CASP4 (Mus musculus)
Description [+]
- Synonyms: CASP4, CASPASE 4, CASP11, CASPASE-11, ICH-3
- Species: Metazoa;Bilateria;Deuterostoma;Chordata;Vertebrata;Mammalia;Rodentia; Mus musculus
- Short gene description: caspase 4, apoptosis-related cysteine peptidase Gene [Source:MGI Symbol;Acc:MGI:107700]
- Family: CASPASE
- Process: immunity,
- Pathways: inflammasome,
- Criteria: manually curated
- Curator comment:
- Human ortholog(s): CASP5 CASP4
- WIKI: CASP4-M_musculus
References [+]
- Murine caspase-11, an ICE-interacting protease, is essential for the activation of ICE.
- Wang S, Miura M, Jung YK, Zhu H, Li E, Yuan J
- We report here the inactivation of a member of the Ice/Ced-3 (caspase) family of cell death genes, casp-11, by gene targeting. Like Ice-deficient mice, casp-11 mutant mice are resistant to endotoxic shock induced by lipopolysaccharide. Production of both IL-1alpha and IL-1beta after lipopolysaccharide stimulation, a crucial event during septic shock and an indication of ICE activation, is blocked in casp-11 mutant mice. casp-11 mutant embryonic fibroblast cells are resistant to apoptosis induced by overexpression of ICE. Furthermore, we found that pro-caspase-11 physically interacts with pro-ICE in cells, and the expression of casp-11 is essential for activation of ICE. Our data suggest that caspase-11 is a component of ICE complex and is required for the activation of ICE. Cell. 1998 Feb 20;92(4):501-9.
- References from Human ortholog(s):
- A novel human protease similar to the interleukin-1 beta converting enzyme induces apoptosis in transfected cells.
- Faucheu C, Diu A, Chan AW, Blanchet AM, Miossec C, Herve F, Collard-Dutilleul V, Gu Y, Aldape RA, Lippke JA, et al.
- We have identified a novel cDNA encoding a protein (named TX) with > 50% overall sequence identity with the interleukin-1 beta converting enzyme (ICE) and approximately 30% sequence identity with the ICE homologs NEDD-2/ICH-1L and CED-3. A computer homology model of TX was constructed based on the X-ray coordinates of the ICE crystal recently published. This model suggests that TX is a cysteine protease, with the P1 aspartic acid substrate specificity retained. Transfection experiments demonstrate that TX is a protease which is able to cleave itself and the p30 ICE precursor, but not to generate mature IL-1 beta from pro-IL-1 beta. In addition, this protein induces apoptosis in transfected COS cells. TX therefore delineates a new member of the growing Ice/ced-3 gene family coding for proteases with cytokine processing activity or involved in programmed cell death. EMBO J. 1995 May 1;14(9):1914-22.
- Involvement of caspase-4 in endoplasmic reticulum stress-induced apoptosis and Abeta-induced cell death.
- Hitomi J, Katayama T, Eguchi Y, Kudo T, Taniguchi M, Koyama Y, Manabe T, Yamagishi S, Bando Y, Imaizumi K, Tsujimoto Y, Tohyama M
- Recent studies have suggested that neuronal death in Alzheimer's disease or ischemia could arise from dysfunction of the endoplasmic reticulum (ER). Although caspase-12 has been implicated in ER stress-induced apoptosis and amyloid-beta (Abeta)-induced apoptosis in rodents, it is controversial whether similar mechanisms operate in humans. We found that human caspase-4, a member of caspase-1 subfamily that includes caspase-12, is localized to the ER membrane, and is cleaved when cells are treated with ER stress-inducing reagents, but not with other apoptotic reagents. Cleavage of caspase-4 is not affected by overexpression of Bcl-2, which prevents signal transduction on the mitochondria, suggesting that caspase-4 is primarily activated in ER stress-induced apoptosis. Furthermore, a reduction of caspase-4 expression by small interfering RNA decreases ER stress-induced apoptosis in some cell lines, but not other ER stress-independent apoptosis. Caspase-4 is also cleaved by administration of Abeta, and Abeta-induced apoptosis is reduced by small interfering RNAs to caspase-4. Thus, caspase-4 can function as an ER stress-specific caspase in humans, and may be involved in pathogenesis of Alzheimer's disease. J Cell Biol. 2004 May 10;165(3):347-56. Epub 2004 May 3.
- Inflammatory caspases: linking an intracellular innate immune system to autoinflammatory diseases.
- Martinon F, Tschopp J
- Caspases not only play an essential role during apoptotic cell death, but a subfamily of them-the inflammatory caspases-are associated with immune responses to microbial pathogens. Activation of inflammatory caspases, such as caspase-1 and caspase-5, occurs upon assembly of an intracellular complex, designated the inflammasome. This results in the cleavage and activation of the proinflammatory cytokines IL-1beta and IL-18. Mutations in one of the scaffold proteins of the inflammasome, NALP3/Cryopyrin, are associated with autoinflammatory disorders underscoring the importance of regulating inflammatory caspase activation. Cell. 2004 May 28;117(5):561-74.
- Identification of a cysteine protease closely related to interleukin-1 beta-converting enzyme.
- Faucheu C, Blanchet AM, Collard-Dutilleul V, Lalanne JL, Diu-Hercend A
- The present study describes the identification and molecular cloning of a new member of the interleukin-1 beta-converting enzyme (ICE) family denoted transcript Y (TY). TY is very closely related to both ICE (51% amino acid identity) and a protein named transcript X (TX) (75% amino acid identity) that we recently identified [Faucheu, C., Diu, A., Chan, A.W.E., Blanchet, A.-M., Miossec, C., Herve, F.,Collard-Dutilleul, V., Gu, Y., Aldape, R., Lippke, J., Rocher, C., Su, M.S.-S., Livingston, D.J., Hercend, T. & Lalanne, J.-L. (1995) EMBO J. 14, 1914-1922]. The amino acids that are implicated in both the ICE catalytic site and in the PI aspartate-binding pocket are conserved in TY. Within the ICE gene family, TY belongs to a subfamily of proteins closely related to the prototype ICE protein. Using transfection experiments into mammalian cells, we demonstrate that TY has protease activity on its own precursor and that this activity is dependent on the presence of a cysteine residue at position 245. However, despite the close similarity between TY and ICE active sites, TY fails to process the interleukin-1 beta precursor. In addition, as already observed for ICE and TX, TY is able to induce apoptosis when overexpressed in COS cells. TY therefore represents a new member of the growing family of apoptosis-inducing ICE-related cysteine proteases. Eur J Biochem. 1996 Feb 15;236(1):207-13.
Structure & Sequence [+]
Pfam domains:
(Pfam is a large collection of protein families.)
| Source | Domain Name | Start | End |
|---|---|---|---|
| PFAM A | CARD | 3 | 90 |
| PFAM A | Peptidase_C14 | 132 | 369 |
Protein sequence [+]
Casp4 | Mus musculus | 10090 | length:373
MAENKHPDKPLKVLEQLGKEVLTEYLEKLVQSNVLKLKEEDKQKFNNAERSDKRWVFVDA
MKKKHSKVGEMLLQTFFSVDPGSHHGEANLEMEEPEESLNTLKLCSPEEFTRLCREKTQE
IYPIKEANGRTRKALIICNTEFKHLSLRYGANFDIIGMKGLLEDLGYDVVVKEELTAEGM
ESEMKDFAALSEHQTSDSTFLVLMSHGTLHGICGTMHSEKTPDVLQYDTIYQIFNNCHCP
GLRDKPKVIIVQACRGGNSGEMWIRESSKPQLCRGVDLPRNMEADAVKLSHVEKDFIAFY
STTPHHLSYRDKTGGSYFITRLISCFRKHACSCHLFDIFLKVQQSFEKASIHSQMPTIDR
ATLTRYFYLFPGN
MKKKHSKVGEMLLQTFFSVDPGSHHGEANLEMEEPEESLNTLKLCSPEEFTRLCREKTQE
IYPIKEANGRTRKALIICNTEFKHLSLRYGANFDIIGMKGLLEDLGYDVVVKEELTAEGM
ESEMKDFAALSEHQTSDSTFLVLMSHGTLHGICGTMHSEKTPDVLQYDTIYQIFNNCHCP
GLRDKPKVIIVQACRGGNSGEMWIRESSKPQLCRGVDLPRNMEADAVKLSHVEKDFIAFY
STTPHHLSYRDKTGGSYFITRLISCFRKHACSCHLFDIFLKVQQSFEKASIHSQMPTIDR
ATLTRYFYLFPGN
Structure links:
Evolution [+]
View protein alignment and tree with Jalview:
Explore tree at phylomeDB: Click here.
Homologs list [+]
| Name | Relationship | Species |
|---|---|---|
| NP_990255.1 | orthology | Chicken |
| XR_019722.1 | orthology | Chimpanzee |
| CASP4 | orthology | Chimpanzee |
| CASPD_BOVIN | orthology | Cow |
| CASP1_CANFA | orthology | Dog |
| T_rubripes_ENSTRUP00000013027 | orthology | Fugu |
| T_rubripes_ENSTRUP00000035020 | orthology | Fugu |
| T_rubripes_ENSTRUP00000019853 | orthology | Fugu |
| CASP12 | orthology | Gasterosteus |
| CASP5 | orthology | Gorilla |
| CASP4 | orthology | Horse |
| CASP4 | orthology | Human |
| CASP5 | orthology | Human |
| A_carolinensis_ENSACAP00000013361 | orthology | Lyzard |
| CASP4 | orthology | Macaca |
| CASP5 | orthology | Macaca |
| CASP12 | orthology | Medaka |
| M_domestica_ENSMODP00000034020 | orthology | Monodelphis |
| CASP5 | orthology | Orangutan |
| CASP4 | orthology | Orangutan |
| CASP4 | orthology | Rabbit |
| Casp4 | orthology | Rat |
| X_tropicalis_ENSXETP00000017024 | orthology | Xenopus |
| LOC566185 | orthology | Zebrafish |
| caspb | orthology | Zebrafish |
| caspa | orthology | Zebrafish |
| A_aegypti_AAEL003444-PA | paralogy | Aedes |
| CASPS4 | paralogy | Anopheles |
| CASPS8 | paralogy | Anopheles |
| CASPS6 | paralogy | Anopheles |
| CASPS14 | paralogy | Anopheles |
| NP_990057.1 | paralogy | Chicken |
| NP_990056.1 | paralogy | Chicken |
| CASP2_CHICK | paralogy | Chicken |
| Q90WU0_CHICK | paralogy | Chicken |
| CASP7 | paralogy | Chicken |
| CASP1 | paralogy | Chimpanzee |
| CASP3_PANTR | paralogy | Chimpanzee |
| CASP9 | paralogy | Chimpanzee |
| CASP2 | paralogy | Chimpanzee |
| CASP12 | paralogy | Chimpanzee |
| C_intestinalis_ENSCINP00000003204 | paralogy | Ciona |
| C_intestinalis_ENSCINP00000002956 | paralogy | Ciona |
| C_intestinalis_ENSCINP00000024485 | paralogy | Ciona |
| C_intestinalis_ENSCINP00000007986 | paralogy | Ciona |
| A0PCH9_BOVIN | paralogy | Cow |
| IPI00688117.2 | paralogy | Cow |
| IPI00707783.1 | paralogy | Cow |
| IPI00689801.3 | paralogy | Cow |
| CASP3_BOVIN | paralogy | Cow |
| NP_001029681.1 | paralogy | Cow |
| IPI00704513.4 | paralogy | Cow |
| CASP14 | paralogy | Dog |
| CASP3_CANFA | paralogy | Dog |
| Q45T68_CANFA | paralogy | Dog |
| CASP2 | paralogy | Dog |
| CASP12 | paralogy | Dog |
| CASP7 | paralogy | Dog |
| Dcp-1 | paralogy | Fly |
| Ice | paralogy | Fly |
| T_rubripes_ENSTRUP00000044662 | paralogy | Fugu |
| CASP2 | paralogy | Fugu |
| CASP9 | paralogy | Fugu |
| NP_001027871.1 | paralogy | Fugu |
| CASP7 | paralogy | Fugu |
| CASP9 | paralogy | Gasterosteus |
| CASP3 (3 of 4) | paralogy | Gasterosteus |
| CASP7 | paralogy | Gasterosteus |
| CASP2 | paralogy | Gasterosteus |
| CASP3 (2 of 4) | paralogy | Gasterosteus |
| CASP3 (1 of 4) | paralogy | Gasterosteus |
| CASP12 | paralogy | Gorilla |
| CASP12 | paralogy | Horse |
| Q3S2Z5_HORSE | paralogy | Horse |
| CASP9 | paralogy | Horse |
| CASP1_HORSE | paralogy | Horse |
| CASP14 | paralogy | Horse |
| CASP2 | paralogy | Horse |
| CASP7 | paralogy | Horse |
| CASP3 | paralogy | Human |
| CASP2 | paralogy | Human |
| CASP9 | paralogy | Human |
| Caspase-14 | paralogy | Human |
| CASP1 | paralogy | Human |
| CASP12 | paralogy | Human |
| CASP7 | paralogy | Lyzard |
| CASP2 | paralogy | Lyzard |
| CASP14 | paralogy | Lyzard |
| Q8SPP8_MACMU | paralogy | Macaca |
| Q8SPU2_MACMU | paralogy | Macaca |
| CASP14 | paralogy | Macaca |
| CASP12 | paralogy | Macaca |
| CASP1 | paralogy | Macaca |
| CASP9 | paralogy | Macaca |
| CASP9 | paralogy | Medaka |
| CASP2 | paralogy | Medaka |
| Q8JIS9_ORYLA | paralogy | Medaka |
| NP_001035238.1 | paralogy | Monodelphis |
| M_domestica_ENSMODP00000034022 | paralogy | Monodelphis |
| NP_001033061.1 | paralogy | Monodelphis |
| CASP2 | paralogy | Monodelphis |
| M_domestica_ENSMODP00000034033 | paralogy | Monodelphis |
| CASP9 | paralogy | Monodelphis |
| NP_001033059.1 | paralogy | Monodelphis |
| CASP8 | paralogy | Monodelphis |
| CASP14 | paralogy | Monodelphis |
| Casp9 | paralogy | Mouse |
| Casp3 | paralogy | Mouse |
| Casp2 | paralogy | Mouse |
| Casp1 | paralogy | Mouse |
| Casp12 | paralogy | Mouse |
| CASP9 | paralogy | Orangutan |
| CASP2 | paralogy | Orangutan |
| CASP3 | paralogy | Orangutan |
| CASP12 | paralogy | Orangutan |
| CASP1 | paralogy | Orangutan |
| CASP9 | paralogy | Ornithorhynchus |
| O_anatinus_ENSOANP00000019254 | paralogy | Ornithorhynchus |
| CASP2 | paralogy | Ornithorhynchus |
| O_anatinus_ENSOANP00000016591 | paralogy | Ornithorhynchus |
| CASP3 | paralogy | Ornithorhynchus |
| CASP2 | paralogy | Rabbit |
| CASP14 | paralogy | Rabbit |
| CASP1 | paralogy | Rabbit |
| Casp9 | paralogy | Rat |
| Casp12 | paralogy | Rat |
| Casp3 | paralogy | Rat |
| Casp1 | paralogy | Rat |
| Casp2 | paralogy | Rat |
| CASP2 | paralogy | Tetraodon |
| CASP7 | paralogy | Tetraodon |
| T_nigroviridis_ENSTNIP00000001216 | paralogy | Tetraodon |
| ced-3 | paralogy | Worm |
| csp-1 | paralogy | Worm |
| casp6 | paralogy | Xenopus |
| CASP2 | paralogy | Xenopus |
| T_guttata_ENSTGUP00000013612 | paralogy | Zebra finch |
| CASP3 | paralogy | Zebra finch |
| T_guttata_ENSTGUP00000004278 | paralogy | Zebra finch |
| CASP9 | paralogy | Zebra finch |
| casp2 | paralogy | Zebrafish |
| A2BGE2_DANRE | paralogy | Zebrafish |
| casp7 | paralogy | Zebrafish |
| casp8l2 | paralogy | Zebrafish |
| LOC795066 | paralogy | Zebrafish |
| LOC563034 | paralogy | Zebrafish |
| NP_001077331.1 | paralogy | Zebrafish |
| LOC100000522 | paralogy | Zebrafish |
| D_rerio_ENSDARP00000047019 | 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:0043066 | negative regulation of apoptosis | biological_proccess | IGI |
| GO:0006915 | apoptosis | biological_proccess | IEA |
| GO:0042981 | regulation of apoptosis | biological_proccess | IEA |
| GO:0004197 | cysteine-type endopeptidase activity | mollecular_function | IEA |
| GO:0005515 | protein binding | mollecular_function | IEA |
| GO:0008233 | peptidase activity | mollecular_function | RCA |
| GO:0016787 | hydrolase activity | mollecular_function | IEA |
| GO:0008234 | cysteine-type peptidase activity | mollecular_function | IEA |
| GO:0005622 | intracellular | cell_component | IEA |
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:107700
- Ensembl genome browser [?] : ENSMUSG00000033538
- Expression info from Arrayexpress [?] : ENSMUSG00000033538
- Protein expression from Protein Atlas: [?] ENSMUSG00000033538
- Community gene edition from Wikigenes: [?] 100044206
Click on [?] for more information.
