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NLRC4 (NLR Family, CARD domain containing 4)

Identity

Other namesIpaf
CARD12
CLAN
CLR2.1
HGNC (Hugo) NLRC4
Location 2p22.3
Location_base_pair Starts at 32303022 and ends at 32344305 bp from pter ( according to hg18-Mar_2006)  [Mapping]
Local_order Galactose enzyme activator 2p22-p11
Solute carrier family 30(Zinc transporter), member 2p22.3
RH-II GuB pseudogene 2p22-p21
NLRC4 2p22-p21
Yip domain family, member 4 2p22.3
 
  Human Chromosome 2 map depicting the position of NLRC4.

DNA/RNA

 
  Schematic showing genome organization of NLRC4 gene.
Description The NLRC4 gene is comprised of 9 exons, spanning 41.3kb on chromosome 2p21-p22.
Transcription Four isoforms arising due to alternate splicing of NLRC4/CLAN cDNA have been identified in Homo sapiens. The longest transcript termed CLAN-A is 3.370kb with an ORF encoding 1024 amino acids. CLAN-B, C and D have exon 4 spliced selectively to other exons forming shorter transcripts. Tumor suppressor p53 activates transcription of full length NLRC4 mRNA by binding to a site in the minimal promoter.
Pseudogene Not Known.

Protein

 
  Schematic showing domain organization of NLRC4 protein.
Description NLRC4 encodes a protein of 1024 residues with a predicted molecular mass of 112kDa. NLRC4 contains an N-terminal CARD (caspase activation and recruitment domain), a central NBD (nucleotide binding domain) and an LRR (leucine rich repeat) domain containing 13 leucine rich repeats at its carboxy terminus. The NBD is essential for activation of caspase-1. The CARD of NLRC4 is involved in interaction with itself and other CARD containing proteins and LRR domain is believed to be a regulatory domain.
Expression NLRC4 is highly expressed in the bone marrow and lung and to a lesser extent in lymph nodes, placenta, and spleen. TNF-a, Doxorubicin, UV radiation and p53 or p73 over expression induce mRNA of NLRC4 in many cell lines. NLRC4 is also induced by over expression of the tyrosine phosphatase, TC-45, which activates p53. P53 response elements have been identified upstream of the transcription start site of the NLRC4 gene.
Localisation Cytosolic.
Function NLRC4 associates with caspase-1 and several other CARD containing proteins, including ASC. The LRR domain may exert an auto inhibitory function on NLRC4 as truncation of this domain makes the protein constitutively active.
NLRC4 is involved in the regulation of caspase-1, which is activated within the "inflammasome", a complex comprising several adaptors and permitting pro-IL-1beta processing and secretion of mature IL-1beta.
It is required for the activation of caspase-1 and IL-1beta secretion in response to bacterial flagellin.
It is involved in restriction of Legionella replication through the regulation of phagosome maturation. NLRC4 knock out mice are resistant to Salmonella typhimurium induced endotoxic shock.
NLRC4 is one of the mediators of the p53-induced apoptosis.
It is also known to have caspase-1 independent functions.
Homology The CARD of NLRC4 bears significant homology to the CARDs of Caspase-1, cIAP-1 and cIAP-2, and ICEBERG. The NBD domain of NLRC4 shows high similarity to the NBD domains of NAIP, NOD1 and NOD2.

Mutations

Germinal Not known in H.sapiens.
Somatic Not known in H.sapiens.

External links

Nomenclature
HGNC (Hugo)NLRC4   16412
Entrez_Gene (NCBI)NLRC4  58484  NLR family, CARD domain containing 4
Cards
AtlasNLRC4ID43189ch2p22
GeneCards (Weizmann)NLRC4
Ensembl (Hinxton)ENSG00000091106 [Gene_View]  NLRC4 [Vega]
AceView (NCBI)NLRC4
Genatlas (Paris)NLRC4
euGene (Indiana)58484
SOURCE (Stanford)NM_021209
Gene Expression (Array Express) ENSG00000091106
Genomic and cartography
GoldenPath (UCSC)NLRC4  -  2p22.3   chr2:32303022-32344305 -  2p22-p21   [Description]    (hg18-Mar_2006)
EnsemblNLRC4 - 2p22-p21 [CytoView]
Mapping of homologs : NCBINLRC4 [Mapview]
OMIM606831   
Gene and transcription
Gene : Genbank (Entrez)AF376061 AK095467 AK292673 AK314762 AL389934
Reference sequence (RefSeq transcript) :SRSNM_021209
Reference transcript : EntrezNM_021209
RefSeq genomic : SRSAC_000045 AC_000134 NC_000002 NT_022184 NW_001838769 NW_927719
RefSeq genomic : EntrezAC_000045 AC_000134 NC_000002 NT_022184 NW_001838769 NW_927719
Consensus coding sequences : CCDS NCBINLRC4
Cluster EST : UnigeneHs.574741 [ SRS ] Hs.574741 [ NCBI ]
Alternative Splicing : Fast-db (Paris)3826
Protein : pattern, domain, 3D structure
Protein : UniProt/SwissProtQ9NPP4 (SRS) Q9NPP4 (Expasy) Q9NPP4 (Uniprot)
With graphics : InterProQ9NPP4
Splice isoforms : VarSplice FASTAQ9NPP4(VarSplice FASTA)
Domaine pattern : Prosite (SRS)CARD (PS50209)    NACHT (PS50837)   
Domain pattern : Prosite (Expaxy)CARD (PS50209)    NACHT (PS50837)   
Domains : Interpro (SRS)CARD    DEATH-like    NACHT_NTPase   
Domains : Interpro (EBI)CARD    DEATH-like    NACHT_NTPase   
Related proteins : CluSTrQ9NPP4
Domain families : Pfam SRSCARD (PF00619)    NACHT (PF05729)   
Domain families : Pfam SangerCARD (PF00619)    NACHT (PF05729)   
Domain families : Pfam NCBIpfam00619    pfam05729   
Blocks (Seattle)Q9NPP4
Crystal structure of protein : PDB SRS
Crystal structure of protein : PDBSum
Crystal structure of protein : IMB
Crystal structure of protein : PDB RSDB
HPRD06014
Protein Interaction databases
DIP (DOE-UCLA)Q9NPP4
IntAct (EBI)Q9NPP4
Polymorphism : SNP, mutations, diseases
Single Nucleotide Polymorphism (SNP) : dbSNP NCBINLRC4
SNP : GeneSNP UtahNLRC4
SNP : HGBaseNLRC4
Genetic variants : HAPMAPNLRC4
Somatic Mutations in Cancer : COSMICNLRC4 
Mutations and Diseases : HGMDNLRC4
Hereditary diseases : OMIM606831   
Hereditary diseases : GENETests606831   
Diseases : Genetic AssociationNLRC4
General knowledge
Homologs : HomoloGeneNLRC4
Homology/Alignments : Family Browser UCSCNLRC4
Phylogenetic Trees/Animal Genes : TreeFamNLRC4
Chemical/Protein Interactions : CTD58484
Keywords Ontology : AmiGOnucleotide binding  magnesium ion binding  protein binding  ATP binding  intracellular  cytoplasm  activation of caspase activity  inflammatory response  detection of bacterium  defense response to bacterium  protein homodimerization activity  positive regulation of apoptosis  regulation of caspase activity  interleukin-1 beta secretion  
Keywords Ontology : EGO-EBInucleotide binding  magnesium ion binding  protein binding  ATP binding  intracellular  cytoplasm  activation of caspase activity  inflammatory response  detection of bacterium  defense response to bacterium  protein homodimerization activity  positive regulation of apoptosis  regulation of caspase activity  interleukin-1 beta secretion  
Pathways : BIOCARTA
Pathways : KEGG
Other databases
Probes
Probes : ImagenesNLRC4 Related clones (RZPD - Berlin)
Literature
PubMed18 Pubmed reference(s) in Entrez
PubGeneNLRC4

Bibliography

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Contributor(s)

Written07-2007Yatender Kumar, Vegesna Radha, Ghanshyam Swarup
Center for cellular and molecular biology, uppal road, Hyderabad- 500 007, India

Citation

This paper should be referenced as such :
Kumar Y, Radha V, Swarup G . NLRC4 (NLR Family, CARD domain containing 4). Atlas Genet Cytogenet Oncol Haematol. July 2007 .
URL : http://AtlasGeneticsOncology.org/Genes/NLRC4ID43189ch2p22.html

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