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NLRC3 Gene

protein-coding   GIFtS: 49
GCID: GC16M003592

NLR Family, CARD Domain Containing 3

  See related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
NLR Family, CARD Domain Containing 31 2     Leucine Rich Repeat And CARD Domain Containing 31
NOD-Like Receptor C31 2     Nucleotide-Binding Oligomerization Domain1
Caterpiller Protein 16.22 3     Nucleotide-Binding Oligomerization Domain, Leucine Rich Repeat And CARD
Domain Containing 32
CLR16.22 3     Protein NLRC32
NOD32 3     Nucleotide-Binding Oligomerization Domain Protein 33
CARD15-Like Protein2 3     

External Ids:    HGNC: 298891   Entrez Gene: 1973582   Ensembl: ENSG000001679847   OMIM: 6156485   UniProtKB: Q7RTR23   

Export aliases for NLRC3 gene to outside databases

Previous GC identifers: GC16M003531 GC16M003591


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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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 burns, and wegener's granulomatosis. An important paralog of this gene is NLRP4.

UniProtKB/Swiss-Prot: NLRC3_HUMAN, Q7RTR2
Function: May modulate T-cell activation. Decreases the transcription of genes that are normally up-regulated
after T-cell stimulation. Delays degradation of NFKBIA/IKBA

Gene Wiki entry for NLRC3 Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence:
NC_000016.10  NC_018927.2  NT_010393.17  
Regulatory elements:
   Regulatory transcription factor binding sites in the NLRC3 gene promoter:
         c-Fos   AP-1   HSF2   ATF-2   ZID   c-Jun   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidNLRC3 promoter sequence
   Search Chromatin IP Primers for NLRC3

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat NLRC3


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 16p13.3   Ensembl cytogenetic band:  16p13.3   HGNC cytogenetic band: 16p13.3

NLRC3 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
NLRC3 gene location

GeneLoc information about chromosome 16         GeneLoc Exon Structure

GeneLoc location for GC16M003592:  view genomic region     (about GC identifiers)

Start:
3,589,033 bp from pter      End:
3,627,401 bp from pter
Size:
38,369 bases      Orientation:
minus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
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UniProtKB/Swiss-Prot: NLRC3_HUMAN, Q7RTR2 (See protein sequence)
Recommended Name: Protein NLRC3  
Size: 1065 amino acids; 114658 Da
Sequence caution: Sequence=BAC03412.1; Type=Erroneous initiation;
Secondary accessions: Q5EY36 Q8NF48 Q8NI01 Q8NI02 Q8TEL3
Alternative splicing: 4 isoforms:  Q7RTR2-1   Q7RTR2-2   Q7RTR2-3   Q7RTR2-4   (No experimental confirmation available)

Explore the universe of human proteins at neXtProt for NLRC3: NX_Q7RTR2

Explore proteomics data for NLRC3 at MOPED

Post-translational modifications: 

  • Modification sites at neXtProt
  • Modification sites at PhosphoSitePlus

  • See NLRC3 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins: NP_849172.2  
    ENSEMBL proteins: 
     ENSP00000474358   ENSP00000414415   ENSP00000352039   ENSP00000301749   ENSP00000323897  

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    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    HGNC Gene Families:
    NLR: Nucleotide-binding domain and leucine rich repeat containing

    IUPHAR Guide to PHARMACOLOGY protein family classification: NLRC3
    NOD-like receptor family

    1 InterPro protein domain:
     IPR007111 NACHT_NTPase

    Graphical View of Domain Structure for InterPro Entry Q7RTR2

    ProtoNet protein and cluster: Q7RTR2

    1 Blocks protein domain: IPB002345 Lipocalin signature

    UniProtKB/Swiss-Prot: NLRC3_HUMAN, Q7RTR2
    Similarity: Belongs to the NLRP family
    Similarity: Contains 16 LRR (leucine-rich) repeats
    Similarity: Contains 1 NACHT domain


    NLRC3 for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: NLRC3_HUMAN, Q7RTR2
    Function: May modulate T-cell activation. Decreases the transcription of genes that are normally up-regulated
    after T-cell stimulation. Delays degradation of NFKBIA/IKBA
    Induction: Down-regulated upon T-cell activation

         Gene Ontology (GO): 3 molecular function terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0003674molecular_function ND--
    GO:0005515protein binding ----
    GO:0005524ATP binding IEA--
         
    NLRC3 for ontologies           About GeneDecksing


    Phenotypes:
         4 MGI mutant phenotypes (inferred from 1 allele(MGI details for Nlrc3):
     growth/size/body  hematopoietic system  homeostasis/metabolism  immune system 

    NLRC3 for phenotypes           About GeneDecksing

    Animal Models:
         MGI mouse knock-out Nlrc3tm1Bhk for NLRC3

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for NLRC3
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    2 qRT-PCR Assays for microRNAs that regulate NLRC3:
    hsa-miR-1290 hsa-miR-2115
    SwitchGear 3'UTR luciferase reporter plasmidNLRC3 3' UTR sequence
    Inhib. RNA
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    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    NLRC3_HUMAN, Q7RTR2: Cytoplasm
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    cytosol2
    nucleus2

    Gene Ontology (GO): 1 cellular component term:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005737cytoplasm IDA15705585

    NLRC3 for ontologies           About GeneDecksing


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for NLRC3 About    
    See pathways by source

    SuperPathContained pathways About
    1NOD-like Receptor Signaling Pathways
    NOD-like Receptor Signaling Pathways0.58

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    1 R&D Systems Pathway for NLRC3
        NOD-like Receptor Signaling Pathways



        Custom Pathway & Disease-focused RT2 Profiler PCR Arrays for NLRC3
    Interactions:

        Search GeneGlobe Interaction Network for NLRC3

    STRING Interaction Network Preview (showing 1 interactants - click image to see more details)

    1 Interacting protein for NLRC3 (Q7RTR23 ENSP000004144154) via UniProtKB, MINT, STRING, and/or I2D
    InteractantInteraction Details
    GeneCardExternal ID(s)
    ELF3P785453, ENSP000003526734I2D: score=1 STRING: ENSP00000352673
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 6):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0007249I-kappaB kinase/NF-kappaB signaling IDA15705585
    GO:0031396regulation of protein ubiquitination ----
    GO:0032088negative regulation of NF-kappaB transcription factor activity IDA15705585
    GO:0032496response to lipopolysaccharide ----
    GO:0042110T cell activation IEP15705585

    NLRC3 for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for NLRC3



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
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    REFSEQ mRNAs for NLRC3 gene: 
    NM_178844.3  

    Unigene Cluster for NLRC3:

    NLR family, CARD domain containing 3
    Hs.592091  [show with all ESTs]
    Unigene Representative Sequence: AK090431
    9 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000603128 ENST00000419350 ENST00000603507 ENST00000604347 ENST00000603055
    ENST00000448023 ENST00000359128 ENST00000301749 ENST00000324659
    miRNA
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    2 qRT-PCR Assays for microRNAs that regulate NLRC3:
    hsa-miR-1290 hsa-miR-2115
    SwitchGear 3'UTR luciferase reporter plasmidNLRC3 3' UTR sequence
    Inhib. RNA
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      QuantiFast Probe-based Assays in human, mouse, rat NLRC3

    Additional mRNA sequence: 

    AF501291.1 AF501292.1 AK074109.1 AK090431.1 AK125583.1 AY601811.1 BC027864.1 FJ889357.1 
    NR_075083.1 

    3 DOTS entries:

    DT.453510  DT.92414904  DT.101971153 

    Selected AceView cDNA sequences (see all 84):

    BM702755 AI683785 CF138331 BQ024950 AA694067 BC027864 AI243707 AI264909 
    AI240419 BF869650 AI199387 AI804488 AI378880 AI090037 AI284346 AI139177 
    NM_178844 BK001112 F11200 F11880 AI381465 BE674491 AI793342 CF138406 

    GeneLoc Exon Structure

    2 Alternative Splicing Database (ASD) splice patterns (SP) for NLRC3    About this scheme

    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:                          -           -                                                                                                               


    ECgene alternative splicing isoforms for NLRC3

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    NLRC3 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: AAAAACACAA
    NLRC3 Expression
    About this image

    NLRC3 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    NLRC3 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.592091

    UniProtKB/Swiss-Prot: NLRC3_HUMAN, Q7RTR2
    Tissue specificity: Detected in peripheral blood mononuclear cells

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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of chordates.

    Orthologs for NLRC3 gene from Selected species (see all 11)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Nlrc31 , 5 NLR family, CARD domain containing 31, 5 81.34(n)1
    80.3(a)1
      16 (2.32 cM)5
    2688571  NM_001081280.11  NP_001074749.11 
     39450075 
    chicken
    (Gallus gallus)
    Aves NLRC31 NLR family, CARD domain containing 3 67.36(n)
    61.32(a)
      416673  XM_003642157.2  XP_003642205.1 
    lizard
    (Anolis carolinensis)
    Reptilia NLRC36
    NLR family, CARD domain containing 3
    60(a)
    1 ↔ 1
    GL343518.1(422416-471713)
    tropical clawed frog
    (Xenopus tropicalis)
    Amphibia nlrc31 NLR family, CARD domain containing 3 57.82(n)
    52.86(a)
      100158644  XM_002932458.2  XP_002932504.1 
    zebrafish
    (Danio rerio)
    Actinopterygii LOC1003342061 protein NLRC3-like 54.89(n)
    48.28(a)
      100334206  XM_002666707.3  XP_002666753.3 


    ENSEMBL Gene Tree for NLRC3 (if available)
    TreeFam Gene Tree for NLRC3 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for NLRC3 gene
    NLRP42  NLRP132  NLRP92  NLRP62  NLRP32  NLRP142  NLRP72  NLRP112  
    NLRP102  NLRP22  NLRP52  NLRP82  NLRP122  
    2 SIMAP similar genes for NLRC3 using alignment to 5 protein entries:     NLRC3_HUMAN (see all proteins):
    FLJ00398    TMOD2

    NLRC3 for paralogs           About GeneDecksing



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for NLRC3 (see all 1102)    About this table    
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 16 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs1994762891,2
    Cuntested13528788(+) GGGCAA/CACAGG 2 -- int10--------
    rs1994759461,2
    Cuntested13529255(+) TTACTC/TGAGAA 3 N D mis10--------
    rs1994762811,2
    Cuntested13542878(-) CCTTCA/CCTCTC 2 -- int10--------
    rs1994759381,2
    Cuntested13549191(-) AATGCC/TCTCCT 3 A syn10--------
    rs1994759371,2
    Cuntested13549285(-) TTTCAA/GGAGCG 3 K R mis10--------
    rs1994759351,2
    Cuntested13550159(-) AGCCCA/GGCCTG 3 S G mis10--------
    rs1994762761,2
    Cuntested13550633(-) CCACTA/CTTCCC 2 -- int10--------
    rs1994759331,2
    Cuntested13550805(-) CAGCCA/GAGCAG 3 K E mis10--------
    rs1819533311,2
    --3524363(+) ACATAC/GGAATA 2 -- ds50010--------
    rs747799911,2
    C,F--3524364(+) CATACG/AAATAG 2 -- ds50012Minor allele frequency- A:0.08NA EA 240

    HapMap Linkage Disequilibrium report for NLRC3 (3589033 - 3627401 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 7 variations for NLRC3:    About this table    
    Variant IDTypeSubtypePubMed ID
    esv2750410CNV Deletion23290073
    nsv1716CNV Insertion18451855
    nsv905213CNV Loss21882294
    nsv833128CNV Loss17160897
    nsv905217CNV Loss21882294
    nsv517451CNV Loss19592680
    nsv905216CNV Loss21882294

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    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 615648    OMIM disorders: --

    3 diseases for NLRC3:    
    About MalaCards
    burns    wegener's granulomatosis    crohn's disease


    NLRC3 for disorders           About GeneDecksing


    Export disorders for NLRC3 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for NLRC3 gene, integrated from 10 sources (see all 12):
    (articles sorted by number of sources associating them with NLRC3)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. CATERPILLER 16.2 (CLR16.2), a novel NBD/LRR family member that negatively regulates T cell function. (PubMed id 15705585)1, 2, 3 Conti B.J....Ting J.P.-Y. (J. Biol. Chem. 2005)
    2. NODs: intracellular proteins involved in inflammation and apoptosis. (PubMed id 12766759)1, 2, 3 Inohara N. and Nunez G. (Nat. Rev. Immunol. 2003)
    3. NLRC3, a Member of the NLR Family of Proteins, Is a Negative Regulator of Innate Immune Signaling Induced by the DNA Sensor STING. (PubMed id 24560620)1 Zhang L....Ting J.P. (Immunity 2014)
    4. Unsolved Mysteries in NLR Biology. (PubMed id 24062750)1 Lupfer C. and Kanneganti T.D. (Front Immunol 2013)
    5. The innate immune sensor NLRC3 attenuates Toll-like receptor signaling via modification of the signaling adaptor TRAF6 and transcription factor NF-I_B. (PubMed id 22863753)1 Schneider M....Ting J.P. (Nat. Immunol. 2012)
    6. Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition. (PubMed id 22505724)1 Udeshi N.D....Carr S.A. (amp 2012)
    7. Post-transcriptional inhibition of luciferase reporter assays by the Nod-like receptor proteins NLRX1 and NLRC3. (PubMed id 22718770)1 Ling A....Girardin S.E. (J. Biol. Chem. 2012)
    8. Genome-scale RNAi screen for host factors required for HIV replication. (PubMed id 18976975)1 Zhou H....Espeseth A.S. (amp 2008)
    9. Downregulation of immune signaling genes in patients with large surface burn injury. (PubMed id 17925653)1 Moore C.B....Cairns B.A. (amp 2007)
    10. CATERPILLER: a novel gene family important in immunity, cell death, and diseases. (PubMed id 15771576)2 Ting J.P.-Y. and Davis B.K. (Annu. Rev. Immunol. 2005)

    (in PubMed, OMIM, and NCBI Bookshelf)
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    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 197358 HGNC: 29889 AceView: NOD3 Ensembl:ENSG00000167984 euGenes: HUgn197358
    ECgene: NLRC3 H-InvDB: NLRC3

    (According to HUGE)
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    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    PharmGKB entry for NLRC3 Pharmacogenomics, SNPs, Pathways

    (Patent information from GeneIP,
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    Patent Information for NLRC3 gene:
    Search GeneIP for patents involving NLRC3

    GeneCards and IP:
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