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

GO curators for mouse genes have assigned the following annotations to the gene product of Cd40. (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 TNF-receptor superfamily. This receptor has been found to be essential in mediating a broad variety of immune and inflammatory responses including T cell-dependent immunoglobulin class switching, memory B cell development, and germinal center formation. AT-hook transcription factor AKNA is reported to coordinately regulate the expression of this receptor and its ligand, which may be important for homotypic cell interactions. Adaptor protein TNFR2 interacts with this receptor and serves as a mediator of the signal transduction. The interaction of this receptor and its ligand is found to be necessary for amyloid-beta-induced microglial activation, and thus is thought to be an early event in Alzheimer disease pathogenesis. Two alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported. [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 Cd40
  • participates in the following biological processes:
    • B cell activation ^[15]
    • defense response to virus ^[7]
    • immune response-regulating cell surface receptor signaling pathway ^[14]
    • positive regulation of B cell proliferation ^{[1, 2, 3, 5, 17]}
    • positive regulation of interleukin-12 production ^[14]
    • positive regulation of isotype switching to IgG isotypes ^[6]
    • regulation of immune response ^[6]
    • regulation of immunoglobulin secretion ^[9]
  • is located in the following cellular components:
    • CD40 receptor complex ^[8]
    • cell surface ^[19]
    • external side of plasma membrane ^{[7, 12, 14, 16, 17]}
    • intracellular membrane-bounded organelle ^[4]
    • plasma membrane ^[8]
• The gene product of Cd40 has been shown to bind to the gene products of Btk, Traf2, Traf6. ^{[8, 10, 13]}
• Researchers have inferred, based on phenotypic analysis of mouse mutants, that the gene product of Cd40
  • participates in the following biological processes:
    • cellular calcium ion homeostasis ^[11]
• Researchers have inferred, based on genetic interactions, that the gene product of Cd40
  • participates in the following biological processes:
    • positive regulation of B cell proliferation based on interactions with Chrnb2 ^[18]

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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 Cd40:
  • participates in the following biological processes:
    • cellular calcium ion homeostasis
    • inflammatory response
    • positive regulation of Cdc42 GTPase activity
    • positive regulation of endothelial cell apoptotic process
    • positive regulation of MAP kinase activity
    • positive regulation of NF-kappaB transcription factor activity
    • positive regulation of protein kinase C signaling cascade
    • positive regulation of protein phosphorylation
    • positive regulation of Rac GTPase activity
    • positive regulation of transcription from RNA polymerase II promoter
    • positive regulation of tyrosine phosphorylation of Stat1 protein
  • performs the following molecular functions:
    • enzyme binding
    • ubiquitin protein ligase binding
  • is located in the following cellular components:
    • cell surface
    • extracellular space

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Summary text for additional MGI annotations

• Automated translation to GO terms of SwissProt keywords that describe Cd40 indicates that it:
  • is located in the following cellular components:
    • extracellular region
    • integral to membrane
    • membrane

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References

1. Aldrich MB et al. (2003) Impaired germinal center maturation in adenosine deaminase deficiency. J Immunol, 171:5562-70. (PubMed:14607964)
2. Byth KF et al. (1996) CD45-null transgenic mice reveal a positive regulatory role for CD45 in early thymocyte development, in the selection of CD4+CD8+ thymocytes, and B cell maturation. J Exp Med, 183:1707-18. (PubMed:8666928)
3. Chappel MS et al. (1996) Cross-linking the murine heat-stable antigen induces apoptosis in B cell precursors and suppresses the anti-CD40-induced proliferation of mature resting B lymphocytes. J Exp Med, 184:1638-49. (PubMed:8920854)
4. Chen W et al. (2006) Efficient induction of antitumor T cell immunity by exosomes derived from heat-shocked lymphoma cells. Eur J Immunol, 36:1598-607. (PubMed:16708399)
5. Chin AI et al. (2002) Involvement of receptor-interacting protein 2 in innate and adaptive immune responses. Nature, 416:190-4. (PubMed:11894097)
6. Gerth AJ et al. (2003) T-bet regulates T-independent IgG2a class switching. Int Immunol, 15:937-44. (PubMed:12882831)
7. Hervas-Stubbs S et al. (2007) Insect baculoviruses strongly potentiate adaptive immune responses by inducing type I IFN. J Immunol, 178:2361-9. (PubMed:17277142)
8. Hostager BS et al. (2010) HOIL-1L interacting protein (HOIP) as an NF-kappaB regulating component of the CD40 signaling complex. PLoS One, 5:e11380. (PubMed:20614026)
9. Hostager BS et al. (2003) Tumor necrosis factor receptor-associated factor 2 (TRAF2)-deficient B lymphocytes reveal novel roles for TRAF2 in CD40 signaling. J Biol Chem, 278:45382-90. (PubMed:12958312)
10. Ishida T et al. (1996) Identification of TRAF6, a novel tumor necrosis factor receptor-associated factor protein that mediates signaling from an amino-terminal domain of the CD40 cytoplasmic region. J Biol Chem, 271:28745-8. (PubMed:8910514)
11. Kim DY et al. (2011) Signal pathways in astrocytes activated by cross-talk between of astrocytes and mast cells through CD40-CD40L. J Neuroinflammation, 8:25. (PubMed:21410936)
12. Kong YY et al. (1995) Differential requirements of CD45 for lymphocyte development and function. Eur J Immunol, 25:3431-6. (PubMed:8566034)
13. Liu X et al. (2011) Intracellular MHC class II molecules promote TLR-triggered innate immune responses by maintaining activation of the kinase Btk. Nat Immunol, 12:416-24. (PubMed:21441935)
14. McKee AS et al. (2004) CD25+CD4+ cells contribute to Th2 polarization during helminth infection by suppressing Th1 response development. J Immunol, 173:1224-31. (PubMed:15240714)
15. Merluzzi S et al. (2004) CD40 stimulation induces Pax5/BSAP and EBF activation through a APE/Ref-1-dependent redox mechanism. J Biol Chem, 279:1777-86. (PubMed:14594818)
16. Pauleau AL et al. (2003) Role of nod2 in the response of macrophages to toll-like receptor agonists. Mol Cell Biol, 23:7531-9. (PubMed:14560001)
17. Sexl V et al. (2000) Stat5a/b contribute to interleukin 7-induced B-cell precursor expansion, but abl- and bcr/abl-induced transformation are independent of stat5 Blood, 96:2277-83. (PubMed:10979977)
18. Skok M et al. (2005) Nicotinic receptors regulate B lymphocyte activation and immune response. Eur J Pharmacol, 517:246-51. (PubMed:15963492)
19. Takekoshi T et al. (2010) Identification of a novel marker for dendritic cell maturation, mouse transmembrane protein 123. J Biol Chem, 285:31876-84. (PubMed:20685650)

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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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