Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTHTKNY)

• DTT Name: Serine/threonine PP2A-alpha (PPP2CA)
• Synonyms: Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform; Replication protein C; RP-C; PP2A-alpha
• Gene Name: PPP2CA
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Phosphoric monoester hydrolase
• UniProt ID: PP2AA_HUMAN
• TTD ID: T40491
• EC Number: EC 3.1.3.16
• Sequence:
  MDEKVFTKELDQWIEQLNECKQLSESQVKSLCEKAKEILTKESNVQEVRCPVTVCGDVHG
  QFHDLMELFRIGGKSPDTNYLFMGDYVDRGYYSVETVTLLVALKVRYRERITILRGNHES
  RQITQVYGFYDECLRKYGNANVWKYFTDLFDYLPLTALVDGQIFCLHGGLSPSIDTLDHI
  RALDRLQEVPHEGPMCDLLWSDPDDRGGWGISPRGAGYTFGQDISETFNHANGLTLVSRA
  HQLVMEGYNWCHDRNVVTIFSAPNYCYRCGNQAAIMELDDTLKYSFLQFDPAPRRGEPHV
  TRRTPDYFL
• Function: PP2A can modulate the activity of phosphorylase B kinase casein kinase 2, mitogen-stimulated S6 kinase, and MAP-2 kinase. Cooperates with SGO2 to protect centromeric cohesin from separase-mediated cleavage in oocytes specifically during meiosis I. Can dephosphorylate SV40 large T antigen and p53/TP53. Activates RAF1 by dephosphorylating it at 'Ser-259'. PP2A is the major phosphatase for microtubule-associated proteins (MAPs).
• KEGG Pathway:
  mRNA surveillance pathway (hsa03015)
  Sphingolipid signaling pathway (hsa04071)
  Oocyte meiosis (hsa04114)
  PI3K-Akt signaling pathway (hsa04151)
  AMPK signaling pathway (hsa04152)
  Adrenergic signaling in cardiomyocytes (hsa04261)
  TGF-beta signaling pathway (hsa04350)
  Hippo signaling pathway (hsa04390)
  Tight junction (hsa04530)
  Dopaminergic synapse (hsa04728)
  Long-term depression (hsa04730)
  Chagas disease (American trypanosomiasis) (hsa05142)
  Hepatitis C (hsa05160)
• Reactome Pathway:
  DARPP-32 events (R-HSA-180024)
  Degradation of beta-catenin by the destruction complex (R-HSA-195253)
  ERK/MAPK targets (R-HSA-198753)
  MASTL Facilitates Mitotic Progression (R-HSA-2465910)
  Separation of Sister Chromatids (R-HSA-2467813)
  Resolution of Sister Chromatid Cohesion (R-HSA-2500257)
  CTLA4 inhibitory signaling (R-HSA-389513)
  Platelet sensitization by LDL (R-HSA-432142)
  Disassembly of the destruction complex and recruitment of AXIN to the membrane (R-HSA-4641262)
  S33 mutants of beta-catenin aren't phosphorylated (R-HSA-5358747)
  S37 mutants of beta-catenin aren't phosphorylated (R-HSA-5358749)
  S45 mutants of beta-catenin aren't phosphorylated (R-HSA-5358751)
  T41 mutants of beta-catenin aren't phosphorylated (R-HSA-5358752)
  RHO GTPases Activate Formins (R-HSA-5663220)
  RAF activation (R-HSA-5673000)
  Negative regulation of MAPK pathway (R-HSA-5675221)
  Mitotic Prometaphase (R-HSA-68877)
  Cyclin D associated events in G1 (R-HSA-69231)
  Cyclin A/B1 associated events during G2/M transition (R-HSA-69273)
  Glycolysis (R-HSA-70171)
  Spry regulation of FGF signaling (R-HSA-1295596)
• BioCyc Pathway: MetaCyc:HS03696-MON

Molecular Interaction Atlas (MIA) of This DTT

2 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
VP-102	DM5T4IS	Molluscum contagiosum infection	1E76	Phase 3	[1]
LB-100	DMC04SR	Astrocytoma	2A00.0Y	Phase 2	[2]

References

• [1] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [2] Inhibition of protein phosphatase 2A enhances cytotoxicity and accessibility of chemotherapeutic drugs to hepatocellular carcinomas. Mol Cancer Ther. 2014 Aug;13(8):2062-72.