Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDLEXH4)

• DOT Name: Single-pass membrane and coiled-coil domain-containing protein 4 (SMCO4)
• Synonyms: Protein FN5
• Gene Name: SMCO4
• UniProt ID: SMCO4_HUMAN
• Pfam ID: PF15012
• Sequence: MRQLKGKPKKETSKDKKERKQAMQEARQQITTVVLPTLAVVVLLIVVFVYVATRPTITE

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Single-pass membrane and coiled-coil domain-containing protein 4 (SMCO4) affects the response to substance of Doxorubicin.	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Single-pass membrane and coiled-coil domain-containing protein 4 (SMCO4).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Single-pass membrane and coiled-coil domain-containing protein 4 (SMCO4).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Single-pass membrane and coiled-coil domain-containing protein 4 (SMCO4).	[12]

10 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 Single-pass membrane and coiled-coil domain-containing protein 4 (SMCO4).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Single-pass membrane and coiled-coil domain-containing protein 4 (SMCO4).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Single-pass membrane and coiled-coil domain-containing protein 4 (SMCO4).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Single-pass membrane and coiled-coil domain-containing protein 4 (SMCO4).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Single-pass membrane and coiled-coil domain-containing protein 4 (SMCO4).	[6]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Single-pass membrane and coiled-coil domain-containing protein 4 (SMCO4).	[7]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Single-pass membrane and coiled-coil domain-containing protein 4 (SMCO4).	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Single-pass membrane and coiled-coil domain-containing protein 4 (SMCO4).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Single-pass membrane and coiled-coil domain-containing protein 4 (SMCO4).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Single-pass membrane and coiled-coil domain-containing protein 4 (SMCO4).	[13]

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] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [6] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [7] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [8] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] 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.
• [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] 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.
• [13] 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.
• [14] 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.