Details of Drug Off-Target (DOT)

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

• DOT Name: Receptor-type tyrosine-protein phosphatase beta (PTPRB)
• Synonyms: Protein-tyrosine phosphatase beta; R-PTP-beta; EC 3.1.3.48; Vascular endothelial protein tyrosine phosphatase; VE-PTP
• Gene Name: PTPRB
• UniProt ID: PTPRB_HUMAN
• PDB ID: 2AHS; 2H02; 2H03; 2H04; 2HC1; 2HC2; 2I3R; 2I3U; 2I4E; 2I4G; 2I4H; 2I5X
• EC Number: 3.1.3.48
• Pfam ID: PF00041 ; PF18861 ; PF00102
• Sequence:
  MLSHGAGLALWITLSLLQTGLAEPERCNFTLAESKASSHSVSIQWRILGSPCNFSLIYSS
  DTLGAALCPTFRIDNTTYGCNLQDLQAGTIYNFRIISLDEERTVVLQTDPLPPARFGVSK
  EKTTSTSLHVWWTPSSGKVTSYEVQLFDENNQKIQGVQIQESTSWNEYTFFNLTAGSKYN
  IAITAVSGGKRSFSVYTNGSTVPSPVKDIGISTKANSLLISWSHGSGNVERYRLMLMDKG
  ILVHGGVVDKHATSYAFHGLTPGYLYNLTVMTEAAGLQNYRWKLVRTAPMEVSNLKVTND
  GSLTSLKVKWQRPPGNVDSYNITLSHKGTIKESRVLAPWITETHFKELVPGRLYQVTVSC
  VSGELSAQKMAVGRTFPDKVANLEANNNGRMRSLVVSWSPPAGDWEQYRILLFNDSVVLL
  NITVGKEETQYVMDDTGLVPGRQYEVEVIVESGNLKNSERCQGRTVPLAVLQLRVKHANE
  TSLSIMWQTPVAEWEKYIISLADRDLLLIHKSLSKDAKEFTFTDLVPGRKYMATVTSISG
  DLKNSSSVKGRTVPAQVTDLHVANQGMTSSLFTNWTQAQGDVEFYQVLLIHENVVIKNES
  ISSETSRYSFHSLKSGSLYSVVVTTVSGGISSRQVVVEGRTVPSSVSGVTVNNSGRNDYL
  SVSWLLAPGDVDNYEVTLSHDGKVVQSLVIAKSVRECSFSSLTPGRLYTVTITTRSGKYE
  NHSFSQERTVPDKVQGVSVSNSARSDYLRVSWVHATGDFDHYEVTIKNKNNFIQTKSIPK
  SENECVFVQLVPGRLYSVTVTTKSGQYEANEQGNGRTIPEPVKDLTLRNRSTEDLHVTWS
  GANGDVDQYEIQLLFNDMKVFPPFHLVNTATEYRFTSLTPGRQYKILVLTISGDVQQSAF
  IEGFTVPSAVKNIHISPNGATDSLTVNWTPGGGDVDSYTVSAFRHSQKVDSQTIPKHVFE
  HTFHRLEAGEQYQIMIASVSGSLKNQINVVGRTVPASVQGVIADNAYSSYSLIVSWQKAA
  GVAERYDILLLTENGILLRNTSEPATTKQHKFEDLTPGKKYKIQILTVSGGLFSKEAQTE
  GRTVPAAVTDLRITENSTRHLSFRWTASEGELSWYNIFLYNPDGNLQERAQVDPLVQSFS
  FQNLLQGRMYKMVIVTHSGELSNESFIFGRTVPASVSHLRGSNRNTTDSLWFNWSPASGD
  FDFYELILYNPNGTKKENWKDKDLTEWRFQGLVPGRKYVLWVVTHSGDLSNKVTAESRTA
  PSPPSLMSFADIANTSLAITWKGPPDWTDYNDFELQWLPRDALTVFNPYNNRKSEGRIVY
  GLRPGRSYQFNVKTVSGDSWKTYSKPIFGSVRTKPDKIQNLHCRPQNSTAIACSWIPPDS
  DFDGYSIECRKMDTQEVEFSRKLEKEKSLLNIMMLVPHKRYLVSIKVQSAGMTSEVVEDS
  TITMIDRPPPPPPHIRVNEKDVLISKSSINFTVNCSWFSDTNGAVKYFTVVVREADGSDE
  LKPEQQHPLPSYLEYRHNASIRVYQTNYFASKCAENPNSNSKSFNIKLGAEMESLGGKCD
  PTQQKFCDGPLKPHTAYRISIRAFTQLFDEDLKEFTKPLYSDTFFSLPITTESEPLFGAI
  EGVSAGLFLIGMLVAVVALLICRQKVSHGRERPSARLSIRRDRPLSVHLNLGQKGNRKTS
  CPIKINQFEGHFMKLQADSNYLLSKEYEELKDVGRNQSCDIALLPENRGKNRYNNILPYD
  ATRVKLSNVDDDPCSDYINASYIPGNNFRREYIVTQGPLPGTKDDFWKMVWEQNVHNIVM
  VTQCVEKGRVKCDHYWPADQDSLYYGDLILQMLSESVLPEWTIREFKICGEEQLDAHRLI
  RHFHYTVWPDHGVPETTQSLIQFVRTVRDYINRSPGAGPTVVHCSAGVGRTGTFIALDRI
  LQQLDSKDSVDIYGAVHDLRLHRVHMVQTECQYVYLHQCVRDVLRARKLRSEQENPLFPI
  YENVNPEYHRDPVYSRH
• Function: Plays an important role in blood vessel remodeling and angiogenesis. Not necessary for the initial formation of blood vessels, but is essential for their maintenance and remodeling. Can induce dephosphorylation of TEK/TIE2, CDH5/VE-cadherin and KDR/VEGFR-2. Regulates angiopoietin-TIE2 signaling in endothelial cells. Acts as a negative regulator of TIE2, and controls TIE2 driven endothelial cell proliferation, which in turn affects blood vessel remodeling during embryonic development and determines blood vessel size during perinatal growth. Essential for the maintenance of endothelial cell contact integrity and for the adhesive function of VE-cadherin in endothelial cells and this requires the presence of plakoglobin.
• KEGG Pathway: Adherens junction (hsa04520)
• Reactome Pathway: Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Receptor-type tyrosine-protein phosphatase beta (PTPRB).	[1]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Receptor-type tyrosine-protein phosphatase beta (PTPRB).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Receptor-type tyrosine-protein phosphatase beta (PTPRB).	[3]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of Receptor-type tyrosine-protein phosphatase beta (PTPRB).	[4]
Cocaine	DMSOX7I	Approved	Cocaine decreases the expression of Receptor-type tyrosine-protein phosphatase beta (PTPRB).	[5]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Receptor-type tyrosine-protein phosphatase beta (PTPRB).	[6]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Receptor-type tyrosine-protein phosphatase beta (PTPRB).	[7]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Receptor-type tyrosine-protein phosphatase beta (PTPRB).	[9]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Receptor-type tyrosine-protein phosphatase beta (PTPRB).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Receptor-type tyrosine-protein phosphatase beta (PTPRB).	[8]

References

• [1] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [2] RNA sequence analysis of inducible pluripotent stem cell-derived cardiomyocytes reveals altered expression of DNA damage and cell cycle genes in response to doxorubicin. Toxicol Appl Pharmacol. 2018 Oct 1;356:44-53.
• [3] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [4] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [5] Gene expression in human hippocampus from cocaine abusers identifies genes which regulate extracellular matrix remodeling. PLoS One. 2007 Nov 14;2(11):e1187. doi: 10.1371/journal.pone.0001187.
• [6] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [7] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [8] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [9] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [10] The contact allergen nickel triggers a unique inflammatory and proangiogenic gene expression pattern via activation of NF-kappaB and hypoxia-inducible factor-1alpha. J Immunol. 2007 Mar 1;178(5):3198-207.