Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMPEI1D)

• DOT Name: Trans-3-hydroxy-L-proline dehydratase (L3HYPDH)
• Synonyms: EC 4.2.1.77; Trans-L-3-hydroxyproline dehydratase
• Gene Name: L3HYPDH
• UniProt ID: T3HPD_HUMAN
• PDB ID: 7QPO
• EC Number: 4.2.1.77
• Pfam ID: PF05544
• Sequence:
  MESALAVPRLPPHDPGTPVLSVVDMHTGGEPLRIVLAGCPEVSGPTLLAKRRYMRQHLDH
  VRRRLMFEPRGHRDMYGAVLVPSELPDAHLGVLFLHNEGYSSMCGHAVLALGRFALDFGL
  VPAPPAGTREARVNIHCPCGLVTAFVACEDGRSHGPVRFHSVPAFVLATDLMVDVPGHGK
  VMVDIAYGGAFYAFVTAEKLGLDICSAKTRDLVDAASAVTEAVKAQFKINHPDSEDLAFL
  YGTILTDGKDAYTKEPTTNICVFADEQVDRSPTGSGVTARIALQYHKGLLELNQMRAFKS
  SATGSVFTGKAVREAKCGDFKAVIVEVSGQAHYTGTASFIIEDDDPLRDGFLLK
• Function: Catalyzes the dehydration of trans-3-hydroxy-L-proline to Delta(1)-pyrroline-2-carboxylate (Pyr2C). May be required to degrade trans-3-hydroxy-L-proline from the diet and originating from the degradation of proteins such as collagen-IV that contain it.
• Tissue Specificity: Ubiquitously expressed.
• KEGG Pathway:
  Arginine and proline metabolism (hsa00330)
  Metabolic pathways (hsa01100)

Molecular Interaction Atlas (MIA) of This DOT

11 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 Trans-3-hydroxy-L-proline dehydratase (L3HYPDH).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Trans-3-hydroxy-L-proline dehydratase (L3HYPDH).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Trans-3-hydroxy-L-proline dehydratase (L3HYPDH).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Trans-3-hydroxy-L-proline dehydratase (L3HYPDH).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Trans-3-hydroxy-L-proline dehydratase (L3HYPDH).	[5]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Trans-3-hydroxy-L-proline dehydratase (L3HYPDH).	[6]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Trans-3-hydroxy-L-proline dehydratase (L3HYPDH).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Trans-3-hydroxy-L-proline dehydratase (L3HYPDH).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Trans-3-hydroxy-L-proline dehydratase (L3HYPDH).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Trans-3-hydroxy-L-proline dehydratase (L3HYPDH).	[10]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Trans-3-hydroxy-L-proline dehydratase (L3HYPDH).	[11]

References

• [1] 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.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] 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.
• [4] 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.
• [5] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [6] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [9] 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.
• [10] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [11] 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.