Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7IEGAZ)

• DOT Name: Sodium/potassium-transporting ATPase subunit beta-1-interacting protein 1 (NKAIN1)
• Synonyms: Na(+)/K(+)-transporting ATPase subunit beta-1-interacting protein 1; Protein FAM77C
• Gene Name: NKAIN1
• Related Disease: Alcohol dependence
• UniProt ID: NKAI1_HUMAN
• Pfam ID: PF05640
• Sequence:
  MGKCSGRCTLVAFCCLQLVAALERQIFDFLGYQWAPILANFLHIMAVILGIFGTVQYRSR
  YLILYAAWLVLWVGWNAFIICFYLEVGQLSQDRDFIMTFNTSLHRSWWMENGPGCLVTPV
  LNSRLALEDHHVISVTGCLLDYPYIEALSSALQIFLALFGFVFACYVSKVFLEEEDSFDF
  IGGFDSYGYQAPQKTSHLQLQPLYTSG

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alcohol dependence	DIS4ZSCO	Strong	Biomarker	[1]

2 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 Sodium/potassium-transporting ATPase subunit beta-1-interacting protein 1 (NKAIN1).	[2]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Sodium/potassium-transporting ATPase subunit beta-1-interacting protein 1 (NKAIN1).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Sodium/potassium-transporting ATPase subunit beta-1-interacting protein 1 (NKAIN1).	[3]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Sodium/potassium-transporting ATPase subunit beta-1-interacting protein 1 (NKAIN1).	[4]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Sodium/potassium-transporting ATPase subunit beta-1-interacting protein 1 (NKAIN1).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Sodium/potassium-transporting ATPase subunit beta-1-interacting protein 1 (NKAIN1).	[6]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Sodium/potassium-transporting ATPase subunit beta-1-interacting protein 1 (NKAIN1).	[7]

References

• [1] NKAIN1-SERINC2 is a functional, replicable and genome-wide significant risk gene region specific for alcohol dependence in subjects of European descent.Drug Alcohol Depend. 2013 May 1;129(3):254-64. doi: 10.1016/j.drugalcdep.2013.02.006. Epub 2013 Feb 28.
• [2] 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.
• [3] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [4] 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.
• [5] 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.
• [6] 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.
• [7] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [8] 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.