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

GO curators for mouse genes have assigned the following annotations to the gene product of Tnfsf4. (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 cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This cytokine is a ligand for receptor TNFRSF4/OX4. It is found to be involved in T cell antigen-presenting cell (APC) interactions. In surface Ig- and CD40-stimulated B cells, this cytokine along with CD70 has been shown to provide CD28-independent costimulatory signals to T cells. This protein and its receptor are reported to directly mediate adhesion of activated T cells to vascular endothelial cells. [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 Tnfsf4
  • participates in the following biological processes:
    • negative regulation of interferon-gamma production ^[4]
    • negative regulation of sequence-specific DNA binding transcription factor activity ^[13]
    • negative regulation of T-helper 1 cell differentiation ^[4]
    • negative regulation of transcription, DNA-dependent ^[13]
    • positive regulation of B cell activation ^[4]
    • positive regulation of CD4-positive, alpha beta T cell costimulation ^[8]
    • positive regulation of CD4-positive, alpha-beta T cell differentiation ^[8]
    • positive regulation of immunoglobulin secretion ^[13]
    • positive regulation of interleukin-13 production ^[2]
    • positive regulation of interleukin-4 production ^{[2, 4]}
    • positive regulation of memory T cell differentiation ^[14]
    • positive regulation of T cell costimulation ^[8]
    • positive regulation of T cell cytokine production ^{[2, 4]}
    • positive regulation of T-helper 2 cell differentiation ^[2]
    • positive regulation of type 2 immune response ^[2]
    • regulation of adaptive immune response ^[7]
    • regulation of inflammatory response ^[1]
    • response to chemical stimulus ^[5]
    • response to virus ^[8]
• Researchers have inferred, based on physical interactions, that the gene product of Tnfsf4
  • participates in the following biological processes:
    • inflammatory response ^[9]
    • negative regulation of cytokine secretion ^[9]
  • performs the following molecular functions:
    • tumor necrosis factor receptor binding ^[9]
    • tumor necrosis factor receptor superfamily binding ^[13]
• Researchers have inferred, based on phenotypic analysis of mouse mutants, that the gene product of Tnfsf4
  • participates in the following biological processes:
    • acute inflammatory response ^[7]
    • chemokine (C-C motif) ligand 11 production ^[1]
    • cholesterol metabolic process ^[10]
    • defense response to nematode ^[3]
    • interleukin-4-dependent isotype switching to IgE isotypes ^[3]
    • memory T cell activation ^[3]
    • negative regulation of regulatory T cell differentiation ^[14]
    • positive regulation of alpha-beta T cell proliferation ^[12]
    • positive regulation of immunoglobulin mediated immune response ^[3]
    • positive regulation of interferon-gamma production ^[14]
    • positive regulation of interleukin-10 production ^[7]
    • positive regulation of interleukin-12 production ^[7]
    • positive regulation of interleukin-4 production ^[3]
    • positive regulation of interleukin-6 production ^[7]
    • positive regulation of type 2 immune response ^{[3, 6]}
    • T-helper 2 cell activation ^[3]
• Based on the experimental annotations above, MGI curators have inferred, that the gene product of Tnfsf4
  • participates in the following biological processes:
    • negative regulation of apoptotic process ^[11]
    • negative regulation of T cell apoptotic process ^[11]

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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 Tnfsf4:
  • participates in the following biological processes:
    • cellular response to lipopolysaccharide
    • cellular response to prostaglandin E stimulus
    • cytokine production
    • negative regulation of interleukin-17 production
    • positive regulation of activated T cell proliferation
    • positive regulation of inflammatory response
    • positive regulation of interferon-gamma production
    • positive regulation of interleukin-2 production
    • positive regulation of interleukin-4 production
    • positive regulation of interleukin-6 production
    • T cell proliferation
  • performs the following molecular functions:
    • tumor necrosis factor receptor superfamily binding
  • is located in the following cellular components:
    • cell surface
    • extracellular space

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Summary text based on GO annotations supported by structural data

• Tnfsf4 encodes a protein or proteins that contain the following InterPro domains: Tumour necrosis factor, Tumour necrosis factor, conserved site, Tumour necrosis factor-like, indicating that the gene product:
  • participates in the following biological processes:
    • immune response
  • is located in the following cellular components:
    • membrane

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Summary text for additional MGI annotations

• Automated translation to GO terms of SwissProt keywords that describe Tnfsf4 indicates that it:
  • performs the following molecular functions:
    • cytokine activity
  • is located in the following cellular components:
    • integral to membrane
    • membrane

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References

1. Arestides RS et al. (2002) Costimulatory molecule OX40L is critical for both Th1 and Th2 responses in allergic inflammation. Eur J Immunol, 32:2874-80. (PubMed:12355440)
2. Blazquez AB et al. (2008) Gastrointestinal dendritic cells promote Th2 skewing via OX40L. J Immunol, 180:4441-50. (PubMed:18354165)
3. Ekkens MJ et al. (2003) The role of OX40 ligand interactions in the development of the Th2 response to the gastrointestinal nematode parasite Heligmosomoides polygyrus. J Immunol, 170:384-93. (PubMed:12496423)
4. Flynn S et al. (1998) CD4 T cell cytokine differentiation: the B cell activation molecule, OX40 ligand, instructs CD4 T cells to express interleukin 4 and upregulates expression of the chemokine receptor, Blr-1. J Exp Med, 188:297-304. (PubMed:9670042)
5. Hodgkins SR et al. (2010) NO2 inhalation induces maturation of pulmonary CD11c+ cells that promote antigenspecific CD4+ T cell polarization. Respir Res, 11:102. (PubMed:20659336)
6. Jenkins SJ et al. (2007) Dendritic cell expression of OX40 ligand acts as a costimulatory, not polarizing, signal for optimal Th2 priming and memory induction in vivo. J Immunol, 179:3515-23. (PubMed:17785785)
7. Karulf M et al. (2010) OX40 ligand regulates inflammation and mortality in the innate immune response to sepsis. J Immunol, 185:4856-62. (PubMed:20844189)
8. Kurche JS et al. (2010) Comparison of OX40 Ligand and CD70 in the Promotion of CD4+ T Cell Responses. J Immunol, 185:2106-15. (PubMed:20639485)
9. Obermeier F et al. (2003) OX40/OX40L interaction induces the expression of CXCR5 and contributes to chronic colitis induced by dextran sulfate sodium in mice. Eur J Immunol, 33:3265-74. (PubMed:14635034)
10. Paigen B et al. (1987) Ath-1, a gene determining atherosclerosis susceptibility and high density lipoprotein levels in mice. Proc Natl Acad Sci U S A, 84:3763-7. (PubMed:3473481)
11. Rogers PR et al. (2001) OX40 promotes Bcl-xL and Bcl-2 expression and is essential for long-term survival of CD4 T cells. Immunity, 15:445-55. (PubMed:11567634)
12. Soroosh P et al. (2006) OX40-OX40 ligand interaction through T cell-T cell contact contributes to CD4 T cell longevity. J Immunol, 176:5975-87. (PubMed:16670306)
13. Stuber E et al. (1995) Cross-linking of OX40 ligand, a member of the TNF/NGF cytokine family, induces proliferation and differentiation in murine splenic B cells. Immunity, 2:507-21. (PubMed:7749983)
14. Xiao X et al. (2008) OX40/OX40L costimulation affects induction of Foxp3+ regulatory T cells in part by expanding memory T cells in vivo. J Immunol, 181:3193-201. (PubMed:18713990)

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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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