Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLNEC2X)

• DOT Name: FGGY carbohydrate kinase domain-containing protein (FGGY)
• Synonyms: D-ribulokinase FGGY; EC 2.7.1.47
• Gene Name: FGGY
• Related Disease:
  Obesity
  Amyotrophic lateral sclerosis
• UniProt ID: FGGY_HUMAN
• EC Number: 2.7.1.47
• Pfam ID: PF02782 ; PF00370
• Sequence:
  MSGGEQKPERYYVGVDVGTGSVRAALVDQSGVLLAFADQPIKNWEPQFNHHEQSSEDIWA
  ACCVVTKKVVQGIDLNQIRGLGFDATCSLVVLDKQFHPLPVNQEGDSHRNVIMWLDHRAV
  SQVNRINETKHSVLQYVGGVMSVEMQAPKLLWLKENLREICWDKAGHFFDLPDFLSWKAT
  GVTARSLCSLVCKWTYSAEKGWDDSFWKMIGLEDFVADNYSKIGNQVLPPGASLGNGLTP
  EAARDLGLLPGIAVAASLIDAHAGGLGVIGADVRGHGLICEGQPVTSRLAVICGTSSCHM
  GISKDPIFVPGVWGPYFSAMVPGFWLNEGGQSVTGKLIDHMVQGHAAFPELQVKATARCQ
  SIYAYLNSHLDLIKKAQPVGFLTVDLHVWPDFHGNRSPLADLTLKGMVTGLKLSQDLDDL
  AILYLATVQAIALGTRFIIEAMEAAGHSISTLFLCGGLSKNPLFVQMHADITGMPVVLSQ
  EVESVLVGAAVLGACASGDFASVQEAMAKMSKVGKVVFPRLQDKKYYDKKYQVFLKLVEH
  QKEYLAIMNDD
• Function: Catalyzes ATP-dependent phosphorylation of D-ribulose at C-5 to form D-ribulose 5-phosphate. Postulated to function in a metabolite repair mechanism by preventing toxic accumulation of free D-ribulose formed by non-specific phosphatase activities. Alternatively, may play a role in regulating D-ribulose 5-phosphate recycling in the pentose phosphate pathway. Can phosphorylate ribitol with low efficiency.
• Tissue Specificity: Expressed in kidney, lung and small intestine and to a lower extent in liver and detected in cerebrospinal fluid (at protein level).
• KEGG Pathway:
  Pentose and glucuro.te interconversions (hsa00040)
  Metabolic pathways (hsa01100)
• BioCyc Pathway: MetaCyc:ENSG00000172456-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Obesity	DIS47Y1K	Strong	Biomarker	[1]
Amyotrophic lateral sclerosis	DISF7HVM	moderate	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of FGGY carbohydrate kinase domain-containing protein (FGGY).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of FGGY carbohydrate kinase domain-containing protein (FGGY).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of FGGY carbohydrate kinase domain-containing protein (FGGY).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of FGGY carbohydrate kinase domain-containing protein (FGGY).	[6]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of FGGY carbohydrate kinase domain-containing protein (FGGY).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of FGGY carbohydrate kinase domain-containing protein (FGGY).	[10]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of FGGY carbohydrate kinase domain-containing protein (FGGY).	[11]

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of FGGY carbohydrate kinase domain-containing protein (FGGY).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of FGGY carbohydrate kinase domain-containing protein (FGGY).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of FGGY carbohydrate kinase domain-containing protein (FGGY).	[12]

References

• [1] Prenatal Exposure to Bisphenol A Disrupts Naturally Occurring Bimodal DNA Methylation at Proximal Promoter of fggy, an Obesity-Relevant Gene Encoding a Carbohydrate Kinase, in Gonadal White Adipose Tissues of CD-1 Mice.Endocrinology. 2018 Feb 1;159(2):779-794. doi: 10.1210/en.2017-00711.
• [2] Analysis of DPP6 and FGGY as candidate genes for amyotrophic lateral sclerosis.Amyotroph Lateral Scler. 2010 Aug;11(4):389-91. doi: 10.3109/17482960903358857.
• [3] 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.
• [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] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [6] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [7] 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.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] 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.
• [10] 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.
• [11] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [12] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.