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

GO curators for mouse genes have assigned the following annotations to the gene product of Rag2. (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.] This gene encodes a protein that is involved in the initiation of V(D)J recombination during B and T cell development. This protein forms a complex with the product of the adjacent recombination activating gene 1, and this complex can form double-strand breaks by cleaving DNA at conserved recombination signal sequences. The recombination activating gene 1 component is thought to contain most of the catalytic activity, while the N-terminal of the recombination activating gene 2 component is thought to form a six-bladed propeller in the active core that serves as a binding scaffold for the tight association of the complex with DNA. A C-terminal plant homeodomain finger-like motif in this protein is necessary for interactions with chromatin components, specifically with histone H3 that is trimethylated at lysine 4. Mutations in this gene cause Omenn syndrome, a form of severe combined immunodeficiency associated with autoimmune-like symptoms. [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 Rag2
  • performs the following molecular functions:
    • chromatin binding ^{[7, 10]}
    • methylated histone residue binding ^{[7, 10]}
    • phosphatidylinositol binding ^[7]
    • phosphatidylinositol-3,4,5-trisphosphate binding ^[3]
    • phosphatidylinositol-3,4-bisphosphate binding ^[3]
    • phosphatidylinositol-3,5-bisphosphate binding ^[3]
    • phosphatidylinositol-4,5-bisphosphate binding ^[3]
    • zinc ion binding ^{[3, 7, 10]}
• The gene product of Rag2 has been shown to bind to the gene products of Rag1. ^[12]
• Researchers have inferred, based on phenotypic analysis of mouse mutants, that the gene product of Rag2
  • participates in the following biological processes:
    • B cell differentiation ^{[1, 2, 8]}
    • B cell homeostatic proliferation ^[13]
    • B cell lineage commitment ^[6]
    • positive regulation of organ growth ^[11]
    • pre-B cell allelic exclusion ^[5]
    • T cell differentiation ^{[1, 2]}
    • T cell differentiation in thymus ^{[4, 8]}
    • T cell lineage commitment ^[6]
    • V(D)J recombination ^{[7, 8]}
• Researchers have inferred, based on genetic interactions, that the gene product of Rag2
  • participates in the following biological processes:
    • positive regulation of organ growth based on interactions with Il7 ^[11]
    • V(D)J recombination based on interactions with Rag1 ^[9]
• Based on the experimental annotations above, MGI curators have inferred, that the gene product of Rag2
  • is located in the following cellular components:
    • nucleus ^[7]

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Summary text based on GO annotations supported by structural data

• Rag2 encodes a protein or proteins that contain the following InterPro domains: Galactose oxidase/kelch, beta-propeller, Kelch-type beta propeller, Recombination activating protein 2, PHD domain, V-D-J recombination activating protein 2, indicating that the gene product:
  • performs the following molecular functions:
    • DNA binding

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Summary text for additional MGI annotations

• Automated translation to GO terms of SwissProt keywords that describe Rag2 indicates that it:
  • participates in the following biological processes:
    • chromatin modification
  • performs the following molecular functions:
    • metal ion binding

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References

1. Cabana VG et al. (2004) Influence of apoA-I and apoE on the formation of serum amyloid A-containing lipoproteins in vivo and in vitro. J Lipid Res, 45:317-25. (PubMed:14595002)
2. Dahl R et al. (2002) Spi-B can functionally replace PU.1 in myeloid but not lymphoid development. EMBO J, 21:2220-30. (PubMed:11980719)
3. Elkin SK et al. (2005) A PHD finger motif in the C terminus of RAG2 modulates recombination activity. J Biol Chem, 280:28701-10. (PubMed:15964836)
4. Gao Y et al. (1998) A critical role for DNA end-joining proteins in both lymphogenesis and neurogenesis. Cell, 95:891-902. (PubMed:9875844)
5. Hewitt SL et al. (2009) RAG-1 and ATM coordinate monoallelic recombination and nuclear positioning of immunoglobulin loci. Nat Immunol, 10:655-64. (PubMed:19448632)
6. Li T et al. (1996) Distinct patterns of Fas cell surface expression during development of T- or B-lymphocyte lineages in normal, scid, and mutant mice lacking or overexpressing p53, bcl-2, or rag-2 genes. Cell Growth Differ, 7:107-14. (PubMed:8788039)
7. Matthews AG et al. (2007) RAG2 PHD finger couples histone H3 lysine 4 trimethylation with V(D)J recombination. Nature, 450:1106-10. (PubMed:18033247)
8. Mombaerts P et al. (1992) RAG-1-deficient mice have no mature B and T lymphocytes. Cell, 68:869-77. (PubMed:1547488)
9. Oettinger MA et al. (1990) RAG-1 and RAG-2, adjacent genes that synergistically activate V(D)J recombination. Science, 248:1517-23. (PubMed:2360047)
10. Ramon-Maiques S et al. (2007) The plant homeodomain finger of RAG2 recognizes histone H3 methylated at both lysine-4 and arginine-2. Proc Natl Acad Sci U S A, 104:18993-8. (PubMed:18025461)
11. von Freeden-Jeffry U et al. (1997) The earliest T lineage-committed cells depend on IL-7 for Bcl-2 expression and normal cell cycle progression. Immunity, 7:147-54. (PubMed:9252127)
12. Yin FF et al. (2009) Structure of the RAG1 nonamer binding domain with DNA reveals a dimer that mediates DNA synapsis. Nat Struct Mol Biol, 16:499-508. (PubMed:19396172)
13. Young F et al. (1997) Constitutive Bcl-2 expression during immunoglobulin heavy chain-promoted B cell differentiation expands novel precursor B cells. Immunity, 6:23-33. (PubMed:9052834)

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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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