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. Component of the RAG complex composed of core components RAG1 and RAG2, and associated component HMGB1 or HMGB2. Cells of the B- and T-lymphocyte lineages. Belongs to the RAG2 family. Note: This description may include information from UniProtKB.
Protein type: Enzyme, misc.
Cellular Component: nucleus
Molecular Function: phosphatidylinositol-4,5-bisphosphate binding; protein binding; phosphatidylinositol-3,4,5-triphosphate binding; DNA binding; zinc ion binding; metal ion binding; chromatin binding; phosphatidylinositol-3,4-bisphosphate binding; phosphoinositide binding; methylated histone residue binding
Biological Process: T cell lineage commitment; B cell homeostatic proliferation; V(D)J recombination; B cell differentiation; B cell lineage commitment; pre-B cell allelic exclusion; T cell differentiation in the thymus; chromatin modification; positive regulation of organ growth; DNA recombination; T cell differentiation
SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.