InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Nlrc4

Summary

InnateDB Protein

IDBP-197892.7

Last Modified

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

Gene Symbol

Nlrc4

Protein Name

NLR family, CARD domain containing 4

Synonyms

Species

Mus musculus

Ensembl Protein

ENSMUSP00000059637

InnateDB Gene

IDBG-197890 (Nlrc4)

Protein Structure

UniProt Annotation

Function

Key component of inflammasomes that indirectly senses specific proteins from pathogenic bacteria and fungi and responds by assembling an inflammasome complex that promotes caspase-1 activation, cytokine production and macrophage pyroptosis. The NLRC4 inflammasome is activated as part of the innate immune response to a range of intracellular bacteria. It senses pathogenic proteins of the type III secretion system (T3SS) and type IV secretion system (T4SS) such as flagellin and PrgJ-like rod proteins via the Naip proteins (Naip1, Naip2 or Naip5): specific Naip proteins recognize and bind pathogenic proteins, driving assembly and activation of the NLRC4 inflammasome. The NLRC4 inflammasome senses Gram-negative bacteria such as L.pneumophila and P.aeruginosa, enteric pathogens S.typhimurium (Salmonella) and S.flexneri and fungal pathogen C.albicans. In intestine, the NLRC4 inflammasome is able to discriminate between commensal and pathogenic bacteria and specifically drives production of interleukin-1 beta (IL1B) in response to infection by Salmonella or P.aeruginosa. In case of L.pneumophila infection the inflammasome acts by activating caspase-7. {ECO:0000269PubMed:15190255, ECO:0000269PubMed:16648852, ECO:0000269PubMed:16648853, ECO:0000269PubMed:18070936, ECO:0000269PubMed:19343209, ECO:0000269PubMed:20133635, ECO:0000269PubMed:20603313, ECO:0000269PubMed:21874021, ECO:0000269PubMed:21918512, ECO:0000269PubMed:22174673, ECO:0000269PubMed:22231517, ECO:0000269PubMed:22484733, ECO:0000269PubMed:22547706, ECO:0000269PubMed:22885697}.

Subcellular Localization

Cytoplasm, cytosol {ECO:0000269PubMed:22885697}.

Disease Associations

Tissue Specificity

Expressed by intestinal mononuclear phagocytes. {ECO:0000269PubMed:22484733}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 7 experimentally validated interaction(s) in this database.
They are also associated with 13 interaction(s) predicted by orthology.

Experimentally validated
Total	7 [view]
Protein-Protein	7 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	13 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0042802	identical protein binding
GO:0042803	protein homodimerization activity

Biological Process

GO:0002218	activation of innate immune response
GO:0006919	activation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0006954	inflammatory response
GO:0016045	detection of bacterium
GO:0042742	defense response to bacterium
GO:0042981	regulation of apoptotic process
GO:0043065	positive regulation of apoptotic process
GO:0043281	regulation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0045087	innate immune response (InnateDB)
GO:0050702	interleukin-1 beta secretion
GO:0051092	positive regulation of NF-kappaB transcription factor activity
GO:0051260	protein homooligomerization
GO:0070269	pyroptosis

Cellular Component

GO:0005622	intracellular
GO:0005829	cytosol
GO:0072557	IPAF inflammasome complex

Protein Structure and Domains

PDB ID

MGI:3036243

InterPro

IPR001315 CARD domain
IPR007111 NACHT nucleoside triphosphatase
IPR011029 Death-like domain
IPR027417 P-loop containing nucleoside triphosphate hydrolase

PFAM

PF00619

PRINTS

PIRSF

SMART

SM00114

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

Q3UP24