{"results":[{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q13158","secondaryAccessions":["Q14866","Q6IBR4"],"uniProtkbId":"FADD_HUMAN","entryAudit":{"firstPublicDate":"1997-11-01","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"1997-11-01","entryVersion":236,"sequenceVersion":1},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"7538907"}],"value":"FAS-associated death domain protein"}},"alternativeNames":[{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"7538907"}],"value":"FAS-associating death domain-containing protein"}},{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"Reference","id":"Ref.3"}],"value":"Growth-inhibiting gene 3 protein"}},{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"7536190"}],"value":"Mediator of receptor induced toxicity"}}]},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"7538907"},{"evidenceCode":"ECO:0000312","source":"HGNC","id":"HGNC:3573"}],"value":"FADD"},"synonyms":[{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"7536190"}],"value":"MORT1"}],"orfNames":[{"evidences":[{"evidenceCode":"ECO:0000303","source":"Reference","id":"Ref.3"}],"value":"GIG3"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16762833"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19118384"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20935634"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21109225"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23955153"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24025841"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24204270"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7538907"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9184224"}],"value":"Apoptotic adapter molecule that recruits caspases CASP8 or CASP10 to the activated FAS/CD95 or TNFRSF1A/TNFR-1 receptors (PubMed:16762833, PubMed:19118384, PubMed:20935634, PubMed:23955153, PubMed:24025841, PubMed:7538907, PubMed:9184224). The resulting aggregate called the death-inducing signaling complex (DISC) performs CASP8 proteolytic activation (PubMed:16762833, PubMed:19118384, PubMed:20935634, PubMed:7538907, PubMed:9184224). Active CASP8 initiates the subsequent cascade of caspases mediating apoptosis (PubMed:16762833). Involved in interferon-mediated antiviral immune response, playing a role in the positive regulation of interferon signaling (PubMed:21109225, PubMed:24204270)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q61160"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10442631"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10825539"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11034606"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12702765"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16127453"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16762833"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18846110"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19118384"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20935634"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21109225"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24204270"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9184224"}],"value":"Can self-associate (PubMed:19118384, PubMed:20935634). Component of the AIM2 PANoptosome complex, a multiprotein complex that drives inflammatory cell death (PANoptosis) (By similarity). Component of the death-induced signaling complex (DISC) composed of cell surface receptor FAS/CD95 or TNFRSF1A, adapter protein FADD and the CASP8 protease; recruitment of CASP8 to the complex is required for processing of CASP8 into the p18 and p10 subunits (PubMed:16762833, PubMed:9184224). Interacts (via death domain) with FAS (via death domain) (PubMed:16762833, PubMed:20935634, PubMed:21109225). Interacts directly (via DED domain) with NOL3 (via CARD domain); inhibits death-inducing signaling complex (DISC) assembly by inhibiting the increase in FAS-FADD binding induced by FAS activation (By similarity). Interacts with CFLAR, PEA15 and MBD4 (PubMed:10442631, PubMed:12702765). When phosphorylated, part of a complex containing HIPK3 and FAS (PubMed:11034606). May interact with MAVS/IPS1 (PubMed:16127453). Interacts with MOCV v-CFLAR protein and PIDD1 (PubMed:10825539). Interacts with RIPK1 and TRADD (By similarity). Interacts with stimulated TNFRSF10B (PubMed:18846110). Interacts with DDX24 (PubMed:24204270)"}],"commentType":"SUBUNIT"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18632871"}],"value":"(Microbial infection) Interacts with human papillomavirus 16/HPV16 protein E6"}],"commentType":"SUBUNIT"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11259186"}],"value":"(Microbial infection) Interacts with molluscum contagiosum virus proteins MC159L/v-CFLAR and 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(DISC)"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23955153"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24025841"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28069818"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28860194"}],"value":"(Microbial infection) Glycosylated at Arg-117 by enteropathogenic E.coli protein NleB1, C.rodentium protein NleB and S.typhimurium protein Ssek1: arginine GlcNAcylation prevents recruitment of caspase-8 or caspase-10 to the activated Fas (CD95) or TNFR-1 receptors"}],"commentType":"PTM"},{"commentType":"DISEASE","disease":{"diseaseId":"Infections, recurrent, associated with encephalopathy, hepatic dysfunction and cardiovascular malformations","diseaseAccession":"DI-03003","acronym":"IEHDCM","description":"A condition with biological features of autoimmune lymphoproliferative syndrome such as high-circulating CD4(-)CD8(-)TCR-alpha-beta(+) T-cell counts, and 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Affected individuals suffer from recurrent, stereotypical episodes of fever, encephalopathy, and mild liver dysfunction sometimes accompanied by generalized seizures. The episodes can be triggered by varicella zoster virus (VZV), measles mumps rubella (MMR) attenuated vaccine, parainfluenza virus, and Epstein-Barr virus (EBV).","diseaseCrossReference":{"database":"MIM","id":"613759"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21109225"}]},"note":{"texts":[{"value":"The disease is caused by variants affecting the gene represented in this entry"}]}}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":208,"modifier":"EXACT"}},"description":"FAS-associated death domain protein","featureId":"PRO_0000191279"},{"type":"Domain","location":{"start":{"value":3,"modifier":"EXACT"},"end":{"value":81,"modifier":"EXACT"}},"description":"DED","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00065"}]},{"type":"Domain","location":{"start":{"value":97,"modifier":"EXACT"},"end":{"value":181,"modifier":"EXACT"}},"description":"Death","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00064"}]},{"type":"Region","location":{"start":{"value":187,"modifier":"EXACT"},"end":{"value":208,"modifier":"EXACT"}},"description":"Disordered","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Modified residue","location":{"start":{"value":194,"modifier":"EXACT"},"end":{"value":194,"modifier":"EXACT"}},"description":"Phosphoserine","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11034606"},{"evidenceCode":"ECO:0007744","source":"PubMed","id":"19690332"},{"evidenceCode":"ECO:0007744","source":"PubMed","id":"21406692"},{"evidenceCode":"ECO:0007744","source":"PubMed","id":"23186163"}]},{"type":"Glycosylation","location":{"start":{"value":117,"modifier":"EXACT"},"end":{"value":117,"modifier":"EXACT"}},"description":"(Microbial infection) N-beta-linked (GlcNAc) arginine","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24025841"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28860194"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30979585"},{"evidenceCode":"ECO:0000305","source":"PubMed","id":"23955153"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"6ACI"}],"featureId":""},{"type":"Natural variant","location":{"start":{"value":105,"modifier":"EXACT"},"end":{"value":105,"modifier":"EXACT"}},"description":"in IEHDCM; reduced folding stability as measured by differential scanning calorimetry of the mutant protein; impairs interaction with FAS; dbSNP:rs387906839","featureCrossReferences":[{"database":"dbSNP","id":"rs387906839"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21109225"}],"featureId":"VAR_065124","alternativeSequence":{"originalSequence":"C","alternativeSequences":["W"]}},{"type":"Mutagenesis","location":{"start":{"value":12,"modifier":"EXACT"},"end":{"value":12,"modifier":"EXACT"}},"description":"Loss of interaction with CASP8.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16762833"}],"alternativeSequence":{"originalSequence":"S","alternativeSequences":["R"]}},{"type":"Mutagenesis","location":{"start":{"value":25,"modifier":"EXACT"},"end":{"value":25,"modifier":"EXACT"}},"description":"Loss of interaction with FAS. 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