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Protein

FAS-associated death domain protein

Gene

FADD

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Apoptotic adaptor molecule that recruits caspase-8 or caspase-10 to the activated Fas (CD95) or TNFR-1 receptors. The resulting aggregate called the death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation. Active caspase-8 initiates the subsequent cascade of caspases mediating apoptosis. Involved in interferon-mediated antiviral immune response, playing a role in the positive regulation of interferon signaling.4 Publications

GO - Molecular functioni

GO - Biological processi

Keywordsi

Biological processApoptosis, Host-virus interaction, Immunity, Innate immunity

Enzyme and pathway databases

ReactomeiR-HSA-140534 via Death Receptors in the presence of ligand
R-HSA-2562578 TRIF-mediated programmed cell death
R-HSA-3371378 Regulation by c-FLIP
R-HSA-5213460 RIPK1-mediated regulated necrosis
R-HSA-5218900 CASP8 activity is inhibited
R-HSA-5357786 TNFR1-induced proapoptotic signaling
R-HSA-69416 Dimerization of procaspase-8
R-HSA-75157 FasL/ CD95L signaling
R-HSA-75158 TRAIL signaling
R-HSA-9013957 TLR3-mediated TICAM1-dependent programmed cell death
R-HSA-933543 NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10
SignaLinkiQ13158
SIGNORiQ13158

Names & Taxonomyi

Protein namesi
Recommended name:
FAS-associated death domain protein
Alternative name(s):
FAS-associating death domain-containing protein
Growth-inhibiting gene 3 protein
Mediator of receptor induced toxicity
Protein FADD
Gene namesi
Name:FADD
Synonyms:MORT1
ORF Names:GIG3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

EuPathDBiHostDB:ENSG00000168040.4
HGNCiHGNC:3573 FADD
MIMi602457 gene
neXtProtiNX_Q13158

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Pathology & Biotechi

Involvement in diseasei

Infections, recurrent, associated with encephalopathy, hepatic dysfunction and cardiovascular malformations (IEHDCM)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA condition with biological features of autoimmune lymphoproliferative syndrome such as high-circulating CD4(-)CD8(-)TCR-alpha-beta(+) T-cell counts, and elevated IL10 and FASL levels. 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).
See also OMIM:613759
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_065124105C → W in IEHDCM; reduced folding stability as measured by differential scanning calorimetry of the mutant protein; impairs interaction with FAS. 1 PublicationCorresponds to variant dbSNP:rs387906839EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi12S → R: Loss of interaction with CASP8. 1 Publication1
Mutagenesisi25F → R: Loss of interaction with FAS. Loss of self-association. Abolishes induction of apoptosis. 1 Publication1
Mutagenesisi33K → E: Loss of self-association. 1 Publication1
Mutagenesisi38R → A: Loss of interaction with CASP8. 1 Publication1
Mutagenesisi44D → R: Loss of interaction with CASP8. Abolishes induction of apoptosis. Decreased interaction with FAS. 1 Publication1
Mutagenesisi51E → R: Loss of interaction with CASP8. 1 Publication1
Mutagenesisi117R → E: Loss of interaction with FAS. 1 Publication1
Mutagenesisi121V → N: Loss of interaction with FAS. 1 Publication1
Mutagenesisi123D → R: Strongly decreased interaction with FAS. 1 Publication1
Mutagenesisi135R → E: Strongly decreased interaction with FAS. 1 Publication1
Mutagenesisi142R → E: Decreased interaction with FAS. 1 Publication1
Mutagenesisi172L → A or E: Loss of interaction with FAS. 2 Publications1
Mutagenesisi172L → K: Strongly decreased interaction with FAS. 2 Publications1
Mutagenesisi175D → K: Strongly decreased interaction with FAS. 1 Publication1
Mutagenesisi176L → E: Decreased interaction with FAS. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi8772
MalaCardsiFADD
MIMi613759 phenotype
OpenTargetsiENSG00000168040
Orphaneti306550 FADD-related immunodeficiency
99806 Oculootodental syndrome
PharmGKBiPA27972

Polymorphism and mutation databases

BioMutaiFADD
DMDMi2498355

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001912791 – 208FAS-associated death domain proteinAdd BLAST208

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei194PhosphoserineCombined sources1 Publication1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ13158
MaxQBiQ13158
PaxDbiQ13158
PeptideAtlasiQ13158
PRIDEiQ13158
ProteomicsDBi59197

PTM databases

iPTMnetiQ13158
PhosphoSitePlusiQ13158

Expressioni

Tissue specificityi

Expressed in a wide variety of tissues, except for peripheral blood mononuclear leukocytes.

Gene expression databases

BgeeiENSG00000168040 Expressed in 211 organ(s), highest expression level in blood
CleanExiHS_FADD
GenevisibleiQ13158 HS

Organism-specific databases

HPAiCAB010209
HPA001464

Interactioni

Subunit structurei

Can self-associate. Interacts with CFLAR, PEA15 and MBD4. When phosphorylated, part of a complex containing HIPK3 and FAS. May interact with MAVS/IPS1. Interacts with MOCV v-CFLAR protein and PIDD1. Interacts (via death domain) with FAS (via death domain). Interacts with CASP8. 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).By similarity9 Publications
(Microbial infection) Interacts with human papillomavirus 16/HPV16 protein E6.1 Publication
(Microbial infection) Interacts with molluscum contagiosum virus proteins MC159L/v-CFLAR and MC160L.1 Publication

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi114302, 68 interactors
ComplexPortaliCPX-1907 Ripoptosome
CORUMiQ13158
DIPiDIP-286N
IntActiQ13158, 43 interactors
MINTiQ13158
STRINGi9606.ENSP00000301838

Structurei

Secondary structure

1208
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ13158
SMRiQ13158
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ13158

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini3 – 81DEDPROSITE-ProRule annotationAdd BLAST79
Domaini97 – 181DeathPROSITE-ProRule annotationAdd BLAST85

Domaini

Contains a death domain involved in the binding of the corresponding domain within Fas receptor.1 Publication
The interaction between the FAS and FADD death domains is crucial for the formation of the death-inducing signaling complex (DISC).1 Publication

Phylogenomic databases

eggNOGiENOG410J0KM Eukaryota
ENOG41122TX LUCA
GeneTreeiENSGT00390000002105
HOGENOMiHOG000112490
HOVERGENiHBG000853
InParanoidiQ13158
KOiK02373
OMAiELKFLCR
OrthoDBiEOG091G0SHT
PhylomeDBiQ13158
TreeFamiTF102046

Family and domain databases

InterProiView protein in InterPro
IPR011029 DEATH-like_dom_sf
IPR000488 Death_domain
IPR001875 DED_dom
IPR016729 FADD
PfamiView protein in Pfam
PF00531 Death, 1 hit
PF01335 DED, 1 hit
PIRSFiPIRSF018586 FADD, 1 hit
SMARTiView protein in SMART
SM00005 DEATH, 1 hit
SM00031 DED, 1 hit
SUPFAMiSSF47986 SSF47986, 1 hit
PROSITEiView protein in PROSITE
PS50017 DEATH_DOMAIN, 1 hit
PS50168 DED, 1 hit

Sequencei

Sequence statusi: Complete.

Q13158-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MDPFLVLLHS VSSSLSSSEL TELKFLCLGR VGKRKLERVQ SGLDLFSMLL
60 70 80 90 100
EQNDLEPGHT ELLRELLASL RRHDLLRRVD DFEAGAAAGA APGEEDLCAA
110 120 130 140 150
FNVICDNVGK DWRRLARQLK VSDTKIDSIE DRYPRNLTER VRESLRIWKN
160 170 180 190 200
TEKENATVAH LVGALRSCQM NLVADLVQEV QQARDLQNRS GAMSPMSWNS

DASTSEAS
Length:208
Mass (Da):23,279
Last modified:November 1, 1997 - v1
Checksum:i0E65E2F852E83507
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti32G → V in CAA59197 (PubMed:7536190).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_065124105C → W in IEHDCM; reduced folding stability as measured by differential scanning calorimetry of the mutant protein; impairs interaction with FAS. 1 PublicationCorresponds to variant dbSNP:rs387906839EnsemblClinVar.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U24231 mRNA Translation: AAA86517.1
X84709 mRNA Translation: CAA59197.1
AY423721 mRNA Translation: AAS00484.1
AK291005 mRNA Translation: BAF83694.1
BT006927 mRNA Translation: AAP35573.1
CR456738 mRNA Translation: CAG33019.1
DQ449938 Genomic DNA Translation: ABD96828.1
CH471076 Genomic DNA Translation: EAW74761.1
BC000334 mRNA Translation: AAH00334.1
CCDSiCCDS8196.1
PIRiA56912
RefSeqiNP_003815.1, NM_003824.3
UniGeneiHs.86131

Genome annotation databases

EnsembliENST00000301838; ENSP00000301838; ENSG00000168040
GeneIDi8772
KEGGihsa:8772
UCSCiuc001opm.3 human

Similar proteinsi

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U24231 mRNA Translation: AAA86517.1
X84709 mRNA Translation: CAA59197.1
AY423721 mRNA Translation: AAS00484.1
AK291005 mRNA Translation: BAF83694.1
BT006927 mRNA Translation: AAP35573.1
CR456738 mRNA Translation: CAG33019.1
DQ449938 Genomic DNA Translation: ABD96828.1
CH471076 Genomic DNA Translation: EAW74761.1
BC000334 mRNA Translation: AAH00334.1
CCDSiCCDS8196.1
PIRiA56912
RefSeqiNP_003815.1, NM_003824.3
UniGeneiHs.86131

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1A1WNMR-A1-83[»]
1A1ZNMR-A1-83[»]
1E3YNMR-A93-192[»]
1E41NMR-A93-192[»]
2GF5NMR-A2-191[»]
3EZQX-ray2.73B/D/F/H/J/L/N/P93-208[»]
3OQ9X-ray6.80H/I/J/K/L93-184[»]
ProteinModelPortaliQ13158
SMRiQ13158
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114302, 68 interactors
ComplexPortaliCPX-1907 Ripoptosome
CORUMiQ13158
DIPiDIP-286N
IntActiQ13158, 43 interactors
MINTiQ13158
STRINGi9606.ENSP00000301838

PTM databases

iPTMnetiQ13158
PhosphoSitePlusiQ13158

Polymorphism and mutation databases

BioMutaiFADD
DMDMi2498355

Proteomic databases

EPDiQ13158
MaxQBiQ13158
PaxDbiQ13158
PeptideAtlasiQ13158
PRIDEiQ13158
ProteomicsDBi59197

Protocols and materials databases

DNASUi8772
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000301838; ENSP00000301838; ENSG00000168040
GeneIDi8772
KEGGihsa:8772
UCSCiuc001opm.3 human

Organism-specific databases

CTDi8772
DisGeNETi8772
EuPathDBiHostDB:ENSG00000168040.4
GeneCardsiFADD
HGNCiHGNC:3573 FADD
HPAiCAB010209
HPA001464
MalaCardsiFADD
MIMi602457 gene
613759 phenotype
neXtProtiNX_Q13158
OpenTargetsiENSG00000168040
Orphaneti306550 FADD-related immunodeficiency
99806 Oculootodental syndrome
PharmGKBiPA27972
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410J0KM Eukaryota
ENOG41122TX LUCA
GeneTreeiENSGT00390000002105
HOGENOMiHOG000112490
HOVERGENiHBG000853
InParanoidiQ13158
KOiK02373
OMAiELKFLCR
OrthoDBiEOG091G0SHT
PhylomeDBiQ13158
TreeFamiTF102046

Enzyme and pathway databases

ReactomeiR-HSA-140534 via Death Receptors in the presence of ligand
R-HSA-2562578 TRIF-mediated programmed cell death
R-HSA-3371378 Regulation by c-FLIP
R-HSA-5213460 RIPK1-mediated regulated necrosis
R-HSA-5218900 CASP8 activity is inhibited
R-HSA-5357786 TNFR1-induced proapoptotic signaling
R-HSA-69416 Dimerization of procaspase-8
R-HSA-75157 FasL/ CD95L signaling
R-HSA-75158 TRAIL signaling
R-HSA-9013957 TLR3-mediated TICAM1-dependent programmed cell death
R-HSA-933543 NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10
SignaLinkiQ13158
SIGNORiQ13158

Miscellaneous databases

EvolutionaryTraceiQ13158
GeneWikiiFADD
GenomeRNAii8772
PROiPR:Q13158
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000168040 Expressed in 211 organ(s), highest expression level in blood
CleanExiHS_FADD
GenevisibleiQ13158 HS

Family and domain databases

InterProiView protein in InterPro
IPR011029 DEATH-like_dom_sf
IPR000488 Death_domain
IPR001875 DED_dom
IPR016729 FADD
PfamiView protein in Pfam
PF00531 Death, 1 hit
PF01335 DED, 1 hit
PIRSFiPIRSF018586 FADD, 1 hit
SMARTiView protein in SMART
SM00005 DEATH, 1 hit
SM00031 DED, 1 hit
SUPFAMiSSF47986 SSF47986, 1 hit
PROSITEiView protein in PROSITE
PS50017 DEATH_DOMAIN, 1 hit
PS50168 DED, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiFADD_HUMAN
AccessioniPrimary (citable) accession number: Q13158
Secondary accession number(s): Q14866, Q6IBR4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: November 7, 2018
This is version 194 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
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Main funding by: National Institutes of Health

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