Details of Drug Off-Target (DOT)

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

• DOT Name: Small EDRK-rich factor 2 (SERF2)
• Synonyms: Gastric cancer-related protein VRG107; Protein 4F5-related; 4F5rel; h4F5rel
• Gene Name: SERF2
• Related Disease: Neuroblastoma
• UniProt ID: SERF2_HUMAN
• Pfam ID: PF04419
• Sequence: MTRGNQRELARQKNMKKQSDSVKGKRRDDGLSAAARKQRDSEIMQQKQKKANEKKEEPK
• Function: Positive regulator of amyloid protein aggregation and proteotoxicity. Induces conformational changes in amyloid proteins, such as HTT, driving them into compact formations preceding the formation of aggregates.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neuroblastoma	DISVZBI4	Limited	Biomarker	[1]

11 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 Small EDRK-rich factor 2 (SERF2).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Small EDRK-rich factor 2 (SERF2).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Small EDRK-rich factor 2 (SERF2).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Small EDRK-rich factor 2 (SERF2).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Small EDRK-rich factor 2 (SERF2).	[6]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Small EDRK-rich factor 2 (SERF2).	[7]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Small EDRK-rich factor 2 (SERF2).	[8]
Mifepristone	DMGZQEF	Approved	Mifepristone increases the expression of Small EDRK-rich factor 2 (SERF2).	[9]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Small EDRK-rich factor 2 (SERF2).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Small EDRK-rich factor 2 (SERF2).	[12]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Small EDRK-rich factor 2 (SERF2).	[13]

1 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 decreases the methylation of Small EDRK-rich factor 2 (SERF2).	[11]

References

• [1] Structural insights into pro-aggregation effects of C. elegans CRAM-1 and its human ortholog SERF2.Sci Rep. 2018 Oct 5;8(1):14891. doi: 10.1038/s41598-018-33143-1.
• [2] 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.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [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] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [8] Pharmacogenomic identification of novel determinants of response to chemotherapy in colon cancer. Cancer Res. 2006 Mar 1;66(5):2765-77.
• [9] Mifepristone induced progesterone withdrawal reveals novel regulatory pathways in human endometrium. Mol Hum Reprod. 2007 Sep;13(9):641-54.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] 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.
• [12] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [13] Molecular targets of chloropicrin in human airway epithelial cells. Toxicol In Vitro. 2017 Aug;42:247-254.