Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZ2VU30)

• DOT Name: Protein maelstrom homolog (MAEL)
• Gene Name: MAEL
• Related Disease:
  Breast cancer
  Breast carcinoma
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Neoplasm
  Oligospermia
  Trichohepatoenteric syndrome
  Advanced cancer
  Gastric cancer
  Stomach cancer
• UniProt ID: MAEL_HUMAN
• PDB ID: 2CTO
• Pfam ID: PF09011 ; PF13017
• Sequence:
  MPNRKASRNAYYFFVQEKIPELRRRGLPVARVADAIPYCSSDWALLREEEKEKYAEMARE
  WRAAQGKDPGPSEKQKPVFTPLRRPGMLVPKQNVSPPDMSALSLKGDQALLGGIFYFLNI
  FSHGELPPHCEQRFLPCEIGCVKYSLQEGIMADFHSFINPGEIPRGFRFHCQAASDSSHK
  IPISNFERGHNQATVLQNLYRFIHPNPGNWPPIYCKSDDRTRVNWCLKHMAKASEIRQDL
  QLLTVEDLVVGIYQQKFLKEPSKTWIRSLLDVAMWDYSSNTRCKWHEENDILFCALAVCK
  KIAYCISNSLATLFGIQLTEAHVPLQDYEASNSVTPKMVVLDAGRYQKLRVGSSGFSHFN
  SSNEEQRSNTPIGDYPSRAKISGQNSSVRGRGITRLLESISNSSSNIHKFSNCDTSLSPY
  MSQKDGYKSFSSLS
• Function: Plays a central role during spermatogenesis by repressing transposable elements and preventing their mobilization, which is essential for the germline integrity. Acts via the piRNA metabolic process, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and governs the methylation and subsequent repression of transposons. Its association with piP-bodies suggests a participation in the secondary piRNAs metabolic process. Required for the localization of germ-cell factors to the meiotic nuage.
• Tissue Specificity: Testis-specific. Expressed in various cancer cell lines, probably due to demethylation of its promoter.
• Reactome Pathway: PIWI-interacting RNA (piRNA) biogenesis (R-HSA-5601884)

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Altered Expression	[1]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[1]
Colon cancer	DISVC52G	Strong	Biomarker	[2]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[2]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Oligospermia	DIS6YJF3	Strong	Biomarker	[3]
Trichohepatoenteric syndrome	DISL3ODF	Strong	Biomarker	[4]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[5]
Gastric cancer	DISXGOUK	moderate	Biomarker	[6]
Stomach cancer	DISKIJSX	moderate	Biomarker	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Protein maelstrom homolog (MAEL).	[7]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Protein maelstrom homolog (MAEL).	[9]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of Protein maelstrom homolog (MAEL).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Protein maelstrom homolog (MAEL).	[13]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the expression of Protein maelstrom homolog (MAEL).	[11]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Protein maelstrom homolog (MAEL).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Protein maelstrom homolog (MAEL).	[8]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the methylation of Protein maelstrom homolog (MAEL).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Protein maelstrom homolog (MAEL).	[12]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Protein maelstrom homolog (MAEL).	[15]

References

• [1] Tissue-specific Co-expression of Long Non-coding and Coding RNAs Associated with Breast Cancer.Sci Rep. 2016 Sep 6;6:32731. doi: 10.1038/srep32731.
• [2] MAEL expression links epithelial-mesenchymal transition and stem cell properties in colorectal cancer.Int J Cancer. 2016 Dec 1;139(11):2502-11. doi: 10.1002/ijc.30388. Epub 2016 Aug 29.
• [3] Causes and Clinical Features of Infertile Men With Nonobstructive Azoospermia and Histopathologic Diagnosis of Hypospermatogenesis.Urology. 2017 Jul;105:62-68. doi: 10.1016/j.urology.2017.03.026. Epub 2017 Mar 22.
• [4] Germline genes hypomethylation and expression define a molecular signature in peripheral blood of ICF patients: implications for diagnosis and etiology.Orphanet J Rare Dis. 2014 Apr 17;9:56. doi: 10.1186/1750-1172-9-56.
• [5] Proteomic analysis reveals that MAEL, a component of nuage, interacts with stress granule proteins in cancer cells.Oncol Rep. 2014 Jan;31(1):342-50. doi: 10.3892/or.2013.2836. Epub 2013 Nov 5.
• [6] MAEL contributes to gastric cancer progression by promoting ILKAP degradation.Oncotarget. 2017 Dec 6;8(69):113331-113344. doi: 10.18632/oncotarget.22970. eCollection 2017 Dec 26.
• [7] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [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] Characterization of DOK1, a candidate tumor suppressor gene, in epithelial ovarian cancer. Mol Oncol. 2011 Oct;5(5):438-53. doi: 10.1016/j.molonc.2011.07.003. Epub 2011 Jul 26.
• [10] 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.
• [11] Comparative proteomics reveals concordant and discordant biochemical effects of caffeine versus epigallocatechin-3-gallate in human endothelial cells. Toxicol Appl Pharmacol. 2019 Sep 1;378:114621. doi: 10.1016/j.taap.2019.114621. Epub 2019 Jun 10.
• [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] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [14] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [15] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.