Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTB2IHCT)

• DOT Name: Mitochondrial intermediate peptidase (MIPEP)
• Synonyms: MIP; EC 3.4.24.59
• Gene Name: MIPEP
• Related Disease:
  Advanced cancer
  Cardiac arrest
  Cardiomyopathy
  Dilated cardiomyopathy
  Left ventricular noncompaction
  Lethal left ventricular non-compaction-seizures-hypotonia-cataract-developmental delay syndrome
  Lung cancer
  Lung carcinoma
  Mitochondrial disease
  Sickle-cell anaemia
• UniProt ID: MIPEP_HUMAN
• EC Number: 3.4.24.59
• Pfam ID: PF01432
• Sequence:
  MLCVGRLGGLGARAAALPPRRAGRGSLEAGIRARRVSTSWSPVGAAFNVKPQGSRLDLFG
  ERRGLFGVPELSAPEGFHIAQEKALRKTELLVDRACSTPPGPQTVLIFDELSDSLCRVAD
  LADFVKIAHPEPAFREAAEEACRSIGTMVEKLNTNVDLYQSLQKLLADKKLVDSLDPETR
  RVAELFMFDFEISGIHLDKEKRKRAVDLNVKILDLSSTFLMGTNFPNKIEKHLLPEHIRR
  NFTSAGDHIIIDGLHAESPDDLVREAAYKIFLYPNAGQLKCLEELLSSRDLLAKLVGYST
  FSHRALQGTIAKNPETVMQFLEKLSDKLSERTLKDFEMIRGMKMKLNPQNSEVMPWDPPY
  YSGVIRAERYNIEPSLYCPFFSLGACMEGLNILLNRLLGISLYAEQPAKGEVWSEDVRKL
  AVVHESEGLLGYIYCDFFQRADKPHQDCHFTIRGGRLKEDGDYQLPVVVLMLNLPRSSRS
  SPTLLTPSMMENLFHEMGHAMHSMLGRTRYQHVTGTRCPTDFAEVPSILMEYFANDYRVV
  NQFARHYQTGQPLPKNMVSRLCESKKVCAAADMQLQVFYATLDQIYHGKHPLRNSTTDIL
  KETQEKFYGLPYVPNTAWQLRFSHLVGYGARYYSYLMSRAVASMVWKECFLQDPFNRAAG
  ERYRREMLAHGGGREPMLMVEGMLQKCPSVDDFVSALVSDLDLDFETFLMDSE
• Function: Cleaves proteins, imported into the mitochondrion, to their mature size.

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Cardiac arrest	DIS9DIA4	Strong	Genetic Variation	[2]
Cardiomyopathy	DISUPZRG	Strong	CausalMutation	[3]
Dilated cardiomyopathy	DISX608J	Strong	CausalMutation	[3]
Left ventricular noncompaction	DISJ4QEG	Strong	CausalMutation	[3]
Lethal left ventricular non-compaction-seizures-hypotonia-cataract-developmental delay syndrome	DISC92JF	Strong	Autosomal recessive	[3]
Lung cancer	DISCM4YA	Strong	Genetic Variation	[4]
Lung carcinoma	DISTR26C	Strong	Genetic Variation	[4]
Mitochondrial disease	DISKAHA3	Moderate	Autosomal recessive	[5]
Sickle-cell anaemia	DIS5YNZB	Limited	Genetic Variation	[6]

1 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 Mitochondrial intermediate peptidase (MIPEP).	[7]

10 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 Mitochondrial intermediate peptidase (MIPEP).	[8]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Mitochondrial intermediate peptidase (MIPEP).	[9]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Mitochondrial intermediate peptidase (MIPEP).	[10]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate affects the expression of Mitochondrial intermediate peptidase (MIPEP).	[11]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Mitochondrial intermediate peptidase (MIPEP).	[12]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Mitochondrial intermediate peptidase (MIPEP).	[13]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Mitochondrial intermediate peptidase (MIPEP).	[14]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Mitochondrial intermediate peptidase (MIPEP).	[15]
Fenretinide	DMRD5SP	Phase 3	Fenretinide affects the expression of Mitochondrial intermediate peptidase (MIPEP).	[16]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Mitochondrial intermediate peptidase (MIPEP).	[17]

References

• [1] ncRNA-Encoded Peptides or Proteins and Cancer.Mol Ther. 2019 Oct 2;27(10):1718-1725. doi: 10.1016/j.ymthe.2019.09.001. Epub 2019 Sep 6.
• [2] The role of BCL11A and HMIP-2 polymorphisms on endogenous and hydroxyurea induced levels of fetal hemoglobin in sickle cell anemia patients from southern Brazil.Blood Cells Mol Dis. 2016 Nov;62:32-37. doi: 10.1016/j.bcmd.2016.11.002. Epub 2016 Nov 9.
• [3] MIPEP recessive variants cause a syndrome of left ventricular non-compaction, hypotonia, and infantile death. Genome Med. 2016 Nov 1;8(1):106. doi: 10.1186/s13073-016-0360-6.
• [4] A genome-wide association study identifies two new lung cancer susceptibility loci at 13q12.12 and 22q12.2 in Han Chinese.Nat Genet. 2011 Jul 3;43(8):792-6. doi: 10.1038/ng.875.
• [5] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [6] The association of HBG2, BCL11A, and HMIP polymorphisms with fetal hemoglobin and clinical phenotype in Iraqi Kurds with sickle cell disease.Int J Lab Hematol. 2019 Feb;41(1):87-93. doi: 10.1111/ijlh.12927. Epub 2018 Sep 14.
• [7] 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.
• [8] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [9] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [10] Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain. Toxicol Lett. 2015 Apr 16;234(2):139-50.
• [11] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [12] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [13] 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.
• [14] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [15] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [16] 4-HPR modulates gene expression in ovarian cells. Int J Cancer. 2006 Sep 1;119(5):1005-13. doi: 10.1002/ijc.21797.
• [17] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.