InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Gene: FADD

Summary

InnateDB Gene

IDBG-62144.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

FADD

Gene Name

Fas (TNFRSF6)-associated via death domain

Synonyms

MORT1

Species

Homo sapiens

Ensembl Gene

ENSG00000168040

Encoded Proteins

IDBP-62146

Fas (TNFRSF6)-associated via death domain

Protein Structure

Useful resources

Stemformatics EHFPI ImmGen

InnateDB Annotation

Summary

PMID 17785432

FADD is an adaptor protein involved in death receptor-mediated apoptosis and a physiological negative regulator of IRAK1/MyD88-dependent responses in innate immune signalling.

PMID 15711932

FADD is part of the viral product dsRNA-triggered death inducing signalling complexes (dsRNA-DISCs) containing TRADD and CASP8.

PMID 21183682

FADD interacts with TRIM21 to negatively regulate the late IFNA pathway in response to viral infections. FADD enhances TRIM21 ubiquitin ligase activity to repress IFNA activation in SeV infected cells. In addition, FADD with TRIM21 can ubiquitinate IRF7 and change its phosphorylation state, consequently interfering with the activity of TRAF6.

PMID 21804564

FADD preserves epithelial barrier integrity and antibacterial defence, maintains homeostasis and prevents chronic intestinal inflammation. (Demonstrated in mouse)

PMID 21979465

Upon cleavage, FADD oligomerizes and activates the caspase cascade to induce killing of tumour cells and intracellular pathogens by innate effector natural killer cells.

PMID 22000287

FADD deficiency induces severe inflammatory skin lesions in mice, revealing a protective role for FADD in epidermal keratinocytes. (Demonstrated in mice)

InnateDB Annotation from Orthologs

Summary

PMID 21183682

[Mus musculus] Fadd interacts with Trim21 to negatively regulate the late Ifna pathway in response to viral infections. Fadd enhances Trim21 ubiquitin ligase activity to repress Ifna activation in SeV infected cells. In addition, Fadd with Trim21 can ubiquitinate Irf7 and change its phosphorylation state, consequently interfering with the activity of Traf6.

PMID 21804564

[Mus musculus] Fadd preserves epithelial barrier integrity and antibacterial defence, maintains homeostasis and prevents chronic intestinal inflammation.

PMID 21979465

[Mus musculus] Upon cleavage, Fadd oligomerizes and activates the caspase cascade to induce killing of tumour cells and intracellular pathogens by innate effector natural killer cells. (Demonstrated in human)

PMID 22000287

[Mus musculus] Fadd deficiency induces severe inflammatory skin lesions in mice, revealing a protective role for Fadd in epidermal keratinocytes.

Entrez Gene

Summary

The protein encoded by this gene is an adaptor molecule that interacts with various cell surface receptors and mediates cell apoptotic signals. Through its C-terminal death domain, this protein can be recruited by TNFRSF6/Fas-receptor, tumor necrosis factor receptor, TNFRSF25, and TNFSF10/TRAIL-receptor, and thus it participates in the death signaling initiated by these receptors. Interaction of this protein with the receptors unmasks the N-terminal effector domain of this protein, which allows it to recruit caspase-8, and thereby activate the cysteine protease cascade. Knockout studies in mice also suggest the importance of this protein in early T cell development. [provided by RefSeq, Jul 2008]

Gene Information

Type

Protein coding

Genomic Location

Chromosome 11:70203163-70207390

Strand

Forward strand

Band

q13.3

Transcripts

ENST00000301838

ENSP00000301838

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 123 experimentally validated interaction(s) in this database.
They are also associated with 19 interaction(s) predicted by orthology.

Experimentally validated
Total	123 [view]
Protein-Protein	121 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	1 [view]
DNA-RNA	0

Predicted by orthology
Total	19 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0002020	protease binding
GO:0005123	death receptor binding
GO:0005164	tumor necrosis factor receptor binding
GO:0005515	protein binding
GO:0032403	protein complex binding
GO:0032813	tumor necrosis factor receptor superfamily binding
GO:0035877	death effector domain binding
GO:0042802	identical protein binding

Biological Process

GO:0001916	positive regulation of T cell mediated cytotoxicity
GO:0002224	toll-like receptor signaling pathway
GO:0002756	MyD88-independent toll-like receptor signaling pathway
GO:0002821	positive regulation of adaptive immune response
GO:0006915	apoptotic process
GO:0006919	activation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0007165	signal transduction
GO:0008625	extrinsic apoptotic signaling pathway via death domain receptors
GO:0016032	viral process
GO:0032729	positive regulation of interferon-gamma production
GO:0032757	positive regulation of interleukin-8 production
GO:0032760	positive regulation of tumor necrosis factor production
GO:0033077	T cell differentiation in thymus
GO:0034138	toll-like receptor 3 signaling pathway
GO:0034142	toll-like receptor 4 signaling pathway
GO:0035666	TRIF-dependent toll-like receptor signaling pathway
GO:0036462	TRAIL-activated apoptotic signaling pathway
GO:0042104	positive regulation of activated T cell proliferation
GO:0042981	regulation of apoptotic process
GO:0043029	T cell homeostasis
GO:0043065	positive regulation of apoptotic process
GO:0043123	positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0045087	innate immune response (InnateDB)
GO:0045651	positive regulation of macrophage differentiation
GO:0045862	positive regulation of proteolysis
GO:0045944	positive regulation of transcription from RNA polymerase II promoter
GO:0048535	lymph node development
GO:0048536	spleen development
GO:0048538	thymus development
GO:0051291	protein heterooligomerization
GO:0051607	defense response to virus
GO:0060340	positive regulation of type I interferon-mediated signaling pathway
GO:0060546	negative regulation of necroptotic process
GO:0070236	negative regulation of activation-induced cell death of T cells
GO:0071260	cellular response to mechanical stimulus
GO:0097049	motor neuron apoptotic process
GO:0097190	apoptotic signaling pathway
GO:0097191	extrinsic apoptotic signaling pathway
GO:0097192	extrinsic apoptotic signaling pathway in absence of ligand
GO:0097202	activation of cysteine-type endopeptidase activity
GO:0097527	necroptotic signaling pathway
GO:1902043	positive regulation of extrinsic apoptotic signaling pathway via death domain receptors
GO:2000454	positive regulation of CD8-positive, alpha-beta cytotoxic T cell extravasation
GO:2001238	positive regulation of extrinsic apoptotic signaling pathway
GO:2001239	regulation of extrinsic apoptotic signaling pathway in absence of ligand

Cellular Component

GO:0005737	cytoplasm
GO:0005829	cytosol
GO:0031264	death-inducing signaling complex
GO:0031265	CD95 death-inducing signaling complex
GO:0043005	neuron projection
GO:0043234	protein complex
GO:0044297	cell body
GO:0045121	membrane raft
GO:0097342	ripoptosome