Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7GGIBP)

• DOT Name: NALCN channel auxiliary factor 2 (NALF2)
• Synonyms: Protein TED; Transmembrane protein 28; Transmembrane protein FAM155B
• Gene Name: NALF2
• UniProt ID: NALF2_HUMAN
• Sequence:
  MFRGAWMWPGKDAAALTICCCCCCWAPRPSDKPCADSERAQRWRLSLASLLFFTVLLADH
  LWLCAGARPRARELSSAMRPPWGAGRERQPVPPRAVLPLPPPPPGEPSAPPGTCGPRYSN
  LTKAAPAAGSRPVCGGVPEPTGLDAACTKLQSLQRLFEPTTPAPPLRPPDSLSRAPAEFP
  SAKKNLLKGHFRNFTLSFCDTYTVWDLLLGMDRPDSLDCSLDTLMGDLLAVVASPGSGAW
  EACSNCIEAYQRLDRHAQEKYDEFDLVLHKYLQAEEYSIRSCTKGCKAVYKAWLCSEYFS
  VTQQECQRWVPCKQYCLEVQTRCPFILPDNEEMVYGGLPGFICTGLLDTSPKRLETKCCD
  VQWVSCEAKKKKFKESEAPKTHQQQFHHSYFHHYHQQYHHYHPHHDPPGRVSNKPALLPV
  SGGSRLSPSRIRLCVLVLMLLHTVVSFSSNQGGGGLGLETLPALEEGLTREE
• Function: Probable component of the NALCN channel complex, a channel that regulates the resting membrane potential and controls neuronal excitability.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of NALCN channel auxiliary factor 2 (NALF2).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of NALCN channel auxiliary factor 2 (NALF2).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of NALCN channel auxiliary factor 2 (NALF2).	[3]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of NALCN channel auxiliary factor 2 (NALF2).	[4]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of NALCN channel auxiliary factor 2 (NALF2).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of NALCN channel auxiliary factor 2 (NALF2).	[7]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of NALCN channel auxiliary factor 2 (NALF2).	[6]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] 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.
• [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] 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.
• [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] 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] Cultured human peripheral blood mononuclear cells alter their gene expression when challenged with endocrine-disrupting chemicals. Toxicology. 2013 Jan 7;303:17-24.