RAG-2

同

recombinase activating gene 2

WordNet

1. play in ragtime; "rag that old tune"
2. a week at British universities during which side-shows and processions of floats are organized to raise money for charities (同)rag_week
3. break into lumps before sorting; "rag ore"
4. a small piece of cloth or paper (同)shred, tag, tag end, tatter
5. a boisterous practical joke (especially by college students)
6. the 18th letter of the Roman alphabet (同)r

PrepTutorEJDIC

1. 『布切れ』;(特に)『ぼろ切れ』,ぼろくず / 《複数形で》ぼろ服 / (一般に)(…の)小片,切れ端,かけら《+『of』+『名』》 / 《話》ぼろ新聞
2. 《米》〈人〉‘を'しかる / 《英》〈人〉‘を'からかう,〈人〉‘に'悪ふざけする / 悪ふざけ,ばか騒ぎ / 大学生が資金集めのために練り歩く愉快な行列
3. ラグタイム(ragtime)の曲
4. resistance / 17歳以下父兄同伴映画の表示 / rook
5. Regular Army正規軍

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/01/21 14:05:28」(JST)

wiki en

[Wiki en表示]

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

Recombination activating protein 2
Identifiers
Symbol	RAG
Pfam	PF03089
InterPro	IPR004321
Available protein structures: Pfam structures PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Recombination activating protein 1
Identifiers
Symbol	RAG
Pfam	PF12940
InterPro	IPR004321
Available protein structures: Pfam structures PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

The recombination activating genes (RAGs) 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. 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. 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.

Function

In the vertebrate immune system, each antibody is customized to attack one particular antigen (foreign proteins and carbohydrates) without attacking the body itself. The human genome has at most 30,000 genes, and yet it generates millions of different antibodies, which allows it to be able to respond to invasion from millions of different antigens. The immune system generates this diversity of antibodies by shuffling, cutting and recombining a few hundred genes (the VDJ genes) to create millions of permutations, in a process called VDJ recombination. 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). 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. 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

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. 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. 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. 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.

Evolution

Based on core sequence homology, it is believed that the RAG-1 protein evolved from a transposon of the Transib superfamily. Although the transposon origins of these genes are well established, there is still no consensus on when the ancestral RAG1/2 became present in the vertebrate genome. Because agnathans lack a core RAG1 element, it was traditionally assumed that RAG1 invaded after the agnathan/gnathastome split 1001 to 590 million years ago (MYA). However, recently the core sequence of RAG1 has been identified in the echinoderm Strongylocentrotus purpuratus (purple star fish) and in the amphioxi Brachiostoma floridae (Florida lancelet). These findings indicate RAG1 may have invaded much earlier in evolutionary history than previously thought. Based on current evidence it is not clear whether RAG1 invaded in a very early ancestor of all deuterostomia (approx. 896 MYA) and was later lost in gnathostomes, or if RAG1 may have possibly invaded the genome multiple times It should also be noted that RAG1/2 is only found in gnathostomes, and not in agnathans. It is currently hypothesized that the invasion of RAG1/2 is the most important evolutionary event in terms of shaping the gnathostome adaptive immune system vs. the agnathan variable lymphocyte receptor system.

See also

• Omenn syndrome
• Severe combined immunodeficiency

References

Bibliography

• Janeway CA, Jr. 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, Moshe J. (August 2004). "Recombination-activating gene proteins: more regulation, please". Immunol. Rev. 200: 83–9. doi:10.1111/j.0105-2896.2004.00164.x. PMID 15242398. 
• De, Pallabi; Rodgers, Karla K. (August 2004). "Putting the pieces together: identification and characterization of structural domains in the V(D)J recombination protein RAG1". Immunol. Rev. 200: 70–82. doi:10.1111/j.0105-2896.2004.00154.x. PMID 15242397. 
• Kapitonov, Vladimir V.; Jurka, Jerzy (May 2005). "RAG1 Core and V(D)J Recombination Signal Sequences Were Derived from Transib Transposons". PLoS Biol. 3 (6): e181. doi:10.1371/journal.pbio.0030181. PMC 1131882. PMID 15898832. 

External links

• Travis, John (November 1998). "The Accidental Immune System; Long ago, a wandering piece of DNA—perhaps from a microbe—created a key strategy". Science News 154 (19): 302. doi:10.2307/4010948.  A simple explanation of recombination activating gene for the general reader.

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

• 1. T-B-NK+ SCID：病因および遺伝学 t b nk scid pathogenesis and genetics
• 2. 重度複合型免疫不全（SCID）：特定の欠損 severe combined immunodeficiency scid specific defects
• 3. 複合免疫不全 combined immunodeficiencies
• 4. T-B-NK+ SCID：臨床症状、診断、および治療 t b nk scid clinical manifestations diagnosis and treatment
• 5. 免疫不全症を引き起こすCD3／T細胞受容体複合体疾患 cd3 t cell receptor complex disorders causing immunodeficiency

English Journal

• CCR9(+) plasmacytoid dendritic cells in the small intestine suppress development of intestinal inflammation in mice.

• Mizuno S, Kanai T, Mikami Y, Sujino T, Ono Y, Hayashi A, Handa T, Matsumoto A, Nakamoto N, Matsuoka K, Hisamatsu T, Takaishi H, Hibi T.SourceDepartment of Gastroenterology and Hepatology, Keio University School of Medicine, Tokyo 160-8582, Japan.
• Immunology letters.Immunol Lett.2012 Aug 30;146(1-2):64-9. Epub 2012 May 22.
• Almost all mice lacking specific molecules associated with regulatory T cells or barrier function develop intestinal inflammation in the colon, but not in the small intestine (SI). Therefore, intestinal homeostasis of the SI may be tightly controlled by other mechanisms. To determine the role of CCR
• PMID 22626536

• β7 integrin controls immunogenic and tolerogenic mucosal B cell responses.

• Schippers A, Kochut A, Pabst O, Frischmann U, Clahsen T, Tenbrock K, Müller W, Wagner N.SourceDepartment of Pediatrics, Medical Faculty, RWTH Aachen University, Aachen D-52074, Germany.
• Clinical immunology (Orlando, Fla.).Clin Immunol.2012 Aug;144(2):87-97. Epub 2012 May 24.
• IgA production in the gut-associated lymphoid tissue represents a pivotal defense mechanism against luminal pathogens. The other important challenge for the GALT is the induction of local and systemic hyporesponsiveness (tolerance) to dietary antigens and luminal bacterial flora to prevent allergies
• PMID 22710445

Japanese Journal

• A novel EGFP-expressing nude mice with complete loss of lymphocytes and NK cells to study tumor-host interactions

• Gotoh Kumiko,Kariya Ryusho,Matsuda Kouki,Hattori Shinichiro,Vaeteewoottacharn Kulthida,Okada Seiji
• BioScience Trends 8(4), 202-205, 2014
• … Enhanced green fluorescent protein (EGFP) expressing Balb/c nude mice strain with Rag-2 and Jak3 double mutants (Nude-R/J-EGFP mice) was established to improve the take rate of human tumors and to distinguish tumor and host cells. …
• NAID 130004690258

• Selective Suppression of Th2 Cell-Mediated Lung Eosinophilic Inflammation by Anti-Major Facilitator Super Family Domain Containing 10 Monoclonal Antibody

• Nishimura Tomoe,Saeki Mayumi,Motoi Yuji,Kitamura Noriko,Mori Akio,Kaminuma Osamu,Hiroi Takachika
• Allergology International 63(Supplement.1), S29-S35, 2014
• … A monoclonal antibody (mAb) against Mfsd10 (M2) showed selective binding and neutralizing activities for eosinophils. … Therefore, in this study, the effects of M2 and an anti-Siglec-F mAb on antigen-immunized and antigen-specific Th2 cell-transferred murine eosinophilic inflammation models were comparatively investigated. …
• NAID 130004477230

• Programmed cell death 1 inhibits inflammatory helper T-cell development through controlling the innate immune response

• Rui Yuxiang,Honjo Tasuku,Chikuma Shunsuke
• Proceedings of the National Academy of Sciences of the United States of America, 2013-09-16
• … Splenocytes from HKMTB-immunized, lymphocyte-deficient PD-1(-/-) recombination activating gene (RAG)2(-/-) mice were found to drive antigen-specific Th17 cell differentiation more efficiently than splenocytes from HKMTB-immunized PD-1(+/+) RAG2(-/-) mice. …
• NAID 120005324915

Related Links

• RAG1/RAG2欠損症 | e-免疫.com -原発性免疫不全症候群に関 ...

参考文献 1) Omenn GS Familial reticuloendotheliosis with eosinophilia. N Engl J Med 1965; 273 : 427-432. 2) Villa A, Santagata S, Bozzi F, et al. Partial V(D)J recombination activity leads to Omenn syndrome. Cell 1998; 93 : 885 ...

• RAG 新座2号店(ラグ ニイザニゴウテン)｜埼玉県・新座市の ...

RAG 新座2号店のクーポン・口コミ・ヘアスタイル情報｜トップ｜バリをイメージした木を基調としたアジアンテイストな店内。 心身ともにリラックスできるような「癒し」がテーマです。 アットホームで、丁寧なカウンセリングを ...

Related Pictures

---

★リンクテーブル★

リンク元	「オーメン症候群」
関連記事	「RA」「R」「RAG」「rag」

「オーメン症候群」

　　[★]

英

Omenn syndrome

同

Omenn症候群

• T細胞やB細胞でおこる遺伝子再構成において、最初の段階で働く酵素RAG-1/RAG-2の機能欠損による
• 先天性疾患
• 重症複合免疫不全の一つの型

病因

• 母親由来のリンパ球による移植片対宿主病（GVHD）
• 組織球の腫瘍性浸潤によるリンパ組織の破壊

etc

治療

• 同種骨髄移植

参考

• 1. OMENN SYNDROME - OMIM

http://omim.org/entry/603554

「RA」

　　[★]

• 右房 right atrium
• 関節リウマチ rheumatoid arthritis。慢性関節リウマチ
• レチノイン酸 retinoic acid
• 不応性貧血 refractory anemia

　

「R」

　　[★]

• レントゲン roentgen
• アルギニン
• respiratory rate
• respiratory quotient
• プリン
• アルキル基 alkyl group
• 化合物の側鎖

　 　

「RAG」

　　[★] recombination-activating gene

「rag」

　　[★]