NLRC4 (NLR Family, CARD domain containing 4)

Other names	Ipaf
	CARD12
	CLAN
	CLR2.1
HGNC (Hugo)	NLRC4
LocusID (NCBI)	58484
Atlas_Id	43189
Location	2p22.3  [Link to chromosome band 2p22]
Location_base_pair	Starts at 32449518 and ends at 32489949 bp from pter ( according to hg19-Feb_2009)  [Mapping NLRC4.png]
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.

	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.

	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.

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