CASP8 (Danio rerio)
Description [+]
- Synonyms: CASP8, CASPASE 8, CASPASE-8, ZCASPASE-8A, MGC92075, ZGC:92075
- Species: Metazoa;Bilateria;Deuterostoma;Chordata;Vertebrata;Pisces; Danio rerio
- Short gene description: caspase 8, apoptosis-related cysteine peptidase [Source:RefSeq_peptide;Acc:NP_571585]
- Family: Caspase
- Process: apoptosis,
- Pathways: extrinsic pathway,
- Criteria: manually curated
- Curator comment: Ectopic expression of Casp8 in zebrafish embryos induces apoptosis [16888647]. Zebrafish Casp8 directly associates with FADD through homophilic death effector domain (DED) interactions [17459614]. Zebrafish Casp8 can mediate apoptosis following death receptor activation in mouse embryonic fibroblast cells that lack endogenous caspase-8 [17459614].
- WIKI: CASP8-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.
- Conserved function of caspase-8 in apoptosis during bony fish evolution.
- Sakata S,Yan Y,Satou Y,Momoi A,Ngo-Hazelett P,Nozaki M,Furutani-Seiki M,Postlethwait JH,Yonehara S,Sakamaki K
- Caspase-8, a member of the caspase family, plays an important role in apoptotic signal transduction in mammals. Here we report the identification and characterization of the caspase-8 (casp8) gene in the zebrafish Danio rerio. The zebrafish casp8 gene has a genomic organization similar to mammalian casp8 genes, consisting of 10 exons. By chromosome mapping, we found that casp8 maps on linkage group 6 (LG6), a zebrafish chromosome segment orthologous to the long arm of human Chr. 2, which carries CASP8. In contrast, the zebrafish casp10-like gene and the cflar gene separately localize on LG9 and LG11, respectively, and these genes form a cluster with CASP8 on the human chromosome. This chromosomal segregation is unique to fish but not other vertebrates. Furthermore, we examined the function of zebrafish Casp8 protein in mammalian cells, and showed that it has pro-apoptotic activity when overexpressed. In addition, this molecule was capable of transmitting apoptotic signals mediated through not only Fas but also the TNF receptor in mouse Casp8-deficient cells. Expression analysis showed that casp8 is maternally expressed, and transcripts continue to be present throughout embryogenesis and into larval stages. These results show that zebrafish casp8 has a structure and function similar to mammalian CASP8 orthologs, and our study suggests that the role of caspase-8 in the apoptotic signal pathway has been conserved over at least 450 million years of vertebrate evolution. Gene. 2007 Jul 1;396(1):134-48. Epub 2007 Mar 27.
Structure & Sequence [+]
Pfam domains:
(Pfam is a large collection of protein families.)
| Source | Domain Name | Start | End |
|---|---|---|---|
| PFAM A | DED | 1 | 82 |
| PFAM A | DED | 99 | 179 |
| PFAM A | Peptidase_C14 | 256 | 473 |
Protein sequence [+]
casp8 | Danio rerio | 7955 | length:476
MDPQIFHEIDENLTSGDVDQLKFLCLDFIPKRRLESVTDAKDLILRLDEQGLLEDELLFP
ELLITIGRIDLLEILKKSKEEVKRNLLRCDNSRKGVSAYRKMLLKISEDMTEENFRAAKF
LLDLPRAKLGRSTSFLDTLIEMEKQQRLGPDNLDELYRILEKCDKQLAVMIERFRNQSHR
DQEQGGRLPLEEVFLNNPVSETMERERRRNSSAGTITTDAETPLNKKKFYISSTAPLGIC
FLRKMLTFLQEFVMLKFLSLSLSADRLAKLFSRMHFQIEVRSDLEAWAIKDEIKQFANKN
HASMGAFVCCILSHGEKGTVLGTDGKPVEIREVTLPFAGCRTLASKPKLFFIQACQGDEN
QAGVWTSDGREDAPEEDEKYEEDAGIIVLRKIPIEADFLIGMATVEHYLSYRHTKEGSIF
IQELCKKMEELCPKKEDMLSILTKVNFEVSKRILKGYKQMPEPRYTLTKKLVLPID
ELLITIGRIDLLEILKKSKEEVKRNLLRCDNSRKGVSAYRKMLLKISEDMTEENFRAAKF
LLDLPRAKLGRSTSFLDTLIEMEKQQRLGPDNLDELYRILEKCDKQLAVMIERFRNQSHR
DQEQGGRLPLEEVFLNNPVSETMERERRRNSSAGTITTDAETPLNKKKFYISSTAPLGIC
FLRKMLTFLQEFVMLKFLSLSLSADRLAKLFSRMHFQIEVRSDLEAWAIKDEIKQFANKN
HASMGAFVCCILSHGEKGTVLGTDGKPVEIREVTLPFAGCRTLASKPKLFFIQACQGDEN
QAGVWTSDGREDAPEEDEKYEEDAGIIVLRKIPIEADFLIGMATVEHYLSYRHTKEGSIF
IQELCKKMEELCPKKEDMLSILTKVNFEVSKRILKGYKQMPEPRYTLTKKLVLPID
Structure links:
Evolution [+]
View protein alignment and tree with Jalview:
Explore tree at phylomeDB: Click here.
Homologs list [+]
| Name | Relationship | Species |
|---|---|---|
| C_intestinalis_ENSCINP00000024485 | orthology | Ciona |
| T_rubripes_ENSTRUP00000024467 | orthology | Fugu |
| G_aculeatus_ENSGACP00000016969 | orthology | Gasterosteus |
| Q56VC9_ORYLA | orthology | Medaka |
| T_nigroviridis_ENSTNIP00000010722 | orthology | Tetraodon |
| A_aegypti_AAEL014348-PA | paralogy | Aedes |
| NP_990057.1 | paralogy | Chicken |
| NP_001038154.1 | paralogy | Chicken |
| CASP10 | paralogy | Chicken |
| NP_990056.1 | paralogy | Chicken |
| CASP2_CHICK | paralogy | Chicken |
| NP_989923.1 | paralogy | Chicken |
| CASP7 | paralogy | Chicken |
| CASP6 | paralogy | Chimpanzee |
| CASP9 | paralogy | Chimpanzee |
| CASP7 | paralogy | Chimpanzee |
| XR_025516.1 | paralogy | Chimpanzee |
| CASP3_PANTR | paralogy | Chimpanzee |
| CASP8 | paralogy | Chimpanzee |
| CFLAR | paralogy | Chimpanzee |
| C_intestinalis_ENSCINP00000011503 | paralogy | Ciona |
| C_intestinalis_ENSCINP00000028692 | paralogy | Ciona |
| C_intestinalis_ENSCINP00000011493 | paralogy | Ciona |
| C_intestinalis_ENSCINP00000003204 | paralogy | Ciona |
| IPI00689801.3 | paralogy | Cow |
| NP_001039435.1 | paralogy | Cow |
| CASP6_BOVIN | paralogy | Cow |
| CASP3_BOVIN | paralogy | Cow |
| IPI00704513.4 | paralogy | Cow |
| CASP7 | paralogy | Dog |
| Q45T68_CANFA | paralogy | Dog |
| CASP6 | paralogy | Dog |
| Q38JA9_CANFA | paralogy | Dog |
| CASP10 | paralogy | Dog |
| CFLAR | paralogy | Dog |
| CASP3_CANFA | paralogy | Dog |
| Ice | paralogy | Fly |
| CASP2 | paralogy | Fugu |
| CASP9 | paralogy | Fugu |
| CASP7 | paralogy | Fugu |
| T_rubripes_ENSTRUP00000024164 | paralogy | Fugu |
| NP_001027871.1 | paralogy | Fugu |
| T_rubripes_ENSTRUP00000044662 | paralogy | Fugu |
| CFLAR | paralogy | Fugu |
| CFLAR | paralogy | Gasterosteus |
| CASP3 (3 of 4) | paralogy | Gasterosteus |
| G_aculeatus_ENSGACP00000016983 | paralogy | Gasterosteus |
| CASP3 (2 of 4) | paralogy | Gasterosteus |
| CASP2 | paralogy | Gasterosteus |
| CASP3 (1 of 4) | paralogy | Gasterosteus |
| CASP7 | paralogy | Gasterosteus |
| CASP6 | paralogy | Gasterosteus |
| CASP3 (4 of 4) | paralogy | Gasterosteus |
| G_aculeatus_ENSGACP00000005791 | paralogy | Gasterosteus |
| CASP9 | paralogy | Gasterosteus |
| CASP7 | paralogy | Gorilla |
| CASP8 | paralogy | Gorilla |
| CFLAR | paralogy | Horse |
| CASP6 | paralogy | Horse |
| Q3S2Z5_HORSE | paralogy | Horse |
| CASP7 | paralogy | Horse |
| CASP9 | paralogy | Horse |
| CASP8 | paralogy | Horse |
| CASP10 | paralogy | Horse |
| CASP3 | paralogy | Human |
| CASP7 | paralogy | Human |
| CASP9 | paralogy | Human |
| CASP10 | paralogy | Human |
| CASP8 | paralogy | Human |
| CASP6 | paralogy | Human |
| CFLAR | paralogy | Human |
| CASP10 | paralogy | Lyzard |
| CASP7 | paralogy | Lyzard |
| CASP6 | paralogy | Lyzard |
| CASP3 | paralogy | Lyzard |
| CASP8 | paralogy | Macaca |
| CASP7 | paralogy | Macaca |
| Q8MJ18_MACMU | paralogy | Macaca |
| CASP9 | paralogy | Macaca |
| CASP10 | paralogy | Macaca |
| Q8SPU2_MACMU | paralogy | Macaca |
| CFLAR | paralogy | Medaka |
| CASP2 | paralogy | Medaka |
| O_latipes_ENSORLP00000013993 | paralogy | Medaka |
| Q8JIS8_ORYLA | paralogy | Medaka |
| Q8JIS9_ORYLA | paralogy | Medaka |
| NP_001033061.1 | paralogy | Monodelphis |
| NP_001033059.1 | paralogy | Monodelphis |
| CFLAR | paralogy | Monodelphis |
| CASP10 | paralogy | Monodelphis |
| CASP8 | paralogy | Monodelphis |
| CASP9 | paralogy | Monodelphis |
| CASP6 | paralogy | Monodelphis |
| Casp8 | paralogy | Mouse |
| Casp6 | paralogy | Mouse |
| Casp9 | paralogy | Mouse |
| Casp7 | paralogy | Mouse |
| Casp3 | paralogy | Mouse |
| CFLAR_PONPY | paralogy | Orangutan |
| Q5RB11_PONPY | paralogy | Orangutan |
| Q5RCR7_PONPY | paralogy | Orangutan |
| CASP3 | paralogy | Orangutan |
| CASP9 | paralogy | Orangutan |
| CASP7 | paralogy | Orangutan |
| CASP6 | paralogy | Orangutan |
| CASP9 | paralogy | Ornithorhynchus |
| CASP8 | paralogy | Ornithorhynchus |
| CASP7 | paralogy | Ornithorhynchus |
| CASP6 | paralogy | Ornithorhynchus |
| O_anatinus_ENSOANP00000001054 | paralogy | Ornithorhynchus |
| CASP3 | paralogy | Ornithorhynchus |
| CASP10 | paralogy | Ornithorhynchus |
| CASP8 | paralogy | Rabbit |
| CASP10 | paralogy | Rabbit |
| CASP7 | paralogy | Rabbit |
| Casp9 | paralogy | Rat |
| Casp3 | paralogy | Rat |
| Casp6 | paralogy | Rat |
| Casp7 | paralogy | Rat |
| Casp8 | paralogy | Rat |
| CASP7 | paralogy | Tetraodon |
| CASP9 | paralogy | Tetraodon |
| CASP3 | paralogy | Tetraodon |
| T_nigroviridis_ENSTNIP00000001216 | paralogy | Tetraodon |
| CASP3 | paralogy | Xenopus |
| CASP2 | paralogy | Xenopus |
| casp7 | paralogy | Xenopus |
| casp10 | paralogy | Xenopus |
| T_guttata_ENSTGUP00000011206 | paralogy | Zebra finch |
| CASP10 | paralogy | Zebra finch |
| T_guttata_ENSTGUP00000004278 | paralogy | Zebra finch |
| CASP9 | paralogy | Zebra finch |
| CASP8 | paralogy | Zebra finch |
| T_guttata_ENSTGUP00000014729 | paralogy | Zebra finch |
| CASP3 | paralogy | Zebra finch |
| casp3b | paralogy | Zebrafish |
| casp7 | paralogy | Zebrafish |
| casp6 | paralogy | Zebrafish |
| casp8l1 | paralogy | Zebrafish |
| LOC100000522 | paralogy | Zebrafish |
| casp8l2 | paralogy | Zebrafish |
| casp3a | paralogy | Zebrafish |
| casp6l1 | paralogy | Zebrafish |
| NP_001077331.1 | paralogy | Zebrafish |
| casp6l2 | paralogy | Zebrafish |
| LOC795066 | paralogy | Zebrafish |
| D_rerio_ENSDARP00000047019 | paralogy | Zebrafish |
| casp2 | paralogy | Zebrafish |
| A2BGE2_DANRE | paralogy | Zebrafish |
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Gene Ontology [+]
| GO id | Name | Ontology type | Evidence |
|---|---|---|---|
| GO:0043065 | positive regulation of apoptosis | biological_proccess | IDA |
| GO:0006508 | proteolysis | biological_proccess | IEA |
| GO:0006915 | apoptosis | biological_proccess | IEA |
| GO:0042981 | regulation of apoptosis | biological_proccess | IEA |
| GO:0005515 | protein binding | mollecular_function | IEA |
| GO:0004197 | cysteine-type endopeptidase activity | mollecular_function | IEA |
| GO:0008234 | cysteine-type peptidase activity | mollecular_function | IEA |
Check GO Evidence Codes here
KEGG Pathways [+]
Information from other databases [+]
- Gene info from ZFIN [?] ZDB-GENE-000713-1
- Ensembl genome browser [?] : ENSDARG00000058325
- Expression info from Arrayexpress [?] : ENSDARG00000058325
- Protein expression from Protein Atlas: [?] ENSDARG00000058325
- Community gene edition from Wikigenes: [?] 58022
Click on [?] for more information.
