Details of Drug Off-Target (DOT)

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

• DOT Name: Serine/threonine-protein phosphatase PP1-beta catalytic subunit (PPP1CB)
• Synonyms: PP-1B; PPP1CD; EC 3.1.3.16; EC 3.1.3.53
• Gene Name: PPP1CB
• Related Disease:
  Noonan syndrome-like disorder with loose anagen hair
  Advanced cancer
  Alzheimer disease
  Cardiac failure
  Congestive heart failure
  Epilepsy
  Intellectual disability
  Megalencephaly
  Noonan syndrome-like disorder with loose anagen hair 2
  Osteogenesis imperfecta
  West syndrome
  Hepatocellular carcinoma
  High blood pressure
  Neoplasm
  Prostate cancer
  Prostate carcinoma
  Metastatic malignant neoplasm
  Congenital heart disease
  Noonan syndrome
• UniProt ID: PP1B_HUMAN
• EC Number: 3.1.3.16; 3.1.3.53
• Pfam ID: PF00149 ; PF16891
• Sequence:
  MADGELNVDSLITRLLEVRGCRPGKIVQMTEAEVRGLCIKSREIFLSQPILLELEAPLKI
  CGDIHGQYTDLLRLFEYGGFPPEANYLFLGDYVDRGKQSLETICLLLAYKIKYPENFFLL
  RGNHECASINRIYGFYDECKRRFNIKLWKTFTDCFNCLPIAAIVDEKIFCCHGGLSPDLQ
  SMEQIRRIMRPTDVPDTGLLCDLLWSDPDKDVQGWGENDRGVSFTFGADVVSKFLNRHDL
  DLICRAHQVVEDGYEFFAKRQLVTLFSAPNYCGEFDNAGGMMSVDETLMCSFQILKPSEK
  KAKYQYGGLNSGRPVTPPRTANPPKKR
• Function: Protein phosphatase that associates with over 200 regulatory proteins to form highly specific holoenzymes which dephosphorylate hundreds of biological targets. Protein phosphatase (PP1) is essential for cell division, it participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis. Involved in regulation of ionic conductances and long-term synaptic plasticity. 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. 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.
• KEGG Pathway:
  mR. surveillance pathway (hsa03015)
  cGMP-PKG sig.ling pathway (hsa04022)
  cAMP sig.ling pathway (hsa04024)
  Oocyte meiosis (hsa04114)
  Cellular senescence (hsa04218)
  Adrenergic sig.ling in cardiomyocytes (hsa04261)
  Vascular smooth muscle contraction (hsa04270)
  Hippo sig.ling pathway (hsa04390)
  Focal adhesion (hsa04510)
  Platelet activation (hsa04611)
  Long-term potentiation (hsa04720)
  Dopaminergic sy.pse (hsa04728)
  Inflammatory mediator regulation of TRP channels (hsa04750)
  Regulation of actin cytoskeleton (hsa04810)
  Insulin sig.ling pathway (hsa04910)
  Oxytocin sig.ling 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:
  Downregulation of TGF-beta receptor signaling (R-HSA-2173788)
  Regulation of PLK1 Activity at G2/M Transition (R-HSA-2565942)
  Circadian Clock (R-HSA-400253)
  RHO GTPases activate PKNs (R-HSA-5625740)
  RHO GTPases activate CIT (R-HSA-5625900)
  RHO GTPases Activate ROCKs (R-HSA-5627117)
  RHO GTPases activate PAKs (R-HSA-5627123)
  RAF activation (R-HSA-5673000)
  SHOC2 M1731 mutant abolishes MRAS complex function (R-HSA-9726840)
  Gain-of-function MRAS complexes activate RAF signaling (R-HSA-9726842)
  Triglyceride catabolism (R-HSA-163560)

Molecular Interaction Atlas (MIA) of This DOT

19 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Noonan syndrome-like disorder with loose anagen hair	DISWMZIV	Definitive	Autosomal dominant	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Alzheimer disease	DISF8S70	Strong	Altered Expression	[3]
Cardiac failure	DISDC067	Strong	Altered Expression	[4]
Congestive heart failure	DIS32MEA	Strong	Altered Expression	[4]
Epilepsy	DISBB28L	Strong	Genetic Variation	[5]
Intellectual disability	DISMBNXP	Strong	Biomarker	[6]
Megalencephaly	DISYW5SV	Strong	Biomarker	[6]
Noonan syndrome-like disorder with loose anagen hair 2	DIS2DH99	Strong	Autosomal dominant	[7]
Osteogenesis imperfecta	DIS7XQSD	Strong	Genetic Variation	[8]
West syndrome	DISLIAU9	Strong	Biomarker	[5]
Hepatocellular carcinoma	DIS0J828	moderate	Genetic Variation	[9]
High blood pressure	DISY2OHH	moderate	Posttranslational Modification	[10]
Neoplasm	DISZKGEW	moderate	Biomarker	[9]
Prostate cancer	DISF190Y	moderate	Biomarker	[11]
Prostate carcinoma	DISMJPLE	moderate	Biomarker	[11]
Metastatic malignant neoplasm	DIS86UK6	Disputed	Biomarker	[12]
Congenital heart disease	DISQBA23	Limited	Genetic Variation	[13]
Noonan syndrome	DIS7Q7DN	Limited	Genetic Variation	[14]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Paclitaxel	DMLB81S	Approved	Serine/threonine-protein phosphatase PP1-beta catalytic subunit (PPP1CB) affects the response to substance of Paclitaxel.	[37]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Serine/threonine-protein phosphatase PP1-beta catalytic subunit (PPP1CB).	[15]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Serine/threonine-protein phosphatase PP1-beta catalytic subunit (PPP1CB).	[32]

23 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 Serine/threonine-protein phosphatase PP1-beta catalytic subunit (PPP1CB).	[16]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Serine/threonine-protein phosphatase PP1-beta catalytic subunit (PPP1CB).	[17]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Serine/threonine-protein phosphatase PP1-beta catalytic subunit (PPP1CB).	[18]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Serine/threonine-protein phosphatase PP1-beta catalytic subunit (PPP1CB).	[19]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Serine/threonine-protein phosphatase PP1-beta catalytic subunit (PPP1CB).	[20]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Serine/threonine-protein phosphatase PP1-beta catalytic subunit (PPP1CB).	[21]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Serine/threonine-protein phosphatase PP1-beta catalytic subunit (PPP1CB).	[22]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Serine/threonine-protein phosphatase PP1-beta catalytic subunit (PPP1CB).	[23]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Serine/threonine-protein phosphatase PP1-beta catalytic subunit (PPP1CB).	[23]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Serine/threonine-protein phosphatase PP1-beta catalytic subunit (PPP1CB).	[24]
Marinol	DM70IK5	Approved	Marinol increases the expression of Serine/threonine-protein phosphatase PP1-beta catalytic subunit (PPP1CB).	[25]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Serine/threonine-protein phosphatase PP1-beta catalytic subunit (PPP1CB).	[26]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Serine/threonine-protein phosphatase PP1-beta catalytic subunit (PPP1CB).	[27]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of Serine/threonine-protein phosphatase PP1-beta catalytic subunit (PPP1CB).	[28]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Serine/threonine-protein phosphatase PP1-beta catalytic subunit (PPP1CB).	[24]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Serine/threonine-protein phosphatase PP1-beta catalytic subunit (PPP1CB).	[29]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate decreases the expression of Serine/threonine-protein phosphatase PP1-beta catalytic subunit (PPP1CB).	[30]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene decreases the expression of Serine/threonine-protein phosphatase PP1-beta catalytic subunit (PPP1CB).	[17]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Serine/threonine-protein phosphatase PP1-beta catalytic subunit (PPP1CB).	[31]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Serine/threonine-protein phosphatase PP1-beta catalytic subunit (PPP1CB).	[33]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Serine/threonine-protein phosphatase PP1-beta catalytic subunit (PPP1CB).	[34]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Serine/threonine-protein phosphatase PP1-beta catalytic subunit (PPP1CB).	[35]
OXYBENZONE	DMMZYX6	Investigative	OXYBENZONE increases the expression of Serine/threonine-protein phosphatase PP1-beta catalytic subunit (PPP1CB).	[36]

References

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