Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCEL6PN)

DOT Name Receptor-type tyrosine-protein phosphatase mu (PTPRM)
Synonyms Protein-tyrosine phosphatase mu; R-PTP-mu; EC 3.1.3.48
Gene Name PTPRM
Related Disease
Adenoma ( )
Carcinoma ( )
Colon cancer ( )
Colon carcinoma ( )
Colorectal adenoma ( )
Neoplasm ( )
Breast cancer ( )
Breast carcinoma ( )
Metastatic malignant neoplasm ( )
Neuroendocrine neoplasm ( )
UniProt ID
PTPRM_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
1RPM; 2C9A; 2V5Y; 8A16; 8A17
EC Number
3.1.3.48
Pfam ID
PF00041 ; PF00047 ; PF00629 ; PF00102
Sequence
MRGLGTCLATLAGLLLTAAGETFSGGCLFDEPYSTCGYSQSEGDDFNWEQVNTLTKPTSD
PWMPSGSFMLVNASGRPEGQRAHLLLPQLKENDTHCIDFHYFVSSKSNSPPGLLNVYVKV
NNGPLGNPIWNISGDPTRTWNRAELAISTFWPNFYQVIFEVITSGHQGYLAIDEVKVLGH
PCTRTPHFLRIQNVEVNAGQFATFQCSAIGRTVAGDRLWLQGIDVRDAPLKEIKVTSSRR
FIASFNVVNTTKRDAGKYRCMIRTEGGVGISNYAELVVKEPPVPIAPPQLASVGATYLWI
QLNANSINGDGPIVAREVEYCTASGSWNDRQPVDSTSYKIGHLDPDTEYEISVLLTRPGE
GGTGSPGPALRTRTKCADPMRGPRKLEVVEVKSRQITIRWEPFGYNVTRCHSYNLTVHYC
YQVGGQEQVREEVSWDTENSHPQHTITNLSPYTNVSVKLILMNPEGRKESQELIVQTDED
LPGAVPTESIQGSTFEEKIFLQWREPTQTYGVITLYEITYKAVSSFDPEIDLSNQSGRVS
KLGNETHFLFFGLYPGTTYSFTIRASTAKGFGPPATNQFTTKISAPSMPAYELETPLNQT
DNTVTVMLKPAHSRGAPVSVYQIVVEEERPRRTKKTTEILKCYPVPIHFQNASLLNSQYY
FAAEFPADSLQAAQPFTIGDNKTYNGYWNTPLLPYKSYRIYFQAASRANGETKIDCVQVA
TKGAATPKPVPEPEKQTDHTVKIAGVIAGILLFVIIFLGVVLVMKKRKLAKKRKETMSST
RQEMTVMVNSMDKSYAEQGTNCDEAFSFMDTHNLNGRSVSSPSSFTMKTNTLSTSVPNSY
YPDETHTMASDTSSLVQSHTYKKREPADVPYQTGQLHPAIRVADLLQHITQMKCAEGYGF
KEEYESFFEGQSAPWDSAKKDENRMKNRYGNIIAYDHSRVRLQTIEGDTNSDYINGNYID
GYHRPNHYIATQGPMQETIYDFWRMVWHENTASIIMVTNLVEVGRVKCCKYWPDDTEIYK
DIKVTLIETELLAEYVIRTFAVEKRGVHEIREIRQFHFTGWPDHGVPYHATGLLGFVRQV
KSKSPPSAGPLVVHCSAGAGRTGCFIVIDIMLDMAEREGVVDIYNCVRELRSRRVNMVQT
EEQYVFIHDAILEACLCGDTSVPASQVRSLYYDMNKLDPQTNSSQIKEEFRTLNMVTPTL
RVEDCSIALLPRNHEKNRCMDILPPDRCLPFLITIDGESSNYINAALMDSYKQPSAFIVT
QHPLPNTVKDFWRLVLDYHCTSVVMLNDVDPAQLCPQYWPENGVHRHGPIQVEFVSADLE
EDIISRIFRIYNAARPQDGYRMVQQFQFLGWPMYRDTPVSKRSFLKLIRQVDKWQEEYNG
GEGRTVVHCLNGGGRSGTFCAISIVCEMLRHQRTVDVFHAVKTLRNNKPNMVDLLDQYKF
CYEVALEYLNSG
Function
Receptor protein-tyrosine phosphatase that mediates homotypic cell-cell interactions and plays a role in adipogenic differentiation via modulation of p120 catenin/CTNND1 phosphorylation. Promotes CTNND1 dephosphorylation and prevents its cytoplasmic localization where it inhibits SLC2A4 membrane trafficking. In turn, SLC2A4 is directed to the plasma membrane and performs its glucose transporter function.
KEGG Pathway
Cell adhesion molecules (hsa04514 )
Adherens junction (hsa04520 )

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Adenoma DIS78ZEV Strong Altered Expression [1]
Carcinoma DISH9F1N Strong Altered Expression [1]
Colon cancer DISVC52G Strong Posttranslational Modification [1]
Colon carcinoma DISJYKUO Strong Posttranslational Modification [1]
Colorectal adenoma DISTSVHM Strong Biomarker [1]
Neoplasm DISZKGEW Strong Altered Expression [2]
Breast cancer DIS7DPX1 moderate Biomarker [3]
Breast carcinoma DIS2UE88 moderate Biomarker [3]
Metastatic malignant neoplasm DIS86UK6 Limited Altered Expression [2]
Neuroendocrine neoplasm DISNPLOO Limited Biomarker [2]
------------------------------------------------------------------------------------
⏷ Show the Full List of 10 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the methylation of Receptor-type tyrosine-protein phosphatase mu (PTPRM). [4]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of Receptor-type tyrosine-protein phosphatase mu (PTPRM). [18]
------------------------------------------------------------------------------------
15 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Receptor-type tyrosine-protein phosphatase mu (PTPRM). [5]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Receptor-type tyrosine-protein phosphatase mu (PTPRM). [6]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Receptor-type tyrosine-protein phosphatase mu (PTPRM). [7]
Temozolomide DMKECZD Approved Temozolomide decreases the expression of Receptor-type tyrosine-protein phosphatase mu (PTPRM). [8]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of Receptor-type tyrosine-protein phosphatase mu (PTPRM). [9]
Vorinostat DMWMPD4 Approved Vorinostat decreases the expression of Receptor-type tyrosine-protein phosphatase mu (PTPRM). [10]
Testosterone DM7HUNW Approved Testosterone increases the expression of Receptor-type tyrosine-protein phosphatase mu (PTPRM). [11]
Triclosan DMZUR4N Approved Triclosan decreases the expression of Receptor-type tyrosine-protein phosphatase mu (PTPRM). [12]
Menadione DMSJDTY Approved Menadione affects the expression of Receptor-type tyrosine-protein phosphatase mu (PTPRM). [13]
Dexamethasone DMMWZET Approved Dexamethasone increases the expression of Receptor-type tyrosine-protein phosphatase mu (PTPRM). [14]
Isotretinoin DM4QTBN Approved Isotretinoin increases the expression of Receptor-type tyrosine-protein phosphatase mu (PTPRM). [15]
Dihydrotestosterone DM3S8XC Phase 4 Dihydrotestosterone increases the expression of Receptor-type tyrosine-protein phosphatase mu (PTPRM). [16]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the mutagenesis of Receptor-type tyrosine-protein phosphatase mu (PTPRM). [17]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Receptor-type tyrosine-protein phosphatase mu (PTPRM). [19]
[3H]methyltrienolone DMTSGOW Investigative [3H]methyltrienolone increases the expression of Receptor-type tyrosine-protein phosphatase mu (PTPRM). [20]
------------------------------------------------------------------------------------
⏷ Show the Full List of 15 Drug(s)

References

1 Loss of PTPRM associates with the pathogenic development of colorectal adenoma-carcinoma sequence.Sci Rep. 2015 Apr 24;5:9633. doi: 10.1038/srep09633.
2 PTPRM, a candidate tumor suppressor gene in small intestinal neuroendocrine tumors.Endocr Connect. 2019 Aug 1;8(8):1126-1135. doi: 10.1530/EC-19-0279.
3 Protein tyrosine phosphatase (PTP or PTPRM), a negative regulator of proliferation and invasion of breast cancer cells, is associated with disease prognosis.PLoS One. 2012;7(11):e50183. doi: 10.1371/journal.pone.0050183. Epub 2012 Nov 20.
4 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
5 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
6 Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
7 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.
8 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.
9 Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
10 Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
11 Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
12 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
13 Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
14 Gene expression profile of human lymphoid CEM cells sensitive and resistant to glucocorticoid-evoked apoptosis. Genomics. 2003 Jun;81(6):543-55.
15 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.
16 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.
17 Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells. Mutat Res Genet Toxicol Environ Mutagen. 2014 Dec;775-776:48-54. doi: 10.1016/j.mrgentox.2014.10.011. Epub 2014 Nov 4.
18 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.
19 Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
20 Identification of genes targeted by the androgen and PKA signaling pathways in prostate cancer cells. Oncogene. 2006 Nov 23;25(55):7311-23.