Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGCYNY7)

• DOT Name: Methionine aminopeptidase 1 (METAP1)
• Synonyms: MAP 1; MetAP 1; EC 3.4.11.18; Peptidase M 1
• Gene Name: METAP1
• UniProt ID: MAP11_HUMAN
• PDB ID: 2B3H ; 2B3K ; 2B3L ; 2G6P ; 2GZ5 ; 2NQ6 ; 2NQ7 ; 4FLI ; 4FLJ ; 4FLK ; 4FLL ; 4HXX ; 4IKR ; 4IKS ; 4IKT ; 4IKU ; 4IU6 ; 4U1B ; 4U69 ; 4U6C ; 4U6E ; 4U6J ; 4U6W ; 4U6Z ; 4U70 ; 4U71 ; 4U73 ; 4U75 ; 4U76 ; 5YKP ; 5YR4 ; 5YR5 ; 5YR6 ; 5YR7 ; 6LZB ; 6LZC ; 8P2K
• EC Number: 3.4.11.18
• Pfam ID: PF00557 ; PF15801
• Sequence:
  MAAVETRVCETDGCSSEAKLQCPTCIKLGIQGSYFCSQECFKGSWATHKLLHKKAKDEKA
  KREVSSWTVEGDINTDPWAGYRYTGKLRPHYPLMPTRPVPSYIQRPDYADHPLGMSESEQ
  ALKGTSQIKLLSSEDIEGMRLVCRLAREVLDVAAGMIKPGVTTEEIDHAVHLACIARNCY
  PSPLNYYNFPKSCCTSVNEVICHGIPDRRPLQEGDIVNVDITLYRNGYHGDLNETFFVGE
  VDDGARKLVQTTYECLMQAIDAVKPGVRYRELGNIIQKHAQANGFSVVRSYCGHGIHKLF
  HTAPNVPHYAKNKAVGVMKSGHVFTIEPMICEGGWQDETWPDGWTAVTRDGKRSAQFEHT
  LLVTDTGCEILTRRLDSARPHFMSQF
• Function: Cotranslationally removes the N-terminal methionine from nascent proteins. The N-terminal methionine is often cleaved when the second residue in the primary sequence is small and uncharged (Met-Ala-, Cys, Gly, Pro, Ser, Thr, or Val). Required for normal progression through the cell cycle.
• Reactome Pathway: Inactivation, recovery and regulation of the phototransduction cascade (R-HSA-2514859)
• BioCyc Pathway: MetaCyc:HS08982-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

3 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 Methionine aminopeptidase 1 (METAP1).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the methylation of Methionine aminopeptidase 1 (METAP1).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Methionine aminopeptidase 1 (METAP1).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Methionine aminopeptidase 1 (METAP1).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Methionine aminopeptidase 1 (METAP1).	[4]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Methionine aminopeptidase 1 (METAP1).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Methionine aminopeptidase 1 (METAP1).	[7]

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] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [3] 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.
• [4] 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.
• [5] 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.
• [6] 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.
• [7] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.