Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXK0SDM)

• DOT Name: Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B gamma isoform (PPP2R2C)
• Synonyms: IMYPNO1; PP2A subunit B isoform B55-gamma; PP2A subunit B isoform PR55-gamma; PP2A subunit B isoform R2-gamma; PP2A subunit B isoform gamma
• Gene Name: PPP2R2C
• Related Disease:
  Advanced cancer
  Bipolar disorder
  Brain cancer
  Brain neoplasm
  Epithelial ovarian cancer
  Hyperinsulinemia
  Lung cancer
  Lung carcinoma
  Non-insulin dependent diabetes
  Ovarian cancer
  Ovarian neoplasm
  Peripheral arterial disease
  Prostate cancer
  Prostate carcinoma
  Prostate neoplasm
  Spastic paralysis
  Hepatocellular carcinoma
  Acute myelogenous leukaemia
  Intellectual disability
  Nasopharyngeal carcinoma
• UniProt ID: 2ABG_HUMAN
• Sequence:
  MGEDTDTRKINHSFLRDHSYVTEADIISTVEFNHTGELLATGDKGGRVVIFQREPESKNA
  PHSQGEYDVYSTFQSHEPEFDYLKSLEIEEKINKIKWLPQQNAAHSLLSTNDKTIKLWKI
  TERDKRPEGYNLKDEEGKLKDLSTVTSLQVPVLKPMDLMVEVSPRRIFANGHTYHINSIS
  VNSDCETYMSADDLRINLWHLAITDRSFNIVDIKPANMEDLTEVITASEFHPHHCNLFVY
  SSSKGSLRLCDMRAAALCDKHSKLFEEPEDPSNRSFFSEIISSVSDVKFSHSGRYMLTRD
  YLTVKVWDLNMEARPIETYQVHDYLRSKLCSLYENDCIFDKFECAWNGSDSVIMTGAYNN
  FFRMFDRNTKRDVTLEASRESSKPRAVLKPRRVCVGGKRRRDDISVDSLDFTKKILHTAW
  HPAENIIAIAATNNLYIFQDKVNSDMH
• 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)
  Hippo sig.ling pathway (hsa04390)
  Tight junction (hsa04530)
  T cell receptor sig.ling pathway (hsa04660)
  Dopaminergic sy.pse (hsa04728)
  Chagas disease (hsa05142)
  Hepatitis C (hsa05160)
  Human papillomavirus infection (hsa05165)

Molecular Interaction Atlas (MIA) of This DOT

20 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Bipolar disorder	DISAM7J2	Strong	Biomarker	[2]
Brain cancer	DISBKFB7	Strong	Biomarker	[3]
Brain neoplasm	DISY3EKS	Strong	Altered Expression	[3]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[4]
Hyperinsulinemia	DISIDWT6	Strong	Genetic Variation	[5]
Lung cancer	DISCM4YA	Strong	Genetic Variation	[6]
Lung carcinoma	DISTR26C	Strong	Genetic Variation	[6]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[7]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[4]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[4]
Peripheral arterial disease	DIS78WFB	Strong	Genetic Variation	[8]
Prostate cancer	DISF190Y	Strong	Biomarker	[9]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[9]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[10]
Spastic paralysis	DISVQ6I2	Strong	Biomarker	[11]
Hepatocellular carcinoma	DIS0J828	moderate	Altered Expression	[12]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[13]
Intellectual disability	DISMBNXP	Limited	Genetic Variation	[14]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Altered Expression	[15]

3 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 55 kDa regulatory subunit B gamma isoform (PPP2R2C).	[16]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B gamma isoform (PPP2R2C).	[28]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B gamma isoform (PPP2R2C).	[29]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B gamma isoform (PPP2R2C).	[17]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B gamma isoform (PPP2R2C).	[18]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B gamma isoform (PPP2R2C).	[19]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B gamma isoform (PPP2R2C).	[20]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B gamma isoform (PPP2R2C).	[21]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B gamma isoform (PPP2R2C).	[22]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B gamma isoform (PPP2R2C).	[20]
Cocaine	DMSOX7I	Approved	Cocaine decreases the expression of Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B gamma isoform (PPP2R2C).	[23]
Testosterone Undecanoate	DMZO10Y	Approved	Testosterone Undecanoate increases the expression of Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B gamma isoform (PPP2R2C).	[24]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B gamma isoform (PPP2R2C).	[25]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B gamma isoform (PPP2R2C).	[26]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B gamma isoform (PPP2R2C).	[18]
OTX-015	DMI8RG1	Phase 1/2	OTX-015 decreases the expression of Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B gamma isoform (PPP2R2C).	[27]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B gamma isoform (PPP2R2C).	[27]
Mivebresib	DMCPF90	Phase 1	Mivebresib decreases the expression of Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B gamma isoform (PPP2R2C).	[27]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B gamma isoform (PPP2R2C).	[30]

References

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• [16] 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.
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• [18] Convergent transcriptional profiles induced by endogenous estrogen and distinct xenoestrogens in breast cancer cells. Carcinogenesis. 2006 Aug;27(8):1567-78.
• [19] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
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