RAG2 - V(D)J recombination-activating protein 2 - human protein (Function)
 
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RAG2 »  V(D)J recombination-activating protein 2  (RAG-2)
 
Gene name:  RAG2
Family name: RAG2
Entry whose protein(s) existence is based on evidence at protein level
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GENE REF ISO

Function

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Overview 
Core 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. DNA cleavage by the RAG complex 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 the RAG complex, RAG2 is not the catalytic component but is required for all known catalytic activities mediated by RAG1. It probably acts as a sensor of chromatin state that recruits the RAG complex to H3K4me3 (By similarity).  
  • CuratedUniProtKB
GO molecular function 
Chromatin bindingdefinition[GO:0003682]  
  • ISSOrtholog Curator
DNA bindingdefinition[GO:0003677] silver  
  • IEAInterPro 2 GO
Methylated histone residue bindingdefinition[GO:0035064]  
  • ISSOrtholog Curator
Phosphatidylinositol bindingdefinition[GO:0035091]  
  • ISSOrtholog Curator
Phosphatidylinositol-3,4,5-trisphosphate bindingdefinition[GO:0005547]  
  • ISSOrtholog Curator
Phosphatidylinositol-3,4-bisphosphate bindingdefinition[GO:0043325]  
  • ISSOrtholog Curator
Phosphatidylinositol-3,5-bisphosphate bindingdefinition[GO:0080025]  
  • ISSOrtholog Curator
Phosphatidylinositol-4,5-bisphosphate bindingdefinition[GO:0005546]  
  • ISSOrtholog Curator
Zinc ion bindingdefinition[GO:0008270]  
  • ISSOrtholog Curator
GO biological process 
B cell differentiationdefinition[GO:0030183]  
  • ISSOrtholog Curator
B cell homeostatic proliferationdefinition[GO:0002358] silver  
  • IEAOrtholog Compara
B cell lineage commitmentdefinition[GO:0002326] silver  
  • IEAOrtholog Compara
Chromatin modificationdefinition[GO:0016568]  
  • IEAUniProtKB KW
Positive regulation of organ growthdefinition[GO:0046622] silver  
  • IEAOrtholog Compara
Pre-B cell allelic exclusiondefinition[GO:0002331]  
  • ISSOrtholog Curator
T cell differentiation in thymusdefinition[GO:0033077]  
  • ISSOrtholog Curator
T cell lineage commitmentdefinition[GO:0002360] silver  
  • IEAOrtholog Compara
V(D)J recombinationdefinition[GO:0033151]  
  • ISSOrtholog Curator
Pathways 
According to KEGG, this protein belongs to the following pathway:
Primary immunodeficiency  hsa05340+5897  
 

Keywords

Biological process 
DNA recombination  definition   [KW-0233]
Molecular function 
Chromatin regulator  definition   [KW-0156]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

GenomeRNAi: 5897
PRO: PR:P55895