V(D)J recombination-activating protein 2 (UniProt: P21784; also known as RAG-2) is encoded by the Rag2 (also known as Rag-2) gene (Gene ID: 19374) in murine species. RAG-2 is a nuclear protein that is a core component of the multiprotein RAG complex. It is predominantly found in maturing lymphoid cells. RAG complex mediates the DNA cleavage phase during V(D)J recombination. During this phase V(D)J recombination assembles a diverse repertoire of immunoglobulin and T-cell receptor genes in developing B and T-lymphocytes through rearrangement of different V (variable), in some cases D (diversity), and J (joining) gene segments. DNA cleavage by the RAG complex is reported to occur by first introducing a nick in the top strand immediately upstream of the heptamer, generating a 3'-hydroxyl group that can attack the phosphodiester bond on the opposite strand in a direct trans-esterification reaction, thereby creating 4 DNA ends: 2 hairpin coding ends and 2 blunt, 5'-phosphorylated ends. The chromatin structure is shown to play a critical role in the V(D)J recombination reactions and the presence of histone H3 trimethylated at Lys4 (H3K4me3) stimulates both the nicking and hairpinning steps. RAG-2 contains an atypical PHD-type zinc finger (a 416-484) that recognizes and binds histone H3 trimethylated on Lys4 (H3K4me3). The introduction of DNA breaks by the RAG complex on one immunoglobulin allele induces ATM-dependent repositioning of the other allele to pericentromeric heterochromatin, preventing accessibility to the RAG complex and recombination of the second allele. Although RAG-2 is not the catalytic component, it is required for all known catalytic activities mediated by RAG1. Mice with defective Rag2 gene fail to produce mature B or T-lymphocytes.
Synonyms: V(D)J recombination-activating protein 2, RAG-2
Application: Research CategoryApoptosis & Cancer
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