Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWG3P6C)

• DOT Name: Headcase protein homolog (HECA)
• Synonyms: hHDC
• Gene Name: HECA
• Related Disease:
  Neoplasm
  Colorectal neoplasm
  Hepatocellular carcinoma
• UniProt ID: HDC_HUMAN
• Pfam ID: PF16002 ; PF15353
• Sequence:
  MPNPKNSKGGRKNKRANSSGDEQENGAGALAAAGAAGAAAGGALAAAAGCGAAAAGAPGA
  GGAAGAGGAGTGAANAAAAAGAAAAGDAKNEAPCATPLICSFGRPVDLEKDDYQKVVCNN
  EHCPCSTWMHLQCFYEWESSILVQFNCIGRARSWNEKQCRQNMWTKKGYDLAFRFCSCRC
  GQGHLKKDTDWYQVKRMQDEKKKKSGSEKNTGRPPGEAAEEAKKCRPPNKPQKGPSHDLP
  RRHSMDRQNSQEKAVGAAAYGARSPGGSPGQSPPTGYSILSPAHFSGPRSSRYLGEFLKN
  AIHLEPHKKAMAGGHVFRNAHFDYSPAGLAVHRGGHFDTPVQFLRRLDLSELLTHIPRHK
  LNTFHVRMEDDAQVGQGEDLRKFILAALSASHRNVVNCALCHRALPVFEQFPLVDGTLFL
  SPSRHDEIEYDVPCHLQGRLMHLYAVCVDCLEGVHKIICIKCKSRWDGSWHQLGTMYTYD
  ILAASPCCQARLNCKHCGKPVIDVRIGMQYFSEYSNVQQCPHCGNLDYHFVKPFSSFKVL
  EAY
• Function: May play an important role in some human cancers. May be part of the regulatory mechanism in the development of epithelial tube networks such as the circulatory system and lungs.
• Tissue Specificity: Expressed in all tissues examined. Highest levels are in the spleen, thymus, peripheral blood and heart. Lowest in the kidney and pancreas.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Biomarker	[1]
Colorectal neoplasm	DISR1UCN	Strong	Biomarker	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[3]

14 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 Headcase protein homolog (HECA).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Headcase protein homolog (HECA).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Headcase protein homolog (HECA).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Headcase protein homolog (HECA).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Headcase protein homolog (HECA).	[8]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Headcase protein homolog (HECA).	[9]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Headcase protein homolog (HECA).	[10]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Headcase protein homolog (HECA).	[11]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Headcase protein homolog (HECA).	[12]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Headcase protein homolog (HECA).	[13]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Headcase protein homolog (HECA).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Headcase protein homolog (HECA).	[16]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Headcase protein homolog (HECA).	[17]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Headcase protein homolog (HECA).	[18]

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 affects the methylation of Headcase protein homolog (HECA).	[15]

References

• [1] Headcase is a Repressor of Lamellocyte Fate in Drosophila melanogaster.Genes (Basel). 2019 Mar 5;10(3):173. doi: 10.3390/genes10030173.
• [2] A homologue of the Drosophila headcase protein is a novel tumor marker for early-stage colorectal cancer.Oncol Rep. 2006 Apr;15(4):919-26.
• [3] The Human Homolog of Drosophila Headcase Acts as a Tumor Suppressor through Its Blocking Effect on the Cell Cycle in Hepatocellular Carcinoma.PLoS One. 2015 Sep 10;10(9):e0137579. doi: 10.1371/journal.pone.0137579. eCollection 2015.
• [4] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [5] 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.
• [6] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [7] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] 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.
• [10] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [11] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [12] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [13] 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.
• [14] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [15] 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.
• [16] 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.
• [17] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [18] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.