Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJGPA4T)

• DOT Name: Jupiter microtubule associated homolog 2 (JPT2)
• Synonyms: Hematological and neurological expressed 1-like protein; HN1-like protein
• Gene Name: JPT2
• Related Disease:
  Breast cancer
  Breast carcinoma
  Hepatocellular carcinoma
  Non-small-cell lung cancer
  Triple negative breast cancer
  Neoplasm
• UniProt ID: JUPI2_HUMAN
• Pfam ID: PF17054
• Sequence:
  MFQVPDSEGGRAGSRAMKPPGGESSNLFGSPEEATPSSRPNRMASNIFGPTEEPQNIPKR
  TNPPGGKGSGIFDESTPVQTRQHLNPPGGKTSDIFGSPVTATSRLAHPNKPKDHVFLCEG
  EEPKSDLKAARSIPAGAEPGEKGSARKAGPAKEQEPMPTVDSHEPRLGPRPRSHNKVLNP
  PGGKSSISFY
• Function: Nicotinic acid adenine dinucleotide phosphate (NAADP) binding protein required for NAADP-evoked intracellular calcium release. Confers NAADP-sensitivity to the two pore channels (TPCs) complex. Enables NAADP to activate Ca(2+) release from the endoplasmic reticulum through ryanodine receptors ; (Microbial infection) Involved in the endolysosomal trafficking of human coronavirus SARS-CoV-2.
• Tissue Specificity: Expressed in liver, kidney, prostate, testis and uterus.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[1]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[2]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[3]
Triple negative breast cancer	DISAMG6N	Strong	Altered Expression	[1]
Neoplasm	DISZKGEW	Limited	Altered Expression	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Topotecan	DMP6G8T	Approved	Jupiter microtubule associated homolog 2 (JPT2) affects the response to substance of Topotecan.	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Jupiter microtubule associated homolog 2 (JPT2).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Jupiter microtubule associated homolog 2 (JPT2).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Jupiter microtubule associated homolog 2 (JPT2).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Jupiter microtubule associated homolog 2 (JPT2).	[7]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Jupiter microtubule associated homolog 2 (JPT2).	[9]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Jupiter microtubule associated homolog 2 (JPT2).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Jupiter microtubule associated homolog 2 (JPT2).	[11]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of Jupiter microtubule associated homolog 2 (JPT2).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Jupiter microtubule associated homolog 2 (JPT2).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Jupiter microtubule associated homolog 2 (JPT2).	[14]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Jupiter microtubule associated homolog 2 (JPT2).	[15]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN increases the expression of Jupiter microtubule associated homolog 2 (JPT2).	[16]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Jupiter microtubule associated homolog 2 (JPT2).	[8]

References

• [1] HN1L Promotes Triple-Negative Breast Cancer Stem Cells through LEPR-STAT3 Pathway.Stem Cell Reports. 2018 Jan 9;10(1):212-227. doi: 10.1016/j.stemcr.2017.11.010. Epub 2017 Dec 14.
• [2] HN1L-mediated transcriptional axis AP-2/METTL13/TCF3-ZEB1 drives tumor growth and metastasis in hepatocellular carcinoma.Cell Death Differ. 2019 Nov;26(11):2268-2283. doi: 10.1038/s41418-019-0301-1. Epub 2019 Feb 18.
• [3] Overexpression of HN1L promotes cell malignant proliferation in non-small cell lung cancer.Cancer Biol Ther. 2017 Nov 2;18(11):904-915. doi: 10.1080/15384047.2017.1385678. Epub 2017 Oct 20.
• [4] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] 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.
• [7] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [8] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [9] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [10] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [11] 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.
• [12] Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach. BMC Syst Biol. 2012 Dec 10;6:152.
• [13] Epigenetic influences of low-dose bisphenol A in primary human breast epithelial cells. Toxicol Appl Pharmacol. 2010 Oct 15;248(2):111-21.
• [14] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [15] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [16] Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.
• [17] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.