Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT89FV4A)

• DOT Name: PHD finger protein 13 (PHF13)
• Synonyms: Survival time-associated PHD finger protein in ovarian cancer 1; SPOC1
• Gene Name: PHF13
• Related Disease:
  Alzheimer disease
  Alzheimer disease 3
  Cardiovascular disease
  Cytomegalovirus infection
  Carcinoma
  Epithelial ovarian cancer
  Neoplasm
  Ovarian cancer
  Ovarian neoplasm
• UniProt ID: PHF13_HUMAN
• PDB ID: 3O70; 3O7A
• Pfam ID: PF20826
• Sequence:
  MDSDSCAAAFHPEEYSPSCKRRRTVEDFNKFCTFVLAYAGYIPYPKEELPLRSSPSPANS
  TAGTIDSDGWDAGFSDIASSVPLPVSDRCFSHLQPTLLQRAKPSNFLLDRKKTDKLKKKK
  KRKRRDSDAPGKEGYRGGLLKLEAADPYVETPTSPTLQDIPQAPSDPCSGWDSDTPSSGS
  CATVSPDQVKEIKTEGKRTIVRQGKQVVFRDEDSTGNDEDIMVDSDDDSWDLVTCFCMKP
  FAGRPMIECNECHTWIHLSCAKIRKSNVPEVFVCQKCRDSKFDIRRSNRSRTGSRKLFLD
• Function: Modulates chromatin structure and DNA damage response by regulating key determinants of chromatin compaction and DNA damage response. Binds H3K4me3-containing chromatin and promotes DNA condensation by recruiting corepressors such as TRIM28 and H3K9 methyltransferase SETDB1. Required for normal chromosome condensation during the early stages of mitosis. Required for normal chromosome separation during mitosis. Increases both chromatin-associated levels and activity of H3K9 methyltransferases, such as SETDB1, thus enhancing H3K9 trimethylation. Essential for testicular stem-cell differentiation and sustained spermatogenesis.

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Biomarker	[1]
Alzheimer disease 3	DISVT69G	Strong	Biomarker	[1]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[2]
Cytomegalovirus infection	DISCEMGC	Strong	Biomarker	[3]
Carcinoma	DISH9F1N	moderate	Altered Expression	[4]
Epithelial ovarian cancer	DIS56MH2	moderate	Altered Expression	[4]
Neoplasm	DISZKGEW	moderate	Biomarker	[4]
Ovarian cancer	DISZJHAP	moderate	Altered Expression	[4]
Ovarian neoplasm	DISEAFTY	moderate	Altered Expression	[4]

8 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 PHD finger protein 13 (PHF13).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of PHD finger protein 13 (PHF13).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of PHD finger protein 13 (PHF13).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of PHD finger protein 13 (PHF13).	[8]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of PHD finger protein 13 (PHF13).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of PHD finger protein 13 (PHF13).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of PHD finger protein 13 (PHF13).	[13]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of PHD finger protein 13 (PHF13).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of PHD finger protein 13 (PHF13).	[11]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of PHD finger protein 13 (PHF13).	[12]

References

• [1] SPOC1-mediated antiviral host cell response is antagonized early in human adenovirus type 5 infection.PLoS Pathog. 2013;9(11):e1003775. doi: 10.1371/journal.ppat.1003775. Epub 2013 Nov 21.
• [2] Leveraging Polygenic Functional Enrichment to Improve GWAS Power.Am J Hum Genet. 2019 Jan 3;104(1):65-75. doi: 10.1016/j.ajhg.2018.11.008. Epub 2018 Dec 27.
• [3] Chromatin-Remodeling Factor SPOC1 Acts as a Cellular Restriction Factor against Human Cytomegalovirus by Repressing the Major Immediate Early Promoter.J Virol. 2018 Jun 29;92(14):e00342-18. doi: 10.1128/JVI.00342-18. Print 2018 Jul 15.
• [4] SPOC1, a novel PHD-finger protein: association with residual disease and survival in ovarian cancer.Int J Cancer. 2005 Sep 10;116(4):547-54. doi: 10.1002/ijc.20912.
• [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] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [9] 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.
• [10] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [11] 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.
• [12] 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.
• [13] 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.
• [14] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.