Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNOYLG9)

DOT Name PHD finger protein 3 (PHF3)
Gene Name PHF3
Related Disease
Inherited retinal dystrophy ( )
Adult glioblastoma ( )
Alcohol dependence ( )
Astrocytoma ( )
Glioblastoma multiforme ( )
Major depressive disorder ( )
Retinitis pigmentosa 25 ( )
Retinitis pigmentosa ( )
UniProt ID
PHF3_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
2DME; 6IC8; 6IC9; 6Q2V; 6Q5Y
Pfam ID
PF00628 ; PF07744 ; PF07500
Sequence
MDIVDTFNHLIPTEHLDDALFLGSNLENEVCEDFSASQNVLEDSLKNMLSDKDPMLGSAS
NQFCLPVLDSNDPNFQMPCSTVVGLDDIMDEGVVKESGNDTIDEEELILPNRNLRDKVEE
NSVRSPRKSPRLMAQEQVRSLRQSTIAKRSNAAPLSNTKKASGKTVSTAKAGVKQPERSQ
VKEEVCMSLKPEYHKENRRCSRNSGQIEVVPEVSVSSSHSSVSSCLEMKDEDGLDSKHKC
NNPGEIDVPSHELNCSLLSETCVTIGEKKNEALMECKAKPVGSPLFKFSDKEEHEQNDSI
SGKTGETVVEEMIATRKVEQDSKETVKLSHEDDHILEDAGSSDISSDAACTNPNKTENSL
VGLPSCVDEVTECNLELKDTMGIADKTENTLERNKIEPLGYCEDAESNRQLESTEFNKSN
LEVVDTSTFGPESNILENAICDVPDQNSKQLNAIESTKIESHETANLQDDRNSQSSSVSY
LESKSVKSKHTKPVIHSKQNMTTDAPKKIVAAKYEVIHSKTKVNVKSVKRNTDVPESQQN
FHRPVKVRKKQIDKEPKIQSCNSGVKSVKNQAHSVLKKTLQDQTLVQIFKPLTHSLSDKS
HAHPGCLKEPHHPAQTGHVSHSSQKQCHKPQQQAPAMKTNSHVKEELEHPGVEHFKEEDK
LKLKKPEKNLQPRQRRSSKSFSLDEPPLFIPDNIATIRREGSDHSSSFESKYMWTPSKQC
GFCKKPHGNRFMVGCGRCDDWFHGDCVGLSLSQAQQMGEEDKEYVCVKCCAEEDKKTEIL
DPDTLENQATVEFHSGDKTMECEKLGLSKHTTNDRTKYIDDTVKHKVKILKRESGEGRNS
SDCRDNEIKKWQLAPLRKMGQPVLPRRSSEEKSEKIPKESTTVTCTGEKASKPGTHEKQE
MKKKKVEKGVLNVHPAASASKPSADQIRQSVRHSLKDILMKRLTDSNLKVPEEKAAKVAT
KIEKELFSFFRDTDAKYKNKYRSLMFNLKDPKNNILFKKVLKGEVTPDHLIRMSPEELAS
KELAAWRRRENRHTIEMIEKEQREVERRPITKITHKGEIEIESDAPMKEQEAAMEIQEPA
ANKSLEKPEGSEKQKEEVDSMSKDTTSQHRQHLFDLNCKICIGRMAPPVDDLSPKKVKVV
VGVARKHSDNEAESIADALSSTSNILASEFFEEEKQESPKSTFSPAPRPEMPGTVEVEST
FLARLNFIWKGFINMPSVAKFVTKAYPVSGSPEYLTEDLPDSIQVGGRISPQTVWDYVEK
IKASGTKEICVVRFTPVTEEDQISYTLLFAYFSSRKRYGVAANNMKQVKDMYLIPLGATD
KIPHPLVPFDGPGLELHRPNLLLGLIIRQKLKRQHSACASTSHIAETPESAPPIALPPDK
KSKIEVSTEEAPEEENDFFNSFTTVLHKQRNKPQQNLQEDLPTAVEPLMEVTKQEPPKPL
RFLPGVLIGWENQPTTLELANKPLPVDDILQSLLGTTGQVYDQAQSVMEQNTVKEIPFLN
EQTNSKIEKTDNVEVTDGENKEIKVKVDNISESTDKSAEIETSVVGSSSISAGSLTSLSL
RGKPPDVSTEAFLTNLSIQSKQEETVESKEKTLKRQLQEDQENNLQDNQTSNSSPCRSNV
GKGNIDGNVSCSENLVANTARSPQFINLKRDPRQAAGRSQPVTTSESKDGDSCRNGEKHM
LPGLSHNKEHLTEQINVEEKLCSAEKNSCVQQSDNLKVAQNSPSVENIQTSQAEQAKPLQ
EDILMQNIETVHPFRRGSAVATSHFEVGNTCPSEFPSKSITFTSRSTSPRTSTNFSPMRP
QQPNLQHLKSSPPGFPFPGPPNFPPQSMFGFPPHLPPPLLPPPGFGFAQNPMVPWPPVVH
LPGQPQRMMGPLSQASRYIGPQNFYQVKDIRRPERRHSDPWGRQDQQQLDRPFNRGKGDR
QRFYSDSHHLKRERHEKEWEQESERHRRRDRSQDKDRDRKSREEGHKDKERARLSHGDRG
TDGKASRDSRNVDKKPDKPKSEDYEKDKEREKSKHREGEKDRDRYHKDRDHTDRTKSKR
Tissue Specificity Ubiquitous. Expression is significantly reduced or lost in glioblastomas, glioblastoma cell lines, anaplastic astrocytomas, and astrocytomas.

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Inherited retinal dystrophy DISGGL77 Definitive Genetic Variation [1]
Adult glioblastoma DISVP4LU Strong Altered Expression [2]
Alcohol dependence DIS4ZSCO Strong Biomarker [3]
Astrocytoma DISL3V18 Strong Altered Expression [2]
Glioblastoma multiforme DISK8246 Strong Biomarker [4]
Major depressive disorder DIS4CL3X Strong Genetic Variation [5]
Retinitis pigmentosa 25 DISTIKZB Strong Genetic Variation [6]
Retinitis pigmentosa DISCGPY8 Limited CausalMutation [7]
------------------------------------------------------------------------------------
⏷ Show the Full List of 8 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
12 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 PHD finger protein 3 (PHF3). [8]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of PHD finger protein 3 (PHF3). [9]
Selenium DM25CGV Approved Selenium decreases the expression of PHD finger protein 3 (PHF3). [11]
Phenobarbital DMXZOCG Approved Phenobarbital affects the expression of PHD finger protein 3 (PHF3). [12]
Testosterone enanthate DMB6871 Approved Testosterone enanthate affects the expression of PHD finger protein 3 (PHF3). [13]
Nicotine DMWX5CO Approved Nicotine increases the expression of PHD finger protein 3 (PHF3). [14]
Melphalan DMOLNHF Approved Melphalan decreases the expression of PHD finger protein 3 (PHF3). [15]
Clorgyline DMCEUJD Approved Clorgyline increases the expression of PHD finger protein 3 (PHF3). [16]
Tocopherol DMBIJZ6 Phase 2 Tocopherol decreases the expression of PHD finger protein 3 (PHF3). [11]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide increases the expression of PHD finger protein 3 (PHF3). [18]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of PHD finger protein 3 (PHF3). [20]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of PHD finger protein 3 (PHF3). [21]
------------------------------------------------------------------------------------
⏷ Show the Full List of 12 Drug(s)
4 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Quercetin DM3NC4M Approved Quercetin increases the phosphorylation of PHD finger protein 3 (PHF3). [10]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of PHD finger protein 3 (PHF3). [17]
TAK-243 DM4GKV2 Phase 1 TAK-243 decreases the sumoylation of PHD finger protein 3 (PHF3). [19]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of PHD finger protein 3 (PHF3). [10]
------------------------------------------------------------------------------------

References

1 Whole Genome Sequencing Increases Molecular Diagnostic Yield Compared with Current Diagnostic Testing for Inherited Retinal Disease.Ophthalmology. 2016 May;123(5):1143-50. doi: 10.1016/j.ophtha.2016.01.009. Epub 2016 Feb 9.
2 PHF3 expression is frequently reduced in glioma.Cytogenet Cell Genet. 2001;94(3-4):131-6. doi: 10.1159/000048804.
3 Common PTP4A1-PHF3-EYS variants are specific for alcohol dependence.Am J Addict. 2014 Jul-Aug;23(4):411-4. doi: 10.1111/j.1521-0391.2013.12115.x. Epub 2013 Sep 13.
4 Autoantibodies against GLEA2 and PHF3 in glioblastoma: tumor-associated autoantibodies correlated with prolonged survival.Int J Cancer. 2005 Nov 10;117(3):456-9. doi: 10.1002/ijc.20929.
5 Genome-wide interaction study of a proxy for stress-sensitivity and its prediction of major depressive disorder.PLoS One. 2018 Dec 20;13(12):e0209160. doi: 10.1371/journal.pone.0209160. eCollection 2018.
6 Nonsyndromic retinitis pigmentosa is highly prevalent in the Jerusalem region with a high frequency of founder mutations.Mol Vis. 2015 Jul 17;21:783-92. eCollection 2015.
7 Molecular genetic analysis using targeted NGS analysis of 677 individuals with retinal dystrophy.Sci Rep. 2019 Feb 4;9(1):1219. doi: 10.1038/s41598-018-38007-2.
8 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
9 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.
10 Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
11 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.
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 Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
14 Nicotinic modulation of gene expression in SH-SY5Y neuroblastoma cells. Brain Res. 2006 Oct 20;1116(1):39-49.
15 Bone marrow osteoblast damage by chemotherapeutic agents. PLoS One. 2012;7(2):e30758. doi: 10.1371/journal.pone.0030758. Epub 2012 Feb 17.
16 Anti-oncogenic and pro-differentiation effects of clorgyline, a monoamine oxidase A inhibitor, on high grade prostate cancer cells. BMC Med Genomics. 2009 Aug 20;2:55. doi: 10.1186/1755-8794-2-55.
17 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.
18 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
19 Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
20 Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
21 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.