Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKI6HM0)

• DOT Name: Hepatocyte growth factor activator (HGFAC)
• Synonyms: HGF activator; HGFA; EC 3.4.21.-
• Gene Name: HGFAC
• UniProt ID: HGFA_HUMAN
• PDB ID: 1YBW; 1YC0; 2R0K; 2R0L; 2WUB; 2WUC; 3K2U
• EC Number: 3.4.21.-
• Pfam ID: PF00008 ; PF00040 ; PF00051 ; PF00089
• Sequence:
  MGRWAWVPSPWPPPGLGPFLLLLLLLLLLPRGFQPQPGGNRTESPEPNATATPAIPTILV
  TSVTSETPATSAPEAEGPQSGGLPPPPRAVPSSSSPQAQALTEDGRPCRFPFRYGGRMLH
  ACTSEGSAHRKWCATTHNYDRDRAWGYCVEATPPPGGPAALDPCASGPCLNGGSCSNTQD
  PQSYHCSCPRAFTGKDCGTEKCFDETRYEYLEGGDRWARVRQGHVEQCECFGGRTWCEGT
  RHTACLSSPCLNGGTCHLIVATGTTVCACPPGFAGRLCNIEPDERCFLGNGTGYRGVAST
  SASGLSCLAWNSDLLYQELHVDSVGAAALLGLGPHAYCRNPDNDERPWCYVVKDSALSWE
  YCRLEACESLTRVQLSPDLLATLPEPASPGRQACGRRHKKRTFLRPRIIGGSSSLPGSHP
  WLAAIYIGDSFCAGSLVHTCWVVSAAHCFSHSPPRDSVSVVLGQHFFNRTTDVTQTFGIE
  KYIPYTLYSVFNPSDHDLVLIRLKKKGDRCATRSQFVQPICLPEPGSTFPAGHKCQIAGW
  GHLDENVSGYSSSLREALVPLVADHKCSSPEVYGADISPNMLCAGYFDCKSDACQGDSGG
  PLACEKNGVAYLYGIISWGDGCGRLHKPGVYTRVANYVDWINDRIRPPRRLVAPS
• Function: Activates hepatocyte growth factor (HGF) by converting it from a single chain to a heterodimeric form.
• Tissue Specificity: Liver.
• Reactome Pathway: MET Receptor Activation (R-HSA-6806942)

Molecular Interaction Atlas (MIA) of This DOT

3 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 Hepatocyte growth factor activator (HGFAC).	[1]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Hepatocyte growth factor activator (HGFAC).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Hepatocyte growth factor activator (HGFAC).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Hepatocyte growth factor activator (HGFAC).	[2]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Hepatocyte growth factor activator (HGFAC).	[4]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Hepatocyte growth factor activator (HGFAC).	[5]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Hepatocyte growth factor activator (HGFAC).	[6]

References

• [1] 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.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [4] Microarray analysis of H2O2-, HNE-, or tBH-treated ARPE-19 cells. Free Radic Biol Med. 2002 Nov 15;33(10):1419-32.
• [5] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [6] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [7] 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.