Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTK5K0B)

• DOT Name: Prolyl 4-hydroxylase subunit alpha-3 (P4HA3)
• Synonyms: 4-PH alpha-3; EC 1.14.11.2; Procollagen-proline,2-oxoglutarate-4-dioxygenase subunit alpha-3
• Gene Name: P4HA3
• UniProt ID: P4HA3_HUMAN
• EC Number: 1.14.11.2
• Pfam ID: PF13640 ; PF08336
• Sequence:
  MGPGARLAALLAVLALGTGDPERAAARGDTFSALTSVARALAPERRLLGLLRRYLRGEEA
  RLRDLTRFYDKVLSLHEDSTTPVANPLLAFTLIKRLQSDWRNVVHSLEASENIRALKDGY
  EKVEQDLPAFEDLEGAARALMRLQDVYMLNVKGLARGVFQRVTGSAITDLYSPKRLFSLT
  GDDCFQVGKVAYDMGDYYHAIPWLEEAVSLFRGSYGEWKTEDEASLEDALDHLAFAYFRA
  GNVSCALSLSREFLLYSPDNKRMARNVLKYERLLAESPNHVVAEAVIQRPNIPHLQTRDT
  YEGLCQTLGSQPTLYQIPSLYCSYETNSNAYLLLQPIRKEVIHLEPYIALYHDFVSDSEA
  QKIRELAEPWLQRSVVASGEKQLQVEYRISKSAWLKDTVDPKLVTLNHRIAALTGLDVRP
  PYAEYLQVVNYGIGGHYEPHFDHATSPSSPLYRMKSGNRVATFMIYLSSVEAGGATAFIY
  ANLSVPVVRNAALFWWNLHRSGEGDSDTLHAGCPVLVGDKWVANKWIHEYGQEFRRPCSS
  SPED
• Function: Catalyzes the post-translational formation of 4-hydroxyproline in -Xaa-Pro-Gly- sequences in collagens and other proteins.
• Tissue Specificity: Highly expressed in placenta, liver and fetal skin. Weakly expressed in fetal epiphyseal cartilage, fetal liver, fibroblast, lung and skeletal muscle. Expressed also in fibrous cap of carotid atherosclerotic lesions.
• KEGG Pathway:
  Arginine and proline metabolism (hsa00330)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Collagen biosynthesis and modifying enzymes (R-HSA-1650814)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Prolyl 4-hydroxylase subunit alpha-3 (P4HA3).	[1]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Prolyl 4-hydroxylase subunit alpha-3 (P4HA3).	[2]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Prolyl 4-hydroxylase subunit alpha-3 (P4HA3).	[3]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Prolyl 4-hydroxylase subunit alpha-3 (P4HA3).	[5]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Prolyl 4-hydroxylase subunit alpha-3 (P4HA3).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Prolyl 4-hydroxylase subunit alpha-3 (P4HA3).	[4]

References

• [1] 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.
• [2] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [3] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [4] 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.
• [5] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
• [6] Regulation of chromatin assembly and cell transformation by formaldehyde exposure in human cells. Environ Health Perspect. 2017 Sep 21;125(9):097019.