Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVYD1VA)

• DOT Name: Calcineurin subunit B type 2 (PPP3R2)
• Synonyms: Calcineurin B-like protein; CBLP; Calcineurin BII; CNBII; PPP3R1-like; Protein phosphatase 2B regulatory subunit 2; Protein phosphatase 3 regulatory subunit B beta isoform
• Gene Name: PPP3R2
• Related Disease: Osteoarthritis
• UniProt ID: CANB2_HUMAN
• Pfam ID: PF13499
• Sequence:
  MGNEASYPAEMCSHFDNDEIKRLGRRFKKLDLDKSGSLSVEEFMSLPELRHNPLVRRVID
  VFDTDGDGEVDFKEFILGTSQFSVKGDEEQKLRFAFSIYDMDKDGYISNGELFQVLKMMV
  GNNLTDWQLQQLVDKTIIILDKDGDGKISFEEFSAVVRDLEIHKKLVLIV
• Function: Regulatory subunit of calcineurin, a calcium-dependent, calmodulin stimulated protein phosphatase. Confers calcium sensitivity.
• Tissue Specificity: Testis-specific.
• KEGG Pathway:
  MAPK sig.ling pathway (hsa04010)
  Calcium sig.ling pathway (hsa04020)
  cGMP-PKG sig.ling pathway (hsa04022)
  Oocyte meiosis (hsa04114)
  Cellular senescence (hsa04218)
  Wnt sig.ling pathway (hsa04310)
  Axon guidance (hsa04360)
  VEGF sig.ling pathway (hsa04370)
  Osteoclast differentiation (hsa04380)
  C-type lectin receptor sig.ling pathway (hsa04625)
  .tural killer cell mediated cytotoxicity (hsa04650)
  Th1 and Th2 cell differentiation (hsa04658)
  Th17 cell differentiation (hsa04659)
  T cell receptor sig.ling pathway (hsa04660)
  B cell receptor sig.ling pathway (hsa04662)
  Long-term potentiation (hsa04720)
  Glutamatergic sy.pse (hsa04724)
  Oxytocin sig.ling pathway (hsa04921)
  Glucagon sig.ling pathway (hsa04922)
  Renin secretion (hsa04924)
  Alzheimer disease (hsa05010)
  Amyotrophic lateral sclerosis (hsa05014)
  Prion disease (hsa05020)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
  Amphetamine addiction (hsa05031)
  Tuberculosis (hsa05152)
  Human cytomegalovirus infection (hsa05163)
  Human T-cell leukemia virus 1 infection (hsa05166)
  Kaposi sarcoma-associated herpesvirus infection (hsa05167)
  Human immunodeficiency virus 1 infection (hsa05170)
  PD-L1 expression and PD-1 checkpoint pathway in cancer (hsa05235)
  Lipid and atherosclerosis (hsa05417)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Osteoarthritis	DIS05URM	moderate	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Calcineurin subunit B type 2 (PPP3R2).	[2]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Calcineurin subunit B type 2 (PPP3R2).	[3]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Calcineurin subunit B type 2 (PPP3R2).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Calcineurin subunit B type 2 (PPP3R2).	[4]

References

• [1] miR-146a facilitates osteoarthritis by regulating cartilage homeostasis via targeting Camk2d and Ppp3r2.Cell Death Dis. 2017 Apr 6;8(4):e2734. doi: 10.1038/cddis.2017.146.
• [2] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [3] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [4] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [5] Cellular reactions to long-term volatile organic compound (VOC) exposures. Sci Rep. 2016 Dec 1;6:37842. doi: 10.1038/srep37842.