NLRC4 (NLR Family, CARD domain containing 4)
2007-07-01 Yatender Kumar , Vegesna Radha , Ghanshyam Swarup AffiliationCenter for cellular, molecular biology, uppal road, Hyderabad- 500 007, India
Identity
HGNC
LOCATION
2p22.3
IMAGE
LEGEND
Human Chromosome 2 map depicting the position of NLRC4.
LOCUSID
ALIAS
AIFEC,CARD12,CLAN,CLAN1,CLANA,CLANB,CLANC,CLAND,CLR2.1,FCAS4,IPAF
FUSION GENES
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.
Proteins
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.
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.
Mutations
Germinal
Not known in H.sapiens.
Somatic
Not known in H.sapiens.
Implicated in
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 16984919 | 2006 | Regulation of Legionella phagosome maturation and infection through flagellin and host Ipaf. | Amer A et al |
| 17506816 | 2007 | Restriction of Legionella pneumophila growth in macrophages requires the concerted action of cytokine and Naip5/Ipaf signalling pathways. | Coers J et al |
| 15107016 | 2004 | Heterotypic interactions among NACHT domains: implications for regulation of innate immune responses. | Damiano JS et al |
| 17126540 | 2007 | Innate recognition of intracellular bacteria. | Delbridge LM et al |
| 16648852 | 2006 | Cytosolic flagellin requires Ipaf for activation of caspase-1 and interleukin 1beta in salmonella-infected macrophages. | Franchi L et al |
| 17110941 | 2006 | Nod-like proteins in immunity, inflammation and disease. | Fritz JH et al |
| 11374873 | 2001 | Human CARD12 is a novel CED4/Apaf-1 family member that induces apoptosis. | Geddes BJ et al |
| 15196924 | 2004 | Ipaf is upregulated by tumor necrosis factor-alpha in human leukemia cells. | Gutierrez O et al |
| 15952891 | 2005 | NOD-LRR proteins: role in host-microbial interactions and inflammatory disease. | Inohara et al |
| 17433728 | 2007 | Pannexin-1-mediated recognition of bacterial molecules activates the cryopyrin inflammasome independent of Toll-like receptor signaling. | Kanneganti TD et al |
| 17442855 | 2007 | Caspase-1 inflammasomes in infection and inflammation. | Lamkanfi M et al |
| 15882992 | 2005 | Nucleotide binding to CARD12 and its role in CARD12-mediated caspase-1 activation. | Lu C et al |
| 17382568 | 2007 | ASC, Ipaf and Cryopyrin/Nalp3: bona fide intracellular adapters of the caspase-1 inflammasome. | Mariathasan S et al |
| 16977329 | 2007 | Inflammatory caspases and inflammasomes: master switches of inflammation. | Martinon F et al |
| 12646168 | 2003 | ASC is an activating adaptor for NF-kappa B and caspase-8-dependent apoptosis. | Masumoto J et al |
| 17435760 | 2007 | A crucial function of SGT1 and HSP90 in inflammasome activity links mammalian and plant innate immune responses. | Mayor A et al |
| 16648853 | 2006 | Cytoplasmic flagellin activates caspase-1 and secretion of interleukin 1beta via Ipaf. | Miao EA et al |
| 17082224 | 2007 | TLRS in the gut. II. Flagellin-induced inflammation and antiapoptosis. | Neish AS et al |
| 16923387 | 2006 | The inflammasome: first line of the immune response to cell stress. | Ogura Y et al |
| 17599094 | 2007 | Activation of the NALP3 inflammasome is triggered by low intracellular potassium concentration. | Pétrilli V et al |
| 17535448 | 2007 | Regulation of p73 by Hck through kinase-dependent and independent mechanisms. | Paliwal P et al |
| 11390368 | 2001 | Identification of Ipaf, a human caspase-1-activating protein related to Apaf-1. | Poyet JL et al |
| 17133080 | 2007 | The role of altered microbial signaling via mutant NODs in intestinal inflammation. | Rescigno M et al |
| 16715062 | 2006 | Cytosolic detection of flagellin: a deadly twist. | Roy CR et al |
| 15580302 | 2005 | Caspase-1 activator Ipaf is a p53-inducible gene involved in apoptosis. | Sadasivam S et al |
| 16817903 | 2006 | Involvement of caspase 1 and its activator Ipaf upstream of mitochondrial events in apoptosis. | Thalappilly S et al |
| 16528382 | 2006 | TIR, CARD and PYRIN: three domains for an antimicrobial triad. | Werts C et al |
Other Information
Locus ID:
NCBI: 58484
MIM: 606831
HGNC: 16412
Ensembl: ENSG00000091106
Variants:
dbSNP: 58484
ClinVar: 58484
TCGA: ENSG00000091106
COSMIC: NLRC4
RNA/Proteins
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 38453949 | 2024 | NFκB and NLRP3/NLRC4 inflammasomes regulate differentiation, activation and functional properties of monocytes in response to distinct SARS-CoV-2 proteins. | 0 |
| 38571451 | 2024 | NLRC4-mediated pyroptosis was involved in coagulation disorders of acute pancreatitis. | 0 |
| 38652550 | 2024 | Human NLRC4 expression promotes cancer survival and associates with type I interferon signaling and immune infiltration. | 0 |
| 38453949 | 2024 | NFκB and NLRP3/NLRC4 inflammasomes regulate differentiation, activation and functional properties of monocytes in response to distinct SARS-CoV-2 proteins. | 0 |
| 38571451 | 2024 | NLRC4-mediated pyroptosis was involved in coagulation disorders of acute pancreatitis. | 0 |
| 38652550 | 2024 | Human NLRC4 expression promotes cancer survival and associates with type I interferon signaling and immune infiltration. | 0 |
| 36797819 | 2023 | Early-onset recurrent panniculitis as a phenotype of NLRC4-associated autoinflammatory syndrome: Characterization of pathogenicity of the p.Ser445Pro NLRC4 variant. | 1 |
| 36899084 | 2023 | Non-canonical NLRC4 inflammasomes in astrocytes contribute to glioma malignancy. | 0 |
| 36941318 | 2023 | LNCGM1082-mediated NLRC4 activation drives resistance to bacterial infection. | 4 |
| 36948192 | 2023 | Ribosome-rescuer PELO catalyzes the oligomeric assembly of NOD-like receptor family proteins via activating their ATPase enzymatic activity. | 6 |
| 37099347 | 2023 | TET2-Driver and NLRC4-Passenger Variants in Adult-Onset Autoinflammation. | 2 |
| 37567492 | 2023 | NLRC4 gain-of-function variant is identified in a patient with systemic lupus erythematosus. | 3 |
| 37586642 | 2023 | Targeting Desulfovibrio vulgaris flagellin-induced NAIP/NLRC4 inflammasome activation in macrophages attenuates ulcerative colitis. | 1 |
| 37846829 | 2023 | [Expressions of NLRP1 and NLRC4 inflammasomes in prostate cancer and their clinical value]. | 0 |
| 36797819 | 2023 | Early-onset recurrent panniculitis as a phenotype of NLRC4-associated autoinflammatory syndrome: Characterization of pathogenicity of the p.Ser445Pro NLRC4 variant. | 1 |
Citation
Yatender Kumar ; Vegesna Radha ; Ghanshyam Swarup
NLRC4 (NLR Family, CARD domain containing 4)
Atlas Genet Cytogenet Oncol Haematol. 2007-07-01
Online version: http://atlasgeneticsoncology.org/gene/43189/nlrc4
