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Q9HC29 (NOD2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 144. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·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
Inflammatory bowel disease protein 1
Gene names
Name:NOD2
Synonyms:CARD15, IBD1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1040 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.7

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. Interacts with CARD9. Ref.4 Ref.5 Ref.6

Subcellular location

Cytoplasm.

Tissue specificity

Monocytes-specific.

Domain

The ATG16L1-binding motif mediates interaction with ATG16L1 (Ref.6).

Involvement in disease

Blau syndrome (BS) [MIM:186580]: Rare autosomal dominant disorder characterized by early-onset granulomatous arthritis, uveitis and skin rash.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8 Ref.10 Ref.11 Ref.12

Inflammatory bowel disease 1 (IBD1) [MIM:266600]: A chronic, relapsing inflammation of the gastrointestinal tract with a complex etiology. It is subdivided into Crohn disease and ulcerative colitis phenotypes. Crohn disease may affect any part of the gastrointestinal tract from the mouth to the anus, but most frequently it involves the terminal ileum and colon. Bowel inflammation is transmural and discontinuous; it may contain granulomas or be associated with intestinal or perianal fistulas. In contrast, in ulcerative colitis, the inflammation is continuous and limited to rectal and colonic mucosal layers; fistulas and granulomas are not observed. Both diseases include extraintestinal inflammation of the skin, eyes, or joints.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.2

Sarcoidosis early-onset (EOS) [MIM:609464]: A form of sarcoidosis manifesting in children younger than 4 years of age. Sarcoidosis is an idiopathic, systemic, inflammatory disease characterized by the formation of immune granulomas in involved organs. Granulomas predominantly invade the lungs and the lymphatic system, but also skin, liver, spleen, eyes and other organs may be involved. Early-onset sarcoidosis is quite rare and has a distinct triad of skin, joint and eye disorders, without apparent pulmonary involvement. Compared with an asymptomatic and sometimes naturally disappearing course of the disease in older children, early-onset sarcoidosis is progressive and in many cases causes severe complications, such as blindness, joint destruction and visceral involvement.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9

Sequence similarities

Contains 2 CARD domains.

Contains 9 LRR (leucine-rich) repeats.

Contains 1 NACHT domain.

Ontologies

Keywords
   Biological processImmunity
Innate immunity
   Cellular componentCytoplasm
   Coding sequence diversityAlternative initiation
Polymorphism
   DiseaseDisease mutation
   DomainLeucine-rich repeat
Repeat
   LigandATP-binding
Nucleotide-binding
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processJNK cascade

Traceable author statement. Source: Reactome

MyD88-dependent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

MyD88-independent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

TRIF-dependent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

activation of MAPK activity

Traceable author statement. Source: Reactome

activation of MAPK activity involved in innate immune response

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

cellular response to muramyl dipeptide

Inferred from direct assay Ref.5. Source: UniProtKB

cellular response to peptidoglycan

Inferred from electronic annotation. Source: Ensembl

cytokine production involved in immune response

Inferred from mutant phenotype PubMed 16260731. Source: UniProtKB

defense response

Traceable author statement PubMed 15967716. Source: HGNC

defense response to Gram-positive bacterium

Inferred from electronic annotation. Source: Ensembl

defense response to bacterium

Inferred from direct assay PubMed 15653568. Source: HGNC

detection of bacterium

Inferred from direct assay PubMed 15653568. Source: HGNC

detection of biotic stimulus

Traceable author statement PubMed 15967716. Source: HGNC

detection of muramyl dipeptide

Inferred from direct assay PubMed 15998797. Source: HGNC

immunoglobulin production involved in immunoglobulin mediated immune response

Inferred from electronic annotation. Source: Ensembl

innate immune response

Inferred from direct assay Ref.7. Source: UniProtKB

innate immune response in mucosa

Inferred from electronic annotation. Source: Ensembl

intracellular signal transduction

Inferred from direct assay PubMed 15653568. Source: HGNC

macrophage inflammatory protein-1 alpha production

Inferred from electronic annotation. Source: Ensembl

maintenance of gastrointestinal epithelium

Inferred from mutant phenotype PubMed 17058067. Source: UniProt

microglial cell activation involved in immune response

Inferred from electronic annotation. Source: Ensembl

negative regulation of NF-kappaB transcription factor activity

Inferred from electronic annotation. Source: Ensembl

negative regulation of T cell mediated immunity

Inferred from electronic annotation. Source: Ensembl

negative regulation of growth of symbiont in host

Inferred from electronic annotation. Source: Ensembl

negative regulation of inflammatory response to antigenic stimulus

Inferred from electronic annotation. Source: Ensembl

negative regulation of interferon-gamma production

Inferred from electronic annotation. Source: Ensembl

negative regulation of interleukin-12 production

Inferred from electronic annotation. Source: Ensembl

negative regulation of interleukin-18 production

Inferred from electronic annotation. Source: Ensembl

negative regulation of interleukin-2 production

Inferred from electronic annotation. Source: Ensembl

negative regulation of macrophage apoptotic process

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

negative regulation of toll-like receptor 2 signaling pathway

Inferred from electronic annotation. Source: Ensembl

negative regulation of tumor necrosis factor production

Inferred from electronic annotation. Source: Ensembl

nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway

Traceable author statement. Source: Reactome

nucleotide-binding oligomerization domain containing 2 signaling pathway

Inferred from direct assay Ref.7. Source: UniProtKB

nucleotide-binding oligomerization domain containing signaling pathway

Traceable author statement. Source: Reactome

pathogen-associated molecular pattern dependent induction by symbiont of host innate immune response

Inferred from electronic annotation. Source: Ensembl

positive regulation of B cell activation

Inferred from direct assay PubMed 20844241. Source: BHF-UCL

positive regulation of ERK1 and ERK2 cascade

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

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

Inferred from direct assay Ref.1. Source: UniProtKB

positive regulation of JNK cascade

Inferred from direct assay PubMed 17187069. Source: MGI

positive regulation of NF-kappaB transcription factor activity

Inferred from direct assay PubMed 11385577Ref.5. Source: UniProtKB

positive regulation of Notch signaling pathway

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

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

Inferred from electronic annotation. Source: Ensembl

positive regulation of dendritic cell antigen processing and presentation

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

positive regulation of dendritic cell cytokine production

Inferred from electronic annotation. Source: Ensembl

positive regulation of epithelial cell proliferation

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

positive regulation of gamma-delta T cell activation

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

positive regulation of humoral immune response mediated by circulating immunoglobulin

Inferred from electronic annotation. Source: Ensembl

positive regulation of interleukin-1 beta production

Inferred from mutant phenotype PubMed 21040358. Source: BHF-UCL

positive regulation of interleukin-1 beta secretion

Inferred from direct assay PubMed 15107016. Source: HGNC

positive regulation of interleukin-10 production

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

positive regulation of interleukin-12 production

Inferred from electronic annotation. Source: Ensembl

positive regulation of interleukin-17 production

Inferred from mutant phenotype PubMed 17919942. Source: UniProtKB

positive regulation of interleukin-6 production

Inferred from direct assay PubMed 16414084. Source: BHF-UCL

positive regulation of nitric-oxide synthase biosynthetic process

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

positive regulation of oxidoreductase activity

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

positive regulation of peptidyl-tyrosine phosphorylation

Inferred from electronic annotation. Source: Ensembl

positive regulation of phagocytosis

Inferred from electronic annotation. Source: Ensembl

positive regulation of phosphatidylinositol 3-kinase activity

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

positive regulation of prostaglandin-E synthase activity

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

positive regulation of prostaglandin-endoperoxide synthase activity

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

positive regulation of stress-activated MAPK cascade

Inferred from direct assay PubMed 17187069. Source: MGI

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay Ref.5. Source: UniProtKB

positive regulation of tumor necrosis factor production

Inferred from mutant phenotype PubMed 21040358. Source: BHF-UCL

positive regulation of type 2 immune response

Inferred from mutant phenotype PubMed 21172192. Source: BHF-UCL

protein oligomerization

Traceable author statement PubMed 15967716. Source: HGNC

regulation of inflammatory response

Inferred by curator PubMed 11385577. Source: BHF-UCL

regulation of neutrophil chemotaxis

Inferred from electronic annotation. Source: Ensembl

response to exogenous dsRNA

Inferred from electronic annotation. Source: Ensembl

response to lipopolysaccharide

Inferred from electronic annotation. Source: Ensembl

response to muramyl dipeptide

Inferred from direct assay PubMed 16414084. Source: BHF-UCL

response to nutrient

Inferred from electronic annotation. Source: Ensembl

stress-activated MAPK cascade

Traceable author statement. Source: Reactome

toll-like receptor 10 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 3 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 4 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 5 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 9 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor TLR1:TLR2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor TLR6:TLR2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

   Cellular_componentcell surface

Inferred from direct assay PubMed 16714539. Source: UniProtKB

cytoplasm

Inferred from direct assay Ref.5. Source: UniProtKB

cytoskeleton

Inferred from direct assay Ref.5. Source: UniProtKB

cytosol

Inferred from direct assay PubMed 15998797. Source: HGNC

plasma membrane

Inferred from direct assay PubMed 15998797. Source: HGNC

protein complex

Inferred from direct assay Ref.5. Source: UniProtKB

vesicle

Inferred from direct assay Ref.5. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

CARD domain binding

Inferred from physical interaction Ref.1. Source: UniProtKB

enzyme binding

Inferred from physical interaction PubMed 15753091. Source: UniProtKB

muramyl dipeptide binding

Inferred from direct assay PubMed 15998797. Source: HGNC

peptidoglycan binding

Inferred from direct assay PubMed 15998797. Source: HGNC

protein binding

Inferred from physical interaction PubMed 11472070PubMed 16714539PubMed 17337451Ref.6. Source: UniProtKB

protein kinase binding

Inferred from physical interaction PubMed 15075345. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative initiation. [Align] [Select]
Isoform 1 (identifier: Q9HC29-1)

Also known as: Nod2;

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.
Note: Can activate NF-kappa-B. More abundant.
Isoform 2 (identifier: Q9HC29-2)

Also known as: Nod2b;

The sequence of this isoform differs from the canonical sequence as follows:
     1-27: Missing.
Note: Can activate NF-kappa-B.
Isoform 3 (identifier: Q9HC29-3)

Also known as: NOD2-C2;

The sequence of this isoform differs from the canonical sequence as follows:
     1-27: Missing.
     216-224: AATCKKYMA → DERTEAQKG
     225-1040: Missing.
Note: Can activate NF-kappa-B.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 10401040Nucleotide-binding oligomerization domain-containing protein 2
PRO_0000004418

Regions

Domain26 – 12297CARD 1
Domain126 – 21893CARD 2
Domain293 – 618326NACHT
Repeat791 – 81222LRR 1
Repeat816 – 83924LRR 2
Repeat844 – 86522LRR 3
Repeat872 – 88413LRR 4
Repeat900 – 92021LRR 5
Repeat928 – 94922LRR 6
Repeat956 – 97621LRR 7
Repeat984 – 100522LRR 8
Repeat1012 – 103221LRR 9
Nucleotide binding299 – 3068ATP Potential
Motif63 – 7715ATG16L1-binding motif

Natural variations

Alternative sequence1 – 2727Missing in isoform 2 and isoform 3.
VSP_018689
Alternative sequence216 – 2249AATCKKYMA → DERTEAQKG in isoform 3.
VSP_046567
Alternative sequence225 – 1040816Missing in isoform 3.
VSP_046568
Natural variant811L → V.
Corresponds to variant rs34936594 [ dbSNP | Ensembl ].
VAR_036871
Natural variant1401A → T Associated with Crohn disease and ulcerative colitis. Ref.2
Corresponds to variant rs34684955 [ dbSNP | Ensembl ].
VAR_012665
Natural variant1571W → R Associated with Crohn disease. Ref.2
VAR_012666
Natural variant1891T → M. Ref.2
Corresponds to variant rs61755182 [ dbSNP | Ensembl ].
VAR_012667
Natural variant2351R → C Associated with Crohn disease. Ref.2
VAR_012668
Natural variant2481L → R Associated with Crohn disease. Ref.2
Corresponds to variant rs104895423 [ dbSNP | Ensembl ].
VAR_012669
Natural variant2681P → S. Ref.2
Corresponds to variant rs2066842 [ dbSNP | Ensembl ].
VAR_012670
Natural variant2891N → S. Ref.2
Corresponds to variant rs5743271 [ dbSNP | Ensembl ].
VAR_012671
Natural variant2911D → N Associated with Crohn disease. Ref.2
VAR_012672
Natural variant2941T → S Associated with Crohn disease.
VAR_012673
Natural variant3011A → V Associated with Crohn disease. Ref.2
VAR_012674
Natural variant3111R → W Associated with Crohn disease and ulcerative colitis. Ref.2
VAR_012675
Natural variant3341R → Q in BS. Ref.8
VAR_012676
Natural variant3341R → W in BS. Ref.8 Ref.12
VAR_012677
Natural variant3481L → V Associated with Crohn disease. Ref.2
VAR_012678
Natural variant3521H → R Associated with Crohn disease. Ref.2
Corresponds to variant rs5743272 [ dbSNP | Ensembl ].
VAR_012679
Natural variant3731R → C Associated with Crohn disease. Ref.2
VAR_012680
Natural variant3821D → E in EOS. Ref.9
VAR_023822
Natural variant3831E → K in BS. Ref.10
VAR_023823
Natural variant4141N → S Associated with Crohn disease. Ref.2
VAR_012681
Natural variant4311S → L Associated with Crohn disease. Ref.2
Corresponds to variant rs104895431 [ dbSNP | Ensembl ].
VAR_012682
Natural variant4321A → V Associated with Crohn disease. Ref.2
Corresponds to variant rs2076754 [ dbSNP | Ensembl ].
VAR_012683
Natural variant4411E → K Associated with Crohn disease. Ref.2
VAR_012684
Natural variant4691L → F in BS. Ref.8
VAR_012685
Natural variant4711R → C.
Corresponds to variant rs1078327 [ dbSNP | Ensembl ].
VAR_036872
Natural variant4961H → L in EOS. Ref.9
VAR_023824
Natural variant6051T → N in BS. Ref.11
VAR_065228
Natural variant6121A → T in EOS; associated with Crohn disease. Ref.2 Ref.9
VAR_012686
Natural variant6121A → V Associated with Crohn disease. Ref.2
VAR_012687
Natural variant6841R → W Associated with Crohn disease. Ref.2
Corresponds to variant rs5743276 [ dbSNP | Ensembl ].
VAR_012688
Natural variant7021R → W Associated with Crohn disease. Ref.2
Corresponds to variant rs2066844 [ dbSNP | Ensembl ].
VAR_012689
Natural variant7031R → C Associated with Crohn disease and ulcerative colitis. Ref.2
Corresponds to variant rs5743277 [ dbSNP | Ensembl ].
VAR_012690
Natural variant7131R → C Associated with Crohn disease. Ref.2
VAR_012691
Natural variant7251A → G Associated with Crohn disease. Ref.2
Corresponds to variant rs5743278 [ dbSNP | Ensembl ].
VAR_012692
Natural variant7551A → V Associated with Crohn disease and ulcerative colitis. Ref.2
Corresponds to variant rs61747625 [ dbSNP | Ensembl ].
VAR_012693
Natural variant7581A → V Associated with Crohn disease. Ref.2
VAR_012694
Natural variant7781E → K Associated with Crohn disease. Ref.2
VAR_012695
Natural variant7901R → Q.
Corresponds to variant rs5743279 [ dbSNP | Ensembl ].
VAR_024402
Natural variant7931V → M Associated with Crohn disease. Ref.2
Corresponds to variant rs104895444 [ dbSNP | Ensembl ].
VAR_012696
Natural variant8431E → K Associated with Crohn disease. Ref.2
VAR_012697
Natural variant8531N → S Associated with Crohn disease. Ref.2
VAR_012698
Natural variant8631M → V Associated with Crohn disease. Ref.2
Corresponds to variant rs104895447 [ dbSNP | Ensembl ].
VAR_012699
Natural variant8851A → T Associated with ulcerative colitis. Ref.2
VAR_012700
Natural variant9081G → R Associated with Crohn disease. Ref.1 Ref.2
Corresponds to variant rs2066845 [ dbSNP | Ensembl ].
VAR_012701
Natural variant9181A → D Associated with Crohn disease. Ref.2
Corresponds to variant rs104895452 [ dbSNP | Ensembl ].
VAR_012702
Natural variant9241G → D Associated with Crohn disease. Ref.2
VAR_012703
Natural variant9551V → I. Ref.2
Corresponds to variant rs5743291 [ dbSNP | Ensembl ].
VAR_012704

Experimental info

Mutagenesis3051K → R: No activation. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Nod2) [UniParc].

Last modified March 1, 2001. Version 1.
Checksum: 0037592D96D7DDFF

FASTA1,040115,283
        10         20         30         40         50         60 
MGEEGGSASH DEEERASVLL GHSPGCEMCS QEAFQAQRSQ LVELLVSGSL EGFESVLDWL 

        70         80         90        100        110        120 
LSWEVLSWED YEGFHLLGQP LSHLARRLLD TVWNKGTWAC QKLIAAAQEA QADSQSPKLH 

       130        140        150        160        170        180 
GCWDPHSLHP ARDLQSHRPA IVRRLHSHVE NMLDLAWERG FVSQYECDEI RLPIFTPSQR 

       190        200        210        220        230        240 
ARRLLDLATV KANGLAAFLL QHVQELPVPL ALPLEAATCK KYMAKLRTTV SAQSRFLSTY 

       250        260        270        280        290        300 
DGAETLCLED IYTENVLEVW ADVGMAGPPQ KSPATLGLEE LFSTPGHLND DADTVLVVGE 

       310        320        330        340        350        360 
AGSGKSTLLQ RLHLLWAAGQ DFQEFLFVFP FSCRQLQCMA KPLSVRTLLF EHCCWPDVGQ 

       370        380        390        400        410        420 
EDIFQLLLDH PDRVLLTFDG FDEFKFRFTD RERHCSPTDP TSVQTLLFNL LQGNLLKNAR 

       430        440        450        460        470        480 
KVVTSRPAAV SAFLRKYIRT EFNLKGFSEQ GIELYLRKRH HEPGVADRLI RLLQETSALH 

       490        500        510        520        530        540 
GLCHLPVFSW MVSKCHQELL LQEGGSPKTT TDMYLLILQH FLLHATPPDS ASQGLGPSLL 

       550        560        570        580        590        600 
RGRLPTLLHL GRLALWGLGM CCYVFSAQQL QAAQVSPDDI SLGFLVRAKG VVPGSTAPLE 

       610        620        630        640        650        660 
FLHITFQCFF AAFYLALSAD VPPALLRHLF NCGRPGNSPM ARLLPTMCIQ ASEGKDSSVA 

       670        680        690        700        710        720 
ALLQKAEPHN LQITAAFLAG LLSREHWGLL AECQTSEKAL LRRQACARWC LARSLRKHFH 

       730        740        750        760        770        780 
SIPPAAPGEA KSVHAMPGFI WLIRSLYEMQ EERLARKAAR GLNVGHLKLT FCSVGPTECA 

       790        800        810        820        830        840 
ALAFVLQHLR RPVALQLDYN SVGDIGVEQL LPCLGVCKAL YLRDNNISDR GICKLIECAL 

       850        860        870        880        890        900 
HCEQLQKLAL FNNKLTDGCA HSMAKLLACR QNFLALRLGN NYITAAGAQV LAEGLRGNTS 

       910        920        930        940        950        960 
LQFLGFWGNR VGDEGAQALA EALGDHQSLR WLSLVGNNIG SVGAQALALM LAKNVMLEEL 

       970        980        990       1000       1010       1020 
CLEENHLQDE GVCSLAEGLK KNSSLKILKL SNNCITYLGA EALLQALERN DTILEVWLRG 

      1030       1040 
NTFSLEEVDK LGCRDTRLLL 

« Hide

Isoform 2 (Nod2b) [UniParc].

Checksum: CB7892AB103A5752
Show »

FASTA1,013112,530
Isoform 3 (NOD2-C2) [UniParc].

Checksum: FC620CEE13BAE115
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FASTA19722,403

References

[1]"Nod2, a Nod1/Apaf-1 family member that is restricted to monocytes and activates NF-kappaB."
Ogura Y., Inohara N., Benito A., Chen F.F., Yamaoka S., Nunez G.
J. Biol. Chem. 276:4812-4818(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), MUTAGENESIS OF LYS-305, VARIANT ARG-908.
Tissue: Mammary gland.
[2]"Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease."
Hugot J.-P., Chamaillard M., Zouali H., Lesage S., Cezard J.-P., Belaiche J., Almer S., Tysk C., O'Morain C.A., Gassull M., Binder V., Finkel Y., Cortot A., Modigliani R., Laurent-Puig P., Gower-Rousseau C., Macry J., Colombel J.-F., Sahbatou M., Thomas G.
Nature 411:599-603(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 2), VARIANTS THR-140; ARG-157; MET-189; CYS-235; ARG-248; SER-268; SER-289; ASN-291; VAL-301; TRP-311; VAL-348; ARG-352; CYS-373; SER-414; LEU-431; VAL-432; LYS-441; VAL-612; THR-612; TRP-684; TRP-702; CYS-703; CYS-713; GLY-725; VAL-755; VAL-758; LYS-778; MET-793; LYS-843; SER-853; VAL-863; THR-885; ARG-908; ASP-918; ASP-924 AND ILE-955, INVOLVEMENT IN IBD1.
Tissue: Leukocyte.
[3]"NOD2-C2 - a novel NOD2 isoform activating NF-kappaB in a muramyl dipeptide-independent manner."
Kramer M., Boeck J., Reichenbach D., Kaether C., Schreiber S., Platzer M., Rosenstiel P., Huse K.
BMC Res. Notes 3:224-224(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
[4]"ITCH K63-ubiquitinates the NOD2 binding protein, RIP2, to influence inflammatory signaling pathways."
Tao M., Scacheri P.C., Marinis J.M., Harhaj E.W., Matesic L.E., Abbott D.W.
Curr. Biol. 19:1255-1263(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RIPK2.
[5]"Control of NOD2 and Rip2-dependent innate immune activation by GEF-H1."
Zhao Y., Alonso C., Ballester I., Song J.H., Chang S.Y., Guleng B., Arihiro S., Murray P.J., Xavier R., Kobayashi K.S., Reinecker H.C.
Inflamm. Bowel Dis. 18:603-612(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN A COMPLEX WITH ARHGEF2 AND RIPK2, INTERACTION WITH RIPK2.
[6]"TMEM59 defines a novel ATG16L1-binding motif that promotes local activation of LC3."
Boada-Romero E., Letek M., Fleischer A., Pallauf K., Ramon-Barros C., Pimentel-Muinos F.X.
EMBO J. 32:566-582(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ATG16L1.
[7]"OTULIN restricts Met1-linked ubiquitination to control innate immune signaling."
Fiil B.K., Damgaard R.B., Wagner S.A., Keusekotten K., Fritsch M., Bekker-Jensen S., Mailand N., Choudhary C., Komander D., Gyrd-Hansen M.
Mol. Cell 50:818-830(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[8]"CARD15 mutations in Blau syndrome."
Miceli-Richard C., Lesage S., Rybojad M., Prieur A.M., Manouvrier-Hanu S., Hafner R., Chamaillard M., Zouali H., Thomas G., Hugot J.-P.
Nat. Genet. 29:19-20(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS BS GLN-334; TRP-334 AND PHE-469.
[9]"Early-onset sarcoidosis and CARD15 mutations with constitutive nuclear factor-kappaB activation: common genetic etiology with Blau syndrome."
Kanazawa N., Okafuji I., Kambe N., Nishikomori R., Nakata-Hizume M., Nagai S., Fuji A., Yuasa T., Manki A., Sakurai Y., Nakajima M., Kobayashi H., Fujiwara I., Tsutsumi H., Utani A., Nishigori C., Heike T., Nakahata T., Miyachi Y.
Blood 105:1195-1197(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS EOS GLU-382; LEU-496 AND THR-612.
[10]"A new CARD15 mutation in Blau syndrome."
van Duist M.M., Albrecht M., Podswiadek M., Giachino D., Lengauer T., Punzi L., De Marchi M.
Eur. J. Hum. Genet. 13:742-747(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT BS LYS-383.
[11]"A novel mutation in the NOD2 gene associated with Blau syndrome: a Norwegian family with four affected members."
Milman N., Ursin K., Rodevand E., Nielsen F.C., Hansen T.V.
Scand. J. Rheumatol. 38:190-197(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT BS ASN-605.
[12]"Sporadic Blau syndrome with onset of widespread granulomatous dermatitis in the newborn period."
Stoevesandt J., Morbach H., Martin T.M., Zierhut M., Girschick H., Hamm H.
Pediatr. Dermatol. 27:69-73(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT BS TRP-334.
+Additional computationally mapped references.

Web resources

INFEVERS

Repertory of FMF and hereditary autoinflammatory disorders mutations

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF178930 mRNA. Translation: AAG33677.1.
AF385089 Genomic DNA. Translation: AAK70867.1.
AF385090 Genomic DNA. Translation: AAK70868.1.
AJ303140 Genomic DNA. Translation: CAC42117.1.
HQ204571 mRNA. Translation: ADN95581.1.
CCDSCCDS10746.1. [Q9HC29-1]
RefSeqNP_071445.1. NM_022162.1. [Q9HC29-1]
XP_005256141.1. XM_005256084.1. [Q9HC29-2]
UniGeneHs.592072.

3D structure databases

ProteinModelPortalQ9HC29.
SMRQ9HC29. Positions 291-316, 747-1029.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid122077. 28 interactions.
DIPDIP-41998N.
IntActQ9HC29. 1 interaction.
MINTMINT-151071.
STRING9606.ENSP00000300589.

Chemistry

BindingDBQ9HC29.
ChEMBLCHEMBL1293266.
GuidetoPHARMACOLOGY1763.

PTM databases

PhosphoSiteQ9HC29.

Polymorphism databases

DMDM20137973.

Proteomic databases

PaxDbQ9HC29.
PRIDEQ9HC29.

Protocols and materials databases

DNASU64127.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000300589; ENSP00000300589; ENSG00000167207. [Q9HC29-1]
GeneID64127.
KEGGhsa:64127.
UCSCuc002egl.1. human. [Q9HC29-1]

Organism-specific databases

CTD64127.
GeneCardsGC16P050729.
HGNCHGNC:5331. NOD2.
HPAHPA041985.
MIM186580. phenotype.
266600. phenotype.
605956. gene.
609464. phenotype.
neXtProtNX_Q9HC29.
Orphanet117. Behcet disease.
90340. Blau syndrome.
206. Crohn disease.
771. Ulcerative colitis.
PharmGKBPA26074.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG248107.
HOGENOMHOG000113814.
HOVERGENHBG050792.
InParanoidQ9HC29.
KOK10165.
OMAVWNKGTW.
OrthoDBEOG7P5T07.
PhylomeDBQ9HC29.
TreeFamTF352118.

Enzyme and pathway databases

ReactomeREACT_6782. TRAF6 Mediated Induction of proinflammatory cytokines.
REACT_6900. Immune System.
SignaLinkQ9HC29.

Gene expression databases

ArrayExpressQ9HC29.
BgeeQ9HC29.
CleanExHS_NOD2.
GenevestigatorQ9HC29.

Family and domain databases

Gene3D1.10.533.10. 2 hits.
InterProIPR001315. CARD.
IPR011029. DEATH-like_dom.
IPR001611. Leu-rich_rpt.
IPR007111. NACHT_NTPase.
IPR027417. P-loop_NTPase.
[Graphical view]
PfamPF00619. CARD. 2 hits.
[Graphical view]
SMARTSM00114. CARD. 1 hit.
[Graphical view]
SUPFAMSSF47986. SSF47986. 2 hits.
SSF52540. SSF52540. 1 hit.
PROSITEPS50209. CARD. 2 hits.
PS51450. LRR. 4 hits.
PS50837. NACHT. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiNOD2.
GenomeRNAi64127.
NextBio35496989.
PROQ9HC29.
SOURCESearch...

Entry information

Entry nameNOD2_HUMAN
AccessionPrimary (citable) accession number: Q9HC29
Secondary accession number(s): E2JEQ6 expand/collapse secondary AC list , Q96RH5, Q96RH6, Q96RH8
Entry history
Integrated into UniProtKB/Swiss-Prot: January 31, 2002
Last sequence update: March 1, 2001
Last modified: July 9, 2014
This is version 144 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM