Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTF3UASX)

• DOT Name: Serine incorporator 1 (SERINC1)
• Synonyms: Tumor differentially expressed protein 1-like; Tumor differentially expressed protein 2
• Gene Name: SERINC1
• Related Disease:
  Hepatocellular carcinoma
  Neoplasm
  Lung neoplasm
  Neoplasm of testis
  Non-small-cell lung cancer
• UniProt ID: SERC1_HUMAN
• Pfam ID: PF03348
• Sequence:
  MGSVLGLCSMASWIPCLCGSAPCLLCRCCPSGNNSTVTRLIYALFLLVGVCVACVMLIPG
  MEEQLNKIPGFCENEKGVVPCNILVGYKAVYRLCFGLAMFYLLLSLLMIKVKSSSDPRAA
  VHNGFWFFKFAAAIAIIIGAFFIPEGTFTTVWFYVGMAGAFCFILIQLVLLIDFAHSWNE
  SWVEKMEEGNSRCWYAALLSATALNYLLSLVAIVLFFVYYTHPASCSENKAFISVNMLLC
  VGASVMSILPKIQESQPRSGLLQSSVITVYTMYLTWSAMTNEPETNCNPSLLSIIGYNTT
  STVPKEGQSVQWWHAQGIIGLILFLLCVFYSSIRTSNNSQVNKLTLTSDESTLIEDGGAR
  SDGSLEDGDDVHRAVDNERDGVTYSYSFFHFMLFLASLYIMMTLTNWYRYEPSREMKSQW
  TAVWVKISSSWIGIVLYVWTLVAPLVLTNRDFD
• Function: Enhances the incorporation of serine into phosphatidylserine and sphingolipids.
• Reactome Pathway: Serine biosynthesis (R-HSA-977347)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Lung neoplasm	DISVARNB	Limited	Altered Expression	[2]
Neoplasm of testis	DISK4XHT	Limited	Biomarker	[2]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Altered Expression	[2]

2 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 Serine incorporator 1 (SERINC1).	[3]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Serine incorporator 1 (SERINC1).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Serine incorporator 1 (SERINC1).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Serine incorporator 1 (SERINC1).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Serine incorporator 1 (SERINC1).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin increases the expression of Serine incorporator 1 (SERINC1).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Serine incorporator 1 (SERINC1).	[8]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Serine incorporator 1 (SERINC1).	[9]
Marinol	DM70IK5	Approved	Marinol increases the expression of Serine incorporator 1 (SERINC1).	[10]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Serine incorporator 1 (SERINC1).	[11]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of Serine incorporator 1 (SERINC1).	[12]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Serine incorporator 1 (SERINC1).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Serine incorporator 1 (SERINC1).	[14]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Serine incorporator 1 (SERINC1).	[11]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Serine incorporator 1 (SERINC1).	[15]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Serine incorporator 1 (SERINC1).	[17]

References

• [1] siRNA-mediated knockdown of hTDE2 retards cell cycle progression through transcriptional activation of p21.Oncol Rep. 2014 Mar;31(3):1314-22. doi: 10.3892/or.2014.2980. Epub 2014 Jan 14.
• [2] Identification of TDE2 gene and its expression in non-small cell lung cancer.Int J Cancer. 2003 Nov 1;107(2):238-43. doi: 10.1002/ijc.11391.
• [3] 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.
• [4] 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.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [8] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [9] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [10] JunD is involved in the antiproliferative effect of Delta9-tetrahydrocannabinol on human breast cancer cells. Oncogene. 2008 Aug 28;27(37):5033-44.
• [11] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [12] Toxicoproteomics reveals an effect of clozapine on autophagy in human liver spheroids. Toxicol Mech Methods. 2023 Jun;33(5):401-410. doi: 10.1080/15376516.2022.2156005. Epub 2022 Dec 19.
• [13] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [14] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [15] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [16] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [17] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.