Details of Drug Off-Target (DOT)

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

• DOT Name: 5-phosphohydroxy-L-lysine phospho-lyase (PHYKPL)
• Synonyms: EC 4.2.3.134; Alanine--glyoxylate aminotransferase 2-like 2
• Gene Name: PHYKPL
• Related Disease:
  Acute myelogenous leukaemia
  Phosphohydroxylysinuria
• UniProt ID: AT2L2_HUMAN
• EC Number: 4.2.3.134
• Pfam ID: PF00202
• Sequence:
  MAADQRPKADTLALRQRLISSSCRLFFPEDPVKIVRAQGQYMYDEQGAEYIDCISNVAHV
  GHCHPLVVQAAHEQNQVLNTNSRYLHDNIVDYAQRLSETLPEQLCVFYFLNSGSEANDLA
  LRLARHYTGHQDVVVLDHAYHGHLSSLIDISPYKFRNLDGQKEWVHVAPLPDTYRGPYRE
  DHPNPAMAYANEVKRVVSSAQEKGRKIAAFFAESLPSVGGQIIPPAGYFSQVAEHIRKAG
  GVFVADEIQVGFGRVGKHFWAFQLQGKDFVPDIVTMGKSIGNGHPVACVAATQPVARAFE
  ATGVEYFNTFGGSPVSCAVGLAVLNVLEKEQLQDHATSVGSFLMQLLGQQKIKHPIVGDV
  RGVGLFIGVDLIKDEATRTPATEEAAYLVSRLKENYVLLSTDGPGRNILKFKPPMCFSLD
  NARQVVAKLDAILTDMEEKVRSCETLRLQP
• Function: Catalyzes the pyridoxal-phosphate-dependent breakdown of 5-phosphohydroxy-L-lysine, converting it to ammonia, inorganic phosphate and 2-aminoadipate semialdehyde.
• KEGG Pathway:
  Lysine degradation (hsa00310)
  Metabolic pathways (hsa01100)
• Reactome Pathway:
  Lysine catabolism (R-HSA-71064)
  Collagen degradation (R-HSA-1442490)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[1]
Phosphohydroxylysinuria	DISYMHY8	Limited	Autosomal recessive	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of 5-phosphohydroxy-L-lysine phospho-lyase (PHYKPL).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of 5-phosphohydroxy-L-lysine phospho-lyase (PHYKPL).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of 5-phosphohydroxy-L-lysine phospho-lyase (PHYKPL).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of 5-phosphohydroxy-L-lysine phospho-lyase (PHYKPL).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of 5-phosphohydroxy-L-lysine phospho-lyase (PHYKPL).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of 5-phosphohydroxy-L-lysine phospho-lyase (PHYKPL).	[8]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of 5-phosphohydroxy-L-lysine phospho-lyase (PHYKPL).	[9]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of 5-phosphohydroxy-L-lysine phospho-lyase (PHYKPL).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of 5-phosphohydroxy-L-lysine phospho-lyase (PHYKPL).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of 5-phosphohydroxy-L-lysine phospho-lyase (PHYKPL).	[11]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of 5-phosphohydroxy-L-lysine phospho-lyase (PHYKPL).	[12]

References

• [1] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [2] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [5] 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.
• [6] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [7] 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.
• [8] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [9] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [10] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [11] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [12] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.