InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Gene: Casp1

Summary

InnateDB Gene

IDBG-131590.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

Casp1

Gene Name

caspase 1

Synonyms

ICE; Il1bc

Species

Mus musculus

Ensembl Gene

ENSMUSG00000025888

Encoded Proteins

IDBP-131592

caspase 1

Protein Structure

Useful resources

Stemformatics EHFPI ImmGen

InnateDB Annotation

Summary

PMID 19362023

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.

PMID 19124602

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.

PMID 21439959

Casp1 is a component of the inflammasome and is required for inflammation in acute pancreatitis.

PMID 21602824

Casp1-dependent inflammatory cell death, or pyroptosis, is only induced by viable, but not heat-killed, E. coli.

PMID 22833538

Naturally occurring variants of Casp1 differ considerably in structure and the ability to activate Il1b. (Demonstrated in human)

PMID 25689249

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.

PMID 26056255

Type 1 regulatory (Tr1) cells suppress Il1b transcription and Casp1 activation via an IL10R �??dependent mechanism

PMID 27214553

Uropathogenic Escherichia coli protein TcpC attenuates activation of the Nlrp3 inflammasome by binding both Nlrp3 and Casp1.

InnateDB Annotation from Orthologs

Summary

PMID 15039421

[Homo sapiens] 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.

PMID 19124602

[Homo sapiens] 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.

PMID 20823203

[Homo sapiens] 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.

PMID 21057511

[Homo sapiens] 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.

PMID 21439959

[Homo sapiens] CASP1 is a component of the inflammasome and is required for inflammation in acute pancreatitis. (Demonstrated in murine model)

PMID 21602824

[Homo sapiens] CASP1-dependent inflammatory cell death, or pyroptosis, is only induced by viable, but not heat-killed, E. coli. (Demonstrated in murine model)

PMID 22833538

[Homo sapiens] Naturally occurring variants of CASP1 differ considerably in structure and the ability to activate IL1B.

PMID 24481253

[Homo sapiens] 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.

PMID 26324708

[Homo sapiens] 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.

Entrez Gene

Summary

This gene does not have any Entrez summary - the following is the summary from its human ortholog ENSG00000137752:
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]

Gene Information

Type

Protein coding

Genomic Location

Chromosome 9:5298517-5307265

Strand

Forward strand

Band

Transcripts

ENSMUST00000027015

ENSMUSP00000027015

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 20 experimentally validated interaction(s) in this database.
They are also associated with 34 interaction(s) predicted by orthology.

Experimentally validated
Total	20 [view]
Protein-Protein	17 [view]
Protein-DNA	2 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	1 [view]
DNA-RNA	0

Predicted by orthology
Total	34 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004175	endopeptidase activity
GO:0004197	cysteine-type endopeptidase activity
GO:0005515	protein binding
GO:0008233	peptidase activity
GO:0008234	cysteine-type peptidase activity

Biological Process

GO:0001666	response to hypoxia
GO:0006508	proteolysis
GO:0006915	apoptotic process
GO:0016485	protein processing
GO:0032496	response to lipopolysaccharide
GO:0032611	interleukin-1 beta production
GO:0033198	response to ATP
GO:0042981	regulation of apoptotic process
GO:0043123	positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0045087	innate immune response (InnateDB)
GO:0050715	positive regulation of cytokine secretion
GO:0050717	positive regulation of interleukin-1 alpha secretion
GO:0050718	positive regulation of interleukin-1 beta secretion
GO:0050727	regulation of inflammatory response
GO:0051882	mitochondrial depolarization
GO:0060081	membrane hyperpolarization
GO:0070269	pyroptosis
GO:0071260	cellular response to mechanical stimulus
GO:0071310	cellular response to organic substance
GO:0097194	execution phase of apoptosis
GO:0097300	programmed necrotic cell death

Cellular Component

GO:0005576	extracellular region
GO:0005622	intracellular
GO:0005737	cytoplasm
GO:0005829	cytosol
GO:0072557	IPAF inflammasome complex
GO:0072558	NLRP1 inflammasome complex
GO:0072559	NLRP3 inflammasome complex
GO:0097169	AIM2 inflammasome complex