Details of Drug Off-Target (DOT)

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

DOT Name PHD finger protein 20-like protein 1 (PHF20L1)
Gene Name PHF20L1
Related Disease
Advanced cancer ( )
Brain cancer ( )
Breast cancer ( )
Breast carcinoma ( )
Neoplasm ( )
Retinoblastoma ( )
Stroke ( )
UniProt ID
P20L1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
2EQM; 2EQU; 2JTF; 6L0X; 6L10; 6L1C; 6L1F; 6L1I; 6L1P
Pfam ID
PF16660 ; PF20826 ; PF18104
Sequence
MSKKPPNRPGITFEIGARLEALDYLQKWYPSRIEKIDYEEGKMLVHFERWSHRYDEWIYW
DSNRLRPLERPALRKEGLKDEEDFFDFKAGEEVLARWTDCRYYPAKIEAINKEGTFTVQF
YDGVIRCLKRMHIKAMPEDAKGQVKSQHPLSWCCPIDPAGSCNQSMGSEDWIALVKAAAA
AAAKNKTGSKPRTSANSNKDKDKDERKWFKVPSKKEETSTCIATPDVEKKEDLPTSSETF
GLHVENVPKMVFPQPESTLSNKRKNNQGNSFQAKRARLNKITGLLASKAVGVDGAEKKED
YNETAPMLEQAISPKPQSQKKNEADISSSANTQKPALLSSTLSSGKARSKKCKHESGDSS
GCIKPPKSPLSPELIQVEDLTLVSQLSSSVINKTSPPQPVNPPRPFKHSERRRRSQRLAT
LPMPDDSVEKVSSPSPATDGKVFSISSQNQQESSVPEVPDVAHLPLEKLGPCLPLDLSRG
SEVTAPVASDSSYRNECPRAEKEDTQMLPNPSSKAIADGRGAPAAAGISKTEKKVKLEDK
SSTAFGKRKEKDKERREKRDKDHYRPKQKKKKKKKKKSKQHDYSDYEDSSLEFLERCSSP
LTRSSGSSLASRSMFTEKTTTYQYPRAILSVDLSGENLSDVDFLDDSSTESLLLSGDEYN
QDFDSTNFEESQDEDDALNEIVRCICEMDEENGFMIQCEECLCWQHSVCMGLLEESIPEQ
YICYICRDPPGQRWSAKYRYDKEWLNNGRMCGLSFFKENYSHLNAKKIVSTHHLLADVYG
VTEVLHGLQLKIGILKNKHHPDLHLWACSGKRKDQDQIIAGVEKKIAQDTVNREEKKYVQ
NHKEPPRLPLKMEGTYITSEHSYQKPQSFGQDCKSLADPGSSDDDDVSSLEEEQEFHMRS
KNSLQYSAKEHGMPEKNPAEGNTVFVYNDKKGTEDPGDSHLQWQLNLLTHIENVQNEVTS
RMDLIEKEVDVLESWLDFTGELEPPDPLARLPQLKRHIKQLLIDMGKVQQIATLCSV
Function
Is a negative regulator of proteasomal degradation of a set of methylated proteins, including DNMT1 and SOX2. Involved in the maintainance of embryonic stem cells pluripotency, through the regulation of SOX2 levels.
Reactome Pathway
Formation of WDR5-containing histone-modifying complexes (R-HSA-9772755 )

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Advanced cancer DISAT1Z9 Strong Biomarker [1]
Brain cancer DISBKFB7 Strong Biomarker [2]
Breast cancer DIS7DPX1 Strong Biomarker [1]
Breast carcinoma DIS2UE88 Strong Biomarker [1]
Neoplasm DISZKGEW Strong Biomarker [2]
Retinoblastoma DISVPNPB Strong Posttranslational Modification [3]
Stroke DISX6UHX moderate Genetic Variation [4]
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⏷ Show the Full List of 7 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
8 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 20-like protein 1 (PHF20L1). [5]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of PHD finger protein 20-like protein 1 (PHF20L1). [6]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide decreases the expression of PHD finger protein 20-like protein 1 (PHF20L1). [8]
Folic acid DMEMBJC Approved Folic acid decreases the expression of PHD finger protein 20-like protein 1 (PHF20L1). [9]
SNDX-275 DMH7W9X Phase 3 SNDX-275 decreases the expression of PHD finger protein 20-like protein 1 (PHF20L1). [10]
Amiodarone DMUTEX3 Phase 2/3 Trial Amiodarone increases the expression of PHD finger protein 20-like protein 1 (PHF20L1). [11]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of PHD finger protein 20-like protein 1 (PHF20L1). [14]
Coumestrol DM40TBU Investigative Coumestrol decreases the expression of PHD finger protein 20-like protein 1 (PHF20L1). [6]
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⏷ Show the Full List of 8 Drug(s)
3 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of PHD finger protein 20-like protein 1 (PHF20L1). [7]
TAK-243 DM4GKV2 Phase 1 TAK-243 increases the sumoylation of PHD finger protein 20-like protein 1 (PHF20L1). [12]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of PHD finger protein 20-like protein 1 (PHF20L1). [13]
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References

1 An integrated genomic analysis of Tudor domain-containing proteins identifies PHD finger protein 20-like 1 (PHF20L1) as a candidate oncogene in breast cancer.Mol Oncol. 2016 Feb;10(2):292-302. doi: 10.1016/j.molonc.2015.10.013. Epub 2015 Oct 28.
2 PHF20L1 antagonizes SOX2 proteolysis triggered by the MLL1/WDR5 complexes. Lab Invest. 2018 Dec;98(12):1627-1641. doi: 10.1038/s41374-018-0106-8. Epub 2018 Aug 8.
3 Tudor-domain protein PHF20L1 reads lysine methylated retinoblastoma tumour suppressor protein.Cell Death Differ. 2017 Dec;24(12):2139-2149. doi: 10.1038/cdd.2017.135. Epub 2017 Aug 25.
4 Genomic risk profiling of ischemic stroke: results of an international genome-wide association meta-analysis.PLoS One. 2011;6(9):e23161. doi: 10.1371/journal.pone.0023161. Epub 2011 Sep 21.
5 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
6 Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
7 Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
8 Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
9 Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
10 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.
11 Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
12 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.
13 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
14 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.