Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5Y53WZ)

• DOT Name: Serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta (PPP2R3B)
• Synonyms: PP2A subunit B isoform PR48; Protein phosphatase 2A 48 kDa regulatory subunit
• Gene Name: PPP2R3B
• Related Disease:
  Melanoma
  Neoplasm
• UniProt ID: P2R3B_HUMAN
• PDB ID: 4I5L; 4I5N; 4MEW
• Pfam ID: PF17958 ; PF13499 ; PF21161
• Sequence:
  MPPGKVLQPVLKMKVDELFLYWLSEASTQRMLQDCLRRIKAPGRDQPTPGDGEQPGAWPT
  APLAAPRPSGLEPPGTPGPGPALPLGAASSPRNAPHVRGTRRSAGTRVVQTRKEEPLPPA
  TSQSIPTFYFPRGRPQDSVNVDAVISKIESTFARFPHERATMDDMGLVAKACGCPLYWKG
  PLFYGAGGERTGSVSVHKFVAMWRKILQNCHDDAAKFVHLLMSPGCNYLVQEDFVPFLQD
  VVNTHPGLSFLKEASEFHSRYITTVIQRIFYAVNRSWSGRITCAELRRSSFLQNVALLEE
  EADINQLTEFFSYEHFYVIYCKFWELDTDHDLLIDADDLARHNDHALSTKMIDRIFSGAV
  TRGRKVQKEGKISYADFVWFLISEEDKKTPTSIEYWFRCMDLDGDGALSMFELEYFYEEQ
  CRRLDSMAIEALPFQDCLCQMLDLVKPRTEGKITLQDLKRCKLANVFFDTFFNIEKYLDH
  EQKEQISLLRDGDSGGPELSDWEKYAAEEYDILVAEETAGEPWEDGFEAELSPVEQKLSA
  LRSPLAQRPFFEAPSPLGAVDLYEYACGDEDLEPL
• Function: The B regulatory subunit might modulate substrate selectivity and catalytic activity, and also might direct the localization of the catalytic enzyme to a particular subcellular compartment.
• KEGG Pathway:
  mR. surveillance pathway (hsa03015)
  Sphingolipid sig.ling pathway (hsa04071)
  PI3K-Akt sig.ling pathway (hsa04151)
  AMPK sig.ling pathway (hsa04152)
  Adrenergic sig.ling in cardiomyocytes (hsa04261)
  T cell receptor sig.ling pathway (hsa04660)
  Dopaminergic sy.pse (hsa04728)
  Human papillomavirus infection (hsa05165)
• Reactome Pathway:
  Cyclin D associated events in G1 (R-HSA-69231)
  Cyclin A/B1/B2 associated events during G2/M transition (R-HSA-69273)
  Inhibition of replication initiation of damaged DNA by RB1/E2F1 (R-HSA-113501)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Melanoma	DIS1RRCY	Limited	Biomarker	[1]
Neoplasm	DISZKGEW	Limited	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta (PPP2R3B).	[2]

6 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta (PPP2R3B).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta (PPP2R3B).	[4]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta (PPP2R3B).	[5]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta (PPP2R3B).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta (PPP2R3B).	[6]
Chlorpyrifos	DMKPUI6	Investigative	Chlorpyrifos increases the expression of Serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta (PPP2R3B).	[7]

References

• [1] The protein phosphatase 2A regulatory subunit PR70 is a gonosomal melanoma tumor suppressor gene.Sci Transl Med. 2016 Dec 14;8(369):369ra177. doi: 10.1126/scitranslmed.aai9188.
• [2] 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.
• [3] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [6] Characterization of the Molecular Alterations Induced by the Prolonged Exposure of Normal Colon Mucosa and Colon Cancer Cells to Low-Dose Bisphenol A. Int J Mol Sci. 2022 Oct 1;23(19):11620. doi: 10.3390/ijms231911620.
• [7] The common insecticides cyfluthrin and chlorpyrifos alter the expression of a subset of genes with diverse functions in primary human astrocytes. Toxicol Sci. 2006 Sep;93(1):125-35. doi: 10.1093/toxsci/kfl046. Epub 2006 Jun 21.