CASP4 (Homo sapiens)
Description [+]
- Synonyms: CASP4, ICE(REL)II, ICH-2, TX
- Species: Metazoa;Bilateria;Deuterostoma;Chordata;Vertebrata;Mammalia;Primates;Hominidae; Homo sapiens
- Short gene description: Caspase-4 Precursor (CASP-4)(EC 3.4.22.57)(ICH-2 protease)(TX protease)(ICE(rel)-II) [Contains Caspase-4 subunit 1;Caspase-4 subunit 2] [Source:UniProtKB/Swiss-Prot;Acc:P49662]
- Family: CASPASE
- Process: immunity,
- Pathways:
- Criteria: manually curated
- Curator comment:
- Mouse ortholog(s): Casp4
- WIKI: CASP4-H_sapiens
References [+]
- 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.
- References from Mouse ortholog(s):
- 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.
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 | 136 | 373 |
Protein sequence [+]
CASP4 | Homo sapiens | 9606 | length:377
MAEGNHRKKPLKVLESLGKDFLTGVLDNLVEQNVLNWKEEEKKKYYDAKTEDKVRVMADS
MQEKQRMAGQMLLQTFFNIDQISPNKKAHPNMEAGPPESGESTDALKLCPHEEFLRLCKE
RAEEIYPIKERNNRTRLALIICNTEFDHLPPRNGADFDITGMKELLEGLDYSVDVEENLT
ARDMESALRAFATRPEHKSSDSTFLVLMSHGILEGICGTVHDEKKPDVLLYDTIFQIFNN
RNCLSLKDKPKVIIVQACRGANRGELWVRDSPASLEVASSQSSENLEEDAVYKTHVEKDF
IAFCSSTPHNVSWRDSTMGSIFITQLITCFQKYSWCCHLEEVFRKVQQSFETPRAKAQMP
TIERLSMTRYFYLFPGN
MQEKQRMAGQMLLQTFFNIDQISPNKKAHPNMEAGPPESGESTDALKLCPHEEFLRLCKE
RAEEIYPIKERNNRTRLALIICNTEFDHLPPRNGADFDITGMKELLEGLDYSVDVEENLT
ARDMESALRAFATRPEHKSSDSTFLVLMSHGILEGICGTVHDEKKPDVLLYDTIFQIFNN
RNCLSLKDKPKVIIVQACRGANRGELWVRDSPASLEVASSQSSENLEEDAVYKTHVEKDF
IAFCSSTPHNVSWRDSTMGSIFITQLITCFQKYSWCCHLEEVFRKVQQSFETPRAKAQMP
TIERLSMTRYFYLFPGN
Structure links:
- Smartdomain prediction information: SM00114
- Smartdomain prediction information: SM00115
- Prosite motif and domain information: PS01121
- Prosite motif and domain information: PS01122
- Profile motif and domain profile information: PS50209
- Profile motif and domain profile information: PS50207
- Profile motif and domain profile information: PS50208
- Interpro domain information: P49662
- PFAM domain and domain family information: P49662
Evolution [+]
View protein alignment and tree with Jalview:
Explore tree at phylomeDB: Click here.
Homologs list [+]
| Name | Relationship | Species |
|---|---|---|
| NP_990255.1 | orthology | Chicken |
| CASP4 | orthology | Chimpanzee |
| CASPD_BOVIN | orthology | Cow |
| CASP1_CANFA | orthology | Dog |
| T_rubripes_ENSTRUP00000013027 | orthology | Fugu |
| T_rubripes_ENSTRUP00000019853 | orthology | Fugu |
| T_rubripes_ENSTRUP00000035020 | orthology | Fugu |
| CASP12 | orthology | Gasterosteus |
| CASP4 | orthology | Horse |
| A_carolinensis_ENSACAP00000013361 | orthology | Lyzard |
| CASP4 | orthology | Macaca |
| CASP12 | orthology | Medaka |
| Casp4 | orthology | Mouse |
| CASP4 | orthology | Orangutan |
| CASP4 | orthology | Rabbit |
| Casp4 | orthology | Rat |
| X_tropicalis_ENSXETP00000017024 | orthology | Xenopus |
| caspa | orthology | Zebrafish |
| LOC566185 | orthology | Zebrafish |
| caspb | orthology | Zebrafish |
| A_aegypti_AAEL003444-PA | paralogy | Aedes |
| A_aegypti_AAEL014348-PA | paralogy | Aedes |
| CASPS4 | paralogy | Anopheles |
| CASPS7 | paralogy | Anopheles |
| CASPS6 | paralogy | Anopheles |
| CASPS8 | paralogy | Anopheles |
| Q90WU0_CHICK | paralogy | Chicken |
| CASP7 | paralogy | Chicken |
| NP_990056.1 | paralogy | Chicken |
| CASP2_CHICK | paralogy | Chicken |
| XR_019722.1 | paralogy | Chimpanzee |
| CASP2 | paralogy | Chimpanzee |
| CASP12 | paralogy | Chimpanzee |
| CASP3_PANTR | paralogy | Chimpanzee |
| CASP9 | paralogy | Chimpanzee |
| CASP1 | paralogy | Chimpanzee |
| C_intestinalis_ENSCINP00000002956 | paralogy | Ciona |
| C_intestinalis_ENSCINP00000024485 | paralogy | Ciona |
| IPI00704513.4 | paralogy | Cow |
| IPI00689801.3 | paralogy | Cow |
| NP_001029681.1 | paralogy | Cow |
| CASP3_BOVIN | paralogy | Cow |
| IPI00707783.1 | paralogy | Cow |
| A0PCH9_BOVIN | paralogy | Cow |
| IPI00688117.2 | paralogy | Cow |
| CASP2 | paralogy | Dog |
| CASP12 | paralogy | Dog |
| CASP14 | paralogy | Dog |
| Q45T68_CANFA | paralogy | Dog |
| CASP3_CANFA | paralogy | Dog |
| Dcp-1 | paralogy | Fly |
| Ice | paralogy | Fly |
| CASP7 | paralogy | Fugu |
| NP_001027871.1 | paralogy | Fugu |
| T_rubripes_ENSTRUP00000044662 | paralogy | Fugu |
| CASP9 | paralogy | Fugu |
| CASP9 | paralogy | Gasterosteus |
| CASP7 | paralogy | Gasterosteus |
| CASP2 | 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 |
| CASP12 | paralogy | Gorilla |
| CASP5 | paralogy | Gorilla |
| CASP2 | paralogy | Horse |
| CASP12 | paralogy | Horse |
| CASP14 | paralogy | Horse |
| CASP7 | paralogy | Horse |
| CASP9 | paralogy | Horse |
| Q3S2Z5_HORSE | paralogy | Horse |
| CASP1_HORSE | paralogy | Horse |
| Caspase-14 | paralogy | Human |
| CASP1 | paralogy | Human |
| CASP3 | paralogy | Human |
| CASP2 | paralogy | Human |
| CASP12 | paralogy | Human |
| CASP9 | paralogy | Human |
| CASP5 | paralogy | Human |
| CASP3 | paralogy | Lyzard |
| CASP2 | paralogy | Lyzard |
| CASP7 | paralogy | Lyzard |
| CASP14 | paralogy | Lyzard |
| CASP5 | paralogy | Macaca |
| CASP1 | paralogy | Macaca |
| Q8SPU2_MACMU | paralogy | Macaca |
| Q8SPP8_MACMU | paralogy | Macaca |
| CASP12 | paralogy | Macaca |
| CASP9 | paralogy | Macaca |
| Q8JIS9_ORYLA | paralogy | Medaka |
| Q8JIS8_ORYLA | paralogy | Medaka |
| CASP2 | paralogy | Medaka |
| CASP9 | paralogy | Medaka |
| CASP2 | paralogy | Monodelphis |
| CASP9 | paralogy | Monodelphis |
| NP_001033059.1 | paralogy | Monodelphis |
| NP_001033061.1 | paralogy | Monodelphis |
| CASP14 | paralogy | Monodelphis |
| M_domestica_ENSMODP00000034020 | paralogy | Monodelphis |
| M_domestica_ENSMODP00000034022 | paralogy | Monodelphis |
| M_domestica_ENSMODP00000034033 | paralogy | Monodelphis |
| CASP8 | paralogy | Monodelphis |
| Casp7 | paralogy | Mouse |
| Casp12 | paralogy | Mouse |
| Casp1 | paralogy | Mouse |
| Casp9 | paralogy | Mouse |
| Casp2 | paralogy | Mouse |
| Casp3 | paralogy | Mouse |
| CASP9 | paralogy | Orangutan |
| CASP12 | paralogy | Orangutan |
| CASP5 | paralogy | Orangutan |
| CASP1 | paralogy | Orangutan |
| CASP3 | paralogy | Orangutan |
| CASP2 | paralogy | Orangutan |
| CASP3 | paralogy | Ornithorhynchus |
| CASP2 | paralogy | Ornithorhynchus |
| CASP9 | paralogy | Ornithorhynchus |
| O_anatinus_ENSOANP00000016591 | paralogy | Ornithorhynchus |
| O_anatinus_ENSOANP00000019254 | paralogy | Ornithorhynchus |
| CASP1 | paralogy | Rabbit |
| CASP14 | paralogy | Rabbit |
| Casp1 | paralogy | Rat |
| Casp3 | paralogy | Rat |
| Casp9 | paralogy | Rat |
| Casp2 | paralogy | Rat |
| Casp12 | paralogy | Rat |
| CASP3 | paralogy | Tetraodon |
| CASP2 | paralogy | Tetraodon |
| CASP7 | paralogy | Tetraodon |
| ced-3 | paralogy | Worm |
| CASP3 | paralogy | Xenopus |
| CASP2 | paralogy | Xenopus |
| casp7 | paralogy | Xenopus |
| CASP3 | paralogy | Zebra finch |
| CASP8 | paralogy | Zebra finch |
| T_guttata_ENSTGUP00000011206 | paralogy | Zebra finch |
| T_guttata_ENSTGUP00000013612 | paralogy | Zebra finch |
| CASP9 | paralogy | Zebra finch |
| LOC795066 | paralogy | Zebrafish |
| casp2 | paralogy | Zebrafish |
| casp3a | paralogy | Zebrafish |
| LOC563034 | paralogy | Zebrafish |
| casp7 | paralogy | Zebrafish |
| D_rerio_ENSDARP00000047019 | paralogy | Zebrafish |
| NP_001077331.1 | paralogy | Zebrafish |
| casp3b | paralogy | Zebrafish |
| LOC100000522 | paralogy | Zebrafish |
| A2BGE2_DANRE | paralogy | Zebrafish |
| casp8l1 | paralogy | Zebrafish |
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Gene Ontology [+]
| GO id | Name | Ontology type | Evidence |
|---|---|---|---|
| GO:0042981 | regulation of apoptosis | biological_proccess | IEA |
| GO:0006917 | induction of apoptosis | biological_proccess | TAS |
| GO:0006508 | proteolysis | biological_proccess | TAS |
| GO:0006915 | apoptosis | biological_proccess | IEA |
| GO:0006508 | proteolysis | biological_proccess | IEA |
| GO:0005515 | protein binding | mollecular_function | IPI |
| GO:0004197 | cysteine-type endopeptidase activity | mollecular_function | IEA |
| GO:0008233 | peptidase activity | mollecular_function | IEA |
| GO:0008234 | cysteine-type peptidase activity | mollecular_function | IEA |
| GO:0005515 | protein binding | mollecular_function | IEA |
| GO:0005622 | intracellular | cell_component | IEA |
Check GO Evidence Codes here
Information from other databases [+]
- Gene info from HGNC [?] :1505
- Gene related info from GeneCards [?] : CASP4
- Ensembl genome browser [?] : ENSG00000196954
- Expression info from Arrayexpress [?] : ENSG00000196954
- Protein expression from Protein Atlas: [?] ENSG00000196954
- Community gene edition from Wikigenes: [?] 837
- OMIM gene information: 602664
- OMIM disease information:
Click on [?] for more information.
