Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCBVH5P)

• DOT Name: PHD finger protein 20 (PHF20)
• Synonyms: Glioma-expressed antigen 2; Hepatocellular carcinoma-associated antigen 58; Novel zinc finger protein; Transcription factor TZP
• Gene Name: PHF20
• Related Disease:
  Bacteremia
  Melanoma
  Narcolepsy
  Adult glioblastoma
  Astrocytoma
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Glioma
  Neoplasm
  Non-small-cell lung cancer
  Osteoporosis
  Ovarian neoplasm
  Thyroid gland carcinoma
  Carcinoma
  Glioblastoma multiforme
  Head and neck carcinoma
  Malignant tumor of nasopharynx
  Nasopharyngeal carcinoma
  Endocarditis
  Colon cancer
  Colon carcinoma
  Epithelial ovarian cancer
  Lung cancer
  Lung carcinoma
  Neuroblastoma
  Ovarian cancer
• UniProt ID: PHF20_HUMAN
• PDB ID: 2LDM; 3P8D; 3Q1J; 3QII; 3SD4; 5TAB; 5TBN
• Pfam ID: PF20826 ; PF12618 ; PF18115
• Sequence:
  MTKHPPNRRGISFEVGAQLEARDRLKNWYPAHIEDIDYEEGKVLIHFKRWNHRYDEWFCW
  DSPYLRPLEKIQLRKEGLHEEDGSSEFQINEQVLACWSDCRFYPAKVTAVNKDGTYTVKF
  YDGVVQTVKHIHVKAFSKDQNIVGNARPKETDHKSLSSSPDKREKFKEQRKATVNVKKDK
  EDKPLKTEKRPKQPDKEGKLICSEKGKVSEKSLPKNEKEDKENISENDREYSGDAQVDKK
  PENDIVKSPQENLREPKRKRGRPPSIAPTAVDSNSQTLQPITLELRRRKISKGCEVPLKR
  PRLDKNSSQEKSKNYSENTDKDLSRRRSSRLSTNGTHEILDPDLVVSDLVDTDPLQDTLS
  STKESEEGQLKSALEAGQVSSALTCHSFGDGSGAAGLELNCPSMGENTMKTEPTSPLVEL
  QEISTVEVTNTFKKTDDFGSSNAPAVDLDHKFRCKVVDCLKFFRKAKLLHYHMKYFHGME
  KSLEPEESPGKRHVQTRGPSASDKPSQETLTRKRVSASSPTTKDKEKNKEKKFKEFVRVK
  PKKKKKKKKKTKPECPCSEEISDTSQEPSPPKAFAVTRCGSSHKPGVHMSPQLHGPESGH
  HKGKVKALEEDNLSESSSESFLWSDDEYGQDVDVTTNPDEELDGDDRYDFEVVRCICEVQ
  EENDFMIQCEECQCWQHGVCMGLLEENVPEKYTCYVCQDPPGQRPGFKYWYDKEWLSRGH
  MHGLAFLEENYSHQNAKKIVATHQLLGDVQRVIEVLHGLQLKMSILQSREHPDLPLWCQP
  WKQHSGEGRSHFRNIPVTDTRSKEEAPSYRTLNGAVEKPRPLALPLPRSVEESYITSEHC
  YQKPRAYYPAVEQKLVVETRGSALDDAVNPLHENGDDSLSPRLGWPLDQDRSKGDSDPKP
  GSPKVKEYVSKKALPEEAPARKLLDRGGEGLLSSQHQWQFNLLTHVESLQDEVTHRMDSI
  EKELDVLESWLDYTGELEPPEPLARLPQLKHCIKQLLMDLGKVQQIALCCST
• Function: Methyllysine-binding protein, component of the MOF histone acetyltransferase protein complex. Not required for maintaining the global histone H4 'Lys-16' acetylation (H4K16ac) levels or locus specific histone acetylation, but instead works downstream in transcriptional regulation of MOF target genes. As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues. Contributes to methyllysine-dependent p53/TP53 stabilization and up-regulation after DNA damage.
• Tissue Specificity: Expressed in heart, kidney, liver, lung, pancreas, placenta, spleen and testis. Not expressed in brain, skeletal muscle, colon, ovary, prostate, small intestine and thymus. Expressed in colon and ovary cancer cell lines while it is not expressed in the respective normal tissues.
• Reactome Pathway:
  Regulation of TP53 Degradation (R-HSA-6804757)
  Regulation of TP53 Activity through Association with Co-factors (R-HSA-6804759)
  Stabilization of p53 (R-HSA-69541)
  Formation of WDR5-containing histone-modifying complexes (R-HSA-9772755)
  HATs acetylate histones (R-HSA-3214847)

Molecular Interaction Atlas (MIA) of This DOT

27 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bacteremia	DIS6N9RZ	Definitive	Biomarker	[1]
Melanoma	DIS1RRCY	Definitive	Genetic Variation	[2]
Narcolepsy	DISLCNLI	Definitive	Genetic Variation	[3]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[4]
Astrocytoma	DISL3V18	Strong	Biomarker	[5]
Breast cancer	DIS7DPX1	Strong	Biomarker	[6]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[6]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[7]
Glioma	DIS5RPEH	Strong	Biomarker	[8]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[9]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[10]
Osteoporosis	DISF2JE0	Strong	Biomarker	[11]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[8]
Thyroid gland carcinoma	DISMNGZ0	Strong	Biomarker	[12]
Carcinoma	DISH9F1N	moderate	Genetic Variation	[9]
Glioblastoma multiforme	DISK8246	moderate	Biomarker	[4]
Head and neck carcinoma	DISOU1DS	moderate	Biomarker	[13]
Malignant tumor of nasopharynx	DISTGIGF	moderate	Biomarker	[14]
Nasopharyngeal carcinoma	DISAOTQ0	moderate	Biomarker	[14]
Endocarditis	DISBU610	Disputed	Biomarker	[15]
Colon cancer	DISVC52G	Limited	Biomarker	[8]
Colon carcinoma	DISJYKUO	Limited	Biomarker	[8]
Epithelial ovarian cancer	DIS56MH2	Limited	Biomarker	[8]
Lung cancer	DISCM4YA	Limited	Biomarker	[8]
Lung carcinoma	DISTR26C	Limited	Biomarker	[8]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[16]
Ovarian cancer	DISZJHAP	Limited	Biomarker	[8]

4 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 (PHF20).	[17]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of PHD finger protein 20 (PHF20).	[18]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of PHD finger protein 20 (PHF20).	[19]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of PHD finger protein 20 (PHF20).	[22]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of PHD finger protein 20 (PHF20).	[20]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of PHD finger protein 20 (PHF20).	[21]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of PHD finger protein 20 (PHF20).	[23]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of PHD finger protein 20 (PHF20).	[24]

References

• [1] Epidemiology of Bloodstream Infections Caused by Escherichia coli and Klebsiella pneumoniae That Are Piperacillin-Tazobactam-Nonsusceptible but Ceftriaxone-Susceptible.Open Forum Infect Dis. 2018 Nov 19;5(12):ofy300. doi: 10.1093/ofid/ofy300. eCollection 2018 Dec.
• [2] Common sequence variants on 20q11.22 confer melanoma susceptibility.Nat Genet. 2008 Jul;40(7):838-40. doi: 10.1038/ng.163. Epub 2008 May 18.
• [3] Genome-wide association database developed in the Japanese Integrated Database Project.J Hum Genet. 2009 Sep;54(9):543-6. doi: 10.1038/jhg.2009.68. Epub 2009 Jul 24.
• [4] Identification of genes and pathways potentially related to PHF20 by gene expression profile analysis of glioblastoma U87 cell line.Cancer Cell Int. 2017 Oct 4;17:87. doi: 10.1186/s12935-017-0459-x. eCollection 2017.
• [5] Glioma-expressed antigen 2 (GLEA2): a novel protein that can elicit immune responses in glioblastoma patients and some controls.Clin Exp Immunol. 2001 Nov;126(2):206-13. doi: 10.1046/j.1365-2249.2001.01635.x.
• [6] ZNF121 interacts with ZBRK1 and BRCA1 to regulate their target genes in mammary epithelial cells.FEBS Open Bio. 2018 Nov 8;8(12):1943-1952. doi: 10.1002/2211-5463.12530. eCollection 2018 Dec.
• [7] ZNF652, a novel zinc finger protein, interacts with the putative breast tumor suppressor CBFA2T3 to repress transcription.Mol Cancer Res. 2006 Sep;4(9):655-65. doi: 10.1158/1541-7786.MCR-05-0249.
• [8] PKB-mediated PHF20 phosphorylation on Ser291 is required for p53 function in DNA damage.Cell Signal. 2013 Jan;25(1):74-84. doi: 10.1016/j.cellsig.2012.09.009. Epub 2012 Sep 11.
• [9] Molecular genetic characterization reveals linear tumor evolution in a pulmonary sarcomatoid carcinomas patient with a novel PHF20-NTRK1 fusion: a case report.BMC Cancer. 2019 Jun 17;19(1):592. doi: 10.1186/s12885-019-5780-4.
• [10] Expression of PHF20 protein contributes to good prognosis of NSCLC and is associated with Bax expression.Int J Clin Exp Pathol. 2015 Oct 1;8(10):12198-206. eCollection 2015.
• [11] Identification of potential pathogenic genes associated with osteoporosis.Bone Joint Res. 2017 Dec;6(12):640-648. doi: 10.1302/2046-3758.612.BJR-2017-0102.R1.
• [12] RREB-1, a novel zinc finger protein, is involved in the differentiation response to Ras in human medullary thyroid carcinomas.Mol Cell Biol. 1996 Oct;16(10):5335-45. doi: 10.1128/MCB.16.10.5335.
• [13] Whole blood transcriptome correlates with treatment response in nasopharyngeal carcinoma.J Exp Clin Cancer Res. 2012 Sep 17;31(1):76. doi: 10.1186/1756-9966-31-76.
• [14] Novel tumor antigens identified by autologous antibody screening of childhood medulloblastoma cDNA libraries.Int J Cancer. 2003 Aug 20;106(2):244-51. doi: 10.1002/ijc.11208.
• [15] Pseudomonas Endocarditis with an unstable phenotype: the challenges of isolate characterization and Carbapenem stewardship with a partial review of the literature.Antimicrob Resist Infect Control. 2017 Aug 29;6:87. doi: 10.1186/s13756-017-0245-5. eCollection 2017.
• [16] PHF20 collaborates with PARP1 to promote stemness and aggressiveness of neuroblastoma cells through activation of SOX2 and OCT4.J Mol Cell Biol. 2018 Apr 1;10(2):147-160. doi: 10.1093/jmcb/mjy007.
• [17] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [18] 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.
• [19] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [20] Epigenetic changes in individuals with arsenicosis. Chem Res Toxicol. 2011 Feb 18;24(2):165-7. doi: 10.1021/tx1004419. Epub 2011 Feb 4.
• [21] 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.
• [22] 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.
• [23] 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.
• [24] 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.