This gene encodes a NOD-like receptor family member. The encoded protein is a cytosolic regulator of innate immunity. This protein directly interacts with stimulator of interferon genes (STING), to prevent its proper trafficking, resulting in disruption of STING-dependent activation of the innate immune response. Alternative splicing results in multiple transcript variants. [pr... See more...

Aliases for NLRC3 Gene

Aliases for NLRC3 Gene

  • NLR Family CARD Domain Containing 3 2 3 5
  • Nucleotide-Binding Oligomerization Domain, Leucine Rich Repeat And CARD Domain Containing 3 2 3
  • NACHT, LRR And CARD Domains-Containing Protein 3 3 4
  • NLR Family CARD Domain-Containing Protein 3 3 4
  • Caterpiller Protein 16.2 3 4
  • NOD-Like Receptor C3 2 3
  • CARD15-Like Protein 3 4
  • CLR16.2 3 4
  • NOD3 3 4
  • Nucleotide-Binding Oligomerization Domain Protein 3 4

External Ids for NLRC3 Gene

Previous GeneCards Identifiers for NLRC3 Gene

  • GC16M003531
  • GC16M003591
  • GC16M003592

Summaries for NLRC3 Gene

Entrez Gene Summary for NLRC3 Gene

  • This gene encodes a NOD-like receptor family member. The encoded protein is a cytosolic regulator of innate immunity. This protein directly interacts with stimulator of interferon genes (STING), to prevent its proper trafficking, resulting in disruption of STING-dependent activation of the innate immune response. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

GeneCards Summary for NLRC3 Gene

NLRC3 (NLR Family CARD Domain Containing 3) is a Protein Coding gene. Diseases associated with NLRC3 include Cecum Adenocarcinoma. Among its related pathways are Cytosolic sensors of pathogen-associated DNA and Innate Immune System. An important paralog of this gene is NLRC5.

UniProtKB/Swiss-Prot Summary for NLRC3 Gene

  • Negative regulator of the innate immune response (PubMed:15705585, PubMed:22863753, PubMed:25277106). Attenuates signaling pathways activated by Toll-like receptors (TLRs) and the DNA sensor STING/TMEM173 in response to pathogen-associated molecular patterns, such as intracellular poly(dA:dT), but not poly(I:C), or in response to DNA virus infection, including that of Herpes simplex virus 1 (HSV1) (By similarity) (PubMed:22863753). May affect TLR4 signaling by acting at the level of TRAF6 ubiquitination, decreasing the activating 'Lys-63'-linked ubiquitination and leaving unchanged the degradative 'Lys-48'-linked ubiquitination (PubMed:22863753). Inhibits the PI3K-AKT-mTOR pathway possibly by directly interacting with the posphatidylinositol 3-kinase regulatory subunit p85 (PIK3R1/PIK3R2) and disrupting the association between PIK3R1/PIK3R2 and the catalytic subunit p110 (PIK3CA/PIK3CB/PIK3CD) and reducing PIK3R1/PIK3R2 activation. Via its regulation of the PI3K-AKT-mTOR pathway, controls cell proliferation, predominantly in intestinal epithelial cells (By similarity). May also affect NOD1- or NOD2-mediated NF-kappa-B activation (PubMed:25277106). Might also affect the inflammatory response by preventing NLRP3 inflammasome formation, CASP1 cleavage and IL1B maturation (PubMed:25277106).

Gene Wiki entry for NLRC3 Gene

Additional gene information for NLRC3 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for NLRC3 Gene

Genomics for NLRC3 Gene

GeneHancer (GH) Regulatory Elements for NLRC3 Gene

Promoters and enhancers for NLRC3 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH16J003575 Promoter/Enhancer 1.5 EPDnew Ensembl ENCODE 510.8 +0.1 133 6.2 SP1 ZIC2 MEF2C POLR2A BCL11A NR2F2 TCF12 NFIC CBFB SMARCC1 NLRC3 CLUAP1 ENSG00000261938 CREBBP SRRM2 DNASE1 NONHSAG018414.2 LOC105371060 SLX4
GH16J003556 Promoter 0.3 EPDnew 500.4 +21.4 21393 0.1 NLRC3 SLX4 NONHSAG018414.2 lnc-CLUAP1-4 LOC101929732 piR-57133-213
GH16J003499 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE CraniofacialAtlas 19.4 +77.2 77218 2.9 RXRA FOXK2 ZBTB40 ZNF217 EP300 CTCF SIN3A TCF12 MYC POLR2G CLUAP1 RF00017-1936 NLRC3 ZNF174 ZNF200 ZSCAN32 TRAP1 ZNF205-AS1 ENSG00000263212
GH16J003509 Enhancer 0.9 Ensembl ENCODE 27.2 +67.9 67872 4.2 SP1 ZIC2 KLF4 TRIM22 CTBP1 CBFB ARNT MEF2B NBN SPI1 NLRC3 ZNF200 CLUAP1 ZNF205-AS1 RF00017-1936 piR-47693-004 ENSG00000263212
GH16J003644 Enhancer 1.4 Ensembl ENCODE CraniofacialAtlas dbSUPER 16.8 -68.1 -68108 3.5 FOXK2 ZNF217 MYC TEAD4 ZNF639 ZNF10 KDM6A FOXA1 ZNF274 GATAD2B NLRC3 CLUAP1 DNASE1 TRAP1 piR-53862 piR-40322 lnc-CLUAP1-8
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around NLRC3 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for NLRC3

Top Transcription factor binding sites by QIAGEN in the NLRC3 gene promoter:
  • AP-1
  • ATF-2
  • c-Fos
  • c-Jun
  • HSF2
  • ZID

Genomic Locations for NLRC3 Gene

Genomic Locations for NLRC3 Gene
chr16:3,539,033-3,578,373
(GRCh38/hg38)
Size:
39,341 bases
Orientation:
Minus strand
chr16:3,589,033-3,627,401
(GRCh37/hg19)
Size:
38,369 bases
Orientation:
Minus strand

Genomic View for NLRC3 Gene

Genes around NLRC3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
NLRC3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for NLRC3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for NLRC3 Gene

Proteins for NLRC3 Gene

  • Protein details for NLRC3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q7RTR2-NLRC3_HUMAN
    Recommended name:
    NLR family CARD domain-containing protein 3
    Protein Accession:
    Q7RTR2
    Secondary Accessions:
    • Q5EY36
    • Q8NF48
    • Q8NI01
    • Q8NI02
    • Q8TEL3

    Protein attributes for NLRC3 Gene

    Size:
    1065 amino acids
    Molecular mass:
    114658 Da
    Quaternary structure:
    • Directly interacts (via CARD) with TMEM173/STING; this interaction reduces TMEM173 trafficking to the perinuclear region in response to interferon stimulatory DNA. Also interacts, but to a lesser extent, with TBK1 (PubMed:24560620). Interacts with TRAF6; this interaction results in decreased TRAF6 'Lys-63'-linked polyubiquitination, but leaves 'Lys-48'-linked chains unchanged, promoting TRAF6 protein degradation (PubMed:22863753). Interacts with PIK3R1/PIK3R2; this interaction disrupts the association between PIK3R1/PIK3R2 and the p110 catalytic subunit PIK3CA/PIK3CB/PIK3CD and reduces PIK3R1/PIK3R2 activation (By similarity). Weakly interacts with PYCARD/ASC. Interacts with CASP1 and CASP5 (PubMed:25277106).
    SequenceCaution:
    • Sequence=BAC03412.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};

    Alternative splice isoforms for NLRC3 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for NLRC3 Gene

Post-translational modifications for NLRC3 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Antibody Products

  • Abcam antibodies for NLRC3
  • Santa Cruz Biotechnology (SCBT) Antibodies for NLRC3

No data available for DME Specific Peptides for NLRC3 Gene

Domains & Families for NLRC3 Gene

Gene Families for NLRC3 Gene

HGNC:
IUPHAR :
Human Protein Atlas (HPA):
  • Plasma proteins
  • Predicted intracellular proteins

Protein Domains for NLRC3 Gene

Blocks:
  • Lipocalin signature
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for NLRC3 Gene

GenScript: Design optimal peptide antigens:
  • NOD3 protein, isoform CRA_c (C3VPR7_HUMAN)
  • Nucleotide-binding oligomerization domain protein 3 (NLRC3_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q7RTR2

UniProtKB/Swiss-Prot:

NLRC3_HUMAN :
  • The leucine-rich repeat domain may reduce the interaction with TMEM173/STING.
  • Belongs to the NLRP family.
Domain:
  • The leucine-rich repeat domain may reduce the interaction with TMEM173/STING.
Family:
  • Belongs to the NLRP family.
genes like me logo Genes that share domains with NLRC3: view

Function for NLRC3 Gene

Molecular function for NLRC3 Gene

UniProtKB/Swiss-Prot Function:
Negative regulator of the innate immune response (PubMed:15705585, PubMed:22863753, PubMed:25277106). Attenuates signaling pathways activated by Toll-like receptors (TLRs) and the DNA sensor STING/TMEM173 in response to pathogen-associated molecular patterns, such as intracellular poly(dA:dT), but not poly(I:C), or in response to DNA virus infection, including that of Herpes simplex virus 1 (HSV1) (By similarity) (PubMed:22863753). May affect TLR4 signaling by acting at the level of TRAF6 ubiquitination, decreasing the activating 'Lys-63'-linked ubiquitination and leaving unchanged the degradative 'Lys-48'-linked ubiquitination (PubMed:22863753). Inhibits the PI3K-AKT-mTOR pathway possibly by directly interacting with the posphatidylinositol 3-kinase regulatory subunit p85 (PIK3R1/PIK3R2) and disrupting the association between PIK3R1/PIK3R2 and the catalytic subunit p110 (PIK3CA/PIK3CB/PIK3CD) and reducing PIK3R1/PIK3R2 activation. Via its regulation of the PI3K-AKT-mTOR pathway, controls cell proliferation, predominantly in intestinal epithelial cells (By similarity). May also affect NOD1- or NOD2-mediated NF-kappa-B activation (PubMed:25277106). Might also affect the inflammatory response by preventing NLRP3 inflammasome formation, CASP1 cleavage and IL1B maturation (PubMed:25277106).
UniProtKB/Swiss-Prot Induction:
In primary T-cells, down-regulated upon T-cell receptor activation (PubMed:15705585). Down-regulated in peritoneal macrophages soon after the beginning of LPS stimulation. Levels start increasing again after 3 days of LPS treatment (PubMed:22863753).

Phenotypes From GWAS Catalog for NLRC3 Gene

Gene Ontology (GO) - Molecular Function for NLRC3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003674 molecular_function ND --
GO:0005515 protein binding IEA,IPI 24560620
GO:0005524 ATP binding IEA --
GO:0036312 phosphatidylinositol 3-kinase regulatory subunit binding ISS --
genes like me logo Genes that share ontologies with NLRC3: view
genes like me logo Genes that share phenotypes with NLRC3: view

Animal Models for NLRC3 Gene

MGI Knock Outs for NLRC3:

Clone Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for NLRC3 Gene

Localization for NLRC3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for NLRC3 Gene

Cytoplasm.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for NLRC3 gene
Compartment Confidence
cytoskeleton 4
cytosol 4
plasma membrane 1
extracellular 1
mitochondrion 1
nucleus 1
endoplasmic reticulum 1
endosome 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (3)
  • Centriolar satellite (2)
  • Vesicles (1)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for NLRC3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IDA,IBA 15705585
GO:0005815 microtubule organizing center IDA --
GO:0005829 cytosol IDA --
GO:0034451 centriolar satellite IDA --
GO:0043231 intracellular membrane-bounded organelle IDA --
genes like me logo Genes that share ontologies with NLRC3: view

Pathways & Interactions for NLRC3 Gene

genes like me logo Genes that share pathways with NLRC3: view

Gene Ontology (GO) - Biological Process for NLRC3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007249 I-kappaB kinase/NF-kappaB signaling IDA 15705585
GO:0014067 negative regulation of phosphatidylinositol 3-kinase signaling ISS --
GO:0032088 negative regulation of NF-kappaB transcription factor activity IDA 15705585
GO:0032687 negative regulation of interferon-alpha production ISS --
GO:0032688 negative regulation of interferon-beta production ISS --
genes like me logo Genes that share ontologies with NLRC3: view

No data available for SIGNOR curated interactions for NLRC3 Gene

Drugs & Compounds for NLRC3 Gene

No Compound Related Data Available

Transcripts for NLRC3 Gene

mRNA/cDNA for NLRC3 Gene

1 REFSEQ mRNAs :
10 NCBI additional mRNA sequence :
5 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for NLRC3 Gene

ExUns: 1a · 1b ^ 2 ^ 3 ^ 4a · 4b · 4c ^ 5a · 5b · 5c ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17 ^ 18 ^ 19 ^ 20
SP1: - - -
SP2: - -

Relevant External Links for NLRC3 Gene

GeneLoc Exon Structure for
NLRC3

Expression for NLRC3 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for NLRC3 Gene

mRNA differential expression in normal tissues according to GTEx for NLRC3 Gene

This gene is overexpressed in Whole Blood (x6.7) and Spleen (x6.4).

Protein differential expression in normal tissues from HIPED for NLRC3 Gene

This gene is overexpressed in Platelet (49.8) and Spleen (8.2).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for NLRC3 Gene



Protein tissue co-expression partners for NLRC3 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for NLRC3

SOURCE GeneReport for Unigene cluster for NLRC3 Gene:

Hs.592091
genes like me logo Genes that share expression patterns with NLRC3: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA Expression by UniProt/SwissProt , Evidence on tissue expression from TISSUES and Phenotype-based relationships between genes and organs from Gene ORGANizer for NLRC3 Gene

Orthologs for NLRC3 Gene

This gene was present in the common ancestor of chordates.

Orthologs for NLRC3 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia NLRC3 31 30
  • 97.86 (n)
OneToOne
cow
(Bos Taurus)
Mammalia NLRC3 31 30
  • 86.35 (n)
OneToOne
dog
(Canis familiaris)
Mammalia NLRC3 31 30
  • 85.41 (n)
OneToOne
rat
(Rattus norvegicus)
Mammalia Nlrc3 30
  • 81.43 (n)
mouse
(Mus musculus)
Mammalia Nlrc3 17 31 30
  • 81.34 (n)
oppossum
(Monodelphis domestica)
Mammalia NLRC3 31
  • 70 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia NLRC3 31
  • 61 (a)
OneToOne
chicken
(Gallus gallus)
Aves NLRC3 31 30
  • 67.36 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia NLRC3 31
  • 60 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia nlrc3 30
  • 57.82 (n)
zebrafish
(Danio rerio)
Actinopterygii LOC100334206 30
  • 54.89 (n)
nlrc3 31
  • 44 (a)
OneToOne
Species where no ortholog for NLRC3 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for NLRC3 Gene

ENSEMBL:
Gene Tree for NLRC3 (if available)
TreeFam:
Gene Tree for NLRC3 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for NLRC3: view image

Paralogs for NLRC3 Gene

(2) SIMAP similar genes for NLRC3 Gene using alignment to 5 proteins:

  • NLRC3_HUMAN
  • B5MDB6_HUMAN
  • C3VPR7_HUMAN
  • C9JLH9_HUMAN
  • H3BLT9_HUMAN
genes like me logo Genes that share paralogs with NLRC3: view

Variants for NLRC3 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for NLRC3 Gene

SNP ID Clinical significance and condition Chr 16 pos Variation AA Info Type
103371 Not Provided: not provided 3,548,149(-) G/A NON_CODING_TRANSCRIPT_VARIANT,SYNONYMOUS_VARIANT
103373 Not Provided: not provided 3,544,314(-) G/A NON_CODING_TRANSCRIPT_VARIANT,SYNONYMOUS_VARIANT
103374 Not Provided: not provided 3,541,823(-) G/A NON_CODING_TRANSCRIPT_VARIANT,THREE_PRIME_UTR_VARIANT
735532 Likely Benign: not provided 3,563,616(-) T/C MISSENSE_VARIANT,NON_CODING_TRANSCRIPT_VARIANT
768745 Benign: not provided 3,564,058(-) C/A MISSENSE_VARIANT,NON_CODING_TRANSCRIPT_VARIANT

Additional dbSNP identifiers (rs#s) for NLRC3 Gene

Structural Variations from Database of Genomic Variants (DGV) for NLRC3 Gene

Variant ID Type Subtype PubMed ID
esv2750410 CNV deletion 23290073
nsv1716 CNV insertion 18451855
nsv517451 CNV loss 19592680
nsv571255 CNV gain 21841781
nsv571256 CNV loss 21841781
nsv833128 CNV loss 17160897

Additional Variant Information for NLRC3 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
NLRC3

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Variation tolerance for NLRC3 Gene

Disorders for NLRC3 Gene

MalaCards: The human disease database

(1) MalaCards diseases for NLRC3 Gene - From: DISEASES

Disorder Aliases PubMed IDs
cecum adenocarcinoma
  • cecal adenocarcinoma
- elite association - COSMIC cancer census association via MalaCards
Search NLRC3 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for NLRC3

genes like me logo Genes that share disorders with NLRC3: view

No data available for UniProtKB/Swiss-Prot and Genatlas for NLRC3 Gene

Publications for NLRC3 Gene

  1. Overexpressed NLRC3 acts as an anti-inflammatory cytosolic protein. (PMID: 25277106) Gültekin Y … Özören N (Journal of innate immunity 2015) 2 3 4 54
  2. CATERPILLER 16.2 (CLR16.2), a novel NBD/LRR family member that negatively regulates T cell function. (PMID: 15705585) Conti BJ … Ting JP (The Journal of biological chemistry 2005) 2 3 4 54
  3. NODs: intracellular proteins involved in inflammation and apoptosis. (PMID: 12766759) Inohara N … Nuñez G (Nature reviews. Immunology 2003) 2 3 4 54
  4. NLRC3, a member of the NLR family of proteins, is a negative regulator of innate immune signaling induced by the DNA sensor STING. (PMID: 24560620) Zhang L … Ting JP (Immunity 2014) 3 4 54
  5. The innate immune sensor NLRC3 attenuates Toll-like receptor signaling via modification of the signaling adaptor TRAF6 and transcription factor NF-κB. (PMID: 22863753) Schneider M … Ting JP (Nature immunology 2012) 3 4 54

Products for NLRC3 Gene

Sources for NLRC3 Gene