Homo sapiens Protein: RAG1 | |||||||||||||||||||||||||||||||||||||
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Summary | |||||||||||||||||||||||||||||||||||||
InnateDB Protein | IDBP-40151.5 | ||||||||||||||||||||||||||||||||||||
Last Modified | 2014-10-13 [Report errors or provide feedback] | ||||||||||||||||||||||||||||||||||||
Gene Symbol | RAG1 | ||||||||||||||||||||||||||||||||||||
Protein Name | recombination activating gene 1 | ||||||||||||||||||||||||||||||||||||
Synonyms | RAG-1; RNF74; | ||||||||||||||||||||||||||||||||||||
Species | Homo sapiens | ||||||||||||||||||||||||||||||||||||
Ensembl Protein | ENSP00000299440 | ||||||||||||||||||||||||||||||||||||
InnateDB Gene | IDBG-40149 (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 (By similarity). {ECO:0000250}. | ||||||||||||||||||||||||||||||||||||
Subcellular Localization | Nucleus {ECO:0000255PROSITE- ProRule:PRU00820}. | ||||||||||||||||||||||||||||||||||||
Disease Associations | Combined cellular and humoral immune defects with granulomas (CHIDG) [MIM:233650]: Immunodeficiency disease with granulomas in the skin, mucous membranes, and internal organs. Other characteristics include hypogammaglobulinemia, a diminished number of T and B-cells, and sparse thymic tissue on ultrasonography. {ECO:0000269PubMed:18463379}. Note=The disease is caused by mutations affecting the gene represented in this entry.Severe combined immunodeficiency autosomal recessive T- cell-negative/B-cell-negative/NK-cell-positive (T(-)B(-)NK(+) SCID) [MIM:601457]: A form of severe combined immunodeficiency (SCID), a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. Patients present in infancy recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T-cell development. {ECO:0000269PubMed:19912631, ECO:0000269PubMed:8810255}. Note=The disease is caused by mutations affecting the gene represented in this entry.Omenn syndrome (OS) [MIM:603554]: Severe immunodeficiency characterized by the presence of activated, anergic, oligoclonal T-cells, hypereosinophilia, and high IgE levels. {ECO:0000269PubMed:10606976, ECO:0000269PubMed:11133745, ECO:0000269PubMed:19912631, ECO:0000269PubMed:21624848, ECO:0000269PubMed:21771083, ECO:0000269PubMed:9630231}. Note=The disease is caused by mutations affecting the gene represented in this entry.Alpha/beta T-cell lymphopenia, with gamma/delta T-cell expansion, severe cytomegalovirus infection and autoimmunity (T- CMVA) [MIM:609889]: An immunological disorder characterized by oligoclonal expansion of TCR gamma/delta T-cells, TCR alpha/beta T-cell lymphopenia, severe, disseminated cytomegalovirus infection and autoimmune cytopenia. {ECO:0000269PubMed:16276422}. Note=The disease is caused by mutations affecting the gene represented in this entry. | ||||||||||||||||||||||||||||||||||||
Tissue Specificity | Maturing lymphoid cells. | ||||||||||||||||||||||||||||||||||||
Comments | |||||||||||||||||||||||||||||||||||||
Interactions | |||||||||||||||||||||||||||||||||||||
Number of Interactions |
This gene and/or its encoded proteins are associated with 29 experimentally validated interaction(s) in this database.
They are also associated with 6 interaction(s) predicted by orthology.
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Gene Ontology | |||||||||||||||||||||||||||||||||||||
Molecular Function |
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Biological Process |
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Cellular Component |
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Protein Structure and Domains | |||||||||||||||||||||||||||||||||||||
PDB ID | |||||||||||||||||||||||||||||||||||||
InterPro |
IPR001841
Zinc finger, RING-type IPR019485 Zinc finger, V(D)J recombination-activating protein 1 |
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PFAM |
PF13639
PF14634 PF10426 |
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PRINTS | |||||||||||||||||||||||||||||||||||||
PIRSF | |||||||||||||||||||||||||||||||||||||
SMART |
SM00184
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TIGRFAMs | |||||||||||||||||||||||||||||||||||||
Post-translational Modifications | |||||||||||||||||||||||||||||||||||||
Modification | |||||||||||||||||||||||||||||||||||||
Cross-References | |||||||||||||||||||||||||||||||||||||
SwissProt | P15918 | ||||||||||||||||||||||||||||||||||||
PhosphoSite | PhosphoSite-P15918 | ||||||||||||||||||||||||||||||||||||
TrEMBL | |||||||||||||||||||||||||||||||||||||
UniProt Splice Variant | |||||||||||||||||||||||||||||||||||||
Entrez Gene | 5896 | ||||||||||||||||||||||||||||||||||||
UniGene | Hs.73958 | ||||||||||||||||||||||||||||||||||||
RefSeq | NP_000439 | ||||||||||||||||||||||||||||||||||||
HUGO | HGNC:9831 | ||||||||||||||||||||||||||||||||||||
OMIM | 179615 | ||||||||||||||||||||||||||||||||||||
CCDS | CCDS7902 | ||||||||||||||||||||||||||||||||||||
HPRD | 01556 | ||||||||||||||||||||||||||||||||||||
IMGT | |||||||||||||||||||||||||||||||||||||
EMBL | AC139427 AY130302 M29474 | ||||||||||||||||||||||||||||||||||||
GenPept | AAA60248 AAM77798 | ||||||||||||||||||||||||||||||||||||