Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDKV2S2)

• DOT Name: Transaldolase (TALDO1)
• Synonyms: EC 2.2.1.2
• Gene Name: TALDO1
• Related Disease:
  Liver cirrhosis
  Transaldolase deficiency
  Acatalasia
  Advanced cancer
  Autoimmune disease
  Breast cancer
  Breast carcinoma
  Chronic kidney disease
  Diabetic kidney disease
  Head-neck squamous cell carcinoma
  Hepatocellular carcinoma
  Hydrops fetalis
  leukaemia
  Leukemia
  Liver failure
  Metabolic disorder
  Multiple sclerosis
  Parkinson disease
  Skin cancer
  Squamous cell carcinoma
  T-cell leukaemia
  Xeroderma pigmentosum
  Rickets
  Sickle-cell anaemia
  T-cell acute lymphoblastic leukaemia
  Type-1/2 diabetes
• UniProt ID: TALDO_HUMAN
• PDB ID: 1F05
• EC Number: 2.2.1.2
• Pfam ID: PF00923
• Sequence:
  MSSSPVKRQRMESALDQLKQFTTVVADTGDFHAIDEYKPQDATTNPSLILAAAQMPAYQE
  LVEEAIAYGRKLGGSQEDQIKNAIDKLFVLFGAEILKKIPGRVSTEVDARLSFDKDAMVA
  RARRLIELYKEAGISKDRILIKLSSTWEGIQAGKELEEQHGIHCNMTLLFSFAQAVACAE
  AGVTLISPFVGRILDWHVANTDKKSYEPLEDPGVKSVTKIYNYYKKFSYKTIVMGASFRN
  TGEIKALAGCDFLTISPKLLGELLQDNAKLVPVLSAKAAQASDLEKIHLDEKSFRWLHNE
  DQMAVEKLSDGIRKFAADAVKLERMLTERMFNAENGK
• Function: Catalyzes the rate-limiting step of the non-oxidative phase in the pentose phosphate pathway. Catalyzes the reversible conversion of sedheptulose-7-phosphate and D-glyceraldehyde 3-phosphate into erythrose-4-phosphate and beta-D-fructose 6-phosphate. Not only acts as a pentose phosphate pathway enzyme, but also affects other metabolite pathways by altering its subcellular localization between the nucleus and the cytoplasm.
• KEGG Pathway:
  Pentose phosphate pathway (hsa00030)
  Metabolic pathways (hsa01100)
  Carbon metabolism (hsa01200)
  Biosynthesis of amino acids (hsa01230)
• Reactome Pathway:
  TALDO1 deficiency (R-HSA-6791055)
  TALDO1 deficiency (R-HSA-6791462)
  Pentose phosphate pathway (R-HSA-71336)
  Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation (R-HSA-8950505)
  NFE2L2 regulates pentose phosphate pathway genes (R-HSA-9818028)
  Insulin effects increased synthesis of Xylulose-5-Phosphate (R-HSA-163754)

Molecular Interaction Atlas (MIA) of This DOT

26 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Liver cirrhosis	DIS4G1GX	Definitive	Biomarker	[1]
Transaldolase deficiency	DIS2FSVR	Definitive	Autosomal recessive	[2]
Acatalasia	DISWKSHU	Strong	Biomarker	[3]
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[4]
Autoimmune disease	DISORMTM	Strong	Biomarker	[5]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[6]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[6]
Chronic kidney disease	DISW82R7	Strong	Biomarker	[7]
Diabetic kidney disease	DISJMWEY	Strong	Biomarker	[8]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Genetic Variation	[9]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[10]
Hydrops fetalis	DISD9BBF	Strong	Genetic Variation	[1]
leukaemia	DISS7D1V	Strong	Genetic Variation	[11]
Leukemia	DISNAKFL	Strong	Genetic Variation	[11]
Liver failure	DISLGEL6	Strong	Biomarker	[12]
Metabolic disorder	DIS71G5H	Strong	Biomarker	[1]
Multiple sclerosis	DISB2WZI	Strong	Biomarker	[13]
Parkinson disease	DISQVHKL	Strong	Biomarker	[14]
Skin cancer	DISTM18U	Strong	Altered Expression	[3]
Squamous cell carcinoma	DISQVIFL	Strong	Genetic Variation	[9]
T-cell leukaemia	DISJ6YIF	Strong	Genetic Variation	[15]
Xeroderma pigmentosum	DISQ9H19	Strong	Altered Expression	[3]
Rickets	DISH89YF	moderate	Biomarker	[16]
Sickle-cell anaemia	DIS5YNZB	Limited	Biomarker	[17]
T-cell acute lymphoblastic leukaemia	DIS17AI2	Limited	Genetic Variation	[18]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[8]

1 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 Transaldolase (TALDO1).	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Transaldolase (TALDO1).	[20]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Transaldolase (TALDO1).	[21]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Transaldolase (TALDO1).	[22]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Transaldolase (TALDO1).	[23]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Transaldolase (TALDO1).	[24]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Transaldolase (TALDO1).	[25]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Transaldolase (TALDO1).	[26]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Transaldolase (TALDO1).	[27]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Transaldolase (TALDO1).	[28]
Selenium	DM25CGV	Approved	Selenium increases the expression of Transaldolase (TALDO1).	[29]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Transaldolase (TALDO1).	[30]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Transaldolase (TALDO1).	[31]
Hydroquinone	DM6AVR4	Approved	Hydroquinone affects the expression of Transaldolase (TALDO1).	[32]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Transaldolase (TALDO1).	[33]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate decreases the expression of Transaldolase (TALDO1).	[34]
Cidofovir	DMA13GD	Approved	Cidofovir increases the expression of Transaldolase (TALDO1).	[24]
Ifosfamide	DMCT3I8	Approved	Ifosfamide increases the expression of Transaldolase (TALDO1).	[24]
Resveratrol	DM3RWXL	Phase 3	Resveratrol affects the expression of Transaldolase (TALDO1).	[35]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Transaldolase (TALDO1).	[26]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Transaldolase (TALDO1).	[36]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Transaldolase (TALDO1).	[37]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone decreases the expression of Transaldolase (TALDO1).	[38]

References

• [1] Transaldolase deficiency: a new cause of hydrops fetalis and neonatal multi-organ disease.J Pediatr. 2006 Nov;149(5):713-7. doi: 10.1016/j.jpeds.2006.08.016.
• [2] Transaldolase deficiency: liver cirrhosis associated with a new inborn error in the pentose phosphate pathway. Am J Hum Genet. 2001 May;68(5):1086-92. doi: 10.1086/320108. Epub 2001 Mar 27.
• [3] Relationship between posttranslational modification of transaldolase and catalase deficiency in UV-sensitive repair-deficient xeroderma pigmentosum fibroblasts and SV40-transformed human cells.Free Radic Biol Med. 2001 Jun 15;30(12):1365-73. doi: 10.1016/s0891-5849(01)00532-9.
• [4] Clinical significance of HOX11L2 expression linked to t(5;14)(q35;q32), of HOX11 expression, and of SIL-TAL fusion in childhood T-cell malignancies: results of EORTC studies 58881 and 58951.Blood. 2004 Jan 15;103(2):442-50. doi: 10.1182/blood-2003-05-1495. Epub 2003 Sep 22.
• [5] Comparative analysis of antibody and cell-mediated autoimmunity to transaldolase and myelin basic protein in patients with multiple sclerosis.J Clin Invest. 1997 Mar 15;99(6):1238-50. doi: 10.1172/JCI119281.
• [6] Synthetic lethality between HER2 and transaldolase in intrinsically resistant HER2-positive breast cancers.Nat Commun. 2018 Oct 15;9(1):4274. doi: 10.1038/s41467-018-06651-x.
• [7] Sodium bicarbonate loading limits tubular cast formation independent of glomerular injury and proteinuria in Dahl salt-sensitive rats.Clin Sci (Lond). 2018 Jun 20;132(11):1179-1197. doi: 10.1042/CS20171630. Print 2018 Jun 15.
• [8] Genetic variability in enzymes of metabolic pathways conferring protection against non-enzymatic glycation versus diabetes-related morbidity and mortality.Clin Chem Lab Med. 2014 Jan 1;52(1):77-83. doi: 10.1515/cclm-2012-0833.
• [9] Genetic variation in Transaldolase 1 and risk of squamous cell carcinoma of the head and neck.Cancer Detect Prev. 2008;32(3):200-8. doi: 10.1016/j.cdp.2008.08.008. Epub 2008 Sep 20.
• [10] Ribose-5-phosphate isomerase A overexpression promotes liver cancer development in transgenic zebrafish via activation of ERK and -catenin pathways.Carcinogenesis. 2019 May 14;40(3):461-473. doi: 10.1093/carcin/bgy155.
• [11] The significance of PTEN and AKT aberrations in pediatric T-cell acute lymphoblastic leukemia.Haematologica. 2012 Sep;97(9):1405-13. doi: 10.3324/haematol.2011.059030. Epub 2012 Apr 4.
• [12] Transaldolase haploinsufficiency in subjects with acetaminophen-induced liver failure.J Inherit Metab Dis. 2020 May;43(3):496-506. doi: 10.1002/jimd.12197. Epub 2020 Jan 1.
• [13] The three-dimensional structure of human transaldolase.FEBS Lett. 2000 Jun 23;475(3):205-8. doi: 10.1016/s0014-5793(00)01658-6.
• [14] Discovery and verification of panels of T-lymphocyte proteins as biomarkers of Parkinson's disease.Sci Rep. 2012;2:953. doi: 10.1038/srep00953. Epub 2012 Dec 11.
• [15] The tal gene undergoes chromosome translocation in T cell leukemia and potentially encodes a helix-loop-helix protein.EMBO J. 1990 Feb;9(2):415-24. doi: 10.1002/j.1460-2075.1990.tb08126.x.
• [16] Transaldolase deficiency in a two-year-old boy with cirrhosis.Mol Genet Metab. 2008 Jun;94(2):255-8. doi: 10.1016/j.ymgme.2008.01.011. Epub 2008 Mar 10.
• [17] Optimized TAL effector nucleases (TALENs) for use in treatment of sickle cell disease.Mol Biosyst. 2012 Apr;8(4):1255-63. doi: 10.1039/c2mb05461b. Epub 2012 Feb 3.
• [18] Genetic rearrangements in relation to immunophenotype and outcome in T-cell acute lymphoblastic leukaemia.Best Pract Res Clin Haematol. 2010 Sep;23(3):307-18. doi: 10.1016/j.beha.2010.08.002. Epub 2010 Oct 30.
• [19] 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.
• [20] 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.
• [21] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [22] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [23] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [24] Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
• [25] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [26] 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.
• [27] 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.
• [28] Proteomic analysis revealed association of aberrant ROS signaling with suberoylanilide hydroxamic acid-induced autophagy in Jurkat T-leukemia cells. Autophagy. 2010 Aug;6(6):711-24. doi: 10.4161/auto.6.6.12397. Epub 2010 Aug 17.
• [29] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [30] 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.
• [31] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [32] Proteomic analysis to identify the cellular responses induced by hydroquinone in human embryonic lung fibroblasts. Toxicol Mech Methods. 2006;16(1):1-6. doi: 10.1080/15376520500191797.
• [33] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [34] Identification of potential biomarkers for predicting acute dermal irritation by proteomic analysis. J Appl Toxicol. 2011 Nov;31(8):762-72.
• [35] Resveratrol downregulates Akt/GSK and ERK signalling pathways in OVCAR-3 ovarian cancer cells. Mol Biosyst. 2012 Apr;8(4):1078-87. doi: 10.1039/c2mb05486h. Epub 2012 Jan 10.
• [36] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [37] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [38] Evaluation of an in vitro model of androgen ablation and identification of the androgen responsive proteome in LNCaP cells. Proteomics. 2007 Jan;7(1):47-63.