Go Annotations as Summary Text (Tabular View) (GO Graph)

GO curators for mouse genes have assigned the following annotations to the gene product of Tlr2. (This text reflects annotations as of Wednesday, January 23, 2013.)

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Summary from NCBI RefSeq

[Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene is a member of the Toll-like receptor (TLR) family which plays a fundamental role in pathogen recognition and activation of innate immunity. TLRs are highly conserved from Drosophila to humans and share structural and functional similarities. They recognize pathogen-associated molecular patterns (PAMPs) that are expressed on infectious agents, and mediate the production of cytokines necessary for the development of effective immunity. The various TLRs exhibit different patterns of expression. This gene is expressed most abundantly in peripheral blood leukocytes, and mediates host response to Gram-positive bacteria and yeast via stimulation of NF-kappaB. [provided by RefSeq, Jul 2008]

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Summary text based on GO annotations supported by experimental evidence in mouse

• Researchers have inferred from direct assay, that the gene product of Tlr2
  • participates in the following biological processes:
    • positive regulation of interferon-beta production ^[11]
    • positive regulation of interleukin-12 production ^[11]
    • positive regulation of interleukin-18 production ^[11]
    • positive regulation of interleukin-6 production ^{[9, 11]}
    • positive regulation of nitric-oxide synthase biosynthetic process ^[11]
    • positive regulation of transcription from RNA polymerase II promoter ^[11]
    • positive regulation of tumor necrosis factor production ^[11]
  • performs the following molecular functions:
    • diacyl lipopeptide binding ^{[5, 6]}
    • lipoteichoic acid binding ^[6]
    • triacyl lipopeptide binding ^[5]
  • is located in the following cellular components:
    • external side of plasma membrane ^[15]
    • plasma membrane ^[2]
• The gene product of Tlr2 has been shown to bind to the gene products of Tirap. ^[7] Researchers have inferred, based on physical interactions, that the gene product of Tlr2
  • performs the following molecular functions:
    • protein heterodimerization activity ^[6]
  • is located in the following cellular components:
    • Toll-like receptor 2-Toll-like receptor 6 protein complex ^[6]
• Researchers have inferred, based on phenotypic analysis of mouse mutants, that the gene product of Tlr2
  • participates in the following biological processes:
    • cell surface pattern recognition receptor signaling pathway ^[2]
    • cellular response to bacterial lipopeptide ^[4]
    • cellular response to lipoteichoic acid ^[4]
    • cellular response to peptidoglycan ^[16]
    • chloramphenicol transport ^[1]
    • defense response to Gram-positive bacterium ^{[3, 4, 12]}
    • induction by symbiont of defense-related host nitric oxide production ^[8]
    • negative regulation of growth of symbiont in host ^{[4, 12]}
    • negative regulation of interleukin-12 production ^[16]
    • negative regulation of interleukin-17 production ^[8]
    • positive regulation of chemokine production ^[8]
    • positive regulation of interleukin-6 production ^{[12, 13]}
    • positive regulation of leukocyte migration ^[10]
    • positive regulation of macrophage cytokine production ^[13]
    • positive regulation of nitric oxide biosynthetic process ^{[8, 13]}
    • positive regulation of tumor necrosis factor biosynthetic process ^[8]
    • positive regulation of tumor necrosis factor production ^{[2, 4, 8, 12, 13]}
    • response to bacterium ^[10]
    • response to molecule of fungal origin ^[2]
    • response to peptidoglycan ^{[10, 13]}
• Researchers have inferred, based on genetic interactions, that the gene product of Tlr2
  • participates in the following biological processes:
    • MyD88-dependent toll-like receptor signaling pathway based on interactions with Myd88 ^[2]
    • positive regulation of cytokine secretion based on interactions with Cd209d ^[14]

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Summary text based on GO annotations supported by experimental evidence in other organisms

• From comparative sequence analysis (see table for details), MGI curators have determined that the gene product of Tlr2:
  • participates in the following biological processes:
    • cellular response to diacyl bacterial lipopeptide
    • cellular response to lipoteichoic acid
    • cellular response to triacyl bacterial lipopeptide
    • defense response to bacterium
    • detection of diacyl bacterial lipopeptide
    • detection of triacyl bacterial lipopeptide
    • I-kappaB phosphorylation
    • inflammatory response
    • microglial cell activation involved in immune response
    • nitric oxide metabolic process
    • pathogen-associated molecular pattern dependent induction by symbiont of host innate immune response
    • positive regulation of chemokine production
    • positive regulation of interleukin-6 production
    • positive regulation of interleukin-8 production
    • positive regulation of NF-kappaB import into nucleus
    • positive regulation of NF-kappaB transcription factor activity
    • positive regulation of toll-like receptor signaling pathway
    • positive regulation of Wnt receptor signaling pathway
    • response to bacterial lipoprotein
    • response to fatty acid
    • toll-like receptor signaling pathway
  • performs the following molecular functions:
    • Gram-positive bacterial cell surface binding
    • lipopeptide binding
    • pattern recognition receptor activity
    • peptidoglycan binding
    • protein heterodimerization activity
    • receptor activity
    • triacyl lipopeptide binding
  • is located in the following cellular components:
    • cell surface
    • cytoplasm
    • plasma membrane
    • Toll-like receptor 1-Toll-like receptor 2 protein complex

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Summary text based on GO annotations supported by structural data

• Tlr2 encodes a protein or proteins that contain the following InterPro domains: Cysteine-rich flanking region, C-terminal, Interleukin-1 receptor, type I/Toll precursor, Leucine-rich repeat, Leucine-rich repeat, typical subtype, Toll-like receptor, Toll/interleukin-1 receptor homology (TIR) domain, indicating that the gene product:
  • participates in the following biological processes:
    • immune response
    • signal transduction
  • performs the following molecular functions:
    • transmembrane signaling receptor activity
  • is located in the following cellular components:
    • integral to membrane
    • intrinsic to membrane

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Summary text for additional MGI annotations

• Automated translation to GO terms of SwissProt keywords that describe Tlr2 indicates that it:
  • is located in the following cellular components:
    • cytoplasmic vesicle
    • integral to membrane
    • membrane

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References

1. Alexopoulou L et al. (2002) Hyporesponsiveness to vaccination with Borrelia burgdorferi OspA in humans and in TLR1- and TLR2-deficient mice. Nat Med, 8:878-84. (PubMed:12091878)
2. Brown GD et al. (2003) Dectin-1 mediates the biological effects of beta-glucans. J Exp Med, 197:1119-24. (PubMed:12719478)
3. Deshmukh HS et al. (2009) Critical role of NOD2 in regulating the immune response to Staphylococcus aureus. Infect Immun, 77:1376-82. (PubMed:19139201)
4. Hoebe K et al. (2005) CD36 is a sensor of diacylglycerides. Nature, 433:523-7. (PubMed:15690042)
5. Jin MS et al. (2007) Crystal structure of the TLR1-TLR2 heterodimer induced by binding of a tri-acylated lipopeptide. Cell, 130:1071-82. (PubMed:17889651)
6. Kang JY et al. (2009) Recognition of lipopeptide patterns by Toll-like receptor 2-Toll-like receptor 6 heterodimer. Immunity, 31:873-84. (PubMed:19931471)
7. Khor CC et al. (2007) A Mal functional variant is associated with protection against invasive pneumococcal disease, bacteremia, malaria and tuberculosis. Nat Genet, 39:523-8. (PubMed:17322885)
8. Kielian T et al. (2005) Toll-like receptor 2 modulates the proinflammatory milieu in Staphylococcus aureus-induced brain abscess. Infect Immun, 73:7428-35. (PubMed:16239543)
9. Kim YG et al. (2008) The cytosolic sensors Nod1 and Nod2 are critical for bacterial recognition and host defense after exposure to Toll-like receptor ligands. Immunity, 28:246-57. (PubMed:18261938)
10. Mullaly SC et al. (2006) The role of TLR2 in vivo following challenge with Staphylococcus aureus and prototypic ligands. J Immunol, 177:8154-63. (PubMed:17114491)
11. Olson JK et al. (2004) Microglia initiate central nervous system innate and adaptive immune responses through multiple TLRs. J Immunol, 173:3916-24. (PubMed:15356140)
12. Takeuchi O et al. (2000) Cutting edge: TLR2-deficient and MyD88-deficient mice are highly susceptible to Staphylococcus aureus infection. J Immunol, 165:5392-6. (PubMed:11067888)
13. Takeuchi O et al. (1999) Differential roles of TLR2 and TLR4 in recognition of gram-negative and gram-positive bacterial cell wall components. Immunity, 11:443-51. (PubMed:10549626)
14. Tanne A et al. (2009) A murine DC-SIGN homologue contributes to early host defense against Mycobacterium tuberculosis. J Exp Med, 206:2205-20. (PubMed:19770268)
15. Watanabe T et al. (2004) NOD2 is a negative regulator of Toll-like receptor 2-mediated T helper type 1 responses. Nat Immunol, 5:800-8. (PubMed:15220916)
16. Watanabe T et al. (2006) Nucleotide binding oligomerization domain 2 deficiency leads to dysregulated TLR2 signaling and induction of antigen-specific colitis. Immunity, 25:473-85. (PubMed:16949315)

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Gene Ontology Evidence Code Abbreviations:

EXP Inferred from experiment

IC Inferred by curator

IDA Inferred from direct assay

IEA Inferred from electronic annotation

IGI Inferred from genetic interaction

IMP Inferred from mutant phenotype

IPI Inferred from physical interaction

ISS Inferred from sequence or structural similarity

ISO Inferred from sequence orthology

ISA Inferred from sequence alignment

ISM Inferred from sequence model

NAS Non-traceable author statement

ND No biological data available

RCA Reviewed computational analysis

TAS Traceable author statement

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