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Protein

Nucleotide-binding oligomerization domain-containing protein 2

Gene

NOD2

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Involved in gastrointestinal immunity. Upon stimulation by muramyl dipeptide (MDP), a fragment of bacterial peptidoglycan, binds the proximal adapter receptor-interacting RIPK2, which recruits ubiquitin ligases as XIAP, BIRC2, BIRC3 and the LUBAC complex, triggering activation of MAP kinases and activation of NF-kappa-B signaling. This in turn leads to the transcriptional activation of hundreds of genes involved in immune response. Required for MDP-induced NLRP1-dependent CASP1 activation and IL1B release in macrophages.By similarity

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi272 – 279ATPPROSITE-ProRule annotation8

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Immunity, Innate immunity

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

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

Names & Taxonomyi

Protein namesi
Recommended name:
Nucleotide-binding oligomerization domain-containing protein 2
Alternative name(s):
Caspase recruitment domain-containing protein 15
Gene namesi
Name:NOD2
Synonyms:CARD15
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Chromosome 18

Subcellular locationi

  • Cytoplasm By similarity
  • Membrane By similarity
  • Basolateral cell membrane By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003758041 – 1013Nucleotide-binding oligomerization domain-containing protein 2Add BLAST1013

Post-translational modificationi

Polyubiquitinated following MDP stimulation, leading to proteasome-mediated degradation.By similarity

Keywords - PTMi

Ubl conjugation

Proteomic databases

PaxDbiQ6E804.
PRIDEiQ6E804.

Expressioni

Gene expression databases

BgeeiENSBTAG00000020936.

Interactioni

Subunit structurei

Component of a signaling complex consisting of ARHGEF2, NOD2 and RIPK2. Interacts (via CARD domain) with RIPK2 (via CARD domain). Interacts with ATG16L1. Interacts (via NACHT domain) with CARD9. Interacts with ANKRD17 (via N-terminus). Interacts with HSPA1A; the interaction enhances NOD2 stability. Interacts (via both CARD domains) with HSP90; the interaction enhances NOD2 stability. Interacts (via CARD domain) with SOCS3; the interaction promotes NOD2 degradation. Interacts (via CARD domain) with ERBBI2P; the interaction inhibits activation of NOD2. 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.By similarity

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000027887.

Structurei

3D structure databases

ProteinModelPortaliQ6E804.
SMRiQ6E804.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 95CARD 1PROSITE-ProRule annotationAdd BLAST95
Domaini99 – 191CARD 2PROSITE-ProRule annotationAdd BLAST93
Domaini266 – 591NACHTPROSITE-ProRule annotationAdd BLAST326
Repeati764 – 785LRR 1Add BLAST22
Repeati789 – 809LRR 2Add BLAST21
Repeati817 – 838LRR 3Add BLAST22
Repeati845 – 866LRR 4Add BLAST22
Repeati873 – 893LRR 5Add BLAST21
Repeati901 – 922LRR 6Add BLAST22
Repeati929 – 949LRR 7Add BLAST21
Repeati957 – 978LRR 8Add BLAST22
Repeati985 – 1008LRR 9Add BLAST24

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni214 – 247Required for CARD9 bindingBy similarityAdd BLAST34

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi36 – 50ATG16L1-binding motifAdd BLAST15

Domaini

The ATG16L1-binding motif mediates interaction with ATG16L1.By similarity
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.By similarity

Sequence similaritiesi

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

Keywords - Domaini

Leucine-rich repeat, Repeat

Phylogenomic databases

eggNOGiKOG4308. Eukaryota.
ENOG410ZBX3. LUCA.
GeneTreeiENSGT00860000133673.
HOGENOMiHOG000113814.
InParanoidiQ6E804.
KOiK10165.
OMAiFDEFKFR.
OrthoDBiEOG091G01CG.
TreeFamiTF352118.

Family and domain databases

Gene3Di1.10.533.10. 2 hits.
3.80.10.10. 1 hit.
InterProiIPR001315. CARD.
IPR011029. DEATH-like_dom.
IPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR007111. NACHT_NTPase.
IPR027417. P-loop_NTPase.
[Graphical view]
PfamiPF00619. CARD. 2 hits.
PF13516. LRR_6. 4 hits.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 2 hits.
SSF52540. SSF52540. 1 hit.
PROSITEiPS50209. CARD. 2 hits.
PS51450. LRR. 5 hits.
PS50837. NACHT. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q6E804-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MCAQDAFQTQ RSQLVELLVS GSLEGFESIL DRLLSREVLS WEDYEGLSLV
60 70 80 90 100
GQPISHLARR LLDTIWNKGT WGCEQLTAAV REAQADSQPP ELPSSWDPHS
110 120 130 140 150
PHPARDLQSH RPAIVRRLYG HVEGVLDLTQ QRGFISQYET DEIRRPIFTS
160 170 180 190 200
SQRARRLLDL ATVKANGLAA FLLQCIQELP VPLALPFEDA ACKKYVSKLR
210 220 230 240 250
TVISAQSRFL STYDGAENLC LEEVYTENVL EIQMEVGMAG PSQQSPTTLG
260 270 280 290 300
LEELFSTRDH FNKEADTVLV VGEAGSGKST LLQQLHLLWA SGRAFQEFLF
310 320 330 340 350
VFPFSCRQLQ CLVKPLSMRT LLFEHCCWPD LGPQDVFQVL LDHPERILLT
360 370 380 390 400
FDGFDEFRFR FTDQERHCCP TAPTSVQSLL FNLLQGNLLK NARKVLTSRP
410 420 430 440 450
SAVSASLRKH VRTELSLKGF SEEGIELYLR KRHREPGVAD RLLCLLRATS
460 470 480 490 500
ALHGLCHLPV FSWMVSKCHE ELLLQGRGSP KTTTDMYLLI LRHFLLHASP
510 520 530 540 550
LPLATHGLGP SLIQGRLPTL LHLGRLALWG LGTCCYVFSA KQLQAAHVDS
560 570 580 590 600
EDLSLGFLVL AKRVVPGSTA PLEFLHITFQ CFFAAFYLAL SADTPPSSLR
610 620 630 640 650
HLFQDHRPES SPLARVLPKL FLRGSRCREG SVAALLQGAE PHNLQITGAF
660 670 680 690 700
LAGLLSQEHR SLLAECQASE TALLRRWDCV RRCLTRSLRE HFRSIPPALP
710 720 730 740 750
GEAKSMHALP GFLWLIRSLY EMQEERLARE AVCRLNVGHL KLTFCGVGPA
760 770 780 790 800
ECAALAFVLR HLRRPVALQL DHNSVGDIGV EQLLPCLGVC KALYLRDNNI
810 820 830 840 850
SDRGICKLVE HALRCEQLQK LALFNNKLTD GCAHSMARLL ACKQNFLALR
860 870 880 890 900
LGNNHITAAG AEVLAQGLRT NNSLQFLGFW GNQVGDEGAQ ALAAALGDHQ
910 920 930 940 950
SLRWLSLVGN NIGSVGAQAL ALMLEKNMAL EELCLEENHV QDEGVCFLAK
960 970 980 990 1000
GLARNSSLKV LKLSNNHISS LGAEALLRAL EKNDTILEVW LRGNTFSPEE
1010
IEKLSHQDTR LLL
Length:1,013
Mass (Da):112,800
Last modified:August 16, 2004 - v1
Checksum:iACAE5F8C4BEFE11B
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti70T → A.1 Publication1
Natural varianti196V → M.1 Publication1
Natural varianti505T → N.1 Publication1
Natural varianti681R → Q.1 Publication1
Natural varianti689R → H.1 Publication1
Natural varianti733C → R.1 Publication1
Natural varianti1007Q → L.1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY518737 mRNA. Translation: AAS09824.1.
AY518748
, AY518739, AY518740, AY518741, AY518742, AY518743, AY518744, AY518745, AY518746, AY518747 Genomic DNA. Translation: AAS09826.1.
RefSeqiNP_001002889.1. NM_001002889.1.
XP_005218524.1. XM_005218467.3.
XP_010812724.1. XM_010814422.2.
XP_015331193.1. XM_015475707.1.
UniGeneiBt.30778.

Genome annotation databases

EnsembliENSBTAT00000027887; ENSBTAP00000027887; ENSBTAG00000020936.
GeneIDi444867.
KEGGibta:444867.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY518737 mRNA. Translation: AAS09824.1.
AY518748
, AY518739, AY518740, AY518741, AY518742, AY518743, AY518744, AY518745, AY518746, AY518747 Genomic DNA. Translation: AAS09826.1.
RefSeqiNP_001002889.1. NM_001002889.1.
XP_005218524.1. XM_005218467.3.
XP_010812724.1. XM_010814422.2.
XP_015331193.1. XM_015475707.1.
UniGeneiBt.30778.

3D structure databases

ProteinModelPortaliQ6E804.
SMRiQ6E804.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000027887.

Proteomic databases

PaxDbiQ6E804.
PRIDEiQ6E804.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSBTAT00000027887; ENSBTAP00000027887; ENSBTAG00000020936.
GeneIDi444867.
KEGGibta:444867.

Organism-specific databases

CTDi64127.

Phylogenomic databases

eggNOGiKOG4308. Eukaryota.
ENOG410ZBX3. LUCA.
GeneTreeiENSGT00860000133673.
HOGENOMiHOG000113814.
InParanoidiQ6E804.
KOiK10165.
OMAiFDEFKFR.
OrthoDBiEOG091G01CG.
TreeFamiTF352118.

Enzyme and pathway databases

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

Gene expression databases

BgeeiENSBTAG00000020936.

Family and domain databases

Gene3Di1.10.533.10. 2 hits.
3.80.10.10. 1 hit.
InterProiIPR001315. CARD.
IPR011029. DEATH-like_dom.
IPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR007111. NACHT_NTPase.
IPR027417. P-loop_NTPase.
[Graphical view]
PfamiPF00619. CARD. 2 hits.
PF13516. LRR_6. 4 hits.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 2 hits.
SSF52540. SSF52540. 1 hit.
PROSITEiPS50209. CARD. 2 hits.
PS51450. LRR. 5 hits.
PS50837. NACHT. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiNOD2_BOVIN
AccessioniPrimary (citable) accession number: Q6E804
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 26, 2009
Last sequence update: August 16, 2004
Last modified: November 30, 2016
This is version 104 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.