Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI3A8RS)

• DOT Name: Phenazine biosynthesis-like domain-containing protein (PBLD)
• Synonyms: EC 5.1.-.-; MAWD-binding protein; MAWDBP; Unknown protein 32 from 2D-page of liver tissue
• Gene Name: PBLD
• Related Disease:
  Gastric cancer
  Neoplasm
  Stomach cancer
  Breast cancer
  Breast carcinoma
  Hepatocellular carcinoma
  Precancerous condition
• UniProt ID: PBLD_HUMAN
• EC Number: 5.1.-.-
• Pfam ID: PF02567
• Sequence:
  MKLPIFIADAFTARAFRGNPAAVCLLENELDEDMHQKIAREMNLSETAFIRKLHPTDNFA
  QSSCFGLRWFTPASEVPLCGHATLASAAVLFHKIKNMNSTLTFVTLSGELRARRAEDGIV
  LDLPLYPAHPQDFHEVEDLIKTAIGNTLVQDICYSPDTQKLLVRLSDVYNRSFLENLKVN
  TENLLQVENTGKVKGLILTLKGEPGGQTQAFDFYSRYFAPWVGVAEDPVTGSAHAVLSSY
  WSQHLGKKEMHAFQCSHRGGELGISLRPDGRVDIRGGAAVVLEGTLTA

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Gastric cancer	DISXGOUK	Strong	Altered Expression	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[1]
Breast cancer	DIS7DPX1	moderate	Biomarker	[2]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[2]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[3]
Precancerous condition	DISV06FL	Limited	Biomarker	[4]

12 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 Phenazine biosynthesis-like domain-containing protein (PBLD).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Phenazine biosynthesis-like domain-containing protein (PBLD).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Phenazine biosynthesis-like domain-containing protein (PBLD).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Phenazine biosynthesis-like domain-containing protein (PBLD).	[6]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Phenazine biosynthesis-like domain-containing protein (PBLD).	[9]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Phenazine biosynthesis-like domain-containing protein (PBLD).	[10]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Phenazine biosynthesis-like domain-containing protein (PBLD).	[11]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Phenazine biosynthesis-like domain-containing protein (PBLD).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Phenazine biosynthesis-like domain-containing protein (PBLD).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Phenazine biosynthesis-like domain-containing protein (PBLD).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Phenazine biosynthesis-like domain-containing protein (PBLD).	[15]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Phenazine biosynthesis-like domain-containing protein (PBLD).	[16]

1 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 Phenazine biosynthesis-like domain-containing protein (PBLD).	[8]

References

• [1] Mitogen-activated protein kinase activator with WD40 repeats (MAWD) and MAWD-binding protein induce cell differentiation in gastric cancer.BMC Cancer. 2015 Sep 15;15:637. doi: 10.1186/s12885-015-1637-7.
• [2] circKDM4C suppresses tumor progression and attenuates doxorubicin resistance by regulating miR-548p/PBLD axis in breast cancer.Oncogene. 2019 Oct;38(42):6850-6866. doi: 10.1038/s41388-019-0926-z. Epub 2019 Aug 12.
• [3] Novel compound cedrelone inhibits hepatocellular carcinoma progression via PBLD and Ras/Rap1.Exp Ther Med. 2019 Dec;18(6):4209-4220. doi: 10.3892/etm.2019.8080. Epub 2019 Oct 7.
• [4] Hepatocellular carcinoma-associated protein markers investigated by MALDI-TOF MS.Mol Med Rep. 2010 Jul-Aug;3(4):589-96. doi: 10.3892/mmr_00000302.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [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] 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.
• [9] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [10] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [11] 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.
• [12] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [13] 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.
• [14] 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.
• [15] The genomic response of Ishikawa cells to bisphenol A exposure is dose- and time-dependent. Toxicology. 2010 Apr 11;270(2-3):137-49. doi: 10.1016/j.tox.2010.02.008. Epub 2010 Feb 17.
• [16] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.