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Protein

NLR family CARD domain-containing protein 3

Gene

NLRC3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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).By similarity3 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi145 – 152ATPPROSITE-ProRule annotation8

GO - Molecular functioni

GO - Biological processi

Keywordsi

LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-3270619. IRF3-mediated induction of type I IFN.

Names & Taxonomyi

Protein namesi
Recommended name:
NLR family CARD domain-containing protein 3
Alternative name(s):
CARD15-like protein
Caterpiller protein 16.21 Publication
Short name:
CLR16.21 Publication
NACHT, LRR and CARD domains-containing protein 3
Nucleotide-binding oligomerization domain protein 3
Gene namesi
Name:NLRC3
Synonyms:NOD3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

HGNCiHGNC:29889. NLRC3.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: HPA
  • microtubule organizing center Source: HPA
  • perinuclear region of cytoplasm Source: UniProtKB

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi457 – 460SLQE → AAAA: Strong decrease of TRAF6-binding. 1 Publication4
Mutagenesisi582 – 585SVEE → AAAA: Almost no effect on TRAF6-binding. 1 Publication4

Organism-specific databases

DisGeNETi197358.
OpenTargetsiENSG00000167984.
PharmGKBiPA162397626.

Polymorphism and mutation databases

BioMutaiNLRC3.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002961871 – 1065NLR family CARD domain-containing protein 3Add BLAST1065

Proteomic databases

MaxQBiQ7RTR2.
PeptideAtlasiQ7RTR2.
PRIDEiQ7RTR2.
TopDownProteomicsiQ7RTR2-3. [Q7RTR2-3]

PTM databases

iPTMnetiQ7RTR2.
PhosphoSitePlusiQ7RTR2.

Expressioni

Inductioni

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).2 Publications

Gene expression databases

BgeeiENSG00000167984.
CleanExiHS_NLRC3.
ExpressionAtlasiQ7RTR2. baseline and differential.
GenevisibleiQ7RTR2. HS.

Organism-specific databases

HPAiHPA048062.

Interactioni

Subunit structurei

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).By similarity3 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi128254. 1 interactor.
IntActiQ7RTR2. 1 interactor.

Structurei

3D structure databases

ProteinModelPortaliQ7RTR2.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini139 – 460NACHTPROSITE-ProRule annotationAdd BLAST322
Repeati617 – 639LRR 1Add BLAST23
Repeati641 – 663LRR 2Add BLAST23
Repeati665 – 688LRR 3Add BLAST24
Repeati693 – 716LRR 4Add BLAST24
Repeati721 – 744LRR 5Add BLAST24
Repeati749 – 772LRR 6Add BLAST24
Repeati777 – 800LRR 7Add BLAST24
Repeati805 – 828LRR 8Add BLAST24
Repeati833 – 856LRR 9Add BLAST24
Repeati861 – 884LRR 10Add BLAST24
Repeati889 – 912LRR 11Add BLAST24
Repeati917 – 940LRR 12Add BLAST24
Repeati945 – 968LRR 13Add BLAST24
Repeati973 – 996LRR 14Add BLAST24
Repeati1001 – 1029LRR 15Add BLAST29
Repeati1031 – 1052LRR 16Add BLAST22

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi457 – 460TRAF6-binding1 Publication4

Domaini

The leucine-rich repeat domain may reduce the interaction with TMEM173/STING.1 Publication

Sequence similaritiesi

Belongs to the NLRP family.Curated

Keywords - Domaini

Leucine-rich repeat, Repeat

Phylogenomic databases

GeneTreeiENSGT00860000133673.
HOGENOMiHOG000108875.
HOVERGENiHBG055285.
InParanoidiQ7RTR2.
PhylomeDBiQ7RTR2.

Family and domain databases

InterProiView protein in InterPro
IPR001611. Leu-rich_rpt.
IPR007111. NACHT_NTPase.
PfamiView protein in Pfam
PF13516. LRR_6. 12 hits.
PROSITEiView protein in PROSITE
PS50837. NACHT. 1 hit.

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q7RTR2-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MRKQEVRTGR EAGQGHGTGS PAEQVKALMD LLAGKGSQGS QAPQALDRTP
60 70 80 90 100
DAPLGPCSND SRIQRHRKAL LSKVGGGPEL GGPWHRLASL LLVEGLTDLQ
110 120 130 140 150
LREHDFTQVE ATRGGGHPAR TVALDRLFLP LSRVSVPPRV SITIGVAGMG
160 170 180 190 200
KTTLVRHFVR LWAHGQVGKD FSLVLPLTFR DLNTHEKLCA DRLICSVFPH
210 220 230 240 250
VGEPSLAVAV PARALLILDG LDECRTPLDF SNTVACTDPK KEIPVDHLIT
260 270 280 290 300
NIIRGNLFPE VSIWITSRPS ASGQIPGGLV DRMTEIRGFN EEEIKVCLEQ
310 320 330 340 350
MFPEDQALLG WMLSQVQADR ALYLMCTVPA FCRLTGMALG HLWRSRTGPQ
360 370 380 390 400
DAELWPPRTL CELYSWYFRM ALSGEGQEKG KASPRIEQVA HGGRKMVGTL
410 420 430 440 450
GRLAFHGLLK KKYVFYEQDM KAFGVDLALL QGAPCSCFLQ REETLASSVA
460 470 480 490 500
YCFTHLSLQE FVAAAYYYGA SRRAIFDLFT ESGVSWPRLG FLTHFRSAAQ
510 520 530 540 550
RAMQAEDGRL DVFLRFLSGL LSPRVNALLA GSLLAQGEHQ AYRTQVAELL
560 570 580 590 600
QGCLRPDAAV CARAINVLHC LHELQHTELA RSVEEAMESG ALARLTGPAH
610 620 630 640 650
RAALAYLLQV SDACAQEANL SLSLSQGVLQ SLLPQLLYCR KLRLDTNQFQ
660 670 680 690 700
DPVMELLGSV LSGKDCRIQK ISLAENQISN KGAKALARSL LVNRSLTSLD
710 720 730 740 750
LRGNSIGPQG AKALADALKI NRTLTSLSLQ GNTVRDDGAR SMAEALASNR
760 770 780 790 800
TLSMLHLQKN SIGPMGAQRM ADALKQNRSL KELMFSSNSI GDGGAKALAE
810 820 830 840 850
ALKVNQGLES LDLQSNSISD AGVAALMGAL CTNQTLLSLS LRENSISPEG
860 870 880 890 900
AQAIAHALCA NSTLKNLDLT ANLLHDQGAR AIAVAVRENR TLTSLHLQWN
910 920 930 940 950
FIQAGAAQAL GQALQLNRSL TSLDLQENAI GDDGACAVAR ALKVNTALTA
960 970 980 990 1000
LYLQVASIGA SGAQVLGEAL AVNRTLEILD LRGNAIGVAG AKALANALKV
1010 1020 1030 1040 1050
NSSLRRLNLQ ENSLGMDGAI CIATALSGNH RLQHINLQGN HIGDSGARMI
1060
SEAIKTNAPT CTVEM
Length:1,065
Mass (Da):114,658
Last modified:July 24, 2007 - v2
Checksum:i9BFFCB21FD134562
GO
Isoform 2 (identifier: Q7RTR2-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MEMDAPRPPSLAVPGAASRPGRLLDGGHGRQQVQALSSQLLEVIPDS

Show »
Length:1,111
Mass (Da):119,415
Checksum:iFEE1E4406C56A5B4
GO
Isoform 3 (identifier: Q7RTR2-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     728-761: SLQGNTVRDDGARSMAEALASNRTLSMLHLQKNS → RVKFMYHKIDCFRRVPEADACNPSTLGGQGRWIT
     762-1065: Missing.

Note: No experimental confirmation available.
Show »
Length:761
Mass (Da):83,456
Checksum:iD15C62D5D14362DF
GO
Isoform 4 (identifier: Q7RTR2-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     869-896: Missing.

Note: No experimental confirmation available.
Show »
Length:1,037
Mass (Da):111,634
Checksum:i3773D36A3AA54050
GO

Sequence cautioni

The sequence BAC03412 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti41Q → H in DAA01245 (PubMed:12766759).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_034606567V → M. Corresponds to variant dbSNP:rs8057436Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0271351M → MEMDAPRPPSLAVPGAASRP GRLLDGGHGRQQVQALSSQL LEVIPDS in isoform 2. 1 Publication1
Alternative sequenceiVSP_027136728 – 761SLQGN…LQKNS → RVKFMYHKIDCFRRVPEADA CNPSTLGGQGRWIT in isoform 3. 1 PublicationAdd BLAST34
Alternative sequenceiVSP_027137762 – 1065Missing in isoform 3. 1 PublicationAdd BLAST304
Alternative sequenceiVSP_027138869 – 896Missing in isoform 4. 1 PublicationAdd BLAST28

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BK001112 mRNA. Translation: DAA01245.1.
AY601811 mRNA. Translation: AAT48367.1.
AK090431 mRNA. Translation: BAC03412.1. Different initiation.
AK074109 mRNA. Translation: BAB84935.1.
AF501291 mRNA. Translation: AAM22459.1.
AF501292 mRNA. Translation: AAM22460.1.
CCDSiCCDS73817.1. [Q7RTR2-1]
RefSeqiNP_849172.2. NM_178844.3. [Q7RTR2-1]
UniGeneiHs.592091.
Hs.741496.

Genome annotation databases

EnsembliENST00000359128; ENSP00000352039; ENSG00000167984. [Q7RTR2-1]
ENST00000615877; ENSP00000482989; ENSG00000167984. [Q7RTR2-3]
GeneIDi197358.
KEGGihsa:197358.
UCSCiuc032dpc.2. human. [Q7RTR2-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BK001112 mRNA. Translation: DAA01245.1.
AY601811 mRNA. Translation: AAT48367.1.
AK090431 mRNA. Translation: BAC03412.1. Different initiation.
AK074109 mRNA. Translation: BAB84935.1.
AF501291 mRNA. Translation: AAM22459.1.
AF501292 mRNA. Translation: AAM22460.1.
CCDSiCCDS73817.1. [Q7RTR2-1]
RefSeqiNP_849172.2. NM_178844.3. [Q7RTR2-1]
UniGeneiHs.592091.
Hs.741496.

3D structure databases

ProteinModelPortaliQ7RTR2.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi128254. 1 interactor.
IntActiQ7RTR2. 1 interactor.

PTM databases

iPTMnetiQ7RTR2.
PhosphoSitePlusiQ7RTR2.

Polymorphism and mutation databases

BioMutaiNLRC3.

Proteomic databases

MaxQBiQ7RTR2.
PeptideAtlasiQ7RTR2.
PRIDEiQ7RTR2.
TopDownProteomicsiQ7RTR2-3. [Q7RTR2-3]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000359128; ENSP00000352039; ENSG00000167984. [Q7RTR2-1]
ENST00000615877; ENSP00000482989; ENSG00000167984. [Q7RTR2-3]
GeneIDi197358.
KEGGihsa:197358.
UCSCiuc032dpc.2. human. [Q7RTR2-1]

Organism-specific databases

CTDi197358.
DisGeNETi197358.
GeneCardsiNLRC3.
HGNCiHGNC:29889. NLRC3.
HPAiHPA048062.
MIMi615648. gene.
neXtProtiNX_Q7RTR2.
OpenTargetsiENSG00000167984.
PharmGKBiPA162397626.
GenAtlasiSearch...

Phylogenomic databases

GeneTreeiENSGT00860000133673.
HOGENOMiHOG000108875.
HOVERGENiHBG055285.
InParanoidiQ7RTR2.
PhylomeDBiQ7RTR2.

Enzyme and pathway databases

ReactomeiR-HSA-3270619. IRF3-mediated induction of type I IFN.

Miscellaneous databases

ChiTaRSiNLRC3. human.
GeneWikiiNLRC3.
GenomeRNAii197358.
PROiPR:Q7RTR2.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000167984.
CleanExiHS_NLRC3.
ExpressionAtlasiQ7RTR2. baseline and differential.
GenevisibleiQ7RTR2. HS.

Family and domain databases

InterProiView protein in InterPro
IPR001611. Leu-rich_rpt.
IPR007111. NACHT_NTPase.
PfamiView protein in Pfam
PF13516. LRR_6. 12 hits.
PROSITEiView protein in PROSITE
PS50837. NACHT. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiNLRC3_HUMAN
AccessioniPrimary (citable) accession number: Q7RTR2
Secondary accession number(s): Q5EY36
, Q8NF48, Q8NI01, Q8NI02, Q8TEL3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 24, 2007
Last sequence update: July 24, 2007
Last modified: June 7, 2017
This is version 118 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.