Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTFLH0E)

• DTT Name: Serine/threonine PP1-alpha (PPP1CA)
• Synonyms: Serine/threonine-protein phosphatase PP1-alpha catalytic subunit; Protein phosphatase 1alpha; PPP1A; PP-1A
• Gene Name: PPP1CA
• DTT Type: Successful target; [1]
• BioChemical Class: Phosphoric monoester hydrolase
• UniProt ID: PP1A_HUMAN
• TTD ID: T59845
• EC Number: EC 3.1.3.16
• Sequence:
  MSDSEKLNLDSIIGRLLEVQGSRPGKNVQLTENEIRGLCLKSREIFLSQPILLELEAPLK
  ICGDIHGQYYDLLRLFEYGGFPPESNYLFLGDYVDRGKQSLETICLLLAYKIKYPENFFL
  LRGNHECASINRIYGFYDECKRRYNIKLWKTFTDCFNCLPIAAIVDEKIFCCHGGLSPDL
  QSMEQIRRIMRPTDVPDQGLLCDLLWSDPDKDVQGWGENDRGVSFTFGAEVVAKFLHKHD
  LDLICRAHQVVEDGYEFFAKRQLVTLFSAPNYCGEFDNAGAMMSVDETLMCSFQILKPAD
  KNKGKYGQFSGLNPGGRPITPPRNSAKAKK
• Function: Protein phosphatase 1 (PP1) is essential for cell division, and participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis. Involved in regulation of ionic conductances and long-term synaptic plasticity. May play an important role in dephosphorylating substrates such as the postsynaptic density-associated Ca(2+)/calmodulin dependent protein kinase II. Component of the PTW/PP1 phosphatase complex, which plays a role in the control of chromatin structure and cell cycle progression during the transition from mitosis into interphase. Regulates NEK2 function in terms of kinase activity and centrosome number and splitting, both in the presence and absence of radiation-induced DNA damage. Regulator of neural tube and optic fissure closure, and enteric neural crest cell (ENCCs) migration during development. In balance with CSNK1D and CSNK1E, determines the circadian period length, through the regulation of the speed and rhythmicity of PER1 and PER2 phosphorylation. May dephosphorylate CSNK1D and CSNK1E. Dephosphorylates the 'Ser-418' residue of FOXP3 in regulatory T-cells (Treg) from patients with rheumatoid arthritis, thereby inactivating FOXP3 and rendering Treg cells functionally defective. Dephosphorylates CENPA. Dephosphorylates the 'Ser-139' residue of ATG16L1 causing dissociation of ATG12-ATG5-ATG16L1 complex, thereby inhibiting autophagy. Protein phosphatase that associates with over 200 regulatory proteins to form highly specific holoenzymes which dephosphorylate hundreds of biological targets.
• KEGG Pathway:
  mRNA surveillance pathway (hsa03015)
  cGMP-PKG signaling pathway (hsa04022)
  cAMP signaling pathway (hsa04024)
  Oocyte meiosis (hsa04114)
  Cellular senescence (hsa04218)
  Adrenergic signaling in cardiomyocytes (hsa04261)
  Vascular smooth muscle contraction (hsa04270)
  Hippo signaling pathway (hsa04390)
  Focal adhesion (hsa04510)
  Platelet activation (hsa04611)
  Long-term potentiation (hsa04720)
  Dopaminergic synapse (hsa04728)
  Inflammatory mediator regulation of TRP channels (hsa04750)
  Regulation of actin cytoskeleton (hsa04810)
  Insulin signaling pathway (hsa04910)
  Oxytocin signaling pathway (hsa04921)
  Insulin resistance (hsa04931)
  Amphetamine addiction (hsa05031)
  Alcoholism (hsa05034)
  Herpes simplex virus 1 infection (hsa05168)
  Proteoglycans in cancer (hsa05205)
  Diabetic cardiomyopathy (hsa05415)
• Reactome Pathway:
  DARPP-32 events (R-HSA-180024)
  Downregulation of TGF-beta receptor signaling (R-HSA-2173788)
  Circadian Clock (R-HSA-400253)
  Triglyceride catabolism (R-HSA-163560)

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cantharidin	DMBP5N3	Molluscum contagiosum infection	1E76	Approved	[1]

5 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CANTHARIDIC_ACID	DME32XU	Discovery agent	N.A.	Investigative	[1]
MICROCYSTIN-LR	DMTMLRN	Discovery agent	N.A.	Investigative	[1]
NORCANTHARIDIN	DM9B6Y1	Discovery agent	N.A.	Investigative	[2]
PALASONIN	DMDTP1R	Discovery agent	N.A.	Investigative	[1]
TAUTOMYCIN	DMC92DQ	Discovery agent	N.A.	Investigative	[1]

References

• [1] Serine-threonine protein phosphatase inhibitors: development of potential therapeutic strategies. J Med Chem. 2002 Mar 14;45(6):1151-75.
• [2] In silico identification and biochemical evaluation of novel inhibitors of NRH:quinone oxidoreductase 2 (NQO2). Bioorg Med Chem Lett. 2010 Dec 15;20(24):7331-6.