Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSIZY2T)

• DOT Name: Transmembrane protein 164 (TMEM164)
• Gene Name: TMEM164
• UniProt ID: TM164_HUMAN
• Pfam ID: PF14808
• Sequence:
  MSRYSYQSLLDWLYGGVDPSFAGNGGPDCAAFLSWQQRLLESVVVLTLALLEILVALRHI
  LRQTKEDGRGSPGSQPEQVTQRPEEGKESLSKNLLLVALCLTFGVEVGFKFATKTVIYLL
  NPCHLVTMMHIFLLACPPCRGAIVVFKLQMHMLNGALLALLFPVVNTRLLPFELEIYYIQ
  HVMLYVVPIYLLWKGGAYTPEPLSSFRWALLSTGLMFFYHFSVLQILGLVTEVNLNNMLC
  PAISDPFYGPWYRIWASGHQTLMTMTHGKLVILFSYMAGPLCKYLLDLLRLPAKKID
• Function: Positive regulator of ferroptosis. Selectively mediates ATG5-dependent autophagosome formation during ferroptosis, rather than during starvation, and regulates the degradation of ferritin, GPX4 and lipid droplets to increase iron accumulation and lipid peroxidation, thereby promoting ferroptotic cell death.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Transmembrane protein 164 (TMEM164).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Transmembrane protein 164 (TMEM164).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Transmembrane protein 164 (TMEM164).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Transmembrane protein 164 (TMEM164).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Transmembrane protein 164 (TMEM164).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Transmembrane protein 164 (TMEM164).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Transmembrane protein 164 (TMEM164).	[5]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Transmembrane protein 164 (TMEM164).	[6]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Transmembrane protein 164 (TMEM164).	[7]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Transmembrane protein 164 (TMEM164).	[8]
ORG2058	DMH1M6N	Investigative	ORG2058 increases the expression of Transmembrane protein 164 (TMEM164).	[11]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [2] 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.
• [3] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [4] 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.
• [5] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [6] Effects of progesterone treatment on expression of genes involved in uterine quiescence. Reprod Sci. 2011 Aug;18(8):781-97.
• [7] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] The antiproliferative effects of progestins in T47D breast cancer cells are tempered by progestin induction of the ETS transcription factor Elf5. Mol Endocrinol. 2010 Jul;24(7):1380-92. doi: 10.1210/me.2009-0516. Epub 2010 Jun 2.