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

GO curators for mouse genes have assigned the following annotations to the gene product of Ccl2. (This text reflects annotations as of Thursday, July 24, 2014.)

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Summary from NCBI RefSeq

[Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene is one of several Cys-Cys (CC) cytokine genes clustered on the q-arm of chromosome 17. Cytokines are a family of secreted proteins involved in immunoregulatory and inflammatory processes. The CC cytokines are proteins characterized by two adjacent cysteines. The cytokine encoded by this gene displays chemotactic activity for monocytes, lymphocytes, basophils and eosinophils, but not neutrophils. This chemokine plays a role in accumulation of leukocytes during inflammation. It may also be involved in the recruitment of monocytes into the arterial wall during artherosclerosis. [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 Ccl2
  • participates in the following biological processes:
    • cellular response to interferon-gamma ^[8]
    • cellular response to interleukin-1 ^[8]
    • cellular response to lipopolysaccharide ^[8]
    • cellular response to tumor necrosis factor ^[8]
    • helper T cell extravasation ^[10]
    • positive regulation of apoptotic cell clearance ^[9]
    • positive regulation of macrophage chemotaxis ^[1]
    • response to wounding ^[6]
  • performs the following molecular functions:
    • G-protein coupled receptor binding ^{[3, 4]}
  • is located in the following cellular components:
    • extracellular space ^{[5, 11]}
• The gene product of Ccl2 has been shown to bind to the gene products of Ccr1. ^[4] Researchers have inferred, based on physical interactions, that the gene product of Ccl2
  • performs the following molecular functions:
    • CCR2 chemokine receptor binding ^[7]
• Researchers have inferred, based on phenotypic analysis of mouse mutants, that the gene product of Ccl2
  • participates in the following biological processes:
    • negative regulation of angiogenesis ^[1]
    • positive regulation of immune complex clearance by monocytes and macrophages ^[1]
    • positive regulation of nitric-oxide synthase biosynthetic process ^[2]
    • positive regulation of T cell activation ^[8]
    • regulation of vascular endothelial growth factor production ^[1]

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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 Ccl2:
  • participates in the following biological processes:
    • cellular calcium ion homeostasis
    • chemokine-mediated signaling pathway
    • cytokine-mediated signaling pathway
    • cytoskeleton organization
    • eosinophil chemotaxis
    • glial cell migration
    • leukocyte migration involved in inflammatory response
    • lymphocyte chemotaxis
    • macrophage chemotaxis
    • neutrophil chemotaxis
    • positive regulation of cell adhesion
    • positive regulation of cell-cell adhesion
    • positive regulation of cellular extravasation
    • positive regulation of collagen biosynthetic process
    • positive regulation of endothelial cell proliferation
    • positive regulation of leukocyte mediated cytotoxicity
    • positive regulation of leukocyte migration
    • positive regulation of macrophage chemotaxis
    • positive regulation of monocyte chemotaxis
    • positive regulation of synaptic transmission
    • positive regulation of tumor necrosis factor production
    • regulation of cell shape
    • response to heat
    • transforming growth factor beta receptor signaling pathway
    • vascular endothelial growth factor receptor signaling pathway
  • performs the following molecular functions:
    • CCR2 chemokine receptor binding
    • chemokine activity
    • heparin binding
  • is located in the following cellular components:
    • axon terminus
    • C-fiber
    • cytoplasm
    • dendrite
    • endocytic vesicle
    • extracellular space
    • neuronal cell body
    • perikaryon
    • perinuclear region of cytoplasm
    • rough endoplasmic reticulum
    • synapse

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Summary text based on GO annotations supported by structural data

• Ccl2 encodes a protein or proteins that contain the following InterPro domains: CC chemokine, conserved site, Chemokine interleukin-8-like domain, indicating that the gene product:
  • participates in the following biological processes:
    • immune response
  • is located in the following cellular components:
    • extracellular region

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Summary text for additional MGI annotations

• Automated translation to GO terms of SwissProt keywords that describe Ccl2 indicates that it:
  • participates in the following biological processes:
    • chemotaxis
    • inflammatory response
  • performs the following molecular functions:
    • cytokine activity
  • is located in the following cellular components:
    • extracellular region

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References

1. Ambati J et al. (2003) An animal model of age-related macular degeneration in senescent Ccl-2- or Ccr-2-deficient mice. Nat Med, 9:1390-7. (PubMed:14566334)
2. Aoki T et al. (2009) Impact of monocyte chemoattractant protein-1 deficiency on cerebral aneurysm formation. Stroke, 40:942-51. (PubMed:19164781)
3. Boring L et al. (1997) Impaired monocyte migration and reduced type 1 (Th1) cytokine responses in C-C chemokine receptor 2 knockout mice. J Clin Invest, 100:2552-61. (PubMed:9366570)
4. Boring L et al. (1996) Molecular cloning and functional expression of murine JE (monocyte chemoattractant protein 1) and murine macrophage inflammatory protein 1alpha receptors: evidence for two closely linked C-C chemokine receptors on chromosome 9. J Biol Chem, 271:7551-8. (PubMed:8631787)
5. Deshmukh HS et al. (2009) Critical role of NOD2 in regulating the immune response to Staphylococcus aureus. Infect Immun, 77:1376-82. (PubMed:19139201)
6. Esteban V et al. (2009) Angiotensin-(1-7) and the g protein-coupled receptor MAS are key players in renal inflammation. PLoS ONE, 4:e5406. (PubMed:19404405)
7. Kurihara T et al. (1996) Cloning and functional expression of mCCR2, a murine receptor for the C-C chemokines JE and FIC. J Biol Chem, 271:11603-7. (PubMed:8662823)
8. Lee I et al. (2003) Blocking the monocyte chemoattractant protein-1/CCR2 chemokine pathway induces permanent survival of islet allografts through a programmed death-1 ligand-1-dependent mechanism. J Immunol, 171:6929-35. (PubMed:14662900)
9. Tanaka T et al. (2010) Monocyte chemoattractant protein-1/CC chemokine ligand 2 enhances apoptotic cell removal by macrophages through Rac1 activation. Biochem Biophys Res Commun, 399:677-82. (PubMed:20691665)
10. Webb A et al. (2008) Evidence for PI-3K-dependent migration of Th17-polarized cells in response to CCR2 and CCR6 agonists. J Leukoc Biol, 84:1202-12. (PubMed:18586982)
11. Yang S et al. (2013) Pellino3 ubiquitinates RIP2 and mediates Nod2-induced signaling and protective effects in colitis. Nat Immunol, 14:927-36. (PubMed:23892723)

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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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