Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTR6I798)

• DOT Name: m-AAA protease-interacting protein 1, mitochondrial (MAIP1)
• Synonyms: Matrix AAA peptidase-interacting protein 1
• Gene Name: MAIP1
• Related Disease: Schizophrenia
• UniProt ID: MAIP1_HUMAN
• Sequence:
  MALAARLLPQFLHSRSLPCGAVRLRTPAVAEVRLPSATLCYFCRCRLGLGAALFPRSARA
  LAASALPAQGSRWPVLSSPGLPAAFASFPACPQRSYSTEEKPQQHQKTKMIVLGFSNPIN
  WVRTRIKAFLIWAYFDKEFSITEFSEGAKQAFAHVSKLLSQCKFDLLEELVAKEVLHALK
  EKVTSLPDNHKNALAANIDEIVFTSTGDISIYYDEKGRKFVNILMCFWYLTSANIPSETL
  RGASVFQVKLGNQNVETKQLLSASYEFQREFTQGVKPDWTIARIEHSKLLE
• Function: Promotes sorting of SMDT1/EMRE in mitochondria by ensuring its maturation. Interacts with the transit peptide region of SMDT1/EMRE precursor protein in the mitochondrial matrix, leading to protect it against protein degradation by YME1L1, thereby ensuring SMDT1/EMRE maturation by the mitochondrial processing peptidase (PMPCA and PMPCB).
• Reactome Pathway: Processing of SMDT1 (R-HSA-8949664)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of m-AAA protease-interacting protein 1, mitochondrial (MAIP1).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of m-AAA protease-interacting protein 1, mitochondrial (MAIP1).	[3]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of m-AAA protease-interacting protein 1, mitochondrial (MAIP1).	[4]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of m-AAA protease-interacting protein 1, mitochondrial (MAIP1).	[6]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of m-AAA protease-interacting protein 1, mitochondrial (MAIP1).	[7]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of m-AAA protease-interacting protein 1, mitochondrial (MAIP1).	[5]

References

• [1] Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia.Mol Autism. 2017 May 22;8:21. doi: 10.1186/s13229-017-0137-9. eCollection 2017.
• [2] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [3] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [4] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [5] Proteomic analysis of the cellular response to a potent sensitiser unveils the dynamics of haptenation in living cells. Toxicology. 2020 Dec 1;445:152603. doi: 10.1016/j.tox.2020.152603. Epub 2020 Sep 28.
• [6] 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.
• [7] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.