Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8OI3EC)

• DOT Name: Mortality factor 4-like protein 2 (MORF4L2)
• Synonyms: MORF-related gene X protein; Protein MSL3-2; Transcription factor-like protein MRGX
• Gene Name: MORF4L2
• Related Disease: Lung adenocarcinoma
• UniProt ID: MO4L2_HUMAN
• Pfam ID: PF05712
• Sequence:
  MSSRKQGSQPRGQQSAEEENFKKPTRSNMQRSKMRGASSGKKTAGPQQKNLEPALPGRWG
  GRSAENPPSGSVRKTRKNKQKTPGNGDGGSTSEAPQPPRKKRARADPTVESEEAFKNRME
  VKVKIPEELKPWLVEDWDLVTRQKQLFQLPAKKNVDAILEEYANCKKSQGNVDNKEYAVN
  EVVAGIKEYFNVMLGTQLLYKFERPQYAEILLAHPDAPMSQVYGAPHLLRLFVRIGAMLA
  YTPLDEKSLALLLGYLHDFLKYLAKNSASLFTASDYKVASAEYHRKAL
• Function: Component of the NuA4 histone acetyltransferase complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histone H4 and H2A. This modification may both alter nucleosome - DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription. This complex may be required for the activation of transcriptional programs associated with oncogene and proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair. The NuA4 complex ATPase and helicase activities seem to be, at least in part, contributed by the association of RUVBL1 and RUVBL2 with EP400. NuA4 may also play a direct role in DNA repair when directly recruited to sites of DNA damage. Also a component of the MSIN3A complex which acts to repress transcription by deacetylation of nucleosomal histones.
• KEGG Pathway: ATP-dependent chromatin remodeling (hsa03082)
• Reactome Pathway: HATs acetylate histones (R-HSA-3214847)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[1]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Mortality factor 4-like protein 2 (MORF4L2) decreases the response to substance of Fluorouracil.	[14]

2 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 Mortality factor 4-like protein 2 (MORF4L2).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Mortality factor 4-like protein 2 (MORF4L2).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Mortality factor 4-like protein 2 (MORF4L2).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Mortality factor 4-like protein 2 (MORF4L2).	[4]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Mortality factor 4-like protein 2 (MORF4L2).	[5]
Azacitidine	DMTA5OE	Approved	Azacitidine decreases the expression of Mortality factor 4-like protein 2 (MORF4L2).	[6]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Mortality factor 4-like protein 2 (MORF4L2).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Mortality factor 4-like protein 2 (MORF4L2).	[9]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Mortality factor 4-like protein 2 (MORF4L2).	[10]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Mortality factor 4-like protein 2 (MORF4L2).	[11]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Mortality factor 4-like protein 2 (MORF4L2).	[12]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of Mortality factor 4-like protein 2 (MORF4L2).	[13]

References

• [1] Enhancement of tumor initiation and expression of KCNMA1, MORF4L2 and ASPM genes in the adenocarcinoma of lung xenograft after vorinostat treatment.Oncotarget. 2015 Apr 20;6(11):8663-75. doi: 10.18632/oncotarget.3536.
• [2] 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.
• [3] 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.
• [4] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [5] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [6] The effect of DNA methylation inhibitor 5-Aza-2'-deoxycytidine on human endometrial stromal cells. Hum Reprod. 2010 Nov;25(11):2859-69.
• [7] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [8] 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.
• [9] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [10] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [11] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [12] Molecular targets of chloropicrin in human airway epithelial cells. Toxicol In Vitro. 2017 Aug;42:247-254.
• [13] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.
• [14] Single-cell transcription site activation predicts chemotherapy response in human colorectal tumors. Cancer Res. 2008 Jul 1;68(13):4977-82. doi: 10.1158/0008-5472.CAN-07-6770.