Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVZJL3U)

• DOT Name: Fucose-1-phosphate guanylyltransferase (FPGT)
• Synonyms: EC 2.7.7.30; GDP-L-fucose diphosphorylase; GDP-L-fucose pyrophosphorylase
• Gene Name: FPGT
• Related Disease:
  Clear cell renal carcinoma
  Papillary renal cell carcinoma
  Renal cell carcinoma
• UniProt ID: FPGT_HUMAN
• EC Number: 2.7.7.30
• Pfam ID: PF07959
• Sequence:
  MRAVRRGLREGGAMAAARDPPEVSLREATQRKLRRFSELRGKLVARGEFWDIVAITAADE
  KQELAYNQQLSEKLKRKELPLGVQYHVFVDPAGAKIGNGGSTLCALQCLEKLYGDKWNSF
  TILLIHSGGYSQRLPNASALGKIFTALPLGNPIYQMLELKLAMYIDFPLNMNPGILVTCA
  DDIELYSIGEFEFIRFDKPGFTALAHPSSLTIGTTHGVFVLDPFDDLKHRDLEYRSCHRF
  LHKPSIEKMYQFNAVCRPGNFCQQDFAGGDIADLKLDSDYVYTDSLFYMDHKSAKMLLAF
  YEKIGTLSCEIDAYGDFLQALGPGATVEYTRNTSNVIKEESELVEMRQRIFHLLKGTSLN
  VVVLNNSKFYHIGTTEEYLFYFTSDNSLKSELGLQSITFSIFPDIPECSGKTSCIIQSIL
  DSRCSVAPGSVVEYSRLGPDVSVGENCIISGSYILTKAALPAHSFVCSLSLKMNRCLKYA
  TMAFGVQDNLKKSVKTLSDIKLLQFFGVCFLSCLDVWNLKVTEELFSGNKTCLSLWTARI
  FPVCSSLSDSVITSLKMLNAVKNKSAFSLNSYKLLSIEEMLIYKDVEDMITYREQIFLEI
  SLKSSLM
• Function: Catalyzes the formation of GDP-L-fucose from GTP and L-fucose-1-phosphate. Functions as a salvage pathway to reutilize L-fucose arising from the turnover of glycoproteins and glycolipids.
• Tissue Specificity: Expressed in many tissues.
• KEGG Pathway:
  Fructose and mannose metabolism (hsa00051)
  Amino sugar and nucleotide sugar metabolism (hsa00520)
  Metabolic pathways (hsa01100)
  Biosynthesis of nucleotide sugars (hsa01250)
• Reactome Pathway: GDP-fucose biosynthesis (R-HSA-6787639)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[1]
Papillary renal cell carcinoma	DIS25HBV	Strong	Biomarker	[1]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[1]

11 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 Fucose-1-phosphate guanylyltransferase (FPGT).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Fucose-1-phosphate guanylyltransferase (FPGT).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Fucose-1-phosphate guanylyltransferase (FPGT).	[4]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Fucose-1-phosphate guanylyltransferase (FPGT).	[5]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Fucose-1-phosphate guanylyltransferase (FPGT).	[6]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Fucose-1-phosphate guanylyltransferase (FPGT).	[7]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Fucose-1-phosphate guanylyltransferase (FPGT).	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Fucose-1-phosphate guanylyltransferase (FPGT).	[9]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Fucose-1-phosphate guanylyltransferase (FPGT).	[10]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride decreases the expression of Fucose-1-phosphate guanylyltransferase (FPGT).	[11]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of Fucose-1-phosphate guanylyltransferase (FPGT).	[12]

References

• [1] Integrated molecular analysis of clear-cell renal cell carcinoma.Nat Genet. 2013 Aug;45(8):860-7. doi: 10.1038/ng.2699. Epub 2013 Jun 24.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [6] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [7] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [8] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [11] The contact allergen nickel triggers a unique inflammatory and proangiogenic gene expression pattern via activation of NF-kappaB and hypoxia-inducible factor-1alpha. J Immunol. 2007 Mar 1;178(5):3198-207.
• [12] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.