Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTT2K3LQ)

• DOT Name: Golgi phosphoprotein 3-like (GOLPH3L)
• Synonyms: GPP34-related protein
• Gene Name: GOLPH3L
• Related Disease:
  Epithelial ovarian cancer
  Ovarian cancer
  Ovarian neoplasm
  Prostate carcinoma
  Schizophrenia
  Rhabdomyosarcoma
• UniProt ID: GLP3L_HUMAN
• Pfam ID: PF05719
• Sequence:
  MTTLTHRARRTEISKNSEKKMESEEDSNWEKSPDNEDSGDSKDIRLTLMEEVLLLGLKDK
  EGYTSFWNDCISSGLRGGILIELAMRGRIYLEPPTMRKKRLLDRKVLLKSDSPTGDVLLD
  ETLKHIKATEPTETVQTWIELLTGETWNPFKLQYQLRNVRERIAKNLVEKGILTTEKQNF
  LLFDMTTHPVTNTTEKQRLVKKLQDSVLERWVNDPQRMDKRTLALLVLAHSSDVLENVFS
  SLTDDKYDVAMNRAKDLVELDPEVEGTKPSATEMIWAVLAAFNKS
• Function: Phosphatidylinositol-4-phosphate-binding protein that may antagonize the action of GOLPH3 which is required for the process of vesicle budding at the Golgi and anterograde transport to the plasma membrane.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[1]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[1]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[1]
Prostate carcinoma	DISMJPLE	Strong	Genetic Variation	[2]
Schizophrenia	DISSRV2N	Strong	Altered Expression	[3]
Rhabdomyosarcoma	DISNR7MS	moderate	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Golgi phosphoprotein 3-like (GOLPH3L).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Golgi phosphoprotein 3-like (GOLPH3L).	[10]

5 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 Golgi phosphoprotein 3-like (GOLPH3L).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Golgi phosphoprotein 3-like (GOLPH3L).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Golgi phosphoprotein 3-like (GOLPH3L).	[8]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Golgi phosphoprotein 3-like (GOLPH3L).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Golgi phosphoprotein 3-like (GOLPH3L).	[11]

References

• [1] The oncogenic Golgi phosphoprotein 3 like overexpression is associated with cisplatin resistance in ovarian carcinoma and activating the NF-B signaling pathway.J Exp Clin Cancer Res. 2017 Oct 4;36(1):137. doi: 10.1186/s13046-017-0607-0.
• [2] Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci.Nat Genet. 2018 Jul;50(7):928-936. doi: 10.1038/s41588-018-0142-8. Epub 2018 Jun 11.
• [3] Differential activity of transcribed enhancers in the prefrontal cortex of 537 cases with schizophrenia and controls.Mol Psychiatry. 2019 Nov;24(11):1685-1695. doi: 10.1038/s41380-018-0059-8. Epub 2018 May 8.
• [4] Role of GOLPH3 and GOLPH3L in the proliferation of human rhabdomyosarcoma.Oncol Rep. 2011 Nov;26(5):1337-42. doi: 10.3892/or.2011.1413. Epub 2011 Aug 5.
• [5] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [6] 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.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] 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.
• [11] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.