Details of Drug Off-Target (DOT)

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

• DOT Name: Protein THEMIS (THEMIS)
• Synonyms: Thymocyte-expressed molecule involved in selection
• Gene Name: THEMIS
• Related Disease:
  Asthma
  Advanced cancer
  Alcohol dependence
  Autoimmune disease
  Barrett esophagus
  Chronic kidney disease
  Coeliac disease
  Crohn disease
  Latent tuberculosis infection
  Multiple sclerosis
  Obesity
  Pleural tuberculosis
  Primary cutaneous T-cell lymphoma
  Type-1 diabetes
  Meningeal tuberculosis
  Pulmonary tuberculosis
  Tuberculosis
  Rheumatoid arthritis
  Cardiomyopathy
  Gonorrhea
  Stroke
• UniProt ID: THMS1_HUMAN
• Pfam ID: PF12736
• Sequence:
  MALSLEEFVHSLDLRTLPRVLEIQAGIYLEGSIYEMFGNECCFSTGEVIKITGLKVKKII
  AEICEQIEGCESLQPFELPMNFPGLFKIVADKTPYLTMEEITRTIHIGPSRLGHPCFYHQ
  KDIKLENLIIKQGEQIMLNSVEEIDGEIMVSCAVARNHQTHSFNLPLSQEGEFYECEDER
  IYTLKEIVEWKIPKNRTRTVNLTDFSNKWDSTNPFPKDFYGTLILKPVYEIQGVMKFRKD
  IIRILPSLDVEVKDITDSYDANWFLQLLSTEDLFEMTSKEFPIVTEVIEAPEGNHLPQSI
  LQPGKTIVIHKKYQASRILASEIRSNFPKRHFLIPTSYKGKFKRRPREFPTAYDLEIAKS
  EKEPLHVVATKAFHSPHDKLSSVSVGDQFLVHQSETTEVLCEGIKKVVNVLACEKILKKS
  YEAALLPLYMEGGFVEVIHDKKQYPISELCKQFRLPFNVKVSVRDLSIEEDVLAATPGLQ
  LEEDITDSYLLISDFANPTECWEIPVGRLNMTVQLVSNFSRDAEPFLVRTLVEEITEEQY
  YMMRRYESSASHPPPRPPKHPSVEETKLTLLTLAEERTVDLPKSPKRHHVDITKKLHPNQ
  AGLDSKVLIGSQNDLVDEEKERSNRGATAIAETFKNEKHQK
• Function: Plays a central role in late thymocyte development by controlling both positive and negative T-cell selection. Required to sustain and/or integrate signals required for proper lineage commitment and maturation of T-cells. Regulates T-cell development through T-cell antigen receptor (TCR) signaling and in particular through the regulation of calcium influx and phosphorylation of Erk.

Molecular Interaction Atlas (MIA) of This DOT

21 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Asthma	DISW9QNS	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Alcohol dependence	DIS4ZSCO	Strong	Biomarker	[3]
Autoimmune disease	DISORMTM	Strong	Biomarker	[4]
Barrett esophagus	DIS416Y7	Strong	Biomarker	[5]
Chronic kidney disease	DISW82R7	Strong	Biomarker	[6]
Coeliac disease	DISIY60C	Strong	Genetic Variation	[7]
Crohn disease	DIS2C5Q8	Strong	Biomarker	[8]
Latent tuberculosis infection	DIS6R1EH	Strong	Genetic Variation	[9]
Multiple sclerosis	DISB2WZI	Strong	Biomarker	[10]
Obesity	DIS47Y1K	Strong	Genetic Variation	[11]
Pleural tuberculosis	DISD09EG	Strong	Altered Expression	[12]
Primary cutaneous T-cell lymphoma	DIS35WVW	Strong	Biomarker	[13]
Type-1 diabetes	DIS7HLUB	Strong	Genetic Variation	[11]
Meningeal tuberculosis	DIS8KHDE	moderate	Biomarker	[14]
Pulmonary tuberculosis	DIS6FLUM	moderate	Biomarker	[14]
Tuberculosis	DIS2YIMD	moderate	Biomarker	[6]
Rheumatoid arthritis	DISTSB4J	Disputed	Biomarker	[15]
Cardiomyopathy	DISUPZRG	Limited	Biomarker	[16]
Gonorrhea	DISQ5AO6	Limited	Biomarker	[17]
Stroke	DISX6UHX	Limited	Biomarker	[18]

1 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Protein THEMIS (THEMIS).	[19]

2 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 Protein THEMIS (THEMIS).	[20]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Protein THEMIS (THEMIS).	[21]

References

• [1] Moderate-to-severe asthma in individuals of European ancestry: a genome-wide association study.Lancet Respir Med. 2019 Jan;7(1):20-34. doi: 10.1016/S2213-2600(18)30389-8. Epub 2018 Dec 11.
• [2] Genomic analysis of cancer tissue reveals that somatic mutations commonly occur in a specific motif.Hum Mutat. 2009 Jan;30(1):39-48. doi: 10.1002/humu.20810.
• [3] Polymorphisms in ABLIM1 are associated with personality traits and alcohol dependence.J Mol Neurosci. 2012 Feb;46(2):265-71. doi: 10.1007/s12031-011-9530-6. Epub 2011 May 6.
• [4] The chromosome 6q22.33 region is associated with age at diagnosis of type 1 diabetes and disease risk in those diagnosed under 5years of age.Diabetologia. 2018 Jan;61(1):147-157. doi: 10.1007/s00125-017-4440-y. Epub 2017 Oct 5.
• [5] Efficient automated assessment of genetic abnormalities detected by fluorescence in situ hybridization on brush cytology in a Barrett esophagus surveillance population.Cancer. 2007 May 15;109(10):1980-8. doi: 10.1002/cncr.22643.
• [6] The Application of T.SPOT-TB Assay for Early Diagnosis of Active Tuberculosis in Chronic Kidney Disease Patients Receiving Immunosuppressive Treatment.J Invest Surg. 2020 Oct;33(9):853-858. doi: 10.1080/08941939.2019.1566417. Epub 2019 Mar 27.
• [7] Common polygenic variation in coeliac disease and confirmation of ZNF335 and NIFA as disease susceptibility loci.Eur J Hum Genet. 2016 Feb;24(2):291-7. doi: 10.1038/ejhg.2015.87. Epub 2015 Apr 29.
• [8] Utility of in vitro interferon- release assay in differential diagnosis between intestinal tuberculosis and Crohn's disease.J Dig Dis. 2013 Feb;14(2):68-75. doi: 10.1111/1751-2980.12017.
• [9] Social network analysis and whole genome sequencing in a cohort study to investigate TB transmission in an educational setting.BMC Infect Dis. 2019 Feb 13;19(1):154. doi: 10.1186/s12879-019-3734-8.
• [10] Increased THEMIS First Exon Usage in CD4+ T-Cells Is Associated with a Genotype that Is Protective against Multiple Sclerosis.PLoS One. 2016 Jul 20;11(7):e0158327. doi: 10.1371/journal.pone.0158327. eCollection 2016.
• [11] Identification of diabetes- and obesity-associated proteomic changes in human spermatozoa by difference gel electrophoresis.Reprod Biomed Online. 2009 Nov;19(5):660-70. doi: 10.1016/j.rbmo.2009.07.001.
• [12] Diagnosis of tuberculous pleurisy with combination of adenosine deaminase and interferon- immunospot assay in a tuberculosis-endemic population: A prospective cohort study.Medicine (Baltimore). 2017 Nov;96(47):e8412. doi: 10.1097/MD.0000000000008412.
• [13] Computer-Aided Discovery of Small Molecule Inhibitors of Thymocyte Selection-Associated High Mobility Group Box Protein (TOX) as Potential Therapeutics for Cutaneous T-Cell Lymphomas.Molecules. 2019 Sep 24;24(19):3459. doi: 10.3390/molecules24193459.
• [14] Evaluation of a New IFN- Release Assay for Rapid Diagnosis of Active Tuberculosis in a High-Incidence Setting.Front Cell Infect Microbiol. 2017 Apr 11;7:117. doi: 10.3389/fcimb.2017.00117. eCollection 2017.
• [15] Biological function integrated prediction of severe radiographic progression in rheumatoid arthritis: a nested case control study.Arthritis Res Ther. 2017 Oct 25;19(1):244. doi: 10.1186/s13075-017-1414-x.
• [16] A genetic linkage map of the Syrian hamster and localization of cardiomyopathy locus on chromosome 9qa2.1-b1 using RLGS spot-mapping.Nat Genet. 1996 May;13(1):87-90. doi: 10.1038/ng0596-87.
• [17] Summary and Trends of the Russian Gonococcal Antimicrobial Surveillance Programme, 2005 to 2016.J Clin Microbiol. 2019 May 24;57(6):e02024-18. doi: 10.1128/JCM.02024-18. Print 2019 Jun.
• [18] Using machine learning to optimize selection of elderly patients for endovascular thrombectomy.J Neurointerv Surg. 2019 Aug;11(8):847-851. doi: 10.1136/neurintsurg-2018-014381. Epub 2019 Feb 2.
• [19] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [20] 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.
• [21] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.