Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZA82J1)

• DOT Name: Receptor-type tyrosine-protein phosphatase alpha (PTPRA)
• Synonyms: Protein-tyrosine phosphatase alpha; R-PTP-alpha; EC 3.1.3.48
• Gene Name: PTPRA
• Related Disease:
  B-cell neoplasm
  Gastric neoplasm
  Melanoma
  Myocardial infarction
  Neuroblastoma
  Acute leukaemia
  Acute lymphocytic leukaemia
  Acute monocytic leukemia
  Adult T-cell leukemia/lymphoma
  Astrocytoma
  Autism spectrum disorder
  Breast carcinoma
  Breast neoplasm
  Childhood acute lymphoblastic leukemia
  Colorectal carcinoma
  Coronary atherosclerosis
  Endometrial carcinoma
  Esophageal cancer
  Hyperinsulinemia
  leukaemia
  Leukemia
  Lung neoplasm
  Medulloblastoma
  Myocardial ischemia
  Pancreatic cancer
  Plasma cell myeloma
  Skin disease
  T-cell leukaemia
  Triple negative breast cancer
  Acute myelogenous leukaemia
  Breast cancer
  Carcinoma
  Periodontitis
  Small-cell lung cancer
  Tuberculosis
  Adult lymphoma
  Brain neoplasm
  Coronary heart disease
  Glioma
  Lung squamous cell carcinoma
  Lymphoma
  Non-small-cell lung cancer
  Parkinson disease
  Pediatric lymphoma
  Prostate cancer
  Prostate carcinoma
• UniProt ID: PTPRA_HUMAN
• PDB ID: 6UZT
• EC Number: 3.1.3.48
• Pfam ID: PF00102
• Sequence:
  MDSWFILVLLGSGLICVSANNATTVAPSVGITRLINSSTAEPVKEEAKTSNPTSSLTSLS
  VAPTFSPNITLGPTYLTTVNSSDSDNGTTRTASTNSIGITISPNGTWLPDNQFTDARTEP
  WEGNSSTAATTPETFPPSGNSDSKDRRDETPIIAVMVALSSLLVIVFIIIVLYMLRFKKY
  KQAGSHSNSFRLSNGRTEDVEPQSVPLLARSPSTNRKYPPLPVDKLEEEINRRMADDNKL
  FREEFNALPACPIQATCEAASKEENKEKNRYVNILPYDHSRVHLTPVEGVPDSDYINASF
  INGYQEKNKFIAAQGPKEETVNDFWRMIWEQNTATIVMVTNLKERKECKCAQYWPDQGCW
  TYGNIRVSVEDVTVLVDYTVRKFCIQQVGDMTNRKPQRLITQFHFTSWPDFGVPFTPIGM
  LKFLKKVKACNPQYAGAIVVHCSAGVGRTGTFVVIDAMLDMMHTERKVDVYGFVSRIRAQ
  RCQMVQTDMQYVFIYQALLEHYLYGDTELEVTSLETHLQKIYNKIPGTSNNGLEEEFKKL
  TSIKIQNDKMRTGNLPANMKKNRVLQIIPYEFNRVIIPVKRGEENTDYVNASFIDGYRQK
  DSYIASQGPLLHTIEDFWRMIWEWKSCSIVMLTELEERGQEKCAQYWPSDGLVSYGDITV
  ELKKEEECESYTVRDLLVTNTRENKSRQIRQFHFHGWPEVGIPSDGKGMISIIAAVQKQQ
  QQSGNHPITVHCSAGAGRTGTFCALSTVLERVKAEGILDVFQTVKSLRLQRPHMVQTLEQ
  YEFCYKVVQEYIDAFSDYANFK
• Function: Tyrosine protein phosphatase which is involved in integrin-mediated focal adhesion formation. Following integrin engagement, specifically recruits BCAR3, BCAR1 and CRK to focal adhesions thereby promoting SRC-mediated phosphorylation of BRAC1 and the subsequent activation of PAK and small GTPase RAC1 and CDC42.
• Reactome Pathway:
  RAF/MAP kinase cascade (R-HSA-5673001)
  NCAM signaling for neurite out-growth (R-HSA-375165)

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
B-cell neoplasm	DISVY326	Definitive	Altered Expression	[1]
Gastric neoplasm	DISOKN4Y	Definitive	Biomarker	[2]
Melanoma	DIS1RRCY	Definitive	Biomarker	[3]
Myocardial infarction	DIS655KI	Definitive	Genetic Variation	[4]
Neuroblastoma	DISVZBI4	Definitive	Biomarker	[5]
Acute leukaemia	DISDQFDI	Strong	Biomarker	[6]
Acute lymphocytic leukaemia	DISPX75S	Strong	Biomarker	[7]
Acute monocytic leukemia	DIS28NEL	Strong	Biomarker	[8]
Adult T-cell leukemia/lymphoma	DIS882XU	Strong	Biomarker	[9]
Astrocytoma	DISL3V18	Strong	Altered Expression	[10]
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[11]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[12]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[13]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Strong	Biomarker	[7]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[14]
Coronary atherosclerosis	DISKNDYU	Strong	Genetic Variation	[15]
Endometrial carcinoma	DISXR5CY	Strong	Altered Expression	[16]
Esophageal cancer	DISGB2VN	Strong	Altered Expression	[17]
Hyperinsulinemia	DISIDWT6	Strong	Genetic Variation	[18]
leukaemia	DISS7D1V	Strong	Biomarker	[19]
Leukemia	DISNAKFL	Strong	Biomarker	[19]
Lung neoplasm	DISVARNB	Strong	Altered Expression	[20]
Medulloblastoma	DISZD2ZL	Strong	Altered Expression	[10]
Myocardial ischemia	DISFTVXF	Strong	Biomarker	[21]
Pancreatic cancer	DISJC981	Strong	Biomarker	[5]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[22]
Skin disease	DISDW8R6	Strong	Biomarker	[23]
T-cell leukaemia	DISJ6YIF	Strong	Biomarker	[9]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[24]
Acute myelogenous leukaemia	DISCSPTN	moderate	Biomarker	[25]
Breast cancer	DIS7DPX1	moderate	Biomarker	[12]
Carcinoma	DISH9F1N	moderate	Biomarker	[26]
Periodontitis	DISI9JOI	moderate	Biomarker	[27]
Small-cell lung cancer	DISK3LZD	moderate	Biomarker	[28]
Tuberculosis	DIS2YIMD	Disputed	Biomarker	[29]
Adult lymphoma	DISK8IZR	Limited	Biomarker	[30]
Brain neoplasm	DISY3EKS	Limited	Biomarker	[31]
Coronary heart disease	DIS5OIP1	Limited	Genetic Variation	[32]
Glioma	DIS5RPEH	Limited	Biomarker	[31]
Lung squamous cell carcinoma	DISXPIBD	Limited	Biomarker	[33]
Lymphoma	DISN6V4S	Limited	Biomarker	[30]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Altered Expression	[34]
Parkinson disease	DISQVHKL	Limited	Genetic Variation	[35]
Pediatric lymphoma	DIS51BK2	Limited	Biomarker	[30]
Prostate cancer	DISF190Y	Limited	Altered Expression	[36]
Prostate carcinoma	DISMJPLE	Limited	Altered Expression	[36]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Receptor-type tyrosine-protein phosphatase alpha (PTPRA).	[37]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Receptor-type tyrosine-protein phosphatase alpha (PTPRA).	[38]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Receptor-type tyrosine-protein phosphatase alpha (PTPRA).	[39]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Receptor-type tyrosine-protein phosphatase alpha (PTPRA).	[40]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Receptor-type tyrosine-protein phosphatase alpha (PTPRA).	[41]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Receptor-type tyrosine-protein phosphatase alpha (PTPRA).	[42]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Receptor-type tyrosine-protein phosphatase alpha (PTPRA).	[41]
Nicotine	DMWX5CO	Approved	Nicotine decreases the expression of Receptor-type tyrosine-protein phosphatase alpha (PTPRA).	[43]
Cocaine	DMSOX7I	Approved	Cocaine decreases the expression of Receptor-type tyrosine-protein phosphatase alpha (PTPRA).	[44]
Mecamylamine	DMGQFYB	Approved	Mecamylamine decreases the expression of Receptor-type tyrosine-protein phosphatase alpha (PTPRA).	[43]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Receptor-type tyrosine-protein phosphatase alpha (PTPRA).	[45]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Receptor-type tyrosine-protein phosphatase alpha (PTPRA).	[46]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Receptor-type tyrosine-protein phosphatase alpha (PTPRA).	[49]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Receptor-type tyrosine-protein phosphatase alpha (PTPRA).	[51]

3 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 Receptor-type tyrosine-protein phosphatase alpha (PTPRA).	[47]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Receptor-type tyrosine-protein phosphatase alpha (PTPRA).	[48]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Receptor-type tyrosine-protein phosphatase alpha (PTPRA).	[50]

References

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