Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZ039U0)

• DOT Name: Serine incorporator 2 (SERINC2)
• Synonyms: Tumor differentially expressed protein 2-like
• Gene Name: SERINC2
• Related Disease:
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Autism spectrum disorder
  Hepatocellular carcinoma
  Neoplasm
  Pervasive developmental disorder
  Alcohol dependence
  Alcohol-induced disorders
  Alcohol-related disorders
  Lung neoplasm
  Neoplasm of testis
  Non-small-cell lung cancer
• UniProt ID: SERC2_HUMAN
• Pfam ID: PF03348
• Sequence:
  MGACLGACSLLSCASCLCGSAPCILCSCCPASRNSTVSRLIFTFFLFLGVLVSIIMLSPG
  VESQLYKLPWVCEEGAGIPTVLQGHIDCGSLLGYRAVYRMCFATAAFFFFFTLLMLCVSS
  SRDPRAAIQNGFWFFKFLILVGLTVGAFYIPDGSFTNIWFYFGVVGSFLFILIQLVLLID
  FAHSWNQRWLGKAEECDSRAWYAGLFFFTLLFYLLSIAAVALMFMYYTEPSGCHEGKVFI
  SLNLTFCVCVSIAAVLPKVQDAQPNSGLLQASVITLYTMFVTWSALSSIPEQKCNPHLPT
  QLGNETVVAGPEGYETQWWDAPSIVGLIIFLLCTLFISLRSSDHRQVNSLMQTEECPPML
  DATQQQQQVAACEGRAFDNEQDGVTYSYSFFHFCLVLASLHVMMTLTNWYKPGETRKMIS
  TWTAVWVKICASWAGLLLYLWTLVAPLLLRNRDFS
• Reactome Pathway: Serine biosynthesis (R-HSA-977347)

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lung adenocarcinoma	DISD51WR	Definitive	Altered Expression	[1]
Lung cancer	DISCM4YA	Definitive	Altered Expression	[1]
Lung carcinoma	DISTR26C	Definitive	Altered Expression	[1]
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[3]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Pervasive developmental disorder	DIS51975	Strong	Biomarker	[2]
Alcohol dependence	DIS4ZSCO	moderate	Genetic Variation	[4]
Alcohol-induced disorders	DIS3SFYT	moderate	Genetic Variation	[4]
Alcohol-related disorders	DIS3K4KK	moderate	Genetic Variation	[4]
Lung neoplasm	DISVARNB	Limited	Altered Expression	[5]
Neoplasm of testis	DISK4XHT	Limited	Biomarker	[5]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Altered Expression	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Serine incorporator 2 (SERINC2).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Serine incorporator 2 (SERINC2).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Serine incorporator 2 (SERINC2).	[8]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Serine incorporator 2 (SERINC2).	[9]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Serine incorporator 2 (SERINC2).	[10]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Serine incorporator 2 (SERINC2).	[11]
Marinol	DM70IK5	Approved	Marinol increases the expression of Serine incorporator 2 (SERINC2).	[12]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Serine incorporator 2 (SERINC2).	[13]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Serine incorporator 2 (SERINC2).	[14]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of Serine incorporator 2 (SERINC2).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Serine incorporator 2 (SERINC2).	[16]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Serine incorporator 2 (SERINC2).	[18]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Serine incorporator 2 (SERINC2).	[17]

References

• [1] SERINC2-knockdown inhibits proliferation, migration and invasion in lung adenocarcinoma.Oncol Lett. 2018 Nov;16(5):5916-5922. doi: 10.3892/ol.2018.9403. Epub 2018 Sep 5.
• [2] Chromosomal microarray analysis in a cohort of underrepresented population identifies SERINC2 as a novel candidate gene for autism spectrum disorder.Sci Rep. 2017 Sep 21;7(1):12096. doi: 10.1038/s41598-017-12317-3.
• [3] 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.
• [4] NKAIN1-SERINC2 is a functional, replicable and genome-wide significant risk gene region specific for alcohol dependence in subjects of European descent.Drug Alcohol Depend. 2013 May 1;129(3):254-64. doi: 10.1016/j.drugalcdep.2013.02.006. Epub 2013 Feb 28.
• [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] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [7] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [10] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [11] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [12] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [13] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [14] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [15] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [16] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [17] 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.
• [18] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.