CASP2 (Danio rerio)
Description [+]
- Synonyms: CASP2, CASPASE 2
- Species: Metazoa;Bilateria;Deuterostoma;Chordata;Vertebrata;Pisces; Danio rerio
- Short gene description: caspase 2, apoptosis-related cysteine protease [Source:RefSeq_peptide;Acc:NP_001036160]
- Family: Caspase
- Process: apoptosis,
- Pathways: undefined,
- Criteria: manually curated
- Curator comment: Ectopic expression of Casp2 in zebrafish embryos induces apoptosis [16888647]. Checkpoint kinase 1 (Chk1) suppresses a Casp2-dependent apoptotic program in zebrafish that can mediate gamma-radiation-induced apoptosis [18510930].
- Human ortholog(s): CASP2
- WIKI: CASP2-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.
- Chk1 suppresses a caspase-2 apoptotic response to DNA damage that bypasses p53, Bcl-2, and caspase-3.
- Sidi S,Sanda T,Kennedy RD,Hagen AT,Jette CA,Hoffmans R,Pascual J,Imamura S,Kishi S,Amatruda JF,Kanki JP,Green DR,D Andrea AA,Look AT
- Evasion of DNA damage-induced cell death, via mutation of the p53 tumor suppressor or overexpression of prosurvival Bcl-2 family proteins, is a key step toward malignant transformation and therapeutic resistance. We report that depletion or acute inhibition of checkpoint kinase 1 (Chk1) is sufficient to restore gamma-radiation-induced apoptosis in p53 mutant zebrafish embryos. Surprisingly, caspase-3 is not activated prior to DNA fragmentation, in contrast to classical intrinsic or extrinsic apoptosis. Rather, an alternative apoptotic program is engaged that cell autonomously requires atm (ataxia telangiectasia mutated), atr (ATM and Rad3-related) and caspase-2, and is not affected by p53 loss or overexpression of bcl-2/xl. Similarly, Chk1 inhibitor-treated human tumor cells hyperactivate ATM, ATR, and caspase-2 after gamma-radiation and trigger a caspase-2-dependent apoptotic program that bypasses p53 deficiency and excess Bcl-2. The evolutionarily conserved Chk1-suppressed pathway defines a novel apoptotic process, whose responsiveness to Chk1 inhibitors and insensitivity to p53 and BCL2 alterations have important implications for cancer therapy. Cell. 2008 May 30;133(5):864-77.
- References from Human ortholog(s):
- Ich-1, an Ice/ced-3-related gene, encodes both positive and negative regulators of programmed cell death.
- Wang L, Miura M, Bergeron L, Zhu H, Yuan J
- We report here the isolation and characterization of Ich-1, a gene related to the C. elegans cell death gene ced-3 and the mammalian homolog of ced-3, interleukin-1 beta-converting enzyme (ICE). Alternative splicing results in two distinct Ich-1 mRNA species. One mRNA species encodes a protein product of 435 amino acids (ICH-1L) that is homologous to both the P20 and P10 subunits of ICE (27% identity) and the entire CED-3 protein (28% identity). The other mRNA encodes a 312 amino acid truncated version of ICH-1L protein (ICH-1S). Overexpression of IchL induces programmed cell death, suggesting that Ich-1 is also a mammalian programmed cell death gene. More interestingly, overexpression of the Ich-1S suppresses Rat-1 cell death induced by serum deprivation. These observations suggest that Ich-1 plays an important role in both positive and negative regulation of programmed cell death in vertebrate animals. Cell. 1994 Sep 9;78(5):739-50.
- Caspase-2: killer, savior and safeguard--emerging versatile roles for an ill-defined caspase.
- Krumschnabel G, Manzl C, Villunger A
- Despite the early discovery of caspase-2, its physiological function has long remained an enigma. A number of recent publications now suggest not just one, but multiple functions, including roles in apoptosis, DNA repair and tumor suppression. How can one enzyme have so many talents? Considering the diversity of interaction partners and the specific mode of pro-apoptotic action proposed in these studies, caspase-2 might in fact represent a primordial protease serving numerous pathways, established before the advent of a more elaborate functionally diversified caspases system. Oncogene. 2009 Sep 3;28(35):3093-6. Epub 2009 Jul 6.
- Defects in regulation of apoptosis in caspase-2-deficient mice.
- Bergeron L, Perez GI, Macdonald G, Shi L, Sun Y, Jurisicova A, Varmuza S, Latham KE, Flaws JA, Salter JC, Hara H, Moskowitz MA, Li E, Greenberg A, Tilly JL, Yuan J
- During embryonic development, a large number of cells die naturally to shape the new organism. Members of the caspase family of proteases are essential intracellular death effectors. Herein, we generated caspase-2-deficient mice to evaluate the requirement for this enzyme in various paradigms of apoptosis. Excess numbers of germ cells were endowed in ovaries of mutant mice and the oocytes were found to be resistant to cell death following exposure to chemotherapeutic drugs. Apoptosis mediated by granzyme B and perforin was defective in caspase-2-deficient B lymphoblasts. In contrast, cell death of motor neurons during development was accelerated in caspase-2-deficient mice. In addition, caspase-2-deficient sympathetic neurons underwent apoptosis more effectively than wild-type neurons when deprived of NGF. Thus, caspase-2 acts both as a positive and negative cell death effector, depending upon cell lineage and stage of development. Genes Dev. 1998 May 1;12(9):1304-14.
Structure & Sequence [+]
Pfam domains:
(Pfam is a large collection of protein families.)
| Source | Domain Name | Start | End |
|---|---|---|---|
| PFAM A | CARD | 12 | 97 |
| PFAM A | Peptidase_C14 | 165 | 425 |
Protein sequence [+]
casp2 | Danio rerio | 7955 | length:433
MLGECGMTKWERLALRRNSVKMLQDLVVDDLLIQCLQQDGILTDSMAESIMAKPTSQGRS
HQLLFLLPKRGPRAFSTFCSALKETEQHHLCKLLMDFTEKDKKNSQYKLSPEICKKKNKH
THTHKSMEMCLDADSPVTTAVLPCTPEFYQSHRPQAYPMRSCPRGLALVLSNVRFDSANT
DLDIRRGGEVDEETLRRLFTELDFKVSLHRDLTAEAMRRCLEQFAQQQEHAAYDCAVVCL
LSHGVEGSVYGTDGQLLELDWVFEVFDNARCPLLQNKPKMFFIQACRGEEMDNGVDQLDG
QERTQSPGCEQRDAGREGERDNREKKEEKERERLRVKLPQRSDMICGFATLKGTAAMRNT
KKGSWFIQELNTAIRQRANNTHLSDILVQVNGQIKSREGYAPGSAHHRCKEMSEFTSSLC
KDLYLFPKYYPSN
HQLLFLLPKRGPRAFSTFCSALKETEQHHLCKLLMDFTEKDKKNSQYKLSPEICKKKNKH
THTHKSMEMCLDADSPVTTAVLPCTPEFYQSHRPQAYPMRSCPRGLALVLSNVRFDSANT
DLDIRRGGEVDEETLRRLFTELDFKVSLHRDLTAEAMRRCLEQFAQQQEHAAYDCAVVCL
LSHGVEGSVYGTDGQLLELDWVFEVFDNARCPLLQNKPKMFFIQACRGEEMDNGVDQLDG
QERTQSPGCEQRDAGREGERDNREKKEEKERERLRVKLPQRSDMICGFATLKGTAAMRNT
KKGSWFIQELNTAIRQRANNTHLSDILVQVNGQIKSREGYAPGSAHHRCKEMSEFTSSLC
KDLYLFPKYYPSN
Structure links:
Evolution [+]
View protein alignment and tree with Jalview:
Explore tree at phylomeDB: Click here.
Homologs list [+]
| Name | Relationship | Species |
|---|---|---|
| CASP2_CHICK | orthology | Chicken |
| CASP2 | orthology | Chimpanzee |
| C_intestinalis_ENSCINP00000002956 | orthology | Ciona |
| IPI00707783.1 | orthology | Cow |
| CASP2 | orthology | Dog |
| CASP2 | orthology | Fugu |
| CASP2 | orthology | Gasterosteus |
| CASP2 | orthology | Gorilla |
| CASP2 | orthology | Horse |
| CASP2 | orthology | Human |
| CASP2 | orthology | Lyzard |
| Q8SPP8_MACMU | orthology | Macaca |
| CASP2 | orthology | Medaka |
| CASP2 | orthology | Monodelphis |
| Casp2 | orthology | Mouse |
| CASP2 | orthology | Orangutan |
| CASP2 | orthology | Ornithorhynchus |
| CASP2 | orthology | Rabbit |
| Casp2 | orthology | Rat |
| CASP2 | orthology | Tetraodon |
| CASP2 | orthology | Xenopus |
| T_guttata_ENSTGUP00000013612 | orthology | Zebra finch |
| A_aegypti_AAEL014348-PA | paralogy | Aedes |
| CASPS7 | paralogy | Anopheles |
| CASPL2 | paralogy | Anopheles |
| CASPS6 | paralogy | Anopheles |
| CASPS8 | paralogy | Anopheles |
| CASPS4 | paralogy | Anopheles |
| Q90WU0_CHICK | paralogy | Chicken |
| CASP10 | paralogy | Chicken |
| NP_989923.1 | paralogy | Chicken |
| CASP7 | paralogy | Chicken |
| NP_990056.1 | paralogy | Chicken |
| NP_990057.1 | paralogy | Chicken |
| CASP8 | paralogy | Chimpanzee |
| XR_025516.1 | paralogy | Chimpanzee |
| CASP3_PANTR | paralogy | Chimpanzee |
| CASP9 | paralogy | Chimpanzee |
| CASP7 | paralogy | Chimpanzee |
| C_intestinalis_ENSCINP00000003204 | paralogy | Ciona |
| C_intestinalis_ENSCINP00000007986 | paralogy | Ciona |
| IPI00704513.4 | paralogy | Cow |
| IPI00689801.3 | paralogy | Cow |
| CASP3_BOVIN | paralogy | Cow |
| NP_001039435.1 | paralogy | Cow |
| CASP7 | paralogy | Dog |
| Q38JA9_CANFA | paralogy | Dog |
| CASP10 | paralogy | Dog |
| Q45T68_CANFA | paralogy | Dog |
| CASP3_CANFA | paralogy | Dog |
| Dcp-1 | paralogy | Fly |
| Ice | paralogy | Fly |
| CASP6 | paralogy | Fugu |
| T_rubripes_ENSTRUP00000024164 | paralogy | Fugu |
| T_rubripes_ENSTRUP00000024467 | paralogy | Fugu |
| CASP7 | paralogy | Fugu |
| NP_001027871.1 | paralogy | Fugu |
| T_rubripes_ENSTRUP00000044662 | paralogy | Fugu |
| CASP9 | paralogy | Fugu |
| G_aculeatus_ENSGACP00000016983 | paralogy | Gasterosteus |
| CASP3 (4 of 4) | paralogy | Gasterosteus |
| CASP3 (3 of 4) | paralogy | Gasterosteus |
| CASP3 (2 of 4) | paralogy | Gasterosteus |
| CASP3 (1 of 4) | paralogy | Gasterosteus |
| G_aculeatus_ENSGACP00000005791 | paralogy | Gasterosteus |
| CASP9 | paralogy | Gasterosteus |
| CASP7 | paralogy | Gasterosteus |
| CASP8 | paralogy | Gorilla |
| CASP9 | paralogy | Gorilla |
| CASP7 | paralogy | Gorilla |
| CASP8 | paralogy | Horse |
| CASP6 | paralogy | Horse |
| CASP7 | paralogy | Horse |
| CASP9 | paralogy | Horse |
| Q3S2Z5_HORSE | paralogy | Horse |
| CASP10 | paralogy | Horse |
| CASP10 | paralogy | Human |
| CASP3 | paralogy | Human |
| CASP8 | paralogy | Human |
| CASP7 | paralogy | Human |
| CASP9 | paralogy | Human |
| CASP10 | paralogy | Lyzard |
| CASP3 | paralogy | Lyzard |
| CASP7 | paralogy | Lyzard |
| CASP6 | paralogy | Lyzard |
| CASP9 | paralogy | Lyzard |
| CASP8 | paralogy | Macaca |
| CASP10 | paralogy | Macaca |
| CASP9 | paralogy | Macaca |
| CASP7 | paralogy | Macaca |
| Q8SPU2_MACMU | paralogy | Macaca |
| CASP9 | paralogy | Medaka |
| Q8JIS9_ORYLA | paralogy | Medaka |
| Q8JIS8_ORYLA | paralogy | Medaka |
| Q56VC9_ORYLA | paralogy | Medaka |
| CASP9 | paralogy | Monodelphis |
| NP_001033059.1 | paralogy | Monodelphis |
| NP_001033061.1 | paralogy | Monodelphis |
| M_domestica_ENSMODP00000034022 | paralogy | Monodelphis |
| M_domestica_ENSMODP00000034033 | paralogy | Monodelphis |
| CASP8 | paralogy | Monodelphis |
| CASP10 | paralogy | Monodelphis |
| Casp7 | paralogy | Mouse |
| Casp8 | paralogy | Mouse |
| Casp9 | paralogy | Mouse |
| Casp3 | paralogy | Mouse |
| CASP9 | paralogy | Orangutan |
| CASP7 | paralogy | Orangutan |
| Q5RB11_PONPY | paralogy | Orangutan |
| Q5RCR7_PONPY | paralogy | Orangutan |
| CASP3 | paralogy | Orangutan |
| CASP3 | paralogy | Ornithorhynchus |
| CASP7 | paralogy | Ornithorhynchus |
| CASP10 | paralogy | Ornithorhynchus |
| CASP8 | paralogy | Ornithorhynchus |
| CASP9 | paralogy | Ornithorhynchus |
| CASP10 | paralogy | Rabbit |
| CASP8 | paralogy | Rabbit |
| CASP7 | paralogy | Rabbit |
| CASP9 | paralogy | Rabbit |
| Casp3 | paralogy | Rat |
| Casp8 | paralogy | Rat |
| Casp9 | paralogy | Rat |
| Casp7 | paralogy | Rat |
| T_nigroviridis_ENSTNIP00000001216 | paralogy | Tetraodon |
| CASP3 | paralogy | Tetraodon |
| T_nigroviridis_ENSTNIP00000010722 | paralogy | Tetraodon |
| CASP9 | paralogy | Tetraodon |
| CASP7 | paralogy | Tetraodon |
| ced-3 | paralogy | Worm |
| X_tropicalis_ENSXETP00000017024 | paralogy | Xenopus |
| casp7 | paralogy | Xenopus |
| CASP3 | paralogy | Xenopus |
| casp10 | paralogy | Xenopus |
| T_guttata_ENSTGUP00000004278 | paralogy | Zebra finch |
| CASP3 | paralogy | Zebra finch |
| CASP8 | paralogy | Zebra finch |
| T_guttata_ENSTGUP00000011206 | paralogy | Zebra finch |
| CASP9 | paralogy | Zebra finch |
| casp3a | paralogy | Zebrafish |
| casp7 | paralogy | Zebrafish |
| casp8l2 | paralogy | Zebrafish |
| D_rerio_ENSDARP00000047019 | paralogy | Zebrafish |
| NP_001077331.1 | paralogy | Zebrafish |
| casp3b | paralogy | Zebrafish |
| A2BGE2_DANRE | paralogy | Zebrafish |
| casp8l1 | paralogy | Zebrafish |
| LOC795066 | paralogy | Zebrafish |
| casp8 | 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:0008630 | DNA damage response, signal transduction resulting in induction of apoptosis | biological_proccess | IGI |
| 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 |
| GO:0008233 | peptidase activity | mollecular_function | IEA |
| GO:0016787 | hydrolase activity | mollecular_function | IEA |
| GO:0005622 | intracellular | cell_component | IEA |
Check GO Evidence Codes here
Information from other databases [+]
- Gene info from ZFIN [?] ZDB-GENE-030825-3
- Ensembl genome browser [?] : ENSDARG00000062052
- Expression info from Arrayexpress [?] : ENSDARG00000062052
- Protein expression from Protein Atlas: [?] ENSDARG00000062052
- Community gene edition from Wikigenes: [?] 373118
- entrezgene: 373118
- refseq_dna: NM_001042695
- refseq_peptide: NP_001036160
Click on [?] for more information.
