ID:RAG1_HUMAN DESCRIPTION: RecName: Full=V(D)J recombination-activating protein 1; Short=RAG-1; AltName: Full=RING finger protein 74; Includes: RecName: Full=Endonuclease RAG1; EC=3.1.-.-; Includes: RecName: Full=E3 ubiquitin-protein ligase RAG1; EC=6.3.2.-; 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). COFACTOR: Binds 1 divalent metal cation per subunit. Magnesium or manganese (By similarity). SUBUNIT: Homodimer. Component of the RAG complex composed of core components RAG1 and RAG2, and associated component HMGB1 or HMGB2 (By similarity). INTERACTION: P16333:NCK1; NbExp=2; IntAct=EBI-1755109, EBI-389883; SUBCELLULAR LOCATION: Nucleus (By similarity). TISSUE SPECIFICITY: Maturing lymphoid cells. DOMAIN: The RING-type zinc finger mediates the E3 ubiquitin- protein ligase activity (By similarity). DOMAIN: The NBD (nonamer binding) DNA-binding domain mediates the specific binding to the nonamer RSS motif by forming a tightly interwoven homodimer that binds and synapses 2 nonamer elements, with each NBD making contact with both DNA molecules. Each RSS is composed of well-conserved heptamer (consensus 5'-CACAGTG-3') and nonamer (consensus 5'-ACAAAAACC-3') sequences separated by a spacer of either 12 bp or 23 bp (By similarity). PTM: Autoubiquitinated in the presence of CDC34/UBCH3 (By similarity). DISEASE: Defects in RAG1 are a cause of combined cellular and humoral immune defects with granulomas (CHIDG) [MIM:233650]. CHIDG is an 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. DISEASE: Defects in RAG1 are a cause of 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. DISEASE: Defects in RAG1 are a cause of Omenn syndrome (OS) [MIM:603554]. OS is a severe immunodeficiency characterized by the presence of activated, anergic, oligoclonal T-cells, hypereosinophilia, and high IgE levels. DISEASE: Defects in RAG1 are the cause of 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. SIMILARITY: Belongs to the RAG1 family. SIMILARITY: Contains 1 NBD (nonamer binding) DNA-binding domain. SIMILARITY: Contains 1 RAG1-type zinc finger. SIMILARITY: Contains 1 RING-type zinc finger. SEQUENCE CAUTION: Sequence=AAM77798.1; Type=Erroneous gene model prediction; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/RAG1"; WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/rag1/"; WEB RESOURCE: Name=RAG1base; Note=RAG1 deficiency database; URL="http://bioinf.uta.fi/RAG1base/"; WEB RESOURCE: Name=Mendelian genes recombination activating gene 1 (RAG1); Note=Leiden Open Variation Database (LOVD); URL="http://www.lovd.nl/RAG1";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P15918
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0002250 adaptive immune response GO:0002331 pre-B cell allelic exclusion GO:0006310 DNA recombination GO:0006325 chromatin organization GO:0006955 immune response GO:0008152 metabolic process GO:0008542 visual learning GO:0010390 histone monoubiquitination 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:0045580 regulation of T cell differentiation GO:0045582 positive 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 GO:2000822 regulation of behavioral fear response
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
