CASP2 (Mus musculus)
Description [+]
- Synonyms: CASP2, CASPASE 2, CASPASE-2, ICH-1, NEDD2
- Species: Metazoa;Bilateria;Deuterostoma;Chordata;Vertebrata;Mammalia;Rodentia; Mus musculus
- Short gene description: caspase 2 Gene [Source:MGI (curated);Acc:Casp2-001]
- Family: CASPASE
- Process: apoptosis,
- Pathways:
- Criteria: manually curated
- Curator comment: The role of caspase-2 during apoptosis is still under debate
- Human ortholog(s): CASP2
- WIKI: CASP2-M_musculus
References [+]
- Induction of apoptosis by the mouse Nedd2 gene, which encodes a protein similar to the product of the Caenorhabditis elegans cell death gene ced-3 and the mammalian IL-1 beta-converting enzyme.
- Kumar S, Kinoshita M, Noda M, Copeland NG, Jenkins NA
- By subtraction cloning we previously identified a set of mouse genes (named Nedd1 through Nedd10) with developmentally down-regulated expression in brain. We now show that one such gene, Nedd2, encodes a protein similar to the mammalian interleukin-1 beta-converting enzyme (ICE) and the product of the Caenorhabditis elegans cell death gene ced-3 (CED-3). Both ICE and CED-3 are known to encode putative cysteine proteases and induce apoptosis when overexpressed in cultured cells. Overexpression of Nedd2 in cultured fibroblast and neuroblastoma cells also resulted in cell death by apoptosis, which was suppressed by the expression of the human bcl-2 gene, indicating that Nedd2 is functionally similar to the ced-3 gene in C. elegans. We also show that during embryonic development, Nedd2 is highly expressed in several types of mouse tissue undergoing high rates of programmed cell death such as central nervous system and kidney. Our data suggest that Nedd2 is an important component of the mammalian programmed cell death machinery. Genes Dev. 1994 Jul 15;8(14):1613-26.
- 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.
- 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 | 37 | 121 |
| PFAM A | Peptidase_C14 | 200 | 445 |
Protein sequence [+]
Casp2 | Mus musculus | 10090 | length:452
MAAPSGRSQSSLHRKGLMAADRRSRILAVCGMHPDHQETLKKNRVVLAKQLLLSELLEHL
LEKDIITLEMRELIQAKGGSFSQNVELLNLLPKRGPQAFDAFCEALRETRQGHLEDLLLT
TLSDIQHVLPPLSCDYDTSLPFSVCESCPPHKQLRLSTDATEHSLDNGDGPPCLLVKPCT
PEFYQAHYQLAYRLQSQPRGLALVLSNVHFTGEKDLEFRSGGDVDHTTLVTLFKLLGYNV
HVLHDQTAQEMQEKLQNFAQLPAHRVTDSCVVALLSHGVEGGIYGVDGKLLQLQEVFRLF
DNANCPSLQNKPKMFFIQACRGDETDRGVDQQDGKNHTQSPGCEESDAGKEELMKMRLPT
RSDMICGYACLKGNAAMRNTKRGSWYIEALTQVFSERACDMHVADMLVKVNALIKEREGY
APGTEFHRCKEMSEYCSTLCQQLYLFPGYPPT
LEKDIITLEMRELIQAKGGSFSQNVELLNLLPKRGPQAFDAFCEALRETRQGHLEDLLLT
TLSDIQHVLPPLSCDYDTSLPFSVCESCPPHKQLRLSTDATEHSLDNGDGPPCLLVKPCT
PEFYQAHYQLAYRLQSQPRGLALVLSNVHFTGEKDLEFRSGGDVDHTTLVTLFKLLGYNV
HVLHDQTAQEMQEKLQNFAQLPAHRVTDSCVVALLSHGVEGGIYGVDGKLLQLQEVFRLF
DNANCPSLQNKPKMFFIQACRGDETDRGVDQQDGKNHTQSPGCEESDAGKEELMKMRLPT
RSDMICGYACLKGNAAMRNTKRGSWYIEALTQVFSERACDMHVADMLVKVNALIKEREGY
APGTEFHRCKEMSEYCSTLCQQLYLFPGYPPT
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_ENSCINP00000007986 | 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 | Orangutan |
| CASP2 | orthology | Ornithorhynchus |
| CASP2 | orthology | Rabbit |
| Casp2 | orthology | Rat |
| CASP2 | orthology | Tetraodon |
| CASP2 | orthology | Xenopus |
| T_guttata_ENSTGUP00000013612 | orthology | Zebra finch |
| casp2 | orthology | Zebrafish |
| A_aegypti_AAEL011562-PA | paralogy | Aedes |
| CASPL2 | paralogy | Anopheles |
| CASPS7 | paralogy | Anopheles |
| CASPS4 | paralogy | Anopheles |
| CASPS8 | paralogy | Anopheles |
| CASP7 | paralogy | Chicken |
| Q90WU0_CHICK | paralogy | Chicken |
| CASP10 | paralogy | Chicken |
| NP_990056.1 | paralogy | Chicken |
| NP_989923.1 | paralogy | Chicken |
| CASP7 | paralogy | Chimpanzee |
| CASP1 | paralogy | Chimpanzee |
| CASP3_PANTR | paralogy | Chimpanzee |
| XR_025516.1 | paralogy | Chimpanzee |
| CASP9 | paralogy | Chimpanzee |
| CASP8 | paralogy | Chimpanzee |
| C_intestinalis_ENSCINP00000003204 | paralogy | Ciona |
| C_intestinalis_ENSCINP00000002956 | paralogy | Ciona |
| C_intestinalis_ENSCINP00000000842 | paralogy | Ciona |
| IPI00704513.4 | paralogy | Cow |
| IPI00689801.3 | paralogy | Cow |
| A0PCH9_BOVIN | paralogy | Cow |
| NP_001039435.1 | paralogy | Cow |
| CASP3_BOVIN | paralogy | Cow |
| CASP3_CANFA | paralogy | Dog |
| CASP6 | paralogy | Dog |
| Q45T68_CANFA | paralogy | Dog |
| Q38JA9_CANFA | paralogy | Dog |
| CASP7 | paralogy | Dog |
| CASP10 | paralogy | Dog |
| CASP14 | paralogy | Dog |
| Dcp-1 | paralogy | Fly |
| Ice | paralogy | Fly |
| CASP7 | paralogy | Fugu |
| NP_001027871.1 | paralogy | Fugu |
| T_rubripes_ENSTRUP00000044662 | paralogy | Fugu |
| T_rubripes_ENSTRUP00000024467 | paralogy | Fugu |
| CASP9 | paralogy | Fugu |
| T_rubripes_ENSTRUP00000024164 | paralogy | Fugu |
| CASP3 (4 of 4) | paralogy | Gasterosteus |
| G_aculeatus_ENSGACP00000005791 | paralogy | Gasterosteus |
| CASP9 | paralogy | Gasterosteus |
| CASP3 (3 of 4) | paralogy | Gasterosteus |
| CASP7 | paralogy | Gasterosteus |
| CASP3 (2 of 4) | paralogy | Gasterosteus |
| CASP3 (1 of 4) | paralogy | Gasterosteus |
| CASP8 | paralogy | Gorilla |
| CASP9 | paralogy | Gorilla |
| CASP7 | paralogy | Gorilla |
| CASP8 | paralogy | Horse |
| CASP10 | paralogy | Horse |
| CASP6 | paralogy | Horse |
| Q3S2Z5_HORSE | paralogy | Horse |
| CASP7 | paralogy | Horse |
| CASP1_HORSE | paralogy | Horse |
| CASP9 | paralogy | Horse |
| CASP6 | paralogy | Human |
| CASP7 | paralogy | Human |
| CASP3 | paralogy | Human |
| CASP9 | paralogy | Human |
| CASP1 | paralogy | Human |
| CASP10 | paralogy | Human |
| CASP8 | paralogy | Human |
| CASP3 | paralogy | Lyzard |
| CASP6 | paralogy | Lyzard |
| CASP7 | paralogy | Lyzard |
| CASP10 | paralogy | Lyzard |
| CASP9 | paralogy | Lyzard |
| CASP10 | paralogy | Macaca |
| CASP8 | paralogy | Macaca |
| Q8SPU2_MACMU | paralogy | Macaca |
| CASP7 | paralogy | Macaca |
| CASP9 | paralogy | Macaca |
| Q8JIS9_ORYLA | paralogy | Medaka |
| CASP9 | paralogy | Medaka |
| Q8JIS8_ORYLA | paralogy | Medaka |
| CASP8 | paralogy | Monodelphis |
| M_domestica_ENSMODP00000034022 | paralogy | Monodelphis |
| NP_001033061.1 | paralogy | Monodelphis |
| CASP9 | paralogy | Monodelphis |
| NP_001033059.1 | paralogy | Monodelphis |
| M_domestica_ENSMODP00000034033 | paralogy | Monodelphis |
| Casp7 | paralogy | Mouse |
| Casp8 | paralogy | Mouse |
| Casp9 | paralogy | Mouse |
| Casp3 | paralogy | Mouse |
| Casp4 | paralogy | Mouse |
| CASP1 | paralogy | Orangutan |
| CASP9 | paralogy | Orangutan |
| Q5RCR7_PONPY | paralogy | Orangutan |
| Q5RB11_PONPY | paralogy | Orangutan |
| CASP3 | paralogy | Orangutan |
| CASP7 | paralogy | Orangutan |
| CASP10 | paralogy | Ornithorhynchus |
| CASP7 | paralogy | Ornithorhynchus |
| CASP9 | paralogy | Ornithorhynchus |
| CASP8 | paralogy | Ornithorhynchus |
| O_anatinus_ENSOANP00000019254 | paralogy | Ornithorhynchus |
| CASP3 | paralogy | Ornithorhynchus |
| CASP7 | paralogy | Rabbit |
| CASP8 | paralogy | Rabbit |
| Casp9 | paralogy | Rat |
| Casp3 | paralogy | Rat |
| Casp1 | paralogy | Rat |
| Casp8 | paralogy | Rat |
| Casp7 | paralogy | Rat |
| CASP7 | paralogy | Tetraodon |
| CASP9 | paralogy | Tetraodon |
| CASP3 | paralogy | Tetraodon |
| T_nigroviridis_ENSTNIP00000001216 | paralogy | Tetraodon |
| ced-3 | paralogy | Worm |
| casp6 | paralogy | Xenopus |
| CASP3 | paralogy | Xenopus |
| casp7 | paralogy | Xenopus |
| CASP3 | paralogy | Zebra finch |
| T_guttata_ENSTGUP00000011206 | paralogy | Zebra finch |
| T_guttata_ENSTGUP00000004278 | paralogy | Zebra finch |
| CASP8 | paralogy | Zebra finch |
| CASP9 | paralogy | Zebra finch |
| D_rerio_ENSDARP00000047019 | paralogy | Zebrafish |
| A2BGE2_DANRE | paralogy | Zebrafish |
| casp3b | paralogy | Zebrafish |
| casp3a | paralogy | Zebrafish |
| casp7 | paralogy | Zebrafish |
| casp8l2 | paralogy | Zebrafish |
| NP_001077331.1 | paralogy | Zebrafish |
| LOC100000522 | paralogy | Zebrafish |
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Gene Ontology [+]
| GO id | Name | Ontology type | Evidence |
|---|---|---|---|
| GO:0006508 | proteolysis | biological_proccess | RCA |
| GO:0006917 | induction of apoptosis | biological_proccess | RCA |
| GO:0042981 | regulation of apoptosis | biological_proccess | IEA |
| GO:0006915 | apoptosis | biological_proccess | IMP |
| GO:0043066 | negative regulation of apoptosis | biological_proccess | ISA |
| GO:0043065 | positive regulation of apoptosis | biological_proccess | IMP |
| GO:0051605 | protein maturation via proteolysis | biological_proccess | IEA |
| GO:0004197 | cysteine-type endopeptidase activity | mollecular_function | IEA |
| GO:0005515 | protein binding | mollecular_function | IPI |
| GO:0008233 | peptidase activity | mollecular_function | RCA |
| GO:0016787 | hydrolase activity | mollecular_function | IEA |
| GO:0008234 | cysteine-type peptidase activity | mollecular_function | IEA |
| GO:0042802 | identical protein binding | mollecular_function | IEA |
| GO:0019904 | protein domain specific binding | mollecular_function | IEA |
| GO:0005622 | intracellular | cell_component | IEA |
| GO:0005634 | nucleus | cell_component | IDA |
| GO:0005737 | cytoplasm | cell_component | IDA |
Check GO Evidence Codes here
Curated Isoforms [+]
Info from The Vertebrate Genome Annotation (VEGA) database.
(*) Canonical transcript and translation forms.
Information from other databases [+]
- Gene info from MGI [?] MGI:97295
- Ensembl genome browser [?] : ENSMUSG00000029863
- Expression info from Arrayexpress [?] : ENSMUSG00000029863
- Protein expression from Protein Atlas: [?] ENSMUSG00000029863
- Community gene edition from Wikigenes: [?] 12366
Click on [?] for more information.
