FADD_HUMAN
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 03-AUG-2022, entry version 217.
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 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 [11]
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 [12]
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 [13]
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 [14]
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 [15]
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 [16]
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 [17]
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 [18]
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 [19]
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 [20]
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 [21]
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 [22]
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 [23]
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 [24]
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 [25]
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 [26]
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 [27]
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 [28]
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 [29]
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 [30]
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 [31]
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 [32]
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 [33]
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 [34] {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 adaptor molecule that recruits caspase-8 or
CC caspase-10 to the activated Fas (CD95) or TNFR-1 receptors
CC (PubMed:7538907, PubMed:23955153, PubMed:19118384, PubMed:20935634,
CC PubMed:16762833, PubMed:24025841). The resulting aggregate called the
CC death-inducing signaling complex (DISC) performs caspase-8 proteolytic
CC activation (PubMed:7538907, PubMed:19118384, PubMed:20935634,
CC PubMed:16762833). Active caspase-8 initiates the subsequent cascade of
CC caspases mediating apoptosis (PubMed:16762833). Involved in interferon-
CC mediated antiviral immune response, playing a role in the positive
CC regulation of interferon signaling (PubMed:21109225).
CC {ECO:0000269|PubMed:16762833, ECO:0000269|PubMed:19118384,
CC ECO:0000269|PubMed:20935634, ECO:0000269|PubMed:21109225,
CC ECO:0000269|PubMed:23955153, ECO:0000269|PubMed:24025841,
CC ECO:0000269|PubMed:7538907}.
CC -!- SUBUNIT: Can self-associate (PubMed:19118384, PubMed:20935634).
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 (via death domain) with FAS (via death
CC domain) (PubMed:21109225, PubMed:16762833, PubMed:20935634). Interacts
CC with CASP8 (PubMed:16762833). Interacts directly (via DED domain) with
CC NOL3 (via CARD domain); inhibits death-inducing signaling complex
CC (DISC) assembly by inhibiting the increase in FAS-FADD binding induced
CC by FAS activation (By similarity). Interacts with RIPK1, TRADD and
CC CASP8 (By similarity). Component of the AIM2 PANoptosome complex, a
CC multiprotein complex that drives inflammatory cell death (PANoptosis)
CC (By similarity). Interacts with stimulated TNFRSF10B (PubMed:18846110).
CC Interacts with stimulated TNFRSF10B (By similarity).
CC {ECO:0000250|UniProtKB:Q61160, ECO:0000269|PubMed:10442631,
CC ECO:0000269|PubMed:10825539, ECO:0000269|PubMed:11034606,
CC ECO:0000269|PubMed:12702765, ECO:0000269|PubMed:16127453,
CC ECO:0000269|PubMed:16762833, ECO:0000269|PubMed:18846110,
CC ECO:0000269|PubMed:19118384, ECO:0000269|PubMed:20935634,
CC ECO:0000269|PubMed:21109225}.
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=44; 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/";
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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 PDBsum; 1A1W; -.
DR PDBsum; 1A1Z; -.
DR PDBsum; 1E3Y; -.
DR PDBsum; 1E41; -.
DR PDBsum; 2GF5; -.
DR PDBsum; 3EZQ; -.
DR PDBsum; 3OQ9; -.
DR PDBsum; 6ACI; -.
DR AlphaFoldDB; Q13158; -.
DR BMRB; Q13158; -.
DR SMR; Q13158; -.
DR BioGRID; 114302; 112.
DR ComplexPortal; CPX-1907; Ripoptosome.
DR CORUM; Q13158; -.
DR DIP; DIP-286N; -.
DR IntAct; Q13158; 79.
DR MINT; Q13158; -.
DR STRING; 9606.ENSP00000301838; -.
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; Q13158; -.
DR PeptideAtlas; Q13158; -.
DR PRIDE; Q13158; -.
DR ProteomicsDB; 59197; -.
DR Antibodypedia; 698; 1037 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 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; 1619689at2759; -.
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 1079 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 179 other tissues.
DR Genevisible; Q13158; HS.
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:0005829; C:cytosol; IDA:ParkinsonsUK-UCL.
DR GO; GO:0031264; C:death-inducing signaling complex; IDA:UniProtKB.
DR GO; GO:0045121; C:membrane raft; IEA:Ensembl.
DR GO; GO:0043005; C:neuron projection; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IEA:Ensembl.
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: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: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:2000454; P:positive regulation of CD8-positive, alpha-beta cytotoxic T cell extravasation; ISS:UniProtKB.
DR GO; GO:2001238; P:positive regulation of extrinsic apoptotic signaling pathway; IMP:UniProtKB.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IEP:UniProtKB.
DR GO; GO:0032729; P:positive regulation of interferon-gamma production; ISS:UniProtKB.
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:0043278; P:response to morphine; IEA:Ensembl.
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 Gene3D; 1.10.533.10; -; 2.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR000488; Death_domain.
DR InterPro; IPR001875; DED_dom.
DR InterPro; IPR016729; FADD.
DR PANTHER; PTHR15077; PTHR15077; 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; SSF47986; 1.
DR PROSITE; PS50017; DEATH_DOMAIN; 1.
DR PROSITE; PS50168; DED; 1.
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 self-
FT 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
