recombination activating gene 1 | |
| Identifiers | |
| Symbol | RAG1 |
| Entrez | 5896 |
| HUGO | 9831 |
| OMIM | 179615 |
| RefSeq | NM_000448 |
| UniProt | P15918 |
| Other data | |
| Locus | Chr. 11 p13 |
recombination activating gene 2 | |
| Identifiers | |
| Symbol | RAG2 |
| Entrez | 5897 |
| HUGO | 9832 |
| OMIM | 179616 |
| RefSeq | NM_000536 |
| UniProt | P55895 |
| Other data | |
| Locus | Chr. 11 p13 |
The recombination activating genes encode enzymes that play an important role in the rearrangement and recombination of the genes of immunoglobulin and T cell receptor molecules during the process of VDJ recombination. The Entrez Global Query Cross-Database Search System is a powerful Federated search engine or Web portal that allows users to search many discrete Health sciences The Human Genome Organisation (HUGO is an organization involved in the Human Genome Project, a project about mapping the human genome The Mendelian Inheritance in Man project is a Database that catalogues all the known Diseases with a genetic component, and—when possible—links them The National Center for Biotechnology Information ( NCBI) is part of the United States National Library of Medicine (NLM a branch of the National Institutes Swiss-Prot is a manually curated Biological database of Protein sequences In the fields of Genetics and Evolutionary computation, a locus (plural loci) is a fixed position on a Chromosome such as the position of a Chromosome 11 is one of the 23 pairs of Chromosomes in Humans People normally have two copies of this chromosome The Entrez Global Query Cross-Database Search System is a powerful Federated search engine or Web portal that allows users to search many discrete Health sciences The Human Genome Organisation (HUGO is an organization involved in the Human Genome Project, a project about mapping the human genome The Mendelian Inheritance in Man project is a Database that catalogues all the known Diseases with a genetic component, and—when possible—links them The National Center for Biotechnology Information ( NCBI) is part of the United States National Library of Medicine (NLM a branch of the National Institutes Swiss-Prot is a manually curated Biological database of Protein sequences In the fields of Genetics and Evolutionary computation, a locus (plural loci) is a fixed position on a Chromosome such as the position of a Chromosome 11 is one of the 23 pairs of Chromosomes in Humans People normally have two copies of this chromosome Enzymes are Biomolecules that catalyze ( ie increase the rates of Chemical reactions Almost all enzymes are Proteins Antibodies (also known as immunoglobulins, abbreviated Ig) are Gamma globulin Proteins that are found in Blood or other Bodily The T cell receptor or TCR is a molecule found on the surface of T lymphocytes (or T cells that is in general responsible for recognizing Antigens bound V(DJ recombination is a mechanism of Genetic recombination that occurs in Vertebrates which randomly selects and assembles segments of Genes encoding There are two recombination activating gene products known as RAG-1 and RAG-2, whose cellular expression is restricted to lymphocytes during their developmental stages. A lymphocyte is a type of White blood cell in the Vertebrate Immune system. RAG-1 and RAG-2 are essential to the generation of mature B and T lymphocytes, two cell types that are crucial components of the adaptive immune system. Immune system|Passive immunity|Innate immune system The adaptive immune system is composed of highly specialized systemic cells and processes that eliminate or prevent Pathogenic
Contents |
Function of RAG proteins
In the vertebrate immune system, each antibody is customized to attack one particular antigen (foreign proteins and carbohydrates) without attacking the body itself or harmless antigens, such as those from harmless (commensal) bacteria. An antigen (from antibody-generating) or immunogen is a substance that prompts the generation of Antibodies and can cause an immune response In Ecology, commensalism is a kind of symbiotic relationship between two organisms where one benefits and the other is not significantly harmed or helped (like a bird The human genome has at most 30,000 genes, and yet it generates millions of different antibodies, which can respond to invasion from millions of different antigens. The immune system generates this diversity of antibodies by shuffling a few hundred genes (the VDJ genes) to create millions of permutations, in a process called VDJ recombination. V(DJ recombination is a mechanism of Genetic recombination that occurs in Vertebrates which randomly selects and assembles segments of Genes encoding RAG-1 and RAG-2 are proteins at the ends of VDJ genes that separate, shuffle, and rejoin the VDJ genes. This shuffling takes place inside B cells and T cells during their maturation.
RAG enzymes work as a multi-subunit complex to induce cleavage of a single double stranded DNA (dsDNA) molecule between the antigen receptor coding segment and a flanking recombination signal sequence (RSS). Deoxyribonucleic acid ( DNA) is a Nucleic acid that contains the genetic instructions used in the development and functioning of all known They do this in two steps. They initially introduce a ‘nick’ in the 5' (upstream) end of the RSS heptamer (a conserved region of 7 nucleotides) that is adjacent to the coding sequence, leaving behind a specific biochemical structure on this region of DNA; a 3'-hydroxyl (OH) group at the coding end and a 5'-phosphate (PO4) group at the RSS end. Hydroxyl in Chemistry stands for a molecule consisting of an Oxygen atom and a Hydrogen atom connected by a Covalent bond. A phosphate, an Inorganic chemical, is a salt of Phosphoric acid. The next step couples these chemical groups, binding the OH-group (on the coding end) to the PO4-group (that is sitting between the RSS and the gene segment on the opposite strand). This produces a 5'-phosphorylated double-stranded break at the RSS and a covalently closed hairpin at the coding end. The RAG proteins remain at these junctions until other enzymes repair the DNA breaks.
The RAG proteins initiate V(D)J recombination, which is essential for the maturation of pre-B and pre-T cells. Activated mature B cells also possess two other remarkable, RAG independent, phenomena of manipulating their own DNA; so-called class-switch recombination (AKA isotype switching) and somatic hypermutation (AKA affinity maturation).
Structure of RAG proteins
As with many enzymes, RAG proteins are fairly large. For example, mouse RAG-1 contains 1040 amino acids and mouse RAG-2 contains 527 amino acids. In Chemistry, an amino acid is a Molecule containing both Amine and Carboxyl Functional groups In Biochemistry, this The enzymatic activity of the RAG proteins is largely concentrated in a core region; residues 384–1008 of RAG-1 and residues 1–387 of RAG-2 retain most of the DNA cleavage activity. The RAG-1 core contains three acidic residues (D600, D708, and E962) in what is called the DDE motif, the major active site for DNA cleavage. In Computer science, ACID ( Atomicity Consistency Isolation Durability) is a set of properties that guarantee that Database transactions are These residues are critical for nicking the DNA strand and for forming the DNA hairpin. Residues 384–454 of RAG-1 comprise a nonamer-binding region (NBR) that specifically binds the conserved nonomer (9 nucleotides) of the RSS and the central domain (amino acids 528–760) of RAG-1 binds specifically to the RSS heptamer. Nucleotides are Organic compounds that consist of three joined structures a nitrogenous base a Sugar, and a Phosphate group The core region of RAG-2 is predicted to form a six-bladed beta-propeller structure that appears less specific than RAG-1 for its target.
See also
References
- Janeway CA, Jr. Omenn syndrome is an Autosomal recessive Severe combined immunodeficiency associated with Mutations in the Recombination activating genes (RAG1 et al (2005). Immunobiology. , 6th ed. , Garland Science. ISBN 0-443-07310-4.
- Abbas AK and Lichtman AH (2003). Cellular and Molecular Immunology, 5th ed. , Saunders, Philadelphia. ISBN 0-7216-0008-5.
- Sadofsky M. "Recombination-activating gene proteins: more regulation, please". Immunol Rev 200: 83–9. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 15242398.
- De P, Rodgers K. "Putting the pieces together: identification and characterization of structural domains in the V(D)J recombination protein RAG1". Immunol Rev 200: 70–82. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 15242397.
External links
The Accidental Immune System; Long ago, a wandering piece of DNA—perhaps from a microbe—created a key strategy, By JOHN TRAVIS. Science News, Nov. 7, 1998. [1] Simple explanation of recombination activating gene for the general reader. [Free full text]
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