Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZVVEV7)

• DOT Name: Nuclear transcription factor Y subunit gamma (NFYC)
• Synonyms: CAAT box DNA-binding protein subunit C; Nuclear transcription factor Y subunit C; NF-YC; Transactivator HSM-1/2
• Gene Name: NFYC
• Related Disease:
  Advanced cancer
  Esophageal squamous cell carcinoma
  Laurin-Sandrow syndrome
  Lung squamous cell carcinoma
  Non-insulin dependent diabetes
  Bipolar disorder
• UniProt ID: NFYC_HUMAN
• PDB ID: 1N1J; 4AWL; 4CSR; 6QMP; 6QMQ; 6QMS; 7AH8
• Pfam ID: PF00125
• Sequence:
  MSTEGGFGGTSSSDAQQSLQSFWPRVMEEIRNLTVKDFRVQELPLARIKKIMKLDEDVKM
  ISAEAPVLFAKAAQIFITELTLRAWIHTEDNKRRTLQRNDIAMAITKFDQFDFLIDIVPR
  DELKPPKRQEEVRQSVTPAEPVQYYFTLAQQPTAVQVQGQQQGQQTTSSTTTIQPGQIII
  AQPQQGQTTPVTMQVGEGQQVQIVQAQPQGQAQQAQSGTGQTMQVMQQIITNTGEIQQIP
  VQLNAGQLQYIRLAQPVSGTQVVQGQIQTLATNAQQGQRNASQGKPRRCLKETLQITQTE
  VQQGQQQFSQFTDGQRNSVQQARVSELTGEAEPREVKATGNSTPCTSSLPTTHPPSHRAG
  ASCVCCSQPQQSSTSPPPSDALQWVVVEVSGTPNQLETHRELHAPLPGMTSLSPLHPSQQ
  LYQIQQVTMPAGQDLAQPMFIQSANQPSDGQAPQVTGD
• Function: Component of the sequence-specific heterotrimeric transcription factor (NF-Y) which specifically recognizes a 5'-CCAAT-3' box motif found in the promoters of its target genes. NF-Y can function as both an activator and a repressor, depending on its interacting cofactors.
• KEGG Pathway:
  Antigen processing and presentation (hsa04612)
  Tuberculosis (hsa05152)
• Reactome Pathway:
  Activation of gene expression by SREBF (SREBP) (R-HSA-2426168)
  ATF4 activates genes in response to endoplasmic reticulum stress (R-HSA-380994)
  ATF6 (ATF6-alpha) activates chaperone genes (R-HSA-381183)
  FOXO-mediated transcription of cell death genes (R-HSA-9614657)
  PPARA activates gene expression (R-HSA-1989781)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Genetic Variation	[2]
Laurin-Sandrow syndrome	DISOYBC3	Strong	Genetic Variation	[3]
Lung squamous cell carcinoma	DISXPIBD	Strong	Genetic Variation	[4]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[5]
Bipolar disorder	DISAM7J2	moderate	Genetic Variation	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Nuclear transcription factor Y subunit gamma (NFYC).	[7]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Nuclear transcription factor Y subunit gamma (NFYC).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Nuclear transcription factor Y subunit gamma (NFYC).	[9]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Nuclear transcription factor Y subunit gamma (NFYC).	[10]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Nuclear transcription factor Y subunit gamma (NFYC).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Nuclear transcription factor Y subunit gamma (NFYC).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Nuclear transcription factor Y subunit gamma (NFYC).	[14]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Nuclear transcription factor Y subunit gamma (NFYC).	[15]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Nuclear transcription factor Y subunit gamma (NFYC).	[16]

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 Nuclear transcription factor Y subunit gamma (NFYC).	[12]

References

• [1] An autoregulatory loop controls the expression of the transcription factor NF-Y.Biochim Biophys Acta Gene Regul Mech. 2018 May;1861(5):509-518. doi: 10.1016/j.bbagrm.2018.02.008. Epub 2018 Mar 2.
• [2] Association of single nucleotide polymorphisms in ERCC2 gene and their haplotypes with esophageal squamous cell carcinoma.Tumour Biol. 2014 May;35(5):4225-31. doi: 10.1007/s13277-013-1553-x. Epub 2014 Jan 4.
• [3] Progression of lumbar spinal stenosis is influenced by polymorphism of thrombospondin 2 gene in the Korean population.Eur Spine J. 2014 Jan;23(1):57-63. doi: 10.1007/s00586-013-2866-6. Epub 2013 Jun 27.
• [4] A point mutation in the NFYC gene generates an antigenic peptide recognized by autologous cytolytic T lymphocytes on a human squamous cell lung carcinoma.Int J Cancer. 2006 Apr 15;118(8):1992-7. doi: 10.1002/ijc.21594.
• [5] Effects of Genetic Variants of Nuclear Receptor Y on the Risk of Type 2 Diabetes Mellitus.J Diabetes Res. 2019 May 7;2019:4902301. doi: 10.1155/2019/4902301. eCollection 2019.
• [6] Genetics of long-term treatment outcome in bipolar disorder.Prog Neuropsychopharmacol Biol Psychiatry. 2016 Feb 4;65:17-24. doi: 10.1016/j.pnpbp.2015.08.008. Epub 2015 Aug 20.
• [7] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [8] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [9] 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.
• [10] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [11] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [12] 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.
• [13] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [14] Bisphenol-A and estradiol exert novel gene regulation in human MCF-7 derived breast cancer cells. Mol Cell Endocrinol. 2004 Jun 30;221(1-2):47-55. doi: 10.1016/j.mce.2004.04.010.
• [15] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [16] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.