UniProt functional annotation for P21784



	UniProt functional annotation for P21784

UniProt code: P21784.

Organism: Mus musculus (Mouse).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.

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

Subunit: Component of the RAG complex composed of core components RAG1 and RAG2, and associated component HMGB1 or HMGB2. {ECO:0000269|PubMed:15964836, ECO:0000269|PubMed:18025461, ECO:0000269|PubMed:9094713, ECO:0000269|PubMed:9184213}.

Subcellular location: Nucleus.

Tissue specificity: Maturing lymphoid cells.

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). {ECO:0000269|PubMed:18025461, ECO:0000269|PubMed:18033247}.

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. {ECO:0000269|PubMed:1547487, ECO:0000269|PubMed:18724932}.

Similarity: Belongs to the RAG2 family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Mus musculus (Mouse).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.



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


Subunit:		Component of the RAG complex composed of core components RAG1 and RAG2, and associated component HMGB1 or HMGB2. {ECO:0000269\|PubMed:15964836, ECO:0000269\|PubMed:18025461, ECO:0000269\|PubMed:9094713, ECO:0000269\|PubMed:9184213}.
Subcellular location:		Nucleus.
Tissue specificity:		Maturing lymphoid cells.
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). {ECO:0000269\|PubMed:18025461, ECO:0000269\|PubMed:18033247}.
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. {ECO:0000269\|PubMed:1547487, ECO:0000269\|PubMed:18724932}.
Similarity:		Belongs to the RAG2 family. {ECO:0000305}.