Details of Drug Off-Target (DOT)

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

• DOT Name: Suppression of tumorigenicity 18 protein (ST18)
• Synonyms: Zinc finger protein 387
• Gene Name: ST18
• Related Disease:
  Alcohol dependence
  Alzheimer disease
  Angle-closure glaucoma
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Frontotemporal dementia
  Glioblastoma multiforme
  Hepatocellular carcinoma
  Lung adenocarcinoma
  Motion sickness
  Pemphigus
  Pemphigus vulgaris
  Primary angle-closure glaucoma
  Acute myelogenous leukaemia
  Neoplasm
• UniProt ID: ST18_HUMAN
• PDB ID: 2CS8
• Pfam ID: PF08474 ; PF01530
• Sequence:
  MDAEAEDKTLRTRSKGTEVPMDSLIQELSVAYDCSMAKKRTAEDQALGVPVNKRKSLLMK
  PRHYSPKADCQEDRSDRTEDDGPLETHGHSTAEEIMIKPMDESLLSTAQENSSRKEDRYS
  CYQELMVKSLMHLGKFEKNVSVQTVSENLNDSGIQSLKAESDEADECFLIHSDDGRDKID
  DSQPPFCSSDDNESNSESAENGWDSGSNFSEETKPPRVPKYVLTDHKKDLLEVPEIKTEG
  DKFIPCENRCDSETERKDPQNALAEPLDGNAQPSFPDVEEEDSESLAVMTEEGSDLEKAK
  GNLSLLEQAIALQAERGCVFHNTYKELDRFLLEHLAGERRQTKVIDMGGRQIFNNKHSPR
  PEKRETKCPIPGCDGTGHVTGLYPHHRSLSGCPHKVRVPLEILAMHENVLKCPTPGCTGR
  GHVNSNRNTHRSLSGCPIAAAEKLAMSQDKNQLDSPQTGQCPDQAHRTSLVKQIEFNFPS
  QAITSPRATVSKEQEKFGKVPFDYASFDAQVFGKRPLIQTVQGRKTPPFPESKHFPNPVK
  FPNRLPSAGAHTQSPGRASSYSYGQCSEDTHIAAAAAILNLSTRCREATDILSNKPQSLH
  AKGAEIEVDENGTLDLSMKKNRILDKSAPLTSSNTSIPTPSSSPFKTSSILVNAAFYQAL
  CDQEGWDTPINYSKTHGKTEEEKEKDPVSSLENLEEKKFPGEASIPSPKPKLHARDLKKE
  LITCPTPGCDGSGHVTGNYASHRSVSGCPLADKTLKSLMAANSQELKCPTPGCDGSGHVT
  GNYASHRSLSGCPRARKGGVKMTPTKEEKEDPELKCPVIGCDGQGHISGKYTSHRTASGC
  PLAAKRQKENPLNGASLSWKLNKQELPHCPLPGCNGLGHVNNVFVTHRSLSGCPLNAQVI
  KKGKVSEELMTIKLKATGGIESDEEIRHLDEEIKELNESNLKIEADMMKLQTQITSMESN
  LKTIEEENKLIEQNNESLLKELAGLSQALISSLADIQLPQMGPISEQNFEAYVNTLTDMY
  SNLERDYSPECKALLESIKQAVKGIHV
• Function: Repressor that binds to DNA sequences containing a bipartite element consisting of a direct repeat of the sequence 5'-AAAGTTT-3' separated by 2-9 nucleotides. Represses basal transcription activity from target promoters. Inhibits colony formation in cultured breast cancer cells.
• Tissue Specificity: Detected at low levels in heart, liver, kidney, skeletal muscle, pancreas, testis, ovary and prostate. Detected at even lower levels in mammary epithelial cells and breast cancer cells.

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alcohol dependence	DIS4ZSCO	Strong	Biomarker	[1]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[2]
Angle-closure glaucoma	DISZ95KY	Strong	Genetic Variation	[3]
Breast cancer	DIS7DPX1	Strong	Biomarker	[4]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[4]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[5]
Frontotemporal dementia	DISKYHXL	Strong	Genetic Variation	[6]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[4]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[7]
Lung adenocarcinoma	DISD51WR	Strong	Genetic Variation	[8]
Motion sickness	DISZ2WZW	Strong	Genetic Variation	[9]
Pemphigus	DISZAZ6M	Strong	Biomarker	[10]
Pemphigus vulgaris	DISENR62	Strong	Genetic Variation	[11]
Primary angle-closure glaucoma	DISX8UKZ	Strong	Genetic Variation	[3]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[12]
Neoplasm	DISZKGEW	Limited	Biomarker	[13]

5 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 Suppression of tumorigenicity 18 protein (ST18).	[14]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Suppression of tumorigenicity 18 protein (ST18).	[15]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of Suppression of tumorigenicity 18 protein (ST18).	[16]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Suppression of tumorigenicity 18 protein (ST18).	[17]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of Suppression of tumorigenicity 18 protein (ST18).	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the methylation of Suppression of tumorigenicity 18 protein (ST18).	[18]

References

• [1] Stress-response pathways are altered in the hippocampus of chronic alcoholics.Alcohol. 2013 Nov;47(7):505-15. doi: 10.1016/j.alcohol.2013.07.002. Epub 2013 Aug 24.
• [2] Genome-wide association study of the rate of cognitive decline in Alzheimer's disease.Alzheimers Dement. 2014 Jan;10(1):45-52. doi: 10.1016/j.jalz.2013.01.008. Epub 2013 Mar 25.
• [3] Integration of Genetic and Biometric Risk Factors for Detection of Primary Angle Closure Glaucoma.Am J Ophthalmol. 2019 Dec;208:160-165. doi: 10.1016/j.ajo.2019.07.022. Epub 2019 Aug 1.
• [4] Myt1 and Myt1l transcription factors limit proliferation in GBM cells by repressing YAP1 expression.Biochim Biophys Acta Gene Regul Mech. 2018 Nov;1861(11):983-995. doi: 10.1016/j.bbagrm.2018.10.005. Epub 2018 Oct 10.
• [5] ST18 is a breast cancer tumor suppressor gene at human chromosome 8q11.2.Oncogene. 2004 Dec 9;23(57):9295-302. doi: 10.1038/sj.onc.1208131.
• [6] Potential genetic modifiers of disease risk and age at onset in patients with frontotemporal lobar degeneration and GRN mutations: a genome-wide association study.Lancet Neurol. 2018 Jun;17(6):548-558. doi: 10.1016/S1474-4422(18)30126-1. Epub 2018 Apr 30.
• [7] Endogenous retrotransposition activates oncogenic pathways in hepatocellular carcinoma.Cell. 2013 Mar 28;153(1):101-11. doi: 10.1016/j.cell.2013.02.032.
• [8] Genomic aberrations in lung adenocarcinoma in never smokers.PLoS One. 2010 Dec 6;5(12):e15145. doi: 10.1371/journal.pone.0015145.
• [9] Genetic variants associated with motion sickness point to roles for inner ear development, neurological processes and glucose homeostasis.Hum Mol Genet. 2015 May 1;24(9):2700-8. doi: 10.1093/hmg/ddv028. Epub 2015 Jan 26.
• [10] The association between ST18 gene polymorphism and severe pemphigus disease among Iranian population.Exp Dermatol. 2018 Dec;27(12):1395-1398. doi: 10.1111/exd.13778. Epub 2018 Oct 22.
• [11] Single-nucleotide polymorphisms associated with pemphigus vulgaris: Potent markers for better treatment and personalized medicine.Int J Immunogenet. 2020 Feb;47(1):41-49. doi: 10.1111/iji.12451. Epub 2019 Jul 24.
• [12] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [13] A critical role for the neural zinc factor ST18 in pancreatic -cell apoptosis.J Biol Chem. 2014 Mar 21;289(12):8413-9. doi: 10.1074/jbc.M114.554915. Epub 2014 Feb 7.
• [14] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [15] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [16] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [17] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [18] 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.
• [19] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.