InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Rag1

Summary

InnateDB Protein

IDBP-193192.6

Last Modified

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

Gene Symbol

Rag1

Protein Name

recombination activating gene 1

Synonyms

Rag-1;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000077584

InnateDB Gene

IDBG-193190 (Rag1)

Protein Structure

UniProt Annotation

Function

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 a 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. {ECO:0000269PubMed:10601032, ECO:0000269PubMed:10678172, ECO:0000269PubMed:12629039, ECO:0000269PubMed:14671314, ECO:0000269PubMed:17028591, ECO:0000269PubMed:19118899, ECO:0000269PubMed:19396172, ECO:0000269PubMed:19448632, ECO:0000269PubMed:19524534, ECO:0000269PubMed:20122409, ECO:0000269PubMed:22157821, ECO:0000269PubMed:2598259, ECO:0000269PubMed:8521468, ECO:0000269PubMed:9094713}.

Subcellular Localization

Nucleus {ECO:0000255PROSITE- ProRule:PRU00820, ECO:0000269PubMed:8284210}.

Disease Associations

Tissue Specificity

Maturing lymphoid cells and central nervous system.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 22 experimentally validated interaction(s) in this database.
They are also associated with 16 interaction(s) predicted by orthology.

Experimentally validated
Total	22 [view]
Protein-Protein	19 [view]
Protein-DNA	3 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	16 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004519	endonuclease activity
GO:0004842	ubiquitin-protein transferase activity
GO:0005515	protein binding
GO:0008270	zinc ion binding
GO:0016788	hydrolase activity, acting on ester bonds
GO:0016881	acid-amino acid ligase activity
GO:0042393	histone binding
GO:0042803	protein homodimerization activity
GO:0043565	sequence-specific DNA binding
GO:0046872	metal ion binding

Biological Process

GO:0002250	adaptive immune response
GO:0002331	pre-B cell allelic exclusion
GO:0006310	DNA recombination
GO:0010390	histone monoubiquitination
GO:0016265	death
GO:0030183	B cell differentiation
GO:0033077	T cell differentiation in thymus
GO:0033151	V(D)J recombination
GO:0043029	T cell homeostasis
GO:0043154	negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0045087	innate immune response (InnateDB)
GO:0045580	regulation of T cell differentiation
GO:0048538	thymus development
GO:0051865	protein autoubiquitination
GO:0070233	negative regulation of T cell apoptotic process
GO:0070244	negative regulation of thymocyte apoptotic process
GO:0090305	nucleic acid phosphodiester bond hydrolysis