Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTP49B2R)

DOT Name	Meiotic recombination protein SPO11 (SPO11)
Synonyms	EC 5.6.2.2; Cancer/testis antigen 35; CT35
Gene Name	SPO11
Related Disease	Malaria ( ) Azoospermia ( ) Male infertility ( ) Oligospermia ( ) Female hypogonadism ( )
UniProt ID	SPO11_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
EC Number	5.6.2.2
Pfam ID	PF03533 ; PF21180 ; PF04406
Sequence	MAFAPMGPEASFFDVLDRHRESLLAALRRGGREPPTGGSRLASSSEVLASIENIIQDIIT SLARNEAPAFTIDNRSSWENIKFEDSVGLQMVSHCTTRKIKSDSPKSAQKFSLILKILSM IYKLVQSNTYATKRDIYYTDSQLFGNQTVVDNIINDISCMLKVSRRSLHILSTSKGLIAG NLRYIEEDGTKVNCTCGATAVAVPSNIQGIRNLVTDAKFVLIVEKDATFQRLLDDNFCNK LSPCIMITGKGVPDLNTRLLVKKLWDTFHVPVFTLVDADPHGIEIMCIYKYGSMSMSFEA HHLTVPAIRWLGLLPSDLKRLNVPKDSLIPLTKRDQMKLDSILRRPYVTCQPFWRKEMEI MADSKMKAEIQALTFLSSDYLSRVYLPNKLKFGGWI
Function	Component of a topoisomerase 6 complex specifically required for meiotic recombination. Together with TOP6BL, mediates DNA cleavage that forms the double-strand breaks (DSB) that initiate meiotic recombination. The complex promotes relaxation of negative and positive supercoiled DNA and DNA decatenation through cleavage and ligation cycles. Essential for the phosphorylation of SMC3, HORMAD1 and HORMAD2.
Tissue Specificity	Highly expressed in testis.
Reactome Pathway	Meiotic recombination (R-HSA-912446 )

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Malaria	DISQ9Y50	Definitive	Biomarker	[1]
Azoospermia	DIS94181	Strong	Genetic Variation	[2]
Male infertility	DISY3YZZ	Strong	Genetic Variation	[3]
Oligospermia	DIS6YJF3	Strong	Genetic Variation	[4]
Female hypogonadism	DISWASB4	moderate	Genetic Variation	[5]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Meiotic recombination protein SPO11 (SPO11).	[6]
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3 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Meiotic recombination protein SPO11 (SPO11).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Meiotic recombination protein SPO11 (SPO11).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Meiotic recombination protein SPO11 (SPO11).	[9]
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References

1	Multifunctional Involvement of a C2H2 Zinc Finger Protein (PbZfp) in Malaria Transmission, Histone Modification, and Susceptibility to DNA Damage Response.mBio. 2017 Aug 29;8(4):e01298-17. doi: 10.1128/mBio.01298-17.
2	Study of single nucleotide polymorphism (rs28368082) in SPO11 gene and its association with male infertility.J Assist Reprod Genet. 2014 Sep;31(9):1205-10. doi: 10.1007/s10815-014-0279-z. Epub 2014 Jul 9.
3	The SPO11-C631T gene polymorphism and male infertility risk: a meta-analysis.Ren Fail. 2017 Nov;39(1):299-305. doi: 10.1080/0886022X.2016.1274661. Epub 2017 Jan 4.
4	A segregating human allele of SPO11 modeled in mice disrupts timing and amounts of meiotic recombination, causing oligospermia and a decreased ovarian reserve?,Tran TN.Biol Reprod. 2019 Aug 1;101(2):347-359. doi: 10.1093/biolre/ioz089.
5	Genetic investigation of four meiotic genes in women with premature ovarian failure.Eur J Endocrinol. 2008 Jan;158(1):107-15. doi: 10.1530/EJE-07-0400.
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	Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
8	Gene expression changes associated with altered growth and differentiation in benzo[a]pyrene or arsenic exposed normal human epidermal keratinocytes. J Appl Toxicol. 2008 May;28(4):491-508.
9	Gene expression is altered after bisphenol A exposure in human fetal oocytes in vitro. Mol Hum Reprod. 2012 Apr;18(4):171-83. doi: 10.1093/molehr/gar074. Epub 2011 Nov 25.