Human Gene NLRC4 (uc021vfq.1) Description and Page Index
  Description: Homo sapiens NLR family, CARD domain containing 4 (NLRC4), transcript variant 3, mRNA.
RefSeq Summary (NM_001199139): This gene encodes a member of the caspase recruitment domain-containing NLR family. Family members play essential roles in innate immune response to a wide range of pathogenic organisms, tissue damage and other cellular stresses. Mutations in this gene result in autoinflammation with infantile enterocolitis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2014].
Transcript (Including UTRs)
   Position: hg19 chr2:32,449,518-32,490,689 Size: 41,172 Total Exon Count: 9 Strand: -
Coding Region
   Position: hg19 chr2:32,449,542-32,481,844 Size: 32,303 Coding Exon Count: 8 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr2:32,449,518-32,490,689)mRNA (may differ from genome)Protein (1024 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
H-INVHGNCHPRDLynxMGIneXtProt
OMIMPubMedReactomeStanford SOURCETreefamUniProtKB
Wikipedia

-  Comments and Description Text from UniProtKB
  ID: NLRC4_HUMAN
DESCRIPTION: RecName: Full=NLR family CARD domain-containing protein 4; AltName: Full=CARD, LRR, and NACHT-containing protein; Short=Clan protein; AltName: Full=Caspase recruitment domain-containing protein 12; AltName: Full=Ice protease-activating factor; Short=Ipaf;
FUNCTION: Key component of inflammasomes that indirectly senses specific proteins from pathogenic bacteria and fungi and responds by assembling an inflammasome complex that promotes caspase-1 activation, cytokine production and macrophage pyroptosis.
SUBUNIT: Component of the NLRC4 inflammasome (By similarity). Homooligomer. Interacts with ASC, pro-caspase-1, NOD2, BCL10 and NALP1 (NAC) by CARD-CARD interaction.
INTERACTION: Self; NbExp=3; IntAct=EBI-1222527, EBI-1222527; P29466:CASP1; NbExp=4; IntAct=EBI-1222527, EBI-516667;
SUBCELLULAR LOCATION: Cytoplasm. Cytoplasm, cytosol (By similarity). Note=Cytoplasmic filaments.
TISSUE SPECIFICITY: Isoform 2 is expressed ubiquitously, although highly expressed in lung and spleen. Isoform 1 is highly expressed in lung, followed by leukocytes especially monocytes, lymph node, colon, brain, prostate, placenta, spleen, bone marrow and fetal liver. Isoform 4 is only detected in brain.
PTM: Phosphorylated at Ser-533 following infection of macrophages with S.typhimurium (Salmonella). Phosphorylation is essential for NLRC4 inflammasome function to promote caspase-1 activation and pyroptosis. PRKCD phosphorylates Ser-533 in vitro (By similarity).
SIMILARITY: Contains 1 CARD domain.
SIMILARITY: Contains 14 LRR (leucine-rich) repeats.
SIMILARITY: Contains 1 NACHT domain.
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/NLRC4ID43189ch2p22.html";

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): NLRC4
CDC HuGE Published Literature: NLRC4

-  MalaCards Disease Associations
  MalaCards Gene Search: NLRC4
Diseases sorted by gene-association score: autoinflammation with infantile enterocolitis* (1691), familial cold autoinflammatory syndrome 4* (1280), familial cold autoinflammatory syndrome* (271), cinca syndrome* (20), legionellosis (18), macrophage activation syndrome (8), legionnaires' disease (6)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 13.85 RPKM in Whole Blood
Total median expression: 43.61 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -35.00144-0.243 Picture PostScript Text
3' UTR -0.3024-0.013 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR001315 - CARD
IPR011029 - DEATH-like
IPR007111 - NACHT_NTPase

Pfam Domains:
PF00619 - Caspase recruitment domain
PF05729 - NACHT domain

SCOP Domains:
47986 - DEATH domain
52047 - RNI-like
52058 - L domain-like
52075 - Outer arm dynein light chain 1
52540 - P-loop containing nucleoside triphosphate hydrolases

ModBase Predicted Comparative 3D Structure on Q9NPP4
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
      
      
      

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0000287 magnesium ion binding
GO:0004842 ubiquitin-protein transferase activity
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0042802 identical protein binding
GO:0042803 protein homodimerization activity
GO:0043027 cysteine-type endopeptidase inhibitor activity involved in apoptotic process

Biological Process:
GO:0002218 activation of innate immune response
GO:0002376 immune system process
GO:0006915 apoptotic process
GO:0006919 activation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0006954 inflammatory response
GO:0009966 regulation of signal transduction
GO:0016045 detection of bacterium
GO:0016567 protein ubiquitination
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
GO:0050702 interleukin-1 beta secretion
GO:0051092 positive regulation of NF-kappaB transcription factor activity
GO:0051260 protein homooligomerization
GO:0070269 pyroptosis
GO:1990001 inhibition of cysteine-type endopeptidase activity involved in apoptotic process
GO:0090307 mitotic spindle assembly

Cellular Component:
GO:0005622 intracellular
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0072557 IPAF inflammasome complex


-  Descriptions from all associated GenBank mRNAs
  LP896190 - Sequence 1054 from Patent EP3253886.
AY032589 - Homo sapiens caspase recruitment domain protein 12 mRNA, complete cds.
AL389934 - Homo sapiens mRNA full length insert cDNA clone EUROIMAGE 2005417.
AY358152 - Homo sapiens clone DNA167923 CARD12 (UNQ6189) mRNA, complete cds.
BC031555 - Homo sapiens NLR family, CARD domain containing 4, mRNA (cDNA clone MGC:35330 IMAGE:5179909), complete cds.
AY027787 - Homo sapiens CLANA (CLAN1) mRNA, complete cds.
AK292673 - Homo sapiens cDNA FLJ78036 complete cds, highly similar to Homo sapiens caspase recruitment domain family, member 12, mRNA.
AK095467 - Homo sapiens cDNA FLJ38148 fis, clone D9OST2003791, highly similar to Caspase recruitment domain-containing protein 12.
AY027788 - Homo sapiens CLANB (CLAN1) mRNA, complete cds.
AF376061 - Homo sapiens caspase recruitment domain protein 12 mRNA, complete cds.
EU832133 - Synthetic construct Homo sapiens clone HAIB:100067162; DKFZo008D1125 NLR family, CARD domain containing 4 protein (NLRC4) gene, encodes complete protein.
AK314762 - Homo sapiens cDNA, FLJ95631, highly similar to Homo sapiens caspase recruitment domain family, member 12 (CARD12),mRNA.
AY035391 - Homo sapiens ICE-protease activating factor mRNA, complete cds.
EU832226 - Synthetic construct Homo sapiens clone HAIB:100067255; DKFZo004D1126 NLR family, CARD domain containing 4 protein (NLRC4) gene, encodes complete protein.
KJ899382 - Synthetic construct Homo sapiens clone ccsbBroadEn_08776 NLRC4 gene, encodes complete protein.
AB590945 - Synthetic construct DNA, clone: pFN21AB0482, Homo sapiens NLRC4 gene for NLR family, CARD domain containing 4, without stop codon, in Flexi system.
CQ873718 - Sequence 137 from Patent WO2004076622.
DD413555 - Regulation of Mammalian Cells.
CU689176 - Synthetic construct Homo sapiens gateway clone IMAGE:100020494 5' read NLRC4 mRNA.
AY027789 - Homo sapiens CLANC (CLAN1) mRNA, complete cds.
AY027790 - Homo sapiens CLAND (CLAN1) mRNA, complete cds.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04621 - NOD-like receptor signaling pathway

Reactome (by CSHL, EBI, and GO)

Protein Q9NPP4 (Reactome details) participates in the following event(s):

R-HSA-844617 IPAF binds procaspase-1
R-HSA-844623 The IPAF inflammasome
R-HSA-6803207 TP53 Regulates Transcription of Caspase Activators and Caspases
R-HSA-622312 Inflammasomes
R-HSA-5633008 TP53 Regulates Transcription of Cell Death Genes
R-HSA-168643 Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways
R-HSA-3700989 Transcriptional Regulation by TP53
R-HSA-168249 Innate Immune System
R-HSA-212436 Generic Transcription Pathway
R-HSA-168256 Immune System
R-HSA-73857 RNA Polymerase II Transcription
R-HSA-74160 Gene expression (Transcription)

-  Other Names for This Gene
  Alternate Gene Symbols: A8K9F8, B2RBQ3, B3KTF0, CARD12, CLAN, CLAN1, D6W580, IPAF, NLRC4_HUMAN, NM_001199139, NP_067032, Q96J81, Q96J82, Q96J83, Q9NPP4, UNQ6189/PRO20215
UCSC ID: uc021vfq.1
RefSeq Accession: NM_001199139
Protein: Q9NPP4 (aka NLRC4_HUMAN)
CCDS: CCDS33174.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_001199139.1
exon count: 9CDS single in 3' UTR: no RNA size: 3254
ORF size: 3075CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 6278.00frame shift in genome: no % Coverage: 99.66
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.