Tbio RAG1 V(D)J recombination-activating protein 1

Protein Summary

Description

Catalytic 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. In the RAG complex, RAG1 mediates the DNA-binding to the conserved recombination signal sequences (RSS) and catalyzes the DNA cleavage activities by introducing a double-strand break between the RSS and the adjacent coding segment. RAG2 is not a catalytic component but is required for all known catalytic activities. DNA cleavage 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 addition to its endonuclease activity, RAG1 also acts as an E3 ubiquitin-protein ligase that mediates monoubiquitination of histone H3. Histone H3 monoubiquitination is required for the joining step of V(D)J recombination. Mediates polyubiquitination of KPNA1 (By similarity). The protein encoded by this gene is involved in activation of immunoglobulin V-D-J recombination. The encoded protein is involved in recognition of the DNA substrate, but stable binding and cleavage activity also requires RAG2. Defects in this gene can be the cause of several diseases. [provided by RefSeq, Jul 2008]

Uniprot Accession IDs

• P15918
• E9PPC4
• Q8IY72
• Q8NER2
• RAG-1

Gene Name

• RAG1

Ensembl ID

• ENST00000299440
• ENSP00000299440
• ENSG00000166349
• ENST00000534663
• ENSP00000434610

Symbol

• RNF74
• RAG-1
• RNF74

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
protein domain	0.99
biological process	0.92
molecular function	0.9
phenotype	0.89
gene perturbation	0.72

Protein Classes

PANTHER Classes

Protein / Nucleic Acid Binding / Nuclease / Endodeoxyribonuclease / V(d)j Recombination-activating Protein 1

Protein / Nucleic Acid Binding / Dna Binding Protein / Endodeoxyribonuclease / V(d)j Recombination-activating Protein 1

Protein / Hydrolase / V(d)j Recombination-activating Protein 1

DTO Classes

Protein / Enzyme / Nuclease / Endodeoxyribonuclease / V(d)j Recombination-activating Protein 1

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1754.03   (req: < 5)

Gene RIFs: 98   (req: <= 3)

Antibodies: 112   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1754.03   (req: >= 5)

Gene RIFs: 98   (req: > 3)

Antibodies: 112   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 25

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0