Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTY72TPO)

• DOT Name: Protein N-terminal glutamine amidohydrolase (NTAQ1)
• Synonyms: EC 3.5.1.122; Protein NH2-terminal glutamine deamidase; N-terminal Gln amidase; Nt(Q)-amidase; WDYHV motif-containing protein 1
• Gene Name: NTAQ1
• UniProt ID: NTAQ1_HUMAN
• PDB ID: 3C9Q; 4W79; 6KGJ
• EC Number: 3.5.1.122
• Pfam ID: PF09764
• Sequence:
  MEGNGPAAVHYQPASPPRDACVYSSCYCEENIWKLCEYIKNHDQYPLEECYAVFISNERK
  MIPIWKQQARPGDGPVIWDYHVVLLHVSSGGQNFIYDLDTVLPFPCLFDTYVEDAFKSDD
  DIHPQFRRKFRVIRADSYLKNFASDRSHMKDSSGNWREPPPPYPCIETGDSKMNLNDFIS
  MDPKVGWGAVYTLSEFTHRFGSKNC
• Function: Mediates the side-chain deamidation of N-terminal glutamine residues to glutamate, an important step in N-end rule pathway of protein degradation. Conversion of the resulting N-terminal glutamine to glutamate renders the protein susceptible to arginylation, polyubiquitination and degradation as specified by the N-end rule. Does not act on substrates with internal or C-terminal glutamine and does not act on non-glutamine residues in any position. Does not deaminate acetylated N-terminal glutamine. With the exception of proline, all tested second-position residues on substrate peptides do not greatly influence the activity. In contrast, a proline at position 2, virtually abolishes deamidation of N-terminal glutamine.
• BioCyc Pathway: MetaCyc:ENSG00000156795-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Protein N-terminal glutamine amidohydrolase (NTAQ1).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Protein N-terminal glutamine amidohydrolase (NTAQ1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Protein N-terminal glutamine amidohydrolase (NTAQ1).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Protein N-terminal glutamine amidohydrolase (NTAQ1).	[4]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Protein N-terminal glutamine amidohydrolase (NTAQ1).	[5]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Protein N-terminal glutamine amidohydrolase (NTAQ1).	[6]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Protein N-terminal glutamine amidohydrolase (NTAQ1).	[7]
APR-246	DMNFADH	Phase 2	APR-246 affects the expression of Protein N-terminal glutamine amidohydrolase (NTAQ1).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of Protein N-terminal glutamine amidohydrolase (NTAQ1).	[9]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] 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.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] 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.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [8] Mutant p53 reactivation by PRIMA-1MET induces multiple signaling pathways converging on apoptosis. Oncogene. 2010 Mar 4;29(9):1329-38. doi: 10.1038/onc.2009.425. Epub 2009 Nov 30.
• [9] Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells. Mutat Res Genet Toxicol Environ Mutagen. 2014 Dec;775-776:48-54. doi: 10.1016/j.mrgentox.2014.10.011. Epub 2014 Nov 4.