RAG1 - V(D)J recombination-activating protein 1 - human protein (Function)
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RAG1 »  V(D)J recombination-activating protein 1  (RAG-1)
Protein also known as:  RING finger protein 74.
Gene name:  RAG1
Family name: RAG1
Entry whose protein(s) existence is based on evidence at protein level
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1 83 2


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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 a 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 (By similarity).  
  • CuratedUniProtKB
GO molecular function 
Acid-amino acid ligase activitydefinition[GO:0016881] silver  
  • IEAInterPro 2 GO
DNA bindingdefinition[GO:0003677]  
Endonuclease activitydefinition[GO:0004519]  
  • ISSOrtholog Curator
Histone bindingdefinition[GO:0042393]  
  • ISSOrtholog Curator
Metal ion bindingdefinition[GO:0046872]  
  • ISSOrtholog Curator
Protein bindingdefinition[GO:0005515]  
  • IPIIntAct
Protein homodimerization activitydefinition[GO:0042803]  
  • ISSOrtholog Curator
Sequence-specific DNA bindingdefinition[GO:0043565]  
  • ISSOrtholog Curator
Ubiquitin-protein transferase activitydefinition[GO:0004842]  
  • ISSOrtholog Curator
Zinc ion bindingdefinition[GO:0008270]  
  • ISSOrtholog Curator
GO biological process 
Adaptive immune responsedefinition[GO:0002250] silver  
  • IEAOrtholog Compara
B cell differentiationdefinition[GO:0030183]  
  • ISSOrtholog Curator
DNA recombinationdefinition[GO:0006310]  
Histone monoubiquitinationdefinition[GO:0010390]  
  • ISSOrtholog Curator
Immune responsedefinition[GO:0006955]  
Negative regulation of cysteine-type endopeptidase activity involved in apoptotic processdefinition[GO:0043154] silver  
  • IEAOrtholog Compara
Negative regulation of thymocyte apoptotic processdefinition[GO:0070244] silver  
  • IEAOrtholog Compara
Nucleic acid phosphodiester bond hydrolysisdefinition[GO:0090305]  
  • IEAOrtholog Compara
  • IEAUniProtKB KW
  • ISSOrtholog Curator
Pre-B cell allelic exclusiondefinition[GO:0002331]  
  • ISSOrtholog Curator
Protein autoubiquitinationdefinition[GO:0051865]  
  • ISSOrtholog Curator
Regulation of T cell differentiationdefinition[GO:0045580] silver  
  • IEAOrtholog Compara
T cell differentiation in thymusdefinition[GO:0033077]  
  • ISSOrtholog Curator
T cell homeostasisdefinition[GO:0043029] silver  
  • IEAOrtholog Compara
Thymus developmentdefinition[GO:0048538] silver  
  • IEAOrtholog Compara
V(D)J recombinationdefinition[GO:0033151]  
  • ISSOrtholog Curator
Enzymatic activity 
It requires the following cofactor
Binds 1 divalent metal cation per subunit. Magnesium or manganese (By similarity).  
  • CuratedUniProtKB
According to KEGG, this protein belongs to the following pathway:
Primary immunodeficiency  hsa05340+5896  


Biological process 
DNA recombination  definition   [KW-0233]
Ubl conjugation pathway  definition   [KW-0833]
Molecular function 
Chromatin regulator  definition   [KW-0156]
Endonuclease  definition   [KW-0255]
Hydrolase  definition   [KW-0378]
Ligase  definition   [KW-0436]
Nuclease  definition   [KW-0540]
Technical term 
Multifunctional enzyme  definition   [KW-0511]
Reference proteome  definition   [KW-1185]

Further external links

GenomeRNAi: 5896
PRO: PR:P15918