Recombination activating protein 1 (RAG1)

Recombination activating protein 1 (RAG1), often referred to as RAG-1, is a critical enzyme involved in the V(D)J recombination process, which is essential for the generation of antigen receptor diversity in the immune system. RAG1, in conjunction with RAG2, forms the V(D)J recombinase complex responsible for DNA cleavage at recombination signal sequences. It possesses endonuclease activity and also functions as a RING-type E3 ubiquitin ligase, mediating histone monoubiquitylation. Mutations in the RAG1 gene are associated with severe immunodeficiencies, including Severe Combined Immunodeficiency (SCID) and Omenn syndrome. Conversely, aberrant or unscheduled RAG1 activity can contribute to autoimmunity and lymphoid malignancies. While a crucial protein, its activity needs to be tightly regulated to prevent disease. RAG1 gene mutations serve as biomarkers for diagnosing related immunodeficiencies. Targeting RAG1 presents significant safety concerns due to the life-threatening nature of immunodeficiency caused by loss-of-function and the risk of autoimmunity/cancer from aberrant activity.

Other names

V(D)J recombination-activating protein 1Endonuclease RAG1E3 ubiquitin-protein ligase RAG1RNF74RAG-1MGC43321RING finger protein 74RING-type E3 ubiquitin transferase RAG1recombination activating gene 1