Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTL6SH28)

• DOT Name: Receptor-type tyrosine-protein phosphatase N2 (PTPRN2)
• Synonyms: R-PTP-N2; EC 3.1.3.-; EC 3.1.3.48; Islet cell autoantigen-related protein; IAR; ICAAR; Phogrin
• Gene Name: PTPRN2
• Related Disease:
  Chronic kidney disease
  Chronic renal failure
  Non-insulin dependent diabetes
  Attention deficit hyperactivity disorder
  Autoimmune disease
  Breast cancer
  Breast carcinoma
  Duane retraction syndrome
  Hepatocellular carcinoma
  Malignant neoplasm
  Metabolic disorder
  Myocardial infarction
  Neoplasm
  Prostate cancer
  Prostate carcinoma
  Schizophrenia
  Type-1/2 diabetes
  Atopic dermatitis
  Prediabetes syndrome
  Psoriasis
• UniProt ID: PTPR2_HUMAN
• PDB ID: 2QEP; 4HTI; 4HTJ
• EC Number: 3.1.3.-; 3.1.3.48
• Pfam ID: PF11548 ; PF14948 ; PF00102
• Sequence:
  MGPPLPLLLLLLLLLPPRVLPAAPSSVPRGRQLPGRLGCLLEEGLCGASEACVNDGVFGR
  CQKVPAMDFYRYEVSPVALQRLRVALQKLSGTGFTWQDDYTQYVMDQELADLPKTYLRRP
  EASSPARPSKHSVGSERRYSREGGAALANALRRHLPFLEALSQAPASDVLARTHTAQDRP
  PAEGDDRFSESILTYVAHTSALTYPPGSRTQLREDLLPRTLGQLQPDELSPKVDSGVDRH
  HLMAALSAYAAQRPPAPPGEGSLEPQYLLRAPSRMPRPLLAPAAPQKWPSPLGDSEDPSS
  TGDGARIHTLLKDLQRQPAEVRGLSGLELDGMAELMAGLMQGVDHGVARGSPGRAALGES
  GEQADGPKATLRGDSFPDDGVQDDDDRLYQEVHRLSATLGGLLQDHGSRLLPGALPFARP
  LDMERKKSEHPESSLSSEEETAGVENVKSQTYSKDLLGQQPHSEPGAAAFGELQNQMPGP
  SKEEQSLPAGAQEALSDGLQLEVQPSEEEARGYIVTDRDPLRPEEGRRLVEDVARLLQVP
  SSAFADVEVLGPAVTFKVSANVQNVTTEDVEKATVDNKDKLEETSGLKILQTGVGSKSKL
  KFLPPQAEQEDSTKFIALTLVSLACILGVLLASGLIYCLRHSSQHRLKEKLSGLGGDPGA
  DATAAYQELCRQRMATRPPDRPEGPHTSRISSVSSQFSDGPIPSPSARSSASSWSEEPVQ
  SNMDISTGHMILSYMEDHLKNKNRLEKEWEALCAYQAEPNSSFVAQREENVPKNRSLAVL
  TYDHSRVLLKAENSHSHSDYINASPIMDHDPRNPAYIATQGPLPATVADFWQMVWESGCV
  VIVMLTPLAENGVRQCYHYWPDEGSNLYHIYEVNLVSEHIWCEDFLVRSFYLKNLQTNET
  RTVTQFHFLSWYDRGVPSSSRSLLDFRRKVNKCYRGRSCPIIVHCSDGAGRSGTYVLIDM
  VLNKMAKGAKEIDIAATLEHLRDQRPGMVQTKEQFEFALTAVAEEVNAILKALPQ
• Function: Plays a role in vesicle-mediated secretory processes. Required for normal accumulation of secretory vesicles in hippocampus, pituitary and pancreatic islets. Required for the accumulation of normal levels of insulin-containing vesicles and preventing their degradation. Plays a role in insulin secretion in response to glucose stimuli. Required for normal accumulation of the neurotransmitters norepinephrine, dopamine and serotonin in the brain. In females, but not in males, required for normal accumulation and secretion of pituitary hormones, such as luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Required to maintain normal levels of renin expression and renin release. May regulate catalytic active protein-tyrosine phosphatases such as PTPRA through dimerization. Has phosphatidylinositol phosphatase activity; the PIPase activity is involved in its ability to regulate insulin secretion. Can dephosphorylate phosphatidylinositol 4,5-biphosphate (PI(4,5)P2), phosphatidylinositol 5-phosphate and phosphatidylinositol 3-phosphate. Regulates PI(4,5)P2 level in the plasma membrane and localization of cofilin at the plasma membrane and thus is indirectly involved in regulation of actin dynamics related to cell migration and metastasis; upon hydrolyzation of PI(4,5)P2 cofilin is released from the plasma membrane and acts in the cytoplasm in severing F-actin filaments.
• Tissue Specificity: Highest levels in brain and pancreas . Lower levels in trachea, prostate, stomach and spinal cord .
• KEGG Pathway: Type I diabetes mellitus (hsa04940)
• Reactome Pathway: Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

20 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chronic kidney disease	DISW82R7	Definitive	Genetic Variation	[1]
Chronic renal failure	DISGG7K6	Definitive	Genetic Variation	[1]
Non-insulin dependent diabetes	DISK1O5Z	Definitive	Genetic Variation	[2]
Attention deficit hyperactivity disorder	DISL8MX9	Strong	Genetic Variation	[3]
Autoimmune disease	DISORMTM	Strong	Biomarker	[4]
Breast cancer	DIS7DPX1	Strong	Biomarker	[5]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[6]
Duane retraction syndrome	DISOEBK2	Strong	Altered Expression	[7]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[8]
Malignant neoplasm	DISS6SNG	Strong	Genetic Variation	[6]
Metabolic disorder	DIS71G5H	Strong	Posttranslational Modification	[9]
Myocardial infarction	DIS655KI	Strong	Genetic Variation	[10]
Neoplasm	DISZKGEW	Strong	Altered Expression	[7]
Prostate cancer	DISF190Y	Strong	Genetic Variation	[11]
Prostate carcinoma	DISMJPLE	Strong	Genetic Variation	[11]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[12]
Type-1/2 diabetes	DISIUHAP	Strong	Altered Expression	[13]
Atopic dermatitis	DISTCP41	Limited	Genetic Variation	[14]
Prediabetes syndrome	DISH2I53	Limited	Biomarker	[15]
Psoriasis	DIS59VMN	Limited	Genetic Variation	[14]

17 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 N2 (PTPRN2).	[16]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Receptor-type tyrosine-protein phosphatase N2 (PTPRN2).	[17]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Receptor-type tyrosine-protein phosphatase N2 (PTPRN2).	[18]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Receptor-type tyrosine-protein phosphatase N2 (PTPRN2).	[19]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Receptor-type tyrosine-protein phosphatase N2 (PTPRN2).	[21]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Receptor-type tyrosine-protein phosphatase N2 (PTPRN2).	[22]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Receptor-type tyrosine-protein phosphatase N2 (PTPRN2).	[23]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Receptor-type tyrosine-protein phosphatase N2 (PTPRN2).	[24]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Receptor-type tyrosine-protein phosphatase N2 (PTPRN2).	[16]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Receptor-type tyrosine-protein phosphatase N2 (PTPRN2).	[24]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Receptor-type tyrosine-protein phosphatase N2 (PTPRN2).	[25]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Receptor-type tyrosine-protein phosphatase N2 (PTPRN2).	[16]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Receptor-type tyrosine-protein phosphatase N2 (PTPRN2).	[27]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Receptor-type tyrosine-protein phosphatase N2 (PTPRN2).	[28]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Receptor-type tyrosine-protein phosphatase N2 (PTPRN2).	[30]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Receptor-type tyrosine-protein phosphatase N2 (PTPRN2).	[31]
ELLAGIC ACID	DMX8BS5	Investigative	ELLAGIC ACID increases the expression of Receptor-type tyrosine-protein phosphatase N2 (PTPRN2).	[32]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Receptor-type tyrosine-protein phosphatase N2 (PTPRN2).	[20]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Receptor-type tyrosine-protein phosphatase N2 (PTPRN2).	[26]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Receptor-type tyrosine-protein phosphatase N2 (PTPRN2).	[29]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the methylation of Receptor-type tyrosine-protein phosphatase N2 (PTPRN2).	[26]

References

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