Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7GBQEB)

• DOT Name: 1,5-anhydro-D-fructose reductase (AKR1E2)
• Synonyms: AF reductase; EC 1.1.1.263; Aldo-keto reductase family 1 member C-like protein 2; Aldo-keto reductase family 1 member E2; LoopADR; Testis aldo-keto reductase; htAKR; Testis-specific protein; hTSP
• Gene Name: AKR1E2
• Related Disease:
  Adult germ cell tumor
  Germ cell tumor
  Germ cell tumour
  Hepatocellular carcinoma
  Nervous system disease
• UniProt ID: AKCL2_HUMAN
• EC Number: 1.1.1.263
• Pfam ID: PF00248
• Sequence:
  MGDIPAVGLSSWKASPGKVTEAVKEAIDAGYRHFDCAYFYHNEREVGAGIRCKIKEGAVR
  REDLFIATKLWCTCHKKSLVETACRKSLKALKLNYLDLYLIHWPMGFKPPHPEWIMSCSE
  LSFCLSHPRVQDLPLDESNMVIPSDTDFLDTWEAMEDLVITGLVKNIGVSNFNHEQLERL
  LNKPGLRFKPLTNQIECHPYLTQKNLISFCQSRDVSVTAYRPLGGSCEGVDLIDNPVIKR
  IAKEHGKSPAQILIRFQIQRNVIVIPGSITPSHIKENIQVFDFELTQHDMDNILSLNRNL
  RLAMFPITKNHKDYPFHIEY
• Function: Catalyzes the NADPH-dependent reduction of 1,5-anhydro-D-fructose (AF) to 1,5-anhydro-D-glucitol. Has low NADPH-dependent reductase activity towards 9,10-phenanthrenequinone (in vitro).
• Tissue Specificity: Specifically expressed in testis . Expressed in testicular germ cells and testis interstitial cells .
• BioCyc Pathway: MetaCyc:HS15341-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult germ cell tumor	DISJUCQ7	Strong	Altered Expression	[1]
Germ cell tumor	DIS62070	Strong	Altered Expression	[1]
Germ cell tumour	DISOF3TK	Strong	Altered Expression	[1]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[2]
Nervous system disease	DISJ7GGT	Limited	Biomarker	[3]

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 1,5-anhydro-D-fructose reductase (AKR1E2).	[4]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of 1,5-anhydro-D-fructose reductase (AKR1E2).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of 1,5-anhydro-D-fructose reductase (AKR1E2).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Malathion	DMXZ84M	Approved	Malathion decreases the expression of 1,5-anhydro-D-fructose reductase (AKR1E2).	[6]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of 1,5-anhydro-D-fructose reductase (AKR1E2).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of 1,5-anhydro-D-fructose reductase (AKR1E2).	[9]

References

• [1] Identification of a TSPY co-expression network associated with DNA hypomethylation and tumor gene expression in somatic cancers.J Genet Genomics. 2016 Oct 20;43(10):577-585. doi: 10.1016/j.jgg.2016.09.003. Epub 2016 Sep 17.
• [2] Hypermethylation of ACP1, BMP4, and TSPYL5 in Hepatocellular Carcinoma and Their Potential Clinical Significance.Dig Dis Sci. 2016 Jan;61(1):149-57. doi: 10.1007/s10620-015-3878-3. Epub 2015 Sep 19.
• [3] Ma1, a novel neuron- and testis-specific protein, is recognized by the serum of patients with paraneoplastic neurological disorders.Brain. 1999 Jan;122 ( Pt 1):27-39. doi: 10.1093/brain/122.1.27.
• [4] 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.
• [5] 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.
• [6] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] 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.
• [9] Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells. Toxicol Appl Pharmacol. 2019 Dec 15;385:114814. doi: 10.1016/j.taap.2019.114814. Epub 2019 Nov 9.