Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTUQ5O3)

• DOT Name: Prolyl 3-hydroxylase OGFOD1 (OGFOD1)
• Synonyms: EC 1.14.11.-; 2-oxoglutarate and iron-dependent oxygenase domain-containing protein 1; Termination and polyadenylation 1 homolog; uS12 prolyl 3-hydroxylase
• Gene Name: OGFOD1
• Related Disease:
  Breast cancer
  Breast carcinoma
  Multiple sclerosis
  Coronary heart disease
• UniProt ID: OGFD1_HUMAN
• PDB ID: 4NHX; 4NHY
• EC Number: 1.14.11.-
• Pfam ID: PF13661 ; PF10637
• Sequence:
  MNGKRPAEPGPARVGKKGKKEVMAEFSDAVTEETLKKQVAEAWSRRTPFSHEVIVMDMDP
  FLHCVIPNFIQSQDFLEGLQKELMNLDFHEKYNDLYKFQQSDDLKKRREPHISTLRKILF
  EDFRSWLSDISKIDLESTIDMSCAKYEFTDALLCHDDELEGRRIAFILYLVPPWDRSMGG
  TLDLYSIDEHFQPKQIVKSLIPSWNKLVFFEVSPVSFHQVSEVLSEEKSRLSISGWFHGP
  SLTRPPNYFEPPIPRSPHIPQDHEILYDWINPTYLDMDYQVQIQEEFEESSEILLKEFLK
  PEKFTKVCEALEHGHVEWSSRGPPNKRFYEKAEESKLPEILKECMKLFRSEALFLLLSNF
  TGLKLHFLAPSEEDEMNDKKEAETTDITEEGTSHSPPEPENNQMAISNNSQQSNEQTDPE
  PEENETKKESSVPMCQGELRHWKTGHYTLIHDHSKAEFALDLILYCGCEGWEPEYGGFTS
  YIAKGEDEELLTVNPESNSLALVYRDRETLKFVKHINHRSLEQKKTFPNRTGFWDFSFIY
  YE
• Function: Prolyl 3-hydroxylase that catalyzes 3-hydroxylation of 'Pro-62' of small ribosomal subunit uS12 (RPS23), thereby regulating protein translation termination efficiency. Involved in stress granule formation.
• Reactome Pathway: Protein hydroxylation (R-HSA-9629569)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Definitive	Biomarker	[1]
Breast carcinoma	DIS2UE88	Definitive	Biomarker	[1]
Multiple sclerosis	DISB2WZI	Strong	Genetic Variation	[2]
Coronary heart disease	DIS5OIP1	Limited	Genetic Variation	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Prolyl 3-hydroxylase OGFOD1 (OGFOD1).	[4]

15 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 Prolyl 3-hydroxylase OGFOD1 (OGFOD1).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Prolyl 3-hydroxylase OGFOD1 (OGFOD1).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Prolyl 3-hydroxylase OGFOD1 (OGFOD1).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Prolyl 3-hydroxylase OGFOD1 (OGFOD1).	[8]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Prolyl 3-hydroxylase OGFOD1 (OGFOD1).	[9]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Prolyl 3-hydroxylase OGFOD1 (OGFOD1).	[10]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Prolyl 3-hydroxylase OGFOD1 (OGFOD1).	[11]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Prolyl 3-hydroxylase OGFOD1 (OGFOD1).	[12]
Vitamin C	DMXJ7O8	Approved	Vitamin C decreases the expression of Prolyl 3-hydroxylase OGFOD1 (OGFOD1).	[10]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Prolyl 3-hydroxylase OGFOD1 (OGFOD1).	[13]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Prolyl 3-hydroxylase OGFOD1 (OGFOD1).	[14]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Prolyl 3-hydroxylase OGFOD1 (OGFOD1).	[15]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Prolyl 3-hydroxylase OGFOD1 (OGFOD1).	[16]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Prolyl 3-hydroxylase OGFOD1 (OGFOD1).	[17]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Prolyl 3-hydroxylase OGFOD1 (OGFOD1).	[18]

References

• [1] OGFOD1 is required for breast cancer cell proliferation and is associated with poor prognosis in breast cancer.Oncotarget. 2015 Aug 14;6(23):19528-41. doi: 10.18632/oncotarget.3683.
• [2] The role of TPA I/D and PAI-1 4G/5G polymorphisms in multiple sclerosis.Dis Markers. 2014;2014:362708. doi: 10.1155/2014/362708. Epub 2014 Apr 16.
• [3] Platelet polymorphisms: frequency distribution and association with coronary artery disease in an Indian population.Platelets. 2011;22(2):85-91. doi: 10.3109/09537104.2010.522275. Epub 2010 Oct 29.
• [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] 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.
• [6] 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.
• [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] The thioxotriazole copper(II) complex A0 induces endoplasmic reticulum stress and paraptotic death in human cancer cells. J Biol Chem. 2009 Sep 4;284(36):24306-19.
• [9] 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.
• [10] Synergistic effects of arsenic trioxide combined with ascorbic acid in human osteosarcoma MG-63 cells: a systems biology analysis. Eur Rev Med Pharmacol Sci. 2014;18(24):3877-88.
• [11] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [12] 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.
• [13] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [14] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [15] 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.
• [16] 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.
• [17] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [18] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.