P21784 · RAG2_MOUSE

  • Protein
    V(D)J recombination-activating protein 2
  • Gene
    Rag2
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

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.

Features

Showing features for binding site.

152750100150200250300350400450500
TypeIDPosition(s)Description
Binding site419Zn2+ 1 (UniProtKB | ChEBI)
Binding site423Zn2+ 1 (UniProtKB | ChEBI)
Binding site446Zn2+ 2 (UniProtKB | ChEBI)
Binding site452Zn2+ 2 (UniProtKB | ChEBI)
Binding site455Zn2+ 1 (UniProtKB | ChEBI)
Binding site458Zn2+ 1 (UniProtKB | ChEBI)
Binding site478Zn2+ 2 (UniProtKB | ChEBI)
Binding site481Zn2+ 2 (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular ComponentDNA recombinase complex
Cellular Componentnucleoplasm
Cellular Componentnucleus
Molecular Functionchromatin binding
Molecular Functionmethylated histone binding
Molecular Functionphosphatidylinositol binding
Molecular Functionphosphatidylinositol-3,4,5-trisphosphate binding
Molecular Functionphosphatidylinositol-3,4-bisphosphate binding
Molecular Functionphosphatidylinositol-3,5-bisphosphate binding
Molecular Functionphosphatidylinositol-4,5-bisphosphate binding
Molecular Functionsequence-specific DNA binding
Molecular Functionubiquitin protein ligase activity
Molecular Functionzinc ion binding
Biological ProcessB cell differentiation
Biological ProcessB cell homeostatic proliferation
Biological ProcessB cell lineage commitment
Biological Processchromatin organization
Biological Processdefense response to bacterium
Biological ProcessDN2 thymocyte differentiation
Biological ProcessDNA recombination
Biological Processmature B cell differentiation involved in immune response
Biological Processnegative regulation of T cell differentiation in thymus
Biological Processorgan growth
Biological Processpositive regulation of organ growth
Biological Processpre-B cell allelic exclusion
Biological ProcessT cell differentiation
Biological ProcessT cell differentiation in thymus
Biological ProcessT cell lineage commitment
Biological ProcessV(D)J recombination

Keywords

Names & Taxonomy

Protein names

  • Recommended name
    V(D)J recombination-activating protein 2
  • Short names
    RAG-2

Gene names

    • Name
      Rag2
    • Synonyms
      Rag-2

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    P21784

Proteomes

Organism-specific databases

Subcellular Location

Phenotypes & Variants

Disruption phenotype

Mice are viable but fail to produce mature B or T-lymphocytes. Very immature lymphoid cells are present in primary lymphoid organs. These cells do not rearrange their immunoglobulin or T-cell receptor loci. Double knockout with TREX1 does not show a visible phenotype.

Features

Showing features for mutagenesis.

TypeIDPosition(s)Description
Mutagenesis128Does not affect the endonuclease activity of the RAG complex.
Mutagenesis199Does not affect the endonuclease activity of the RAG complex.
Mutagenesis202Does not affect the endonuclease activity of the RAG complex.
Mutagenesis280Does not affect the endonuclease activity of the RAG complex.
Mutagenesis310Does not affect the endonuclease activity of the RAG complex.
Mutagenesis358Does not affect the endonuclease activity of the RAG complex.
Mutagenesis374Does not affect the endonuclease activity of the RAG complex.
Mutagenesis402Reduced interaction with histones.
Mutagenesis403Reduced interaction with histones.
Mutagenesis406Reduced interaction with histones.
Mutagenesis407Reduced interaction with histones.
Mutagenesis408Induces a slight reduction in V(D)J recombination without affecting interaction with histones.
Mutagenesis415Abolishes binding to H3K4me3 without affecting phosphoinositide-binding.
Mutagenesis440Binds PtdIns(4,5)P2 at wild-type level.
Mutagenesis443Abolishes binding to H3K4me3 without affecting phosphoinositide-binding.
Mutagenesis445Still binds H3K4me3 and H3R2me2 but with reduced affinity.
Mutagenesis453Abolishes binding to H3K4me3 without affecting phosphoinositide-binding. Impairs enzymatic activity of the RAG complex.
Mutagenesis464Leads to a strong reduction in PtdIns(4,5)P2-binding.
Mutagenesis468Leads to a strong reduction in PtdIns(4,5)P2-binding.

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 43 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

PTM/Processing

Features

Showing features for chain.

TypeIDPosition(s)Description
ChainPRO_00001671381-527V(D)J recombination-activating protein 2

Proteomic databases

PTM databases

Expression

Tissue specificity

Maturing lymphoid cells.

Gene expression databases

Interaction

Subunit

Component of the RAG complex composed of core components RAG1 and RAG2, and associated component HMGB1 or HMGB2.

Binary interactions

TypeEntry 1Entry 2Number of experimentsIntact
BINARY P21784Rag1 P159194EBI-7602123, EBI-7602168

Protein-protein interaction databases

Miscellaneous

Family & Domains

Features

Showing features for region, compositional bias, zinc finger.

TypeIDPosition(s)Description
Region359-380Disordered
Compositional bias360-374Polar residues
Zinc finger416-484PHD-type; atypical
Region490-511Disordered

Domain

The atypical PHD-type zinc finger recognizes and binds histone H3 trimethylated on 'Lys-4' (H3K4me3). The presence Tyr-445 instead of a carboxylate in classical PHD-type zinc fingers results in an enhanced binding to H3K4me3 in presence of dimethylated on 'Arg-2' (H3R2me2) rather than inhibited. The atypical PHD-type zinc finger also binds various phosphoinositides, such as phosphatidylinositol 3,4-bisphosphate binding (PtdIns(3,4)P2), phosphatidylinositol 3,5-bisphosphate binding (PtdIns(3,5)P2), phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) and phosphatidylinositol 3,4,5-trisphosphate binding (PtdIns(3,4,5)P3).

Sequence similarities

Belongs to the RAG2 family.

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    527
  • Mass (Da)
    59,074
  • Last updated
    1998-07-15 v2
  • Checksum
    51086F95A4A664A7
MSLQMVTVGHNIALIQPGFSLMNFDGQVFFFGQKGWPKRSCPTGVFHFDIKQNHLKLKPAIFSKDSCYLPPLRYPATCSYKGSIDSDKHQYIIHGGKTPNNELSDKIYIMSVACKNNKKVTFRCTEKDLVGDVPEPRYGHSIDVVYSRGKSMGVLFGGRSYMPSTQRTTEKWNSVADCLPHVFLIDFEFGCATSYILPELQDGLSFHVSIARNDTVYILGGHSLASNIRPANLYRIRVDLPLGTPAVNCTVLPGGISVSSAILTQTNNDEFVIVGGYQLENQKRMVCSLVSLGDNTIEISEMETPDWTSDIKHSKIWFGSNMGNGTIFLGIPGDNKQAMSEAFYFYTLRCSEEDLSEDQKIVSNSQTSTEDPGDSTPFEDSEEFCFSAEATSFDGDDEFDTYNEDDEDDESVTGYWITCCPTCDVDINTWVPFYSTELNKPAMIYCSHGDGHWVHAQCMDLEERTLIHLSEGSNKYYCNEHVQIARALQTPKRNPPLQKPPMKSLHKKGSGKVLTPAKKSFLRRLFD

Features

Showing features for compositional bias.

TypeIDPosition(s)Description
Compositional bias360-374Polar residues

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
M64796
EMBL· GenBank· DDBJ
AAB82302.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

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