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Protein

Nucleotide-binding oligomerization domain-containing protein 2

Gene

NOD2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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, INAVA 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). Component of an autophagy-mediated antibacterial pathway together with ATG16L1 (PubMed:20637199). Plays also a role in sensing single-stranded RNA (ssRNA) from viruses. Interacts with mitochondrial antiviral signaling/MAVS, leading to activation of interferon regulatory factor-3/IRF3 and expression of type I interferon (PubMed:19701189).5 Publications

Regions

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

GO - Molecular functioni

GO - Biological processi

Keywordsi

Biological processImmunity, Innate immunity
LigandATP-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-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
R-HSA-9020702 Interleukin-1 signaling
SignaLinkiQ9HC29
SIGNORiQ9HC29

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

EuPathDBiHostDB:ENSG00000167207.11
HGNCiHGNC:5331 NOD2
MIMi605956 gene
neXtProtiNX_Q9HC29

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Mitochondrion

Pathology & Biotechi

Involvement in diseasei

Blau syndrome (BLAUS)13 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant inflammatory disorder characterized by the formation of immune granulomas invading the skin, joints and eye. Other organs may be involved. Clinical manifestations are variable and include early-onset granulomatous arthritis, uveitis and skin rash. Blindness, joint destruction and visceral involvement have been reported in severe cases.
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; abolishes interaction with LDOC1, ANKHD1, PPP2R3B, ENTR1 and TRIM41; decreases interaction with RIPK2 and PPP1R12C; no effect on interaction with CHMP5. 6 PublicationsCorresponds to variant dbSNP:rs104895461EnsemblClinVar.1
Natural variantiVAR_012677334R → W in BLAUS; no disruption of NOD2-CARD9 interaction; hyperactive. 7 PublicationsCorresponds to variant dbSNP:rs104895462EnsemblClinVar.1
Natural variantiVAR_023822382D → E in BLAUS; hyperactive. 2 PublicationsCorresponds to variant dbSNP:rs104895476EnsemblClinVar.1
Natural variantiVAR_073231383E → G in BLAUS; unknown pathological significance; hyperactive. 2 PublicationsCorresponds to variant dbSNP:rs104895493EnsemblClinVar.1
Natural variantiVAR_023823383E → K in BLAUS; hyperactive. 3 PublicationsCorresponds to variant dbSNP:rs104895477EnsemblClinVar.1
Natural variantiVAR_012685469L → F in BLAUS; hyperactive. 2 PublicationsCorresponds to variant dbSNP:rs104895460EnsemblClinVar.1
Natural variantiVAR_073235481G → D in BLAUS; atypical form with cardiac infiltration; sporadic case; unknown pathological significance; hyperactive. 2 PublicationsCorresponds to variant dbSNP:rs104895494EnsemblClinVar.1
Natural variantiVAR_073236490W → L in BLAUS; unknown pathological significance; hyperactive. 2 PublicationsCorresponds to variant dbSNP:rs104895480EnsemblClinVar.1
Natural variantiVAR_073237495C → Y in BLAUS; unknown pathological significance; hyperactive. 3 PublicationsCorresponds to variant dbSNP:rs104895478EnsemblClinVar.1
Natural variantiVAR_023824496H → L in BLAUS; hyperactive. 3 PublicationsCorresponds to variant dbSNP:rs104895472EnsemblClinVar.1
Natural variantiVAR_073180507P → S in BLAUS. 1 Publication1
Natural variantiVAR_073238513M → T in BLAUS; hyperactive. 3 PublicationsCorresponds to variant dbSNP:rs104895473EnsemblClinVar.1
Natural variantiVAR_073240587R → C in BLAUS; unknown pathological significance; not hyperactive. 2 PublicationsCorresponds to variant dbSNP:rs104895479EnsemblClinVar.1
Natural variantiVAR_065228605T → N in BLAUS; hyperactive. 2 Publications1
Natural variantiVAR_073241605T → P in BLAUS; hyperactive. 3 PublicationsCorresponds to variant dbSNP:rs104895474EnsemblClinVar.1
Natural variantiVAR_073242670N → K in BLAUS; hyperactive. 3 PublicationsCorresponds to variant dbSNP:rs104895475EnsemblClinVar.1
Inflammatory bowel disease 1 (IBD1)6 Publications
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:266600
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_073228113D → N in IBD1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs104895468EnsemblClinVar.1
Natural variantiVAR_012665140A → T in IBD1; also found in patients with ulcerative colitis; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs34684955EnsemblClinVar.1
Natural variantiVAR_012666157W → R in IBD1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs104895420EnsemblClinVar.1
Natural variantiVAR_012668235R → C in IBD1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs104895422EnsemblClinVar.1
Natural variantiVAR_012669248L → R in IBD1; unknown pathological significance; no disruption of NOD2-CARD9 interaction. 2 PublicationsCorresponds to variant dbSNP:rs104895423EnsemblClinVar.1
Natural variantiVAR_012672291D → N in IBD1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs104895424EnsemblClinVar.1
Natural variantiVAR_012673294T → S in IBD1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs104895425EnsemblClinVar.1
Natural variantiVAR_012674301A → V in IBD1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs104895426EnsemblClinVar.1
Natural variantiVAR_012675311R → W in IBD1; also found in patients with ulcerative colitis; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs104895427EnsemblClinVar.1
Natural variantiVAR_012678348L → V in IBD1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs104895428EnsemblClinVar.1
Natural variantiVAR_012679352H → R in IBD1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs5743272EnsemblClinVar.1
Natural variantiVAR_073229357D → A in IBD1; unknown pathological significance; no disruption of NOD2-CARD9 interaction. 2 PublicationsCorresponds to variant dbSNP:rs104895469EnsemblClinVar.1
Natural variantiVAR_073230363I → F in IBD1; unknown pathological significance; no disruption of NOD2-CARD9 interaction. 2 PublicationsCorresponds to variant dbSNP:rs104895470EnsemblClinVar.1
Natural variantiVAR_012680373R → C in IBD1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs145293873EnsemblClinVar.1
Natural variantiVAR_012681414N → S in IBD1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs104895429EnsemblClinVar.1
Natural variantiVAR_012682431S → L in IBD1; unknown pathological significance; no disruption of NOD2-CARD9 interaction. 2 PublicationsCorresponds to variant dbSNP:rs104895431EnsemblClinVar.1
Natural variantiVAR_012683432A → V in IBD1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs2076754Ensembl.1
Natural variantiVAR_012684441E → K in IBD1; unknown pathological significance; no disruption of NOD2-CARD9 interaction. 2 PublicationsCorresponds to variant dbSNP:rs104895432EnsemblClinVar.1
Natural variantiVAR_073239550L → V in IBD1; unknown pathological significance; no disruption of NOD2-CARD9 interaction. 2 PublicationsCorresponds to variant dbSNP:rs104895471EnsemblClinVar.1
Natural variantiVAR_012687612A → V in IBD1; unknown pathological significance; no disruption of NOD2-CARD9 interaction. 2 PublicationsCorresponds to variant dbSNP:rs104895439EnsemblClinVar.1
Natural variantiVAR_012688684R → W in IBD1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs5743276EnsemblClinVar.1
Natural variantiVAR_012690703R → C in IBD1; also found in patients with ulcerative colitis; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs5743277EnsemblClinVar.1
Natural variantiVAR_012691713R → C in IBD1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs104895440EnsemblClinVar.1
Natural variantiVAR_073243713R → H in IBD1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs104895483EnsemblClinVar.1
Natural variantiVAR_012692725A → G in IBD1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs5743278EnsemblClinVar.1
Natural variantiVAR_012693755A → V in IBD1; also found in patients with ulcerative colitis; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs61747625EnsemblClinVar.1
Natural variantiVAR_012694758A → V in IBD1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs104895442EnsemblClinVar.1
Natural variantiVAR_073244760R → C in IBD1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs3813758Ensembl.1
Natural variantiVAR_012695778E → K in IBD1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs104895443EnsemblClinVar.1
Natural variantiVAR_073245790R → W in IBD1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs62029861Ensembl.1
Natural variantiVAR_012696793V → M in IBD1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs104895444EnsemblClinVar.1
Natural variantiVAR_012697843E → K in IBD1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs104895445EnsemblClinVar.1
Natural variantiVAR_073249852N → S in IBD1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs104895467EnsemblClinVar.1
Natural variantiVAR_012698853N → S in IBD1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs104895446EnsemblClinVar.1
Natural variantiVAR_012699863M → V in IBD1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs104895447EnsemblClinVar.1
Natural variantiVAR_012700885A → T in IBD1; unknown pathological significance. 1 Publication1
Natural variantiVAR_012703924G → D in IBD1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs104895453EnsemblClinVar.1
Yao syndrome (YAOS)2 Publications
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionAn autoinflammatory disease characterized by periodic fever, dermatitis, polyarthritis, leg swelling, and gastrointestinal and sicca-like symptoms. YAOS is a complex disease with multifactorial inheritance.
See also OMIM:617321

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
617321 phenotype
OpenTargetsiENSG00000167207
Orphaneti90340 Blau syndrome
206 NON RARE IN EUROPE: Crohn disease
771 NON RARE IN EUROPE: 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
ProteomicsDBi81629
81630 [Q9HC29-2]

PTM databases

iPTMnetiQ9HC29
PhosphoSitePlusiQ9HC29

Expressioni

Tissue specificityi

Expressed in intestinal mucosa, mainly in Paneth cells and, at lower extent, in the glandular epithelium.1 Publication

Inductioni

Up-regulated by muramyl-dipeptide and lipopolysaccharide.1 Publication

Gene expression databases

BgeeiENSG00000167207 Expressed in 126 organ(s), highest expression level in ectocervix
CleanExiHS_NOD2
ExpressionAtlasiQ9HC29 baseline and differential
GenevisibleiQ9HC29 HS

Organism-specific databases

HPAiHPA041985
HPA054494

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, PubMed:27812135). Interacts with ATG16L1 (PubMed:20637199, 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). Interacts with MAPKBP1; the interaction is enhanced in the presence of muramyl dipeptide (MDP) (PubMed:22700971). Interacts with INAVA; the interaction takes place upon PRR stimulation (PubMed:28436939). Interacts with ANKHD1, C10ORF67, CHMP5, DOCK7, ENTR1, KRT15, LDOC1, PPP1R12C, PPP2R3B, TRIM41 and VIM (PubMed:27812135).13 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi122077, 33 interactors
DIPiDIP-41998N
IntActiQ9HC29, 23 interactors
MINTiQ9HC29
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

Keywords - Domaini

Leucine-rich repeat, Repeat

Phylogenomic databases

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

Family and domain databases

Gene3Di3.80.10.10, 1 hit
InterProiView protein in InterPro
IPR001315 CARD
IPR011029 DEATH-like_dom_sf
IPR001611 Leu-rich_rpt
IPR032675 LRR_dom_sf
IPR007111 NACHT_NTPase
IPR027417 P-loop_NTPase
PfamiView protein in Pfam
PF00619 CARD, 1 hit
PF13516 LRR_6, 3 hits
PF05729 NACHT, 1 hit
SUPFAMiSSF47986 SSF47986, 2 hits
SSF52540 SSF52540, 1 hit
PROSITEiView protein in PROSITE
PS50209 CARD, 2 hits
PS51450 LRR, 4 hits
PS50837 NACHT, 1 hit

Sequences (3+)i

Sequence statusi: Complete.

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

This entry has 3 described isoforms and 5 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E9PK30E9PK30_HUMAN
Nucleotide-binding oligomerization ...
NOD2
146Annotation score:
A0A286YF65A0A286YF65_HUMAN
Nucleotide-binding oligomerization ...
NOD2
793Annotation score:
H0YF53H0YF53_HUMAN
Nucleotide-binding oligomerization ...
NOD2
169Annotation score:
J3QL80J3QL80_HUMAN
Nucleotide-binding oligomerization ...
NOD2
60Annotation score:
E9PLF7E9PLF7_HUMAN
Nucleotide-binding oligomerization ...
NOD2
35Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03687181L → V. Corresponds to variant dbSNP:rs34936594EnsemblClinVar.1
Natural variantiVAR_073228113D → N in IBD1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs104895468EnsemblClinVar.1
Natural variantiVAR_012665140A → T in IBD1; also found in patients with ulcerative colitis; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs34684955EnsemblClinVar.1
Natural variantiVAR_012666157W → R in IBD1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs104895420EnsemblClinVar.1
Natural variantiVAR_012667189T → M1 PublicationCorresponds to variant dbSNP:rs61755182EnsemblClinVar.1
Natural variantiVAR_012668235R → C in IBD1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs104895422EnsemblClinVar.1
Natural variantiVAR_012669248L → R in IBD1; unknown pathological significance; no disruption of NOD2-CARD9 interaction. 2 PublicationsCorresponds to variant dbSNP:rs104895423EnsemblClinVar.1
Natural variantiVAR_012670268P → S3 PublicationsCorresponds to variant dbSNP:rs2066842EnsemblClinVar.1
Natural variantiVAR_012671289N → S2 PublicationsCorresponds to variant dbSNP:rs5743271EnsemblClinVar.1
Natural variantiVAR_012672291D → N in IBD1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs104895424EnsemblClinVar.1
Natural variantiVAR_012673294T → S in IBD1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs104895425EnsemblClinVar.1
Natural variantiVAR_012674301A → V in IBD1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs104895426EnsemblClinVar.1
Natural variantiVAR_012675311R → W in IBD1; also found in patients with ulcerative colitis; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs104895427EnsemblClinVar.1
Natural variantiVAR_012676334R → Q in BLAUS; somatic mosaicism in 4.9% to 11% of peripheral blood cells; hyperactive; abolishes interaction with LDOC1, ANKHD1, PPP2R3B, ENTR1 and TRIM41; decreases interaction with RIPK2 and PPP1R12C; no effect on interaction with CHMP5. 6 PublicationsCorresponds to variant dbSNP:rs104895461EnsemblClinVar.1
Natural variantiVAR_012677334R → W in BLAUS; no disruption of NOD2-CARD9 interaction; hyperactive. 7 PublicationsCorresponds to variant dbSNP:rs104895462EnsemblClinVar.1
Natural variantiVAR_012678348L → V in IBD1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs104895428EnsemblClinVar.1
Natural variantiVAR_012679352H → R in IBD1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs5743272EnsemblClinVar.1
Natural variantiVAR_073229357D → A in IBD1; unknown pathological significance; no disruption of NOD2-CARD9 interaction. 2 PublicationsCorresponds to variant dbSNP:rs104895469EnsemblClinVar.1
Natural variantiVAR_073230363I → F in IBD1; unknown pathological significance; no disruption of NOD2-CARD9 interaction. 2 PublicationsCorresponds to variant dbSNP:rs104895470EnsemblClinVar.1
Natural variantiVAR_012680373R → C in IBD1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs145293873EnsemblClinVar.1
Natural variantiVAR_023822382D → E in BLAUS; hyperactive. 2 PublicationsCorresponds to variant dbSNP:rs104895476EnsemblClinVar.1
Natural variantiVAR_073231383E → G in BLAUS; unknown pathological significance; hyperactive. 2 PublicationsCorresponds to variant dbSNP:rs104895493EnsemblClinVar.1
Natural variantiVAR_023823383E → K in BLAUS; hyperactive. 3 PublicationsCorresponds to variant dbSNP:rs104895477EnsemblClinVar.1
Natural variantiVAR_073232391R → C1 PublicationCorresponds to variant dbSNP:rs104895481EnsemblClinVar.1
Natural variantiVAR_012681414N → S in IBD1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs104895429EnsemblClinVar.1
Natural variantiVAR_012682431S → L in IBD1; unknown pathological significance; no disruption of NOD2-CARD9 interaction. 2 PublicationsCorresponds to variant dbSNP:rs104895431EnsemblClinVar.1
Natural variantiVAR_012683432A → V in IBD1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs2076754Ensembl.1
Natural variantiVAR_012684441E → K in IBD1; unknown pathological significance; no disruption of NOD2-CARD9 interaction. 2 PublicationsCorresponds to variant dbSNP:rs104895432EnsemblClinVar.1
Natural variantiVAR_073233463P → A Polymorphism; no disruption of NOD2-CARD9 interaction. 2 PublicationsCorresponds to variant dbSNP:rs104895482EnsemblClinVar.1
Natural variantiVAR_073234464G → W Polymorphism; hyperactive. 1 PublicationCorresponds to variant dbSNP:rs104895492EnsemblClinVar.1
Natural variantiVAR_012685469L → F in BLAUS; hyperactive. 2 PublicationsCorresponds to variant dbSNP:rs104895460EnsemblClinVar.1
Natural variantiVAR_036872471R → C Polymorphism; does not affect activity. 1 PublicationCorresponds to variant dbSNP:rs1078327EnsemblClinVar.1
Natural variantiVAR_073235481G → D in BLAUS; atypical form with cardiac infiltration; sporadic case; unknown pathological significance; hyperactive. 2 PublicationsCorresponds to variant dbSNP:rs104895494EnsemblClinVar.1
Natural variantiVAR_073236490W → L in BLAUS; unknown pathological significance; hyperactive. 2 PublicationsCorresponds to variant dbSNP:rs104895480EnsemblClinVar.1
Natural variantiVAR_073237495C → Y in BLAUS; unknown pathological significance; hyperactive. 3 PublicationsCorresponds to variant dbSNP:rs104895478EnsemblClinVar.1
Natural variantiVAR_023824496H → L in BLAUS; hyperactive. 3 PublicationsCorresponds to variant dbSNP:rs104895472EnsemblClinVar.1
Natural variantiVAR_073180507P → S in BLAUS. 1 Publication1
Natural variantiVAR_073238513M → T in BLAUS; hyperactive. 3 PublicationsCorresponds to variant dbSNP:rs104895473EnsemblClinVar.1
Natural variantiVAR_073239550L → V in IBD1; unknown pathological significance; no disruption of NOD2-CARD9 interaction. 2 PublicationsCorresponds to variant dbSNP:rs104895471EnsemblClinVar.1
Natural variantiVAR_073240587R → C in BLAUS; unknown pathological significance; not hyperactive. 2 PublicationsCorresponds to variant dbSNP:rs104895479EnsemblClinVar.1
Natural variantiVAR_065228605T → N in BLAUS; hyperactive. 2 Publications1
Natural variantiVAR_073241605T → P in BLAUS; hyperactive. 3 PublicationsCorresponds to variant dbSNP:rs104895474EnsemblClinVar.1
Natural variantiVAR_012686612A → T in BLAUS and IBD1; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs104895438EnsemblClinVar.1
Natural variantiVAR_012687612A → V in IBD1; unknown pathological significance; no disruption of NOD2-CARD9 interaction. 2 PublicationsCorresponds to variant dbSNP:rs104895439EnsemblClinVar.1
Natural variantiVAR_073242670N → K in BLAUS; hyperactive. 3 PublicationsCorresponds to variant dbSNP:rs104895475EnsemblClinVar.1
Natural variantiVAR_012688684R → W in IBD1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs5743276EnsemblClinVar.1
Natural variantiVAR_012689702R → W in IBD1 and YAOS; associated with disease susceptibility; no disruption of NOD2-CARD9 interaction; decreases half-life of protein; abolishes interaction with ANKHD1, ENTR1 and TRIM41; increases interaction with RIPK2 and PPP2R3B; decreases interaction with LDOC1 and PPP1R12C; no effect on interaction with CHMP5. 6 PublicationsCorresponds to variant dbSNP:rs2066844EnsemblClinVar.1
Natural variantiVAR_012690703R → C in IBD1; also found in patients with ulcerative colitis; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs5743277EnsemblClinVar.1
Natural variantiVAR_012691713R → C in IBD1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs104895440EnsemblClinVar.1
Natural variantiVAR_073243713R → H in IBD1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs104895483EnsemblClinVar.1
Natural variantiVAR_012692725A → G in IBD1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs5743278EnsemblClinVar.1
Natural variantiVAR_012693755A → V in IBD1; also found in patients with ulcerative colitis; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs61747625EnsemblClinVar.1
Natural variantiVAR_012694758A → V in IBD1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs104895442EnsemblClinVar.1
Natural variantiVAR_073244760R → C in IBD1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs3813758Ensembl.1
Natural variantiVAR_012695778E → K in IBD1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs104895443EnsemblClinVar.1
Natural variantiVAR_024402790R → Q. Corresponds to variant dbSNP:rs5743279EnsemblClinVar.1
Natural variantiVAR_073245790R → W in IBD1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs62029861Ensembl.1
Natural variantiVAR_073246791R → W1 PublicationCorresponds to variant dbSNP:rs104895484EnsemblClinVar.1
Natural variantiVAR_012696793V → M in IBD1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs104895444EnsemblClinVar.1
Natural variantiVAR_073247825N → K1 PublicationCorresponds to variant dbSNP:rs104895485EnsemblClinVar.1
Natural variantiVAR_012697843E → K in IBD1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs104895445EnsemblClinVar.1
Natural variantiVAR_073248849A → V1 PublicationCorresponds to variant dbSNP:rs104895486EnsemblClinVar.1
Natural variantiVAR_073249852N → S in IBD1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs104895467EnsemblClinVar.1
Natural variantiVAR_012698853N → S in IBD1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs104895446EnsemblClinVar.1
Natural variantiVAR_012699863M → V in IBD1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs104895447EnsemblClinVar.1
Natural variantiVAR_012700885A → T in IBD1; unknown pathological significance. 1 Publication1
Natural variantiVAR_012701908G → R in IBD1 and YAOS; associated with disease susceptibility; decreases half-life of protein; abolishes interaction with ANKHD1, ENTR1 and TRIM41; decreases interaction with RIPK2 and PPP1R12C; no effect on interaction with CHMP5, LDOC1 and PPP2R3B. 6 PublicationsCorresponds to variant dbSNP:rs2066845EnsemblClinVar.1
Natural variantiVAR_012702918A → D1 PublicationCorresponds to variant dbSNP:rs104895452EnsemblClinVar.1
Natural variantiVAR_012703924G → D in IBD1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs104895453EnsemblClinVar.1
Natural variantiVAR_012704955V → I1 PublicationCorresponds to variant dbSNP:rs5743291EnsemblClinVar.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]
CCDS86525.1 [Q9HC29-2]
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]
ENST00000647318; ENSP00000495993; ENSG00000167207 [Q9HC29-2]
GeneIDi64127
KEGGihsa:64127
UCSCiuc002egm.2 human [Q9HC29-1]

Keywords - Coding sequence diversityi

Alternative initiation, Polymorphism

Similar proteinsi

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]
CCDS86525.1 [Q9HC29-2]
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, 23 interactors
MINTiQ9HC29
STRINGi9606.ENSP00000300589

Chemistry databases

BindingDBiQ9HC29
ChEMBLiCHEMBL1293266
GuidetoPHARMACOLOGYi1763

PTM databases

iPTMnetiQ9HC29
PhosphoSitePlusiQ9HC29

Polymorphism and mutation databases

BioMutaiNOD2
DMDMi20137973

Proteomic databases

EPDiQ9HC29
PaxDbiQ9HC29
PeptideAtlasiQ9HC29
PRIDEiQ9HC29
ProteomicsDBi81629
81630 [Q9HC29-2]

Protocols and materials databases

DNASUi64127
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000300589; ENSP00000300589; ENSG00000167207 [Q9HC29-1]
ENST00000647318; ENSP00000495993; ENSG00000167207 [Q9HC29-2]
GeneIDi64127
KEGGihsa:64127
UCSCiuc002egm.2 human [Q9HC29-1]

Organism-specific databases

CTDi64127
DisGeNETi64127
EuPathDBiHostDB:ENSG00000167207.11
GeneCardsiNOD2
HGNCiHGNC:5331 NOD2
HPAiHPA041985
HPA054494
MalaCardsiNOD2
MIMi186580 phenotype
266600 phenotype
605956 gene
617321 phenotype
neXtProtiNX_Q9HC29
OpenTargetsiENSG00000167207
Orphaneti90340 Blau syndrome
206 NON RARE IN EUROPE: Crohn disease
771 NON RARE IN EUROPE: Ulcerative colitis
PharmGKBiPA26074
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4308 Eukaryota
ENOG410ZBX3 LUCA
GeneTreeiENSGT00860000133673
HOGENOMiHOG000113814
HOVERGENiHBG050792
InParanoidiQ9HC29
KOiK10165
OMAiLHCEQLQ
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-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
R-HSA-9020702 Interleukin-1 signaling
SignaLinkiQ9HC29
SIGNORiQ9HC29

Miscellaneous databases

GeneWikiiNOD2
GenomeRNAii64127
PROiPR:Q9HC29
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000167207 Expressed in 126 organ(s), highest expression level in ectocervix
CleanExiHS_NOD2
ExpressionAtlasiQ9HC29 baseline and differential
GenevisibleiQ9HC29 HS

Family and domain databases

Gene3Di3.80.10.10, 1 hit
InterProiView protein in InterPro
IPR001315 CARD
IPR011029 DEATH-like_dom_sf
IPR001611 Leu-rich_rpt
IPR032675 LRR_dom_sf
IPR007111 NACHT_NTPase
IPR027417 P-loop_NTPase
PfamiView protein in Pfam
PF00619 CARD, 1 hit
PF13516 LRR_6, 3 hits
PF05729 NACHT, 1 hit
SUPFAMiSSF47986 SSF47986, 2 hits
SSF52540 SSF52540, 1 hit
PROSITEiView protein in PROSITE
PS50209 CARD, 2 hits
PS51450 LRR, 4 hits
PS50837 NACHT, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiNOD2_HUMAN
AccessioniPrimary (citable) accession number: Q9HC29
Secondary accession number(s): E2JEQ6
, Q96RH5, Q96RH6, Q96RH8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 31, 2002
Last sequence update: March 1, 2001
Last modified: November 7, 2018
This is version 188 of the entry and version 1 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
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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