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Q8K3Z0

- NOD2_MOUSE

UniProt

Q8K3Z0 - NOD2_MOUSE

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
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    • History
      Entry version 113 (01 Oct 2014)
      Sequence version 1 (01 Oct 2002)
      Previous versions | rss
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    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 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. negative regulation of growth of symbiont in host Source: MGI
    19. negative regulation of inflammatory response to antigenic stimulus Source: MGI
    20. negative regulation of interferon-gamma production Source: MGI
    21. negative regulation of interleukin-12 production Source: MGI
    22. negative regulation of interleukin-18 production Source: MGI
    23. negative regulation of interleukin-2 production Source: MGI
    24. negative regulation of macrophage apoptotic process Source: BHF-UCL
    25. negative regulation of NF-kappaB transcription factor activity Source: MGI
    26. negative regulation of T cell mediated immunity Source: MGI
    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 antibacterial peptide biosynthetic process Source: MGI
    31. positive regulation of biosynthetic process of antibacterial peptides active against Gram-positive bacteria Source: MGI
    32. positive regulation of dendritic cell antigen processing and presentation Source: BHF-UCL
    33. positive regulation of epithelial cell proliferation Source: BHF-UCL
    34. positive regulation of ERK1 and ERK2 cascade Source: BHF-UCL
    35. positive regulation of humoral immune response mediated by circulating immunoglobulin Source: MGI
    36. positive regulation of I-kappaB kinase/NF-kappaB signaling Source: HGNC
    37. positive regulation of innate immune response Source: MGI
    38. positive regulation of interleukin-10 production Source: BHF-UCL
    39. positive regulation of interleukin-12 production Source: MGI
    40. positive regulation of interleukin-17 production Source: UniProtKB
    41. positive regulation of interleukin-1 beta secretion Source: UniProtKB
    42. positive regulation of interleukin-6 production Source: MGI
    43. positive regulation of JNK cascade Source: MGI
    44. positive regulation of MAPK cascade Source: MGI
    45. positive regulation of NF-kappaB transcription factor activity Source: HGNC
    46. positive regulation of nitric-oxide synthase biosynthetic process Source: BHF-UCL
    47. positive regulation of Notch signaling pathway 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-endoperoxide synthase activity Source: BHF-UCL
    53. positive regulation of prostaglandin-E 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

    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

    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

    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.By similarity1 Publication

    Protein-protein interaction databases

    DIPiDIP-46115N.

    Structurei

    3D structure databases

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

    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 1, 2014
    This is version 113 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