Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZT3GV1)

• DOT Name: PHD finger protein 14 (PHF14)
• Gene Name: PHF14
• Related Disease:
  Adenocarcinoma
  Adult glioblastoma
  Alzheimer disease
  Cerebellar disorder
  Colon cancer
  Colon carcinoma
  Dandy-Walker syndrome
  Glioblastoma multiforme
  Glioma
  Lung cancer
  Lung carcinoma
  Neoplasm
  Renal fibrosis
  Respiratory failure
  Skin cancer
  Arteriosclerosis
  Atherosclerosis
  High blood pressure
  Pulmonary disease
  Stroke
  Bladder cancer
  Urinary bladder cancer
  Urinary bladder neoplasm
• UniProt ID: PHF14_HUMAN
• Pfam ID: PF00628 ; PF13831 ; PF13832
• Sequence:
  MDRSSKRRQVKPLAASLLEALDYDSSDDSDFKVGDASDSEGSGNGSEDASKDSGEGSCSD
  SEENILEEELNEDIKVKEEQLKNSAEEEVLSSEKQLIKMEKKEEEENGERPRKKKEKEKE
  KEKEKEKEKEREKEKEKATVSENVAASAAATTPATSPPAVNTSPSVPTTTTATEEQVSEP
  KKWNLRRNRPLLDFVSMEELNDMDDYDSEDDNDWRPTVVKRKGRSASQKEGSDGDNEDDE
  DEGSGSDEDENDEGNDEDHSSPASEGGCKKKKSKVLSRNSADDEELTNDSLTLSQSKSNE
  DSLILEKSQNWSSQKMDHILICCVCLGDNSEDADEIIQCDNCGITVHEGCYGVDGESDSI
  MSSASENSTEPWFCDACKCGVSPSCELCPNQDGIFKETDAGRWVHIVCALYVPGVAFGDI
  DKLRPVTLTEMNYSKYGAKECSFCEDPRFARTGVCISCDAGMCRAYFHVTCAQKEGLLSE
  AAAEEDIADPFFAYCKQHADRLDRKWKRKNYLALQSYCKMSLQEREKQLSPEAQARINAR
  LQQYRAKAELARSTRPQAWVPREKLPRPLTSSASAIRKLMRKAELMGISTDIFPVDNSDT
  SSSVDGRRKHKQPALTADFVNYYFERNMRMIQIQENMAEQKNIKDKLENEQEKLHVEYNK
  LCESLEELQNLNGKLRSEGQGIWALLGRITGQKLNIPAILRAPKERKPSKKEGGTQKTST
  LPAVLYSCGICKKNHDQHLLLLCDTCKLHYHLGCLDPPLTRMPRKTKNSYWQCSECDQAG
  SSDMEADMAMETLPDGTKRSRRQIKEPVKFVPQDVPPEPKKIPIRNTRTRGRKRSFVPEE
  EKHEERVPRERRQRQSVLQKKPKAEDLRTECATCKGTGDNENLVRCDECRLCYHFGCLDP
  PLKKSPKQTGYGWICQECDSSSSKEDENEAERKNISQELNMEQKNPKK
• Function: Histone-binding protein. Binds preferentially to unmodified histone H3 but can also bind to a lesser extent to histone H3 trimethylated at 'Lys-9' (H3K9me3) as well as to histone H3 monomethylated at 'Lys-27' (H3K27ac) and trimethylated at 'Lys-27' (H3K27me3). Represses PDGFRA expression, thus playing a role in regulation of mesenchymal cell proliferation. Suppresses the expression of CDKN1A/p21 by reducing the level of trimethylation of histone H3 'Lys-4', leading to enhanced proliferation of germinal center B cells.

Molecular Interaction Atlas (MIA) of This DOT

23 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[1]
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[2]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[3]
Cerebellar disorder	DIS2O7WM	Strong	Genetic Variation	[4]
Colon cancer	DISVC52G	Strong	Altered Expression	[5]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[5]
Dandy-Walker syndrome	DIS4HC6W	Strong	Genetic Variation	[4]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[2]
Glioma	DIS5RPEH	Strong	Altered Expression	[2]
Lung cancer	DISCM4YA	Strong	Biomarker	[1]
Lung carcinoma	DISTR26C	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Altered Expression	[2]
Renal fibrosis	DISMHI3I	Strong	Biomarker	[6]
Respiratory failure	DISVMYJO	Strong	Biomarker	[7]
Skin cancer	DISTM18U	Strong	Altered Expression	[5]
Arteriosclerosis	DISK5QGC	moderate	Genetic Variation	[8]
Atherosclerosis	DISMN9J3	moderate	Genetic Variation	[8]
High blood pressure	DISY2OHH	moderate	Genetic Variation	[9]
Pulmonary disease	DIS6060I	moderate	Genetic Variation	[8]
Stroke	DISX6UHX	moderate	Genetic Variation	[10]
Bladder cancer	DISUHNM0	Limited	Biomarker	[11]
Urinary bladder cancer	DISDV4T7	Limited	Biomarker	[11]
Urinary bladder neoplasm	DIS7HACE	Limited	Biomarker	[11]

10 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 14 (PHF14).	[12]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of PHD finger protein 14 (PHF14).	[13]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of PHD finger protein 14 (PHF14).	[14]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of PHD finger protein 14 (PHF14).	[15]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of PHD finger protein 14 (PHF14).	[16]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of PHD finger protein 14 (PHF14).	[17]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of PHD finger protein 14 (PHF14).	[18]
Clorgyline	DMCEUJD	Approved	Clorgyline increases the expression of PHD finger protein 14 (PHF14).	[19]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of PHD finger protein 14 (PHF14).	[21]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of PHD finger protein 14 (PHF14).	[25]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the phosphorylation of PHD finger protein 14 (PHF14).	[20]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of PHD finger protein 14 (PHF14).	[22]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of PHD finger protein 14 (PHF14).	[23]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the methylation of PHD finger protein 14 (PHF14).	[24]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of PHD finger protein 14 (PHF14).	[23]

References

• [1] A novel PHD-finger protein 14/KIF4A complex overexpressed in lung cancer is involved in cell mitosis regulation and tumorigenesis.Oncotarget. 2017 Mar 21;8(12):19684-19698. doi: 10.18632/oncotarget.14962.
• [2] Silencing expression of PHF14 in glioblastoma promotes apoptosis, mitigates proliferation and invasiveness via Wnt signal pathway.Cancer Cell Int. 2019 Nov 27;19:314. doi: 10.1186/s12935-019-1040-6. eCollection 2019.
• [3] Family-based association analyses of imputed genotypes reveal genome-wide significant association of Alzheimer's disease with OSBPL6, PTPRG, and PDCL3.Mol Psychiatry. 2016 Nov;21(11):1608-1612. doi: 10.1038/mp.2015.218. Epub 2016 Feb 2.
• [4] Prenatal diagnosis and molecular characterization of a novel locus for Dandy-Walker malformation on chromosome 7p21.3.Eur J Med Genet. 2012 Aug-Sep;55(8-9):472-5. doi: 10.1016/j.ejmg.2012.04.008. Epub 2012 May 19.
• [5] Pulsed SILAC-based proteomic analysis unveils hypoxia- and serum starvation-induced de novo protein synthesis with PHD finger protein 14 (PHF14) as a hypoxia sensitive epigenetic regulator in cell cycle progression.Oncotarget. 2019 Mar 15;10(22):2136-2150. doi: 10.18632/oncotarget.26669. eCollection 2019 Mar 15.
• [6] PHF14: an innate inhibitor against the progression of renal fibrosis following folic acid-induced kidney injury.Sci Rep. 2017 Jan 3;7:39888. doi: 10.1038/srep39888.
• [7] Depletion of PHF14, a novel histone-binding protein gene, causes neonatal lethality in mice due to respiratory failure.Acta Biochim Biophys Sin (Shanghai). 2013 Aug;45(8):622-33. doi: 10.1093/abbs/gmt055. Epub 2013 May 20.
• [8] Novel DNA methylation sites associated with cigarette smoking among African Americans.Epigenetics. 2019 Apr;14(4):383-391. doi: 10.1080/15592294.2019.1588683. Epub 2019 Mar 27.
• [9] Filtering genetic variants and placing informative priors based on putative biological function.BMC Genet. 2016 Feb 3;17 Suppl 2(Suppl 2):8. doi: 10.1186/s12863-015-0313-x.
• [10] Genetic mapping and exome sequencing identify 2 mutations associated with stroke protection in pediatric patients with sickle cell anemia.Blood. 2013 Apr 18;121(16):3237-45. doi: 10.1182/blood-2012-10-464156. Epub 2013 Feb 19.
• [11] LINC00612 enhances the proliferation and invasion ability of bladder cancer cells as ceRNA by sponging miR-590 to elevate expression of PHF14.J Exp Clin Cancer Res. 2019 Apr 2;38(1):143. doi: 10.1186/s13046-019-1149-4.
• [12] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [13] 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.
• [14] 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.
• [15] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [16] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [17] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [18] 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.
• [19] 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.
• [20] Phosphoproteomics reveals resveratrol-dependent inhibition of Akt/mTORC1/S6K1 signaling. J Proteome Res. 2014 Dec 5;13(12):5734-42. doi: 10.1021/pr500714a. Epub 2014 Oct 29.
• [21] Regulation of gene expression and inhibition of experimental prostate cancer bone metastasis by dietary genistein. Neoplasia. 2004 Jul-Aug;6(4):354-63. doi: 10.1593/neo.03478.
• [22] 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.
• [23] 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.
• [24] 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.
• [25] 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.