ターミナルデオキシヌクレオチジルトランスフェラーゼ terminal deoxynucleotidyl transferase
WordNet
- the 20th letter of the Roman alphabet (同)t
PrepTutorEJDIC
- tritiumの化学記号
Wikipedia preview
出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/09/18 02:51:47」(JST)
[Wiki en表示]
| DNA nucleotidylexotransferase |
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Amino acids 19-125 of human DNA nucleotidylexotransferase. PDB rendering based on 2coe.
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| Available structures |
| PDB |
Ortholog search: PDBe, RCSB |
| List of PDB id codes |
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2COE
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| Identifiers |
| Symbols |
DNTT ; TDT |
| External IDs |
OMIM: 187410 MGI: 98659 HomoloGene: 3014 ChEMBL: 4810 GeneCards: DNTT Gene |
| EC number |
2.7.7.31 |
| Gene ontology |
| Molecular function |
• DNA binding
• DNA-directed DNA polymerase activity
• DNA nucleotidylexotransferase activity
• protein binding
• metal ion binding
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| Cellular component |
• nucleus
• nucleoplasm
• cytoplasm
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| Biological process |
• DNA metabolic process
• DNA modification
• DNA biosynthetic process
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| Sources: Amigo / QuickGO |
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| Orthologs |
| Species |
Human |
Mouse |
| Entrez |
1791 |
21673 |
| Ensembl |
ENSG00000107447 |
ENSMUSG00000025014 |
| UniProt |
P04053 |
P09838 |
| RefSeq (mRNA) |
NM_001017520 |
NM_001043228 |
| RefSeq (protein) |
NP_001017520 |
NP_001036693 |
| Location (UCSC) |
Chr 10:
96.3 – 96.34 Mb |
Chr 19:
41.03 – 41.06 Mb |
| PubMed search |
[1] |
[2] |
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Terminal deoxynucleotidyl transferase (TdT), also known as DNA nucleotidylexotransferase (DNTT) or terminal transferase, is a specialized DNA polymerase expressed in immature, pre-B, pre-T lymphoid cells, and acute lymphoblastic leukemia/lymphoma cells. TdT adds N-nucleotides to the V,D, and J exons during antibody gene recombination, enabling the phenomenon of junctional diversity. In humans, terminal transferase is encoded by the DNTT gene.[1][2]
TdT is absent in fetal liver HSCs, significantly impairing junctional diversity in B-cells during the fetal period.[3]
Contents
- 1 Function
- 2 Uses
- 3 See also
- 4 References
- 5 Further reading
- 6 External links
Function
TdT catalyses the addition of nucleotides to the 3' terminus of a DNA molecule. Unlike most DNA polymerases, it does not require a template. The preferred substrate of this enzyme is a 3'-overhang, but it can also add nucleotides to blunt or recessed 3' ends. Cobalt is a necessary cofactor, however the enzyme catalyzes reaction upon Mg and Mn administration in vitro.
Uses
Terminal transferase has applications in molecular biology. It can be used in RACE to add nucleotides that can then be used as a template for a primer in subsequent PCR. It can also be used to add nucleotides labeled with radioactive isotopes, for example in the TUNEL assay (Terminal deoxynucleotidyl transferase dUTP Nick End Labeling) for the demonstration of apoptosis (which is marked, in part, by fragmented DNA). Also used in the immunofluorescence assay for the diagnosis of acute lymphoblastic leukemia.[4]
In immunohistochemistry, antibodies to TdT can be used to demonstrate the presence of immature T and B cells and multipotent haematopoietic stem cells, which possess the antigen, while mature lymphoid cells are always TdT-negative. While TdT-positive cells are found in small numbers in healthy lymph nodes and tonsils, the malignant cells of acute lymphoblastic leukaemia are also TdT-positive, and the antibody can, therefore, be used as part of a panel to diagnose this disease and to distinguish it from, for example, small cell tumours of childhood.[5]
See also
References
- ^ Isobe M, Huebner K, Erikson J, Peterson RC, Bollum FJ, Chang LM, Croce CM (September 1985). "Chromosome localization of the gene for human terminal deoxynucleotidyltransferase to region 10q23-q25". Proc. Natl. Acad. Sci. U.S.A. 82 (17): 5836–40. doi:10.1073/pnas.82.17.5836. PMC 390648. PMID 3862101.
- ^ Yang-Feng TL, Landau NR, Baltimore D, Francke U (1986). "The terminal deoxynucleotidyltransferase gene is located on human chromosome 10 (10q23-q24) and on mouse chromosome 19". Cytogenet. Cell Genet. 43 (3-4): 121–6. doi:10.1159/000132309. PMID 3467897.
- ^ Hardy, Richard (2008). "Chapter 7: B Lymphocyte Development and Biology". In Paul, William. Fundamental Immunology (Book) (6th ed.). Philadelphia: Lippincott Williams & Wilkins. pp. 237–269. ISBN 0-7817-6519-6.
- ^ Faber J, Kantarjian H, Roberts MW, Keating M, Freireich E, Albitar M (January 2000). "Terminal deoxynucleotidyl transferase-negative acute lymphoblastic leukemia". Arch. Pathol. Lab. Med. 124 (1): 92–7. PMID 10629138.
- ^ Leong, Anthony S-Y; Cooper, Kumarason; Leong, F Joel W-M (2003). Manual of Diagnostic Cytology (2 ed.). Greenwich Medical Media, Ltd. pp. 413–414. ISBN 1-84110-100-1.
Further reading
- O'Malley DP, Orazi A (2006). "Terminal deoxynucleotidyl transferase-positive cells in spleen, appendix and branchial cleft cysts in pediatric patients.". Haematologica 91 (8): 1139–40. PMID 16885057.
- Yamashita N, Shimazaki N, Ibe S et al. (2001). "Terminal deoxynucleotidyltransferase directly interacts with a novel nuclear protein that is homologous to p65.". Genes Cells 6 (7): 641–52. doi:10.1046/j.1365-2443.2001.00449.x. PMID 11473582.
- Chang LM, Bollum FJ (1986). "Molecular biology of terminal transferase.". CRC Crit. Rev. Biochem. 21 (1): 27–52. doi:10.3109/10409238609113608. PMID 3524991.
- Maezawa S, Hayano T, Koiwai K et al. (2008). "Bood POZ containing gene type 2 is a human counterpart of yeast Btb3p and promotes the degradation of terminal deoxynucleotidyltransferase.". Genes Cells 13 (5): 439–57. doi:10.1111/j.1365-2443.2008.01179.x. PMID 18429817.
- Taplin ME, Frantz ME, Canning C et al. (1996). "Evidence against T-cell development in the adult human intestinal mucosa based upon lack of terminal deoxynucleotidyltransferase expression.". Immunology 87 (3): 402–7. doi:10.1046/j.1365-2567.1996.496571.x. PMC 1384108. PMID 8778025.
- Grupe A, Li Y, Rowland C et al. (2006). "A scan of chromosome 10 identifies a novel locus showing strong association with late-onset Alzheimer disease.". Am. J. Hum. Genet. 78 (1): 78–88. doi:10.1086/498851. PMC 1380225. PMID 16385451.
- Dworzak MN, Fritsch G, Fröschl G et al. (1998). "Four-color flow cytometric investigation of terminal deoxynucleotidyl transferase-positive lymphoid precursors in pediatric bone marrow: CD79a expression precedes CD19 in early B-cell ontogeny.". Blood 92 (9): 3203–9. PMID 9787156.
- Fujita K, Shimazaki N, Ohta Y et al. (2003). "Terminal deoxynucleotidyltransferase forms a ternary complex with a novel chromatin remodeling protein with 82 kDa and core histone.". Genes Cells 8 (6): 559–71. doi:10.1046/j.1365-2443.2003.00656.x. PMID 12786946.
- Kubota T, Maezawa S, Koiwai K et al. (2007). "Identification of functional domains in TdIF1 and its inhibitory mechanism for TdT activity.". Genes Cells 12 (8): 941–59. doi:10.1111/j.1365-2443.2007.01105.x. PMID 17663723.
- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library.". Gene 200 (1-2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
- Bridges SL (1998). "Frequent N addition and clonal relatedness among immunoglobulin lambda light chains expressed in rheumatoid arthritis synovia and PBL, and the influence of V lambda gene segment utilization on CDR3 length.". Mol. Med. 4 (8): 525–53. PMC 2230400. PMID 9742508.
- Liu L, McGavran L, Lovell MA et al. (2004). "Nonpositive terminal deoxynucleotidyl transferase in pediatric precursor B-lymphoblastic leukemia.". Am. J. Clin. Pathol. 121 (6): 810–5. doi:10.1309/QD18-PPV1-NH3T-EUTF. PMID 15198352.
- Yang B, Gathy KN, Coleman MS (1994). "Mutational analysis of residues in the nucleotide binding domain of human terminal deoxynucleotidyl transferase.". J. Biol. Chem. 269 (16): 11859–68. PMID 8163485.
- Gerhard DS, Wagner L, Feingold EA et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
- Thai TH, Kearney JF (2004). "Distinct and opposite activities of human terminal deoxynucleotidyltransferase splice variants.". J. Immunol. 173 (6): 4009–19. doi:10.4049/jimmunol.173.6.4009. PMID 15356150.
- Shimazaki N, Fujita K, Koiwai O (2002). "[Expression and function of terminal deoxynucleotidyl-transferase and discovery of novel DNA polymerase mu]". Seikagaku 74 (3): 227–32. PMID 11974916.
- Mahajan KN, Mitchell BS (2003). "Role of human Pso4 in mammalian DNA repair and association with terminal deoxynucleotidyl transferase.". Proc. Natl. Acad. Sci. U.S.A. 100 (19): 10746–51. doi:10.1073/pnas.1631060100. PMC 196874. PMID 12960389.
- Strausberg RL, Feingold EA, Grouse LH et al. (2002). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Mahajan KN, Gangi-Peterson L, Sorscher DH et al. (1999). "Association of terminal deoxynucleotidyl transferase with Ku.". Proc. Natl. Acad. Sci. U.S.A. 96 (24): 13926–31. doi:10.1073/pnas.96.24.13926. PMC 24167. PMID 10570175.
- Ibe S, Fujita K, Toyomoto T et al. (2001). "Terminal deoxynucleotidyltransferase is negatively regulated by direct interaction with proliferating cell nuclear antigen.". Genes Cells 6 (9): 815–24. doi:10.1046/j.1365-2443.2001.00460.x. PMID 11554927.
External links
- Terminal Deoxyribonucleotidyltransferase at the US National Library of Medicine Medical Subject Headings (MeSH)
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Transferases: phosphorus-containing groups (EC 2.7)
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2.7.1-2.7.4:
phosphotransferase/kinase
(PO4) |
| 2.7.1: OH acceptor |
- Hexo-
- Gluco-
- Fructo-
- Galacto-
- Phosphofructo-
- 1
- Liver
- Muscle
- Platelet
- 2
- Riboflavin
- Shikimate
- Thymidine
- NAD+
- Glycerol
- Pantothenate
- Mevalonate
- Pyruvate
- Deoxycytidine
- PFP
- Diacylglycerol
- Phosphoinositide 3
- Class I PI 3
- Class II PI 3
- Sphingosine
- Glucose-1,6-bisphosphate synthase
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| 2.7.2: COOH acceptor |
- Phosphoglycerate
- Aspartate kinase
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| 2.7.3: N acceptor |
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| 2.7.4: PO4 acceptor |
- Phosphomevalonate
- Adenylate
- Nucleoside-diphosphate
- Uridylate
- Guanylate
- Thiamine-diphosphate
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2.7.6: diphosphotransferase
(P2O7) |
- Ribose-phosphate diphosphokinase
- Thiamine diphosphokinase
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2.7.7: nucleotidyltransferase
(PO4-nucleoside) |
| Polymerase |
| DNA polymerase |
- DNA-directed DNA polymerase
- I
- II
- III
- IV
- V
- RNA-directed DNA polymerase
- Reverse transcriptase
- Telomerase
- DNA nucleotidylexotransferase/Terminal deoxynucleotidyl transferase
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| RNA nucleotidyltransferase |
- RNA polymerase/DNA-directed RNA polymerase
- RNA polymerase I
- RNA polymerase II
- RNA polymerase III
- RNA polymerase IV
- Primase
- RNA-dependent RNA polymerase
- PNPase
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Phosphorolytic
3' to 5' exoribonuclease |
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| Nucleotidyltransferase |
- UTP—glucose-1-phosphate uridylyltransferase
- Galactose—1-phosphate uridylyltransferase
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| Guanylyltransferase |
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| Other |
- Recombinase (Integrase)
- Transposase
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| 2.7.8: miscellaneous |
| Phosphatidyltransferases |
- CDP-diacylglycerol—glycerol-3-phosphate 3-phosphatidyltransferase
- CDP-diacylglycerol—serine O-phosphatidyltransferase
- CDP-diacylglycerol—inositol 3-phosphatidyltransferase
- CDP-diacylglycerol—choline O-phosphatidyltransferase
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| Glycosyl-1-phosphotransferase |
- N-acetylglucosamine-1-phosphate transferase
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2.7.10-2.7.13: protein kinase
(PO4; protein acceptor) |
| 2.7.10: protein-tyrosine |
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| 2.7.11: protein-serine/threonine |
- see serine/threonine-specific protein kinases
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| 2.7.12: protein-dual-specificity |
- see serine/threonine-specific protein kinases
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| 2.7.13: protein-histidine |
- Protein-histidine pros-kinase
- Protein-histidine tele-kinase
- Histidine kinase
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- Biochemistry overview
- Enzymes overview
- By EC number: 1.1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
- 10
- 11
- 13
- 14
- 15-18
- 2.1
- 3.1
- 4.1
- 5.1
- 6.1-3
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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.
English Journal
- Association study of CARD8 (p.C10X) and NLRP3 (p.Q705K) variants with rheumatoid arthritis in French and Tunisian populations.
- Ben Hamad M, Cornelis F, Marzouk S, Chabchoub G, Bahloul Z, Rebai A, Fakhfakh F, Ayadi H, Petit-Teixeira E, Maalej A.SourceLaboratory of Human Molecular Genetics, Faculty of Medicine, Sfax, Tunisia GenHotel-EA3886, Evry-Val-d'Essonne University, Evry-Genopole, GenHotel-Auvergne, CHU Clermont-Ferrand, France Department of Internal Medicine, University Hospital Hedi Chaker, Sfax, Tunisia Department of Bioinformatics, Center of Biotechnology, Sfax, Tunisia.
- International journal of immunogenetics.Int J Immunogenet.2012 Apr;39(2):131-6. doi: 10.1111/j.1744-313X.2011.01070.x. Epub 2011 Dec 1.
- The objective of the study was to investigate the association of caspase activating and recruitment domain 8 (CARD8) and nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain containing 3 (NLRP3) polymorphisms with rheumatoid arthritis (RA) in Tunisian and French population
- PMID 22128899
- Carotid body growth during chronic postnatal hyperoxia.
- Dmitrieff EF, Piro SE, Broge TA Jr, Dunmire KB, Bavis RW.SourceDepartment of Biology, Bates College, Lewiston, ME 04240, USA.
- Respiratory physiology & neurobiology.Respir Physiol Neurobiol.2012 Mar 15;180(2-3):193-203. Epub 2011 Nov 22.
- Rats reared in hyperoxia have smaller carotid bodies as adults. To study the time course and mechanisms underlying these changes, rats were reared in 60% O(2) from birth and their carotid bodies were harvested at various postnatal ages (P0-P7, P14). The carotid bodies of hyperoxia-reared rats were s
- PMID 22138179
Japanese Journal
- 白内障手術時に得られた前嚢における水晶体上皮細胞のアポトーシス
- 山本 香織/篠崎 和美/堀 貞夫
- 東京女子医科大学雑誌 82(E1), E101-E108, 2012-01-31
- … アポトーシス細胞の検出には、TdT-mediated dUTP-biotin nick end labeling:TUNEL反応を施した。 …
- NAID 110008767960
- Visualization of Heavy Ion Tracks by Labeling 3'-OH Termini of Induced DNA Strand Breaks
- KONISHI Teruaki,TAKEYASU Akihiro,NATSUME Toshiyuki,FURUSAWA Yoshiya,HIEDA Kotaro
- Journal of radiation research 52(4), 433-440, 2011-07-16
- … The 3-OH termini of DNA were labeled with BrdU-triphosphate catalyzed by TdT. … This method of TUNEL (TdT-mediated dUTP Nick End labeling) is based on the specific binding of TdT to 3-OH termini of DNA. …
- NAID 10029122061
Related Links
- TDT is the leading developer and innovator of modular signal-processing workstations for science and engineering. TDT provides powerful cost-effective solutions for neurophysiological and psychophysical research.
Related Pictures
★リンクテーブル★
[★]
- 57歳の男性。発熱と倦怠感を主訴に来院した。1か月前に右頸部腫瘤に気付いた。2週間前から38℃台の発熱と倦怠感をきたし、軽快しないため受診した。右頸部に径1.5cmのリンパ節を3個触知する。腹部は平坦、軟で、肝・脾を触知しない。既往歴と家族歴に特記すべきことはない。意識は清明。身長 170cm、体重 68kg。体温 37.4℃。脈拍 100/分、整。血圧 132/90mmHg。呼吸数 24/分。SpO2 98%(room air)。血液所見：赤血球 210万、Hb 7.4g/dL、Ht 23%、白血球 16,000(異常細胞 60%)、血小板 5万。骨髄血塗抹May-Giemsa染色標本(別冊No. 23)を別に示す。骨髄細胞の染色体分析では正常男性核型であった。異常細胞のペルオキシダーゼ反応は陰性。表面マーカー解析ではCD19 陽性、CD20 陰性、CD33 陰性、TdT(terminal deoxynucleotidyl transferase)陽性であった。
- 診断はどれか。
[正答]
※国試ナビ4※ ［113D053］←［国試_113］→［113D055］
[★]
- 英
- malignant lymphoma
- ラ
- lymphoma malignum
- 関
悪性リンパ腫とマーカー
- 悪性リンパ腫.xls
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sIg
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CD5
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CD10
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CD19
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CD20
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CD23
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CD43
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bcl
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cyclin
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TdT
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その他
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転座
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小リンパ性リンパ腫 small lymphocytic lymphoma
慢性リンパ性白血病 chronic lymphocytic leukemia
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濾胞性リンパ腫 FL
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bcl2 ＋
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MALTリンパ腫
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マントル細胞リンパ腫 MCL
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びまん性大細胞性B細胞リンパ腫 DLBL
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bcl6 ＋
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前駆Bリンパ芽球性リンパ腫
急性Bリンパ球性白血病 LBL/ALL
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バーキットリンパ腫 BL
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Myc, Ki-67
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ｔ（8,14)Myc；IgH ～80%
t(2,8)κ；Myc ～15%
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ホジキンリンパ腫
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CD15, CD30, CD45 -
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t(8,22)Myc；λ ～10%
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成人T細胞白血病 ATL
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CD2, CD3, CD4, CD25, HLA-DR, CD8 -
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病期
参考
- http://www.rinpashu.com/inspection/
国試
[★]
- 英
- chronic myeloid leukemia chronic myelogenous leukemia chronic myelocytic leukemia CML
- 関
- 白血病、染色体異常
- 血液・造血器 081030I
- first aid step1 2006 p.294,303,304,309,310,
概念
- 造血幹細胞に遺伝子的な変異が生じ、正常な分化能を保持したまま腫瘍性に増殖し、特に顆粒球系の血球の増殖をきたす。
- 白血球は著増、血小板は増加するが、赤血球は正常もしくは減少する。
- 慢性に経過するが、急性転化(blastic crisis)により急性白血病と同様の病態をとりうる。
検査
- 赤血球：→or↓
- 白血球：↑↑↑
- 血小板：↑ → 急性転化例では↓
- 好中球アルカリホスファターゼ：低値
- NAPスコア：低下 → 急性転化例では↑
- 血清ビタミンB12、LDH、尿酸、リゾチーム：高値 → 白血球の破壊による
- 白血病裂孔：なし → 分化能は保たれているため
- 染色体：Ph染色体の出現
- → 急性転化例では複数のPh染色体、環状Ph1、形態異常をきたしたPh染色体の出現がみられる(QB.G247)。頻度：複数のPh染色体の出現＞トリソミー＞17番同腕染色体＞19トリソミー？(+19) (WCH.2243)。染色体の変化は血液学的な変化に数ヶ月先だって起こるが、必ずしもblast crisisに繋がるわけではない(WCH.2243)。急性転化例の2/3では骨髄性、1/3でリンパ性にtransformationする。後者の場合、MPO染色陰性、PAS染色陽性、B細胞表面抗原の発現(多くの場合CD10,CD19を発現し,sIgは欠く)、TdT発現(抗体の遺伝子再構成における多様性付与に関与)。(WCH.2243)
治療
- イマチニブが第一選択となる。適応があれば同種幹細胞移植。
治療に用いる薬物・治療法
- イマチニブ
- 自己幹細胞移植：？
- 同種幹細胞移植
- 白血球除去(leukapheresis)・脾摘
- インターフェロンα：イマチニブが登場する前は、同種幹細胞移植ができない症例において治療の選択肢の一つであった。
- ヒドロキシウレア：。インターフェロンと併用して使われる。代謝拮抗薬。DNA合成を阻害する。骨髄抑制、二次発癌は稀。
- シタラビン：Ara-CTPとなり、DNA合成過程のシチジン二リン酸(CDP)還元酵素やDNAポリメラーゼを阻害
慢性期
- 参考2
移行期
- 参考2
急性期
- 参考2
- 1. myeloid crisisに対してはAML、lymphoid crisisに対してはALLに対する寛解導入療法に準じた化学療法を行う。
- 2. 同種幹細胞移植
国試
参考
- http://www.gan-pro.com/professional/cancer/child-leukemia/chronic-myelogenous-leukemia.html
[★]
- 英
- terminal deoxynucleotidyl transferase, TdT
- 関
- B細胞、ターミナルトランスフェラーゼ
- lymphoi-speciic emzyme
- adds nucleotides randomly to the single-strand ends.
- TCRやBCRの各鎖をコードする遺伝子のV,D,Jセグメントの遺伝子再構成において、altermisによってニックが入った末端はヌクレアーゼやTdTにより塩基が付与されたりする。これによって多様性が生じる
[★]
- 英
- terminal transferase
- 同
- ターミナルデオキシヌクレオチジルトランスフェラーゼ terminal deoxynucleotidyl transferase TdT、ターミナルヌクレオチジルトランスフェラーゼ terminal nucleotidyl transferase
- 関
- 末端転移酵素
- B細胞やT細胞で発現し、遺伝子再構成における多様性の付与に関与している。
[★]
- 英
- terminal deoxynucleotidyl transferase、TdT
- 関
- ターミナルヌクレオチドトランスフェラーゼ、ヌクレオチドトランスフェラーゼ、末端デオキシヌクレオチドトランスフェラーゼ、デオキシヌクレオチド転移酵素、DNAヌクレオチジルエキソトランスフェラーゼ
[★]
- 英
- terminal deoxynucleotidyl transferase activity, TdT activity
- 関
- ターミナルデオキシヌクレオチジルトランスフェラーゼ
[★]
タネル染色
- 関
- terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling、TUNEL staining
[★]
[★]