Details of Drug Off-Target (DOT)

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

• DOT Name: Astrocytic phosphoprotein PEA-15 (PEA15)
• Synonyms: 15 kDa phosphoprotein enriched in astrocytes; Phosphoprotein enriched in diabetes; PED
• Gene Name: PEA15
• Related Disease:
  Bone osteosarcoma
  Breast cancer
  Gastric cancer
  Osteosarcoma
  Stomach cancer
  Advanced cancer
  Age-related macular degeneration
  Astrocytoma
  Brain neoplasm
  Breast neoplasm
  Carcinoma of esophagus
  Depression
  Diabetic kidney disease
  Endometriosis
  Familial hypercholesterolemia
  Glioma
  Hepatitis C virus infection
  Hyperinsulinemia
  Lung cancer
  Lung carcinoma
  Lung neoplasm
  Major depressive disorder
  Malignant glioma
  Metabolic disorder
  Metastatic malignant neoplasm
  Neoplasm
  Neuroblastoma
  Non-insulin dependent diabetes
  Ovarian neoplasm
  Polycystic ovarian syndrome
  Renal cell carcinoma
  Small lymphocytic lymphoma
  Status epilepticus seizure
  Thyroid cancer
  Thyroid gland carcinoma
  Thyroid tumor
  Type-1/2 diabetes
  Carcinoma of liver and intrahepatic biliary tract
  Epithelial ovarian cancer
  Hepatocellular carcinoma
  Liver cancer
  Ovarian cancer
  Triple negative breast cancer
  Adult glioblastoma
  Breast carcinoma
  Glioblastoma multiforme
  Colorectal carcinoma
  Non-small-cell lung cancer
  Parkinson disease
• UniProt ID: PEA15_HUMAN
• PDB ID: 4IZ5; 4IZA; 6P6B; 6P6C
• Pfam ID: PF01335
• Sequence:
  MAEYGTLLQDLTNNITLEDLEQLKSACKEDIPSEKSEEITTGSAWFSFLESHNKLDKDNL
  SYIEHIFEISRRPDLLTMVVDYRTRVLKISEEDELDTKLTRIPSAKKYKDIIRQPSEEEI
  IKLAPPPKKA
• Function: Blocks Ras-mediated inhibition of integrin activation and modulates the ERK MAP kinase cascade. Inhibits RPS6KA3 activities by retaining it in the cytoplasm. Inhibits both TNFRSF6- and TNFRSF1A-mediated CASP8 activity and apoptosis. Regulates glucose transport by controlling both the content of SLC2A1 glucose transporters on the plasma membrane and the insulin-dependent trafficking of SLC2A4 from the cell interior to the surface.
• Tissue Specificity: Ubiquitously expressed. Most abundant in tissues such as heart, brain, muscle and adipose tissue which utilize glucose as an energy source. Lower expression in glucose-producing tissues. Higher levels of expression are found in tissues from individuals with type 2 diabetes than in controls.
• Reactome Pathway:
  RAF/MAP kinase cascade (R-HSA-5673001)
  RAF-independent MAPK1/3 activation (R-HSA-112409)

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bone osteosarcoma	DIST1004	Definitive	Altered Expression	[1]
Breast cancer	DIS7DPX1	Definitive	Altered Expression	[2]
Gastric cancer	DISXGOUK	Definitive	Biomarker	[3]
Osteosarcoma	DISLQ7E2	Definitive	Altered Expression	[1]
Stomach cancer	DISKIJSX	Definitive	Biomarker	[3]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[4]
Age-related macular degeneration	DIS0XS2C	Strong	Biomarker	[5]
Astrocytoma	DISL3V18	Strong	Biomarker	[6]
Brain neoplasm	DISY3EKS	Strong	Biomarker	[7]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[8]
Carcinoma of esophagus	DISS6G4D	Strong	Altered Expression	[9]
Depression	DIS3XJ69	Strong	Biomarker	[10]
Diabetic kidney disease	DISJMWEY	Strong	Altered Expression	[11]
Endometriosis	DISX1AG8	Strong	Biomarker	[12]
Familial hypercholesterolemia	DISC06IX	Strong	Genetic Variation	[13]
Glioma	DIS5RPEH	Strong	Biomarker	[14]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[15]
Hyperinsulinemia	DISIDWT6	Strong	Altered Expression	[16]
Lung cancer	DISCM4YA	Strong	Altered Expression	[17]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[17]
Lung neoplasm	DISVARNB	Strong	Biomarker	[1]
Major depressive disorder	DIS4CL3X	Strong	Altered Expression	[18]
Malignant glioma	DISFXKOV	Strong	Biomarker	[14]
Metabolic disorder	DIS71G5H	Strong	Biomarker	[13]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[4]
Neoplasm	DISZKGEW	Strong	Altered Expression	[3]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[19]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[20]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[21]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Altered Expression	[16]
Renal cell carcinoma	DISQZ2X8	Strong	Altered Expression	[22]
Small lymphocytic lymphoma	DIS30POX	Strong	Biomarker	[23]
Status epilepticus seizure	DISY3BIC	Strong	Genetic Variation	[24]
Thyroid cancer	DIS3VLDH	Strong	Altered Expression	[25]
Thyroid gland carcinoma	DISMNGZ0	Strong	Altered Expression	[25]
Thyroid tumor	DISLVKMD	Strong	Altered Expression	[25]
Type-1/2 diabetes	DISIUHAP	Strong	Altered Expression	[26]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	moderate	Biomarker	[27]
Epithelial ovarian cancer	DIS56MH2	moderate	Altered Expression	[21]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[27]
Liver cancer	DISDE4BI	moderate	Biomarker	[27]
Ovarian cancer	DISZJHAP	moderate	Altered Expression	[21]
Triple negative breast cancer	DISAMG6N	moderate	Altered Expression	[28]
Adult glioblastoma	DISVP4LU	Disputed	Altered Expression	[29]
Breast carcinoma	DIS2UE88	Disputed	Altered Expression	[2]
Glioblastoma multiforme	DISK8246	Disputed	Altered Expression	[29]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[4]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Altered Expression	[30]
Parkinson disease	DISQVHKL	Limited	Biomarker	[19]

3 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 Astrocytic phosphoprotein PEA-15 (PEA15).	[31]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Astrocytic phosphoprotein PEA-15 (PEA15).	[39]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Astrocytic phosphoprotein PEA-15 (PEA15).	[50]

24 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 Astrocytic phosphoprotein PEA-15 (PEA15).	[32]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Astrocytic phosphoprotein PEA-15 (PEA15).	[33]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Astrocytic phosphoprotein PEA-15 (PEA15).	[34]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Astrocytic phosphoprotein PEA-15 (PEA15).	[35]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Astrocytic phosphoprotein PEA-15 (PEA15).	[36]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Astrocytic phosphoprotein PEA-15 (PEA15).	[37]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Astrocytic phosphoprotein PEA-15 (PEA15).	[38]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Astrocytic phosphoprotein PEA-15 (PEA15).	[40]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Astrocytic phosphoprotein PEA-15 (PEA15).	[41]
Marinol	DM70IK5	Approved	Marinol increases the expression of Astrocytic phosphoprotein PEA-15 (PEA15).	[42]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Astrocytic phosphoprotein PEA-15 (PEA15).	[43]
Selenium	DM25CGV	Approved	Selenium increases the expression of Astrocytic phosphoprotein PEA-15 (PEA15).	[44]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Astrocytic phosphoprotein PEA-15 (PEA15).	[45]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Astrocytic phosphoprotein PEA-15 (PEA15).	[46]
Rigosertib	DMOSTXF	Phase 3	Rigosertib increases the expression of Astrocytic phosphoprotein PEA-15 (PEA15).	[47]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Astrocytic phosphoprotein PEA-15 (PEA15).	[44]
APR-246	DMNFADH	Phase 2	APR-246 increases the expression of Astrocytic phosphoprotein PEA-15 (PEA15).	[48]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Astrocytic phosphoprotein PEA-15 (PEA15).	[32]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Astrocytic phosphoprotein PEA-15 (PEA15).	[49]
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 decreases the expression of Astrocytic phosphoprotein PEA-15 (PEA15).	[51]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Astrocytic phosphoprotein PEA-15 (PEA15).	[52]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Astrocytic phosphoprotein PEA-15 (PEA15).	[53]
chloropicrin	DMSGBQA	Investigative	chloropicrin affects the expression of Astrocytic phosphoprotein PEA-15 (PEA15).	[54]
AM251	DMTAWHL	Investigative	AM251 increases the expression of Astrocytic phosphoprotein PEA-15 (PEA15).	[55]

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