Details of Drug Off-Target (DOT)

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

• DOT Name: Homeobox protein Hox-A5 (HOXA5)
• Synonyms: Homeobox protein Hox-1C
• Gene Name: HOXA5
• UniProt ID: HXA5_HUMAN
• Pfam ID: PF00046
• Sequence:
  MSSYFVNSFCGRYPNGPDYQLHNYGDHSSVSEQFRDSASMHSGRYGYGYNGMDLSVGRSG
  SGHFGSGERARSYAASASAAPAEPRYSQPATSTHSPQPDPLPCSAVAPSPGSDSHHGGKN
  SLSNSSGASADAGSTHISSREGVGTASGAEEDAPASSEQASAQSEPSPAPPAQPQIYPWM
  RKLHISHDNIGGPEGKRARTAYTRYQTLELEKEFHFNRYLTRRRRIEIAHALCLSERQIK
  IWFQNRRMKWKKDNKLKSMSMAAAGGAFRP
• Function: Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. Also binds to its own promoter. Binds specifically to the motif 5'-CYYNATTA[TG]Y-3'.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Etoposide	DMNH3PG	Approved	Homeobox protein Hox-A5 (HOXA5) affects the response to substance of Etoposide.	[17]
Mitoxantrone	DMM39BF	Approved	Homeobox protein Hox-A5 (HOXA5) affects the response to substance of Mitoxantrone.	[17]

3 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 Homeobox protein Hox-A5 (HOXA5).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Homeobox protein Hox-A5 (HOXA5).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Homeobox protein Hox-A5 (HOXA5).	[14]

14 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 Homeobox protein Hox-A5 (HOXA5).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Homeobox protein Hox-A5 (HOXA5).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Homeobox protein Hox-A5 (HOXA5).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Homeobox protein Hox-A5 (HOXA5).	[5]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Homeobox protein Hox-A5 (HOXA5).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Homeobox protein Hox-A5 (HOXA5).	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Homeobox protein Hox-A5 (HOXA5).	[8]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Homeobox protein Hox-A5 (HOXA5).	[9]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Homeobox protein Hox-A5 (HOXA5).	[9]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of Homeobox protein Hox-A5 (HOXA5).	[10]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Homeobox protein Hox-A5 (HOXA5).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Homeobox protein Hox-A5 (HOXA5).	[13]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Homeobox protein Hox-A5 (HOXA5).	[15]
geraniol	DMS3CBD	Investigative	geraniol increases the expression of Homeobox protein Hox-A5 (HOXA5).	[16]

References

• [1] 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.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] 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.
• [6] 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.
• [7] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [8] Aberrantly expressed genes in HaCaT keratinocytes chronically exposed to arsenic trioxide. Biomark Insights. 2011 Feb 8;6:7-16.
• [9] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [10] 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.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [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] Synergistic activity of BET protein antagonist-based combinations in mantle cell lymphoma cells sensitive or resistant to ibrutinib. Blood. 2015 Sep 24;126(13):1565-74.
• [14] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [15] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [16] Geraniol suppresses prostate cancer growth through down-regulation of E2F8. Cancer Med. 2016 Oct;5(10):2899-2908.
• [17] 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.