Version 5.4
| Homo sapiens Gene: CASP1 | |||||||||||||||||||||||||||||||||||||||||||||||||
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| Summary | |||||||||||||||||||||||||||||||||||||||||||||||||
| InnateDB Gene | IDBG-69618.7 | ||||||||||||||||||||||||||||||||||||||||||||||||
| Last Modified | 2014-10-13 [Report errors or provide feedback] | ||||||||||||||||||||||||||||||||||||||||||||||||
| Gene Symbol | CASP1 | ||||||||||||||||||||||||||||||||||||||||||||||||
| Gene Name | caspase 1, apoptosis-related cysteine peptidase | ||||||||||||||||||||||||||||||||||||||||||||||||
| Synonyms | ICE; IL1BC; P45 | ||||||||||||||||||||||||||||||||||||||||||||||||
| Species | Homo sapiens | ||||||||||||||||||||||||||||||||||||||||||||||||
| Ensembl Gene | ENSG00000137752 | ||||||||||||||||||||||||||||||||||||||||||||||||
| Encoded Proteins |
caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase)
caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase)
caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase)
caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase)
caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase)
caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase)
caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase)
caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase)
caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase)
caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase)
caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase)
caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase)
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| Protein Structure | |||||||||||||||||||||||||||||||||||||||||||||||||
| Useful resources | Stemformatics EHFPI ImmGen | ||||||||||||||||||||||||||||||||||||||||||||||||
| InnateDB Annotation | |||||||||||||||||||||||||||||||||||||||||||||||||
| Summary |
CASP1 activates NF-kappaB independent of its enzymatic activity and contributes to inflammation by proteolysis of pro-IL1B (IL-1 beta) and RIPK2 activation of NF-kappaB and MAPK1.
CASP1 is part of the inflammasome complex, along with pathogen-specific nucleotide oligomerization and binding domain (NOD)-like receptors (NLRs) and in some cases the scaffolding protein ASC. Formation of the membrane-associated inflammasome complex in murine macrophages, results in cleavage of cytosolic CASP1 substrates and cell death.
CASP1 activity is required for discrimination between translocon-positive and -negative bacteria in bone-marrow derived cells and interleukin-1 receptor signalling. Activation of CASP1 by bacteria expressing Type 3 secretion systems allows for rapid recognition of bacteria expressing conserved functions associated with virulence.
CASP1 clears intracellular bacteria in vivo independently of IL1B (IL-1-beta) and IL18 and establishes pyroptosis as an efficient mechanism of bacterial clearance by the innate immune system. CASP1-induced pyroptotic cell death releases bacteria from macrophages and exposes the bacteria to uptake and killing by reactive oxygen species in neutrophils.
CASP1 is a component of the inflammasome and is required for inflammation in acute pancreatitis. (Demonstrated in murine model)
CASP1-dependent inflammatory cell death, or pyroptosis, is only induced by viable, but not heat-killed, E. coli. (Demonstrated in murine model)
Naturally occurring variants of CASP1 differ considerably in structure and the ability to activate IL1B.
The precursor and mature forms of IL37 are secreted from activated cells upon inflammasome activation and CASP1 processing of IL37 is important for its anti-inflammatory activity.
20-kDa IL1B generated from CASP1 cleaved pro-IL1B limits the available pro-IL1B for generation of CASP1 cleaved 17-kDa IL1B, thus reducing inflammation.
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| InnateDB Annotation from Orthologs | |||||||||||||||||||||||||||||||||||||||||||||||||
| Summary |
[Mus musculus] Casp1 is involved in key innate and healing responses to influenza A virus where Casp1(-/-) mice exhibited increased morbidity after infection with a pathogenic influenza A virus correlating with decreased neutrophil and monocyte recruitment and reduced Il1b (IL-1-beta), Il18 (IL-18), Tnf (TNF-alpha), Il6 (IL-6), Cxcl1 (KC), and Cxcl2 (MIP-2) production.
[Mus musculus] Casp1 is part of the inflammasome complex, along with pathogen-specific nucleotide oligomerization and binding domain (NOD)-like receptors (NLRs) and in some cases the scaffolding protein ASC. Formation of the membrane-associated inflammasome complex in murine macrophages, results in cleavage of cytosolic Casp1 substrates and cell death.
[Mus musculus] Casp1 is a component of the inflammasome and is required for inflammation in acute pancreatitis.
[Mus musculus] Casp1-dependent inflammatory cell death, or pyroptosis, is only induced by viable, but not heat-killed, E. coli.
[Mus musculus] Naturally occurring variants of Casp1 differ considerably in structure and the ability to activate Il1b.
(Demonstrated in human)
[Mus musculus] Activation of the Nlrp3 inflammasome is detrimental during leishmaniasis. Mice lacking the inflammasome components Nlrp3, Pycard, Casp1 exhibit defective Il1b and Il18 production at the infection site and are resistant to cutaneous Leishmania major infection.
[Mus musculus] Type 1 regulatory (Tr1) cells suppress Il1b transcription and Casp1 activation via an IL10R â??dependent mechanism
[Mus musculus] Uropathogenic Escherichia coli protein TcpC attenuates activation of the Nlrp3 inflammasome by binding both Nlrp3 and Casp1.
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| Entrez Gene | |||||||||||||||||||||||||||||||||||||||||||||||||
| Summary |
This gene encodes a protein which is a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes which undergo proteolytic processing at conserved aspartic residues to produce 2 subunits, large and small, that dimerize to form the active enzyme. This gene was identified by its ability to proteolytically cleave and activate the inactive precursor of interleukin-1, a cytokine involved in the processes such as inflammation, septic shock, and wound healing. This gene has been shown to induce cell apoptosis and may function in various developmental stages. Studies of a similar gene in mouse suggest a role in the pathogenesis of Huntington disease. Alternative splicing results in transcript variants encoding distinct isoforms. [provided by RefSeq, Mar 2012] |
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| Gene Information | |||||||||||||||||||||||||||||||||||||||||||||||||
| Type | Protein coding | ||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic Location | Chromosome 11:105025443-105035250 | ||||||||||||||||||||||||||||||||||||||||||||||||
| Strand | Reverse strand | ||||||||||||||||||||||||||||||||||||||||||||||||
| Band | q22.3 | ||||||||||||||||||||||||||||||||||||||||||||||||
| Transcripts | |||||||||||||||||||||||||||||||||||||||||||||||||
| Interactions | |||||||||||||||||||||||||||||||||||||||||||||||||
| Number of Interactions |
This gene and/or its encoded proteins are associated with 82 experimentally validated interaction(s) in this database.
They are also associated with 5 interaction(s) predicted by orthology.
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| Gene Ontology | |||||||||||||||||||||||||||||||||||||||||||||||||
Molecular Function |
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| Biological Process |
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| Cellular Component |
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| Orthologs | |||||||||||||||||||||||||||||||||||||||||||||||||
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Species
Mus musculus
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Gene ID
Gene Order
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| Pathways | |||||||||||||||||||||||||||||||||||||||||||||||||
| NETPATH |
AndrogenReceptor pathway
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| REACTOME |
NOD1/2 Signaling Pathway pathway
The AIM2 inflammasome pathway
The IPAF inflammasome pathway
The NLRP3 inflammasome pathway
Inflammasomes pathway
Interleukin-1 processing pathway
Cytokine Signaling in Immune system pathway
Innate Immune System pathway
Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways pathway
Immune System pathway
Signaling by Interleukins pathway
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| KEGG |
Amyotrophic lateral sclerosis (ALS) pathway
NOD-like receptor signaling pathway pathway
Cytosolic DNA-sensing pathway pathway
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| INOH | |||||||||||||||||||||||||||||||||||||||||||||||||
| PID NCI |
Cellular roles of Anthrax toxin
Direct p53 effectors
IFN-gamma pathway
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| Cross-References | |||||||||||||||||||||||||||||||||||||||||||||||||
| SwissProt | |||||||||||||||||||||||||||||||||||||||||||||||||
| TrEMBL | B4DVD8 | ||||||||||||||||||||||||||||||||||||||||||||||||
| UniProt Splice Variant | |||||||||||||||||||||||||||||||||||||||||||||||||
| Entrez Gene | 834 | ||||||||||||||||||||||||||||||||||||||||||||||||
| UniGene | Hs.2490 | ||||||||||||||||||||||||||||||||||||||||||||||||
| RefSeq | NM_001223 NM_001257118 NM_001257119 NM_033292 NM_033293 NM_033294 NM_033295 XM_006718924 | ||||||||||||||||||||||||||||||||||||||||||||||||
| HUGO | HGNC:1499 | ||||||||||||||||||||||||||||||||||||||||||||||||
| OMIM | 147678 | ||||||||||||||||||||||||||||||||||||||||||||||||
| CCDS | CCDS53704 CCDS8329 CCDS8330 CCDS8331 CCDS8332 | ||||||||||||||||||||||||||||||||||||||||||||||||
| HPRD | 00977 | ||||||||||||||||||||||||||||||||||||||||||||||||
| IMGT | |||||||||||||||||||||||||||||||||||||||||||||||||
| EMBL | AK301037 AP001153 | ||||||||||||||||||||||||||||||||||||||||||||||||
| GenPept | BAG62650 | ||||||||||||||||||||||||||||||||||||||||||||||||
| RNA Seq Atlas | 834 | ||||||||||||||||||||||||||||||||||||||||||||||||