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Protein

FAS-associated death domain protein

Gene

FADD

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

  • caspase binding Source: AgBase
  • death effector domain binding Source: UniProtKB
  • death receptor binding Source: ProtInc
  • identical protein binding Source: IntAct
  • protease binding Source: UniProtKB
  • tumor necrosis factor receptor superfamily binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Apoptosis, Host-virus interaction, Immunity, Innate immunity

Enzyme and pathway databases

BioCyciZFISH:ENSG00000168040-MONOMER.
ReactomeiR-HSA-140534. Ligand-dependent caspase activation.
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-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

HGNCiHGNC:3573. FADD.

Subcellular locationi

GO - Cellular componenti

  • CD95 death-inducing signaling complex Source: UniProtKB
  • cell body Source: Ensembl
  • cytoplasm Source: UniProtKB
  • cytosol Source: ParkinsonsUK-UCL
  • death-inducing signaling complex Source: UniProtKB
  • membrane raft Source: Ensembl
  • neuron projection Source: Ensembl
  • plasma membrane Source: UniProtKB
  • ripoptosome Source: UniProtKB
Complete GO annotation...

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 rs387906839dbSNPEnsembl.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.

PTM databases

iPTMnetiQ13158.
PhosphoSitePlusiQ13158.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSG00000168040.
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

Binary interactionsi

WithEntry#Exp.IntActNotes
itself5EBI-494804,EBI-494804
CASP8Q1479039EBI-494804,EBI-78060
CASP8Q14790-15EBI-494804,EBI-288309
CASP8Q14790-54EBI-494804,EBI-288326
FASP2544533EBI-494804,EBI-494743
FasP254465EBI-494804,EBI-296206From a different organism.
FASLGP480233EBI-494804,EBI-495538
LRRK2Q5S0074EBI-494804,EBI-5323863
MBD4O952436EBI-494804,EBI-348011
MYD88Q998363EBI-494804,EBI-447677
PARK7Q994979EBI-494804,EBI-1164361
PLK1P533509EBI-494804,EBI-476768
RIPK1Q135469EBI-494804,EBI-358507
TRADDQ156283EBI-494804,EBI-359215

GO - Molecular functioni

  • caspase binding Source: AgBase
  • death effector domain binding Source: UniProtKB
  • death receptor binding Source: ProtInc
  • identical protein binding Source: IntAct
  • protease binding Source: UniProtKB
  • tumor necrosis factor receptor superfamily binding Source: UniProtKB

Protein-protein interaction databases

BioGridi114302. 64 interactors.
DIPiDIP-286N.
IntActiQ13158. 36 interactors.
MINTiMINT-91814.
STRINGi9606.ENSP00000301838.

Structurei

Secondary structure

1208
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi3 – 13Combined sources11
Helixi16 – 30Combined sources15
Helixi34 – 38Combined sources5
Beta strandi40 – 42Combined sources3
Helixi43 – 51Combined sources9
Helixi61 – 70Combined sources10
Helixi74 – 82Combined sources9
Beta strandi88 – 91Combined sources4
Helixi94 – 105Combined sources12
Beta strandi109 – 111Combined sources3
Helixi112 – 118Combined sources7
Helixi123 – 132Combined sources10
Beta strandi133 – 135Combined sources3
Helixi137 – 151Combined sources15
Turni153 – 155Combined sources3
Helixi158 – 167Combined sources10
Helixi171 – 190Combined sources20

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...

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

Sequence similaritiesi

Contains 1 death domain.PROSITE-ProRule annotation
Contains 1 DED (death effector) domain.PROSITE-ProRule annotation

Phylogenomic databases

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

Family and domain databases

Gene3Di1.10.533.10. 2 hits.
InterProiIPR011029. DEATH-like_dom.
IPR000488. Death_domain.
IPR001875. DED_dom.
IPR016729. FADD.
[Graphical view]
PfamiPF00531. Death. 1 hit.
PF01335. DED. 1 hit.
[Graphical view]
PIRSFiPIRSF018586. FADD. 1 hit.
SMARTiSM00005. DEATH. 1 hit.
SM00031. DED. 1 hit.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
PROSITEiPS50017. DEATH_DOMAIN. 1 hit.
PS50168. DED. 1 hit.
[Graphical view]

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 rs387906839dbSNPEnsembl.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.

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. 64 interactors.
DIPiDIP-286N.
IntActiQ13158. 36 interactors.
MINTiMINT-91814.
STRINGi9606.ENSP00000301838.

PTM databases

iPTMnetiQ13158.
PhosphoSitePlusiQ13158.

Polymorphism and mutation databases

BioMutaiFADD.
DMDMi2498355.

Proteomic databases

EPDiQ13158.
MaxQBiQ13158.
PaxDbiQ13158.
PeptideAtlasiQ13158.
PRIDEiQ13158.

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.
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.
OMAiCQMNLVA.
OrthoDBiEOG091G0SHT.
PhylomeDBiQ13158.
TreeFamiTF102046.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000168040-MONOMER.
ReactomeiR-HSA-140534. Ligand-dependent caspase activation.
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-933543. NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10.
SignaLinkiQ13158.
SIGNORiQ13158.

Miscellaneous databases

EvolutionaryTraceiQ13158.
GeneWikiiFADD.
GenomeRNAii8772.
PROiQ13158.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000168040.
CleanExiHS_FADD.
GenevisibleiQ13158. HS.

Family and domain databases

Gene3Di1.10.533.10. 2 hits.
InterProiIPR011029. DEATH-like_dom.
IPR000488. Death_domain.
IPR001875. DED_dom.
IPR016729. FADD.
[Graphical view]
PfamiPF00531. Death. 1 hit.
PF01335. DED. 1 hit.
[Graphical view]
PIRSFiPIRSF018586. FADD. 1 hit.
SMARTiSM00005. DEATH. 1 hit.
SM00031. DED. 1 hit.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
PROSITEiPS50017. DEATH_DOMAIN. 1 hit.
PS50168. DED. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiFADD_HUMAN
AccessioniPrimary (citable) accession number: Q13158
Secondary accession number(s): Q14866, Q6IBR4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: November 30, 2016
This is version 175 of the entry and version 1 of the sequence. [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 chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.