Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTER1D66)

• DOT Name: Spermatogenesis-associated protein 2-like protein (SPATA2L)
• Synonyms: SPATA2-like protein
• Gene Name: SPATA2L
• UniProt ID: SPA2L_HUMAN
• Pfam ID: PF21388
• Sequence:
  MGSSSLSEDYRQCLERELRRGRAGVCGDPSLRAVLWQILVEDFDLHGALQDDALALLTDG
  LWGRADLAPALRGLARAFELLELAAVHLYLLPWRKEFTTIKTFSGGYVHVLKGVLSDDLL
  LKSFQKMGYVRRDSHRLMVTALPPACQLVQVALGCFALRLECEILGEVLAQLGTSVLPAE
  ELLQARRASGDVASCVAWLQQRLAQDEEPPPLPPRGSPAAYRAPLDLYRDLQEDEGSEDA
  SLYGEPSPGPDSPPAELAYRPPLWEQSAKLWGTGGRAWEPPAEELPQASSPPYGALEEGL
  EPEPSAFSFLSLRRELSRPGDLATPESSAAASPRRIRAEGVPASAYRSVSEPPGYQAHSC
  LSPGALPTLCCDTCRQLHAAHCAALPACRPGHSLRVLLGDAQRRLWLQRAQMDTLLYNSP
  GARP
• KEGG Pathway: Necroptosis (hsa04217)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Spermatogenesis-associated protein 2-like protein (SPATA2L).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Spermatogenesis-associated protein 2-like protein (SPATA2L).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Spermatogenesis-associated protein 2-like protein (SPATA2L).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Spermatogenesis-associated protein 2-like protein (SPATA2L).	[4]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Spermatogenesis-associated protein 2-like protein (SPATA2L).	[5]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Spermatogenesis-associated protein 2-like protein (SPATA2L).	[6]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Spermatogenesis-associated protein 2-like protein (SPATA2L).	[7]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Spermatogenesis-associated protein 2-like protein (SPATA2L).	[8]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Spermatogenesis-associated protein 2-like protein (SPATA2L).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Spermatogenesis-associated protein 2-like protein (SPATA2L).	[9]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] 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.
• [6] 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.
• [7] Changes in gene expressions elicited by physiological concentrations of genistein on human endometrial cancer cells. Mol Carcinog. 2006 Oct;45(10):752-63.
• [8] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [9] 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.
• [10] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.