RAG2
Core component of the RAG complex, a multiprotein complex that mediates the DNA cleavage phase during V(D)J recombination. 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 occurs in 2 steps: a first nick is introduced 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 transesterification reaction, thereby creating 4 DNA ends: 2 hairpin coding ends and 2 blunt, 5'-phosphorylated ends. The chromatin structure plays an essential role in the V(D)J recombination reactions and the presence of histone H3 trimethylated at 'Lys-4' (H3K4me3) stimulates both the nicking and haipinning steps. The RAG complex also plays a role in pre-B cell allelic exclusion, a process leading to expression of a single immunoglobulin heavy chain allele to enforce clonality and monospecific recognition by the B-cell antigen receptor (BCR) expressed on individual B-lymphocytes. 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. In the RAG complex, RAG2 is not the catalytic component but is required for all known catalytic activities mediated by RAG1. It probably acts as a sensor of chromatin state that recruits the RAG complex to H3K4me3. Belongs to the RAG2 family. Cells of the B- and T-lymphocyte lineages. Note: This description may include information from UniProtKB.
Protein type: Cell development/differentiation; Histone-binding; Lipid-binding
Cellular Component: DNA recombinase complex; nucleoplasm
Molecular Function: chromatin binding; methylated histone binding; phosphatidylinositol binding; phosphatidylinositol-3,4,5-trisphosphate binding; phosphatidylinositol-3,4-bisphosphate binding; phosphatidylinositol-3,5-bisphosphate binding; phosphatidylinositol-4,5-bisphosphate binding; sequence-specific DNA binding; ubiquitin protein ligase activity; zinc ion binding
Biological Process: B cell differentiation; B cell homeostatic proliferation; B cell lineage commitment; chromatin organization; defense response to bacterium; DN2 thymocyte differentiation; mature B cell differentiation involved in immune response; negative regulation of T cell differentiation in thymus; organ growth; positive regulation of organ growth; pre-B cell allelic exclusion; T cell differentiation in thymus; T cell lineage commitment; V(D)J recombination
