ID FADD_HUMAN Reviewed; 208 AA. AC Q13158; Q14866; Q6IBR4; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1997, sequence version 1. DT 27-MAR-2024, entry version 226. DE RecName: Full=FAS-associated death domain protein {ECO:0000303|PubMed:7538907}; DE AltName: Full=FAS-associating death domain-containing protein {ECO:0000303|PubMed:7538907}; DE AltName: Full=Growth-inhibiting gene 3 protein {ECO:0000303|Ref.3}; DE AltName: Full=Mediator of receptor induced toxicity {ECO:0000303|PubMed:7536190}; GN Name=FADD {ECO:0000303|PubMed:7538907, ECO:0000312|HGNC:HGNC:3573}; GN Synonyms=MORT1 {ECO:0000303|PubMed:7536190}; GN ORFNames=GIG3 {ECO:0000303|Ref.3}; 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], FUNCTION, AND TISSUE SPECIFICITY. RC TISSUE=Umbilical vein endothelial cell; RX PubMed=7538907; DOI=10.1016/0092-8674(95)90071-3; RA Chinnaiyan A.M., O'Rourke K., Tewari M., Dixit V.M.; RT "FADD, a novel death domain-containing protein, interacts with the death RT domain of Fas and initiates apoptosis."; RL Cell 81:505-512(1995). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=7536190; DOI=10.1074/jbc.270.14.7795; RA Boldin M.P., Varfolomeev E.E., Pancer Z., Mett I.L., Camonis J.H., RA Wallach D.; RT "A novel protein that interacts with the death domain of Fas/APO1 contains RT a sequence motif related to the death domain."; RL J. Biol. Chem. 270:7795-7798(1995). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Kim J.W.; RT "Identification of a human growth inhibition gene 3 (GIG3)."; RL Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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 (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RG NIEHS SNPs program; RL Submitted (MAR-2006) to the EMBL/GenBank/DDBJ databases. 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]. RC TISSUE=Lung; 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, AND IDENTIFICATION IN DISC COMPLEX. RX PubMed=9184224; DOI=10.1093/emboj/16.10.2794; RA Medema J.P., Scaffidi C., Kischkel F.C., Shevchenko A., Mann M., RA Krammer P.H., Peter M.E.; RT "FLICE is activated by association with the CD95 death-inducing signaling RT complex (DISC)."; RL EMBO J. 16:2794-2804(1997). RN [11] RP INTERACTION WITH PEA15. RX PubMed=10442631; DOI=10.1038/sj.onc.1202831; RA Condorelli G., Vigliotta G., Cafieri A., Trencia A., Andalo P., Oriente F., RA Miele C., Caruso M., Formisano P., Beguinot F.; RT "PED/PEA-15: an anti-apoptotic molecule that regulates FAS/TNFR1-induced RT apoptosis."; RL Oncogene 18:4409-4415(1999). RN [12] RP INTERACTION WITH PIDD1. RX PubMed=10825539; DOI=10.1016/s0167-4838(00)00029-7; RA Telliez J.-B., Bean K.M., Lin L.-L.; RT "LRDD, a novel leucine rich repeat and death domain containing protein."; RL Biochim. Biophys. Acta 1478:280-288(2000). RN [13] RP IDENTIFICATION IN A COMPLEX WITH HIPK3 AND FAS, AND PHOSPHORYLATION AT RP SER-194. RX PubMed=11034606; DOI=10.1084/jem.192.8.1165; RA Rochat-Steiner V., Becker K., Micheau O., Schneider P., Burns K., RA Tschopp J.; RT "FIST/HIPK3: a Fas/FADD-interacting serine/threonine kinase that induces RT FADD phosphorylation and inhibits Fas-mediated Jun NH2-terminal kinase RT activation."; RL J. Exp. Med. 192:1165-1174(2000). RN [14] RP INTERACTION WITH MOLLUSCUM CONTAGIOSUM VIRUS PROTEIN MC159L AND MC160L RP (MICROBIAL INFECTION). RX PubMed=11259186; DOI=10.1006/viro.2001.0834; RA Shisler J.L., Moss B.; RT "Molluscum contagiosum virus inhibitors of apoptosis: The MC159 v-FLIP RT protein blocks Fas-induced activation of procaspases and degradation of the RT related MC160 protein."; RL Virology 282:14-25(2001). RN [15] RP INTERACTION WITH MBD4. RX PubMed=12702765; DOI=10.1073/pnas.0431215100; RA Screaton R.A., Kiessling S., Sansom O.J., Millar C.B., Maddison K., RA Bird A., Clarke A.R., Frisch S.M.; RT "Fas-associated death domain protein interacts with methyl-CpG binding RT domain protein 4: a potential link between genome surveillance and RT apoptosis."; RL Proc. Natl. Acad. Sci. U.S.A. 100:5211-5216(2003). RN [16] RP INTERACTION WITH MAVS. RX PubMed=16127453; DOI=10.1038/ni1243; RA Kawai T., Takahashi K., Sato S., Coban C., Kumar H., Kato H., Ishii K.J., RA Takeuchi O., Akira S.; RT "IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon RT induction."; RL Nat. Immunol. 6:981-988(2005). RN [17] RP INTERACTION WITH TNFRSF10B. RX PubMed=18846110; DOI=10.1038/cdd.2008.124; RA Sun M., Song L., Li Y., Zhou T., Jope R.S.; RT "Identification of an antiapoptotic protein complex at death receptors."; RL Cell Death Differ. 15:1887-1900(2008). RN [18] RP INTERACTION WITH HUMAN PAPILLOMAVIRUS 16/HPV16 PROTEIN E6 (MICROBIAL RP INFECTION). RX PubMed=18632871; DOI=10.1128/jvi.00538-08; RA Tungteakkhun S.S., Filippova M., Neidigh J.W., Fodor N., RA Duerksen-Hughes P.J.; RT "The interaction between human papillomavirus type 16 and FADD is mediated RT by a novel E6 binding domain."; RL J. Virol. 82:9600-9614(2008). RN [19] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [20] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-194, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [21] RP FUNCTION IN INTERFERON-MEDIATED IMMUNITY, INTERACTION WITH FAS, VARIANT RP IEHDCM TRP-105, AND CHARACTERIZATION OF VARIANT IEHDCM TRP-105. RX PubMed=21109225; DOI=10.1016/j.ajhg.2010.10.028; RA Bolze A., Byun M., McDonald D., Morgan N.V., Abhyankar A., Premkumar L., RA Puel A., Bacon C.M., Rieux-Laucat F., Pang K., Britland A., Abel L., RA Cant A., Maher E.R., Riedl S.J., Hambleton S., Casanova J.L.; RT "Whole-exome-sequencing-based discovery of human FADD deficiency."; RL Am. J. Hum. Genet. 87:873-881(2010). RN [22] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [23] 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 [24] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-194, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [25] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-194, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [26] RP FUNCTION, AND GLYCOSYLATION AT ARG-117 (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 FUNCTION, GLYCOSYLATION AT ARG-117 (MICROBIAL INFECTION), AND MUTAGENESIS RP OF ARG-117. RX PubMed=24025841; DOI=10.1038/nature12524; RA Pearson J.S., Giogha C., Ong S.Y., Kennedy C.L., Kelly M., Robinson K.S., RA Lung T.W., Mansell A., Riedmaier P., Oates C.V., Zaid A., Muehlen S., RA Crepin V.F., Marches O., Ang C.S., Williamson N.A., O'Reilly L.A., RA Bankovacki A., Nachbur U., Infusini G., Webb A.I., Silke J., Strasser A., RA Frankel G., Hartland E.L.; RT "A type III effector antagonizes death receptor signalling during bacterial RT gut infection."; RL Nature 501:247-251(2013). RN [28] 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 [29] RP GLYCOSYLATION AT ARG-117 (MICROBIAL INFECTION). RX PubMed=28860194; DOI=10.1074/jbc.m117.805036; RA Scott N.E., Giogha C., Pollock G.L., Kennedy C.L., Webb A.I., RA Williamson N.A., Pearson J.S., Hartland E.L.; RT "The bacterial arginine glycosyltransferase effector NleB preferentially RT modifies Fas-associated death domain protein (FADD)."; RL J. Biol. Chem. 292:17337-17350(2017). RN [30] RP STRUCTURE BY NMR OF 1-83. RX PubMed=9582077; DOI=10.1038/31972; RA Eberstadt M., Huang B., Chen Z., Meadows R.P., Ng S.C., Zheng L., RA Lenardo M.J., Fesik S.W.; RT "NMR structure and mutagenesis of the FADD (Mort1) death-effector domain."; RL Nature 392:941-945(1998). RN [31] RP STRUCTURE BY NMR OF 93-192. RX PubMed=10964568; DOI=10.1006/jmbi.2000.4011; RA Berglund H., Olerenshaw D., Sankar A., Federwisch M., McDonald N.Q., RA Driscoll P.C.; RT "The three-dimensional solution structure and dynamic properties of the RT human FADD death domain."; RL J. Mol. Biol. 302:171-188(2000). RN [32] RP STRUCTURE BY NMR OF 2-191, FUNCTION, INTERACTION WITH FAS AND CASP8, AND RP MUTAGENESIS OF SER-12; PHE-25; LYS-33; ARG-38; ASP-44 AND GLU-51. RX PubMed=16762833; DOI=10.1016/j.molcel.2006.04.018; RA Carrington P.E., Sandu C., Wei Y., Hill J.M., Morisawa G., Huang T., RA Gavathiotis E., Wei Y., Werner M.H.; RT "The structure of FADD and its mode of interaction with procaspase-8."; RL Mol. Cell 22:599-610(2006). RN [33] RP X-RAY CRYSTALLOGRAPHY (2.73 ANGSTROMS) OF 93-208 IN COMPLEX WITH FAS, RP FUNCTION, SUBUNIT, ELECTRON MICROSCOPY, DOMAIN, AND MUTAGENESIS OF LEU-172 RP AND LEU-176. RX PubMed=19118384; DOI=10.1038/nature07606; RA Scott F.L., Stec B., Pop C., Dobaczewska M.K., Lee J.J., Monosov E., RA Robinson H., Salvesen G.S., Schwarzenbacher R., Riedl S.J.; RT "The Fas-FADD death domain complex structure unravels signalling by RT receptor clustering."; RL Nature 457:1019-1022(2009). RN [34] RP X-RAY CRYSTALLOGRAPHY (6.80 ANGSTROMS) OF 93-184 IN COMPLEX WITH FAS, RP ELECTRON MICROSCOPY, FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, RP SUBUNIT, AND MUTAGENESIS OF ARG-117; ASP-123; ARG-135; ARG-142; LEU-172 AND RP ASP-175. RX PubMed=20935634; DOI=10.1038/nsmb.1920; RA Wang L., Yang J.K., Kabaleeswaran V., Rice A.J., Cruz A.C., Park A.Y., RA Yin Q., Damko E., Jang S.B., Raunser S., Robinson C.V., Siegel R.M., RA Walz T., Wu H.; RT "The Fas-FADD death domain complex structure reveals the basis of DISC RT assembly and disease mutations."; RL Nat. Struct. Mol. Biol. 17:1324-1329(2010). RN [35] {ECO:0007744|PDB:6ACI} RP X-RAY CRYSTALLOGRAPHY (1.87 ANGSTROMS) OF 93-184 IN COMPLEX WITH E.COLI RP PROTEIN NLEB1, GLYCOSYLATION AT ARG-117 (MICROBIAL INFECTION), AND RP MUTAGENESIS OF ARG-117. 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: Apoptotic adapter molecule that recruits caspases CASP8 or CC CASP10 to the activated FAS/CD95 or TNFRSF1A/TNFR-1 receptors CC (PubMed:7538907, PubMed:23955153, PubMed:19118384, PubMed:20935634, CC PubMed:16762833, PubMed:24025841, PubMed:9184224). The resulting CC aggregate called the death-inducing signaling complex (DISC) performs CC CASP8 proteolytic activation (PubMed:7538907, PubMed:19118384, CC PubMed:20935634, PubMed:16762833, PubMed:9184224). Active CASP8 CC initiates the subsequent cascade of caspases mediating apoptosis CC (PubMed:16762833). Involved in interferon-mediated antiviral immune CC response, playing a role in the positive regulation of interferon CC signaling (PubMed:21109225). {ECO:0000269|PubMed:16762833, CC ECO:0000269|PubMed:19118384, ECO:0000269|PubMed:20935634, CC ECO:0000269|PubMed:21109225, ECO:0000269|PubMed:23955153, CC ECO:0000269|PubMed:24025841, ECO:0000269|PubMed:7538907, CC ECO:0000269|PubMed:9184224}. CC -!- SUBUNIT: Can self-associate (PubMed:19118384, PubMed:20935634). CC Component of the AIM2 PANoptosome complex, a multiprotein complex that CC drives inflammatory cell death (PANoptosis) (By similarity). Component CC of the death-induced signaling complex (DISC) composed of cell surface CC receptor FAS/CD95 or TNFRSF1A, adapter protein FADD and the CASP8 CC protease; recruitment of CASP8 to the complex is required for CC processing of CASP8 into the p18 and p10 subunits (PubMed:9184224, CC PubMed:16762833). Interacts (via death domain) with FAS (via death CC domain) (PubMed:21109225, PubMed:16762833, PubMed:20935634). Interacts CC directly (via DED domain) with NOL3 (via CARD domain); inhibits death- CC inducing signaling complex (DISC) assembly by inhibiting the increase CC in FAS-FADD binding induced by FAS activation (By similarity). CC Interacts with CFLAR, PEA15 and MBD4 (PubMed:10442631, CC PubMed:12702765). When phosphorylated, part of a complex containing CC HIPK3 and FAS (PubMed:11034606). May interact with MAVS/IPS1 CC (PubMed:16127453). Interacts with MOCV v-CFLAR protein and PIDD1 CC (PubMed:10825539). Interacts with RIPK1 and TRADD (By similarity). CC Interacts with stimulated TNFRSF10B (PubMed:18846110). Interacts with CC stimulated TNFRSF10B (By similarity). {ECO:0000250|UniProtKB:Q61160, CC ECO:0000269|PubMed:10442631, ECO:0000269|PubMed:10825539, CC ECO:0000269|PubMed:11034606, ECO:0000269|PubMed:12702765, CC ECO:0000269|PubMed:16127453, ECO:0000269|PubMed:16762833, CC ECO:0000269|PubMed:18846110, ECO:0000269|PubMed:19118384, CC ECO:0000269|PubMed:20935634, ECO:0000269|PubMed:21109225, CC ECO:0000269|PubMed:9184224}. CC -!- SUBUNIT: (Microbial infection) Interacts with human papillomavirus CC 16/HPV16 protein E6. {ECO:0000269|PubMed:18632871}. CC -!- SUBUNIT: (Microbial infection) Interacts with molluscum contagiosum CC virus proteins MC159L/v-CFLAR and MC160L. CC {ECO:0000269|PubMed:11259186}. CC -!- INTERACTION: CC Q13158; P62324: BTG1; NbExp=5; IntAct=EBI-494804, EBI-742279; CC Q13158; Q14790: CASP8; NbExp=45; IntAct=EBI-494804, EBI-78060; CC Q13158; Q14790-1: CASP8; NbExp=5; IntAct=EBI-494804, EBI-288309; CC Q13158; Q14790-5: CASP8; NbExp=4; IntAct=EBI-494804, EBI-288326; CC Q13158; Q96D03: DDIT4L; NbExp=3; IntAct=EBI-494804, EBI-742054; CC Q13158; Q13158: FADD; NbExp=12; IntAct=EBI-494804, EBI-494804; CC Q13158; B7ZLH0: FAM22F; NbExp=3; IntAct=EBI-494804, EBI-10220102; CC Q13158; P25445: FAS; NbExp=21; IntAct=EBI-494804, EBI-494743; CC Q13158; P25445-1: FAS; NbExp=17; IntAct=EBI-494804, EBI-15749113; CC Q13158; P48023: FASLG; NbExp=4; IntAct=EBI-494804, EBI-495538; CC Q13158; Q5S007: LRRK2; NbExp=4; IntAct=EBI-494804, EBI-5323863; CC Q13158; O95243: MBD4; NbExp=6; IntAct=EBI-494804, EBI-348011; CC Q13158; Q99836: MYD88; NbExp=3; IntAct=EBI-494804, EBI-447677; CC Q13158; Q99497: PARK7; NbExp=9; IntAct=EBI-494804, EBI-1164361; CC Q13158; P53350: PLK1; NbExp=9; IntAct=EBI-494804, EBI-476768; CC Q13158; Q13546: RIPK1; NbExp=11; IntAct=EBI-494804, EBI-358507; CC Q13158; P78317: RNF4; NbExp=5; IntAct=EBI-494804, EBI-2340927; CC Q13158; O00560: SDCBP; NbExp=6; IntAct=EBI-494804, EBI-727004; CC Q13158; Q15560: TCEA2; NbExp=3; IntAct=EBI-494804, EBI-710310; CC Q13158; Q15628: TRADD; NbExp=7; IntAct=EBI-494804, EBI-359215; CC Q13158; Q7KZS0: UBE2I; NbExp=3; IntAct=EBI-494804, EBI-10180829; CC Q13158; Q6PEW1: ZCCHC12; NbExp=3; IntAct=EBI-494804, EBI-748373; CC Q13158; Q9UJ78-2: ZMYM5; NbExp=3; IntAct=EBI-494804, EBI-17634549; CC Q13158; P25446: Fas; Xeno; NbExp=8; IntAct=EBI-494804, EBI-296206; CC Q13158; B7UI21: nleB1; Xeno; NbExp=7; IntAct=EBI-494804, EBI-16070376; CC -!- TISSUE SPECIFICITY: Expressed in a wide variety of tissues, except for CC peripheral blood mononuclear leukocytes. {ECO:0000269|PubMed:7538907}. CC -!- DOMAIN: Contains a death domain involved in the binding of the CC corresponding domain within Fas receptor. CC {ECO:0000269|PubMed:19118384}. CC -!- DOMAIN: The interaction between the FAS and FADD death domains is CC crucial for the formation of the death-inducing signaling complex CC (DISC). {ECO:0000269|PubMed:19118384}. CC -!- PTM: (Microbial infection) Glycosylated at Arg-117 by enteropathogenic CC E.coli protein NleB1, C.rodentium protein NleB and S.typhimurium CC protein Ssek1: arginine GlcNAcylation prevents recruitment of caspase-8 CC or caspase-10 to the activated Fas (CD95) or TNFR-1 receptors. CC {ECO:0000269|PubMed:23955153, ECO:0000269|PubMed:24025841, CC ECO:0000269|PubMed:28069818, ECO:0000269|PubMed:28860194}. CC -!- DISEASE: Infections, recurrent, associated with encephalopathy, hepatic CC dysfunction and cardiovascular malformations (IEHDCM) [MIM:613759]: A CC condition with biological features of autoimmune lymphoproliferative CC syndrome such as high-circulating CD4(-)CD8(-)TCR-alpha-beta(+) T-cell CC counts, and elevated IL10 and FASL levels. Affected individuals suffer CC from recurrent, stereotypical episodes of fever, encephalopathy, and CC mild liver dysfunction sometimes accompanied by generalized seizures. CC The episodes can be triggered by varicella zoster virus (VZV), measles CC mumps rubella (MMR) attenuated vaccine, parainfluenza virus, and CC Epstein-Barr virus (EBV). {ECO:0000269|PubMed:21109225}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/fadd/"; 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; U24231; AAA86517.1; -; mRNA. DR EMBL; X84709; CAA59197.1; -; mRNA. DR EMBL; AY423721; AAS00484.1; -; mRNA. DR EMBL; AK291005; BAF83694.1; -; mRNA. DR EMBL; BT006927; AAP35573.1; -; mRNA. DR EMBL; CR456738; CAG33019.1; -; mRNA. DR EMBL; DQ449938; ABD96828.1; -; Genomic_DNA. DR EMBL; CH471076; EAW74761.1; -; Genomic_DNA. DR EMBL; BC000334; AAH00334.1; -; mRNA. DR CCDS; CCDS8196.1; -. DR PIR; A56912; A56912. DR RefSeq; NP_003815.1; NM_003824.3. DR PDB; 1A1W; NMR; -; A=1-83. DR PDB; 1A1Z; NMR; -; A=1-83. DR PDB; 1E3Y; NMR; -; A=93-192. DR PDB; 1E41; NMR; -; A=93-192. DR PDB; 2GF5; NMR; -; A=2-191. DR PDB; 3EZQ; X-ray; 2.73 A; B/D/F/H/J/L/N/P=93-208. DR PDB; 3OQ9; X-ray; 6.80 A; H/I/J/K/L=93-184. DR PDB; 6ACI; X-ray; 1.87 A; H=93-184. DR PDB; 7LXC; NMR; -; A=16-42. DR PDBsum; 1A1W; -. DR PDBsum; 1A1Z; -. DR PDBsum; 1E3Y; -. DR PDBsum; 1E41; -. DR PDBsum; 2GF5; -. DR PDBsum; 3EZQ; -. DR PDBsum; 3OQ9; -. DR PDBsum; 6ACI; -. DR PDBsum; 7LXC; -. DR AlphaFoldDB; Q13158; -. DR BMRB; Q13158; -. DR SMR; Q13158; -. DR BioGRID; 114302; 115. DR ComplexPortal; CPX-1907; Ripoptosome. DR CORUM; Q13158; -. DR DIP; DIP-286N; -. DR IntAct; Q13158; 81. DR MINT; Q13158; -. DR STRING; 9606.ENSP00000301838; -. DR GlyCosmos; Q13158; 1 site, No reported glycans. DR GlyGen; Q13158; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q13158; -. DR MetOSite; Q13158; -. DR PhosphoSitePlus; Q13158; -. DR BioMuta; FADD; -. DR DMDM; 2498355; -. DR EPD; Q13158; -. DR jPOST; Q13158; -. DR MassIVE; Q13158; -. DR MaxQB; Q13158; -. DR PaxDb; 9606-ENSP00000301838; -. DR PeptideAtlas; Q13158; -. DR ProteomicsDB; 59197; -. DR Pumba; Q13158; -. DR Antibodypedia; 698; 1164 antibodies from 42 providers. DR DNASU; 8772; -. DR Ensembl; ENST00000301838.5; ENSP00000301838.5; ENSG00000168040.5. DR GeneID; 8772; -. DR KEGG; hsa:8772; -. DR MANE-Select; ENST00000301838.5; ENSP00000301838.5; NM_003824.4; NP_003815.1. DR UCSC; uc001opm.3; human. DR AGR; HGNC:3573; -. DR CTD; 8772; -. DR DisGeNET; 8772; -. DR GeneCards; FADD; -. DR HGNC; HGNC:3573; FADD. DR HPA; ENSG00000168040; Low tissue specificity. DR MalaCards; FADD; -. DR MIM; 602457; gene. DR MIM; 613759; phenotype. DR neXtProt; NX_Q13158; -. DR OpenTargets; ENSG00000168040; -. DR Orphanet; 306550; FADD-related immunodeficiency. DR Orphanet; 99806; Oculootodental syndrome. DR PharmGKB; PA27972; -. DR VEuPathDB; HostDB:ENSG00000168040; -. DR eggNOG; ENOG502S2RV; Eukaryota. DR GeneTree; ENSGT00390000002105; -. DR HOGENOM; CLU_087961_0_0_1; -. DR InParanoid; Q13158; -. DR OMA; CKMNLVA; -. DR OrthoDB; 2960517at2759; -. DR PhylomeDB; Q13158; -. DR TreeFam; TF102046; -. DR PathwayCommons; Q13158; -. DR Reactome; R-HSA-140534; Caspase activation via Death Receptors in the presence of ligand. DR Reactome; R-HSA-2562578; TRIF-mediated programmed cell death. 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-5675482; Regulation of necroptotic cell death. DR Reactome; R-HSA-69416; Dimerization of procaspase-8. DR Reactome; R-HSA-75157; FasL/ CD95L signaling. DR Reactome; R-HSA-75158; TRAIL signaling. DR Reactome; R-HSA-9013957; TLR3-mediated TICAM1-dependent programmed cell death. DR Reactome; R-HSA-933543; NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10. DR Reactome; R-HSA-9693928; Defective RIPK1-mediated regulated necrosis. DR SignaLink; Q13158; -. DR SIGNOR; Q13158; -. DR BioGRID-ORCS; 8772; 70 hits in 1158 CRISPR screens. DR ChiTaRS; FADD; human. DR EvolutionaryTrace; Q13158; -. DR GeneWiki; FADD; -. DR GenomeRNAi; 8772; -. DR Pharos; Q13158; Tbio. DR PRO; PR:Q13158; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; Q13158; Protein. DR Bgee; ENSG00000168040; Expressed in endometrium epithelium and 181 other cell types or tissues. DR GO; GO:0031265; C:CD95 death-inducing signaling complex; IDA:UniProtKB. DR GO; GO:0044297; C:cell body; IEA:Ensembl. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0009898; C:cytoplasmic side of plasma membrane; IC:UniProt. DR GO; GO:0005829; C:cytosol; IDA:ParkinsonsUK-UCL. DR GO; GO:0031264; C:death-inducing signaling complex; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0097342; C:ripoptosome; IDA:UniProtKB. DR GO; GO:0089720; F:caspase binding; IDA:UniProtKB. DR GO; GO:0035877; F:death effector domain binding; IPI:UniProtKB. DR GO; GO:0005123; F:death receptor binding; IBA:GO_Central. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0060090; F:molecular adaptor activity; IDA:UniProt. DR GO; GO:0002020; F:protease binding; IPI:UniProtKB. DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl. DR GO; GO:0033612; F:receptor serine/threonine kinase binding; IEA:Ensembl. DR GO; GO:0035591; F:signaling adaptor activity; IEA:Ensembl. DR GO; GO:0005164; F:tumor necrosis factor receptor binding; IEA:Ensembl. DR GO; GO:0032813; F:tumor necrosis factor receptor superfamily binding; IPI:UniProtKB. DR GO; GO:0097202; P:activation of cysteine-type endopeptidase activity; IDA:BHF-UCL. DR GO; GO:0006915; P:apoptotic process; IMP:UniProtKB. DR GO; GO:0097190; P:apoptotic signaling pathway; IDA:BHF-UCL. DR GO; GO:0048148; P:behavioral response to cocaine; IEA:Ensembl. DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEP:UniProtKB. DR GO; GO:0071550; P:death-inducing signaling complex assembly; IDA:UniProtKB. DR GO; GO:0051607; P:defense response to virus; IMP:UniProtKB. DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; IDA:UniProtKB. DR GO; GO:0097192; P:extrinsic apoptotic signaling pathway in absence of ligand; IEA:Ensembl. DR GO; GO:0008625; P:extrinsic apoptotic signaling pathway via death domain receptors; IDA:UniProtKB. DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW. DR GO; GO:0001822; P:kidney development; IEA:Ensembl. DR GO; GO:0048535; P:lymph node development; ISS:UniProtKB. DR GO; GO:0097049; P:motor neuron apoptotic process; IEA:Ensembl. DR GO; GO:0097527; P:necroptotic signaling pathway; IMP:BHF-UCL. DR GO; GO:0070236; P:negative regulation of activation-induced cell death of T cells; ISS:UniProtKB. DR GO; GO:0060546; P:negative regulation of necroptotic process; IEA:Ensembl. DR GO; GO:0042104; P:positive regulation of activated T cell proliferation; ISS:UniProtKB. DR GO; GO:0002821; P:positive regulation of adaptive immune response; ISS:UniProtKB. DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:UniProtKB. DR GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; IEP:UniProtKB. DR GO; GO:2000454; P:positive regulation of CD8-positive, alpha-beta cytotoxic T cell extravasation; ISS:UniProtKB. DR GO; GO:1900119; P:positive regulation of execution phase of apoptosis; IEA:Ensembl. DR GO; GO:2001238; P:positive regulation of extrinsic apoptotic signaling pathway; IMP:UniProtKB. DR GO; GO:0045089; P:positive regulation of innate immune response; IBA:GO_Central. DR GO; GO:0032757; P:positive regulation of interleukin-8 production; IDA:BHF-UCL. DR GO; GO:0045651; P:positive regulation of macrophage differentiation; IMP:UniProtKB. DR GO; GO:0045862; P:positive regulation of proteolysis; IDA:BHF-UCL. DR GO; GO:0001916; P:positive regulation of T cell mediated cytotoxicity; ISS:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL. DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IDA:BHF-UCL. DR GO; GO:0060340; P:positive regulation of type I interferon-mediated signaling pathway; IMP:UniProtKB. DR GO; GO:0032729; P:positive regulation of type II interferon production; ISS:UniProtKB. DR GO; GO:0048536; P:spleen development; ISS:UniProtKB. DR GO; GO:0033077; P:T cell differentiation in thymus; ISS:UniProtKB. DR GO; GO:0043029; P:T cell homeostasis; ISS:UniProtKB. DR GO; GO:0048538; P:thymus development; ISS:UniProtKB. DR GO; GO:0036462; P:TRAIL-activated apoptotic signaling pathway; IDA:ParkinsonsUK-UCL. DR CDD; cd08306; Death_FADD; 1. DR CDD; cd08336; DED_FADD; 1. DR Gene3D; 1.10.533.10; Death Domain, Fas; 2. DR InterPro; IPR011029; DEATH-like_dom_sf. DR InterPro; IPR000488; Death_domain. DR InterPro; IPR001875; DED_dom. DR InterPro; IPR016729; FADD_DD. DR InterPro; IPR049634; FADD_vert. DR PANTHER; PTHR15077:SF9; FAS-ASSOCIATED DEATH DOMAIN PROTEIN; 1. DR PANTHER; PTHR15077; FAS-ASSOCIATING DEATH DOMAIN-CONTAINING PROTEIN FADD; 1. DR Pfam; PF00531; Death; 1. DR Pfam; PF01335; DED; 1. DR PIRSF; PIRSF018586; FADD; 1. DR SMART; SM00005; DEATH; 1. DR SMART; SM00031; DED; 1. DR SUPFAM; SSF47986; DEATH domain; 1. DR PROSITE; PS50017; DEATH_DOMAIN; 1. DR PROSITE; PS50168; DED; 1. DR Genevisible; Q13158; HS. PE 1: Evidence at protein level; KW 3D-structure; Apoptosis; Disease variant; Glycoprotein; KW Host-virus interaction; Immunity; Innate immunity; Phosphoprotein; KW Reference proteome. FT CHAIN 1..208 FT /note="FAS-associated death domain protein" FT /id="PRO_0000191279" FT DOMAIN 3..81 FT /note="DED" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00065" FT DOMAIN 97..181 FT /note="Death" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00064" FT REGION 187..208 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 194 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:11034606, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163" FT CARBOHYD 117 FT /note="(Microbial infection) N-beta-linked (GlcNAc) FT arginine" FT /evidence="ECO:0000269|PubMed:24025841, FT ECO:0000269|PubMed:28860194, ECO:0000269|PubMed:30979585, FT ECO:0000305|PubMed:23955153, ECO:0007744|PDB:6ACI" FT VARIANT 105 FT /note="C -> W (in IEHDCM; reduced folding stability as FT measured by differential scanning calorimetry of the mutant FT protein; impairs interaction with FAS; dbSNP:rs387906839)" FT /evidence="ECO:0000269|PubMed:21109225" FT /id="VAR_065124" FT MUTAGEN 12 FT /note="S->R: Loss of interaction with CASP8." FT /evidence="ECO:0000269|PubMed:16762833" FT MUTAGEN 25 FT /note="F->R: Loss of interaction with FAS. Loss of FT self-association. Abolishes induction of apoptosis." FT /evidence="ECO:0000269|PubMed:16762833" FT MUTAGEN 33 FT /note="K->E: Loss of self-association." FT /evidence="ECO:0000269|PubMed:16762833" FT MUTAGEN 38 FT /note="R->A: Loss of interaction with CASP8." FT /evidence="ECO:0000269|PubMed:16762833" FT MUTAGEN 44 FT /note="D->R: Loss of interaction with CASP8. Abolishes FT induction of apoptosis. Decreased interaction with FAS." FT /evidence="ECO:0000269|PubMed:16762833" FT MUTAGEN 51 FT /note="E->R: Loss of interaction with CASP8." FT /evidence="ECO:0000269|PubMed:16762833" FT MUTAGEN 117 FT /note="R->A: Abolished GlcNAcylation by E.coli NleB1." FT /evidence="ECO:0000269|PubMed:23955153, FT ECO:0000269|PubMed:30979585" FT MUTAGEN 117 FT /note="R->E: Loss of interaction with FAS." FT /evidence="ECO:0000269|PubMed:20935634" FT MUTAGEN 121 FT /note="V->N: Loss of interaction with FAS." FT /evidence="ECO:0000269|PubMed:7538907" FT MUTAGEN 123 FT /note="D->R: Strongly decreased interaction with FAS." FT /evidence="ECO:0000269|PubMed:20935634" FT MUTAGEN 135 FT /note="R->E: Strongly decreased interaction with FAS." FT /evidence="ECO:0000269|PubMed:20935634" FT MUTAGEN 142 FT /note="R->E: Decreased interaction with FAS." FT /evidence="ECO:0000269|PubMed:20935634" FT MUTAGEN 172 FT /note="L->A,E: Loss of interaction with FAS." FT /evidence="ECO:0000269|PubMed:19118384, FT ECO:0000269|PubMed:20935634" FT MUTAGEN 172 FT /note="L->K: Strongly decreased interaction with FAS." FT /evidence="ECO:0000269|PubMed:19118384, FT ECO:0000269|PubMed:20935634" FT MUTAGEN 175 FT /note="D->K: Strongly decreased interaction with FAS." FT /evidence="ECO:0000269|PubMed:20935634" FT MUTAGEN 176 FT /note="L->E: Decreased interaction with FAS." FT /evidence="ECO:0000269|PubMed:19118384" FT CONFLICT 32 FT /note="G -> V (in Ref. 2; CAA59197)" FT /evidence="ECO:0000305" FT HELIX 3..13 FT /evidence="ECO:0007829|PDB:1A1W" FT HELIX 16..30 FT /evidence="ECO:0007829|PDB:1A1W" FT HELIX 34..38 FT /evidence="ECO:0007829|PDB:1A1W" FT STRAND 40..42 FT /evidence="ECO:0007829|PDB:1A1W" FT HELIX 43..51 FT /evidence="ECO:0007829|PDB:1A1W" FT HELIX 61..70 FT /evidence="ECO:0007829|PDB:1A1W" FT HELIX 74..82 FT /evidence="ECO:0007829|PDB:1A1W" FT STRAND 91..93 FT /evidence="ECO:0007829|PDB:1E3Y" FT HELIX 97..107 FT /evidence="ECO:0007829|PDB:6ACI" FT STRAND 109..111 FT /evidence="ECO:0007829|PDB:1E41" FT HELIX 112..118 FT /evidence="ECO:0007829|PDB:6ACI" FT HELIX 123..132 FT /evidence="ECO:0007829|PDB:6ACI" FT STRAND 133..135 FT /evidence="ECO:0007829|PDB:2GF5" FT HELIX 137..152 FT /evidence="ECO:0007829|PDB:6ACI" FT HELIX 153..155 FT /evidence="ECO:0007829|PDB:6ACI" FT HELIX 158..167 FT /evidence="ECO:0007829|PDB:6ACI" FT HELIX 171..181 FT /evidence="ECO:0007829|PDB:6ACI" FT TURN 186..189 FT /evidence="ECO:0007829|PDB:1E41" SQ SEQUENCE 208 AA; 23279 MW; 0E65E2F852E83507 CRC64; MDPFLVLLHS VSSSLSSSEL TELKFLCLGR VGKRKLERVQ SGLDLFSMLL EQNDLEPGHT ELLRELLASL RRHDLLRRVD DFEAGAAAGA APGEEDLCAA FNVICDNVGK DWRRLARQLK VSDTKIDSIE DRYPRNLTER VRESLRIWKN TEKENATVAH LVGALRSCQM NLVADLVQEV QQARDLQNRS GAMSPMSWNS DASTSEAS //