HDR (Danio rerio)
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 [+]
hdr | Danio rerio | 7955 | length:420
MRYITLLVLLLLNVINAARSHGDLAWAHRSVKNRLSRDVSCREGLEYPHENICCLNCPAG
TYVKKACAAAAEKGVCAPCEFDTYTEHDHGLLKCISCDKCRIDQETIEKCTSTQNTRCKC
RNGSFCLPDQACEVCKKCSRCKEDEETEKSCTAISNTVCRKRSSPGSSTSMTFIVIMPLI
VLLACVLCIVYWTKSKQNKTAAPVTSRSPREMVKICMGDSEEVREEKQNDHNSRIDDSSQ
LQPFLEQNYVVGTSVPHPSEAEKDKGLGDSLPNTANSSQTSLAICAVPSDLQSCHTNQSS
SSVLAWQPPALESESSRRLVPLSGEESLKKTFDFFEEIDVHYHNRFFRLIGLSDNAIKSA
ESLFPEDRVYELLKIWMEKEGLKADFNSLIDALIYLDQRLSAENIIAKAINNSCFKYEEE
TYVKKACAAAAEKGVCAPCEFDTYTEHDHGLLKCISCDKCRIDQETIEKCTSTQNTRCKC
RNGSFCLPDQACEVCKKCSRCKEDEETEKSCTAISNTVCRKRSSPGSSTSMTFIVIMPLI
VLLACVLCIVYWTKSKQNKTAAPVTSRSPREMVKICMGDSEEVREEKQNDHNSRIDDSSQ
LQPFLEQNYVVGTSVPHPSEAEKDKGLGDSLPNTANSSQTSLAICAVPSDLQSCHTNQSS
SSVLAWQPPALESESSRRLVPLSGEESLKKTFDFFEEIDVHYHNRFFRLIGLSDNAIKSA
ESLFPEDRVYELLKIWMEKEGLKADFNSLIDALIYLDQRLSAENIIAKAINNSCFKYEEE
Structure links:
Evolution [+]
View protein alignment and tree with Jalview:  
Explore tree at phylomeDB:   Click here.
Homologs list [+]
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 |
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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 |
Check GO Evidence Codes here
Information from other databases [+]
- Gene info from ZFIN [?] ZDB-GENE-030826-5
- Ensembl genome browser [?] : ENSDARG00000004392
- Expression info from Arrayexpress [?] : ENSDARG00000004392
- Protein expression from Protein Atlas: [?] ENSDARG00000004392
Click on [?] for more information.