Apoptosis Database

Description [+]

Synonyms: TNFRSFA, TUMOR NECROSIS FACTOR RECEPTOR SUPERFAMILY MEMBER A, OTR, WU:FC27C09, TNF, OVARIAN TNF RECEPTOR
Species: Metazoa;Bilateria;Deuterostoma;Chordata;Vertebrata;Pisces; Danio rerio
Short gene description: tumor necrosis factor receptor superfamily, member a [Source:RefSeq_peptide;Acc:NP_571915]
Family: Death receptor
Process: apoptosis,
Pathways: extrinsic pathway,
Criteria: manually curated
Curator comment: Ectopic expression of Tnfrsfa in zebrafish embryos and human cell lines induces apoptosis [16888647] . Tnfrsfa directly associates with the zebrafish Apo2L/TRAIL orthologs Tnfsf10l and Tnfsf10l2 [16888647] .
WIKI: TNFRSFA-D_rerio

References [+]

Delineation of the cell-extrinsic apoptosis pathway in the zebrafish.
Eimon PM, Kratz E, Varfolomeev E, Hymowitz SG, Stern H, Zha J, Ashkenazi A
The mammalian extrinsic apoptosis pathway is triggered by Fas ligand (FasL) and Apo2 ligand/tumor necrosis factor (TNF)-related apoptosis-inducing ligand (Apo2L/TRAIL). Ligand binding to cognate receptors activates initiator caspases directly in a death-inducing signaling complex. In Drosophila, TNF ligand binding activates initiator caspases indirectly, through JNK. We characterized the extrinsic pathway in zebrafish to determine how it operates in a nonmammalian vertebrate. We identified homologs of FasL and Apo2L/TRAIL, their receptors, and other components of the cell death machinery. Studies with three Apo2L/TRAIL homologs demonstrated that they bind the receptors zHDR (previously linked to hematopoiesis) and ovarian TNFR (zOTR). Ectopic expression of these ligands during embryogenesis induced apoptosis in erythroblasts and notochord cells. Inhibition of zHDR, zOTR, the adaptor zFADD, or caspase-8-like proteases blocked ligand-induced apoptosis, as did antiapoptotic Bcl-2 family members. Thus, the extrinsic apoptosis pathway in zebrafish closely resembles its mammalian counterpart and cooperates with the intrinsic pathway to trigger tissue-specific apoptosis during embryogenesis in response to ectopic Apo2L/TRAIL expression. Cell Death Differ. 2006 Oct;13(10):1619-30. Epub 2006 Aug 4.

Molecular cloning and expression of a TNF receptor and two TNF ligands in the fish ovary.
Bobe J, Goetz FW
Using degenerative primers, partial cDNAs of a TNF (tumor necrosis factor) receptor and two TNF ligands were obtained by PCR of zebrafish and trout cDNAs, or cDNA libraries. These fragments were then used to screen cDNA libraries of appropriate tissues to obtain clones containing full coding sequences. A zebrafish cDNA was obtained that presumably codes for a 438 amino acid ovarian TNF receptor (OTR) that was identified as a death-domain-containing member of the TNF receptor family. On Northern blots, the OTR cDNA hybridized with a 3.4-kb transcript that is abundant in the zebrafish ovary but lightly detected in all other tissues tested. A zebrafish cDNA presumably coding for a 214 amino acid protein with sequence similarity to mammalian TRAIL (TNF-related apoptosis inducing ligand), was also isolated. In addition, a fragment of the brook trout TRAIL homologue was obtained. Finally, a full-length brook trout cDNA, that presumably codes for a 255 amino acid protein with sequence similarity to mammalian TNF-alpha and lymphotoxin-alpha, was isolated. This study is the first report of a death-domain-containing TNF receptor and the first published report of a TNF ligand in fish. Comp Biochem Physiol B Biochem Mol Biol. 2001 Jun;129(2-3):475-81.

Structure & Sequence [+]

Pfam domains: (Pfam is a large collection of protein families.)

Source	Domain Name	Start	End
PFAM A	TNFR_c6	83	122
PFAM A	Death	348	428

Protein sequence [+]

Structure links:

Smartdomain prediction information: SM00208
Smartdomain prediction information: SM00005
Prosite motif and domain information: PS00652

Evolution [+]

Name	Relationship	Species
NP_989717.1	orthology	Chicken
T_rubripes_ENSTRUP00000013812	orthology	Fugu
G_aculeatus_ENSGACP00000020911	orthology	Gasterosteus
A_carolinensis_ENSACAP00000000071	orthology	Lyzard
O_latipes_ENSORLP00000003602	orthology	Medaka
TNFRSF10D	orthology	Tetraodon
Q9DGH7_CHICK	paralogy	Chicken
NP_001025950.1	paralogy	Chicken
NM_204115.1	paralogy	Chicken
CD27	paralogy	Chimpanzee
TNFRSF10B	paralogy	Chimpanzee
TNFRSF10C	paralogy	Chimpanzee
TNFRSF14	paralogy	Chimpanzee
TNR1A_BOVIN	paralogy	Cow
NP_001075903.1	paralogy	Cow
CD27	paralogy	Dog
O97530_CANFA	paralogy	Dog
T_rubripes_ENSTRUP00000010129	paralogy	Fugu
G_aculeatus_ENSGACP00000011439	paralogy	Gasterosteus
TNFRSF21	paralogy	Gasterosteus
G_aculeatus_ENSGACP00000007142	paralogy	Gasterosteus
E_caballus_ENSECAP00000022015	paralogy	Horse
TNFRSF1A	paralogy	Horse
TRAIL-R3 / TNFSF10C	paralogy	Human
TNFRSF14	paralogy	Human
TRAIL-R2, TNFRSF10B	paralogy	Human
CD27	paralogy	Human
TNFRSF10A	paralogy	Macaca
TNFRSF14	paralogy	Macaca
CD27	paralogy	Macaca
TNFRSF1A	paralogy	Macaca
O_latipes_ENSORLP00000020293	paralogy	Medaka
TNFRSF1A	paralogy	Monodelphis
M_domestica_ENSMODP00000011508	paralogy	Monodelphis
Tnfrsf14	paralogy	Mouse
Tnfrsf4	paralogy	Mouse
Cd27	paralogy	Mouse
Tnfrsf10b	paralogy	Mouse
TNFRSF10B	paralogy	Orangutan
TNFRSF10D	paralogy	Orangutan
TNFRSF25	paralogy	Ornithorhynchus
Tnfrsf4	paralogy	Rat
Tnfrsf1a	paralogy	Rat
MGC112688	paralogy	Rat
Tnfrsf10b	paralogy	Rat
EDA2R	paralogy	Xenopus
hdr	paralogy	Zebrafish
fas	paralogy	Zebrafish
ngfrl	paralogy	Zebrafish
zgc:153759	paralogy	Zebrafish
LOC572204	paralogy	Zebrafish

Gene Ontology [+]

GO id	Name	Ontology type	Evidence
GO:0043065	positive regulation of apoptosis	biological_proccess	IDA
GO:0007165	signal transduction	biological_proccess	IEA
GO:0005515	protein binding	mollecular_function	IEA
GO:0004872	receptor activity	mollecular_function	IEA

Information from other databases [+]

TNFRSFA (Danio rerio)