Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0RHMNG)

• DOT Name: Chemokine-like protein TAFA-4 (TAFA4)
• Gene Name: TAFA4
• Related Disease:
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Carcinoma
  Advanced cancer
  Prostate cancer
  Prostate carcinoma
• UniProt ID: TAFA4_HUMAN
• Pfam ID: PF12020
• Sequence:
  MRSPRMRVCAKSVLLSHWLFLAYVLMVCCKLMSASSQHLRGHAGHHQIKQGTCEVVAVHR
  CCNKNRIEERSQTVKCSCFPGQVAGTTRAQPSCVEASIVIQKWWCHMNPCLEGEDCKVLP
  DYSGWSCSSGNKVKTTKVTR
• Function: Modulates injury-induced and chemical pain hypersensitivity. Ligand of FPR1, can chemoattract macrophages, promote phagocytosis and increase ROS release.
• Tissue Specificity: Expressed in brain . Expressed in LPS-stimulated monocytes and macrophages, especially in polarized M1 .

Molecular Interaction Atlas (MIA) of This DOT

7 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]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[1]
Carcinoma	DISH9F1N	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	Limited	Posttranslational Modification	[3]
Prostate cancer	DISF190Y	Limited	Biomarker	[4]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Chemokine-like protein TAFA-4 (TAFA4).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Chemokine-like protein TAFA-4 (TAFA4).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Chemokine-like protein TAFA-4 (TAFA4).	[7]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Chemokine-like protein TAFA-4 (TAFA4).	[8]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Chemokine-like protein TAFA-4 (TAFA4).	[9]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Chemokine-like protein TAFA-4 (TAFA4).	[10]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Chemokine-like protein TAFA-4 (TAFA4).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Chemokine-like protein TAFA-4 (TAFA4).	[14]

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 Chemokine-like protein TAFA-4 (TAFA4).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Chemokine-like protein TAFA-4 (TAFA4).	[13]

References

• [1] Identification of 20 genes aberrantly methylated in human breast cancers.Int J Cancer. 2005 Sep 1;116(3):407-14. doi: 10.1002/ijc.21054.
• [2] Methylation analysis of the FAM19A4 gene in cervical scrapes is highly efficient in detecting cervical carcinomas and advanced CIN2/3 lesions.Cancer Prev Res (Phila). 2014 Dec;7(12):1251-7. doi: 10.1158/1940-6207.CAPR-14-0237. Epub 2014 Oct 3.
• [3] Intra- and inter-laboratory agreement of the FAM19A4/mir124-2 methylation test: Results from an international study.J Clin Lab Anal. 2019 May;33(4):e22854. doi: 10.1002/jcla.22854. Epub 2019 Feb 13.
• [4] Identification of Novel Epigenetic Markers of Prostate Cancer by NotI-Microarray Analysis.Dis Markers. 2015;2015:241301. doi: 10.1155/2015/241301. Epub 2015 Sep 28.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [6] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [7] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [8] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [9] Cardiac toxicity from ethanol exposure in human-induced pluripotent stem cell-derived cardiomyocytes. Toxicol Sci. 2019 May 1;169(1):280-292.
• [10] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [11] 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.
• [12] 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.
• [13] 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.
• [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.