Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTC1WT8O)

• DOT Name: MICOS complex subunit MIC27 (APOOL)
• Synonyms: Apolipoprotein O-like; Protein FAM121A
• Gene Name: APOOL
• UniProt ID: MIC27_HUMAN
• Pfam ID: PF09769
• Sequence:
  MAAIRMGKLTTMPAGLIYASVSVHAAKQEESKKQLVKPEQLPIYTAPPLQSKYVEEQPGH
  LQMGFASIRTATGCYIGWCKGVYVFVKNGIMDTVQFGKDAYVYLKNPPRDFLPKMGVITV
  SGLAGLVSARKGSKFKKITYPLGLATLGATVCYPVQSVIIAKVTAKKVYATSQQIFGAVK
  SLWTKSSKEESLPKPKEKTKLGSSSEIEVPAKTTHVLKHSVPLPTELSSEAKTKSESTSG
  ATQFMPDPKLMDHGQSHPEDIDMYSTRS
• Function: Component of the MICOS complex, a large protein complex of the mitochondrial inner membrane that plays crucial roles in the maintenance of crista junctions, inner membrane architecture, and formation of contact sites to the outer membrane. Specifically binds to cardiolipin (in vitro) but not to the precursor lipid phosphatidylglycerol. Plays a crucial role in crista junction formation and mitochondrial function ,.
• Reactome Pathway:
  Cristae formation (R-HSA-8949613)
  Platelet degranulation (R-HSA-114608)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of MICOS complex subunit MIC27 (APOOL).	[1]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of MICOS complex subunit MIC27 (APOOL).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of MICOS complex subunit MIC27 (APOOL).	[10]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of MICOS complex subunit MIC27 (APOOL).	[11]

8 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 MICOS complex subunit MIC27 (APOOL).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of MICOS complex subunit MIC27 (APOOL).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of MICOS complex subunit MIC27 (APOOL).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of MICOS complex subunit MIC27 (APOOL).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of MICOS complex subunit MIC27 (APOOL).	[7]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of MICOS complex subunit MIC27 (APOOL).	[8]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of MICOS complex subunit MIC27 (APOOL).	[9]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of MICOS complex subunit MIC27 (APOOL).	[12]

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] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [6] 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.
• [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] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [9] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [10] 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.
• [11] 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.
• [12] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.