P21784 · RAG2_MOUSE
- ProteinV(D)J recombination-activating protein 2
- GeneRag2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids527 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 419 | Zn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 423 | Zn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 446 | Zn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 452 | Zn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 455 | Zn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 458 | Zn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 478 | Zn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 481 | Zn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: H |
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Names & Taxonomy
Protein names
- Recommended nameV(D)J recombination-activating protein 2
- Short namesRAG-2
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionP21784
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.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 128 | Does not affect the endonuclease activity of the RAG complex. | ||||
Sequence: D → N | ||||||
Mutagenesis | 199 | Does not affect the endonuclease activity of the RAG complex. | ||||
Sequence: E → Q | ||||||
Mutagenesis | 202 | Does not affect the endonuclease activity of the RAG complex. | ||||
Sequence: D → N | ||||||
Mutagenesis | 280 | Does not affect the endonuclease activity of the RAG complex. | ||||
Sequence: E → Q | ||||||
Mutagenesis | 310 | Does not affect the endonuclease activity of the RAG complex. | ||||
Sequence: D → N | ||||||
Mutagenesis | 358 | Does not affect the endonuclease activity of the RAG complex. | ||||
Sequence: D → N | ||||||
Mutagenesis | 374 | Does not affect the endonuclease activity of the RAG complex. | ||||
Sequence: D → N | ||||||
Mutagenesis | 402 | Reduced interaction with histones. | ||||
Sequence: Y → A | ||||||
Mutagenesis | 403 | Reduced interaction with histones. | ||||
Sequence: N → A | ||||||
Mutagenesis | 406 | Reduced interaction with histones. | ||||
Sequence: D → A | ||||||
Mutagenesis | 407 | Reduced interaction with histones. | ||||
Sequence: E → A | ||||||
Mutagenesis | 408 | Induces a slight reduction in V(D)J recombination without affecting interaction with histones. | ||||
Sequence: D → A | ||||||
Mutagenesis | 415 | Abolishes binding to H3K4me3 without affecting phosphoinositide-binding. | ||||
Sequence: Y → A | ||||||
Mutagenesis | 440 | Binds PtdIns(4,5)P2 at wild-type level. | ||||
Sequence: K → A | ||||||
Mutagenesis | 443 | Abolishes binding to H3K4me3 without affecting phosphoinositide-binding. | ||||
Sequence: M → A | ||||||
Mutagenesis | 445 | Still binds H3K4me3 and H3R2me2 but with reduced affinity. | ||||
Sequence: Y → A or D | ||||||
Mutagenesis | 453 | Abolishes binding to H3K4me3 without affecting phosphoinositide-binding. Impairs enzymatic activity of the RAG complex. | ||||
Sequence: W → R | ||||||
Mutagenesis | 464 | Leads to a strong reduction in PtdIns(4,5)P2-binding. | ||||
Sequence: R → A | ||||||
Mutagenesis | 468 | Leads to a strong reduction in PtdIns(4,5)P2-binding. | ||||
Sequence: H → A |
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.
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000167138 | 1-527 | V(D)J recombination-activating protein 2 | |||
Sequence: MSLQMVTVGHNIALIQPGFSLMNFDGQVFFFGQKGWPKRSCPTGVFHFDIKQNHLKLKPAIFSKDSCYLPPLRYPATCSYKGSIDSDKHQYIIHGGKTPNNELSDKIYIMSVACKNNKKVTFRCTEKDLVGDVPEPRYGHSIDVVYSRGKSMGVLFGGRSYMPSTQRTTEKWNSVADCLPHVFLIDFEFGCATSYILPELQDGLSFHVSIARNDTVYILGGHSLASNIRPANLYRIRVDLPLGTPAVNCTVLPGGISVSSAILTQTNNDEFVIVGGYQLENQKRMVCSLVSLGDNTIEISEMETPDWTSDIKHSKIWFGSNMGNGTIFLGIPGDNKQAMSEAFYFYTLRCSEEDLSEDQKIVSNSQTSTEDPGDSTPFEDSEEFCFSAEATSFDGDDEFDTYNEDDEDDESVTGYWITCCPTCDVDINTWVPFYSTELNKPAMIYCSHGDGHWVHAQCMDLEERTLIHLSEGSNKYYCNEHVQIARALQTPKRNPPLQKPPMKSLHKKGSGKVLTPAKKSFLRRLFD |
Proteomic databases
PTM databases
Expression
Interaction
Subunit
Component of the RAG complex composed of core components RAG1 and RAG2, and associated component HMGB1 or HMGB2.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P21784 | Rag1 P15919 | 4 | EBI-7602123, EBI-7602168 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, compositional bias, zinc finger.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 359-380 | Disordered | ||||
Sequence: QKIVSNSQTSTEDPGDSTPFED | ||||||
Compositional bias | 360-374 | Polar residues | ||||
Sequence: KIVSNSQTSTEDPGD | ||||||
Zinc finger | 416-484 | PHD-type; atypical | ||||
Sequence: WITCCPTCDVDINTWVPFYSTELNKPAMIYCSHGDGHWVHAQCMDLEERTLIHLSEGSNKYYCNEHVQI | ||||||
Region | 490-511 | Disordered | ||||
Sequence: TPKRNPPLQKPPMKSLHKKGSG |
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
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length527
- Mass (Da)59,074
- Last updated1998-07-15 v2
- Checksum51086F95A4A664A7
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 360-374 | Polar residues | ||||
Sequence: KIVSNSQTSTEDPGD |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
M64796 EMBL· GenBank· DDBJ | AAB82302.1 EMBL· GenBank· DDBJ | mRNA |