RAG1
Catalytic 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. In the RAG complex, RAG1 mediates the DNA-binding to the conserved recombination signal sequences (RSS) and catalyzes the DNA cleavage activities by introducing a double-strand break between the RSS and the adjacent coding segment. RAG2 is not a catalytic component but is required for all known catalytic activities. DNA cleavage 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 addition to its endonuclease activity, RAG1 also acts as an E3 ubiquitin-protein ligase that mediates monoubiquitination of histone H3. Histone H3 monoubiquitination is required for the joining step of V(D)J recombination. Mediates polyubiquitination of KPNA1. Belongs to the RAG1 family. Maturing lymphoid cells. 2 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
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Protein type: DNA-binding; EC 3.1.-.-; EC 6.3.2.-; EC 6.3.2.19; Ligase; Ubiquitin conjugating system; Ubiquitin ligase |
Chromosomal Location of human Ortholog: 11p12 |
Cellular Component:
DNA recombinase complex; endodeoxyribonuclease complex; nucleoplasm; nucleus
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Molecular Function:
DNA binding; double-stranded DNA endonuclease activity; endonuclease activity; histone binding; metal ion binding; protein binding; protein homodimerization activity; sequence-specific DNA binding; ubiquitin protein ligase activity; ubiquitin-protein transferase activity; zinc ion binding
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Biological Process:
adaptive immune response; B cell differentiation; chromatin organization; DNA recombination; immune response; negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; negative regulation of thymocyte apoptotic process; positive regulation of T cell differentiation; pre-B cell allelic exclusion; protein autoubiquitination; regulation of behavioral fear response; T cell differentiation in thymus; T cell homeostasis; thymus development; V(D)J recombination; visual learning
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Disease: Alpha/beta T-cell Lymphopenia With Gamma/delta T-cell Expansion, Severe Cytomegalovirus Infection, And Autoimmunity; Combined Cellular And Humoral Immune Defects With Granulomas; Omenn Syndrome; Severe Combined Immunodeficiency, Autosomal Recessive, T Cell-negative, B Cell-negative, Nk Cell-positive
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Reference #:
P15918
(UniProtKB)
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Alt. Names/Synonyms: E3 ubiquitin-protein ligase RAG1; Endonuclease RAG1; MGC43321; RAG-1; RAG1; recombination activating 1; recombination activating gene 1; recombination activating protein 1; RING finger protein 74; RING-type E3 ubiquitin transferase RAG1; RNF74; V(D)J recombination-activating protein 1
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Gene Symbols: RAG1
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Molecular weight:
119,097 Da
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Basal Isoelectric point:
8.94
Predict pI for various phosphorylation states
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Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology®
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