Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKL1FNX)

• DOT Name: ATP-dependent RNA helicase DDX3Y (DDX3Y)
• Synonyms: EC 3.6.4.13; DEAD box protein 3, Y-chromosomal
• Gene Name: DDX3Y
• Related Disease:
  46,XY complete gonadal dysgenesis
  Advanced cancer
  Azoospermia
  Complete androgen insensitivity syndrome
  Disorder of sexual differentiation
  Graft-versus-host disease
  Neoplasm
  Oligospermia
  Seminoma
  Chronic obstructive pulmonary disease
  Immune system disorder
• UniProt ID: DDX3Y_HUMAN
• EC Number: 3.6.4.13
• Pfam ID: PF00270 ; PF00271
• Sequence:
  MSHVVVKNDPELDQQLANLDLNSEKQSGGASTASKGRYIPPHLRNREASKGFHDKDSSGW
  SCSKDKDAYSSFGSRDSRGKPGYFSERGSGSRGRFDDRGRSDYDGIGNRERPGFGRFERS
  GHSRWCDKSVEDDWSKPLPPSERLEQELFSGGNTGINFEKYDDIPVEATGSNCPPHIENF
  SDIDMGEIIMGNIELTRYTRPTPVQKHAIPIIKGKRDLMACAQTGSGKTAAFLLPILSQI
  YTDGPGEALKAVKENGRYGRRKQYPISLVLAPTRELAVQIYEEARKFSYRSRVRPCVVYG
  GADIGQQIRDLERGCHLLVATPGRLVDMMERGKIGLDFCKYLVLDEADRMLDMGFEPQIR
  RIVEQDTMPPKGVRHTMMFSATFPKEIQMLARDFLDEYIFLAVGRVGSTSENITQKVVWV
  EDLDKRSFLLDILGATGSDSLTLVFVETKKGADSLEDFLYHEGYACTSIHGDRSQRDREE
  ALHQFRSGKSPILVATAVAARGLDISNVRHVINFDLPSDIEEYVHRIGRTGRVGNLGLAT
  SFFNEKNMNITKDLLDLLVEAKQEVPSWLENMAYEHHYKGGSRGRSKSNRFSGGFGARDY
  RQSSGSSSSGFGASRGSSSRSGGGGYGNSRGFGGGGYGGFYNSDGYGGNYNSQGVDWWGN
• Function: Probable ATP-dependent RNA helicase. During immune response, may enhance IFNB1 expression via IRF3/IRF7 pathway.
• Tissue Specificity: Widely expressed at the mRNA level, with highest levels in testis . Testis-specific (at protein level). Expressed predominantly in spermatogonia, but occasionally detected in some pre-leptotene/leptotene spermatocytes .

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
46,XY complete gonadal dysgenesis	DISLF3LT	Strong	Genetic Variation	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Azoospermia	DIS94181	Strong	Genetic Variation	[2]
Complete androgen insensitivity syndrome	DISQL418	Strong	Biomarker	[1]
Disorder of sexual differentiation	DISRMAEZ	Strong	Biomarker	[1]
Graft-versus-host disease	DIS0QADF	Strong	Biomarker	[3]
Neoplasm	DISZKGEW	Strong	Altered Expression	[4]
Oligospermia	DIS6YJF3	Strong	Altered Expression	[5]
Seminoma	DIS3J8LJ	Strong	Biomarker	[6]
Chronic obstructive pulmonary disease	DISQCIRF	moderate	Biomarker	[7]
Immune system disorder	DISAEGPH	moderate	Biomarker	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of ATP-dependent RNA helicase DDX3Y (DDX3Y).	[9]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of ATP-dependent RNA helicase DDX3Y (DDX3Y).	[10]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of ATP-dependent RNA helicase DDX3Y (DDX3Y).	[11]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of ATP-dependent RNA helicase DDX3Y (DDX3Y).	[12]
Selenium	DM25CGV	Approved	Selenium decreases the expression of ATP-dependent RNA helicase DDX3Y (DDX3Y).	[13]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of ATP-dependent RNA helicase DDX3Y (DDX3Y).	[12]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of ATP-dependent RNA helicase DDX3Y (DDX3Y).	[14]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene decreases the expression of ATP-dependent RNA helicase DDX3Y (DDX3Y).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of ATP-dependent RNA helicase DDX3Y (DDX3Y).	[16]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of ATP-dependent RNA helicase DDX3Y (DDX3Y).	[17]

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 decreases the methylation of ATP-dependent RNA helicase DDX3Y (DDX3Y).	[15]

References

• [1] Gonadoblastoma Y locus genes expressed in germ cells of individuals with dysgenetic gonads and a Y chromosome in their karyotypes include DDX3Y and TSPY.Hum Reprod. 2019 Apr 1;34(4):770-779. doi: 10.1093/humrep/dez004.
• [2] Progress in understanding the molecular functions of DDX3Y (DBY) in male germ cell development and maintenance.Biosci Trends. 2017 Mar 22;11(1):46-53. doi: 10.5582/bst.2016.01216. Epub 2017 Feb 12.
• [3] The DBY gene codes for an HLA-DQ5-restricted human male-specific minor histocompatibility antigen involved in graft-versus-host disease.Blood. 2002 Apr 15;99(8):3027-32. doi: 10.1182/blood.v99.8.3027.
• [4] Chaperone protein HSC70 regulates intercellular transfer of Y chromosome antigen DBY.J Clin Invest. 2019 Jun 17;129(7):2952-2963. doi: 10.1172/JCI123105. eCollection 2019 Jun 17.
• [5] Quantification of DDX3Y, RBMY1, DAZ and TSPY mRNAs in testes of patients with severe impairment of spermatogenesis.Mol Hum Reprod. 2007 Oct;13(10):705-12. doi: 10.1093/molehr/gam057. Epub 2007 Sep 19.
• [6] AZFa protein DDX3Y is differentially expressed in human male germ cells during development and in testicular tumours: new evidence for phenotypic plasticity of germ cells.Hum Reprod. 2012 Jun;27(6):1547-55. doi: 10.1093/humrep/des047. Epub 2012 Mar 30.
• [7] Analysis of protein-protein interaction network in chronic obstructive pulmonary disease.Genet Mol Res. 2014 Oct 31;13(4):8862-9. doi: 10.4238/2014.October.31.1.
• [8] Gender differences of B cell signature in healthy subjects underlie disparities in incidence and course of SLE related to estrogen.J Immunol Res. 2014;2014:814598. doi: 10.1155/2014/814598. Epub 2014 Feb 13.
• [9] 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.
• [10] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [11] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [12] Comparative gene expression profiling reveals partially overlapping but distinct genomic actions of different antiestrogens in human breast cancer cells. J Cell Biochem. 2006 Aug 1;98(5):1163-84.
• [13] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [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] 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.
• [16] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [17] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.