3 target death domain proteins in the
RT TNF and TRAIL signaling pathways.";
RL Mol. Cell. Proteomics 18:1138-1156(2019).
RN [24]
RP GLYCOSYLATION AT ARG-235 AND ARG-245 (MICROBIAL INFECTION), AND MUTAGENESIS
RP OF ARG-235 AND ARG-245.
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 [25]
RP STRUCTURE BY NMR OF 1-179.
RX PubMed=10911999; DOI=10.1016/s1097-2765(00)80270-1;
RA Tsao D.H., McDonagh T., Telliez J.-B., Hsu S., Malakian K., Xu G.Y.,
RA Lin L.L.;
RT "Solution structure of N-TRADD and characterization of the interaction of
RT N-TRADD and C-TRAF2, a key step in the TNFR1 signaling pathway.";
RL Mol. Cell 5:1051-1057(2000).
RN [26]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1-179 IN COMPLEX WITH TRAF2.
RX PubMed=10892748; DOI=10.1016/s0092-8674(00)80889-2;
RA Park Y.C., Ye H., Hsia C., Segal D., Rich R.L., Liou H.C., Myszka D.G.,
RA Wu H.;
RT "A novel mechanism of TRAF signaling revealed by structural and functional
RT analyses of the TRADD-TRAF2 interaction.";
RL Cell 101:777-787(2000).
RN [27] {ECO:0007744|PDB:6AC0}
RP X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) OF 195-312, AND GLYCOSYLATION AT
RP ARG-235 (MICROBIAL INFECTION).
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: Adapter molecule for TNFRSF1A/TNFR1 that specifically
CC associates with the cytoplasmic domain of activated TNFRSF1A/TNFR1
CC mediating its interaction with FADD (PubMed:7758105, PubMed:8612133,
CC PubMed:23955153). Overexpression of TRADD leads to two major TNF-
CC induced responses, apoptosis and activation of NF-kappa-B
CC (PubMed:7758105, PubMed:8612133). The nuclear form acts as a tumor
CC suppressor by preventing ubiquitination and degradation of isoform
CC p19ARF/ARF of CDKN2A by TRIP12: acts by interacting with TRIP12,
CC leading to disrupt interaction between TRIP12 and isoform p19ARF/ARF of
CC CDKN2A (By similarity). {ECO:0000250|UniProtKB:Q3U0V2,
CC ECO:0000269|PubMed:23955153, ECO:0000269|PubMed:7758105,
CC ECO:0000269|PubMed:8612133}.
CC -!- SUBUNIT: Stimulation of TNF-alpha receptor TNFRSF1A leads to the
CC formation of two distinct signaling complexes (PubMed:7758105,
CC PubMed:8612133, PubMed:14585990, PubMed:21307340). Plasma membrane-
CC bound complex I is composed of TNFRSF1A, TRADD, RIPK1, TRAF2 and
CC BIRC2/c-IAP1 or BIRC3 which interacts with CHUCK/IKK-alpha, IKBKB/IKK-
CC beta and IKBKG/IKK-gamma promoting cell survival (PubMed:7758105,
CC PubMed:8612133, PubMed:14585990, PubMed:21307340). Subsequently, TRADD,
CC RIPK1 and TRAF2 dissociate from TNFRSF1A and form cytoplasmic complex
CC II with FADD and caspase CASP8 promoting cell apoptosis
CC (PubMed:21307340). Within complex I, interacts with TNFRSF1A/TNFR1,
CC TRAF2 and kinase RIPK1 (PubMed:7758105, PubMed:10892748,
CC PubMed:8612133). Within complex I, interacts with TRPC4AP; the
CC interaction promotes NF-kappa B activation (PubMed:14585990). UXT1
CC associates with complex I; the interaction prevents the formation of
CC complex II (PubMed:21307340). Within complex I Interacts with scaffold
CC protein DAB2IP (PubMed:15310755). Interacts with autophagy receptor
CC SQSTM1 (PubMed:10356400). Interacts with E3 ligase TRIP12 (By
CC similarity). Interacts with kinase HIPK2 (PubMed:11032752). Interacts
CC with keratin KRT14 (PubMed:11684708). Interacts with keratin KRT18
CC (PubMed:11684708). Interacts with keratins KRT16 and KRT17 (By
CC similarity). Interacts with FADD (By similarity). Interacts with TOMM70
CC (PubMed:20628368). {ECO:0000250|UniProtKB:Q3U0V2,
CC ECO:0000269|PubMed:10356400, ECO:0000269|PubMed:10892748,
CC ECO:0000269|PubMed:11032752, ECO:0000269|PubMed:11684708,
CC ECO:0000269|PubMed:14585990, ECO:0000269|PubMed:15310755,
CC ECO:0000269|PubMed:20628368, ECO:0000269|PubMed:21307340,
CC ECO:0000269|PubMed:24130170, ECO:0000269|PubMed:7758105,
CC ECO:0000269|PubMed:8612133}.
CC -!- INTERACTION:
CC Q15628; Q13158: FADD; NbExp=7; IntAct=EBI-359215, EBI-494804;
CC Q15628; P05783: KRT18; NbExp=11; IntAct=EBI-359215, EBI-297888;
CC Q15628; P19438: TNFRSF1A; NbExp=13; IntAct=EBI-359215, EBI-299451;
CC Q15628; Q15628: TRADD; NbExp=5; IntAct=EBI-359215, EBI-359215;
CC Q15628; Q12933: TRAF2; NbExp=13; IntAct=EBI-359215, EBI-355744;
CC Q15628; P03230: LMP1; Xeno; NbExp=4; IntAct=EBI-359215, EBI-6973030;
CC Q15628; B7UI21: nleB1; Xeno; NbExp=7; IntAct=EBI-359215, EBI-16070376;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q3U0V2}. Cytoplasm
CC {ECO:0000269|PubMed:11684708}. Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:11684708}. Note=Shuttles between the cytoplasm and
CC the nucleus. {ECO:0000250|UniProtKB:Q3U0V2}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q15628-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q15628-2; Sequence=VSP_056526;
CC -!- TISSUE SPECIFICITY: Found in all examined tissues.
CC {ECO:0000269|PubMed:7758105}.
CC -!- DOMAIN: Requires the intact death domain to associate with
CC TNFRSF1A/TNFR1. {ECO:0000269|PubMed:7758105}.
CC -!- PTM: (Microbial infection) Glycosylated at Arg-235 by enteropathogenic
CC E.coli protein NleB1, C.rodentium protein NleB and S.typhimurium
CC proteins Ssek1 and Ssek3: arginine GlcNAcylation prevents
CC homotypic/heterotypic death domain interactions and assembly of the
CC oligomeric TNFRSF1A/TNFR1 complex, thereby disrupting TNF signaling.
CC {ECO:0000269|PubMed:23955153, ECO:0000269|PubMed:28069818,
CC ECO:0000269|PubMed:29449376, ECO:0000269|PubMed:30902834,
CC ECO:0000269|PubMed:32766249}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA98482.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/tradd/";
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DR EMBL; L41690; AAA98482.1; ALT_INIT; mRNA.
DR EMBL; AJ311614; CAC38018.2; -; Genomic_DNA.
DR EMBL; AJ311615; CAC38018.2; JOINED; Genomic_DNA.
DR EMBL; AJ311616; CAC38018.2; JOINED; Genomic_DNA.
DR EMBL; AY995114; AAX89407.1; -; Genomic_DNA.
DR EMBL; BT006934; AAP35580.1; -; mRNA.
DR EMBL; AY575851; AAS68637.1; -; Genomic_DNA.
DR EMBL; AK090673; BAG52211.1; -; mRNA.
DR EMBL; AK315654; BAG38020.1; -; mRNA.
DR EMBL; AC074143; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471092; EAW83081.1; -; Genomic_DNA.
DR EMBL; BC004491; AAH04491.1; -; mRNA.
DR CCDS; CCDS10829.1; -. [Q15628-1]
DR PIR; A56911; A56911.
DR RefSeq; NP_001310481.1; NM_001323552.1. [Q15628-1]
DR RefSeq; NP_003780.1; NM_003789.3. [Q15628-1]
DR RefSeq; XP_005256270.1; XM_005256213.3. [Q15628-2]
DR RefSeq; XP_016879304.1; XM_017023815.1. [Q15628-1]
DR PDB; 1F2H; NMR; -; A=1-169.
DR PDB; 1F3V; X-ray; 2.00 A; A=1-179.
DR PDB; 5XME; NMR; -; A=199-312.
DR PDB; 6AC0; X-ray; 1.45 A; A=195-312.
DR PDB; 7CSQ; NMR; -; B=199-312.
DR PDBsum; 1F2H; -.
DR PDBsum; 1F3V; -.
DR PDBsum; 5XME; -.
DR PDBsum; 6AC0; -.
DR PDBsum; 7CSQ; -.
DR AlphaFoldDB; Q15628; -.
DR BMRB; Q15628; -.
DR SMR; Q15628; -.
DR BioGRID; 114257; 102.
DR CORUM; Q15628; -.
DR DIP; DIP-285N; -.
DR IntAct; Q15628; 71.
DR MINT; Q15628; -.
DR STRING; 9606.ENSP00000341268; -.
DR iPTMnet; Q15628; -.
DR PhosphoSitePlus; Q15628; -.
DR BioMuta; TRADD; -.
DR DMDM; 6094511; -.
DR EPD; Q15628; -.
DR jPOST; Q15628; -.
DR MassIVE; Q15628; -.
DR MaxQB; Q15628; -.
DR PaxDb; Q15628; -.
DR PeptideAtlas; Q15628; -.
DR PRIDE; Q15628; -.
DR ProteomicsDB; 60663; -. [Q15628-1]
DR Antibodypedia; 3894; 535 antibodies from 43 providers.
DR DNASU; 8717; -.
DR Ensembl; ENST00000345057.9; ENSP00000341268.4; ENSG00000102871.16. [Q15628-1]
DR Ensembl; ENST00000486556.1; ENSP00000462591.1; ENSG00000102871.16. [Q15628-2]
DR GeneID; 8717; -.
DR KEGG; hsa:8717; -.
DR MANE-Select; ENST00000345057.9; ENSP00000341268.4; NM_003789.4; NP_003780.1.
DR UCSC; uc002erh.2; human. [Q15628-1]
DR CTD; 8717; -.
DR DisGeNET; 8717; -.
DR GeneCards; TRADD; -.
DR HGNC; HGNC:12030; TRADD.
DR HPA; ENSG00000102871; Low tissue specificity.
DR MIM; 603500; gene.
DR neXtProt; NX_Q15628; -.
DR OpenTargets; ENSG00000102871; -.
DR PharmGKB; PA36707; -.
DR VEuPathDB; HostDB:ENSG00000102871; -.
DR eggNOG; ENOG502RXWE; Eukaryota.
DR GeneTree; ENSGT00390000002016; -.
DR HOGENOM; CLU_052183_0_0_1; -.
DR InParanoid; Q15628; -.
DR OMA; QPCSRFL; -.
DR OrthoDB; 1024816at2759; -.
DR PhylomeDB; Q15628; -.
DR TreeFam; TF331882; -.
DR PathwayCommons; Q15628; -.
DR Reactome; R-HSA-140534; Caspase activation via Death Receptors in the presence of ligand.
DR Reactome; R-HSA-3371378; Regulation by c-FLIP.
DR Reactome; R-HSA-5213460; RIPK1-mediated regulated necrosis.
DR Reactome; R-HSA-5218900; CASP8 activity is inhibited.
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-5675482; Regulation of necroptotic cell death.
DR Reactome; R-HSA-69416; Dimerization of procaspase-8.
DR Reactome; R-HSA-75893; TNF signaling.
DR Reactome; R-HSA-9693928; Defective RIPK1-mediated regulated necrosis.
DR SignaLink; Q15628; -.
DR SIGNOR; Q15628; -.
DR BioGRID-ORCS; 8717; 17 hits in 1086 CRISPR screens.
DR EvolutionaryTrace; Q15628; -.
DR GeneWiki; TRADD; -.
DR GenomeRNAi; 8717; -.
DR Pharos; Q15628; Tbio.
DR PRO; PR:Q15628; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q15628; protein.
DR Bgee; ENSG00000102871; Expressed in pancreatic ductal cell and 193 other tissues.
DR Genevisible; Q15628; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0031264; C:death-inducing signaling complex; TAS:UniProtKB.
DR GO; GO:0045121; C:membrane raft; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0043235; C:receptor complex; IDA:BHF-UCL.
DR GO; GO:0002947; C:tumor necrosis factor receptor superfamily complex; IDA:UniProtKB.
DR GO; GO:0070513; F:death domain binding; IPI:BHF-UCL.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0019900; F:kinase binding; IPI:BHF-UCL.
DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
DR GO; GO:0005068; F:transmembrane receptor protein tyrosine kinase adaptor activity; IPI:BHF-UCL.
DR GO; GO:0005164; F:tumor necrosis factor receptor binding; IEA:Ensembl.
DR GO; GO:0006915; P:apoptotic process; TAS:ProtInc.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IMP:ARUK-UCL.
DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; IMP:UniProtKB.
DR GO; GO:0008625; P:extrinsic apoptotic signaling pathway via death domain receptors; TAS:BHF-UCL.
DR GO; GO:0043065; P:positive regulation of apoptotic process; TAS:UniProtKB.
DR GO; GO:0030335; P:positive regulation of cell migration; IMP:ARUK-UCL.
DR GO; GO:0051798; P:positive regulation of hair follicle development; IEA:Ensembl.
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; IMP:ARUK-UCL.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IMP:ARUK-UCL.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; IMP:ARUK-UCL.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; TAS:BHF-UCL.
DR Gene3D; 1.10.533.10; -; 1.
DR Gene3D; 3.30.70.680; -; 1.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR000488; Death_domain.
DR InterPro; IPR035712; TRADD.
DR InterPro; IPR009095; TRADD_N.
DR InterPro; IPR036729; TRADD_N_sf.
DR PANTHER; PTHR14913; PTHR14913; 1.
DR Pfam; PF00531; Death; 1.
DR Pfam; PF09034; TRADD_N; 1.
DR SMART; SM00005; DEATH; 1.
DR SUPFAM; SSF47986; SSF47986; 1.
DR SUPFAM; SSF55044; SSF55044; 1.
DR PROSITE; PS50017; DEATH_DOMAIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Apoptosis; Cytoplasm; Cytoskeleton;
KW Glycoprotein; Nucleus; Reference proteome.
FT CHAIN 1..312
FT /note="Tumor necrosis factor receptor type 1-associated
FT DEATH domain protein"
FT /id="PRO_0000065602"
FT DOMAIN 179..289
FT /note="Death"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00064"
FT REGION 170..195
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 222..289
FT /note="Interaction with KRT14 and KRT18"
FT /evidence="ECO:0000269|PubMed:11684708"
FT MOTIF 147..163
FT /note="Nuclear export signal"
FT /evidence="ECO:0000250|UniProtKB:Q3U0V2"
FT MOTIF 231..244
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:Q3U0V2"
FT CARBOHYD 235
FT /note="(Microbial infection) N-beta-linked (GlcNAc)
FT arginine"
FT /evidence="ECO:0000269|PubMed:23955153,
FT ECO:0000269|PubMed:30979585, ECO:0000269|PubMed:32766249,
FT ECO:0007744|PDB:6AC0"
FT CARBOHYD 245
FT /note="(Microbial infection) N-beta-linked (GlcNAc)
FT arginine"
FT /evidence="ECO:0000269|PubMed:32766249"
FT VAR_SEQ 1..60
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056526"
FT MUTAGEN 235
FT /note="R->A,K: Abolished GlcNAcylation by E.coli NleB1.
FT Abolished ability to self-oligomerize. Strongly reduced
FT GlcNAcylation by S.typhimurium Ssek1; when associated with
FT A-245."
FT /evidence="ECO:0000269|PubMed:23955153,
FT ECO:0000269|PubMed:32766249"
FT MUTAGEN 245
FT /note="R->A: Strongly reduced GlcNAcylation by
FT S.typhimurium Ssek1; when associated with A-235."
FT /evidence="ECO:0000269|PubMed:32766249"
FT STRAND 12..25
FT /evidence="ECO:0007829|PDB:1F3V"
FT HELIX 28..33
FT /evidence="ECO:0007829|PDB:1F3V"
FT TURN 35..37
FT /evidence="ECO:0007829|PDB:1F3V"
FT HELIX 38..52
FT /evidence="ECO:0007829|PDB:1F3V"
FT TURN 56..58
FT /evidence="ECO:0007829|PDB:1F3V"
FT STRAND 59..66
FT /evidence="ECO:0007829|PDB:1F3V"
FT STRAND 68..79
FT /evidence="ECO:0007829|PDB:1F3V"
FT HELIX 80..91
FT /evidence="ECO:0007829|PDB:1F3V"
FT HELIX 94..106
FT /evidence="ECO:0007829|PDB:1F3V"
FT STRAND 114..120
FT /evidence="ECO:0007829|PDB:1F3V"
FT HELIX 125..128
FT /evidence="ECO:0007829|PDB:1F3V"
FT HELIX 132..141
FT /evidence="ECO:0007829|PDB:1F3V"
FT HELIX 150..162
FT /evidence="ECO:0007829|PDB:1F3V"
FT STRAND 200..204
FT /evidence="ECO:0007829|PDB:6AC0"
FT STRAND 207..210
FT /evidence="ECO:0007829|PDB:6AC0"
FT HELIX 216..225
FT /evidence="ECO:0007829|PDB:6AC0"
FT HELIX 227..229
FT /evidence="ECO:0007829|PDB:6AC0"
FT HELIX 230..238
FT /evidence="ECO:0007829|PDB:6AC0"
FT HELIX 242..244
FT /evidence="ECO:0007829|PDB:6AC0"
FT HELIX 248..256
FT /evidence="ECO:0007829|PDB:6AC0"
FT HELIX 257..259
FT /evidence="ECO:0007829|PDB:6AC0"
FT HELIX 261..276
FT /evidence="ECO:0007829|PDB:6AC0"
FT HELIX 277..279
FT /evidence="ECO:0007829|PDB:6AC0"
FT HELIX 282..291
FT /evidence="ECO:0007829|PDB:6AC0"
FT HELIX 295..301
FT /evidence="ECO:0007829|PDB:6AC0"
FT STRAND 306..308
FT /evidence="ECO:0007829|PDB:5XME"
SQ SEQUENCE 312 AA; 34247 MW; 5645D7E63E5FF05A CRC64;
MAAGQNGHEE WVGSAYLFVE SSLDKVVLSD AYAHPQQKVA VYRALQAALA ESGGSPDVLQ
MLKIHRSDPQ LIVQLRFCGR QPCGRFLRAY REGALRAALQ RSLAAALAQH SVPLQLELRA
GAERLDALLA DEERCLSCIL AQQPDRLRDE ELAELEDALR NLKCGSGARG GDGEVASAPL
QPPVPSLSEV KPPPPPPPAQ TFLFQGQPVV NRPLSLKDQQ TFARSVGLKW RKVGRSLQRG
CRALRDPALD SLAYEYEREG LYEQAFQLLR RFVQAEGRRA TLQRLVEALE ENELTSLAED
LLGLTDPNGG LA
