======= RAG2 ======= == Gene Information == * **Official Symbol**: RAG2 * **Official Name**: recombination activating 2 * **Aliases and Previous Symbols**: N/A * **Entrez ID**: [[https://www.ncbi.nlm.nih.gov/gene/?term=5897|5897]] * **UniProt**: [[https://www.uniprot.org/uniprot/P55895|P55895]] * **Interactions**: [[https://thebiogrid.org/search.php?search=RAG2&organism=9606|BioGRID]] * **PubMed articles**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20RAG2|Open PubMed]] * **OMIM**: [[https://omim.org/entry/179616|Open OMIM]] == Function Summary == * **Entrez Summary**: 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]. * **UniProt Summary**: 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 (By similarity). {ECO:0000250}. |RAG2| |DNA recombinase complex| |B cell homeostatic proliferation| |pre-B cell allelic exclusion| |pre-B cell differentiation| |B cell lineage commitment| |immature B cell differentiation| |V(D)J recombination| |T cell lineage commitment| |phosphatidylinositol-3,5-bisphosphate binding| |phosphatidylinositol-3,4-bisphosphate binding| |somatic cell DNA recombination| |somatic diversification of immune receptors via germline recombination within a single locus| |phosphatidylinositol-3,4,5-trisphosphate binding| |B cell proliferation| |T cell differentiation in thymus| |positive regulation of organ growth| |somatic diversification of immune receptors| |methylated histone binding| |phosphatidylinositol-4,5-bisphosphate binding| |lymphocyte proliferation| |mononuclear cell proliferation| |phosphatidylinositol binding| |regulation of organ growth| |leukocyte proliferation| |B cell differentiation| |T cell differentiation| |B cell activation| |positive regulation of developmental growth| |ubiquitin protein ligase activity| |DNA recombination| |T cell activation| |lymphocyte differentiation| |cell fate commitment| |positive regulation of growth| |regulation of developmental growth| |defense response to bacterium| |leukocyte differentiation| |lymphocyte activation| |chromatin binding| |sequence-specific DNA binding| |cell population proliferation| |hemopoiesis| |hematopoietic or lymphoid organ development| |immune system development| |regulation of growth| |protein ubiquitination| |response to bacterium| |chromatin organization| |DNA metabolic process| |protein modification by small protein conjugation| |zinc ion binding| |leukocyte activation| |defense response to other organism| |protein modification by small protein conjugation or removal| |chromosome organization| |cell activation| |response to other organism| |response to external biotic stimulus| |response to biotic stimulus| |defense response| |positive regulation of developmental process| |homeostatic process| |positive regulation of multicellular organismal process| \\ === CRISPR Data === No hits were found. No correlation found to any other genes in chemogenomics. Global Fraction of Cell Lines Where Essential: 0/726 ^Tissue^Fraction Of Cell Lines Where Essential^ |1290807.0|0/1| |909776.0|0/1| |bile duct|0/28| |blood|0/28| |bone|0/25| |breast|0/33| |central nervous system|0/56| |cervix|0/4| |colorectal|0/17| |esophagus|0/13| |fibroblast|0/1| |gastric|0/15| |kidney|0/21| |liver|0/20| |lung|0/75| |lymphocyte|0/14| |ovary|0/26| |pancreas|0/24| |peripheral nervous system|0/16| |plasma cell|0/15| |prostate|0/1| |skin|0/24| |soft tissue|0/7| |thyroid|0/2| |upper aerodigestive|0/22| |urinary tract|0/29| |uterus|0/5| == Essentiality in NALM6 == * **Essentiality Rank**: 11535 * **Expression level (log2 read counts)**: 6.99 {{:chemogenomics:nalm6 dist.png?nolink |}}