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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

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 kinase binding Source: HGNC

GO - Biological processi

  1. activation of immune response Source: MGI
  2. activation of MAPK activity involved in innate immune response Source: BHF-UCL
  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 bacterium Source: HGNC
  8. defense response to Gram-positive bacterium Source: MGI
  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. maintenance of gastrointestinal epithelium Source: Ensembl
  19. microglial cell activation involved in immune response Source: Ensembl
  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 NF-kappaB transcription factor activity Source: MGI
  28. negative regulation of T cell mediated immunity Source: MGI
  29. negative regulation of toll-like receptor 2 signaling pathway Source: MGI
  30. negative regulation of tumor necrosis factor production Source: MGI
  31. nucleotide-binding oligomerization domain containing 2 signaling pathway Source: UniProtKB
  32. pathogen-associated molecular pattern dependent induction by symbiont of host innate immune response Source: Ensembl
  33. positive regulation of antibacterial peptide biosynthetic process Source: MGI
  34. positive regulation of B cell activation Source: Ensembl
  35. positive regulation of biosynthetic process of antibacterial peptides active against Gram-positive bacteria Source: MGI
  36. positive regulation of dendritic cell antigen processing and presentation Source: BHF-UCL
  37. positive regulation of dendritic cell cytokine production Source: Ensembl
  38. positive regulation of epithelial cell proliferation Source: BHF-UCL
  39. positive regulation of ERK1 and ERK2 cascade Source: BHF-UCL
  40. positive regulation of humoral immune response mediated by circulating immunoglobulin Source: MGI
  41. positive regulation of I-kappaB kinase/NF-kappaB signaling Source: HGNC
  42. positive regulation of innate immune response Source: MGI
  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-1 beta secretion Source: UniProtKB
  47. positive regulation of interleukin-6 production Source: MGI
  48. positive regulation of JNK cascade Source: MGI
  49. positive regulation of MAPK cascade Source: MGI
  50. positive regulation of NF-kappaB transcription factor activity Source: HGNC
  51. positive regulation of nitric-oxide synthase biosynthetic process Source: BHF-UCL
  52. positive regulation of Notch signaling pathway Source: BHF-UCL
  53. positive regulation of oxidoreductase activity Source: BHF-UCL
  54. positive regulation of peptidyl-tyrosine phosphorylation Source: MGI
  55. positive regulation of phagocytosis Source: MGI
  56. positive regulation of phosphatidylinositol 3-kinase activity Source: BHF-UCL
  57. positive regulation of prostaglandin-endoperoxide synthase activity Source: BHF-UCL
  58. positive regulation of prostaglandin-E synthase activity Source: BHF-UCL
  59. positive regulation of protein ubiquitination Source: UniProtKB
  60. positive regulation of stress-activated MAPK cascade Source: MGI
  61. positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  62. positive regulation of tumor necrosis factor production Source: MGI
  63. positive regulation of type 2 immune response Source: BHF-UCL
  64. protein oligomerization Source: HGNC
  65. regulation of inflammatory response Source: MGI
  66. regulation of neutrophil chemotaxis Source: MGI
  67. response to exogenous dsRNA Source: MGI
  68. response to lipopolysaccharide Source: MGI
  69. response to muramyl dipeptide Source: HGNC
  70. response to nutrient Source: Ensembl
  71. response to peptidoglycan Source: MGI
  72. 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. COP9 signalosome Source: Ensembl
  3. cytoplasm Source: UniProtKB
  4. cytoskeleton Source: UniProtKB
  5. cytosol Source: HGNC
  6. plasma membrane Source: HGNC
  7. protein complex Source: UniProtKB
  8. 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 2PRO_0000144091Add
BLAST

Proteomic databases

PRIDEiQ8K3Z0.

PTM databases

PhosphoSiteiQ8K3Z0.

Expressioni

Gene expression databases

BgeeiQ8K3Z0.
ExpressionAtlasiQ8K3Z0. baseline and differential.
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.By similarity1 Publication

Protein-protein interaction databases

DIPiDIP-46115N.

Structurei

3D structure databases

ProteinModelPortaliQ8K3Z0.
SMRiQ8K3Z0. Positions 270-295, 760-1004.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

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

Motif

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

Domaini

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

Sequence similaritiesi

Contains 2 CARD domains.PROSITE-ProRule annotation
Contains 10 LRR (leucine-rich) repeats.Curated
Contains 1 NACHT domain.PROSITE-ProRule annotation

Keywords - Domaini

Leucine-rich repeat, Repeat

Phylogenomic databases

eggNOGiNOG248107.
GeneTreeiENSGT00710000106284.
HOGENOMiHOG000113814.
HOVERGENiHBG050792.
InParanoidiQ8K3Z0.
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

        10         20         30         40         50
MRSSCCDMCS QEEFQAQRSQ LVALLISGSL EGFESILDWL LSWDVLSRED
60 70 80 90 100
YEGLSLPGQP LSHSARRLLD TVWNKGVWGC QKLLEAVQEA QANSHTFELY
110 120 130 140 150
GSWDTHSLHP TRDLQSHRPA IVRRLYNHVE AMLELAREGG FLSQYECEEI
160 170 180 190 200
RLPIFTSSQR ARRLLDLAAV KANGLAAFLL QHVRELPAPL PLPYEAAECQ
210 220 230 240 250
KFISKLRTMV LTQSRFLSTY DGSENLCLED IYTENILELQ TEVGTAGALQ
260 270 280 290 300
KSPAILGLED LFDTHGHLNR DADTILVVGE AGSGKSTLLQ RLHLLWATGR
310 320 330 340 350
SFQEFLFIFP FSCRQLQCVA KPLSLRTLLF EHCCWPDVAQ DDVFQFLLDH
360 370 380 390 400
PDRVLLTFDG LDEFKFRFTD RERHCSPIDP TSVQTLLFNL LQGNLLKNAC
410 420 430 440 450
KVLTSRPDAV SALLRKFVRT ELQLKGFSEE GIQLYLRKHH REPGVADRLI
460 470 480 490 500
QLIQATSALH GLCHLPVFSW MVSRCHRELL LQNRGFPTTS TDMYLLILQH
510 520 530 540 550
FLLHASPPDS SPLGLGPGLL QSRLSTLLHL GHLALRGLAM SCYVFSAQQL
560 570 580 590 600
QAAQVDSDDI SLGFLVRAQS SVPGSKAPLE FLHITFQCFF AAFYLAVSAD
610 620 630 640 650
TSVASLKHLF SCGRLGSSLL GRLLPNLCIQ GSRVKKGSEA ALLQKAEPHN
660 670 680 690 700
LQITAAFLAG LLSQQHRDLL AACQVSERVL LQRQARARSC LAHSLREHFH
710 720 730 740 750
SIPPAVPGET KSMHAMPGFI WLIRSLYEMQ EEQLAQEAVR RLDIGHLKLT
760 770 780 790 800
FCRVGPAECA ALAFVLQHLQ RPVALQLDYN SVGDVGVEQL RPCLGVCTAL
810 820 830 840 850
YLRDNNISDR GARTLVECAL RCEQLQKLAL FNNKLTDACA CSMAKLLAHK
860 870 880 890 900
QNFLSLRVGN NHITAAGAEV LAQGLKSNTS LKFLGFWGNS VGDKGTQALA
910 920 930 940 950
EVVADHQNLK WLSLVGNNIG SMGAEALALM LEKNKSLEEL CLEENHICDE
960 970 980 990 1000
GVYSLAEGLK RNSTLKFLKL SNNGITYRGA EALLQALSRN SAILEVWLRG
1010 1020
NTFSLEEIQT LSSRDARLLL
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. 1 PublicationVSP_007069
Alternative sequencei195 – 1951E → EGYSLCRSRCDRGFTLICLF CIL in isoform 2. 1 PublicationVSP_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, 760-1004.
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.
InParanoidi Q8K3Z0.
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

Bgeei Q8K3Z0.
ExpressionAtlasi Q8K3Z0. baseline and differential.
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: October 29, 2014
This is version 114 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