Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1XJGFG)

• DOT Name: Ephrin type-A receptor 10 (EPHA10)
• Synonyms: EC 2.7.10.1
• Gene Name: EPHA10
• Related Disease:
  Advanced cancer
  Acute myelogenous leukaemia
  Breast cancer
  Breast carcinoma
  Hearing loss, autosomal dominant 88
• UniProt ID: EPHAA_HUMAN
• EC Number: 2.7.10.1
• Pfam ID: PF14575 ; PF01404 ; PF00041 ; PF07714 ; PF00536
• Sequence:
  METCAGPHPLRLFLCRMQLCLALLLGPWRPGTAEEVILLDSKASQAELGWTALPSNGWEE
  ISGVDEHDRPIRTYQVCNVLEPNQDNWLQTGWISRGRGQRIFVELQFTLRDCSSIPGAAG
  TCKETFNVYYLETEADLGRGRPRLGGSRPRKIDTIAADESFTQGDLGERKMKLNTEVREI
  GPLSRRGFHLAFQDVGACVALVSVRVYYKQCRATVRGLATFPATAAESAFSTLVEVAGTC
  VAHSEGEPGSPPRMHCGADGEWLVPVGRCSCSAGFQERGDFCEACPPGFYKVSPRRPLCS
  PCPEHSRALENASTFCVCQDSYARSPTDPPSASCTRPPSAPRDLQYSLSRSPLVLRLRWL
  PPADSGGRSDVTYSLLCLRCGREGPAGACEPCGPRVAFLPRQAGLRERAATLLHLRPGAR
  YTVRVAALNGVSGPAAAAGTTYAQVTVSTGPGAPWEEDEIRRDRVEPQSVSLSWREPIPA
  GAPGANDTEYEIRYYEKGQSEQTYSMVKTGAPTVTVTNLKPATRYVFQIRAASPGPSWEA
  QSFNPSIEVQTLGEAASGSRDQSPAIVVTVVTISALLVLGSVMSVLAIWRRPCSYGKGGG
  DAHDEEELYFHFKVPTRRTFLDPQSCGDLLQAVHLFAKELDAKSVTLERSLGGGRFGELC
  CGCLQLPGRQELLVAVHMLRDSASDSQRLGFLAEALTLGQFDHSHIVRLEGVVTRGSTLM
  IVTEYMSHGALDGFLRRHEGQLVAGQLMGLLPGLASAMKYLSEMGYVHRGLAARHVLVSS
  DLVCKISGFGRGPRDRSEAVYTTMSGRSPALWAAPETLQFGHFSSASDVWSFGIIMWEVM
  AFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPNLLHRLMLDCWQKDPGERPRFSQIHSIL
  SKMVQDPEPPKCALTTCPRPPTPLADRAFSTFPSFGSVGAWLEALDLCRYKDSFAAAGYG
  SLEAVAEMTAQDLVSLGISLAEHREALLSGISALQARVLQLQGQGVQV
• Function: Receptor for members of the ephrin-A family. Binds to EFNA3, EFNA4 and EFNA5.
• Tissue Specificity: Mainly expressed in testis.
• Reactome Pathway:
  EPHA-mediated growth cone collapse (R-HSA-3928663)
  EPH-ephrin mediated repulsion of cells (R-HSA-3928665)
  EPH-Ephrin signaling (R-HSA-2682334)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[2]
Breast cancer	DIS7DPX1	moderate	Biomarker	[3]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[3]
Hearing loss, autosomal dominant 88	DISTPVR5	Limited	Autosomal dominant	[4]

4 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 Ephrin type-A receptor 10 (EPHA10).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the methylation of Ephrin type-A receptor 10 (EPHA10).	[6]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Ephrin type-A receptor 10 (EPHA10).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Ephrin type-A receptor 10 (EPHA10).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Ephrin type-A receptor 10 (EPHA10).	[7]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Ephrin type-A receptor 10 (EPHA10).	[9]
Malathion	DMXZ84M	Approved	Malathion increases the expression of Ephrin type-A receptor 10 (EPHA10).	[10]
Permethrin	DMZ0Q1G	Approved	Permethrin increases the expression of Ephrin type-A receptor 10 (EPHA10).	[10]
Thalidomide	DM70BU5	Approved	Thalidomide decreases the expression of Ephrin type-A receptor 10 (EPHA10).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Ephrin type-A receptor 10 (EPHA10).	[11]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Ephrin type-A receptor 10 (EPHA10).	[13]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of Ephrin type-A receptor 10 (EPHA10).	[14]

References

• [1] Juxtacrine Signaling Inhibits Antitumor Immunity by Upregulating PD-L1 Expression.Cancer Res. 2018 Jul 15;78(14):3761-3768. doi: 10.1158/0008-5472.CAN-18-0040. Epub 2018 May 22.
• [2] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [3] Development and Evaluation of Antibody Proteomics Technology for Rapid and Comprehensive Identification of Potential Biomarkers and Therapeutic Targets.Biol Pharm Bull. 2018;41(5):663-669. doi: 10.1248/bpb.b17-01041.
• [4] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [5] 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.
• [6] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [7] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [8] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [9] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [10] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [11] Early Transcriptomic Changes upon Thalidomide Exposure Influence the Later Neuronal Development in Human Embryonic Stem Cell-Derived Spheres. Int J Mol Sci. 2020 Aug 3;21(15):5564. doi: 10.3390/ijms21155564.
• [12] 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.
• [13] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
• [14] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.