Details of Drug Off-Target (DOT)

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

• DOT Name: Tyrosine-protein phosphatase non-receptor type 21 (PTPN21)
• Synonyms: EC 3.1.3.48; Protein-tyrosine phosphatase D1
• Gene Name: PTPN21
• Related Disease:
  Graves disease
  Schizophrenia
• UniProt ID: PTN21_HUMAN
• PDB ID: 8GVL; 8GVV; 8GWH; 8GXE
• EC Number: 3.1.3.48
• Pfam ID: PF09380 ; PF00373 ; PF09379 ; PF00102
• Sequence:
  MPLPFGLKLKRTRRYTVSSKSCLVARIQLLNNEFVEFTLSVESTGQESLEAVAQRLELRE
  VTYFSLWYYNKQNQRRWVDLEKPLKKQLDKYALEPTVYFGVVFYVPSVSQLQQEITRYQY
  YLQLKKDILEGSIPCTLEQAIQLAGLAVQADFGDFDQYESQDFLQKFALFPVGWLQDEKV
  LEEATQKVALLHQKYRGLTAPDAEMLYMQEVERMDGYGEESYPAKDSQGSDISIGACLEG
  IFVKHKNGRHPVVFRWHDIANMSHNKSFFALELANKEETIQFQTEDMETAKYIWRLCVAR
  HKFYRLNQCNLQTQTVTVNPIRRRSSSRMSLPKPQPYVMPPPPQLHYNGHYTEPYASSQD
  NLFVPNQNGYYCHSQTSLDRAQIDLNGRIRNGSVYSAHSTNSLNNPQPYLQPSPMSSNPS
  ITGSDVMRPDYLPSHRHSAVIPPSYRPTPDYETVMKQLNRGLVHAERQSHSLRNLNIGSS
  YAYSRPAALVYSQPEIREHAQLPSPAAAHCPFSLSYSFHSPSPYPYPAERRPVVGAVSVP
  ELTNAQLQAQDYPSPNIMRTQVYRPPPPYPPPRPANSTPDLSRHLYISSSNPDLITRRVH
  HSVQTFQEDSLPVAHSLQEVSEPLTAARHAQLHKRNSIEVAGLSHGLEGLRLKERTLSAS
  AAEVAPRAVSVGSQPSVFTERTQREGPEEAEGLRYGHKKSLSDATMLIHSSEEEEDEDFE
  EESGARAPPARAREPRPGLAQDPPGCPRVLLAGPLHILEPKAHVPDAEKRMMDSSPVRTT
  AEAQRPWRDGLLMPSMSESDLTTSGRYRARRDSLKKRPVSDLLSGKKNIVEGLPPLGGMK
  KTRVDAKKIGPLKLAALNGLSLSRVPLPDEGKEVATRATNDERCKILEQRLEQGMVFTEY
  ERILKKRLVDGECSTARLPENAERNRFQDVLPYDDVRVELVPTKENNTGYINASHIKVSV
  SGIEWDYIATQGPLQNTCQDFWQMVWEQGIAIIAMVTAEEEGGREKSFRYWPRLGSRHNT
  VTYGRFKITTRFRTDSGCYATTGLKMKHLLTGQERTVWHLQYTDWPEHGCPEDLKGFLSY
  LEEIQSVRRHTNSTSDPQSPNPPLLVHCSAGVGRTGVVILSEIMIACLEHNEVLDIPRVL
  DMLRQQRMMLVQTLCQYTFVYRVLIQFLKSSRLI

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Graves disease	DISU4KOQ	Strong	Biomarker	[1]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[2]

16 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 Tyrosine-protein phosphatase non-receptor type 21 (PTPN21).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Tyrosine-protein phosphatase non-receptor type 21 (PTPN21).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Tyrosine-protein phosphatase non-receptor type 21 (PTPN21).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Tyrosine-protein phosphatase non-receptor type 21 (PTPN21).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Tyrosine-protein phosphatase non-receptor type 21 (PTPN21).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Tyrosine-protein phosphatase non-receptor type 21 (PTPN21).	[8]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Tyrosine-protein phosphatase non-receptor type 21 (PTPN21).	[9]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Tyrosine-protein phosphatase non-receptor type 21 (PTPN21).	[10]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Tyrosine-protein phosphatase non-receptor type 21 (PTPN21).	[10]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Tyrosine-protein phosphatase non-receptor type 21 (PTPN21).	[11]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Tyrosine-protein phosphatase non-receptor type 21 (PTPN21).	[12]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Tyrosine-protein phosphatase non-receptor type 21 (PTPN21).	[13]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Tyrosine-protein phosphatase non-receptor type 21 (PTPN21).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Tyrosine-protein phosphatase non-receptor type 21 (PTPN21).	[15]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Tyrosine-protein phosphatase non-receptor type 21 (PTPN21).	[16]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Tyrosine-protein phosphatase non-receptor type 21 (PTPN21).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Tyrosine-protein phosphatase non-receptor type 21 (PTPN21).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Tyrosine-protein phosphatase non-receptor type 21 (PTPN21).	[18]

References

• [1] Use of Tag single nucleotide polymorphisms (SNPs) to screen PTPN21: no association with Graves' disease.Clin Endocrinol (Oxf). 2006 Sep;65(3):380-4. doi: 10.1111/j.1365-2265.2006.02608.x.
• [2] Two non-synonymous markers in PTPN21, identified by genome-wide association study data-mining and replication, are associated with schizophrenia.Schizophr Res. 2011 Sep;131(1-3):43-51. doi: 10.1016/j.schres.2011.06.023. Epub 2011 Jul 14.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [9] Endoplasmic reticulum stress contributes to arsenic trioxide-induced intrinsic apoptosis in human umbilical and bone marrow mesenchymal stem cells. Environ Toxicol. 2016 Mar;31(3):314-28.
• [10] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [11] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [12] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [13] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [14] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [15] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [16] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [17] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [18] 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.