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
extend overview
1 89 2
GENE REF ISO

Function

 show evidences
Overview 
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).  
1
  • UniProtKB
GO molecular function 
Acid-amino acid ligase activitydefinition[GO:0016881] silver  
1
  • InterPro 2 GO
DNA bindingdefinition[GO:0003677]  
1
  • PINC
Endonuclease activitydefinition[GO:0004519]  
1
  • Ortholog Curator
Histone bindingdefinition[GO:0042393]  
1
  • Ortholog Curator
Metal ion bindingdefinition[GO:0046872]  
1
  • Ortholog Curator
Protein bindingdefinition[GO:0005515]  
1
  • IntAct
Protein homodimerization activitydefinition[GO:0042803]  
1
  • Ortholog Curator
Sequence-specific DNA bindingdefinition[GO:0043565]  
1
  • Ortholog Curator
Ubiquitin-protein transferase activitydefinition[GO:0004842]  
1
  • Ortholog Curator
Zinc ion bindingdefinition[GO:0008270]  
1
  • Ortholog Curator
GO biological process 
Adaptive immune responsedefinition[GO:0002250] silver  
1
  • Ortholog Compara
B cell differentiationdefinition[GO:0030183]  
1
  • Ortholog Curator
DNA recombinationdefinition[GO:0006310]  
1
  • PINC
Histone monoubiquitinationdefinition[GO:0010390]  
1
  • Ortholog Curator
Immune responsedefinition[GO:0006955]  
1
  • PINC
Negative regulation of cysteine-type endopeptidase activity involved in apoptotic processdefinition[GO:0043154] silver  
1
  • Ortholog Compara
Negative regulation of thymocyte apoptotic processdefinition[GO:0070244] silver  
1
  • Ortholog Compara
Nucleic acid phosphodiester bond hydrolysisdefinition[GO:0090305]  
3
  • Ortholog Compara
  • Ortholog Curator
  • UniProtKB KW
Pre-B cell allelic exclusiondefinition[GO:0002331]  
1
  • Ortholog Curator
Protein autoubiquitinationdefinition[GO:0051865]  
1
  • Ortholog Curator
Regulation of T cell differentiationdefinition[GO:0045580] silver  
1
  • Ortholog Compara
T cell differentiation in thymusdefinition[GO:0033077]  
1
  • Ortholog Curator
T cell homeostasisdefinition[GO:0043029] silver  
1
  • Ortholog Compara
Thymus developmentdefinition[GO:0048538] silver  
1
  • Ortholog Compara
V(D)J recombinationdefinition[GO:0033151]  
1
  • Ortholog Curator
Enzymatic activity 
It requires the following cofactor
 Mg(2+) : Binds 1 divalent metal cation per subunit. Mg(2+) or Mn(2+).  
1
  • UniProtKB
Pathways 
According to KEGG, this protein belongs to the following pathway:
Primary immunodeficiency  hsa05340+5896  
 

Keywords

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