Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTA75FET)

• DOT Name: SEC14-like protein 1 (SEC14L1)
• Gene Name: SEC14L1
• Related Disease:
  Breast cancer
  Breast carcinoma
  Neoplasm
  Ovarian neoplasm
  Prostate cancer
  Retinitis pigmentosa
  Prostate carcinoma
  Tuberculosis
  Advanced cancer
• UniProt ID: S14L1_HUMAN
• Pfam ID: PF00650 ; PF03765 ; PF04707
• Sequence:
  MVQKYQSPVRVYKYPFELIMAAYERRFPTCPLIPMFVGSDTVNEFKSEDGAIHVIERRCK
  LDVDAPRLLKKIAGVDYVYFVQKNSLNSRERTLHIEAYNETFSNRVIINEHCCYTVHPEN
  EDWTCFEQSASLDIKSFFGFESTVEKIAMKQYTSNIKKGKEIIEYYLRQLEEEGITFVPR
  WSPPSITTSSETSSSSSKKQAASMAVVIPEAALKEGLSGDALSSPSAPEPVVGTPDDKLD
  ADYIKRYLGDLTPLQESCLIRLRQWLQETHKGKIPKDEHILRFLRARDFNIDKAREIMCQ
  SLTWRKQHQVDYILETWTPPQVLQDYYAGGWHHHDKDGRPLYVLRLGQMDTKGLVRALGE
  EALLRYVLSINEEGLRRCEENTKVFGRPISSWTCLVDLEGLNMRHLWRPGVKALLRIIEV
  VEANYPETLGRLLILRAPRVFPVLWTLVSPFIDDNTRRKFLIYAGNDYQGPGGLLDYIDK
  EIIPDFLSGECMCEVPEGGLVPKSLYRTAEELENEDLKLWTETIYQSASVFKGAPHEILI
  QIVDASSVITWDFDVCKGDIVFNIYHSKRSPQPPKKDSLGAHSITSPGGNNVQLIDKVWQ
  LGRDYSMVESPLICKEGESVQGSHVTRWPGFYILQWKFHSMPACAASSLPRVDDVLASLQ
  VSSHKCKVMYYTEVIGSEDFRGSMTSLESSHSGFSQLSAATTSSSQSHSSSMISR
• Function: May play a role in innate immunity by inhibiting the antiviral RIG-I signaling pathway. In this pathway, functions as a negative regulator of RIGI, the cytoplasmic sensor of viral nucleic acids. Prevents the interaction of RIGI with MAVS/IPS1, an important step in signal propagation. May also regulate the SLC18A3 and SLC5A7 cholinergic transporters.
• Tissue Specificity: Ubiquitous.

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Altered Expression	[1]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[1]
Neoplasm	DISZKGEW	Strong	Altered Expression	[2]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[3]
Prostate cancer	DISF190Y	Strong	Biomarker	[2]
Retinitis pigmentosa	DISCGPY8	Strong	Altered Expression	[3]
Prostate carcinoma	DISMJPLE	moderate	Biomarker	[4]
Tuberculosis	DIS2YIMD	Disputed	Genetic Variation	[5]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[2]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	SEC14-like protein 1 (SEC14L1) affects the response to substance of Fluorouracil.	[20]
Topotecan	DMP6G8T	Approved	SEC14-like protein 1 (SEC14L1) affects the response to substance of Topotecan.	[20]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of SEC14-like protein 1 (SEC14L1).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of SEC14-like protein 1 (SEC14L1).	[17]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of SEC14-like protein 1 (SEC14L1).	[18]

11 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 SEC14-like protein 1 (SEC14L1).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of SEC14-like protein 1 (SEC14L1).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of SEC14-like protein 1 (SEC14L1).	[9]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of SEC14-like protein 1 (SEC14L1).	[10]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of SEC14-like protein 1 (SEC14L1).	[11]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of SEC14-like protein 1 (SEC14L1).	[12]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of SEC14-like protein 1 (SEC14L1).	[13]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of SEC14-like protein 1 (SEC14L1).	[14]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of SEC14-like protein 1 (SEC14L1).	[15]
Seocalcitol	DMKL9QO	Phase 3	Seocalcitol increases the expression of SEC14-like protein 1 (SEC14L1).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of SEC14-like protein 1 (SEC14L1).	[19]

References

• [1] Saccharomyces cerevisiae-like 1 (SEC14L1) is a prognostic factor in breast cancer associated with lymphovascular invasion.Mod Pathol. 2018 Nov;31(11):1675-1682. doi: 10.1038/s41379-018-0092-9. Epub 2018 Jun 28.
• [2] Saccharomyces cerevisiae-like 1 overexpression is frequent in prostate cancer and has markedly different effects in Ets-related gene fusion-positive and fusion-negative cancers.Hum Pathol. 2015 Apr;46(4):514-23. doi: 10.1016/j.humpath.2014.06.006. Epub 2014 Jun 26.
• [3] Genomic characterization of human SEC14L1 splice variants within a 17q25 candidate tumor suppressor gene region and identification of an unrelated embedded expressed sequence tag.Mamm Genome. 2001 Dec;12(12):925-9. doi: 10.1007/s00335-001-2073-3.
• [4] A 12-gene expression signature is associated with aggressive histological in prostate cancer: SEC14L1 and TCEB1 genes are potential markers of progression.Am J Pathol. 2012 Nov;181(5):1585-94. doi: 10.1016/j.ajpath.2012.08.005.
• [5] Identification of biomarkers for Mycobacterium tuberculosis infection and disease in BCG-vaccinated young children in Southern India.Genes Immun. 2013 Sep;14(6):356-64. doi: 10.1038/gene.2013.26. Epub 2013 May 16.
• [6] 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.
• [7] 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.
• [8] 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.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [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] Gene expression in endometrial cancer cells (Ishikawa) after short time high dose exposure to progesterone. Steroids. 2008 Jan;73(1):116-28.
• [13] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [14] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [15] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [16] Expression profiling in squamous carcinoma cells reveals pleiotropic effects of vitamin D3 analog EB1089 signaling on cell proliferation, differentiation, and immune system regulation. Mol Endocrinol. 2002 Jun;16(6):1243-56.
• [17] 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.
• [18] 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.
• [19] Characterization of the Molecular Alterations Induced by the Prolonged Exposure of Normal Colon Mucosa and Colon Cancer Cells to Low-Dose Bisphenol A. Int J Mol Sci. 2022 Oct 1;23(19):11620. doi: 10.3390/ijms231911620.
• [20] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.