NLRC4 (NLR Family, CARD domain containing 4)

Identity

Other names	Ipaf
	CARD12
	CLAN
	CLR2.1
HGNC	NLRC4
Location	2p22.3
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	NLRC4   16412
Entrez_Gene	NLRC4  58484  NLR family, CARD domain containing 4
	Cards
Atlas	NLRC4ID43189ch2p22
GeneCards	NLRC4
Ensembl	NLRC4 [Search_View]   ENSG00000091106 [Gene_View]
Genatlas	NLRC4
GeneLynx	NLRC4
eGenome	NLRC4
euGene	58484
	Genomic and cartography
GoldenPath	NLRC4  -  2p22.3   chr2:32303022-32344305 -  2p22-p21   [Description]    (hg18-Mar_2006)
Ensembl	NLRC4 - 2p22-p21 [CytoView]
NCBI	Mapview
OMIM	Disease map [OMIM]
HomoloGene	NLRC4
	Gene and transcription
Genbank	AF376061 [ ENTREZ ]
Genbank	AK095467 [ ENTREZ ]
Genbank	AK292673 [ ENTREZ ]
Genbank	AK314762 [ ENTREZ ]
Genbank	AL389934 [ ENTREZ ]
RefSeq	NM_021209 [ SRS ]    NM_021209 [ ENTREZ ]
RefSeq	AC_000045 [ SRS ]    AC_000045 [ ENTREZ ]
RefSeq	AC_000134 [ SRS ]    AC_000134 [ ENTREZ ]
RefSeq	NC_000002 [ SRS ]    NC_000002 [ ENTREZ ]
RefSeq	NT_022184 [ SRS ]    NT_022184 [ ENTREZ ]
RefSeq	NW_001838769 [ SRS ]    NW_001838769 [ ENTREZ ]
RefSeq	NW_927719 [ SRS ]    NW_927719 [ ENTREZ ]
AceView	NLRC4 AceView - NCBI
Unigene	Hs.574741 [ SRS ]    Hs.574741 [ NCBI ]     HS574741 [ spliceNest ]
Fast-db	3826 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	Q9NPP4 [ SRS]    Q9NPP4 [ EXPASY ]     Q9NPP4 [ INTERPRO ]     Q9NPP4 [ UNIPROT ]
Prosite	PS50209 CARD [ SRS ]    PS50209 CARD [ Expasy ]
Prosite	PS50837 NACHT [ SRS ]    PS50837 NACHT [ Expasy ]
Interpro	IPR001315 CARD [ SRS ]    IPR001315 CARD [ EBI ]
Interpro	IPR011029 DEATH_like [ SRS ]    IPR011029 DEATH_like [ EBI ]
Interpro	IPR001611 LRR [ SRS ]    IPR001611 LRR [ EBI ]
Interpro	IPR007111 NACHT_NTPase [ SRS ]    IPR007111 NACHT_NTPase [ EBI ]
CluSTr	Q9NPP4
Pfam	PF00619 CARD [ SRS ]    PF00619 CARD [ Sanger ]    pfam00619 [ NCBI-CDD ]
Pfam	PF05729 NACHT [ SRS ]    PF05729 NACHT [ Sanger ]    pfam05729 [ NCBI-CDD ]
Blocks	Q9NPP4
HPRD	06014
	Protein Interaction databases
DIP	Q9NPP4
IntAct	Q9NPP4
	Polymorphism : SNP, mutations, diseases
OMIM	606831    [ map ]
GENECLINICS	606831
SNP	NLRC4 [dbSNP-NCBI]
SNP	NM_021209 [SNP-NCI]
SNP	NLRC4 [GeneSNPs - Utah]  NLRC4] [HGBASE - SRS]
HAPMAP	NLRC4 [HAPMAP]
COSMIC	NLRC4 [Somatic mutation (COSMIC-CGP-Sanger)]
HGMD	NLRC4
	General knowledge
Family Browser	NLRC4 [UCSC Family Browser]
SOURCE	NM_021209
SMD	Hs.574741
SAGE	Hs.574741
GO	nucleotide binding [Amigo]  nucleotide binding
GO	magnesium ion binding [Amigo]  magnesium ion binding
GO	protein binding [Amigo]  protein binding
GO	ATP binding [Amigo]  ATP binding
GO	intracellular [Amigo]  intracellular
GO	cytoplasm [Amigo]  cytoplasm
GO	caspase activation [Amigo]  caspase activation
GO	detection of bacterium [Amigo]  detection of bacterium
GO	defense response to bacterium [Amigo]  defense response to bacterium
GO	protein homodimerization activity [Amigo]  protein homodimerization activity
GO	positive regulation of apoptosis [Amigo]  positive regulation of apoptosis
GO	interleukin-1 beta secretion [Amigo]  interleukin-1 beta secretion
PubGene	NLRC4
TreeFam	NLRC4
CTD	58484 [Comparative ToxicoGenomics Database]
	Other databases
	Probes
Probe	NLRC4 Related clones (RZPD - Berlin)
	PubMed
PubMed	17 Pubmed reference(s) in LocusLink

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Contributor(s)

Written	07-2007	Yatender 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

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Mon Aug 11 21:15:54 2008