Apoptosis Database

Description [+]

Synonyms: HDR, HEMATOPOIETIC DEATH RECEPTOR, ZGC:103531, ZH-DR, MGC103531
Species: Metazoa;Bilateria;Deuterostoma;Chordata;Vertebrata;Pisces; Danio rerio
Short gene description: hematopoietic death receptor [Source:RefSeq_peptide;Acc:NP_919372]
Family: Death receptor
Process: apoptosis,
Pathways: extrinsic pathway,
Criteria: manually curated
Curator comment: Ectopic expression of HDR in zebrafish embryos and human cell lines induces apoptosis [16888647]. HDR directly associates with the zebrafish Apo2L/TRAIL orthologs tnfsf10l and tnfsf10l3 [16888647]. Inhibition of HDR in zebrafish embryos and adult fish leads to an accumulation of red blood cells [10934476],[16413388].
WIKI: HDR-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.

Stimulation of erythropoiesis by inhibiting a new hematopoietic death receptor in transgenic zebrafish.
Long Q,Huang H,Shafizadeh E,Liu N,Lin S
Still not available. Nat Cell Biol. 2000 Aug;2(8):549-52.

Regulation of primitive hematopoiesis in zebrafish embryos by the death receptor gene.
Kwan TT,Liang R,Verfaillie CM,Ekker SC,Chan LC,Lin S,Leung AY
OBJECTIVE: We investigated the regulatory mechanism of primitive hematopoiesis in zebrafish (Danio rerio) embryos with particular reference to the role of a death receptor (zDR) gene, based on a morpholino (MO) knockdown approach. METHODS: MOs targeting the zDR and chordin (Chd) were injected into naturally spawned embryos at one- to four-cell stage. A random sequence (RS) MO was used as a control. Effects on hemoglobin formation (Hb), apoptosis, and lineage-specific gene expression were examined. Embryos injected with zDR, Chd, and RS-MOs were denoted zDR(mo), zChd(mo), and zRS(mo), respectively. Those co-injected with Chd+zDR-MOs and Chd+RS-MOs were abbreviated zChd+DR(mo) and zChd+RS(mo). RESULTS: zDR mRNA expression was restricted to the intermediate cell mass of wild-type (WT) and zChd(mo) embryos. At 48 hours postfertilization, zDR(mo) embryos showed increased Hb compared with WT or zRS(mo) embryos (2.36 x 10(-2) +/- 1.13 x 10(-3) vs 1.85 x 10(-2) +/- 5.60 x 10(-4) vs 1.79 x 10(-2) +/- 1.31 x 10(-3) U, p < 0.05). zChd+DR(mo) embryos also showed increased Hb compared with zChd(mo) or zChd+RS(mo) embryos (4.60 x 10(-2) +/- 2.79 x 10(-3) vs 3.17 x 10(-2) +/- 1.07 x 10(-3) vs 3.05 x 10(-2) +/- 1.25 x 10(-3) U, p < 0.05). zDR-MO reduced apoptosis, as shown by reduced terminal transferase-mediated dUTP nick end-labeling staining in zChd+DR(mo) compared with zChd+RS(mo) embryos and caspase-3 activity in zDR(mo) vs zRS(mo) (0.525 +/- 0.094 vs 0.953 +/- 0.113 U, p < 0.05), and zChd+DR(mo) vs zChd+RS(mo) embryos (0.247 +/- 0.121 vs 1.180 +/- 0.082, p < 0.05). zChd+DR(mo) embryos showed upregulation of erythroid-specific embryonic hemoglobin gene expression but not that of a myeloid-specific myeloperoxidase gene. CONCLUSION: Knockdown of zDR in zebrafish embryos decreased apoptosis and increased Hb, suggesting that zDR may regulate primitive hematopoiesis during development. Exp Hematol. 2006 Jan;34(1):27-34.

Structure & Sequence [+]

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

Source	Domain Name	Start	End
PFAM A	TNFR_c6	79	118
PFAM A	Death	329	409

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
Tnfrsf23	orthology	Mouse
NM_204115.1	paralogy	Chicken
Q9DGH7_CHICK	paralogy	Chicken
TNFRSF10A	paralogy	Chimpanzee
TNFRSF10B	paralogy	Chimpanzee
TNR1A_BOVIN	paralogy	Cow
NP_001092513.1	paralogy	Cow
TNFRSF8	paralogy	Dog
LTBR	paralogy	Dog
FAS	paralogy	Dog
T_rubripes_ENSTRUP00000013812	paralogy	Fugu
T_rubripes_ENSTRUP00000010129	paralogy	Fugu
G_aculeatus_ENSGACP00000007142	paralogy	Gasterosteus
G_aculeatus_ENSGACP00000020911	paralogy	Gasterosteus
TNFRSF10A	paralogy	Gorilla
TNFRSF1A	paralogy	Horse
E_caballus_ENSECAP00000022015	paralogy	Horse
FAS	paralogy	Horse
TRAIL-R1, DR4	paralogy	Human
TRAIL-R2, TNFRSF10B	paralogy	Human
TNFRSF10A	paralogy	Macaca
O_latipes_ENSORLP00000003602	paralogy	Medaka
O_latipes_ENSORLP00000020293	paralogy	Medaka
M_domestica_ENSMODP00000011508	paralogy	Monodelphis
Tnfrsf21	paralogy	Mouse
Tnfrsf10b	paralogy	Mouse
TNFRSF10B	paralogy	Orangutan
TNFRSF10A	paralogy	Orangutan
TNFRSF1A	paralogy	Ornithorhynchus
Tnfrsf1a	paralogy	Rat
TNFRSF10D	paralogy	Tetraodon
LOC572204	paralogy	Zebrafish
tnfrsfa	paralogy	Zebrafish
fas	paralogy	Zebrafish

Gene Ontology [+]

GO id	Name	Ontology type	Evidence
GO:0007165	signal transduction	biological_proccess	IEA
GO:0006915	apoptosis	biological_proccess	IEA
GO:0006955	immune response	biological_proccess	IEA
GO:0005515	protein binding	mollecular_function	IEA
GO:0004872	receptor activity	mollecular_function	IEA
GO:0004888	transmembrane receptor activity	mollecular_function	IEA
GO:0016020	membrane	cell_component	IEA

Information from other databases [+]

HDR (Danio rerio)