Details of Drug Off-Target (DOT)

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

• DOT Name: Histone H4 transcription factor (HINFP)
• Synonyms: Histone nuclear factor P; HiNF-P; MBD2-interacting zinc finger protein; Methyl-CpG-binding protein 2-interacting zinc finger protein
• Gene Name: HINFP
• Related Disease:
  Ataxia-telangiectasia
  Prostate neoplasm
• UniProt ID: HINFP_HUMAN
• Pfam ID: PF00096 ; PF13894
• Sequence:
  MPPPGKVPRKENLWLQCEWGSCSFVCSTMEKFFEHVTQHLQQHLHGSGEEEEEEEEDDPL
  EEEFSCLWQECGFCSLDSSADLIRHVYFHCYHTKLKQWGLQALQSQADLGPCILDFQSRN
  VIPDIPDHFLCLWEHCENSFDNPEWFYRHVEAHSLCCEYEAVGKDNPVVLCGWKGCTCTF
  KDRSKLREHLRSHTQEKVVACPTCGGMFANNTKFLDHIRRQTSLDQQHFQCSHCSKRFAT
  ERLLRDHMRNHVNHYKCPLCDMTCPLPSSLRNHMRFRHSEDRPFKCDCCDYSCKNLIDLQ
  KHLDTHSEEPAYRCDFENCTFSARSLCSIKSHYRKVHEGDSEPRYKCHVCDKCFTRGNNL
  TVHLRKKHQFKWPSGHPRFRYKEHEDGYMRLQLVRYESVELTQQLLRQPQEGSGLGTSLN
  ESSLQGIILETVPGEPGRKEEEEEGKGSEGTALSASQDNPSSVIHVVNQTNAQGQQEIVY
  YVLSEAPGEPPPAPEPPSGGIMEKLQGIAEEPEIQMV
• Function: Transcriptional repressor that binds to the consensus sequence 5'-CGGACGTT-3' and to the RB1 promoter. Transcriptional activator that promotes histone H4 gene transcription at the G1/S phase transition in conjunction with NPAT. Also activates transcription of the ATM and PRKDC genes. Autoregulates its expression by associating with its own promoter.
• Tissue Specificity: Ubiquitous. Highly expressed in brain, heart, skeletal muscle, spleen, kidney, small intestine, placenta and liver.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Ataxia-telangiectasia	DISP3EVR	Strong	Biomarker	[1]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[2]

7 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 Histone H4 transcription factor (HINFP).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Histone H4 transcription factor (HINFP).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Histone H4 transcription factor (HINFP).	[5]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Histone H4 transcription factor (HINFP).	[6]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Histone H4 transcription factor (HINFP).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Histone H4 transcription factor (HINFP).	[8]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Histone H4 transcription factor (HINFP).	[9]

References

• [1] HiNF-P is a bifunctional regulator of cell cycle controlled histone H4 gene transcription.J Cell Biochem. 2007 May 1;101(1):181-91. doi: 10.1002/jcb.21157.
• [2] CpG island promoter methylation and silencing of 14-3-3sigma gene expression in LNCaP and Tramp-C1 prostate cancer cell lines is associated with methyl-CpG-binding protein MBD2.Oncogene. 2006 Aug 3;25(33):4559-72. doi: 10.1038/sj.onc.1209462. Epub 2006 Jun 19.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] 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.
• [5] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [6] Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells. Toxicol Appl Pharmacol. 2012 Jun 1;261(2):204-16.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] 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.
• [9] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.