Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTR9DPT)

• DOT Name: Polyadenylate-binding protein 3 (PABPC3)
• Synonyms: PABP-3; Poly(A)-binding protein 3; Testis-specific poly(A)-binding protein
• Gene Name: PABPC3
• Related Disease: Oligospermia
• UniProt ID: PABP3_HUMAN
• PDB ID: 2D9P; 4IVE
• Pfam ID: PF00658 ; PF00076
• Sequence:
  MNPSTPSYPTASLYVGDLHPDVTEAMLYEKFSPAGPILSIRICRDLITSGSSNYAYVNFQ
  HTKDAEHALDTMNFDVIKGKPVRIMWSQRDPSLRKSGVGNIFVKNLDKSINNKALYDTVS
  AFGNILSCNVVCDENGSKGYGFVHFETHEAAERAIKKMNGMLLNGRKVFVGQFKSRKERE
  AELGARAKEFPNVYIKNFGEDMDDERLKDLFGKFGPALSVKVMTDESGKSKGFGFVSFER
  HEDAQKAVDEMNGKELNGKQIYVGRAQKKVERQTELKRTFEQMKQDRITRYQVVNLYVKN
  LDDGIDDERLRKAFSPFGTITSAKVMMEGGRSKGFGFVCFSSPEEATKAVTEMNGRIVAT
  KPLYVALAQRKEERQAYLTNEYMQRMASVRAVPNQRAPPSGYFMTAVPQTQNHAAYYPPS
  QIARLRPSPRWTAQGARPHPFQNKPSAIRPGAPRVPFSTMRPASSQVPRVMSTQRVANTS
  TQTVGPRPAAAAAAAATPAVRTVPRYKYAAGVRNPQQHRNAQPQVTMQQLAVHVQGQETL
  TASRLASAPPQKQKQMLGERLFPLIQAMHPTLAGKITGMLLEIDNSELLYMLESPESLRS
  KVDEAVAVLQAHQAKEATQKAVNSATGVPTV
• Function: Binds the poly(A) tail of mRNA. May be involved in cytoplasmic regulatory processes of mRNA metabolism. Binds poly(A) with a slightly lower affinity as compared to PABPC1.
• Tissue Specificity: Testis specific.
• KEGG Pathway:
  mR. surveillance pathway (hsa03015)
  R. degradation (hsa03018)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Oligospermia	DIS6YJF3	Strong	Biomarker	[1]

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 Polyadenylate-binding protein 3 (PABPC3).	[2]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Polyadenylate-binding protein 3 (PABPC3).	[3]
Decitabine	DMQL8XJ	Approved	Decitabine decreases the expression of Polyadenylate-binding protein 3 (PABPC3).	[4]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Polyadenylate-binding protein 3 (PABPC3).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Polyadenylate-binding protein 3 (PABPC3).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Polyadenylate-binding protein 3 (PABPC3).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Polyadenylate-binding protein 3 (PABPC3).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Polyadenylate-binding protein 3 (PABPC3).	[5]

References

• [1] The poly(A)-binding protein genes, EPAB, PABPC1, and PABPC3 are differentially expressed in infertile men with non-obstructive azoospermia.J Assist Reprod Genet. 2016 Mar;33(3):335-348. doi: 10.1007/s10815-016-0654-z. Epub 2016 Feb 3.
• [2] 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.
• [3] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [4] DNA methylation inhibits p53-mediated survivin repression. Oncogene. 2009 May 14;28(19):2046-50. doi: 10.1038/onc.2009.62. Epub 2009 Apr 13.
• [5] 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.
• [6] 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.
• [7] 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.
• [8] 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.