Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBV5PAI)

• DOT Name: N-acetylglucosamine-6-phosphate deacetylase (AMDHD2)
• Synonyms: GlcNAc 6-P deacetylase; EC 3.5.1.25; Amidohydrolase domain-containing protein 2
• Gene Name: AMDHD2
• UniProt ID: NAGA_HUMAN
• PDB ID: 7NUT; 7NUU
• EC Number: 3.5.1.25
• Pfam ID: PF01979
• Sequence:
  MRGEQGAAGARVLQFTNCRILRGGKLLREDLWVRGGRILDPEKLFFEERRVADERRDCGG
  RILAPGFIDVQINGGFGVDFSQATEDVGSGVALVARRILSHGVTSFCPTLVTSPPEVYHK
  VVPQIPVKSGGPHGAGVLGLHLEGPFISREKRGAHPEAHLRSFEADAFQDLLATYGPLDN
  VRIVTLAPELGRSHEVIRALTARGICVSLGHSVADLRAAEDAVWSGATFITHLFNAMLPF
  HHRDPGIVGLLTSDRLPAGRCIFYGMIADGTHTNPAALRIAHRAHPQGLVLVTDAIPALG
  LGNGRHTLGQQEVEVDGLTAYVAGTKTLSGSIAPMDVCVRHFLQATGCSMESALEAASLH
  PAQLLGLEKSKGTLDFGADADFVVLDDSLHVQATYISGELVWQADAARQ
• Function: Hydrolyzes the N-glycolyl group from N-glycolylglucosamine 6-phosphate (GlcNGc-6-P) in the N-glycolylneuraminic acid (Neu5Gc) degradation pathway. Although human is not able to catalyze formation of Neu5Gc due to the inactive CMAHP enzyme, Neu5Gc is present in food and must be degraded.
• KEGG Pathway:
  Amino sugar and nucleotide sugar metabolism (hsa00520)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Synthesis of UDP-N-acetyl-glucosamine (R-HSA-446210)

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 N-acetylglucosamine-6-phosphate deacetylase (AMDHD2).	[1]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of N-acetylglucosamine-6-phosphate deacetylase (AMDHD2).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of N-acetylglucosamine-6-phosphate deacetylase (AMDHD2).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of N-acetylglucosamine-6-phosphate deacetylase (AMDHD2).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of N-acetylglucosamine-6-phosphate deacetylase (AMDHD2).	[3]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of N-acetylglucosamine-6-phosphate deacetylase (AMDHD2).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of N-acetylglucosamine-6-phosphate deacetylase (AMDHD2).	[7]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of N-acetylglucosamine-6-phosphate deacetylase (AMDHD2).	[8]

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] 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.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [5] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [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] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
• [8] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.