Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZTLWJ0)

• DOT Name: Hyccin 2 (HYCC2)
• Gene Name: HYCC2
• UniProt ID: HYCC2_HUMAN
• Pfam ID: PF09790
• Sequence:
  MLGTDRCVVEEWLSEFKALPDTQITSYAATLHRKKTLVPALYKVIQDSNNELLEPVCHQL
  FELYRSSEVRLKRFTLQFLPELMWVYLRLTVSRDRQSNGCIEALLLGIYNLEIADKDGNN
  KVLSFTIPSLSKPSIYHEPSTIGSMALTEGALCQHDLIRVVYSDLHPQRETFTAQNRFEV
  LSFLMLCYNSAIVYMPASSYQSLCRMGSRVCVSGFPRQHEKHWKELCGRIVLDPEFMVQL
  LTGVYYAMYNGQWDLGQEVLDDIIYRAQLELFSQPLLVANAMKNSLPFDAPDSTQEGQKV
  LKVEVTPTVPRISRTAITTASIRRHRWRREGAEGVNGGEESVNLNDADEGFSSGASLSSQ
  PIGTKPSSSSQRGSLRKVATGRSAKDKETASAIKSSESPRDSVVRKQYVQQPTDLSVDSV
  ELTPMKKHLSLPAGQVVPKINSLSLIRTASASSSKSFDYVNGSQASTSIGVGTEGGTNLA
  ANNANRYSTVSLQEDRLGQAGEGKELLSPGAPLTKQSRSPSFNMQLISQV
• Function: Component of a complex required to localize phosphatidylinositol 4-kinase (PI4K) to the plasma membrane.

Molecular Interaction Atlas (MIA) of This DOT

4 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 Hyccin 2 (HYCC2).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Hyccin 2 (HYCC2).	[8]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Hyccin 2 (HYCC2).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Hyccin 2 (HYCC2).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Hyccin 2 (HYCC2).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Hyccin 2 (HYCC2).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Hyccin 2 (HYCC2).	[4]
Marinol	DM70IK5	Approved	Marinol increases the expression of Hyccin 2 (HYCC2).	[5]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Hyccin 2 (HYCC2).	[6]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Hyccin 2 (HYCC2).	[7]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Hyccin 2 (HYCC2).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Hyccin 2 (HYCC2).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Hyccin 2 (HYCC2).	[13]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Hyccin 2 (HYCC2).	[14]

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] 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.
• [3] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Delta9-tetrahydrocannabinol inhibits cytotrophoblast cell proliferation and modulates gene transcription. Mol Hum Reprod. 2006 May;12(5):321-33. doi: 10.1093/molehr/gal036. Epub 2006 Apr 5.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [8] 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.
• [9] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [10] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [11] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [12] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [13] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [14] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.