Details of Drug Off-Target (DOT)

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

• DOT Name: Huntingtin-interacting protein K (HYPK)
• Synonyms: Huntingtin yeast partner K
• Gene Name: HYPK
• Related Disease:
  B-cell neoplasm
  Huntington disease
• UniProt ID: HYPK_HUMAN
• PDB ID: 6C95; 6PW9
• Pfam ID: PF19026
• Sequence:
  MATEGDVELELETETSGPERPPEKPRKHDSGAADLERVTDYAEEKEIQSSNLETAMSVIG
  DRRSREQKAKQEREKELAKVTIKKEDLELIMTEMEISRAAAERSLREHMGNVVEALIALT
  N
• Function: Component of several N-terminal acetyltransferase complexes. Inhibits the N-terminal acetylation activity of the N-terminal acetyltransferase NAA10-NAA15 complex (also called the NatA complex). Has chaperone-like activity preventing polyglutamine (polyQ) aggregation of HTT in neuronal cells probably while associated with the NatA complex. May play a role in the NatA complex-mediated N-terminal acetylation of PCNP.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
B-cell neoplasm	DISVY326	Strong	Biomarker	[1]
Huntington disease	DISQPLA4	Strong	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Huntingtin-interacting protein K (HYPK).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Huntingtin-interacting protein K (HYPK).	[4]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Huntingtin-interacting protein K (HYPK).	[5]
Irinotecan	DMP6SC2	Approved	Irinotecan affects the expression of Huntingtin-interacting protein K (HYPK).	[6]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Huntingtin-interacting protein K (HYPK).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Huntingtin-interacting protein K (HYPK).	[8]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Huntingtin-interacting protein K (HYPK).	[9]

References

• [1] Evidence of altered depression and dementia-related proteins in the brains of young rats after ovariectomy.J Neurochem. 2018 Sep;146(6):703-721. doi: 10.1111/jnc.14537. Epub 2018 Aug 9.
• [2] Chaperone-like protein HYPK and its interacting partners augment autophagy.Eur J Cell Biol. 2016 Jun-Jul;95(6-7):182-94. doi: 10.1016/j.ejcb.2016.03.003. Epub 2016 Apr 1.
• [3] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [4] 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.
• [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] Clinical determinants of response to irinotecan-based therapy derived from cell line models. Clin Cancer Res. 2008 Oct 15;14(20):6647-55.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.
• [9] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.