Details of Drug Off-Target (DOT)

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

• DOT Name: Tyrosine-protein phosphatase non-receptor type 13 (PTPN13)
• Synonyms: EC 3.1.3.48; Fas-associated protein-tyrosine phosphatase 1; FAP-1; PTP-BAS; Protein-tyrosine phosphatase 1E; PTP-E1; hPTPE1; Protein-tyrosine phosphatase PTPL1
• Gene Name: PTPN13
• UniProt ID: PTN13_HUMAN
• PDB ID: 1D5G; 1Q7X; 1WCH; 2M0Z; 2M10; 3LNX; 3LNY; 3PDZ; 5GLJ; 7QCX; 7QCY; 7XTY
• EC Number: 3.1.3.48
• Pfam ID: PF09380 ; PF00373 ; PF09379 ; PF00595 ; PF16599 ; PF00102
• Sequence:
  MHVSLAEALEVRGGPLQEEEIWAVLNQSAESLQELFRKVSLADPAALGFIISPWSLLLLP
  SGSVSFTDENISNQDLRAFTAPEVLQNQSLTSLSDVEKIHIYSLGMTLYWGADYEVPQSQ
  PIKLGDHLNSILLGMCEDVIYARVSVRTVLDACSAHIRNSNCAPSFSYVKHLVKLVLGNL
  SGTDQLSCNSEQKPDRSQAIRDRLRGKGLPTGRSSTSDVLDIQKPPLSHQTFLNKGLSKS
  MGFLSIKDTQDENYFKDILSDNSGREDSENTFSPYQFKTSGPEKKPIPGIDVLSKKKIWA
  SSMDLLCTADRDFSSGETATYRRCHPEAVTVRTSTTPRKKEARYSDGSIALDIFGPQKMD
  PIYHTRELPTSSAISSALDRIRERQKKLQVLREAMNVEEPVRRYKTYHGDVFSTSSESPS
  IISSESDFRQVRRSEASKRFESSSGLPGVDETLSQGQSQRPSRQYETPFEGNLINQEIML
  KRQEEELMQLQAKMALRQSRLSLYPGDTIKASMLDITRDPLREIALETAMTQRKLRNFFG
  PEFVKMTIEPFISLDLPRSILTKKGKNEDNRRKVNIMLLNGQRLELTCDTKTICKDVFDM
  VVAHIGLVEHHLFALATLKDNEYFFVDPDLKLTKVAPEGWKEEPKKKTKATVNFTLFFRI
  KFFMDDVSLIQHTLTCHQYYLQLRKDILEERMHCDDETSLLLASLALQAEYGDYQPEVHG
  VSYFRMEHYLPARVMEKLDLSYIKEELPKLHNTYVGASEKETELEFLKVCQRLTEYGVHF
  HRVHPEKKSQTGILLGVCSKGVLVFEVHNGVRTLVLRFPWRETKKISFSKKKITLQNTSD
  GIKHGFQTDNSKICQYLLHLCSYQHKFQLQMRARQSNQDAQDIERASFRSLNLQAESVRG
  FNMGRAISTGSLASSTLNKLAVRPLSVQAEILKRLSCSELSLYQPLQNSSKEKNDKASWE
  EKPREMSKSYHDLSQASLYPHRKNVIVNMEPPPQTVAELVGKPSHQMSRSDAESLAGVTK
  LNNSKSVASLNRSPERRKHESDSSSIEDPGQAYVLGMTMHSSGNSSSQVPLKENDVLHKR
  WSIVSSPEREITLVNLKKDAKYGLGFQIIGGEKMGRLDLGIFISSVAPGGPADLDGCLKP
  GDRLISVNSVSLEGVSHHAAIEILQNAPEDVTLVISQPKEKISKVPSTPVHLTNEMKNYM
  KKSSYMQDSAIDSSSKDHHWSRGTLRHISENSFGPSGGLREGSLSSQDSRTESASLSQSQ
  VNGFFASHLGDQTWQESQHGSPSPSVISKATEKETFTDSNQSKTKKPGISDVTDYSDRGD
  SDMDEATYSSSQDHQTPKQESSSSVNTSNKMNFKTFSSSPPKPGDIFEVELAKNDNSLGI
  SVTGGVNTSVRHGGIYVKAVIPQGAAESDGRIHKGDRVLAVNGVSLEGATHKQAVETLRN
  TGQVVHLLLEKGQSPTSKEHVPVTPQCTLSDQNAQGQGPEKVKKTTQVKDYSFVTEENTF
  EVKLFKNSSGLGFSFSREDNLIPEQINASIVRVKKLFPGQPAAESGKIDVGDVILKVNGA
  SLKGLSQQEVISALRGTAPEVFLLLCRPPPGVLPEIDTALLTPLQSPAQVLPNSSKDSSQ
  PSCVEQSTSSDENEMSDKSKKQCKSPSRRDSYSDSSGSGEDDLVTAPANISNSTWSSALH
  QTLSNMVSQAQSHHEAPKSQEDTICTMFYYPQKIPNKPEFEDSNPSPLPPDMAPGQSYQP
  QSESASSSSMDKYHIHHISEPTRQENWTPLKNDLENHLEDFELEVELLITLIKSEKGSLG
  FTVTKGNQRIGCYVHDVIQDPAKSDGRLKPGDRLIKVNDTDVTNMTHTDAVNLLRAASKT
  VRLVIGRVLELPRIPMLPHLLPDITLTCNKEELGFSLCGGHDSLYQVVYISDINPRSVAA
  IEGNLQLLDVIHYVNGVSTQGMTLEEVNRALDMSLPSLVLKATRNDLPVVPSSKRSAVSA
  PKSTKGNGSYSVGSCSQPALTPNDSFSTVAGEEINEISYPKGKCSTYQIKGSPNLTLPKE
  SYIQEDDIYDDSQEAEVIQSLLDVVDEEAQNLLNENNAAGYSCGPGTLKMNGKLSEERTE
  DTDCDGSPLPEYFTEATKMNGCEEYCEEKVKSESLIQKPQEKKTDDDEITWGNDELPIER
  TNHEDSDKDHSFLTNDELAVLPVVKVLPSGKYTGANLKSVIRVLRGLLDQGIPSKELENL
  QELKPLDQCLIGQTKENRRKNRYKNILPYDATRVPLGDEGGYINASFIKIPVGKEEFVYI
  ACQGPLPTTVGDFWQMIWEQKSTVIAMMTQEVEGEKIKCQRYWPNILGKTTMVSNRLRLA
  LVRMQQLKGFVVRAMTLEDIQTREVRHISHLNFTAWPDHDTPSQPDDLLTFISYMRHIHR
  SGPIITHCSAGIGRSGTLICIDVVLGLISQDLDFDISDLVRCMRLQRHGMVQTEDQYIFC
  YQVILYVLTRLQAEEEQKQQPQLLK
• Function: Tyrosine phosphatase which negatively regulates FAS-induced apoptosis and NGFR-mediated pro-apoptotic signaling. May regulate phosphoinositide 3-kinase (PI3K) signaling through dephosphorylation of PIK3R2.
• Tissue Specificity: Expressed in keratinocytes (at protein level) . Present in most tissues with the exception of the liver and skeletal muscle. Most abundant in lung, kidney and fetal brain.
• KEGG Pathway: Apoptosis (hsa04210)
• Reactome Pathway:
  Interleukin-37 signaling (R-HSA-9008059)
  RND3 GTPase cycle (R-HSA-9696264)
  RND2 GTPase cycle (R-HSA-9696270)
  RND1 GTPase cycle (R-HSA-9696273)
  Synthesis of PIPs at the plasma membrane (R-HSA-1660499)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Paclitaxel	DMLB81S	Approved	Tyrosine-protein phosphatase non-receptor type 13 (PTPN13) increases the response to substance of Paclitaxel.	[19]
Capecitabine	DMTS85L	Approved	Tyrosine-protein phosphatase non-receptor type 13 (PTPN13) decreases the response to substance of Capecitabine.	[19]

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 13 (PTPN13).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Tyrosine-protein phosphatase non-receptor type 13 (PTPN13).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Tyrosine-protein phosphatase non-receptor type 13 (PTPN13).	[3]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Tyrosine-protein phosphatase non-receptor type 13 (PTPN13).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Tyrosine-protein phosphatase non-receptor type 13 (PTPN13).	[5]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Tyrosine-protein phosphatase non-receptor type 13 (PTPN13).	[6]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Tyrosine-protein phosphatase non-receptor type 13 (PTPN13).	[7]
Menthol	DMG2KW7	Approved	Menthol increases the expression of Tyrosine-protein phosphatase non-receptor type 13 (PTPN13).	[8]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Tyrosine-protein phosphatase non-receptor type 13 (PTPN13).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Tyrosine-protein phosphatase non-receptor type 13 (PTPN13).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Tyrosine-protein phosphatase non-receptor type 13 (PTPN13).	[12]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Tyrosine-protein phosphatase non-receptor type 13 (PTPN13).	[13]
LY-117018	DMUHG0F	Terminated	LY-117018 increases the expression of Tyrosine-protein phosphatase non-receptor type 13 (PTPN13).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Tyrosine-protein phosphatase non-receptor type 13 (PTPN13).	[16]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Tyrosine-protein phosphatase non-receptor type 13 (PTPN13).	[17]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Tyrosine-protein phosphatase non-receptor type 13 (PTPN13).	[18]

2 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 decreases the methylation of Tyrosine-protein phosphatase non-receptor type 13 (PTPN13).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Tyrosine-protein phosphatase non-receptor type 13 (PTPN13).	[15]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [3] Response rate of fibrosarcoma cells to cytotoxic drugs on the expression level correlates to the therapeutic response rate of fibrosarcomas and is mediated by regulation of apoptotic pathways. BMC Cancer. 2005 Jul 7;5:74. doi: 10.1186/1471-2407-5-74.
• [4] Analysis of estrogen agonism and antagonism of tamoxifen, raloxifene, and ICI182780 in endometrial cancer cells: a putative role for the epidermal growth factor receptor ligand amphiregulin. J Soc Gynecol Investig. 2005 Oct;12(7):e55-67.
• [5] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [6] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [7] In vitro and in vivo irinotecan-induced changes in expression profiles of cell cycle and apoptosis-associated genes in acute myeloid leukemia cells. Mol Cancer Ther. 2005 Jun;4(6):885-900.
• [8] Repurposing L-menthol for systems medicine and cancer therapeutics? L-menthol induces apoptosis through caspase 10 and by suppressing HSP90. OMICS. 2016 Jan;20(1):53-64.
• [9] Gene expression profiling identifies activating transcription factor 3 as a novel contributor to the proapoptotic effect of curcumin. Mol Cancer Ther. 2005 Feb;4(2):233-41.
• [10] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [11] 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.
• [12] 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.
• [13] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [14] Anti-growth factor activities of benzothiophenes in human breast cancer cells. J Steroid Biochem Mol Biol. 2005 Apr;94(5):451-60. doi: 10.1016/j.jsbmb.2004.12.043. Epub 2005 Mar 28.
• [15] 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.
• [16] 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.
• [17] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [18] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [19] Gene expression analysis using human cancer xenografts to identify novel predictive marker genes for the efficacy of 5-fluorouracil-based drugs. Cancer Sci. 2006 Jun;97(6):510-22. doi: 10.1111/j.1349-7006.2006.00204.x.