Q9HC29 (NOD2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1040 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Induces NF-kappa-B via RICK (CARDIAK, RIP2) and IKK-gamma. Confers responsiveness to intracellular bacterial lipopolysaccharides (LPS).
Subunit structure	Binds to RIPK2/RICK by CARD-CARD interaction. Interacts with ATG16L1. Ref.3 Ref.4
Subcellular location	Cytoplasm.
Tissue specificity	Monocytes-specific.
Domain	The ATG16L1-binding motif mediates interaction with ATG16L1 (Ref.4).
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.5 Ref.7 Ref.8 Ref.9 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.6
Sequence similarities	Contains 2 CARD domains. Contains 9 LRR (leucine-rich) repeats. Contains 1 NACHT domain.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative initiation Polymorphism
Disease	Disease mutation
Domain	Leucine-rich repeat Repeat
Ligand	ATP-binding Nucleotide-binding
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	JNK cascade Traceable author statement. Source: Reactome MyD88-dependent toll-like receptor signaling pathway Traceable author statement. Source: Reactome TRIF-dependent toll-like receptor signaling pathway Traceable author statement. Source: Reactome Toll signaling pathway 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 peptidoglycan Inferred from electronic annotation. Source: Compara cytokine production involved in immune response Inferred from mutant phenotype PubMed 16260731. Source: UniProtKB defense response to Gram-positive bacterium Inferred from electronic annotation. Source: Compara 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 muramyl dipeptide Inferred from direct assay PubMed 15998797. Source: HGNC immunoglobulin production involved in immunoglobulin mediated immune response Inferred from electronic annotation. Source: Compara innate immune response Non-traceable author statement PubMed 17690884. Source: UniProtKB innate immune response in mucosa Inferred from electronic annotation. Source: Compara macrophage inflammatory protein-1 alpha production Inferred from electronic annotation. Source: Compara microglial cell activation involved in immune response Inferred from electronic annotation. Source: Compara negative regulation of NF-kappaB transcription factor activity Inferred from electronic annotation. Source: Compara negative regulation of T cell mediated immunity Inferred from electronic annotation. Source: Compara negative regulation of growth of symbiont in host Inferred from electronic annotation. Source: Compara negative regulation of inflammatory response to antigenic stimulus Inferred from electronic annotation. Source: Compara negative regulation of interferon-gamma production Inferred from electronic annotation. Source: Compara negative regulation of interleukin-12 production Inferred from electronic annotation. Source: Compara negative regulation of interleukin-18 production Inferred from electronic annotation. Source: Compara negative regulation of interleukin-2 production Inferred from electronic annotation. Source: Compara 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: Compara negative regulation of tumor necrosis factor production Inferred from electronic annotation. Source: Compara nucleotide-binding oligomerization domain containing 2 signaling pathway Inferred from direct assay PubMed 12527755. Source: MGI pathogen-associated molecular pattern dependent induction by symbiont of host innate immune response Inferred from electronic annotation. Source: Compara 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 cascade 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 11385577. 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: Compara 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: Compara 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: Compara 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: Compara 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 peptidyl-tyrosine phosphorylation Inferred from electronic annotation. Source: Compara positive regulation of phagocytosis Inferred from electronic annotation. Source: Compara 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 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: Compara response to exogenous dsRNA Inferred from electronic annotation. Source: Compara response to lipopolysaccharide Inferred from electronic annotation. Source: Compara response to nutrient Inferred from electronic annotation. Source: Compara toll-like receptor 1 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
Cellular_component	cell surface Inferred from direct assay PubMed 16714539. Source: UniProtKB cytosol Inferred from direct assay PubMed 15998797. Source: HGNC plasma membrane Inferred from direct assay PubMed 15998797. Source: HGNC vesicle Inferred from direct assay PubMed 15998797. Source: HGNC
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW muramyl dipeptide binding Inferred from direct assay PubMed 15998797. Source: HGNC peptidoglycan binding Inferred from direct assay PubMed 15998797. Source: HGNC
Complete GO annotation...

Alternative products

This entry describes 2 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.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1040	1040	Nucleotide-binding oligomerization domain-containing protein 2		PRO_0000004418
Regions
	Domain	26 – 122	97	CARD 1
	Domain	126 – 218	93	CARD 2
	Domain	293 – 618	326	NACHT
	Repeat	791 – 812	22	LRR 1
	Repeat	816 – 839	24	LRR 2
	Repeat	844 – 865	22	LRR 3
	Repeat	872 – 884	13	LRR 4
	Repeat	900 – 920	21	LRR 5
	Repeat	928 – 949	22	LRR 6
	Repeat	956 – 976	21	LRR 7
	Repeat	984 – 1005	22	LRR 8
	Repeat	1012 – 1032	21	LRR 9
	Nucleotide binding	299 – 306	8	ATP Potential
	Motif	63 – 77	15	ATG16L1-binding motif
Natural variations
	Alternative sequence	1 – 27	27	Missing in isoform 2.		VSP_018689
	Natural variant	81	1	L → V. Corresponds to variant rs34936594 [ dbSNP | Ensembl ].		VAR_036871
	Natural variant	140	1	A → T Associated with Crohn disease and ulcerative colitis. Ref.2 Corresponds to variant rs34684955 [ dbSNP | Ensembl ].		VAR_012665
	Natural variant	157	1	W → R Associated with Crohn disease. Ref.2		VAR_012666
	Natural variant	189	1	T → M. Ref.2		VAR_012667
	Natural variant	235	1	R → C Associated with Crohn disease. Ref.2		VAR_012668
	Natural variant	248	1	L → R Associated with Crohn disease. Ref.2		VAR_012669
	Natural variant	268	1	P → S. Ref.2 Corresponds to variant rs2066842 [ dbSNP | Ensembl ].		VAR_012670
	Natural variant	289	1	N → S. Ref.2 Corresponds to variant rs5743271 [ dbSNP | Ensembl ].		VAR_012671
	Natural variant	291	1	D → N Associated with Crohn disease. Ref.2		VAR_012672
	Natural variant	294	1	T → S Associated with Crohn disease.		VAR_012673
	Natural variant	301	1	A → V Associated with Crohn disease. Ref.2		VAR_012674
	Natural variant	311	1	R → W Associated with Crohn disease and ulcerative colitis. Ref.2		VAR_012675
	Natural variant	334	1	R → Q in BS. Ref.5		VAR_012676
	Natural variant	334	1	R → W in BS. Ref.5 Ref.9		VAR_012677
	Natural variant	348	1	L → V Associated with Crohn disease. Ref.2		VAR_012678
	Natural variant	352	1	H → R Associated with Crohn disease. Ref.2 Corresponds to variant rs5743272 [ dbSNP | Ensembl ].		VAR_012679
	Natural variant	373	1	R → C Associated with Crohn disease. Ref.2		VAR_012680
	Natural variant	382	1	D → E in EOS. Ref.6		VAR_023822
	Natural variant	383	1	E → K in BS. Ref.7		VAR_023823
	Natural variant	414	1	N → S Associated with Crohn disease. Ref.2		VAR_012681
	Natural variant	431	1	S → L Associated with Crohn disease. Ref.2		VAR_012682
	Natural variant	432	1	A → V Associated with Crohn disease. Ref.2 Corresponds to variant rs2076754 [ dbSNP | Ensembl ].		VAR_012683
	Natural variant	441	1	E → K Associated with Crohn disease. Ref.2		VAR_012684
	Natural variant	469	1	L → F in BS. Ref.5		VAR_012685
	Natural variant	471	1	R → C. Corresponds to variant rs1078327 [ dbSNP | Ensembl ].		VAR_036872
	Natural variant	496	1	H → L in EOS. Ref.6		VAR_023824
	Natural variant	605	1	T → N in BS. Ref.8		VAR_065228
	Natural variant	612	1	A → T in EOS; associated with Crohn disease. Ref.2 Ref.6		VAR_012686
	Natural variant	612	1	A → V Associated with Crohn disease. Ref.2		VAR_012687
	Natural variant	684	1	R → W Associated with Crohn disease. Ref.2 Corresponds to variant rs5743276 [ dbSNP | Ensembl ].		VAR_012688
	Natural variant	702	1	R → W Associated with Crohn disease. Ref.2 Corresponds to variant rs2066844 [ dbSNP | Ensembl ].		VAR_012689
	Natural variant	703	1	R → C Associated with Crohn disease and ulcerative colitis. Ref.2 Corresponds to variant rs5743277 [ dbSNP | Ensembl ].		VAR_012690
	Natural variant	713	1	R → C Associated with Crohn disease. Ref.2		VAR_012691
	Natural variant	725	1	A → G Associated with Crohn disease. Ref.2 Corresponds to variant rs5743278 [ dbSNP | Ensembl ].		VAR_012692
	Natural variant	755	1	A → V Associated with Crohn disease and ulcerative colitis. Ref.2		VAR_012693
	Natural variant	758	1	A → V Associated with Crohn disease. Ref.2		VAR_012694
	Natural variant	778	1	E → K Associated with Crohn disease. Ref.2		VAR_012695
	Natural variant	790	1	R → Q. Corresponds to variant rs5743279 [ dbSNP | Ensembl ].		VAR_024402
	Natural variant	793	1	V → M Associated with Crohn disease. Ref.2		VAR_012696
	Natural variant	843	1	E → K Associated with Crohn disease. Ref.2		VAR_012697
	Natural variant	853	1	N → S Associated with Crohn disease. Ref.2		VAR_012698
	Natural variant	863	1	M → V Associated with Crohn disease. Ref.2		VAR_012699
	Natural variant	885	1	A → T Associated with ulcerative colitis. Ref.2		VAR_012700
	Natural variant	908	1	G → R Associated with Crohn disease. Ref.1 Ref.2 Corresponds to variant rs2066845 [ dbSNP | Ensembl ].		VAR_012701
	Natural variant	918	1	A → D Associated with Crohn disease. Ref.2		VAR_012702
	Natural variant	924	1	G → D Associated with Crohn disease. Ref.2		VAR_012703
	Natural variant	955	1	V → I. Ref.2 Corresponds to variant rs5743291 [ dbSNP | Ensembl ].		VAR_012704
Experimental info
	Mutagenesis	305	1	K → R: No activation. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Nod2) [UniParc]. Last modified March 1, 2001. Version 1. Checksum: 0037592D96D7DDFF	FASTA	1,040	115,283
	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
	Isoform 2 (Nod2b) [UniParc]. Checksum: CB7892AB103A5752	FASTA	1,013	112,530
	10 20 30 40 50 60 MCSQEAFQAQ RSQLVELLVS GSLEGFESVL DWLLSWEVLS WEDYEGFHLL GQPLSHLARR 70 80 90 100 110 120 LLDTVWNKGT WACQKLIAAA QEAQADSQSP KLHGCWDPHS LHPARDLQSH RPAIVRRLHS 130 140 150 160 170 180 HVENMLDLAW ERGFVSQYEC DEIRLPIFTP SQRARRLLDL ATVKANGLAA FLLQHVQELP 190 200 210 220 230 240 VPLALPLEAA TCKKYMAKLR TTVSAQSRFL STYDGAETLC LEDIYTENVL EVWADVGMAG 250 260 270 280 290 300 PPQKSPATLG LEELFSTPGH LNDDADTVLV VGEAGSGKST LLQRLHLLWA AGQDFQEFLF 310 320 330 340 350 360 VFPFSCRQLQ CMAKPLSVRT LLFEHCCWPD VGQEDIFQLL LDHPDRVLLT FDGFDEFKFR 370 380 390 400 410 420 FTDRERHCSP TDPTSVQTLL FNLLQGNLLK NARKVVTSRP AAVSAFLRKY IRTEFNLKGF 430 440 450 460 470 480 SEQGIELYLR KRHHEPGVAD RLIRLLQETS ALHGLCHLPV FSWMVSKCHQ ELLLQEGGSP 490 500 510 520 530 540 KTTTDMYLLI LQHFLLHATP PDSASQGLGP SLLRGRLPTL LHLGRLALWG LGMCCYVFSA 550 560 570 580 590 600 QQLQAAQVSP DDISLGFLVR AKGVVPGSTA PLEFLHITFQ CFFAAFYLAL SADVPPALLR 610 620 630 640 650 660 HLFNCGRPGN SPMARLLPTM CIQASEGKDS SVAALLQKAE PHNLQITAAF LAGLLSREHW 670 680 690 700 710 720 GLLAECQTSE KALLRRQACA RWCLARSLRK HFHSIPPAAP GEAKSVHAMP GFIWLIRSLY 730 740 750 760 770 780 EMQEERLARK AARGLNVGHL KLTFCSVGPT ECAALAFVLQ HLRRPVALQL DYNSVGDIGV 790 800 810 820 830 840 EQLLPCLGVC KALYLRDNNI SDRGICKLIE CALHCEQLQK LALFNNKLTD GCAHSMAKLL 850 860 870 880 890 900 ACRQNFLALR LGNNYITAAG AQVLAEGLRG NTSLQFLGFW GNRVGDEGAQ ALAEALGDHQ 910 920 930 940 950 960 SLRWLSLVGN NIGSVGAQAL ALMLAKNVML EELCLEENHL QDEGVCSLAE GLKKNSSLKI 970 980 990 1000 1010 LKLSNNCITY LGAEALLQAL ERNDTILEVW LRGNTFSLEE VDKLGCRDTR LLL

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 (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]	"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/RICK.
[4]	"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.
[5]	"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.
[6]	"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.
[7]	"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.
[8]	"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.
[9]	"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

GeneReviews

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.
IPI	IPI00005559. IPI00759531.
RefSeq	NP_071445.1. NM_022162.1.
UniGene	Hs.592072.
3D structure databases
ProteinModelPortal	Q9HC29.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-41998N.
MINT	MINT-151071.
STRING	9606.ENSP00000300589.
PTM databases
PhosphoSite	Q9HC29.
Polymorphism databases
DMDM	20137973.
Proteomic databases
PaxDb	Q9HC29.
PRIDE	Q9HC29.
Protocols and materials databases
DNASU	64127.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000300589; ENSP00000300589; ENSG00000167207.
GeneID	64127.
KEGG	hsa:64127.
UCSC	uc002egl.1. human.
Organism-specific databases
CTD	64127.
GeneCards	GC16P050729.
HGNC	HGNC:5331. NOD2.
MIM	186580. phenotype. 266600. phenotype. 605956. gene. 609464. phenotype.
neXtProt	NX_Q9HC29.
Orphanet	90340. Blau syndrome. 206. Crohn disease. 90341. Early-onset sarcoidosis. 771. Ulcerative colitis.
PharmGKB	PA26074.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG248107.
HOGENOM	HOG000113814.
HOVERGEN	HBG050792.
InParanoid	Q9HC29.
KO	K10165.
OMA	QYECDEI.
OrthoDB	EOG4WM4T6.
PhylomeDB	Q9HC29.
Enzyme and pathway databases
Pathway_Interaction_DB	nfkappabcanonicalpathway. Canonical NF-kappaB pathway.
Reactome	REACT_6782. TRAF6 Mediated Induction of proinflammatory cytokines. REACT_6900. Immune System.
Gene expression databases
ArrayExpress	Q9HC29.
Bgee	Q9HC29.
CleanEx	HS_NOD2.
Genevestigator	Q9HC29.
GermOnline	ENSG00000167207. Homo sapiens.
Family and domain databases
Gene3D	1.10.533.10. 2 hits.
InterPro	IPR001315. CARD. IPR011029. DEATH-like_dom. IPR001611. Leu-rich_rpt. IPR007111. NACHT_NTPase. [Graphical view]
Pfam	PF00619. CARD. 2 hits. [Graphical view]
SMART	SM00114. CARD. 1 hit. [Graphical view]
SUPFAM	SSF47986. DEATH_like. 2 hits.
PROSITE	PS50209. CARD. 2 hits. PS51450. LRR. 4 hits. PS50837. NACHT. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q9HC29.
ChEMBL	CHEMBL1293266.
GenomeRNAi	64127.
NextBio	66012.
SOURCE	Search...

Entry information

Entry name

NOD2_HUMAN

Accession

Primary (citable) accession number: Q9HC29
Secondary accession number(s): Q96RH5, Q96RH6, Q96RH8

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 31, 2002
Last sequence update:	March 1, 2001
Last modified:	May 1, 2013
This is version 130 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.