Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQ1LAJ1)

• DOT Name: Serine incorporator 3 (SERINC3)
• Synonyms: Tumor differentially expressed protein 1
• Gene Name: SERINC3
• Related Disease:
  Neoplasm
  Prostate cancer
  Prostate neoplasm
  Keratoconus
  leukaemia
  Leukemia
  Neoplasm of testis
• UniProt ID: SERC3_HUMAN
• PDB ID: 7RU6; 7RUG
• Pfam ID: PF03348
• Sequence:
  MGAVLGVFSLASWVPCLCSGASCLLCSCCPNSKNSTVTRLIYAFILLLSTVVSYIMQRKE
  METYLKKIPGFCEGGFKIHEADINADKDCDVLVGYKAVYRISFAMAIFFFVFSLLMFKVK
  TSKDLRAAVHNGFWFFKIAALIGIMVGSFYIPGGYFSSVWFVVGMIGAALFILIQLVLLV
  DFAHSWNESWVNRMEEGNPRLWYAALLSFTSAFYILSIICVGLLYTYYTKPDGCTENKFF
  ISINLILCVVASIISIHPKIQEHQPRSGLLQSSLITLYTMYLTWSAMSNEPDRSCNPNLM
  SFITRITAPTLAPGNSTAVVPTPTPPSKSGSLLDSDNFIGLFVFVLCLLYSSIRTSTNSQ
  VDKLTLSGSDSVILGDTTTSGASDEEDGQPRRAVDNEKEGVQYSYSLFHLMLCLASLYIM
  MTLTSWYSPDAKFQSMTSKWPAVWVKISSSWVCLLLYVWTLVAPLVLTSRDFS
• Function: Restriction factor required to restrict infectivity of lentiviruses, such as HIV-1: acts by inhibiting an early step of viral infection. Impairs the penetration of the viral particle into the cytoplasm.
• Tissue Specificity: Ubiquitous. Expression levels were increased fourfold to tenfold in lung tumor tissues compared with normal pulmonary tissues.
• KEGG Pathway: Viral life cycle - HIV-1 (hsa03250)
• Reactome Pathway: Serine biosynthesis (R-HSA-977347)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Strong	Altered Expression	[1]
Prostate cancer	DISF190Y	Strong	Biomarker	[2]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[2]
Keratoconus	DISOONXH	moderate	Biomarker	[3]
leukaemia	DISS7D1V	Limited	Biomarker	[4]
Leukemia	DISNAKFL	Limited	Biomarker	[4]
Neoplasm of testis	DISK4XHT	Limited	Altered Expression	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Serine incorporator 3 (SERINC3).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Serine incorporator 3 (SERINC3).	[7]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Serine incorporator 3 (SERINC3).	[8]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Serine incorporator 3 (SERINC3).	[9]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Serine incorporator 3 (SERINC3).	[10]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Serine incorporator 3 (SERINC3).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Serine incorporator 3 (SERINC3).	[11]

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 genes potentially involved in the acquisition of androgen-independent and metastatic tumor growth in an autochthonous genetically engineered mouse prostate cancer model.Prostate. 2007 Jan 1;67(1):83-106. doi: 10.1002/pros.20505.
• [3] Genetic epidemiological study of keratoconus: evidence for major gene determination.Am J Med Genet. 2000 Aug 28;93(5):403-9.
• [4] Potent Enhancement of HIV-1 Replication by Nef in the Absence of SERINC3 and SERINC5.mBio. 2019 Jun 11;10(3):e01071-19. doi: 10.1128/mBio.01071-19.
• [5] 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.
• [6] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [7] 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.
• [8] Nicotinic modulation of gene expression in SH-SY5Y neuroblastoma cells. Brain Res. 2006 Oct 20;1116(1):39-49.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [11] 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.
• [12] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.