Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFSEF12)

DOT Name DNA nucleotidylexotransferase (DNTT)
Synonyms EC 2.7.7.31; Terminal addition enzyme; Terminal deoxynucleotidyltransferase; Terminal transferase
Gene Name DNTT
Related Disease
Multiple sclerosis ( )
Non-small-cell lung cancer ( )
T lymphoblastic leukaemia ( )
T-cell acute lymphoblastic leukaemia ( )
Acute lymphocytic leukaemia ( )
Adult T-cell leukemia/lymphoma ( )
Alzheimer disease ( )
Anorexia nervosa cachexia ( )
Bipolar disorder ( )
Blast phase chronic myelogenous leukemia, BCR-ABL1 positive ( )
Dilated cardiomyopathy ( )
Dilated cardiomyopathy 1A ( )
Dystonia ( )
Graves disease ( )
High blood pressure ( )
Hirschsprung disease ( )
Neoplasm ( )
Prostate cancer ( )
Systemic lupus erythematosus ( )
T-cell leukaemia ( )
Ventricular septal defect ( )
Tetralogy of fallot ( )
Crohn disease ( )
Schizoaffective disorder ( )
Acute myelogenous leukaemia ( )
Adult lymphoma ( )
Coronary heart disease ( )
Follicular lymphoma ( )
Inflammatory bowel disease ( )
leukaemia ( )
Leukemia ( )
Lymphoid leukemia ( )
Lymphoma ( )
Non-insulin dependent diabetes ( )
Pediatric lymphoma ( )
Prostate carcinoma ( )
Thalassemia ( )
Type-1 diabetes ( )
Van der Woude syndrome ( )
UniProt ID
TDT_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
2COE; 5W4E
EC Number
2.7.7.31
Pfam ID
PF00533 ; PF14791 ; PF10391 ; PF14716 ; PF01909
Sequence
MDPPRASHLSPRKKRPRQTGALMASSPQDIKFQDLVVFILEKKMGTTRRAFLMELARRKG
FRVENELSDSVTHIVAENNSGSDVLEWLQAQKVQVSSQPELLDVSWLIECIRAGKPVEMT
GKHQLVVRRDYSDSTNPGPPKTPPIAVQKISQYACQRRTTLNNCNQIFTDAFDILAENCE
FRENEDSCVTFMRAASVLKSLPFTIISMKDTEGIPCLGSKVKGIIEEIIEDGESSEVKAV
LNDERYQSFKLFTSVFGVGLKTSEKWFRMGFRTLSKVRSDKSLKFTRMQKAGFLYYEDLV
SCVTRAEAEAVSVLVKEAVWAFLPDAFVTMTGGFRRGKKMGHDVDFLITSPGSTEDEEQL
LQKVMNLWEKKGLLLYYDLVESTFEKLRLPSRKVDALDHFQKCFLIFKLPRQRVDSDQSS
WQEGKTWKAIRVDLVLCPYERRAFALLGWTGSRQFERDLRRYATHERKMILDNHALYDKT
KRIFLKAESEEEIFAHLGLDYIEPWERNA
Function
Template-independent DNA polymerase which catalyzes the random addition of deoxynucleoside 5'-triphosphate to the 3'-end of a DNA initiator. One of the in vivo functions of this enzyme is the addition of nucleotides at the junction (N region) of rearranged Ig heavy chain and T-cell receptor gene segments during the maturation of B- and T-cells.
KEGG Pathway
Non-homologous end-joining (hsa03450 )
Hematopoietic cell lineage (hsa04640 )

Molecular Interaction Atlas (MIA) of This DOT

39 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Multiple sclerosis DISB2WZI Definitive Genetic Variation [1]
Non-small-cell lung cancer DIS5Y6R9 Definitive Altered Expression [2]
T lymphoblastic leukaemia DIS2PNPP Definitive Altered Expression [3]
T-cell acute lymphoblastic leukaemia DIS17AI2 Definitive Biomarker [4]
Acute lymphocytic leukaemia DISPX75S Strong Biomarker [5]
Adult T-cell leukemia/lymphoma DIS882XU Strong Altered Expression [5]
Alzheimer disease DISF8S70 Strong Genetic Variation [6]
Anorexia nervosa cachexia DISFO5RQ Strong Genetic Variation [7]
Bipolar disorder DISAM7J2 Strong Biomarker [8]
Blast phase chronic myelogenous leukemia, BCR-ABL1 positive DIS3KLUX Strong Altered Expression [9]
Dilated cardiomyopathy DISX608J Strong Biomarker [10]
Dilated cardiomyopathy 1A DIS0RK9Z Strong Biomarker [10]
Dystonia DISJLFGW Strong Genetic Variation [11]
Graves disease DISU4KOQ Strong Biomarker [12]
High blood pressure DISY2OHH Strong Biomarker [13]
Hirschsprung disease DISUUSM1 Strong Biomarker [14]
Neoplasm DISZKGEW Strong Biomarker [15]
Prostate cancer DISF190Y Strong Genetic Variation [16]
Systemic lupus erythematosus DISI1SZ7 Strong Biomarker [14]
T-cell leukaemia DISJ6YIF Strong Altered Expression [5]
Ventricular septal defect DISICO41 Strong Biomarker [17]
Tetralogy of fallot DISMHFNW moderate Biomarker [18]
Crohn disease DIS2C5Q8 Disputed Genetic Variation [19]
Schizoaffective disorder DISLBW6B Disputed Genetic Variation [20]
Acute myelogenous leukaemia DISCSPTN Limited Altered Expression [21]
Adult lymphoma DISK8IZR Limited Biomarker [22]
Coronary heart disease DIS5OIP1 Limited Biomarker [23]
Follicular lymphoma DISVEUR6 Limited Biomarker [24]
Inflammatory bowel disease DISGN23E Limited Biomarker [25]
leukaemia DISS7D1V Limited Posttranslational Modification [26]
Leukemia DISNAKFL Limited Posttranslational Modification [26]
Lymphoid leukemia DIS65TYQ Limited Altered Expression [21]
Lymphoma DISN6V4S Limited Biomarker [22]
Non-insulin dependent diabetes DISK1O5Z Limited Genetic Variation [27]
Pediatric lymphoma DIS51BK2 Limited Biomarker [22]
Prostate carcinoma DISMJPLE Limited Biomarker [28]
Thalassemia DIS76XZB Limited Biomarker [29]
Type-1 diabetes DIS7HLUB Limited Genetic Variation [30]
Van der Woude syndrome DISADZS1 Limited Biomarker [31]
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⏷ Show the Full List of 39 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of DNA nucleotidylexotransferase (DNTT). [32]
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References

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2 Expression of nuclear factor-kappaB and its clinical significance in nonsmall-cell lung cancer.Ann Thorac Surg. 2006 Jul;82(1):243-8. doi: 10.1016/j.athoracsur.2006.01.049.
3 Reconstruction of rearranged T-cell receptor loci by whole genome and transcriptome sequencing gives insights into the initial steps of T-cell prolymphocytic leukemia.Genes Chromosomes Cancer. 2020 Apr;59(4):261-267. doi: 10.1002/gcc.22821. Epub 2019 Nov 29.
4 Protein signaling and regulation of gene transcription in leukemia: role of the Casein Kinase II-Ikaros axis.J Investig Med. 2016 Mar;64(3):735-9. doi: 10.1136/jim-2016-000075. Epub 2016 Feb 9.
5 Expression of terminal deoxynucleotidyltransferase gene in a case of adult T-cell leukemia.Int J Hematol. 1991 Feb;54(1):37-40.
6 Analysis of association between Alzheimer disease and the K variant of butyrylcholinesterase (BCHE-K).Neurosci Lett. 1999 Jul 9;269(2):115-9. doi: 10.1016/s0304-3940(99)00426-7.
7 Dual contribution of NR2B subunit of NMDA receptor and SK3 Ca(2+)-activated K+ channel to genetic predisposition to anorexia nervosa.J Psychiatr Res. 2007 Jan-Feb;41(1-2):160-7. doi: 10.1016/j.jpsychires.2005.07.010. Epub 2005 Sep 12.
8 Chromosome 4 workshop.Psychiatr Genet. 1998 Summer;8(2):67-71. doi: 10.1097/00041444-199800820-00008.
9 Relation of "lymphoid" phenotype and response to chemotherapy incorporating vincristine-prednisolone in the acute phase of Ph1 positive leukemia.Cancer. 1979 Feb;43(2):426-34. doi: 10.1002/1097-0142(197902)43:2<426::aid-cncr2820430204>3.0.co;2-h.
10 Myocardial apoptotic index based on in situ DNA nick end-labeling of endomyocardial biopsies does not predict prognosis of dilated cardiomyopathy.Chest. 2005 Aug;128(2):1060-2. doi: 10.1378/chest.128.2.1060.
11 Planning genetic studies on primary adult-onset dystonia: sample size estimates based on examination of first-degree relatives.J Neurol Sci. 2006 Dec 21;251(1-2):29-34. doi: 10.1016/j.jns.2006.08.009. Epub 2006 Oct 31.
12 Screening of SNPs at 18 positional candidate genes, located within the GD-1 locus on chromosome 14q23-q32, for susceptibility to Graves' disease: a TDT study.Mol Genet Metab. 2004 Nov;83(3):264-70. doi: 10.1016/j.ymgme.2004.07.011.
13 Lipoprotein lipase gene is linked and associated with hypertension in Taiwan young-onset hypertension genetic study.J Biomed Sci. 2005;12(4):651-8. doi: 10.1007/s11373-005-7707-0. Epub 2005 Nov 10.
14 An entropy-based genome-wide transmission/disequilibrium test.Hum Genet. 2007 May;121(3-4):357-67. doi: 10.1007/s00439-007-0322-6. Epub 2007 Feb 13.
15 A novel sphingosine kinase inhibitor induces autophagy in tumor cells.J Pharmacol Exp Ther. 2010 May;333(2):454-64. doi: 10.1124/jpet.109.163337. Epub 2010 Feb 23.
16 Polymorphic GGC repeats in the androgen receptor gene are associated with hereditary and sporadic prostate cancer risk.Hum Genet. 2002 Feb;110(2):122-9. doi: 10.1007/s00439-001-0662-6. Epub 2002 Jan 23.
17 VEGF C-634G polymorphism is associated with protection from isolated ventricular septal defect: case-control and TDT studies.Eur J Hum Genet. 2007 Dec;15(12):1246-51. doi: 10.1038/sj.ejhg.5201890. Epub 2007 Jul 11.
18 Genetic variation in VEGF does not contribute significantly to the risk of congenital cardiovascular malformation.PLoS One. 2009;4(3):e4978. doi: 10.1371/journal.pone.0004978. Epub 2009 Mar 24.
19 Analysis of the influence of OCTN1/2 variants within the IBD5 locus on disease susceptibility and growth indices in early onset inflammatory bowel disease.Gut. 2006 Aug;55(8):1114-23. doi: 10.1136/gut.2005.082107. Epub 2006 Feb 9.
20 Weak association of the platelet-derived growth factor beta (PDGFB) and PDGF receptor beta (PDGFRB) genes with schizophrenia and schizoaffective disorder.World J Biol Psychiatry. 2011 Mar;12(2):127-33. doi: 10.3109/15622975.2010.520333. Epub 2010 Oct 18.
21 Differential expression of terminal transferase (TdT) in acute lymphocytic leukaemia expressing myeloid antigens and TdT positive acute myeloid leukaemia as compared to myeloid antigen negative acute lymphocytic leukaemia.Br J Haematol. 1993 Jul;84(3):416-22. doi: 10.1111/j.1365-2141.1993.tb03095.x.
22 Isolation and characterization of bovine and mouse terminal deoxynucleotidyltransferase cDNAs expressible in mammalian cells.Nucleic Acids Res. 1986 Jul 25;14(14):5777-92. doi: 10.1093/nar/14.14.5777.
23 Four SNPS on chromosome 9p21 confer risk to premature, familial CAD and MI in an American Caucasian population (GeneQuest).Ann Hum Genet. 2008 Sep;72(Pt 5):654-7. doi: 10.1111/j.1469-1809.2008.00454.x. Epub 2008 May 26.
24 Evolution of B-cell malignancy: pre-B-cell leukemia resulting from MYC activation in a B-cell neoplasm with a rearranged BCL2 gene.Proc Natl Acad Sci U S A. 1988 Nov;85(22):8548-52. doi: 10.1073/pnas.85.22.8548.
25 TNFSF15 polymorphisms are associated with susceptibility to inflammatory bowel disease in a new European cohort.Am J Gastroenterol. 2009 Feb;104(2):384-91. doi: 10.1038/ajg.2008.36. Epub 2009 Jan 13.
26 Protein phosphatase 1 (PP1) and Casein Kinase II (CK2) regulate Ikaros-mediated repression of TdT in thymocytes and T-cell leukemia.Pediatr Blood Cancer. 2014 Dec;61(12):2230-5. doi: 10.1002/pbc.25221. Epub 2014 Sep 11.
27 Utility of large consanguineous family-based model for investigating the genetics of type 2 diabetes mellitus.Gene. 2014 Sep 10;548(1):22-8. doi: 10.1016/j.gene.2014.06.053. Epub 2014 Jun 30.
28 Involvement of Cdk5/p25 in digoxin-triggered prostate cancer cell apoptosis.J Biol Chem. 2004 Jul 9;279(28):29302-7. doi: 10.1074/jbc.M403664200. Epub 2004 Apr 30.
29 Beyond transfusion therapy: new therapies in thalassemia including drugs, alternate donor transplant, and gene therapy.Hematology Am Soc Hematol Educ Program. 2018 Nov 30;2018(1):361-370. doi: 10.1182/asheducation-2018.1.361.
30 Association of a functional 17beta-estradiol sensitive IL6-174G/C promoter polymorphism with early-onset type 1 diabetes in females.Hum Mol Genet. 2003 May 15;12(10):1101-10. doi: 10.1093/hmg/ddg132.
31 Possible relationship between the van der Woude syndrome (vWS) locus and nonsyndromic cleft lip with or without cleft palate (NSCL/P).Am J Med Genet. 2001 Nov 15;104(1):86-92. doi: 10.1002/1096-8628(20011115)104:1<86::aid-ajmg10053>3.0.co;2-e.
32 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.