FADD (Homo sapiens)
Description [+]
- Synonyms: FADD, MORT1, GIG3
- Species: Metazoa;Bilateria;Deuterostoma;Chordata;Vertebrata;Mammalia;Primates;Hominidae; Homo sapiens
- Short gene description: Protein FADD (FAS-associated death domain protein)(FAS-associating death domain-containing protein)(Mediator of receptor induced toxicity) [Source:UniProtKB/Swiss-Prot;Acc:Q13158]
- Family: Death Domain-containing protein : DD adapter protein Death effector domain-containing protein : DED adapter protein
- Process: apoptosis,
- Pathways: extrinsic pathway,
- Criteria: manually curated
- Curator comment:
- Mouse ortholog(s): Fadd
- WIKI: FADD-H_sapiens
References [+]
- FADD, a novel death domain-containing protein, interacts with the death domain of Fas and initiates apoptosis.
- Chinnaiyan AM, O'Rourke K, Tewari M, Dixit VM
- Using the cytoplasmic domain of Fas in the yeast two-hybrid system, we have identified a novel interacting protein, FADD, which binds Fas and Fas-FD5, a mutant of Fas possessing enhanced killing activity, but not the functionally inactive mutants Fas-LPR and Fas-FD8. FADD contains a death domain homologous to the death domains of Fas and TNFR-1. A point mutation in FADD, analogous to the lpr mutation of Fas, abolishes its ability to bind Fas, suggesting a death domain to death domain interaction. Overexpression of FADD in MCF7 and BJAB cells induces apoptosis, which, like Fas-induced apoptosis, is blocked by CrmA, a specific inhibitor of the interleukin-1 beta-converting enzyme. These findings suggest that FADD may play an important role in the proximal signal transduction of Fas. Cell. 1995 May 19;81(4):505-12.
- References from Mouse ortholog(s):
- Fas-mediated apoptosis and activation-induced T-cell proliferation are defective in mice lacking FADD/Mort1.
- Zhang J, Cado D, Chen A, Kabra NH, Winoto A
- Programmed cell death, or apoptosis, is important in homeostasis of the immune system: for example, non-functional or autoreactive lymphocytes are eliminated through apoptosis. One member of the tumour necrosis factor receptor (TNFR) family, Fas (also known as CD95 or Apo-1), can trigger cell death and is essential for lymphocyte homeostasis. FADD/Mort1 is a Fas-associated protein that is thought to mediate apoptosis by recruiting the protease caspase-8. A dominant-negative mutant of FADD inhibits apoptosis initiated by Fas and other TNFR family members. Other proteins, notably Daxx, also bind Fas and presumably mediate a FADD-independent apoptotic pathway. Here we investigate the role of FADD in vivo by generating FADD-deficient mice. As homozygous mice die in utero, we generated FADD-/- embryonic stem cells and FADD-/- chimaeras in a background devoid of the recombination activating gene RAG-1, which activates rearrangement of the immunoglobulin and T-cell receptor genes. We found that thymocyte subpopulations were apparently normal in newborn chimaeras. Fas-induced apoptosis was completely blocked, indicating that there are no redundant Fas apoptotic pathways. As these mice age, their thymocytes decrease to an undetectable level, although peripheral T cells are present in all older FADD-/- chimaeras. Unexpectedly, activation-induced proliferation is impaired in these FADD-/- T cells, despite production of the cytokine interleukin (IL)-2. These results and the similarities between FADD-/- mice and mice lacking the beta-subunit of the IL-2 receptor suggest that there is an unexpected connection between cell proliferation and apoptosis. Nature. 1998 Mar 19;392(6673):296-300.
Structure & Sequence [+]
Pfam domains:
(Pfam is a large collection of protein families.)
| Source | Domain Name | Start | End |
|---|---|---|---|
| PFAM A | DED | 4 | 87 |
| PFAM A | Death | 98 | 181 |
Protein sequence [+]
FADD | Homo sapiens | 9606 | length:208
MDPFLVLLHSVSSSLSSSELTELKFLCLGRVGKRKLERVQSGLDLFSMLLEQNDLEPGHT
ELLRELLASLRRHDLLRRVDDFEAGAAAGAAPGEEDLCAAFNVICDNVGKDWRRLARQLK
VSDTKIDSIEDRYPRNLTERVRESLRIWKNTEKENATVAHLVGALRSCQMNLVADLVQEV
QQARDLQNRSGAMSPMSWNSDASTSEAS
ELLRELLASLRRHDLLRRVDDFEAGAAAGAAPGEEDLCAAFNVICDNVGKDWRRLARQLK
VSDTKIDSIEDRYPRNLTERVRESLRIWKNTEKENATVAHLVGALRSCQMNLVADLVQEV
QQARDLQNRSGAMSPMSWNSDASTSEAS
Structure links:
- Smartdomain prediction information: SM00031
- Smartdomain prediction information: SM00005
- Profile motif and domain profile information: PS50017
- Profile motif and domain profile information: PS50168
- Interpro domain information: Q13158
- PFAM domain and domain family information: Q13158
- Protein 3D structures from PDB: 1A1W
Evolution [+]
View protein alignment and tree with Jalview:
Explore tree at phylomeDB: Click here.
Homologs list [+]
| Name | Relationship | Species |
|---|---|---|
| FADD | orthology | Chicken |
| FADD | orthology | Chimpanzee |
| FADD_BOVIN | orthology | Cow |
| FADD | orthology | Dog |
| FADD | orthology | Gasterosteus |
| FADD | orthology | Gorilla |
| FADD | orthology | Horse |
| FADD | orthology | Lyzard |
| FADD | orthology | Macaca |
| Q56VD0_ORYLA | orthology | Medaka |
| FADD | orthology | Monodelphis |
| Fadd | orthology | Mouse |
| FADD | orthology | Orangutan |
| FADD | orthology | Ornithorhynchus |
| FADD | orthology | Rabbit |
| Fadd | orthology | Rat |
| FADD | orthology | Tetraodon |
| FADD | orthology | Xenopus |
| FADD | orthology | Zebra finch |
| fadd | orthology | Zebrafish |
| CASP10 | paralogy | Chicken |
| ANK1 | paralogy | Chimpanzee |
| RIPK1 | paralogy | Gorilla |
| ANK1 | paralogy | Human |
| RIPK1 | paralogy | Lyzard |
| RIPK1 | paralogy | Monodelphis |
| CASP8 | paralogy | Monodelphis |
| Casp8 | paralogy | Mouse |
| Ripk1 | paralogy | Mouse |
| RIPK1 | paralogy | Orangutan |
| RIPK1 | paralogy | Ornithorhynchus |
| CASP8 | paralogy | Ornithorhynchus |
| RIPK1 | paralogy | Rabbit |
| Casp8 | paralogy | Rat |
| NP_001100820.1 | paralogy | Rat |
| RIPK1 | paralogy | Tetraodon |
| T_nigroviridis_ENSTNIP00000010722 | paralogy | Tetraodon |
| CASP8 | paralogy | Zebra finch |
| zgc:101738 | paralogy | Zebrafish |
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Gene Ontology [+]
| GO id | Name | Ontology type | Evidence |
|---|---|---|---|
| GO:0070265 | necrotic cell death | biological_proccess | IMP |
| GO:0007165 | signal transduction | biological_proccess | IEA |
| GO:0042981 | regulation of apoptosis | biological_proccess | IEA |
| GO:0008625 | induction of apoptosis via death domain receptors | biological_proccess | TAS |
| GO:0008633 | activation of pro-apoptotic gene products | biological_proccess | EXP |
| GO:0043123 | positive regulation of I-kappaB kinase/NF-kappaB cascade | biological_proccess | IEP |
| GO:0044419 | interspecies interaction between organisms | biological_proccess | IEA |
| GO:0051291 | protein heterooligomerization | biological_proccess | IEA |
| GO:0042802 | identical protein binding | mollecular_function | IPI |
| GO:0005123 | death receptor binding | mollecular_function | TAS |
| GO:0005515 | protein binding | mollecular_function | IEA |
| GO:0031264 | death-inducing signaling complex | cell_component | IDA |
| GO:0005829 | cytosol | cell_component | EXP |
| GO:0043234 | protein complex | cell_component | IEA |
| GO:0045121 | membrane raft | cell_component | IEA |
Check GO Evidence Codes here
KEGG Pathways [+]
Information from other databases [+]
- Gene info from HGNC [?] :3573
- Gene related info from GeneCards [?] : FADD
- Ensembl genome browser [?] : ENSG00000168040
- Expression info from Arrayexpress [?] : ENSG00000168040
- Protein expression from Protein Atlas: [?] ENSG00000168040
- Community gene edition from Wikigenes: [?] 8772
- OMIM gene information: 602457
- OMIM disease information:
Click on [?] for more information.
