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Q8K3Z0 (NOD2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 109. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Nucleotide-binding oligomerization domain-containing protein 2
Alternative name(s):
Caspase recruitment domain-containing protein 15
Gene names
Name:Nod2
Synonyms:Card15
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1020 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Recognizes muramyl dipeptide (MDP) constituents of bacterial peptidoglycans and plays a key role in gastrointestinal immunity: upon stimulation, binds the proximal adapter receptor-interacting RIPK2, which recruits ubiquitin ligases as XIAP, BIRC2, BIRC3 and the LUBAC complex, triggering activation of MAP kinases and activation of NF-kappa-B signaling, leading to activate the transcription of hundreds of genes involved in immune response. Ref.4

Subunit structure

Found in a signaling complex consisting of ARHGEF2, NOD2 and RIPK2. Interacts (via CARD domain) with RIPK2 (via CARD domain). Interacts with ATG16L1 By similarity. Interacts with CARD9. Ref.3

Subcellular location

Cytoplasm By similarity.

Domain

The ATG16L1-binding motif mediates interaction with ATG16L1 By similarity.

Sequence similarities

Contains 2 CARD domains.

Contains 10 LRR (leucine-rich) repeats.

Contains 1 NACHT domain.

Sequence caution

The sequence AAH44774.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Biological processImmunity
Innate immunity
   Cellular componentCytoplasm
   Coding sequence diversityAlternative splicing
   DomainLeucine-rich repeat
Repeat
   LigandATP-binding
Nucleotide-binding
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactivation of MAPK activity involved in innate immune response

Inferred from direct assay PubMed 21156799. Source: BHF-UCL

activation of immune response

Inferred from mutant phenotype PubMed 15692051. Source: MGI

cellular response to muramyl dipeptide

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to peptidoglycan

Inferred from mutant phenotype PubMed 16949315. Source: MGI

cytokine production involved in immune response

Inferred from sequence or structural similarity. Source: UniProtKB

defense response

Traceable author statement PubMed 15967716. Source: HGNC

defense response to Gram-positive bacterium

Inferred from mutant phenotype PubMed 15692051PubMed 18261938PubMed 19139201. Source: MGI

defense response to bacterium

Inferred from sequence or structural similarity. Source: HGNC

detection of bacterium

Inferred from sequence or structural similarity. Source: HGNC

detection of biotic stimulus

Traceable author statement PubMed 15967716. Source: HGNC

detection of muramyl dipeptide

Inferred from sequence or structural similarity. Source: HGNC

immunoglobulin production involved in immunoglobulin mediated immune response

Inferred from mutant phenotype PubMed 15692051. Source: MGI

inflammatory response

Traceable author statement PubMed 15967716. Source: HGNC

innate immune response

Inferred from sequence or structural similarity. Source: UniProtKB

innate immune response in mucosa

Inferred from mutant phenotype PubMed 15692051. Source: MGI

intracellular signal transduction

Inferred from sequence or structural similarity. Source: UniProtKB

macrophage inflammatory protein-1 alpha production

Inferred from mutant phenotype PubMed 19139201. Source: MGI

negative regulation of NF-kappaB transcription factor activity

Inferred from mutant phenotype PubMed 15220916. Source: MGI

negative regulation of T cell mediated immunity

Inferred from mutant phenotype PubMed 16949315. Source: MGI

negative regulation of growth of symbiont in host

Inferred from mutant phenotype PubMed 19139201. Source: MGI

negative regulation of inflammatory response to antigenic stimulus

Inferred from mutant phenotype PubMed 16949315. Source: MGI

negative regulation of interferon-gamma production

Inferred from mutant phenotype PubMed 15220916PubMed 19139201. Source: MGI

negative regulation of interleukin-12 production

Inferred from direct assay PubMed 15220916. Source: MGI

negative regulation of interleukin-18 production

Inferred from mutant phenotype PubMed 15220916. Source: MGI

negative regulation of interleukin-2 production

Inferred from mutant phenotype PubMed 19139201. Source: MGI

negative regulation of macrophage apoptotic process

Inferred from direct assay PubMed 21156799. Source: BHF-UCL

negative regulation of toll-like receptor 2 signaling pathway

Inferred from mutant phenotype PubMed 15220916. Source: MGI

negative regulation of tumor necrosis factor production

Inferred from mutant phenotype PubMed 19139201. Source: MGI

nucleotide-binding oligomerization domain containing 2 signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of ERK1 and ERK2 cascade

Inferred from direct assay PubMed 21156799. Source: BHF-UCL

positive regulation of I-kappaB kinase/NF-kappaB signaling

Inferred from sequence or structural similarity. Source: HGNC

positive regulation of JNK cascade

Inferred from direct assay PubMed 18261938. Source: MGI

positive regulation of MAPK cascade

Inferred from mutant phenotype PubMed 15692051. Source: MGI

positive regulation of NF-kappaB transcription factor activity

Inferred from sequence or structural similarity. Source: HGNC

positive regulation of Notch signaling pathway

Inferred from direct assay PubMed 21156799. Source: BHF-UCL

positive regulation of antibacterial peptide biosynthetic process

Inferred from direct assay PubMed 18167348. Source: MGI

positive regulation of biosynthetic process of antibacterial peptides active against Gram-positive bacteria

Inferred from mutant phenotype PubMed 15692051. Source: MGI

positive regulation of dendritic cell antigen processing and presentation

Inferred from mutant phenotype PubMed 20008287. Source: BHF-UCL

positive regulation of epithelial cell proliferation

Inferred from mutant phenotype PubMed 18855982. Source: BHF-UCL

positive regulation of humoral immune response mediated by circulating immunoglobulin

Inferred from mutant phenotype PubMed 15692051. Source: MGI

positive regulation of innate immune response

Inferred from mutant phenotype PubMed 15692051. Source: MGI

positive regulation of interleukin-1 beta secretion

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of interleukin-10 production

Inferred from mutant phenotype PubMed 21156799. Source: BHF-UCL

positive regulation of interleukin-12 production

Inferred from direct assay PubMed 15220916. Source: MGI

positive regulation of interleukin-17 production

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of interleukin-6 production

Inferred from direct assay PubMed 18261938. Source: MGI

positive regulation of nitric-oxide synthase biosynthetic process

Inferred from mutant phenotype PubMed 21156799. Source: BHF-UCL

positive regulation of oxidoreductase activity

Inferred from direct assay PubMed 21156799. Source: BHF-UCL

positive regulation of peptidyl-tyrosine phosphorylation

Inferred from mutant phenotype PubMed 15692051. Source: MGI

positive regulation of phagocytosis

Inferred from mutant phenotype PubMed 19139201. Source: MGI

positive regulation of phosphatidylinositol 3-kinase activity

Inferred from mutant phenotype PubMed 21156799. Source: BHF-UCL

positive regulation of prostaglandin-E synthase activity

Inferred from direct assay PubMed 21156799. Source: BHF-UCL

positive regulation of prostaglandin-endoperoxide synthase activity

Inferred from direct assay PubMed 21156799. Source: BHF-UCL

positive regulation of protein ubiquitination

Inferred from direct assay PubMed 15620648. Source: UniProtKB

positive regulation of stress-activated MAPK cascade

Inferred from direct assay PubMed 18261938. Source: MGI

positive regulation of transcription from RNA polymerase II promoter

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of tumor necrosis factor production

Inferred from direct assay PubMed 18261938. Source: MGI

positive regulation of type 2 immune response

Inferred from sequence or structural similarity. Source: BHF-UCL

protein oligomerization

Traceable author statement PubMed 15967716. Source: HGNC

regulation of inflammatory response

Inferred from mutant phenotype PubMed 19218085. Source: MGI

regulation of neutrophil chemotaxis

Inferred from mutant phenotype PubMed 19139201. Source: MGI

response to exogenous dsRNA

Inferred from mutant phenotype PubMed 15692051. Source: MGI

response to lipopolysaccharide

Inferred from mutant phenotype PubMed 14560001PubMed 15692051. Source: MGI

response to muramyl dipeptide

Inferred from sequence or structural similarity. Source: HGNC

response to peptidoglycan

Inferred from direct assay PubMed 15220916. Source: MGI

signal transduction

Traceable author statement PubMed 15967716. Source: HGNC

   Cellular_componentcell surface

Inferred from sequence or structural similarity. Source: UniProtKB

cytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

cytoskeleton

Inferred from sequence or structural similarity. Source: UniProtKB

cytosol

Inferred from sequence or structural similarity. Source: HGNC

plasma membrane

Inferred from sequence or structural similarity. Source: HGNC

protein complex

Inferred from sequence or structural similarity. Source: UniProtKB

vesicle

Inferred from sequence or structural similarity. Source: HGNC

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

CARD domain binding

Inferred from sequence or structural similarity. Source: HGNC

endodeoxyribonuclease activity, producing 5'-phosphomonoesters

Inferred from electronic annotation. Source: InterPro

enzyme binding

Inferred from sequence or structural similarity. Source: HGNC

muramyl dipeptide binding

Inferred from sequence or structural similarity. Source: HGNC

peptidoglycan binding

Inferred from sequence or structural similarity. Source: HGNC

protein kinase binding

Inferred from sequence or structural similarity. Source: HGNC

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8K3Z0-1)

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.
Isoform 2 (identifier: Q8K3Z0-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-7: Missing.
     195-195: E → EGYSLCRSRCDRGFTLICLFCIL
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 10201020Nucleotide-binding oligomerization domain-containing protein 2
PRO_0000144091

Regions

Domain6 – 10499CARD 1
Domain106 – 20095CARD 2
Domain273 – 600328NACHT
Repeat685 – 70925LRR 1
Repeat726 – 74924LRR 2
Repeat766 – 79227LRR 3
Repeat794 – 81724LRR 4
Repeat822 – 84524LRR 5
Repeat850 – 87324LRR 6
Repeat906 – 92924LRR 7
Repeat934 – 96229LRR 8
Repeat963 – 98523LRR 9
Repeat1005 – 101915LRR 10
Motif43 – 5715ATG16L1-binding motif

Natural variations

Alternative sequence1 – 77Missing in isoform 2.
VSP_007069
Alternative sequence1951E → EGYSLCRSRCDRGFTLICLF CIL in isoform 2.
VSP_007070
Natural variant2121T → A in strain: NMRI. Ref.2
Natural variant2401Q → R in strain: NMRI. Ref.2
Natural variant4221L → C in strain: NMRI; requires 2 nucleotide substitutions. Ref.2
Natural variant4851G → V in strain: NMRI. Ref.2
Natural variant6031V → A in strain: NMRI. Ref.2
Natural variant6751V → I in strain: NMRI. Ref.2
Natural variant9251E → Q in strain: NMRI. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 1, 2002. Version 1.
Checksum: 25504905ECF70FBB

FASTA1,020113,562
        10         20         30         40         50         60 
MRSSCCDMCS QEEFQAQRSQ LVALLISGSL EGFESILDWL LSWDVLSRED YEGLSLPGQP 

        70         80         90        100        110        120 
LSHSARRLLD TVWNKGVWGC QKLLEAVQEA QANSHTFELY GSWDTHSLHP TRDLQSHRPA 

       130        140        150        160        170        180 
IVRRLYNHVE AMLELAREGG FLSQYECEEI RLPIFTSSQR ARRLLDLAAV KANGLAAFLL 

       190        200        210        220        230        240 
QHVRELPAPL PLPYEAAECQ KFISKLRTMV LTQSRFLSTY DGSENLCLED IYTENILELQ 

       250        260        270        280        290        300 
TEVGTAGALQ KSPAILGLED LFDTHGHLNR DADTILVVGE AGSGKSTLLQ RLHLLWATGR 

       310        320        330        340        350        360 
SFQEFLFIFP FSCRQLQCVA KPLSLRTLLF EHCCWPDVAQ DDVFQFLLDH PDRVLLTFDG 

       370        380        390        400        410        420 
LDEFKFRFTD RERHCSPIDP TSVQTLLFNL LQGNLLKNAC KVLTSRPDAV SALLRKFVRT 

       430        440        450        460        470        480 
ELQLKGFSEE GIQLYLRKHH REPGVADRLI QLIQATSALH GLCHLPVFSW MVSRCHRELL 

       490        500        510        520        530        540 
LQNRGFPTTS TDMYLLILQH FLLHASPPDS SPLGLGPGLL QSRLSTLLHL GHLALRGLAM 

       550        560        570        580        590        600 
SCYVFSAQQL QAAQVDSDDI SLGFLVRAQS SVPGSKAPLE FLHITFQCFF AAFYLAVSAD 

       610        620        630        640        650        660 
TSVASLKHLF SCGRLGSSLL GRLLPNLCIQ GSRVKKGSEA ALLQKAEPHN LQITAAFLAG 

       670        680        690        700        710        720 
LLSQQHRDLL AACQVSERVL LQRQARARSC LAHSLREHFH SIPPAVPGET KSMHAMPGFI 

       730        740        750        760        770        780 
WLIRSLYEMQ EEQLAQEAVR RLDIGHLKLT FCRVGPAECA ALAFVLQHLQ RPVALQLDYN 

       790        800        810        820        830        840 
SVGDVGVEQL RPCLGVCTAL YLRDNNISDR GARTLVECAL RCEQLQKLAL FNNKLTDACA 

       850        860        870        880        890        900 
CSMAKLLAHK QNFLSLRVGN NHITAAGAEV LAQGLKSNTS LKFLGFWGNS VGDKGTQALA 

       910        920        930        940        950        960 
EVVADHQNLK WLSLVGNNIG SMGAEALALM LEKNKSLEEL CLEENHICDE GVYSLAEGLK 

       970        980        990       1000       1010       1020 
RNSTLKFLKL SNNGITYRGA EALLQALSRN SAILEVWLRG NTFSLEEIQT LSSRDARLLL 

« Hide

Isoform 2 [UniParc].

Checksum: 7F0E533DC98068FD
Show »

FASTA1,035115,301

References

« Hide 'large scale' references
[1]"Cloning, sequencing and expression analysis of the mouse Nod2/Card15 gene."
Iwanaga Y., Davey M.P., Martin T.M., Planck S.R., DePriest M.L., Baugh M.M., Suing C.M., Rosenbaum J.T.
Inflamm. Res. 52:272-276(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Strain: BALB/c.
Tissue: Monocyte.
[2]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANTS ALA-212; ARG-240; CYS-422; VAL-485; ALA-603; ILE-675 AND GLN-925.
Strain: NMRI.
Tissue: Mammary cancer.
[3]"The adaptor protein CARD9 is required for innate immune responses to intracellular pathogens."
Hsu Y.M., Zhang Y., You Y., Wang D., Li H., Duramad O., Qin X.F., Dong C., Lin X.
Nat. Immunol. 8:198-205(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CARD9.
[4]"The ubiquitin ligase XIAP recruits LUBAC for NOD2 signaling in inflammation and innate immunity."
Damgaard R.B., Nachbur U., Yabal M., Wong W.W., Fiil B.K., Kastirr M., Rieser E., Rickard J.A., Bankovacki A., Peschel C., Ruland J., Bekker-Jensen S., Mailand N., Kaufmann T., Strasser A., Walczak H., Silke J., Jost P.J., Gyrd-Hansen M.
Mol. Cell 46:746-758(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF520774 mRNA. Translation: AAM76073.1.
BC044774 mRNA. Translation: AAH44774.1. Different initiation.
UniGeneMm.222633.

3D structure databases

ProteinModelPortalQ8K3Z0.
SMRQ8K3Z0. Positions 104-191, 747-1004.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-46115N.

PTM databases

PhosphoSiteQ8K3Z0.

Proteomic databases

PRIDEQ8K3Z0.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000054324; ENSMUSP00000050538; ENSMUSG00000055994. [Q8K3Z0-2]
ENSMUST00000109634; ENSMUSP00000105262; ENSMUSG00000055994. [Q8K3Z0-1]
UCSCuc009mrq.1. mouse. [Q8K3Z0-1]

Organism-specific databases

MGIMGI:2429397. Nod2.

Phylogenomic databases

eggNOGNOG248107.
GeneTreeENSGT00710000106284.
HOGENOMHOG000113814.
HOVERGENHBG050792.
OMAVWNKGTW.
PhylomeDBQ8K3Z0.
TreeFamTF352118.

Enzyme and pathway databases

ReactomeREACT_98458. Immune System.

Gene expression databases

ArrayExpressQ8K3Z0.
BgeeQ8K3Z0.
GenevestigatorQ8K3Z0.

Family and domain databases

Gene3D1.10.533.10. 2 hits.
InterProIPR001315. CARD.
IPR011029. DEATH-like_dom.
IPR018228. DNase_TatD-rel_CS.
IPR007111. NACHT_NTPase.
IPR027417. P-loop_NTPase.
[Graphical view]
PfamPF00619. CARD. 2 hits.
[Graphical view]
SUPFAMSSF47986. SSF47986. 2 hits.
SSF52540. SSF52540. 1 hit.
PROSITEPS50209. CARD. 2 hits.
PS50837. NACHT. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

PROQ8K3Z0.
SOURCESearch...

Entry information

Entry nameNOD2_MOUSE
AccessionPrimary (citable) accession number: Q8K3Z0
Entry history
Integrated into UniProtKB/Swiss-Prot: March 28, 2003
Last sequence update: October 1, 2002
Last modified: April 16, 2014
This is version 109 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot