Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3COPVF)

• DOT Name: Serine incorporator 5 (SERINC5)
• Gene Name: SERINC5
• Related Disease:
  leukaemia
  Leukemia
• UniProt ID: SERC5_HUMAN
• Pfam ID: PF03348
• Sequence:
  MSAQCCAGQLACCCGSAGCSLCCDCCPRIRQSLSTRFMYALYFILVVVLCCIMMSTTVAH
  KMKEHIPFFEDMCKGIKAGDTCEKLVGYSAVYRVCFGMACFFFIFCLLTLKINNSKSCRA
  HIHNGFWFFKLLLLGAMCSGAFFIPDQDTFLNAWRYVGAVGGFLFIGIQLLLLVEFAHKW
  NKNWTAGTASNKLWYASLALVTLIMYSIATGGLVLMAVFYTQKDSCMENKILLGVNGGLC
  LLISLVAISPWVQNRQPHSGLLQSGVISCYVTYLTFSALSSKPAEVVLDEHGKNVTICVP
  DFGQDLYRDENLVTILGTSLLIGCILYSCLTSTTRSSSDALQGRYAAPELEIARCCFCFS
  PGGEDTEEQQPGKEGPRVIYDEKKGTVYIYSYFHFVFFLASLYVMMTVTNWFNHVRSAFH
  LLP
• 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. Enhances the incorporation of serine into phosphatidylserine and sphingolipids. May play a role in providing serine molecules for the formation of myelin glycosphingolipids in oligodendrocytes.
• Tissue Specificity: Highly expressed in placenta, skeletal muscle, spleen, thymus, testis and peripheral leukocyte and is expressed weakly in the heart, liver and fetal brain.
• KEGG Pathway: Viral life cycle - HIV-1 (hsa03250)
• Reactome Pathway: Serine biosynthesis (R-HSA-977347)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
leukaemia	DISS7D1V	Limited	Biomarker	[1]
Leukemia	DISNAKFL	Limited	Biomarker	[1]

15 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 Serine incorporator 5 (SERINC5).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Serine incorporator 5 (SERINC5).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Serine incorporator 5 (SERINC5).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Serine incorporator 5 (SERINC5).	[5]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Serine incorporator 5 (SERINC5).	[6]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Serine incorporator 5 (SERINC5).	[8]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Serine incorporator 5 (SERINC5).	[9]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Serine incorporator 5 (SERINC5).	[10]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene decreases the expression of Serine incorporator 5 (SERINC5).	[4]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Serine incorporator 5 (SERINC5).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Serine incorporator 5 (SERINC5).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Serine incorporator 5 (SERINC5).	[15]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Serine incorporator 5 (SERINC5).	[8]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Serine incorporator 5 (SERINC5).	[16]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Serine incorporator 5 (SERINC5).	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Serine incorporator 5 (SERINC5).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Serine incorporator 5 (SERINC5).	[11]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Serine incorporator 5 (SERINC5).	[13]

References

• [1] 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.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [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] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [7] 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.
• [8] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [9] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [12] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [13] 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.
• [14] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
• [15] 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.
• [16] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [17] Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.