Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJF0U48)

DOT Name Protein N-terminal asparagine amidohydrolase (NTAN1)
Synonyms
EC 3.5.1.121; Protein NH2-terminal asparagine amidohydrolase; PNAA; Protein NH2-terminal asparagine deamidase; PNAD; Protein N-terminal Asn amidase; Protein N-terminal asparagine amidase; Protein NTN-amidase
Gene Name NTAN1
Related Disease
Chronic kidney disease ( )
Chronic renal failure ( )
Legionnaires' disease ( )
UniProt ID
NTAN1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
6A0E; 6A0F; 6A0H; 6A0I
EC Number
3.5.1.121
Pfam ID
PF14736
Sequence
MPLLVEGRRVRLPQSAGDLVRAHPPLEERARLLRGQSVQQVGPQGLLYVQQRELAVTSPK
DGSISILGSDDATTCHIVVLRHTGNGATCLTHCDGTDTKAEVPLIMNSIKSFSDHAQCGR
LEVHLVGGFSDDRQLSQKLTHQLLSEFDRQEDDIHLVTLCVTELNDREENENHFPVIYGI
AVNIKTAEIYRASFQDRGPEEQLRAARTLAGGPMISIYDAETEQLRIGPYSWTPFPHVDF
WLHQDDKQILENLSTSPLAEPPHFVEHIRSTLMFLKKHPSPAHTLFSGNKALLYKKNEDG
LWEKISSPGS
Function
N-terminal asparagine deamidase that mediates deamidation of N-terminal asparagine residues to aspartate. Required for the ubiquitin-dependent turnover of intracellular proteins that initiate with Met-Asn. These proteins are acetylated on the retained initiator methionine and can subsequently be modified by the removal of N-acetyl methionine by acylaminoacid hydrolase (AAH). Conversion of the resulting N-terminal asparagine to aspartate by NTAN1/PNAD renders the protein susceptible to arginylation, polyubiquitination and degradation as specified by the N-end rule. This enzyme does not act on substrates with internal or C-terminal asparagines and does not act on glutamine residues in any position, nor on acetylated N-terminal peptidyl Asn.
BioCyc Pathway
MetaCyc:ENSG00000157045-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Chronic kidney disease DISW82R7 Definitive Genetic Variation [1]
Chronic renal failure DISGG7K6 Definitive Genetic Variation [1]
Legionnaires' disease DIS8V4GQ Strong Biomarker [2]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
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 Protein N-terminal asparagine amidohydrolase (NTAN1). [3]
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7 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 Protein N-terminal asparagine amidohydrolase (NTAN1). [4]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Protein N-terminal asparagine amidohydrolase (NTAN1). [5]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Protein N-terminal asparagine amidohydrolase (NTAN1). [6]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Protein N-terminal asparagine amidohydrolase (NTAN1). [7]
Quercetin DM3NC4M Approved Quercetin increases the expression of Protein N-terminal asparagine amidohydrolase (NTAN1). [8]
Isotretinoin DM4QTBN Approved Isotretinoin decreases the expression of Protein N-terminal asparagine amidohydrolase (NTAN1). [9]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Protein N-terminal asparagine amidohydrolase (NTAN1). [10]
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⏷ Show the Full List of 7 Drug(s)

References

1 Genome-Wide Association Studies of Metabolites in Patients with CKD Identify Multiple Loci and Illuminate Tubular Transport Mechanisms.J Am Soc Nephrol. 2018 May;29(5):1513-1524. doi: 10.1681/ASN.2017101099. Epub 2018 Mar 15.
2 microRNA-125a-3p is regulated by MyD88 in Legionella pneumophila infection and targets NTAN1.PLoS One. 2017 Apr 26;12(4):e0176204. doi: 10.1371/journal.pone.0176204. eCollection 2017.
3 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.
4 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
5 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
6 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
7 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.
8 Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
9 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.
10 Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.