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Q8K3Z0

- NOD2_MOUSE

UniProt

Q8K3Z0 - NOD2_MOUSE

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Protein
Nucleotide-binding oligomerization domain-containing protein 2
Gene
Nod2, Card15
Organism
Mus musculus (Mouse)
Status
Reviewed - 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

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. CARD domain binding Source: HGNC
  3. endodeoxyribonuclease activity, producing 5'-phosphomonoesters Source: InterPro
  4. enzyme binding Source: HGNC
  5. muramyl dipeptide binding Source: HGNC
  6. peptidoglycan binding Source: HGNC
  7. protein binding Source: MGI
  8. protein kinase binding Source: HGNC

GO - Biological processi

  1. activation of MAPK activity involved in innate immune response Source: BHF-UCL
  2. activation of immune response Source: MGI
  3. cellular response to muramyl dipeptide Source: UniProtKB
  4. cellular response to peptidoglycan Source: MGI
  5. cytokine production involved in immune response Source: UniProtKB
  6. defense response Source: HGNC
  7. defense response to Gram-positive bacterium Source: MGI
  8. defense response to bacterium Source: HGNC
  9. detection of bacterium Source: HGNC
  10. detection of biotic stimulus Source: HGNC
  11. detection of muramyl dipeptide Source: HGNC
  12. immunoglobulin production involved in immunoglobulin mediated immune response Source: MGI
  13. inflammatory response Source: HGNC
  14. innate immune response Source: UniProtKB
  15. innate immune response in mucosa Source: MGI
  16. intracellular signal transduction Source: UniProtKB
  17. macrophage inflammatory protein-1 alpha production Source: MGI
  18. negative regulation of NF-kappaB transcription factor activity Source: MGI
  19. negative regulation of T cell mediated immunity Source: MGI
  20. negative regulation of growth of symbiont in host Source: MGI
  21. negative regulation of inflammatory response to antigenic stimulus Source: MGI
  22. negative regulation of interferon-gamma production Source: MGI
  23. negative regulation of interleukin-12 production Source: MGI
  24. negative regulation of interleukin-18 production Source: MGI
  25. negative regulation of interleukin-2 production Source: MGI
  26. negative regulation of macrophage apoptotic process Source: BHF-UCL
  27. negative regulation of toll-like receptor 2 signaling pathway Source: MGI
  28. negative regulation of tumor necrosis factor production Source: MGI
  29. nucleotide-binding oligomerization domain containing 2 signaling pathway Source: UniProtKB
  30. positive regulation of ERK1 and ERK2 cascade Source: BHF-UCL
  31. positive regulation of I-kappaB kinase/NF-kappaB signaling Source: HGNC
  32. positive regulation of JNK cascade Source: MGI
  33. positive regulation of MAPK cascade Source: MGI
  34. positive regulation of NF-kappaB transcription factor activity Source: HGNC
  35. positive regulation of Notch signaling pathway Source: BHF-UCL
  36. positive regulation of antibacterial peptide biosynthetic process Source: MGI
  37. positive regulation of biosynthetic process of antibacterial peptides active against Gram-positive bacteria Source: MGI
  38. positive regulation of dendritic cell antigen processing and presentation Source: BHF-UCL
  39. positive regulation of epithelial cell proliferation Source: BHF-UCL
  40. positive regulation of humoral immune response mediated by circulating immunoglobulin Source: MGI
  41. positive regulation of innate immune response Source: MGI
  42. positive regulation of interleukin-1 beta secretion Source: UniProtKB
  43. positive regulation of interleukin-10 production Source: BHF-UCL
  44. positive regulation of interleukin-12 production Source: MGI
  45. positive regulation of interleukin-17 production Source: UniProtKB
  46. positive regulation of interleukin-6 production Source: MGI
  47. positive regulation of nitric-oxide synthase biosynthetic process Source: BHF-UCL
  48. positive regulation of oxidoreductase activity Source: BHF-UCL
  49. positive regulation of peptidyl-tyrosine phosphorylation Source: MGI
  50. positive regulation of phagocytosis Source: MGI
  51. positive regulation of phosphatidylinositol 3-kinase activity Source: BHF-UCL
  52. positive regulation of prostaglandin-E synthase activity Source: BHF-UCL
  53. positive regulation of prostaglandin-endoperoxide synthase activity Source: BHF-UCL
  54. positive regulation of protein ubiquitination Source: UniProtKB
  55. positive regulation of stress-activated MAPK cascade Source: MGI
  56. positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  57. positive regulation of tumor necrosis factor production Source: MGI
  58. positive regulation of type 2 immune response Source: BHF-UCL
  59. protein oligomerization Source: HGNC
  60. regulation of inflammatory response Source: MGI
  61. regulation of neutrophil chemotaxis Source: MGI
  62. response to exogenous dsRNA Source: MGI
  63. response to lipopolysaccharide Source: MGI
  64. response to muramyl dipeptide Source: HGNC
  65. response to peptidoglycan Source: MGI
  66. signal transduction Source: HGNC
Complete GO annotation...

Keywords - Biological processi

Immunity, Innate immunity

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiREACT_204812. JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1.
REACT_211125. NOD1/2 Signaling Pathway.
REACT_219800. TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
REACT_224208. Interleukin-1 signaling.

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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 8

Organism-specific databases

MGIiMGI:2429397. Nod2.

Subcellular locationi

Cytoplasm By similarity

GO - Cellular componenti

  1. cell surface Source: UniProtKB
  2. cytoplasm Source: UniProtKB
  3. cytoskeleton Source: UniProtKB
  4. cytosol Source: HGNC
  5. plasma membrane Source: HGNC
  6. protein complex Source: UniProtKB
  7. vesicle Source: HGNC
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 10201020Nucleotide-binding oligomerization domain-containing protein 2
PRO_0000144091Add
BLAST

Proteomic databases

PRIDEiQ8K3Z0.

PTM databases

PhosphoSiteiQ8K3Z0.

Expressioni

Gene expression databases

ArrayExpressiQ8K3Z0.
BgeeiQ8K3Z0.
GenevestigatoriQ8K3Z0.

Interactioni

Subunit structurei

Found in a signaling complex consisting of ARHGEF2, NOD2 and RIPK2. Interacts (via CARD domain) with RIPK2 (via CARD domain). Interacts with ATG16L1 By similarity. Interacts with CARD9.1 Publication

Protein-protein interaction databases

DIPiDIP-46115N.

Structurei

3D structure databases

ProteinModelPortaliQ8K3Z0.
SMRiQ8K3Z0. Positions 270-295, 747-1015.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini6 – 10499CARD 1
Add
BLAST
Domaini106 – 20095CARD 2
Add
BLAST
Domaini273 – 600328NACHT
Add
BLAST
Repeati685 – 70925LRR 1
Add
BLAST
Repeati726 – 74924LRR 2
Add
BLAST
Repeati766 – 79227LRR 3
Add
BLAST
Repeati794 – 81724LRR 4
Add
BLAST
Repeati822 – 84524LRR 5
Add
BLAST
Repeati850 – 87324LRR 6
Add
BLAST
Repeati906 – 92924LRR 7
Add
BLAST
Repeati934 – 96229LRR 8
Add
BLAST
Repeati963 – 98523LRR 9
Add
BLAST
Repeati1005 – 101915LRR 10
Add
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi43 – 5715ATG16L1-binding motif
Add
BLAST

Domaini

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

Sequence similaritiesi

Contains 2 CARD domains.
Contains 1 NACHT domain.

Keywords - Domaini

Leucine-rich repeat, Repeat

Phylogenomic databases

eggNOGiNOG248107.
GeneTreeiENSGT00710000106284.
HOGENOMiHOG000113814.
HOVERGENiHBG050792.
OMAiVWNKGTW.
PhylomeDBiQ8K3Z0.
TreeFamiTF352118.

Family and domain databases

Gene3Di1.10.533.10. 2 hits.
InterProiIPR001315. CARD.
IPR011029. DEATH-like_dom.
IPR018228. DNase_TatD-rel_CS.
IPR007111. NACHT_NTPase.
IPR027417. P-loop_NTPase.
[Graphical view]
PfamiPF00619. CARD. 2 hits.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 2 hits.
SSF52540. SSF52540. 1 hit.
PROSITEiPS50209. CARD. 2 hits.
PS50837. NACHT. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: Q8K3Z0-1) [UniParc]FASTAAdd to Basket

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

MRSSCCDMCS QEEFQAQRSQ LVALLISGSL EGFESILDWL LSWDVLSRED     50
YEGLSLPGQP LSHSARRLLD TVWNKGVWGC QKLLEAVQEA QANSHTFELY 100
GSWDTHSLHP TRDLQSHRPA IVRRLYNHVE AMLELAREGG FLSQYECEEI 150
RLPIFTSSQR ARRLLDLAAV KANGLAAFLL QHVRELPAPL PLPYEAAECQ 200
KFISKLRTMV LTQSRFLSTY DGSENLCLED IYTENILELQ TEVGTAGALQ 250
KSPAILGLED LFDTHGHLNR DADTILVVGE AGSGKSTLLQ RLHLLWATGR 300
SFQEFLFIFP FSCRQLQCVA KPLSLRTLLF EHCCWPDVAQ DDVFQFLLDH 350
PDRVLLTFDG LDEFKFRFTD RERHCSPIDP TSVQTLLFNL LQGNLLKNAC 400
KVLTSRPDAV SALLRKFVRT ELQLKGFSEE GIQLYLRKHH REPGVADRLI 450
QLIQATSALH GLCHLPVFSW MVSRCHRELL LQNRGFPTTS TDMYLLILQH 500
FLLHASPPDS SPLGLGPGLL QSRLSTLLHL GHLALRGLAM SCYVFSAQQL 550
QAAQVDSDDI SLGFLVRAQS SVPGSKAPLE FLHITFQCFF AAFYLAVSAD 600
TSVASLKHLF SCGRLGSSLL GRLLPNLCIQ GSRVKKGSEA ALLQKAEPHN 650
LQITAAFLAG LLSQQHRDLL AACQVSERVL LQRQARARSC LAHSLREHFH 700
SIPPAVPGET KSMHAMPGFI WLIRSLYEMQ EEQLAQEAVR RLDIGHLKLT 750
FCRVGPAECA ALAFVLQHLQ RPVALQLDYN SVGDVGVEQL RPCLGVCTAL 800
YLRDNNISDR GARTLVECAL RCEQLQKLAL FNNKLTDACA CSMAKLLAHK 850
QNFLSLRVGN NHITAAGAEV LAQGLKSNTS LKFLGFWGNS VGDKGTQALA 900
EVVADHQNLK WLSLVGNNIG SMGAEALALM LEKNKSLEEL CLEENHICDE 950
GVYSLAEGLK RNSTLKFLKL SNNGITYRGA EALLQALSRN SAILEVWLRG 1000
NTFSLEEIQT LSSRDARLLL 1020
Length:1,020
Mass (Da):113,562
Last modified:October 1, 2002 - v1
Checksum:i25504905ECF70FBB
GO
Isoform 2 (identifier: Q8K3Z0-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-7: Missing.
     195-195: E → EGYSLCRSRCDRGFTLICLFCIL

Note: No experimental confirmation available.

Show »
Length:1,035
Mass (Da):115,301
Checksum:i7F0E533DC98068FD
GO

Sequence cautioni

The sequence AAH44774.1 differs from that shown. Reason: Erroneous initiation.

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti212 – 2121T → A in strain: NMRI. 1 Publication
Natural varianti240 – 2401Q → R in strain: NMRI. 1 Publication
Natural varianti422 – 4221L → C in strain: NMRI; requires 2 nucleotide substitutions. 1 Publication
Natural varianti485 – 4851G → V in strain: NMRI. 1 Publication
Natural varianti603 – 6031V → A in strain: NMRI. 1 Publication
Natural varianti675 – 6751V → I in strain: NMRI. 1 Publication
Natural varianti925 – 9251E → Q in strain: NMRI. 1 Publication

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 77Missing in isoform 2.
VSP_007069
Alternative sequencei195 – 1951E → EGYSLCRSRCDRGFTLICLF CIL in isoform 2.
VSP_007070

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF520774 mRNA. Translation: AAM76073.1.
BC044774 mRNA. Translation: AAH44774.1. Different initiation.
UniGeneiMm.222633.

Genome annotation databases

EnsembliENSMUST00000054324; ENSMUSP00000050538; ENSMUSG00000055994. [Q8K3Z0-2]
ENSMUST00000109634; ENSMUSP00000105262; ENSMUSG00000055994. [Q8K3Z0-1]
UCSCiuc009mrq.1. mouse. [Q8K3Z0-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF520774 mRNA. Translation: AAM76073.1 .
BC044774 mRNA. Translation: AAH44774.1 . Different initiation.
UniGenei Mm.222633.

3D structure databases

ProteinModelPortali Q8K3Z0.
SMRi Q8K3Z0. Positions 270-295, 747-1015.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

DIPi DIP-46115N.

PTM databases

PhosphoSitei Q8K3Z0.

Proteomic databases

PRIDEi Q8K3Z0.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000054324 ; ENSMUSP00000050538 ; ENSMUSG00000055994 . [Q8K3Z0-2 ]
ENSMUST00000109634 ; ENSMUSP00000105262 ; ENSMUSG00000055994 . [Q8K3Z0-1 ]
UCSCi uc009mrq.1. mouse. [Q8K3Z0-1 ]

Organism-specific databases

MGIi MGI:2429397. Nod2.

Phylogenomic databases

eggNOGi NOG248107.
GeneTreei ENSGT00710000106284.
HOGENOMi HOG000113814.
HOVERGENi HBG050792.
OMAi VWNKGTW.
PhylomeDBi Q8K3Z0.
TreeFami TF352118.

Enzyme and pathway databases

Reactomei REACT_204812. JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1.
REACT_211125. NOD1/2 Signaling Pathway.
REACT_219800. TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
REACT_224208. Interleukin-1 signaling.

Miscellaneous databases

PROi Q8K3Z0.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q8K3Z0.
Bgeei Q8K3Z0.
Genevestigatori Q8K3Z0.

Family and domain databases

Gene3Di 1.10.533.10. 2 hits.
InterProi IPR001315. CARD.
IPR011029. DEATH-like_dom.
IPR018228. DNase_TatD-rel_CS.
IPR007111. NACHT_NTPase.
IPR027417. P-loop_NTPase.
[Graphical view ]
Pfami PF00619. CARD. 2 hits.
[Graphical view ]
SUPFAMi SSF47986. SSF47986. 2 hits.
SSF52540. SSF52540. 1 hit.
PROSITEi PS50209. CARD. 2 hits.
PS50837. NACHT. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning, sequencing and expression analysis of the mouse Nod2/Card15 gene."
    Iwanaga Y., Davey M.P., Martin T.M., Planck S.R., DePriest M.L., Baugh M.M., Suing C.M., Rosenbaum J.T.
    Inflamm. Res. 52:272-276(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Strain: BALB/c.
    Tissue: Monocyte.
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANTS ALA-212; ARG-240; CYS-422; VAL-485; ALA-603; ILE-675 AND GLN-925.
    Strain: NMRI.
    Tissue: Mammary cancer.
  3. "The adaptor protein CARD9 is required for innate immune responses to intracellular pathogens."
    Hsu Y.M., Zhang Y., You Y., Wang D., Li H., Duramad O., Qin X.F., Dong C., Lin X.
    Nat. Immunol. 8:198-205(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH CARD9.
  4. Cited for: FUNCTION.

Entry informationi

Entry nameiNOD2_MOUSE
AccessioniPrimary (citable) accession number: Q8K3Z0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 28, 2003
Last sequence update: October 1, 2002
Last modified: September 3, 2014
This is version 112 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi