V(D)J recombinase-1 (V(D)J recombination-activating protein-1, RING finger protein 74, RAG1)

Function

• role in V(D)J recombination
• RAG1/RAG2 complex initiates V(D)J recombination by binding to conserved recombination signal sequences (RSS) & introducing a double-strand break between the RSS & the adjacent coding segment
• breaks are generated in 2 steps, nicking of one strand (hydrolysis), followed by hairpin formation (transesterification)
• RAG1/RAG2 complex functions as a transposase in vitro, & possesses RSS-independent endonuclease activity (end processing) & hairpin opening.
• RAG1 alone can bind to RSS but stable, efficient binding requires RAG2
• all known catalytic activities require the presence of both proteins
• established hallmarks of the Ig or TCR recombinase system include site specificity organized around signal sequences, N-region addition, & nibbling at the coding sequence junctions
• in connection with RAG2, RAG1 confers V(D)J recombinase activity on virtually any cell type

Cofactor: binds 1 Mg+2 or Mn+2 per subunit

Structure

• specific binding to the nonamer RSS motif is mediated by the nonamer binding domain (NBD)
• contains 1 NBD (nonamer binding) DNA-binding domain
• contains 1 RING-type Zn+2 finger

Compartment

nucleus

Expression

maturing lymphoid cells

Pathology

• defects in RAG1 are a cause of:
  • severe combined immunodeficiency, B-cell-negative
  • Omenn syndrome

More general terms

• recombinase
• ring finger protein

Component of

• RAG1/RAG2 complex

Database

• UniProt: http://www.uniprot.org/uniprot/P15918.html
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:5896
• OMIM: https://mirror.omim.org/entry/179615
• OMIM: https://mirror.omim.org/entry/601457
• OMIM: https://mirror.omim.org/entry/603554