CASP1 (Homo sapiens)
Description [+]
- Synonyms: CASP1, ICE, CASPASE-1, CASPASE 1, CASP1
- Species: Metazoa;Bilateria;Deuterostoma;Chordata;Vertebrata;Mammalia;Primates;Hominidae; Homo sapiens
- Short gene description: Caspase-1 Precursor (CASP-1)(EC 3.4.22.36)(Interleukin-1 beta convertase)(IL-1BC)(Interleukin-1 beta-converting enzyme)(IL-1 beta-converting enzyme)(ICE)(p45) [Contains Caspase-1 subunit p20;Caspase-1 subunit p10] [Source:UniProtKB/Swiss-Prot;Acc:P29466]
- Family: Caspase
- Process: immunity,
- Pathways: inflammasome,
- Criteria: manually curated
- Curator comment: Caspase-1 is instrumental in processing the precursor forms of interleukin-1beta and interleukin-18 to their biologically active forms. Although quite a few other substrates for caspase-1 have been claimed, these have invariably been found using non-physiological concentrations of caspase-1 (i.e. at concentrations in excess of 200 nanoMolar, sometimes ridiculously so) and are therefore unlikely to be genuine substrates. So, to date, there are two natural substrates for caspase-1 known (IL-1beta and IL-18).
- Mouse ortholog(s): Casp1
- WIKI: CASP1-H_sapiens
References [+]
- Molecular cloning of the interleukin-1 beta converting enzyme.
- Cerretti DP, Kozlosky CJ, Mosley B, Nelson N, Van Ness K, Greenstreet TA, March CJ, Kronheim SR, Druck T, Cannizzaro LA, et al.
- Interleukin-1 beta (IL-1 beta) mediates a wide range of immune and inflammatory responses. The active cytokine is generated by proteolytic cleavage of an inactive precursor. A complementary DNA encoding a protease that carries out this cleavage has been cloned. Recombinant expression in COS-7 cells enabled the cells to process precursor IL-1 beta to the mature form. Sequence analysis indicated that the enzyme itself may undergo proteolytic processing. The gene encoding the protease was mapped to chromosomal band 11q23, a site frequently involved in rearrangement in human cancers. Science. 1992 Apr 3;256(5053):97-100.
- The PYRIN-CARD protein ASC is an activating adaptor for caspase-1.
- Srinivasula SM, Poyet JL, Razmara M, Datta P, Zhang Z, Alnemri ES
- The PYRIN and CARD domains are members of the six-helix bundle death domain-fold superfamily that mediates assembly of large signaling complexes in the apoptotic and inflammatory signaling pathways. Here we show that the PYRIN-CARD protein ASC functions as a caspase-1-activating adaptor. ASC interacted specifically with procaspase-1 via CARD-CARD interactions and induced its oligomerization. Consistent with these results ectopic expression of full-length ASC, but not its isolated CARD or PYRIN domain, with procaspase-1 induced activation of procaspase-1 and processing of pro-interleukin-1beta in transfected cells. Substitution of the PYRIN domain of ASC with an inducible FKBP12 oligomerization domain produced a molecule that can induce caspase-1 activation in response to stimulation with the oligomerization drug AP20187, suggesting that the PYRIN domain functions as an oligomerization domain, whereas the CARD domain functions as the effector domain in the caspase-1 activation pathway. Furthermore stable expression of an isolated CARD of ASC in THP-1 cells diminished interleukin-1beta generation in response to pro-inflammatory cytokines. These results indicate that ASC is involved in the caspase-1 signaling pathway by mediating the assembly of a caspase-1-inflammasome signaling complex in response to pro-inflammatory cytokine stimulation. J Biol Chem. 2002 Jun 14;277(24):21119-22. Epub 2002 Apr 19.
- References from Mouse ortholog(s):
- Characterization of mice deficient in interleukin-1 beta converting enzyme.
- Li P, Allen H, Banerjee S, Seshadri T
- Interleukin-1 beta converting enzyme (ICE) processes the inactive prolL-1 beta to the proinflammatory mature IL-1 beta. ICE belongs to a family of cysteine proteases that have been implicated in apoptosis. To address the biological functions of ICE, we generated ICE-deficient mice through gene targeting technology. ICE-deficient mice developed normally, appeared healthy, and were fertile. Peritoneal macrophages from ICE-deficient mice underwent apoptosis normally upon ATP treatment. Thymocytes from young ICE-deficient mice also underwent apoptosis when triggered by dexamethasone, gamma irradiation, or aging. ICE-deficient mice had a major defect in the production of mature IL-1 beta and had impaired IL-1 alpha production on LPS stimulation in vitro and in vivo. ICE-deficient mice were resistant to LPS-induced endotoxic shock. J Cell Biochem. 1997 Jan;64(1):27-32.
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 | 163 | 400 |
Protein sequence [+]
CASP1 | Homo sapiens | 9606 | length:404
MADKVLKEKRKLFIRSMGEGTINGLLDELLQTRVLNKEEMEKVKRENATVMDKTRALIDS
VIPKGAQACQICITYICEEDSYLAGTLGLSADQTSGNYLNMQDSQGVLSSFPAPQAVQDN
PAMPTSSGSEGNVKLCSLEEAQRIWKQKSAEIYPIMDKSSRTRLALIICNEEFDSIPRRT
GAEVDITGMTMLLQNLGYSVDVKKNLTASDMTTELEAFAHRPEHKTSDSTFLVFMSHGIR
EGICGKKHSEQVPDILQLNAIFNMLNTKNCPSLKDKPKVIIIQACRGDSPGVVWFKDSVG
VSGNLSLPTTEEFEDDAIKKAHIEKDFIAFCSSTPDNVSWRHPTMGSVFIGRLIEHMQEY
ACSCDVEEIFRKVRFSFEQPDGRAQMPTTERVTLTRCFYLFPGH
VIPKGAQACQICITYICEEDSYLAGTLGLSADQTSGNYLNMQDSQGVLSSFPAPQAVQDN
PAMPTSSGSEGNVKLCSLEEAQRIWKQKSAEIYPIMDKSSRTRLALIICNEEFDSIPRRT
GAEVDITGMTMLLQNLGYSVDVKKNLTASDMTTELEAFAHRPEHKTSDSTFLVFMSHGIR
EGICGKKHSEQVPDILQLNAIFNMLNTKNCPSLKDKPKVIIIQACRGDSPGVVWFKDSVG
VSGNLSLPTTEEFEDDAIKKAHIEKDFIAFCSSTPDNVSWRHPTMGSVFIGRLIEHMQEY
ACSCDVEEIFRKVRFSFEQPDGRAQMPTTERVTLTRCFYLFPGH
Structure links:
- Smartdomain prediction information: SM00114
- Smartdomain prediction information: SM00115
- Prosite motif and domain information: PS00455
- 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: P29466
- PFAM domain and domain family information: P29466
- Protein 3D structures from PDB: 1BMQ
Evolution [+]
View protein alignment and tree with Jalview:
Explore tree at phylomeDB: Click here.
Homologs list [+]
| Name | Relationship | Species |
|---|---|---|
| NP_990255.1 | orthology | Chicken |
| CASP1 | orthology | Chimpanzee |
| A0PCH9_BOVIN | orthology | Cow |
| T_rubripes_ENSTRUP00000013027 | orthology | Fugu |
| T_rubripes_ENSTRUP00000035020 | orthology | Fugu |
| T_rubripes_ENSTRUP00000019853 | orthology | Fugu |
| CASP12 | orthology | Gasterosteus |
| CASP1_HORSE | orthology | Horse |
| A_carolinensis_ENSACAP00000013361 | orthology | Lyzard |
| CASP1 | orthology | Macaca |
| CASP12 | orthology | Medaka |
| M_domestica_ENSMODP00000034033 | orthology | Monodelphis |
| M_domestica_ENSMODP00000034022 | orthology | Monodelphis |
| Casp1 | orthology | Mouse |
| CASP1 | orthology | Orangutan |
| O_anatinus_ENSOANP00000016591 | orthology | Ornithorhynchus |
| CASP1 | orthology | Rabbit |
| Casp1 | orthology | Rat |
| X_tropicalis_ENSXETP00000017024 | orthology | Xenopus |
| LOC566185 | orthology | Zebrafish |
| caspb | orthology | Zebrafish |
| caspa | orthology | Zebrafish |
| A_aegypti_AAEL003444-PA | paralogy | Aedes |
| CASPS3 | paralogy | Anopheles |
| CASPS8 | paralogy | Anopheles |
| CASPS6 | paralogy | Anopheles |
| CASPS7 | paralogy | Anopheles |
| CASPS4 | paralogy | Anopheles |
| CASP2_CHICK | paralogy | Chicken |
| NP_990057.1 | paralogy | Chicken |
| NP_989923.1 | paralogy | Chicken |
| Q90WU0_CHICK | paralogy | Chicken |
| CASP2 | paralogy | Chimpanzee |
| CARD16 | paralogy | Chimpanzee |
| CASP12 | paralogy | Chimpanzee |
| XR_019722.1 | paralogy | Chimpanzee |
| CASP4 | paralogy | Chimpanzee |
| CASP3_PANTR | paralogy | Chimpanzee |
| CASP9 | paralogy | Chimpanzee |
| XR_025516.1 | paralogy | Chimpanzee |
| C_intestinalis_ENSCINP00000003204 | paralogy | Ciona |
| C_intestinalis_ENSCINP00000002956 | paralogy | Ciona |
| C_intestinalis_ENSCINP00000007986 | paralogy | Ciona |
| IPI00704513.4 | paralogy | Cow |
| IPI00707783.1 | paralogy | Cow |
| CASPD_BOVIN | paralogy | Cow |
| IPI00688117.2 | paralogy | Cow |
| NP_001039435.1 | paralogy | Cow |
| CASP3_BOVIN | paralogy | Cow |
| CASP1_CANFA | paralogy | Dog |
| CASP14 | paralogy | Dog |
| CASP3_CANFA | paralogy | Dog |
| CASP12 | paralogy | Dog |
| CASP2 | paralogy | Dog |
| Q45T68_CANFA | paralogy | Dog |
| CASP10 | paralogy | Dog |
| Dcp-1 | paralogy | Fly |
| Ice | paralogy | Fly |
| NP_001027871.1 | paralogy | Fugu |
| T_rubripes_ENSTRUP00000044662 | paralogy | Fugu |
| CASP7 | paralogy | Gasterosteus |
| CASP2 | paralogy | Gasterosteus |
| CASP3 (4 of 4) | paralogy | Gasterosteus |
| CASP3 (2 of 4) | paralogy | Gasterosteus |
| CASP12 | paralogy | Gorilla |
| CASP5 | paralogy | Gorilla |
| CASP14 | paralogy | Horse |
| CASP2 | paralogy | Horse |
| CASP8 | paralogy | Horse |
| CASP10 | paralogy | Horse |
| CASP12 | paralogy | Horse |
| Q3S2Z5_HORSE | paralogy | Horse |
| CASP7 | paralogy | Horse |
| CASP4 | paralogy | Horse |
| CASP9 | paralogy | Horse |
| CASP3 | paralogy | Human |
| CASP2 | paralogy | Human |
| CASP4 | paralogy | Human |
| CASP9 | paralogy | Human |
| Caspase-14 | paralogy | Human |
| CASP12 | paralogy | Human |
| CASP5 | paralogy | Human |
| CASP10 | paralogy | Human |
| CARD16 | paralogy | Human |
| CASP6 | paralogy | Lyzard |
| CASP2 | paralogy | Lyzard |
| Q8SPP8_MACMU | paralogy | Macaca |
| Q8SPU2_MACMU | paralogy | Macaca |
| CASP12 | paralogy | Macaca |
| CASP14 | paralogy | Macaca |
| CASP4 | paralogy | Macaca |
| CASP5 | paralogy | Macaca |
| CASP9 | paralogy | Macaca |
| CASP10 | paralogy | Macaca |
| Q8JIS9_ORYLA | paralogy | Medaka |
| CASP9 | paralogy | Medaka |
| NP_001033061.1 | paralogy | Monodelphis |
| CASP9 | paralogy | Monodelphis |
| M_domestica_ENSMODP00000034020 | paralogy | Monodelphis |
| CASP2 | paralogy | Monodelphis |
| NP_001033059.1 | paralogy | Monodelphis |
| CASP6 | paralogy | Monodelphis |
| CASP14 | paralogy | Monodelphis |
| Casp9 | paralogy | Mouse |
| Casp7 | paralogy | Mouse |
| Casp4 | paralogy | Mouse |
| Casp2 | paralogy | Mouse |
| Casp3 | paralogy | Mouse |
| Casp12 | paralogy | Mouse |
| Caspase-14 | paralogy | Mouse |
| CASP2 | paralogy | Orangutan |
| CASP9 | paralogy | Orangutan |
| Q5RB11_PONPY | paralogy | Orangutan |
| CASP3 | paralogy | Orangutan |
| CASP4 | paralogy | Orangutan |
| CASP12 | paralogy | Orangutan |
| CASP5 | paralogy | Orangutan |
| CASP3 | paralogy | Ornithorhynchus |
| CASP9 | paralogy | Ornithorhynchus |
| O_anatinus_ENSOANP00000019254 | paralogy | Ornithorhynchus |
| CASP14 | paralogy | Rabbit |
| CASP4 | paralogy | Rabbit |
| Casp2 | paralogy | Rat |
| Casp14_predicted | paralogy | Rat |
| Casp9 | paralogy | Rat |
| Casp4 | paralogy | Rat |
| Casp12 | paralogy | Rat |
| CASP7 | paralogy | Tetraodon |
| CASP9 | paralogy | Tetraodon |
| CASP2 | paralogy | Tetraodon |
| CASP3 | paralogy | Tetraodon |
| ced-3 | paralogy | Worm |
| CASP2 | paralogy | Xenopus |
| casp7 | paralogy | Xenopus |
| T_guttata_ENSTGUP00000011206 | paralogy | Zebra finch |
| CASP3 | paralogy | Zebra finch |
| T_guttata_ENSTGUP00000013612 | paralogy | Zebra finch |
| T_guttata_ENSTGUP00000004278 | paralogy | Zebra finch |
| CASP8 | paralogy | Zebra finch |
| CASP9 | paralogy | Zebra finch |
| D_rerio_ENSDARP00000047019 | paralogy | Zebrafish |
| casp2 | paralogy | Zebrafish |
| A2BGE2_DANRE | paralogy | Zebrafish |
| casp3b | paralogy | Zebrafish |
| casp3a | paralogy | Zebrafish |
| casp7 | paralogy | Zebrafish |
| LOC563034 | paralogy | Zebrafish |
| NP_001077331.1 | paralogy | Zebrafish |
| LOC100000522 | paralogy | Zebrafish |
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Gene Ontology [+]
| GO id | Name | Ontology type | Evidence |
|---|---|---|---|
| GO:0042981 | regulation of apoptosis | biological_proccess | IEA |
| GO:0007165 | signal transduction | biological_proccess | TAS |
| GO:0043123 | positive regulation of I-kappaB kinase/NF-kappaB cascade | biological_proccess | IEP |
| GO:0006508 | proteolysis | biological_proccess | IDA |
| GO:0006915 | apoptosis | biological_proccess | IEA |
| GO:0006917 | induction of apoptosis | biological_proccess | IEA |
| GO:0050718 | positive regulation of interleukin-1 beta secretion | biological_proccess | IEA |
| GO:0008219 | cell death | biological_proccess | IEA |
| GO:0001666 | response to hypoxia | biological_proccess | IEA |
| GO:0016485 | protein processing | biological_proccess | IEA |
| GO:0042221 | response to chemical stimulus | biological_proccess | IEA |
| GO:0033198 | response to ATP | biological_proccess | IEA |
| GO:0050715 | positive regulation of cytokine secretion | biological_proccess | IEA |
| GO:0050717 | positive regulation of interleukin-1 alpha secretion | biological_proccess | IEA |
| GO:0006508 | proteolysis | biological_proccess | IEA |
| GO:0004197 | cysteine-type endopeptidase activity | mollecular_function | TAS |
| GO:0008656 | caspase activator activity | mollecular_function | TAS |
| GO:0008233 | peptidase activity | mollecular_function | IEA |
| GO:0005515 | protein binding | mollecular_function | IPI |
| GO:0008234 | cysteine-type peptidase activity | mollecular_function | IEA |
| GO:0005515 | protein binding | mollecular_function | IEA |
| GO:0004197 | cysteine-type endopeptidase activity | mollecular_function | IEA |
| GO:0004869 | cysteine-type endopeptidase inhibitor activity | mollecular_function | IEA |
| GO:0030414 | peptidase inhibitor activity | mollecular_function | IEA |
| GO:0005622 | intracellular | cell_component | IEA |
| GO:0005737 | cytoplasm | cell_component | IEA |
| GO:0005576 | extracellular region | cell_component | IEA |
Check GO Evidence Codes here
KEGG Pathways [+]
Curated Isoforms [+]
| Transcript | Translation |
|---|---|
| OTTHUMT00000109396 * | OTTHUMP00000045728 * |
Info from The Vertebrate Genome Annotation (VEGA) database.
(*) Canonical transcript and translation forms.
Information from other databases [+]
- Gene info from HGNC [?] :1499
- Gene related info from GeneCards [?] : CASP1
- Ensembl genome browser [?] : ENSG00000137752
- Expression info from Arrayexpress [?] : ENSG00000137752
- Protein expression from Protein Atlas: [?] ENSG00000137752
- Community gene edition from Wikigenes: [?] 834
- OMIM gene information: 147678
- OMIM disease information:
Click on [?] for more information.
