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Protein

Nucleotide-binding oligomerization domain-containing protein 2

Gene

NOD2

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

Functioni

Involved in gastrointestinal immunity. Upon stimulation by muramyl dipeptide (MDP), a fragment of bacterial peptidoglycan, 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. This in turn leads to the transcriptional activation of hundreds of genes involved in immune response. Required for MDP-induced NLRP1-dependent CASP1 activation and IL1B release in macrophages (PubMed:18511561).2 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi299 – 306ATPPROSITE-ProRule annotation8

GO - Molecular functioni

  • actin binding Source: UniProtKB
  • ATP binding Source: UniProtKB-KW
  • CARD domain binding Source: UniProtKB
  • enzyme binding Source: UniProtKB
  • Hsp70 protein binding Source: UniProtKB
  • Hsp90 protein binding Source: UniProtKB
  • muramyl dipeptide binding Source: HGNC
  • peptidoglycan binding Source: HGNC
  • protein kinase binding Source: UniProtKB

GO - Biological processi

  • activation of MAPK activity Source: Reactome
  • activation of MAPK activity involved in innate immune response Source: BHF-UCL
  • cellular response to muramyl dipeptide Source: UniProtKB
  • cellular response to organic cyclic compound Source: Ensembl
  • cytokine production involved in immune response Source: UniProtKB
  • cytokine secretion involved in immune response Source: CACAO
  • defense response Source: HGNC
  • defense response to bacterium Source: HGNC
  • detection of bacterium Source: HGNC
  • detection of biotic stimulus Source: HGNC
  • detection of muramyl dipeptide Source: HGNC
  • innate immune response Source: UniProtKB
  • intracellular signal transduction Source: HGNC
  • JNK cascade Source: Reactome
  • maintenance of gastrointestinal epithelium Source: UniProtKB
  • negative regulation of macrophage apoptotic process Source: BHF-UCL
  • nucleotide-binding oligomerization domain containing 2 signaling pathway Source: UniProtKB
  • nucleotide-binding oligomerization domain containing signaling pathway Source: Reactome
  • positive regulation of B cell activation Source: BHF-UCL
  • positive regulation of cytokine production involved in inflammatory response Source: CACAO
  • positive regulation of dendritic cell antigen processing and presentation Source: BHF-UCL
  • positive regulation of dendritic cell cytokine production Source: Ensembl
  • positive regulation of epithelial cell proliferation Source: BHF-UCL
  • positive regulation of ERK1 and ERK2 cascade Source: BHF-UCL
  • positive regulation of gamma-delta T cell activation Source: BHF-UCL
  • positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  • positive regulation of interleukin-10 production Source: BHF-UCL
  • positive regulation of interleukin-17 production Source: UniProtKB
  • positive regulation of interleukin-1 beta production Source: BHF-UCL
  • positive regulation of interleukin-1 beta secretion Source: HGNC
  • positive regulation of interleukin-6 production Source: BHF-UCL
  • positive regulation of interleukin-8 production Source: UniProtKB
  • positive regulation of JNK cascade Source: MGI
  • positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
  • positive regulation of NIK/NF-kappaB signaling Source: UniProtKB
  • positive regulation of nitric-oxide synthase biosynthetic process Source: BHF-UCL
  • positive regulation of Notch signaling pathway Source: BHF-UCL
  • positive regulation of oxidoreductase activity Source: BHF-UCL
  • positive regulation of phosphatidylinositol 3-kinase activity Source: BHF-UCL
  • positive regulation of prostaglandin-endoperoxide synthase activity Source: BHF-UCL
  • positive regulation of prostaglandin-E synthase activity Source: BHF-UCL
  • positive regulation of stress-activated MAPK cascade Source: MGI
  • positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • positive regulation of tumor necrosis factor production Source: BHF-UCL
  • positive regulation of type 2 immune response Source: BHF-UCL
  • protein oligomerization Source: HGNC
  • regulation of inflammatory response Source: BHF-UCL
  • response to muramyl dipeptide Source: UniProtKB
  • response to nutrient Source: Ensembl
Complete GO annotation...

Keywords - Biological processi

Immunity, Innate immunity

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-168638. NOD1/2 Signaling Pathway.
R-HSA-445989. TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
R-HSA-446652. Interleukin-1 signaling.
R-HSA-450302. activated TAK1 mediates p38 MAPK activation.
R-HSA-450321. JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1.
R-HSA-5689896. Ovarian tumor domain proteases.
SignaLinkiQ9HC29.

Names & Taxonomyi

Protein namesi
Recommended name:
Nucleotide-binding oligomerization domain-containing protein 2
Alternative name(s):
Caspase recruitment domain-containing protein 15
Inflammatory bowel disease protein 1
Gene namesi
Name:NOD2
Synonyms:CARD15, IBD1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

HGNCiHGNC:5331. NOD2.

Subcellular locationi

  • Cytoplasm 2 Publications
  • Membrane 1 Publication
  • Basolateral cell membrane 1 Publication

GO - Cellular componenti

  • basolateral plasma membrane Source: UniProtKB
  • cell surface Source: UniProtKB
  • cytoplasm Source: UniProtKB
  • cytoskeleton Source: UniProtKB
  • cytosol Source: HGNC
  • plasma membrane Source: UniProtKB
  • protein complex Source: UniProtKB
  • vesicle Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Involvement in diseasei

Blau syndrome (BLAUS)10 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA rare autosomal dominant disorder characterized by early-onset granulomatous arthritis, uveitis and skin rash.
See also OMIM:186580
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_012676334R → Q in BLAUS; somatic mosaicism in 4.9% to 11% of peripheral blood cells; hyperactive. 5 PublicationsCorresponds to variant rs104895461dbSNPEnsembl.1
Natural variantiVAR_012677334R → W in BLAUS and EOS; no disruption of NOD2-CARD9 interaction; hyperactive. 7 PublicationsCorresponds to variant rs104895462dbSNPEnsembl.1
Natural variantiVAR_023823383E → K in BLAUS; hyperactive. 3 PublicationsCorresponds to variant rs104895477dbSNPEnsembl.1
Natural variantiVAR_012685469L → F in BLAUS; hyperactive. 2 PublicationsCorresponds to variant rs104895460dbSNPEnsembl.1
Natural variantiVAR_073236490W → L in BLAUS; unknown pathological significance; hyperactive. 2 PublicationsCorresponds to variant rs104895480dbSNPEnsembl.1
Natural variantiVAR_073237495C → Y in BLAUS; unknown pathological significance; hyperactive. 3 PublicationsCorresponds to variant rs104895478dbSNPEnsembl.1
Natural variantiVAR_073180507P → S in BLAUS. 1 Publication1
Natural variantiVAR_073240587R → C in BLAUS; unknown pathological significance; not hyperactive. 2 PublicationsCorresponds to variant rs104895479dbSNPEnsembl.1
Natural variantiVAR_065228605T → N in BLAUS; hyperactive. 2 Publications1
Sarcoidosis early-onset (EOS)4 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:609464
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_012677334R → W in BLAUS and EOS; no disruption of NOD2-CARD9 interaction; hyperactive. 7 PublicationsCorresponds to variant rs104895462dbSNPEnsembl.1
Natural variantiVAR_023822382D → E in EOS; hyperactive. 2 PublicationsCorresponds to variant rs104895476dbSNPEnsembl.1
Natural variantiVAR_073235481G → D in EOS; atypical form of EOS with cardiac infiltration; sporadic case; unknown pathological significance; hyperactive. 2 PublicationsCorresponds to variant rs104895494dbSNPEnsembl.1
Natural variantiVAR_023824496H → L in EOS; hyperactive. 3 PublicationsCorresponds to variant rs104895472dbSNPEnsembl.1
Natural variantiVAR_073238513M → T in EOS; hyperactive. 3 PublicationsCorresponds to variant rs104895473dbSNPEnsembl.1
Natural variantiVAR_073241605T → P in EOS; hyperactive. 3 PublicationsCorresponds to variant rs104895474dbSNPEnsembl.1
Natural variantiVAR_012686612A → T in EOS; also found in patients with Crohn disease; unknown pathological significance. 2 PublicationsCorresponds to variant rs104895438dbSNPEnsembl.1
Natural variantiVAR_073242670N → K in EOS; hyperactive. 3 PublicationsCorresponds to variant rs104895475dbSNPEnsembl.1

Variations affecting NOD2 cause susceptibility to Crohn disease, one of the phenotypes of the inflammatory bowel disease 1 (IBD1). 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. The disease includes extraintestinal inflammation of the skin, eyes, or joints.

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi305K → R: No activation. 1 Publication1
Mutagenesisi379D → A: No disruption in NOD2-CARD9 interaction. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi64127.
MalaCardsiNOD2.
MIMi186580. phenotype.
266600. phenotype.
609464. phenotype.
OpenTargetsiENSG00000167207.
Orphaneti117. Behcet disease.
90340. Blau syndrome.
206. Crohn disease.
771. Ulcerative colitis.
PharmGKBiPA26074.

Chemistry databases

ChEMBLiCHEMBL1293266.
GuidetoPHARMACOLOGYi1763.

Polymorphism and mutation databases

BioMutaiNOD2.
DMDMi20137973.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000044181 – 1040Nucleotide-binding oligomerization domain-containing protein 2Add BLAST1040

Post-translational modificationi

Polyubiquitinated following MDP stimulation, leading to proteasome-mediated degradation (PubMed:23019338).1 Publication

Keywords - PTMi

Ubl conjugation

Proteomic databases

EPDiQ9HC29.
PaxDbiQ9HC29.
PeptideAtlasiQ9HC29.
PRIDEiQ9HC29.

PTM databases

iPTMnetiQ9HC29.
PhosphoSitePlusiQ9HC29.

Expressioni

Tissue specificityi

Monocytes-specific.

Gene expression databases

BgeeiENSG00000167207.
CleanExiHS_NOD2.
ExpressionAtlasiQ9HC29. baseline and differential.
GenevisibleiQ9HC29. HS.

Organism-specific databases

HPAiHPA041985.

Interactioni

Subunit structurei

Component of a signaling complex consisting of ARHGEF2, NOD2 and RIPK2 (PubMed:21887730). Interacts (via CARD domain) with RIPK2 (via CARD domain) (PubMed:19592251, PubMed:21887730). Interacts with ATG16L1 (PubMed:23376921). Interacts (via NACHT domain) with CARD9 (PubMed:24960071). Interacts with ANKRD17 (via N-terminus) (PubMed:23711367). Interacts with HSPA1A; the interaction enhances NOD2 stability (PubMed:24790089). Interacts (via both CARD domains) with HSP90; the interaction enhances NOD2 stability (PubMed:23019338). Interacts (via CARD domain) with SOCS3; the interaction promotes NOD2 degradation (PubMed:23019338). Interacts (via CARD domain) with ERBBI2P; the interaction inhibits activation of NOD2 (PubMed:16203728). Interacts (via CARD domain) with CASP1; this interaction leads to IL1B processing. Also interacts with CASP4. Interacts with NLRP1; this interaction is enhanced in the presence of muramyl dipeptide (MDP) and leads to increased IL1B release (PubMed:18511561).9 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ERBINQ96RT14EBI-7445625,EBI-993903
ERBINQ96RT1-25EBI-7445625,EBI-8449250
FIS1Q9Y3D62EBI-7445625,EBI-3385283
GALNT2Q104712EBI-7445625,EBI-10226985
KAT5Q929932EBI-7445625,EBI-399080
NDUFA13Q9P0J06EBI-7445625,EBI-372742
PPP2R5EQ165372EBI-7445625,EBI-968374
RIPK2O433532EBI-7445625,EBI-358522
TLE1Q047242EBI-7445625,EBI-711424
TRIM27P1437310EBI-7445625,EBI-719493
VIMP086707EBI-7445625,EBI-353844

GO - Molecular functioni

  • actin binding Source: UniProtKB
  • CARD domain binding Source: UniProtKB
  • enzyme binding Source: UniProtKB
  • Hsp70 protein binding Source: UniProtKB
  • Hsp90 protein binding Source: UniProtKB
  • protein kinase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi122077. 33 interactors.
DIPiDIP-41998N.
IntActiQ9HC29. 15 interactors.
MINTiMINT-151071.
STRINGi9606.ENSP00000300589.

Chemistry databases

BindingDBiQ9HC29.

Structurei

3D structure databases

ProteinModelPortaliQ9HC29.
SMRiQ9HC29.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini26 – 122CARD 1PROSITE-ProRule annotationAdd BLAST97
Domaini126 – 218CARD 2PROSITE-ProRule annotationAdd BLAST93
Domaini293 – 618NACHTPROSITE-ProRule annotationAdd BLAST326
Repeati791 – 812LRR 1Add BLAST22
Repeati816 – 839LRR 2Add BLAST24
Repeati844 – 865LRR 3Add BLAST22
Repeati872 – 884LRR 4Add BLAST13
Repeati900 – 920LRR 5Add BLAST21
Repeati928 – 949LRR 6Add BLAST22
Repeati956 – 976LRR 7Add BLAST21
Repeati984 – 1005LRR 8Add BLAST22
Repeati1012 – 1032LRR 9Add BLAST21

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni241 – 274Required for CARD9 binding1 PublicationAdd BLAST34

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi63 – 77ATG16L1-binding motifAdd BLAST15

Domaini

The ATG16L1-binding motif mediates interaction with ATG16L1.1 Publication
Intramolecular interactions between the N-terminal moiety and the leucine-rich repeats (LRR) may be important for autoinhibition in the absence of activating signal. In the absence of LRRs, the protein becomes a constitutive activator of CASP1 cleavage and proIL1B processing.1 Publication

Sequence similaritiesi

Contains 2 CARD domains.PROSITE-ProRule annotation
Contains 9 LRR (leucine-rich) repeats.Curated
Contains 1 NACHT domain.PROSITE-ProRule annotation

Keywords - Domaini

Leucine-rich repeat, Repeat

Phylogenomic databases

eggNOGiKOG4308. Eukaryota.
ENOG410ZBX3. LUCA.
GeneTreeiENSGT00860000133673.
HOGENOMiHOG000113814.
HOVERGENiHBG050792.
InParanoidiQ9HC29.
KOiK10165.
OMAiFDEFKFR.
OrthoDBiEOG091G01CG.
PhylomeDBiQ9HC29.
TreeFamiTF352118.

Family and domain databases

Gene3Di1.10.533.10. 2 hits.
3.40.50.300. 1 hit.
3.80.10.10. 1 hit.
InterProiIPR001315. CARD.
IPR011029. DEATH-like_dom.
IPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR007111. NACHT_NTPase.
IPR027417. P-loop_NTPase.
[Graphical view]
PfamiPF00619. CARD. 1 hit.
PF13516. LRR_6. 3 hits.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 2 hits.
SSF52540. SSF52540. 1 hit.
PROSITEiPS50209. CARD. 2 hits.
PS51450. LRR. 4 hits.
PS50837. NACHT. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative initiation. AlignAdd to basket

Isoform 1 (identifier: Q9HC29-1) [UniParc]FASTAAdd to basket
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.

« Hide

        10         20         30         40         50
MGEEGGSASH DEEERASVLL GHSPGCEMCS QEAFQAQRSQ LVELLVSGSL
60 70 80 90 100
EGFESVLDWL LSWEVLSWED YEGFHLLGQP LSHLARRLLD TVWNKGTWAC
110 120 130 140 150
QKLIAAAQEA QADSQSPKLH GCWDPHSLHP ARDLQSHRPA IVRRLHSHVE
160 170 180 190 200
NMLDLAWERG FVSQYECDEI RLPIFTPSQR ARRLLDLATV KANGLAAFLL
210 220 230 240 250
QHVQELPVPL ALPLEAATCK KYMAKLRTTV SAQSRFLSTY DGAETLCLED
260 270 280 290 300
IYTENVLEVW ADVGMAGPPQ KSPATLGLEE LFSTPGHLND DADTVLVVGE
310 320 330 340 350
AGSGKSTLLQ RLHLLWAAGQ DFQEFLFVFP FSCRQLQCMA KPLSVRTLLF
360 370 380 390 400
EHCCWPDVGQ EDIFQLLLDH PDRVLLTFDG FDEFKFRFTD RERHCSPTDP
410 420 430 440 450
TSVQTLLFNL LQGNLLKNAR KVVTSRPAAV SAFLRKYIRT EFNLKGFSEQ
460 470 480 490 500
GIELYLRKRH HEPGVADRLI RLLQETSALH GLCHLPVFSW MVSKCHQELL
510 520 530 540 550
LQEGGSPKTT TDMYLLILQH FLLHATPPDS ASQGLGPSLL RGRLPTLLHL
560 570 580 590 600
GRLALWGLGM CCYVFSAQQL QAAQVSPDDI SLGFLVRAKG VVPGSTAPLE
610 620 630 640 650
FLHITFQCFF AAFYLALSAD VPPALLRHLF NCGRPGNSPM ARLLPTMCIQ
660 670 680 690 700
ASEGKDSSVA ALLQKAEPHN LQITAAFLAG LLSREHWGLL AECQTSEKAL
710 720 730 740 750
LRRQACARWC LARSLRKHFH SIPPAAPGEA KSVHAMPGFI WLIRSLYEMQ
760 770 780 790 800
EERLARKAAR GLNVGHLKLT FCSVGPTECA ALAFVLQHLR RPVALQLDYN
810 820 830 840 850
SVGDIGVEQL LPCLGVCKAL YLRDNNISDR GICKLIECAL HCEQLQKLAL
860 870 880 890 900
FNNKLTDGCA HSMAKLLACR QNFLALRLGN NYITAAGAQV LAEGLRGNTS
910 920 930 940 950
LQFLGFWGNR VGDEGAQALA EALGDHQSLR WLSLVGNNIG SVGAQALALM
960 970 980 990 1000
LAKNVMLEEL CLEENHLQDE GVCSLAEGLK KNSSLKILKL SNNCITYLGA
1010 1020 1030 1040
EALLQALERN DTILEVWLRG NTFSLEEVDK LGCRDTRLLL
Note: Can activate NF-kappa-B. More abundant.
Length:1,040
Mass (Da):115,283
Last modified:March 1, 2001 - v1
Checksum:i0037592D96D7DDFF
GO
Isoform 2 (identifier: Q9HC29-2) [UniParc]FASTAAdd to basket
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.
Show »
Length:1,013
Mass (Da):112,530
Checksum:iCB7892AB103A5752
GO
Isoform 3 (identifier: Q9HC29-3) [UniParc]FASTAAdd to basket
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.
Show »
Length:197
Mass (Da):22,403
Checksum:iFC620CEE13BAE115
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03687181L → V.Corresponds to variant rs34936594dbSNPEnsembl.1
Natural variantiVAR_073228113D → N Found in a patient with Crohn disease; unknown pathological significance. 1 PublicationCorresponds to variant rs104895468dbSNPEnsembl.1
Natural variantiVAR_012665140A → T Found in patients with Crohn disease; also found in patients with ulcerative colitis; unknown pathological significance. 1 PublicationCorresponds to variant rs34684955dbSNPEnsembl.1
Natural variantiVAR_012666157W → R Found in patients with Crohn disease; unknown pathological significance. 1 PublicationCorresponds to variant rs104895420dbSNPEnsembl.1
Natural variantiVAR_012667189T → M.1 PublicationCorresponds to variant rs61755182dbSNPEnsembl.1
Natural variantiVAR_012668235R → C Found in patients with Crohn disease; unknown pathological significance. 1 PublicationCorresponds to variant rs104895422dbSNPEnsembl.1
Natural variantiVAR_012669248L → R Found in patients with Crohn disease; unknown pathological significance; no disruption of NOD2-CARD9 interaction. 2 PublicationsCorresponds to variant rs104895423dbSNPEnsembl.1
Natural variantiVAR_012670268P → S.3 PublicationsCorresponds to variant rs2066842dbSNPEnsembl.1
Natural variantiVAR_012671289N → S.2 PublicationsCorresponds to variant rs5743271dbSNPEnsembl.1
Natural variantiVAR_012672291D → N Found in patients with Crohn disease; unknown pathological significance. 1 PublicationCorresponds to variant rs104895424dbSNPEnsembl.1
Natural variantiVAR_012673294T → S Found in patients with Crohn disease; unknown pathological significance. Corresponds to variant rs104895425dbSNPEnsembl.1
Natural variantiVAR_012674301A → V Found in patients with Crohn disease; unknown pathological significance. 1 PublicationCorresponds to variant rs104895426dbSNPEnsembl.1
Natural variantiVAR_012675311R → W Found in patients with Crohn disease; also found in patients with ulcerative colitis; unknown pathological significance. 2 PublicationsCorresponds to variant rs104895427dbSNPEnsembl.1
Natural variantiVAR_012676334R → Q in BLAUS; somatic mosaicism in 4.9% to 11% of peripheral blood cells; hyperactive. 5 PublicationsCorresponds to variant rs104895461dbSNPEnsembl.1
Natural variantiVAR_012677334R → W in BLAUS and EOS; no disruption of NOD2-CARD9 interaction; hyperactive. 7 PublicationsCorresponds to variant rs104895462dbSNPEnsembl.1
Natural variantiVAR_012678348L → V Found in patients with Crohn disease; unknown pathological significance. 1 PublicationCorresponds to variant rs104895428dbSNPEnsembl.1
Natural variantiVAR_012679352H → R Found in patients with Crohn disease; unknown pathological significance. 1 PublicationCorresponds to variant rs5743272dbSNPEnsembl.1
Natural variantiVAR_073229357D → A Found in a patient with Crohn disease; unknown pathological significance; no disruption of NOD2-CARD9 interaction. 2 PublicationsCorresponds to variant rs104895469dbSNPEnsembl.1
Natural variantiVAR_073230363I → F Found in a patient with Crohn disease; unknown pathological significance; no disruption of NOD2-CARD9 interaction. 2 PublicationsCorresponds to variant rs104895470dbSNPEnsembl.1
Natural variantiVAR_012680373R → C Found in patients with Crohn disease; unknown pathological significance. 1 PublicationCorresponds to variant rs145293873dbSNPEnsembl.1
Natural variantiVAR_023822382D → E in EOS; hyperactive. 2 PublicationsCorresponds to variant rs104895476dbSNPEnsembl.1
Natural variantiVAR_073231383E → G Found in a family with Blau syndrome/early-onset sarcoidosis symptoms; unknown pathological significance; hyperactive. 2 PublicationsCorresponds to variant rs104895493dbSNPEnsembl.1
Natural variantiVAR_023823383E → K in BLAUS; hyperactive. 3 PublicationsCorresponds to variant rs104895477dbSNPEnsembl.1
Natural variantiVAR_073232391R → C.1 PublicationCorresponds to variant rs104895481dbSNPEnsembl.1
Natural variantiVAR_012681414N → S Found in patients with Crohn disease; unknown pathological significance. 1 PublicationCorresponds to variant rs104895429dbSNPEnsembl.1
Natural variantiVAR_012682431S → L Found in patients with Crohn disease; unknown pathological significance; no disruption of NOD2-CARD9 interaction. 2 PublicationsCorresponds to variant rs104895431dbSNPEnsembl.1
Natural variantiVAR_012683432A → V Found in patients with Crohn disease; unknown pathological significance. 1 PublicationCorresponds to variant rs2076754dbSNPEnsembl.1
Natural variantiVAR_012684441E → K Found in patients with Crohn disease; unknown pathological significance; no disruption of NOD2-CARD9 interaction. 2 PublicationsCorresponds to variant rs104895432dbSNPEnsembl.1
Natural variantiVAR_073233463P → A Polymorphism; no disruption of NOD2-CARD9 interaction. 2 PublicationsCorresponds to variant rs104895482dbSNPEnsembl.1
Natural variantiVAR_073234464G → W Polymorphism; hyperactive. 1 PublicationCorresponds to variant rs104895492dbSNPEnsembl.1
Natural variantiVAR_012685469L → F in BLAUS; hyperactive. 2 PublicationsCorresponds to variant rs104895460dbSNPEnsembl.1
Natural variantiVAR_036872471R → C Polymorphism; does not affect activity. 1 PublicationCorresponds to variant rs1078327dbSNPEnsembl.1
Natural variantiVAR_073235481G → D in EOS; atypical form of EOS with cardiac infiltration; sporadic case; unknown pathological significance; hyperactive. 2 PublicationsCorresponds to variant rs104895494dbSNPEnsembl.1
Natural variantiVAR_073236490W → L in BLAUS; unknown pathological significance; hyperactive. 2 PublicationsCorresponds to variant rs104895480dbSNPEnsembl.1
Natural variantiVAR_073237495C → Y in BLAUS; unknown pathological significance; hyperactive. 3 PublicationsCorresponds to variant rs104895478dbSNPEnsembl.1
Natural variantiVAR_023824496H → L in EOS; hyperactive. 3 PublicationsCorresponds to variant rs104895472dbSNPEnsembl.1
Natural variantiVAR_073180507P → S in BLAUS. 1 Publication1
Natural variantiVAR_073238513M → T in EOS; hyperactive. 3 PublicationsCorresponds to variant rs104895473dbSNPEnsembl.1
Natural variantiVAR_073239550L → V Found in a patient with Crohn disease; unknown pathological significance; no disruption of NOD2-CARD9 interaction. 2 PublicationsCorresponds to variant rs104895471dbSNPEnsembl.1
Natural variantiVAR_073240587R → C in BLAUS; unknown pathological significance; not hyperactive. 2 PublicationsCorresponds to variant rs104895479dbSNPEnsembl.1
Natural variantiVAR_065228605T → N in BLAUS; hyperactive. 2 Publications1
Natural variantiVAR_073241605T → P in EOS; hyperactive. 3 PublicationsCorresponds to variant rs104895474dbSNPEnsembl.1
Natural variantiVAR_012686612A → T in EOS; also found in patients with Crohn disease; unknown pathological significance. 2 PublicationsCorresponds to variant rs104895438dbSNPEnsembl.1
Natural variantiVAR_012687612A → V Found in patients with Crohn disease; unknown pathological significance; no disruption of NOD2-CARD9 interaction. 2 PublicationsCorresponds to variant rs104895439dbSNPEnsembl.1
Natural variantiVAR_073242670N → K in EOS; hyperactive. 3 PublicationsCorresponds to variant rs104895475dbSNPEnsembl.1
Natural variantiVAR_012688684R → W Found in patients with Crohn disease; unknown pathological significance. 1 PublicationCorresponds to variant rs5743276dbSNPEnsembl.1
Natural variantiVAR_012689702R → W Probable disease-associated mutation found in patients with Crohn disease; no disruption of NOD2-CARD9 interaction; decreases half-life of protein. 4 PublicationsCorresponds to variant rs2066844dbSNPEnsembl.1
Natural variantiVAR_012690703R → C Found in patients with Crohn disease; also found in patients with ulcerative colitis; unknown pathological significance. 2 PublicationsCorresponds to variant rs5743277dbSNPEnsembl.1
Natural variantiVAR_012691713R → C Found in patients with Crohn disease; unknown pathological significance. 1 PublicationCorresponds to variant rs104895440dbSNPEnsembl.1
Natural variantiVAR_073243713R → H Found in a patient with Crohn disease; unknown pathological significance. 1 PublicationCorresponds to variant rs104895483dbSNPEnsembl.1
Natural variantiVAR_012692725A → G Found in patients with Crohn disease; unknown pathological significance. 1 PublicationCorresponds to variant rs5743278dbSNPEnsembl.1
Natural variantiVAR_012693755A → V Found in patients with Crohn disease; also found in patients with ulcerative colitis; unknown pathological significance. 2 PublicationsCorresponds to variant rs61747625dbSNPEnsembl.1
Natural variantiVAR_012694758A → V Found in patients with Crohn disease; unknown pathological significance. 1 PublicationCorresponds to variant rs104895442dbSNPEnsembl.1
Natural variantiVAR_073244760R → C Found in a patient with Crohn disease; unknown pathological significance. 1 PublicationCorresponds to variant rs3813758dbSNPEnsembl.1
Natural variantiVAR_012695778E → K Found in patients with Crohn disease; unknown pathological significance. 1 PublicationCorresponds to variant rs104895443dbSNPEnsembl.1
Natural variantiVAR_024402790R → Q.Corresponds to variant rs5743279dbSNPEnsembl.1
Natural variantiVAR_073245790R → W Found in a patient with Crohn disease; unknown pathological significance. 1 PublicationCorresponds to variant rs62029861dbSNPEnsembl.1
Natural variantiVAR_073246791R → W.1 PublicationCorresponds to variant rs104895484dbSNPEnsembl.1
Natural variantiVAR_012696793V → M Found in patients with Crohn disease; unknown pathological significance. 1 PublicationCorresponds to variant rs104895444dbSNPEnsembl.1
Natural variantiVAR_073247825N → K.1 PublicationCorresponds to variant rs104895485dbSNPEnsembl.1
Natural variantiVAR_012697843E → K Found in patients with Crohn disease; unknown pathological significance. 1 PublicationCorresponds to variant rs104895445dbSNPEnsembl.1
Natural variantiVAR_073248849A → V.1 PublicationCorresponds to variant rs104895486dbSNPEnsembl.1
Natural variantiVAR_073249852N → S Found in a patient with Crohn disease; unknown pathological significance. 1 PublicationCorresponds to variant rs104895467dbSNPEnsembl.1
Natural variantiVAR_012698853N → S Found in patients with Crohn disease; unknown pathological significance. 1 PublicationCorresponds to variant rs104895446dbSNPEnsembl.1
Natural variantiVAR_012699863M → V Found in patients with Crohn disease; unknown pathological significance. 1 PublicationCorresponds to variant rs104895447dbSNPEnsembl.1
Natural variantiVAR_012700885A → T Found in patients with ulcerative colitis; unknown pathological significance. 1 Publication1
Natural variantiVAR_012701908G → R Probable disease-associated mutation found in patients with Crohn disease; decreases half-life of protein. 4 PublicationsCorresponds to variant rs2066845dbSNPEnsembl.1
Natural variantiVAR_012702918A → D.1 PublicationCorresponds to variant rs104895452dbSNPEnsembl.1
Natural variantiVAR_012703924G → D Found in patients with Crohn disease; unknown pathological significance. 1 PublicationCorresponds to variant rs104895453dbSNPEnsembl.1
Natural variantiVAR_012704955V → I.1 PublicationCorresponds to variant rs5743291dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0186891 – 27Missing in isoform 2 and isoform 3. 2 PublicationsAdd BLAST27
Alternative sequenceiVSP_046567216 – 224AATCKKYMA → DERTEAQKG in isoform 3. 1 Publication9
Alternative sequenceiVSP_046568225 – 1040Missing in isoform 3. 1 PublicationAdd BLAST816

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS10746.1. [Q9HC29-1]
RefSeqiNP_001280486.1. NM_001293557.1. [Q9HC29-2]
NP_071445.1. NM_022162.2. [Q9HC29-1]
XP_005256141.1. XM_005256084.3. [Q9HC29-2]
UniGeneiHs.592072.

Genome annotation databases

EnsembliENST00000300589; ENSP00000300589; ENSG00000167207. [Q9HC29-1]
GeneIDi64127.
KEGGihsa:64127.
UCSCiuc002egm.2. human. [Q9HC29-1]

Keywords - Coding sequence diversityi

Alternative initiation, Polymorphism

Cross-referencesi

Web resourcesi

INFEVERS

Repertory of FMF and hereditary autoinflammatory disorders mutations

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS10746.1. [Q9HC29-1]
RefSeqiNP_001280486.1. NM_001293557.1. [Q9HC29-2]
NP_071445.1. NM_022162.2. [Q9HC29-1]
XP_005256141.1. XM_005256084.3. [Q9HC29-2]
UniGeneiHs.592072.

3D structure databases

ProteinModelPortaliQ9HC29.
SMRiQ9HC29.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi122077. 33 interactors.
DIPiDIP-41998N.
IntActiQ9HC29. 15 interactors.
MINTiMINT-151071.
STRINGi9606.ENSP00000300589.

Chemistry databases

BindingDBiQ9HC29.
ChEMBLiCHEMBL1293266.
GuidetoPHARMACOLOGYi1763.

PTM databases

iPTMnetiQ9HC29.
PhosphoSitePlusiQ9HC29.

Polymorphism and mutation databases

BioMutaiNOD2.
DMDMi20137973.

Proteomic databases

EPDiQ9HC29.
PaxDbiQ9HC29.
PeptideAtlasiQ9HC29.
PRIDEiQ9HC29.

Protocols and materials databases

DNASUi64127.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000300589; ENSP00000300589; ENSG00000167207. [Q9HC29-1]
GeneIDi64127.
KEGGihsa:64127.
UCSCiuc002egm.2. human. [Q9HC29-1]

Organism-specific databases

CTDi64127.
DisGeNETi64127.
GeneCardsiNOD2.
HGNCiHGNC:5331. NOD2.
HPAiHPA041985.
MalaCardsiNOD2.
MIMi186580. phenotype.
266600. phenotype.
605956. gene.
609464. phenotype.
neXtProtiNX_Q9HC29.
OpenTargetsiENSG00000167207.
Orphaneti117. Behcet disease.
90340. Blau syndrome.
206. Crohn disease.
771. Ulcerative colitis.
PharmGKBiPA26074.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4308. Eukaryota.
ENOG410ZBX3. LUCA.
GeneTreeiENSGT00860000133673.
HOGENOMiHOG000113814.
HOVERGENiHBG050792.
InParanoidiQ9HC29.
KOiK10165.
OMAiFDEFKFR.
OrthoDBiEOG091G01CG.
PhylomeDBiQ9HC29.
TreeFamiTF352118.

Enzyme and pathway databases

ReactomeiR-HSA-168638. NOD1/2 Signaling Pathway.
R-HSA-445989. TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
R-HSA-446652. Interleukin-1 signaling.
R-HSA-450302. activated TAK1 mediates p38 MAPK activation.
R-HSA-450321. JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1.
R-HSA-5689896. Ovarian tumor domain proteases.
SignaLinkiQ9HC29.

Miscellaneous databases

GeneWikiiNOD2.
GenomeRNAii64127.
PROiQ9HC29.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000167207.
CleanExiHS_NOD2.
ExpressionAtlasiQ9HC29. baseline and differential.
GenevisibleiQ9HC29. HS.

Family and domain databases

Gene3Di1.10.533.10. 2 hits.
3.40.50.300. 1 hit.
3.80.10.10. 1 hit.
InterProiIPR001315. CARD.
IPR011029. DEATH-like_dom.
IPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR007111. NACHT_NTPase.
IPR027417. P-loop_NTPase.
[Graphical view]
PfamiPF00619. CARD. 1 hit.
PF13516. LRR_6. 3 hits.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 2 hits.
SSF52540. SSF52540. 1 hit.
PROSITEiPS50209. CARD. 2 hits.
PS51450. LRR. 4 hits.
PS50837. NACHT. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiNOD2_HUMAN
AccessioniPrimary (citable) accession number: Q9HC29
Secondary accession number(s): E2JEQ6
, Q96RH5, Q96RH6, Q96RH8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 31, 2002
Last sequence update: March 1, 2001
Last modified: November 30, 2016
This is version 169 of the entry and version 1 of the sequence. [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.