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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

Recognizes muramyl dipeptide (MDP) constituents of bacterial peptidoglycans and plays a key role in gastrointestinal immunity: upon stimulation, binds the proximal adapter receptor-interacting RIPK2, which recruits ubiquitin ligases as XIAP, BIRC2, BIRC3 and the LUBAC complex, triggering activation of MAP kinases and activation of NF-kappa-B signaling, leading to activate the transcription of hundreds of genes involved in immune response.1 Publication

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi299 – 3068ATPPROSITE-ProRule annotation

GO - Molecular functioni

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

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Immunity, Innate immunity

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiREACT_21281. TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
REACT_21368. JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1.
REACT_21399. activated TAK1 mediates p38 MAPK activation.
REACT_22442. Interleukin-1 signaling.
REACT_75776. NOD1/2 Signaling Pathway.
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
ProteomesiUP000005640 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-SubCell
  • cell surface Source: UniProtKB
  • cytoplasm Source: UniProtKB
  • cytoskeleton Source: UniProtKB
  • cytosol Source: HGNC
  • plasma membrane Source: HGNC
  • 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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti334 – 3341R → Q in BLAUS; somatic mosaicism in 4.9% to 11% of peripheral blood cells; hyperactive. 5 Publications
Corresponds to variant rs104895461 [ dbSNP | Ensembl ].
VAR_012676
Natural varianti334 – 3341R → W in BLAUS and EOS; no disruption of NOD2-CARD9 interaction; hyperactive. 7 Publications
Corresponds to variant rs104895462 [ dbSNP | Ensembl ].
VAR_012677
Natural varianti383 – 3831E → K in BLAUS; hyperactive. 3 Publications
Corresponds to variant rs104895477 [ dbSNP | Ensembl ].
VAR_023823
Natural varianti469 – 4691L → F in BLAUS; hyperactive. 2 Publications
Corresponds to variant rs104895460 [ dbSNP | Ensembl ].
VAR_012685
Natural varianti490 – 4901W → L in BLAUS; unknown pathological significance; hyperactive. 2 Publications
Corresponds to variant rs104895480 [ dbSNP | Ensembl ].
VAR_073236
Natural varianti495 – 4951C → Y in BLAUS; unknown pathological significance; hyperactive. 3 Publications
Corresponds to variant rs104895478 [ dbSNP | Ensembl ].
VAR_073237
Natural varianti507 – 5071P → S in BLAUS. 1 Publication
VAR_073180
Natural varianti587 – 5871R → C in BLAUS; unknown pathological significance; not hyperactive. 2 Publications
Corresponds to variant rs104895479 [ dbSNP | Ensembl ].
VAR_073240
Natural varianti605 – 6051T → N in BLAUS; hyperactive. 2 Publications
VAR_065228
Inflammatory bowel disease 1 (IBD1)1 Publication

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
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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti334 – 3341R → W in BLAUS and EOS; no disruption of NOD2-CARD9 interaction; hyperactive. 7 Publications
Corresponds to variant rs104895462 [ dbSNP | Ensembl ].
VAR_012677
Natural varianti382 – 3821D → E in EOS; hyperactive. 2 Publications
VAR_023822
Natural varianti481 – 4811G → D in EOS; atypical form of EOS with cardiac infiltration; sporadic case; unknown pathological significance; hyperactive. 2 Publications
Corresponds to variant rs104895494 [ dbSNP | Ensembl ].
VAR_073235
Natural varianti496 – 4961H → L in EOS; hyperactive. 3 Publications
Corresponds to variant rs104895472 [ dbSNP | Ensembl ].
VAR_023824
Natural varianti513 – 5131M → T in EOS; hyperactive. 3 Publications
Corresponds to variant rs104895473 [ dbSNP | Ensembl ].
VAR_073238
Natural varianti605 – 6051T → P in EOS; hyperactive. 3 Publications
Corresponds to variant rs104895474 [ dbSNP | Ensembl ].
VAR_073241
Natural varianti612 – 6121A → T in EOS; associated with Crohn disease. 2 Publications
VAR_012686
Natural varianti670 – 6701N → K in EOS; hyperactive. 3 Publications
Corresponds to variant rs104895475 [ dbSNP | Ensembl ].
VAR_073242

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi305 – 3051K → R: No activation. 1 Publication
Mutagenesisi379 – 3791D → A: No disruption in NOD2-CARD9 interaction. 1 Publication

Keywords - Diseasei

Disease mutation

Organism-specific databases

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

Polymorphism and mutation databases

BioMutaiNOD2.
DMDMi20137973.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 10401040Nucleotide-binding oligomerization domain-containing protein 2PRO_0000004418Add
BLAST

Post-translational modificationi

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

Keywords - PTMi

Ubl conjugation

Proteomic databases

PaxDbiQ9HC29.
PRIDEiQ9HC29.

PTM databases

PhosphoSiteiQ9HC29.

Expressioni

Tissue specificityi

Monocytes-specific.

Gene expression databases

BgeeiQ9HC29.
CleanExiHS_NOD2.
ExpressionAtlasiQ9HC29. baseline and differential.
GenevisibleiQ9HC29. HS.

Organism-specific databases

HPAiHPA041985.

Interactioni

Subunit structurei

Found in 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).8 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
RIPK2O433532EBI-7445625,EBI-358522
TRIM27P1437310EBI-7445625,EBI-719493

Protein-protein interaction databases

BioGridi122077. 30 interactions.
DIPiDIP-41998N.
IntActiQ9HC29. 7 interactions.
MINTiMINT-151071.
STRINGi9606.ENSP00000300589.

Structurei

3D structure databases

ProteinModelPortaliQ9HC29.
SMRiQ9HC29. Positions 291-316, 747-1029.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini26 – 12297CARD 1PROSITE-ProRule annotationAdd
BLAST
Domaini126 – 21893CARD 2PROSITE-ProRule annotationAdd
BLAST
Domaini293 – 618326NACHTPROSITE-ProRule annotationAdd
BLAST
Repeati791 – 81222LRR 1Add
BLAST
Repeati816 – 83924LRR 2Add
BLAST
Repeati844 – 86522LRR 3Add
BLAST
Repeati872 – 88413LRR 4Add
BLAST
Repeati900 – 92021LRR 5Add
BLAST
Repeati928 – 94922LRR 6Add
BLAST
Repeati956 – 97621LRR 7Add
BLAST
Repeati984 – 100522LRR 8Add
BLAST
Repeati1012 – 103221LRR 9Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni241 – 27434Required for CARD9 binding1 PublicationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi63 – 7715ATG16L1-binding motifAdd
BLAST

Domaini

The ATG16L1-binding motif mediates interaction with ATG16L1.1 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

eggNOGiNOG248107.
GeneTreeiENSGT00790000123007.
HOGENOMiHOG000113814.
HOVERGENiHBG050792.
InParanoidiQ9HC29.
KOiK10165.
OMAiNVGHLKL.
OrthoDBiEOG7P5T07.
PhylomeDBiQ9HC29.
TreeFamiTF352118.

Family and domain databases

Gene3Di1.10.533.10. 2 hits.
InterProiIPR001315. CARD.
IPR011029. DEATH-like_dom.
IPR001611. Leu-rich_rpt.
IPR007111. NACHT_NTPase.
IPR027417. P-loop_NTPase.
[Graphical view]
PfamiPF00619. CARD. 2 hits.
[Graphical view]
SMARTiSM00114. CARD. 1 hit.
[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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti81 – 811L → V.
Corresponds to variant rs34936594 [ dbSNP | Ensembl ].
VAR_036871
Natural varianti113 – 1131D → N Found in a patient with Crohn disease; unknown pathological significance. 1 Publication
Corresponds to variant rs104895468 [ dbSNP | Ensembl ].
VAR_073228
Natural varianti140 – 1401A → T Associated with Crohn disease and ulcerative colitis. 1 Publication
Corresponds to variant rs34684955 [ dbSNP | Ensembl ].
VAR_012665
Natural varianti157 – 1571W → R Associated with Crohn disease. 1 Publication
VAR_012666
Natural varianti189 – 1891T → M.1 Publication
Corresponds to variant rs61755182 [ dbSNP | Ensembl ].
VAR_012667
Natural varianti235 – 2351R → C Associated with Crohn disease. 1 Publication
VAR_012668
Natural varianti248 – 2481L → R Associated with Crohn disease; no disruption of NOD2-CARD9 interaction. 2 Publications
Corresponds to variant rs104895423 [ dbSNP | Ensembl ].
VAR_012669
Natural varianti268 – 2681P → S.3 Publications
Corresponds to variant rs2066842 [ dbSNP | Ensembl ].
VAR_012670
Natural varianti289 – 2891N → S.2 Publications
Corresponds to variant rs5743271 [ dbSNP | Ensembl ].
VAR_012671
Natural varianti291 – 2911D → N Associated with Crohn disease. 1 Publication
VAR_012672
Natural varianti294 – 2941T → S Associated with Crohn disease.
VAR_012673
Natural varianti301 – 3011A → V Associated with Crohn disease. 1 Publication
VAR_012674
Natural varianti311 – 3111R → W Associated with Crohn disease and ulcerative colitis. 2 Publications
VAR_012675
Natural varianti334 – 3341R → Q in BLAUS; somatic mosaicism in 4.9% to 11% of peripheral blood cells; hyperactive. 5 Publications
Corresponds to variant rs104895461 [ dbSNP | Ensembl ].
VAR_012676
Natural varianti334 – 3341R → W in BLAUS and EOS; no disruption of NOD2-CARD9 interaction; hyperactive. 7 Publications
Corresponds to variant rs104895462 [ dbSNP | Ensembl ].
VAR_012677
Natural varianti348 – 3481L → V Associated with Crohn disease. 1 Publication
VAR_012678
Natural varianti352 – 3521H → R Associated with Crohn disease. 1 Publication
Corresponds to variant rs5743272 [ dbSNP | Ensembl ].
VAR_012679
Natural varianti357 – 3571D → A Found in a patient with Crohn disease; unknown pathological significance; no disruption of NOD2-CARD9 interaction. 2 Publications
Corresponds to variant rs104895469 [ dbSNP | Ensembl ].
VAR_073229
Natural varianti363 – 3631I → F Found in a patient with Crohn disease; unknown pathological significance; no disruption of NOD2-CARD9 interaction. 2 Publications
Corresponds to variant rs104895470 [ dbSNP | Ensembl ].
VAR_073230
Natural varianti373 – 3731R → C Associated with Crohn disease. 1 Publication
VAR_012680
Natural varianti382 – 3821D → E in EOS; hyperactive. 2 Publications
VAR_023822
Natural varianti383 – 3831E → G Found in a family with Blau syndrome/early-onset sarcoidosis symptoms; unknown pathological significance; hyperactive. 2 Publications
Corresponds to variant rs104895493 [ dbSNP | Ensembl ].
VAR_073231
Natural varianti383 – 3831E → K in BLAUS; hyperactive. 3 Publications
Corresponds to variant rs104895477 [ dbSNP | Ensembl ].
VAR_023823
Natural varianti391 – 3911R → C.1 Publication
Corresponds to variant rs104895481 [ dbSNP | Ensembl ].
VAR_073232
Natural varianti414 – 4141N → S Associated with Crohn disease. 1 Publication
VAR_012681
Natural varianti431 – 4311S → L Associated with Crohn disease; no disruption of NOD2-CARD9 interaction. 2 Publications
Corresponds to variant rs104895431 [ dbSNP | Ensembl ].
VAR_012682
Natural varianti432 – 4321A → V Associated with Crohn disease. 1 Publication
Corresponds to variant rs2076754 [ dbSNP | Ensembl ].
VAR_012683
Natural varianti441 – 4411E → K Associated with Crohn disease; no disruption of NOD2-CARD9 interaction. 2 Publications
Corresponds to variant rs104895432 [ dbSNP | Ensembl ].
VAR_012684
Natural varianti463 – 4631P → A Polymorphism; no disruption of NOD2-CARD9 interaction. 2 Publications
Corresponds to variant rs104895482 [ dbSNP | Ensembl ].
VAR_073233
Natural varianti464 – 4641G → W Polymorphism; hyperactive. 1 Publication
Corresponds to variant rs104895492 [ dbSNP | Ensembl ].
VAR_073234
Natural varianti469 – 4691L → F in BLAUS; hyperactive. 2 Publications
Corresponds to variant rs104895460 [ dbSNP | Ensembl ].
VAR_012685
Natural varianti471 – 4711R → C Polymorphism; does not affect activity. 1 Publication
Corresponds to variant rs1078327 [ dbSNP | Ensembl ].
VAR_036872
Natural varianti481 – 4811G → D in EOS; atypical form of EOS with cardiac infiltration; sporadic case; unknown pathological significance; hyperactive. 2 Publications
Corresponds to variant rs104895494 [ dbSNP | Ensembl ].
VAR_073235
Natural varianti490 – 4901W → L in BLAUS; unknown pathological significance; hyperactive. 2 Publications
Corresponds to variant rs104895480 [ dbSNP | Ensembl ].
VAR_073236
Natural varianti495 – 4951C → Y in BLAUS; unknown pathological significance; hyperactive. 3 Publications
Corresponds to variant rs104895478 [ dbSNP | Ensembl ].
VAR_073237
Natural varianti496 – 4961H → L in EOS; hyperactive. 3 Publications
Corresponds to variant rs104895472 [ dbSNP | Ensembl ].
VAR_023824
Natural varianti507 – 5071P → S in BLAUS. 1 Publication
VAR_073180
Natural varianti513 – 5131M → T in EOS; hyperactive. 3 Publications
Corresponds to variant rs104895473 [ dbSNP | Ensembl ].
VAR_073238
Natural varianti550 – 5501L → V Found in a patient with Crohn disease; unknown pathological significance; no disruption of NOD2-CARD9 interaction. 2 Publications
Corresponds to variant rs104895471 [ dbSNP | Ensembl ].
VAR_073239
Natural varianti587 – 5871R → C in BLAUS; unknown pathological significance; not hyperactive. 2 Publications
Corresponds to variant rs104895479 [ dbSNP | Ensembl ].
VAR_073240
Natural varianti605 – 6051T → N in BLAUS; hyperactive. 2 Publications
VAR_065228
Natural varianti605 – 6051T → P in EOS; hyperactive. 3 Publications
Corresponds to variant rs104895474 [ dbSNP | Ensembl ].
VAR_073241
Natural varianti612 – 6121A → T in EOS; associated with Crohn disease. 2 Publications
VAR_012686
Natural varianti612 – 6121A → V Associated with Crohn disease; no disruption of NOD2-CARD9 interaction. 2 Publications
Corresponds to variant rs104895439 [ dbSNP | Ensembl ].
VAR_012687
Natural varianti670 – 6701N → K in EOS; hyperactive. 3 Publications
Corresponds to variant rs104895475 [ dbSNP | Ensembl ].
VAR_073242
Natural varianti684 – 6841R → W Associated with Crohn disease. 1 Publication
Corresponds to variant rs5743276 [ dbSNP | Ensembl ].
VAR_012688
Natural varianti702 – 7021R → W Associated with Crohn disease; no disruption of NOD2-CARD9 interaction; decreases half-life of protein. 3 Publications
Corresponds to variant rs2066844 [ dbSNP | Ensembl ].
VAR_012689
Natural varianti703 – 7031R → C Associated with Crohn disease and ulcerative colitis. 2 Publications
Corresponds to variant rs5743277 [ dbSNP | Ensembl ].
VAR_012690
Natural varianti713 – 7131R → C Associated with Crohn disease. 1 Publication
VAR_012691
Natural varianti713 – 7131R → H Found in a patient with Crohn disease; unknown pathological significance. 1 Publication
Corresponds to variant rs104895483 [ dbSNP | Ensembl ].
VAR_073243
Natural varianti725 – 7251A → G Associated with Crohn disease. 1 Publication
Corresponds to variant rs5743278 [ dbSNP | Ensembl ].
VAR_012692
Natural varianti755 – 7551A → V Associated with Crohn disease and ulcerative colitis. 1 Publication
Corresponds to variant rs61747625 [ dbSNP | Ensembl ].
VAR_012693
Natural varianti758 – 7581A → V Associated with Crohn disease. 1 Publication
VAR_012694
Natural varianti760 – 7601R → C Found in a patient with Crohn disease; unknown pathological significance. 1 Publication
Corresponds to variant rs3813758 [ dbSNP | Ensembl ].
VAR_073244
Natural varianti778 – 7781E → K Associated with Crohn disease. 1 Publication
VAR_012695
Natural varianti790 – 7901R → Q.
Corresponds to variant rs5743279 [ dbSNP | Ensembl ].
VAR_024402
Natural varianti790 – 7901R → W Found in a patient with Crohn disease; unknown pathological significance. 1 Publication
Corresponds to variant rs62029861 [ dbSNP | Ensembl ].
VAR_073245
Natural varianti791 – 7911R → W.1 Publication
Corresponds to variant rs104895484 [ dbSNP | Ensembl ].
VAR_073246
Natural varianti793 – 7931V → M Associated with Crohn disease. 1 Publication
Corresponds to variant rs104895444 [ dbSNP | Ensembl ].
VAR_012696
Natural varianti825 – 8251N → K.1 Publication
Corresponds to variant rs104895485 [ dbSNP | Ensembl ].
VAR_073247
Natural varianti843 – 8431E → K Associated with Crohn disease. 1 Publication
VAR_012697
Natural varianti849 – 8491A → V.1 Publication
Corresponds to variant rs104895486 [ dbSNP | Ensembl ].
VAR_073248
Natural varianti852 – 8521N → S Found in a patient with Crohn disease; unknown pathological significance. 1 Publication
Corresponds to variant rs104895467 [ dbSNP | Ensembl ].
VAR_073249
Natural varianti853 – 8531N → S Associated with Crohn disease. 1 Publication
VAR_012698
Natural varianti863 – 8631M → V Associated with Crohn disease. 1 Publication
Corresponds to variant rs104895447 [ dbSNP | Ensembl ].
VAR_012699
Natural varianti885 – 8851A → T Associated with ulcerative colitis. 1 Publication
VAR_012700
Natural varianti908 – 9081G → R Associated with Crohn disease; decreases half-life of protein. 3 Publications
Corresponds to variant rs2066845 [ dbSNP | Ensembl ].
VAR_012701
Natural varianti918 – 9181A → D Associated with Crohn disease. 1 Publication
Corresponds to variant rs104895452 [ dbSNP | Ensembl ].
VAR_012702
Natural varianti924 – 9241G → D Associated with Crohn disease. 1 Publication
VAR_012703
Natural varianti955 – 9551V → I.1 Publication
Corresponds to variant rs5743291 [ dbSNP | Ensembl ].
VAR_012704

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 2727Missing in isoform 2 and isoform 3. 2 PublicationsVSP_018689Add
BLAST
Alternative sequencei216 – 2249AATCKKYMA → DERTEAQKG in isoform 3. 1 PublicationVSP_046567
Alternative sequencei225 – 1040816Missing in isoform 3. 1 PublicationVSP_046568Add
BLAST

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_005256084.2. [Q9HC29-2]
UniGeneiHs.592072.

Genome annotation databases

EnsembliENST00000300589; ENSP00000300589; ENSG00000167207. [Q9HC29-1]
GeneIDi64127.
KEGGihsa:64127.
UCSCiuc002egl.1. 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_005256084.2. [Q9HC29-2]
UniGeneiHs.592072.

3D structure databases

ProteinModelPortaliQ9HC29.
SMRiQ9HC29. Positions 291-316, 747-1029.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi122077. 30 interactions.
DIPiDIP-41998N.
IntActiQ9HC29. 7 interactions.
MINTiMINT-151071.
STRINGi9606.ENSP00000300589.

Chemistry

BindingDBiQ9HC29.
ChEMBLiCHEMBL1293266.
GuidetoPHARMACOLOGYi1763.

PTM databases

PhosphoSiteiQ9HC29.

Polymorphism and mutation databases

BioMutaiNOD2.
DMDMi20137973.

Proteomic databases

PaxDbiQ9HC29.
PRIDEiQ9HC29.

Protocols and materials databases

DNASUi64127.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000300589; ENSP00000300589; ENSG00000167207. [Q9HC29-1]
GeneIDi64127.
KEGGihsa:64127.
UCSCiuc002egl.1. human. [Q9HC29-1]

Organism-specific databases

CTDi64127.
GeneCardsiGC16P050729.
HGNCiHGNC:5331. NOD2.
HPAiHPA041985.
MIMi186580. phenotype.
266600. phenotype.
605956. gene.
609464. phenotype.
neXtProtiNX_Q9HC29.
Orphaneti117. Behcet disease.
90340. Blau syndrome.
206. Crohn disease.
771. Ulcerative colitis.
PharmGKBiPA26074.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG248107.
GeneTreeiENSGT00790000123007.
HOGENOMiHOG000113814.
HOVERGENiHBG050792.
InParanoidiQ9HC29.
KOiK10165.
OMAiNVGHLKL.
OrthoDBiEOG7P5T07.
PhylomeDBiQ9HC29.
TreeFamiTF352118.

Enzyme and pathway databases

ReactomeiREACT_21281. TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
REACT_21368. JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1.
REACT_21399. activated TAK1 mediates p38 MAPK activation.
REACT_22442. Interleukin-1 signaling.
REACT_75776. NOD1/2 Signaling Pathway.
SignaLinkiQ9HC29.

Miscellaneous databases

GeneWikiiNOD2.
GenomeRNAii64127.
NextBioi35496989.
PROiQ9HC29.
SOURCEiSearch...

Gene expression databases

BgeeiQ9HC29.
CleanExiHS_NOD2.
ExpressionAtlasiQ9HC29. baseline and differential.
GenevisibleiQ9HC29. HS.

Family and domain databases

Gene3Di1.10.533.10. 2 hits.
InterProiIPR001315. CARD.
IPR011029. DEATH-like_dom.
IPR001611. Leu-rich_rpt.
IPR007111. NACHT_NTPase.
IPR027417. P-loop_NTPase.
[Graphical view]
PfamiPF00619. CARD. 2 hits.
[Graphical view]
SMARTiSM00114. CARD. 1 hit.
[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...

Publicationsi

  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. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 2), VARIANTS THR-140; ARG-157; MET-189; CYS-235; ARG-248; SER-268; SER-289; ASN-291; VAL-301; TRP-311; VAL-348; ARG-352; CYS-373; SER-414; LEU-431; VAL-432; LYS-441; VAL-612; THR-612; TRP-684; TRP-702; CYS-703; CYS-713; GLY-725; VAL-755; VAL-758; LYS-778; MET-793; LYS-843; SER-853; VAL-863; THR-885; ARG-908; ASP-918; ASP-924 AND ILE-955, INVOLVEMENT IN IBD1.
    Tissue: Leukocyte.
  3. "NOD2-C2 - a novel NOD2 isoform activating NF-kappaB in a muramyl dipeptide-independent manner."
    Kramer M., Boeck J., Reichenbach D., Kaether C., Schreiber S., Platzer M., Rosenstiel P., Huse K.
    BMC Res. Notes 3:224-224(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
  4. "A role for Erbin in the regulation of Nod2-dependent NF-kappaB signaling."
    McDonald C., Chen F.F., Ollendorff V., Ogura Y., Marchetto S., Lecine P., Borg J.P., Nunez G.
    J. Biol. Chem. 280:40301-40309(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH ERBBI2P, SUBCELLULAR LOCATION.
  5. "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.
  6. Cited for: IDENTIFICATION IN A COMPLEX WITH ARHGEF2 AND RIPK2, INTERACTION WITH RIPK2.
  7. "Proteasomal degradation of Nod2 protein mediates tolerance to bacterial cell wall components."
    Lee K.H., Biswas A., Liu Y.J., Kobayashi K.S.
    J. Biol. Chem. 287:39800-39811(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HSP90 AND SOCS3, POLYUBIQUITINATION.
  8. "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.
  9. "A role for the Ankyrin repeat containing protein Ankrd17 in Nod1- and Nod2-mediated inflammatory responses."
    Menning M., Kufer T.A.
    FEBS Lett. 587:2137-2142(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH ANKRD17.
  10. Cited for: FUNCTION.
  11. "Interaction between NOD2 and CARD9 involves the NOD2 NACHT and the linker region between the NOD2 CARDs and NACHT domain."
    Parkhouse R., Boyle J.P., Mayle S., Sawmynaden K., Rittinger K., Monie T.P.
    FEBS Lett. 588:2830-2836(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH CARD9, VARIANTS ALA-357; PHE-363; ALA-463 AND VAL-550, CHARACTERIZATION OF VARIANTS ARG-248; ALA-357; PHE-363; LEU-431; LYS-441; ALA-463; VAL-550; VAL-612 AND TRP-702, CHARACTERIZATION OF VARIANT BS TRP-334, MUTAGENESIS OF ASP-379.
  12. "Blau syndrome polymorphisms in NOD2 identify nucleotide hydrolysis and helical domain 1 as signalling regulators."
    Parkhouse R., Boyle J.P., Monie T.P.
    FEBS Lett. 588:3382-3389(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS BLAUS GLN-334; TRP-334; LYS-383; PHE-469 AND ASN-605, CHARACTERIZATION OF VARIANTS EOS ASP-481; LEU-496; THR-513; PRO-605 AND LYS-670, CHARACTERIZATION OF VARIANTS GLY-383; CYS-471; LEU-490; TYR-495 AND CYS-587.
  13. "The molecular chaperone HSP70 binds to and stabilizes NOD2, an important protein involved in Crohn disease."
    Mohanan V., Grimes C.L.
    J. Biol. Chem. 289:18987-18998(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HSPA1A, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS TRP-702 AND ARG-908.
  14. Cited for: VARIANTS BLAUS GLN-334; TRP-334 AND PHE-469.
  15. "Crohn disease: frequency and nature of CARD15 mutations in Ashkenazi and Sephardi/Oriental Jewish families."
    Tukel T., Shalata A., Present D., Rachmilewitz D., Mayer L., Grant D., Risch N., Desnick R.J.
    Am. J. Hum. Genet. 74:623-636(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS ASN-113; ALA-357; PHE-363; VAL-550 AND SER-852.
  16. "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 TRP-334; GLU-382; LEU-496; THR-513; PRO-605; THR-612 AND LYS-670, CHARACTERIZATION OF VARIANTS EOS GLU-382; LEU-496; THR-513; PRO-605 AND LYS-670.
  17. Cited for: VARIANT BLAUS LYS-383.
  18. "Eight novel CARD15 variants detected by DNA sequence analysis of the CARD15 gene in 111 patients with inflammatory bowel disease."
    Schnitzler F., Brand S., Staudinger T., Pfennig S., Hofbauer K., Seiderer J., Tillack C., Goke B., Ochsenkuhn T., Lohse P.
    Immunogenetics 58:99-106(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS SER-268; SER-289; TRP-311; CYS-391; ALA-463; CYS-703; HIS-713; CYS-760; TRP-790; TRP-791; LYS-825 AND VAL-849.
  19. "NOD2-associated pediatric granulomatous arthritis, an expanding phenotype: study of an international registry and a national cohort in Spain."
    Rose C.D., Arostegui J.I., Martin T.M., Espada G., Scalzi L., Yague J., Rosenbaum J.T., Modesto C., Cristina Arnal M., Merino R., Garcia-Consuegra J., Carballo Silva M.A., Wouters C.H.
    Arthritis Rheum. 60:1797-1803(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS BLAUS GLN-334; TRP-334; LYS-383; LEU-490; TYR-495 AND CYS-587.
  20. "Role of the NOD2 genotype in the clinical phenotype of Blau syndrome and early-onset sarcoidosis."
    Okafuji I., Nishikomori R., Kanazawa N., Kambe N., Fujisawa A., Yamazaki S., Saito M., Yoshioka T., Kawai T., Sakai H., Tanizaki H., Heike T., Miyachi Y., Nakahata T.
    Arthritis Rheum. 60:242-250(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT GLY-383, VARIANTS BLAUS GLN-334; TRP-334 AND TYR-495, VARIANTS EOS GLU-382; LEU-496; THR-513; PRO-605 AND LYS-670.
  21. "Cardiac infiltration in early-onset sarcoidosis associated with a novel heterozygous mutation, G481D, in CARD15."
    Okada S., Konishi N., Tsumura M., Shirao K., Yasunaga S., Sakai H., Nishikomori R., Takihara Y., Kobayashi M.
    Rheumatology 48:706-707(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT EOS ASP-481.
  22. "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 BLAUS ASN-605.
  23. "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 BLAUS TRP-334.
  24. Cited for: VARIANT BLAUS SER-507.
  25. Cited for: VARIANT BLAUS GLN-334, VARIANT SER-268.

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: June 24, 2015
This is version 154 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

External Data

Dasty 3

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 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.