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

GO curators for mouse genes have assigned the following annotations to the gene product of Rag1. (This text reflects annotations as of Tuesday, May 21, 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 involved in activation of immunoglobulin V-D-J recombination. The encoded protein is involved in recognition of the DNA substrate, but stable binding and cleavage activity also requires RAG2. Defects in this gene can be the cause of several diseases. [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 Rag1
  • participates in the following biological processes:
    • B cell differentiation ^[11]
    • histone monoubiquitination ^[3]
    • protein autoubiquitination ^[6]
  • performs the following molecular functions:
    • histone binding ^[3]
    • protein homodimerization activity ^{[2, 16]}
    • sequence-specific DNA binding ^[16]
    • ubiquitin-protein ligase activity ^{[3, 6, 17]}
    • zinc ion binding ^[2]
  • is located in the following cellular components:
    • nucleus ^[14]
• The gene product of Rag1 has been shown to bind to the gene products of Gmeb1, Rag2. ^{[8, 16]}
• Researchers have inferred, based on phenotypic analysis of mouse mutants, that the gene product of Rag1
  • participates in the following biological processes:
    • adaptive immune response ^[15]
    • B cell differentiation ^[12]
    • death ^[5]
    • negative regulation of cysteine-type endopeptidase activity involved in apoptotic process ^[9]
    • negative regulation of thymocyte apoptotic process ^[9]
    • pre-B cell allelic exclusion ^[4]
    • T cell differentiation in thymus ^{[10, 12]}
    • V(D)J recombination ^{[3, 7, 12, 14]}
  • performs the following molecular functions:
    • endonuclease activity ^{[7, 16]}
    • metal ion binding ^[7]
    • sequence-specific DNA binding ^[7]
• Researchers have inferred, based on genetic interactions, that the gene product of Rag1
  • participates in the following biological processes:
    • negative regulation of T cell apoptotic process based on interactions with Slc46a2 ^[1]
    • regulation of T cell differentiation based on interactions with Slc46a2 ^[1]
    • T cell homeostasis based on interactions with Slc46a2 ^[1]
    • thymus development based on interactions with Slc46a2 ^[1]
    • V(D)J recombination based on interactions with Rag2 ^[13]

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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 Rag1:
  • participates in the following biological processes:
    • B cell differentiation
    • histone monoubiquitination
    • pre-B cell allelic exclusion
    • protein autoubiquitination
    • T cell differentiation in thymus
    • V(D)J recombination
  • performs the following molecular functions:
    • endonuclease activity
    • histone binding
    • metal ion binding
    • protein homodimerization activity
    • sequence-specific DNA binding
    • ubiquitin-protein ligase activity
    • zinc ion binding
  • is located in the following cellular components:
    • nucleus

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Summary text based on GO annotations supported by structural data

• Rag1 encodes a protein or proteins that contain the following InterPro domains: RAG nonamer-binding domain, Recombination-activation protein 1, Zinc finger C2H2-type/integrase DNA-binding domain, Zinc finger, C2H2-like, Zinc finger, RING-type, Zinc finger, RING-type, conserved site, Zinc finger, RING/FYVE/PHD-type, Zinc finger, V(D)J recombination-activating protein 1, indicating that the gene product:
  • performs the following molecular functions:
    • acid-amino acid ligase activity
    • hydrolase activity, acting on ester bonds
    • nucleic acid binding

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Summary text for additional MGI annotations

• Automated translation to GO terms of SwissProt keywords that describe Rag1 indicates that it:
  • participates in the following biological processes:
    • chromatin modification
    • metabolic process
  • performs the following molecular functions:
    • catalytic activity
    • DNA binding
    • hydrolase activity
    • ligase activity
    • nuclease activity

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References

1. Ahn S et al. (2008) TSCOT+ thymic epithelial cell-mediated sensitive CD4 tolerance by direct presentation. PLoS Biol, 6:e191. (PubMed:18684012)
2. Bellon SF et al. (1997) Crystal structure of the RAG1 dimerization domain reveals multiple zinc-binding motifs including a novel zinc binuclear cluster. Nat Struct Biol, 4:586-91. (PubMed:9228952)
3. Grazini U et al. (2010) The RING domain of RAG1 ubiquitylates histone H3: a novel activity in chromatin-mediated regulation of V(D)J joining. Mol Cell, 37:282-93. (PubMed:20122409)
4. 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)
5. Hotchkiss RS et al. (1999) Overexpression of Bcl-2 in transgenic mice decreases apoptosis and improves survival in sepsis. J Immunol, 162:4148-56. (PubMed:10201940)
6. Jones JM et al. (2003) Autoubiquitylation of the V(D)J recombinase protein RAG1. Proc Natl Acad Sci U S A, 100:15446-51. (PubMed:14671314)
7. Kim DR et al. (1999) Mutations of acidic residues in RAG1 define the active site of the V(D)J recombinase. Genes Dev, 13:3070-80. (PubMed:10601033)
8. Maitra R et al. (2009) A WW-like module in the RAG1 N-terminal domain contributes to previously unidentified protein-protein interactions. Nucleic Acids Res, 37:3301-9. (PubMed:19324890)
9. Mandal M et al. (2005) The BCL2A1 gene as a pre-T cell receptor-induced regulator of thymocyte survival. J Exp Med, 201:603-14. (PubMed:15728238)
10. Maraskovsky E et al. (1997) Bcl-2 can rescue T lymphocyte development in interleukin-7 receptor-deficient mice but not in mutant rag-1-/- mice. Cell, 89:1011-9. (PubMed:9215624)
11. Miyamoto A et al. (2002) Increased proliferation of B cells and auto-immunity in mice lacking protein kinase Cdelta. Nature, 416:865-9. (PubMed:11976687)
12. Mombaerts P et al. (1992) RAG-1-deficient mice have no mature B and T lymphocytes. Cell, 68:869-77. (PubMed:1547488)
13. 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)
14. Sadofsky MJ et al. (1993) Expression and V(D)J recombination activity of mutated RAG-1 proteins [published erratum appears in Nucleic Acids Res 1994 Feb 11;22(3):550] Nucleic Acids Res, 21:5644-50. (PubMed:8284210)
15. Shui JW et al. (2012) HVEM signalling at mucosal barriers provides host defence against pathogenic bacteria. Nature, 488:222-5. (PubMed:22801499)
16. 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)
17. Yurchenko V et al. (2003) The RAG1 N-terminal domain is an E3 ubiquitin ligase. Genes Dev, 17:581-5. (PubMed:12629039)

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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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