Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT314JB6)

• DOT Name: Protein JTB (JTB)
• Synonyms: Jumping translocation breakpoint protein; Prostate androgen-regulated protein; PAR protein
• Gene Name: JTB
• Related Disease:
  Myocardial infarction
  Rheumatoid arthritis
  Atrial fibrillation
  Bone osteosarcoma
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Carcinoma of esophagus
  Drug dependence
  Epithelial ovarian cancer
  Esophageal cancer
  Ewing sarcoma
  Gray platelet syndrome
  Hepatitis B virus infection
  Hepatocellular carcinoma
  Klinefelter syndrome
  Lung cancer
  Lung carcinoma
  Neoplasm
  Neoplasm of esophagus
  Osteosarcoma
  Pneumonia
  Pneumonitis
  Pouchitis
  Prostate cancer
  Prostate carcinoma
  Prostate neoplasm
  Pulmonary fibrosis
  Systemic lupus erythematosus
  Influenza
  Advanced cancer
  Amyotrophic lateral sclerosis
  Parkinson disease
• UniProt ID: JTB_HUMAN
• PDB ID: 2KJX
• Pfam ID: PF05439
• Sequence:
  MLAGAGRPGLPQGRHLCWLLCAFTLKLCQAEAPVQEEKLSASTSNLPCWLVEEFVVAEEC
  SPCSNFRAKTTPECGPTGYVEKITCSSSKRNEFKSCRSALMEQRLFWKFEGAVVCVALIF
  ACLVIIRQRQLDRKALEKVRKQIESI
• Function: Required for normal cytokinesis during mitosis. Plays a role in the regulation of cell proliferation. May be a component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis. The CPC complex has essential functions at the centromere in ensuring correct chromosome alignment and segregation and is required for chromatin-induced microtubule stabilization and spindle assembly. Increases AURKB activity. Inhibits apoptosis induced by TGFB1. Overexpression induces swelling of mitochondria and reduces mitochondrial membrane potential.
• Tissue Specificity: Ubiquitous. Expressed in all normal human tissues studied but overexpressed or underexpressed in many of their malignant counterparts.

Molecular Interaction Atlas (MIA) of This DOT

33 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Myocardial infarction	DIS655KI	Definitive	Genetic Variation	[1]
Rheumatoid arthritis	DISTSB4J	Definitive	Altered Expression	[2]
Atrial fibrillation	DIS15W6U	Strong	Altered Expression	[3]
Bone osteosarcoma	DIST1004	Strong	Altered Expression	[4]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[5]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[5]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[6]
Carcinoma of esophagus	DISS6G4D	Strong	Biomarker	[7]
Drug dependence	DIS9IXRC	Strong	Genetic Variation	[8]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[9]
Esophageal cancer	DISGB2VN	Strong	Biomarker	[7]
Ewing sarcoma	DISQYLV3	Strong	Altered Expression	[10]
Gray platelet syndrome	DISLOTCW	Strong	Biomarker	[11]
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[12]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[12]
Klinefelter syndrome	DISOUI7W	Strong	Genetic Variation	[13]
Lung cancer	DISCM4YA	Strong	Biomarker	[14]
Lung carcinoma	DISTR26C	Strong	Biomarker	[14]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[15]
Neoplasm of esophagus	DISOLKAQ	Strong	Biomarker	[7]
Osteosarcoma	DISLQ7E2	Strong	Altered Expression	[4]
Pneumonia	DIS8EF3M	Strong	Biomarker	[16]
Pneumonitis	DIS88E0K	Strong	Biomarker	[16]
Pouchitis	DISE28DD	Strong	Altered Expression	[17]
Prostate cancer	DISF190Y	Strong	Altered Expression	[18]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[18]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[19]
Pulmonary fibrosis	DISQKVLA	Strong	Biomarker	[16]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[13]
Influenza	DIS3PNU3	moderate	Biomarker	[20]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[21]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Biomarker	[22]
Parkinson disease	DISQVHKL	Limited	Biomarker	[23]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Protein JTB (JTB) affects the response to substance of Acetaminophen.	[33]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Protein JTB (JTB).	[24]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Protein JTB (JTB).	[25]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Protein JTB (JTB).	[26]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Protein JTB (JTB).	[27]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Protein JTB (JTB).	[29]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Protein JTB (JTB).	[30]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Protein JTB (JTB).	[31]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Protein JTB (JTB).	[32]

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 Protein JTB (JTB).	[28]

References

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• [2] Methotrexate upregulates circadian transcriptional factors PAR bZIP to induce apoptosis on rheumatoid arthritis synovial fibroblasts.Arthritis Res Ther. 2018 Mar 22;20(1):55. doi: 10.1186/s13075-018-1552-9.
• [3] Thrombin induces protease-activated receptor 1 signaling and activation of human atrial fibroblasts and dabigatran prevents these effects.Int J Cardiol. 2018 Nov 15;271:219-227. doi: 10.1016/j.ijcard.2018.05.033. Epub 2018 May 24.
• [4] Hydrogen peroxide-induced poly(ADP-ribosyl)ation regulates osteogenic differentiation-associated cell death.Free Radic Biol Med. 2012 Oct 15;53(8):1552-64. doi: 10.1016/j.freeradbiomed.2012.08.567. Epub 2012 Aug 20.
• [5] Identification of distinct miRNA target regulation between breast cancer molecular subtypes using AGO2-PAR-CLIP and patient datasets. Genome Biol. 2014 Jan 7;15(1):R9.
• [6] Overabundant FANCD2, alone and combined with NQO1, is a sensitive marker of adverse prognosis in breast cancer.Ann Oncol. 2013 Nov;24(11):2780-5. doi: 10.1093/annonc/mdt290. Epub 2013 Jul 29.
• [7] Effect and mechanism of PAR-2 on the proliferation of esophageal cancer cells.Eur Rev Med Pharmacol Sci. 2016 Nov;20(22):4688-4696.
• [8] Opioid-Induced Hyperalgesia Is Associated with Dysregulation of Circadian Rhythm and Adaptive Immune Pathways in the Mouse Trigeminal Ganglia and Nucleus Accumbens.Mol Neurobiol. 2019 Dec;56(12):7929-7949. doi: 10.1007/s12035-019-01650-5. Epub 2019 May 25.
• [9] Tissue factor-factor VIIa complex triggers protease activated receptor 2-dependent growth factor release and migration in ovarian cancer.Gynecol Oncol. 2017 Apr;145(1):167-175. doi: 10.1016/j.ygyno.2017.01.022. Epub 2017 Jan 29.
• [10] The role of miR-17-92 in the miRegulatory landscape of Ewing sarcoma.Oncotarget. 2017 Feb 14;8(7):10980-10993. doi: 10.18632/oncotarget.14091.
• [11] Defective platelet responsiveness to thrombin and protease-activated receptors agonists in a novel case of gray platelet syndrome: correlation between the platelet defect and the alpha-granule content in the patient and four relatives.J Thromb Haemost. 2007 Mar;5(3):551-9. doi: 10.1111/j.1538-7836.2007.02329.x. Epub 2006 Nov 28.
• [12] HBsAg inhibits the translocation of JTB into mitochondria in HepG2 cells and potentially plays a role in HCC progression.PLoS One. 2012;7(5):e36914. doi: 10.1371/journal.pone.0036914. Epub 2012 May 15.
• [13] Identification and characterization of an Xp22.33;Yp11.2 translocation causing a triplication of several genes of the pseudoautosomal region 1 in an XX male patient with severe systemic lupus erythematosus.Arthritis Rheum. 2006 Apr;54(4):1270-8. doi: 10.1002/art.21733.
• [14] Hydrophobic oxime ethers: a versatile class of pDNA and siRNA transfection lipids.ChemMedChem. 2011 Nov 4;6(11):2063-9. doi: 10.1002/cmdc.201100259. Epub 2011 Aug 31.
• [15] A phase 1 study of veliparib, a PARP-1/2 inhibitor, with gemcitabine and radiotherapy in locally advanced pancreatic cancer.EBioMedicine. 2019 Feb;40:375-381. doi: 10.1016/j.ebiom.2018.12.060. Epub 2019 Jan 8.
• [16] Herbal decoctosome is a novel form of medicine.Sci China Life Sci. 2019 Mar;62(3):333-348. doi: 10.1007/s11427-018-9508-0. Epub 2019 Mar 21.
• [17] Faecal Proteases from Pouchitis Patients Activate Protease Activating Receptor-2 to Disrupt the Epithelial Barrier.J Crohns Colitis. 2019 Dec 10;13(12):1558-1568. doi: 10.1093/ecco-jcc/jjz086.
• [18] Stable lower PAR expression decreased DU145 prostate cancer cell growth in SCID mice.Prostate. 2001 Nov 1;49(3):200-7. doi: 10.1002/pros.1135.
• [19] Protease-activated receptor-1 is upregulated in reactive stroma of primary prostate cancer and bone metastasis.Prostate. 2009 May 15;69(7):727-36. doi: 10.1002/pros.20920.
• [20] Protease-Activated Receptor 2 Agonist as Adjuvant: Augmenting Development of Protective Memory CD8 T Cell Responses Induced by Influenza Virosomes.J Immunol. 2019 Jul 15;203(2):441-452. doi: 10.4049/jimmunol.1800915. Epub 2019 Jun 10.
• [21] Selective small molecule PARG inhibitor causes replication fork stalling and cancer cell death.Nat Commun. 2019 Dec 11;10(1):5654. doi: 10.1038/s41467-019-13508-4.
• [22] Vorapaxar and Amyotrophic Lateral Sclerosis: Coincidence or Adverse Association?.Am J Ther. 2017 Mar/Apr;24(2):e139-e143. doi: 10.1097/MJT.0000000000000395.
• [23] Multiple risk factors for Parkinson's disease.J Neurol Sci. 2004 Feb 15;217(2):169-74. doi: 10.1016/j.jns.2003.09.014.
• [24] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [25] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [26] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [27] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [28] 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.
• [29] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [30] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [31] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [32] Analysis of the prostate cancer cell line LNCaP transcriptome using a sequencing-by-synthesis approach. BMC Genomics. 2006 Sep 29;7:246. doi: 10.1186/1471-2164-7-246.
• [33] Interindividual variation in gene expression responses and metabolite formation in acetaminophen-exposed primary human hepatocytes. Arch Toxicol. 2016 May;90(5):1103-15. doi: 10.1007/s00204-015-1545-2. Epub 2015 Jun 24.