FADD Fas associated via death domain [Homo sapiens (human)] - Gene

Summary

Official Symbol: FADDprovided by HGNC
Official Full Name: Fas associated via death domainprovided by HGNC
Primary source: HGNC:HGNC:3573
See related: Ensembl:ENSG00000168040 MIM:602457
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: GIG3; MORT1
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]
Expression: Ubiquitous expression in kidney (RPKM 9.3), colon (RPKM 8.7) and 25 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 11q13.3

Exon count:: 2

Annotation release	Status	Assembly	Chr	Location
109.20200228	current	GRCh38.p13 (GCF_000001405.39)	11	NC_000011.10 (70203296..70207390)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	11	NC_000011.9 (70049269..70053508)

Chromosome 11 - NC_000011.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Elevated levels of FADD and caspase-8, but not caspase-3, are associated with increased incidence of ischemic stroke.
Title: FADD (Fas-Associated Protein With Death Domain), Caspase-3, and Caspase-8 and Incidence of Ischemic Stroke.
this study has mapped for the first time the domain within LRRK2 that mediates the interaction with FADD, thereby activating the molecular machinery of the extrinsic death pathway.
Title: A motif within the armadillo repeat of Parkinson's-linked LRRK2 interacts with FADD to hijack the extrinsic death pathway.
The data identify FADD as a novel component of the noncanonical TLR4/IFN-beta signaling pathway and demonstrate that both Fas and its adaptor FADD can differentially regulate the production of LPS-induced proinflammatory cytokines and type I interferons.
Title: Engagement of Fas differentially regulates the production of LPS-induced proinflammatory cytokines and type I interferons.
REVIEW: recent knowledge of the biological roles of FADD, a pleiotropic molecule having multiple partners, and its impact in cancer, innate immunity, and inflammation
Title: FADD at the Crossroads between Cancer and Inflammation.
our study revealed that miR-633/FADD axis played a significant role in the chemoresistance and Foxo3a regulated this pathway in gastric cancer
Title: Foxo3a-dependent miR-633 regulates chemotherapeutic sensitivity in gastric cancer by targeting Fas-associated death domain.
SPOP inhibits NF-kappaB (nuclear factor kappa-light-chain-enhancer of activated B cells) activity and its target genes expression via FADD in non-small cell lung cancer
Title: SPOP promotes FADD degradation and inhibits NF-κB activity in non-small cell lung cancer.
K6-linked ubiquitylation of FADD by CHIP is a crucial checkpoint in cytokine-dependent extrinsic apoptosis.
Title: K6 linked polyubiquitylation of FADD by CHIP prevents death inducing signaling complex formation suppressing cell death.
Overexpression of FADD and Caspase-8 suppresses proliferation whilst promoting the apoptosis of human GBM cells.
Title: Overexpression of FADD and Caspase-8 inhibits proliferation and promotes apoptosis of human glioblastoma cells.
FADD expression and its phosphorylation can be reliable biomarkers with prognostic value for T-cell lymphoblastic lymphoma stratification.
Title: Deregulated FADD expression and phosphorylation in T-cell lymphoblastic lymphoma.
FADD interference down-regulated Rheb expression and repressed mTORC1 activity in breast cancer cell lines. The autophagy was induced by FADD deficiency in MCF7 or MDA-231 cells but rescued by recovering Rheb expression.
Title: Fas-associated protein with death domain (FADD) regulates autophagy through promoting the expression of Ras homolog enriched in brain (Rheb) in human breast adenocarcinoma cells.

Submit: New GeneRIF Correction See all GeneRIFs (142)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Infections, recurrent, with encephalopathy, hepatic dysfunction, and cardiovascular malformations MedGen: C3151062 OMIM: 613759 GeneReviews: Not available	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 gp120-induced neuron apoptosis requires the upregulation of the death receptor Fas and its associated death proteins, FADD and CASP8	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Homology

Homologs of the FADD gene: The FADD gene is conserved in chimpanzee, Rhesus monkey, cow, mouse, rat, chicken, zebrafish, and frog.
Orthologs from Annotation Pipeline: 296 organisms have orthologs with human gene FADD
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
caspase binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
caspase binding	IPI Inferred from Physical Interaction more info	PubMed
death effector domain binding	IPI Inferred from Physical Interaction more info	PubMed
death receptor binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
protease binding	IPI Inferred from Physical Interaction more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein-containing complex binding	IEA Inferred from Electronic Annotation more info
receptor serine/threonine kinase binding	IEA Inferred from Electronic Annotation more info
tumor necrosis factor receptor binding	IEA Inferred from Electronic Annotation more info
tumor necrosis factor receptor superfamily binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
T cell differentiation in thymus	ISS Inferred from Sequence or Structural Similarity more info
T cell homeostasis	ISS Inferred from Sequence or Structural Similarity more info
TRAIL-activated apoptotic signaling pathway	IBA Inferred from Biological aspect of Ancestor more info	PubMed
TRAIL-activated apoptotic signaling pathway	IDA Inferred from Direct Assay more info	PubMed
TRIF-dependent toll-like receptor signaling pathway	TAS Traceable Author Statement more info
activation of cysteine-type endopeptidase activity	IDA Inferred from Direct Assay more info	PubMed
activation of cysteine-type endopeptidase activity involved in apoptotic process	TAS Traceable Author Statement more info
apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
apoptotic signaling pathway	IDA Inferred from Direct Assay more info	PubMed
apoptotic signaling pathway	TAS Traceable Author Statement more info
behavioral response to cocaine	IEA Inferred from Electronic Annotation more info
cell surface receptor signaling pathway	TAS Traceable Author Statement more info
cellular response to mechanical stimulus	IEP Inferred from Expression Pattern more info	PubMed
death-inducing signaling complex assembly	TAS Traceable Author Statement more info
defense response to virus	IMP Inferred from Mutant Phenotype more info	PubMed
extrinsic apoptotic signaling pathway	IDA Inferred from Direct Assay more info	PubMed
extrinsic apoptotic signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
extrinsic apoptotic signaling pathway	TAS Traceable Author Statement more info	PubMed
extrinsic apoptotic signaling pathway in absence of ligand	IEA Inferred from Electronic Annotation more info
extrinsic apoptotic signaling pathway via death domain receptors	TAS Traceable Author Statement more info	PubMed
innate immune response	IEA Inferred from Electronic Annotation more info
kidney development	IEA Inferred from Electronic Annotation more info
lymph node development	ISS Inferred from Sequence or Structural Similarity more info
motor neuron apoptotic process	IEA Inferred from Electronic Annotation more info
necroptotic signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of activation-induced cell death of T cells	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of extrinsic apoptotic signaling pathway via death domain receptors	TAS Traceable Author Statement more info
negative regulation of necroptotic process	IEA Inferred from Electronic Annotation more info
positive regulation of CD8-positive, alpha-beta cytotoxic T cell extravasation	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of I-kappaB kinase/NF-kappaB signaling	IEP Inferred from Expression Pattern more info	PubMed
positive regulation of T cell mediated cytotoxicity	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of activated T cell proliferation	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of adaptive immune response	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of apoptotic process	IDA Inferred from Direct Assay more info	PubMed
positive regulation of apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of extrinsic apoptotic signaling pathway	IBA Inferred from Biological aspect of Ancestor more info	PubMed
positive regulation of extrinsic apoptotic signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of interferon-gamma production	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of interleukin-8 production	IDA Inferred from Direct Assay more info	PubMed
positive regulation of macrophage differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of proteolysis	IDA Inferred from Direct Assay more info	PubMed
positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
positive regulation of tumor necrosis factor production	IDA Inferred from Direct Assay more info	PubMed
positive regulation of type I interferon-mediated signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of extrinsic apoptotic signaling pathway via death domain receptors	TAS Traceable Author Statement more info
response to morphine	IEA Inferred from Electronic Annotation more info
spleen development	ISS Inferred from Sequence or Structural Similarity more info
thymus development	ISS Inferred from Sequence or Structural Similarity more info
toll-like receptor 3 signaling pathway	TAS Traceable Author Statement more info
viral process	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
CD95 death-inducing signaling complex	IBA Inferred from Biological aspect of Ancestor more info	PubMed
CD95 death-inducing signaling complex	IDA Inferred from Direct Assay more info	PubMed
cell body	IEA Inferred from Electronic Annotation more info
cytoplasm	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cytoplasm	IDA Inferred from Direct Assay more info	PubMed
cytosol	IDA Inferred from Direct Assay more info	PubMed
cytosol	TAS Traceable Author Statement more info
death-inducing signaling complex	IDA Inferred from Direct Assay more info	PubMed
death-inducing signaling complex	TAS Traceable Author Statement more info	PubMed
membrane raft	IEA Inferred from Electronic Annotation more info
neuron projection	IEA Inferred from Electronic Annotation more info
nucleus	IEA Inferred from Electronic Annotation more info
plasma membrane	IDA Inferred from Direct Assay more info	PubMed
ripoptosome	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: FAS-associated death domain protein

Names: Fas (TNFRSF6)-associated via death domain; Fas-associating death domain-containing protein; Fas-associating protein with death domain; growth-inhibiting gene 3 protein; mediator of receptor-induced toxicity

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_027966.1 RefSeqGene

Range

5001..9240

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_228

mRNA and Protein(s)

NM_003824.4 → NP_003815.1 FAS-associated death domain protein

See identical proteins and their annotated locations for NP_003815.1

Status: REVIEWED

Source sequence(s)

AI886015, AL575732, AP000879, BC000334

Consensus CDS

CCDS8196.1

UniProtKB/Swiss-Prot

Q13158

Related

ENSP00000301838.4, ENST00000301838.4

Conserved Domains (2) summary

cd08306
Location:97 → 181

Death_FADD; Fas-associated Death Domain protein-protein interaction domain

cd08336
Location:24 → 82

DED_FADD; Death Effector Domain found in Fas-Associated via Death Domain