Human Metabolome Database: Showing Protein Nucleotide-binding oligomerization domain-containing protein 2 (HMDBP13953)

Identification Biological properties Gene properties Protein properties External links References XML Show 0 metabolites

Identification

HMDB Protein ID

HMDBP13953

Secondary Accession Numbers

None

Name

Nucleotide-binding oligomerization domain-containing protein 2

Synonyms

Caspase recruitment domain-containing protein 15

Gene Name

NOD2

Protein Type

Unknown

Biological Properties

General Function

Not Available

Specific Function

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, INAVA 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 (PubMed:22607974). Required for MDP-induced NLRP1-dependent CASP1 activation and IL1B release in macrophages (PubMed:18511561). Component of an autophagy-mediated antibacterial pathway together with ATG16L1. Plays also a role in sensing single-stranded RNA (ssRNA) from viruses. Interacts with mitochondrial antiviral signaling/MAVS, leading to activation of interferon regulatory factor-3/IRF3 and expression of type I interferon.

Pathways

Not Available

Reactions

Not Available

GO Classification

Biological Process
detection of muramyl dipeptide
positive regulation of tumor necrosis factor production
positive regulation of phosphatidylinositol 3-kinase activity
response to peptidoglycan
cellular response to peptidoglycan
positive regulation of protein ubiquitination
positive regulation of innate immune response
cellular response to muramyl dipeptide
positive regulation of humoral immune response mediated by circulating immunoglobulin
detection of biotic stimulus
positive regulation of phagocytosis
negative regulation of interleukin-12 production
negative regulation of interferon-gamma production
detection of bacterium
maintenance of gastrointestinal epithelium
defense response
positive regulation of MAP kinase activity
defense response to Gram-positive bacterium
cellular response to organic cyclic compound
negative regulation of interleukin-18 production
positive regulation of B cell activation
positive regulation of interleukin-17 production
positive regulation of cytokine production involved in immune response
pattern recognition receptor signaling pathway
nucleotide-binding oligomerization domain containing 2 signaling pathway
activation of immune response
positive regulation of MAPK cascade
positive regulation of stress-activated MAPK cascade
positive regulation of monocyte chemotactic protein-1 production
positive regulation of dendritic cell cytokine production
innate immune response in mucosa
positive regulation of interleukin-8 production
positive regulation of interleukin-10 production
negative regulation of macrophage apoptotic process
positive regulation of NIK/NF-kappaB signaling
positive regulation of interleukin-6 production
positive regulation of interleukin-1 beta production
positive regulation of cytokine production involved in inflammatory response
negative regulation of toll-like receptor 2 signaling pathway
positive regulation of protein K63-linked ubiquitination
signal transduction
negative regulation of NF-kappaB transcription factor activity
positive regulation of dendritic cell antigen processing and presentation
cellular response to lipopolysaccharide
inflammatory response
response to lipopolysaccharide
positive regulation of prostaglandin-E synthase activity
positive regulation of prostaglandin-endoperoxide synthase activity
intracellular signal transduction
positive regulation of biosynthetic process of antibacterial peptides active against Gram-positive bacteria
positive regulation of cell proliferation
regulation of inflammatory response
positive regulation of xenophagy
innate immune response
response to nutrient
regulation of neutrophil chemotaxis
response to muramyl dipeptide
positive regulation of antibacterial peptide biosynthetic process
positive regulation of JNK cascade
positive regulation of nitric-oxide synthase biosynthetic process
positive regulation of peptidyl-tyrosine phosphorylation
defense response to bacterium
negative regulation of interleukin-2 production
positive regulation of type 2 immune response
positive regulation of interleukin-12 production
negative regulation of tumor necrosis factor production
negative regulation of inflammatory response to antigenic stimulus
positive regulation of Notch signaling pathway
response to exogenous dsRNA
positive regulation of epithelial cell proliferation
negative regulation of T cell mediated immunity
positive regulation of transcription from RNA polymerase II promoter
positive regulation of ERK1 and ERK2 cascade
positive regulation of NF-kappaB transcription factor activity
positive regulation of oxidoreductase activity
positive regulation of I-kappaB kinase/NF-kappaB cascade
Cellular Component
cytoplasm
cytosol
protein-containing complex
plasma membrane
anchored to plasma membrane
cell surface
Golgi apparatus
vesicle
phagocytic vesicle
basolateral plasma membrane
cytoskeleton
Molecular Function
enzyme binding
endodeoxyribonuclease activity, producing 5'-phosphomonoesters
ATP binding
protein kinase binding
actin binding
peptidoglycan binding
Hsp70 protein binding
Hsp90 protein binding
muramyl dipeptide binding
CARD domain binding
protein-containing complex binding
pattern recognition receptor activity

Cellular Location

Not Available

Gene Properties

Chromosome Location

Not Available

Locus

Not Available

SNPs

Not Available

Gene Sequence

Not Available

Protein Properties

Number of Residues

Not Available

Molecular Weight

113560.465

Theoretical pI

Not Available

Pfam Domain Function

CARD (PF00619 )
NACHT (PF05729 )
LRR_6 (PF13516 )
NLRC4_HD2 (PF17776 )
NOD2_WH (PF17779 )

Signals

Not Available

Transmembrane Regions

Not Available

Protein Sequence

Not Available

External Links

GenBank ID Protein

Not Available

UniProtKB/Swiss-Prot ID

Q8K3Z0

UniProtKB/Swiss-Prot Entry Name

NOD2_MOUSE

PDB IDs

Not Available

GenBank Gene ID

Not Available

GeneCard ID

Not Available

GenAtlas ID

Not Available

HGNC ID

Not Available

References

General References

Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
McDonald C, Chen FF, Ollendorff V, Ogura Y, Marchetto S, Lecine P, Borg JP, Nunez G: A role for Erbin in the regulation of Nod2-dependent NF-kappaB signaling. J Biol Chem. 2005 Dec 2;280(48):40301-9. doi: 10.1074/jbc.M508538200. Epub 2005 Oct 3. [PubMed:16203728 ]
Hsu LC, Ali SR, McGillivray S, Tseng PH, Mariathasan S, Humke EW, Eckmann L, Powell JJ, Nizet V, Dixit VM, Karin M: A NOD2-NALP1 complex mediates caspase-1-dependent IL-1beta secretion in response to Bacillus anthracis infection and muramyl dipeptide. Proc Natl Acad Sci U S A. 2008 Jun 3;105(22):7803-8. doi: 10.1073/pnas.0802726105. Epub 2008 May 29. [PubMed:18511561 ]
Lee KH, Biswas A, Liu YJ, Kobayashi KS: Proteasomal degradation of Nod2 protein mediates tolerance to bacterial cell wall components. J Biol Chem. 2012 Nov 16;287(47):39800-11. doi: 10.1074/jbc.M112.410027. Epub 2012 Sep 27. [PubMed:23019338 ]
Iwanaga Y, Davey MP, Martin TM, Planck SR, DePriest ML, Baugh MM, Suing CM, Rosenbaum JT: Cloning, sequencing and expression analysis of the mouse NOD2/CARD15 gene. Inflamm Res. 2003 Jun;52(6):272-6. doi: 10.1007/s00011-003-1170-z. [PubMed:12835899 ]
Hsu YM, Zhang Y, You Y, Wang D, Li H, Duramad O, Qin XF, Dong C, Lin X: The adaptor protein CARD9 is required for innate immune responses to intracellular pathogens. Nat Immunol. 2007 Feb;8(2):198-205. doi: 10.1038/ni1426. Epub 2006 Dec 24. [PubMed:17187069 ]
Damgaard RB, Nachbur U, Yabal M, Wong WW, Fiil BK, Kastirr M, Rieser E, Rickard JA, Bankovacki A, Peschel C, Ruland J, Bekker-Jensen S, Mailand N, Kaufmann T, Strasser A, Walczak H, Silke J, Jost PJ, Gyrd-Hansen M: The ubiquitin ligase XIAP recruits LUBAC for NOD2 signaling in inflammation and innate immunity. Mol Cell. 2012 Jun 29;46(6):746-58. doi: 10.1016/j.molcel.2012.04.014. Epub 2012 May 17. [PubMed:22607974 ]