InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Rag2

Summary

InnateDB Protein

IDBP-258576.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

Rag2

Protein Name

recombination activating gene 2

Synonyms

Rag-2;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000106858

InnateDB Gene

IDBG-193167 (Rag2)

Protein Structure

UniProt Annotation

Function

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. {ECO:0000269PubMed:16111638, ECO:0000269PubMed:19448632, ECO:0000269PubMed:19524534, ECO:0000269PubMed:2360047, ECO:0000269PubMed:8521468, ECO:0000269PubMed:9094713}.

Subcellular Localization

Nucleus.

Disease Associations

Tissue Specificity

Maturing lymphoid cells.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 14 experimentally validated interaction(s) in this database.
They are also associated with 6 interaction(s) predicted by orthology.

Experimentally validated
Total	14 [view]
Protein-Protein	6 [view]
Protein-DNA	7 [view]
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	6 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003677	DNA binding
GO:0003682	chromatin binding
GO:0005515	protein binding
GO:0005546	phosphatidylinositol-4,5-bisphosphate binding
GO:0005547	phosphatidylinositol-3,4,5-trisphosphate binding
GO:0008270	zinc ion binding
GO:0035064	methylated histone binding
GO:0035091	phosphatidylinositol binding
GO:0043325	phosphatidylinositol-3,4-bisphosphate binding
GO:0080025	phosphatidylinositol-3,5-bisphosphate binding

Biological Process

GO:0002326	B cell lineage commitment
GO:0002331	pre-B cell allelic exclusion
GO:0002358	B cell homeostatic proliferation
GO:0002360	T cell lineage commitment
GO:0006310	DNA recombination
GO:0016568	chromatin modification
GO:0030183	B cell differentiation
GO:0030217	T cell differentiation
GO:0033077	T cell differentiation in thymus
GO:0033151	V(D)J recombination
GO:0046622	positive regulation of organ growth