Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7AL3KJ)

• DOT Name: Sulfotransferase 4A1 (SULT4A1)
• Synonyms: ST4A1; EC 2.8.2.-; Brain sulfotransferase-like protein; hBR-STL; hBR-STL-1; Nervous system sulfotransferase; NST
• Gene Name: SULT4A1
• Related Disease:
  Acute coronary syndrome
  Breast cancer
  Breast lobular carcinoma
  Malignant peripheral nerve sheath tumor
  Mucinous adenocarcinoma
  Neoplasm
  Schizoaffective disorder
  Breast carcinoma
  Carcinoma
  Megalencephaly
• UniProt ID: ST4A1_HUMAN
• PDB ID: 1ZD1
• EC Number: 2.8.2.-
• Pfam ID: PF00685
• Sequence:
  MAESEAETPSTPGEFESKYFEFHGVRLPPFCRGKMEEIANFPVRPSDVWIVTYPKSGTSL
  LQEVVYLVSQGADPDEIGLMNIDEQLPVLEYPQPGLDIIKELTSPRLIKSHLPYRFLPSD
  LHNGDSKVIYMARNPKDLVVSYYQFHRSLRTMSYRGTFQEFCRRFMNDKLGYGSWFEHVQ
  EFWEHRMDSNVLFLKYEDMHRDLVTMVEQLARFLGVSCDKAQLEALTEHCHQLVDQCCNA
  EALPVGRGRVGLWKDIFTVSMNEKFDLVYKQKMGKCDLTFDFYL
• Function: Atypical sulfotransferase family member with very low affinity for 3'-phospho-5'-adenylyl sulfate (PAPS) and very low catalytic activity towards L-triiodothyronine, thyroxine, estrone, p-nitrophenol, 2-naphthylamine, and 2-beta-naphthol. May have a role in the metabolism of drugs and neurotransmitters in the CNS.
• Tissue Specificity: Highly expressed in the cerebral cortex and frontal lobe, slightly less in the cerebellum, occipital and temporal lobes, relatively low in the medulla and putamen, and lowest in the spinal cord. No expression detected in the pancreas . Highly expressed in fetal brain and occipital lobe, slightly less in the whole brain, frontal lobe, hippocampus, and lung, very low expression in cerebellum, medulla oblongata, temporal lobe, testis, kidney and appendix .
• Reactome Pathway: Cytosolic sulfonation of small molecules (R-HSA-156584)

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute coronary syndrome	DIS7DYEW	Strong	Biomarker	[1]
Breast cancer	DIS7DPX1	Strong	Biomarker	[2]
Breast lobular carcinoma	DISBY98Q	Strong	Genetic Variation	[3]
Malignant peripheral nerve sheath tumor	DIS0JTN6	Strong	Biomarker	[4]
Mucinous adenocarcinoma	DISKNFE8	Strong	Biomarker	[5]
Neoplasm	DISZKGEW	Strong	Biomarker	[6]
Schizoaffective disorder	DISLBW6B	Strong	Biomarker	[7]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[2]
Carcinoma	DISH9F1N	moderate	Biomarker	[8]
Megalencephaly	DISYW5SV	Limited	Genetic Variation	[9]

This DOT Affected the Regulation of Drug Effects of 4 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Liothyronine	DM6IR3P	Approved	Sulfotransferase 4A1 (SULT4A1) increases the metabolism of Liothyronine.	[16]
Estrone	DM5T6US	Approved	Sulfotransferase 4A1 (SULT4A1) increases the metabolism of Estrone.	[16]
Mononitrophenol	DM4QO9G	Investigative	Sulfotransferase 4A1 (SULT4A1) increases the metabolism of Mononitrophenol.	[16]
L-thyroxine	DM83HWL	Investigative	Sulfotransferase 4A1 (SULT4A1) increases the metabolism of L-thyroxine.	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Sulfotransferase 4A1 (SULT4A1).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Sulfotransferase 4A1 (SULT4A1).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Sulfotransferase 4A1 (SULT4A1).	[11]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Sulfotransferase 4A1 (SULT4A1).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Sulfotransferase 4A1 (SULT4A1).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Sulfotransferase 4A1 (SULT4A1).	[15]

References

• [1] The antithrombotic activity of the active fractions from the fruits of Celastrus orbiculatus Thunb through the anti-coagulation, anti-platelet activation and anti-fibrinolysis pathways.J Ethnopharmacol. 2019 Sep 15;241:111974. doi: 10.1016/j.jep.2019.111974. Epub 2019 May 24.
• [2] Genomic profiling of histological special types of breast cancer.Breast Cancer Res Treat. 2013 Nov;142(2):257-69. doi: 10.1007/s10549-013-2740-6. Epub 2013 Oct 27.
• [3] Transcriptomic analysis of tubular carcinomas of the breast reveals similarities and differences with molecular subtype-matched ductal and lobular carcinomas.J Pathol. 2010 Sep;222(1):64-75. doi: 10.1002/path.2743.
• [4] Neurofibromatosis-associated nerve sheath tumors. Case report and review of the literature.Neurosurg Focus. 2006 Jan 15;20(1):E1. doi: 10.3171/foc.2006.20.1.2.
• [5] Mucinous carcinoma of the breast is genomically distinct from invasive ductal carcinomas of no special type.J Pathol. 2010 Nov;222(3):282-98. doi: 10.1002/path.2763.
• [6] Invasive Duct Carcinoma of the Breast With Dominant Signet-Ring Cell Differentiation: A Microsatellite Stable Tumor With Aggressive Behavior.Appl Immunohistochem Mol Morphol. 2017 Nov/Dec;25(10):720-724. doi: 10.1097/PAI.0000000000000366.
• [7] SULT4A1 haplotype: conflicting results on its role as a biomarker of antipsychotic response.Pharmacogenomics. 2014;15(12):1557-64. doi: 10.2217/pgs.14.105.
• [8] Equivocal (HER2 IHC 2+) breast carcinomas: gene-protein assay testing reveals association between genetic heterogeneity, individual cell amplification status and potential treatment benefits.Histopathology. 2019 Jan;74(2):300-310. doi: 10.1111/his.13733. Epub 2018 Nov 11.
• [9] Interstitial 22q13 deletions not involving SHANK3 gene: a new contiguous gene syndrome.Am J Med Genet A. 2014 Jul;164A(7):1666-76. doi: 10.1002/ajmg.a.36513. Epub 2014 Apr 3.
• [10] Effect of prenatal arsenic exposure on DNA methylation and leukocyte subpopulations in cord blood. Epigenetics. 2014 May;9(5):774-82. doi: 10.4161/epi.28153. Epub 2014 Feb 13.
• [11] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [12] Metabolic patterns and biotransformation activities of resveratrol in human glioblastoma cells: relevance with therapeutic efficacies. PLoS One. 2011;6(11):e27484.
• [13] 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.
• [14] 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.
• [15] 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.
• [16] Highly conserved mouse and human brain sulfotransferases: molecular cloning, expression, and functional characterization. Gene. 2002 Feb 20;285(1-2):39-47. doi: 10.1016/s0378-1119(02)00431-6.