Homo sapiens Gene: NLRC4
Summary
InnateDB Gene IDBG-43398.6
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol NLRC4
Gene Name NLR family, CARD domain containing 4
Synonyms
Species Homo sapiens
Ensembl Gene ENSG00000091106
Encoded Proteins
NLR family, CARD domain containing 4
NLR family, CARD domain containing 4
NLR family, CARD domain containing 4
NLR family, CARD domain containing 4
Protein Structure
Useful resources Stemformatics EHFPI ImmGen
InnateDB Annotation
Summary
NLRC4 is part of the NOD-like receptor family of proteins that consists of more than 20 related family members, that is present in the cytosol and recognizes intracellular ligands.
NLR4C and other NLR proteins function to control IL-1, NF-kappaB, and host response to pathogens, including distinct forms of cell death. NLR4C is important for CASP1 activation and IL-1 processing.
NLRC4 expressed in monocytes associates with NOD2 following exposure to bacterial peptidoglycan, implying a regulatory role for interaction of NACHT-domain containing proteins in the innate immune response.
NLR4C detects the basal body rod component of the T3SS apparatus (rod protein) from S. typhimurium (PrgJ), Burkholderia pseudomallei (BsaK), Escherichia coli (EprJ and EscI), Shigella flexneri (MxiI), and Pseudomonas aeruginosa (PscI) and the specific detection of the virulence machinery permits the discrimination between pathogenic and non-pathogenic bacteria.
The NLRC4 inflammasome is important for control of mucosal Candida infection, impacting on inflammatory cell recruitment to infected tissues, as well as protecting against the systemic dissemination of infection. (Demonstrated in mouse)
Flagellin-induced NLRC4 inflammasome activation in splenic dendritic cells triggers antigen-independent IFN-gamma production by memory T cells. (Demonstrated in mouse)
NLRC4 is important for host survival and bacterial clearance, as well as neutrophil-mediated inflammation in the lungs following Klebsiella pneumoniae infection. (Demonstrated in mouse)
NLRC4-dependent production of IL1B by intestinal phagocytes is a mechanism that discriminates pathogenic from commensal bacteria in the intestinal host defence. (Demonstrated in mouse)
NLRC4 SerÔ??533 phosphorylation is essential for procaspase-1 recruitment to the NLRC4 inflammasome complex after S. typhimurium infection. (Demonstrated in mouse)
InnateDB Annotation from Orthologs
Summary
[Mus musculus] The Nlrc4 inflammasome is important for control of mucosal Candida infection, impacting on inflammatory cell recruitment to infected tissues, as well as protecting against the systemic dissemination of infection.
[Mus musculus] Flagellin-induced Nlrc4 inflammasome activation in splenic dendritic cells triggers antigen-independent IFN-gamma production by memory T cells.
[Mus musculus] Nlrc4 is important for host survival and bacterial clearance, as well as neutrophil-mediated inflammation in the lungs following Klebsiella pneumoniae infection.
[Mus musculus] Nlrc4-dependent production of Il1b by intestinal phagocytes is a mechanism that discriminates pathogenic from commensal bacteria in the intestinal host defence.
[Mus musculus] Nlrc4 SerÔ??533 phosphorylation is essential for procaspase-1 recruitment to the Nlrc4 inflammasome complex after S. typhimurium infection.
[Mus musculus] Microglial cells employ the NAIP5/NLRC4 inflammasome to monitor and clear central nervous system infections by flagellated bacteria.
[Mus musculus] Flagellin induces Tlr5-dependent Il22 production and Nlrc4-dependent Il18 production to promote a protective gene expression program in intestinal epithelial cells and elimination of rotavirus-infected cells.
[Mus musculus] Actin polymerization is required for Nlrc4-dependent regulation of intracellular bacterial burden, inflammasome assembly, pyroptosis, and Il1b production.
Entrez Gene
Summary In C. elegans, Ced4 binds and activates Ced3, an apoptotic initiator caspase, via caspase-associated recruitment domains (CARDs). Human Ced4 homologs include APAF1 (MIM 602233), NOD1/CARD4 (MIM 605980), and NOD2/CARD15 (MIM 605956). These proteins have at least 1 N-terminal CARD domain followed by a centrally located nucleotide-binding domain (NBD or NACHT) and a C-terminal regulatory domain, found only in mammals, that contains either WD40 repeats or leucine-rich repeats (LRRs). CARD12 is a member of the Ced4 family and can induce apoptosis.[supplied by OMIM, Mar 2008]
Gene Information
Type Protein coding
Genomic Location Chromosome 2:32224453-32265854
Strand Reverse strand
Band p22.3
Transcripts
ENST00000360906 ENSP00000354159
ENST00000342905 ENSP00000339666
ENST00000402280 ENSP00000385428
ENST00000404025 ENSP00000385090
Interactions
Number of Interactions This gene and/or its encoded proteins are associated with 31 experimentally validated interaction(s) in this database.
They are also associated with 1 interaction(s) predicted by orthology.
Experimentally validated
Total 31 [view]
Protein-Protein 30 [view]
Protein-DNA 1 [view]
Protein-RNA 0
DNA-DNA 0
RNA-RNA 0
DNA-RNA 0
Predicted by orthology
Total 1 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0000287 magnesium ion binding
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:0035872 nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway
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
Orthologs
Species
Mus musculus
Bos taurus
Gene ID
Gene Order
Method
Confidence
Comments
SSD Ortholog
Ortholog supports species divergence
Not yet available
SSD Ortholog
Ortholog supports species divergence
Pathways
NETPATH
REACTOME
The IPAF inflammasome pathway
Innate Immune System pathway
Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways pathway
Immune System pathway
Inflammasomes pathway
KEGG
NOD-like receptor signaling pathway pathway
INOH
PID BIOCARTA
PID NCI
Direct p53 effectors
Cross-References
SwissProt
TrEMBL
UniProt Splice Variant
Entrez Gene
UniGene Hs.574741
RefSeq NM_001199138 NM_001199139 NM_021209
HUGO
OMIM
CCDS CCDS33174
HPRD 06014
IMGT
EMBL
GenPept
RNA Seq Atlas