Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT790UA2)

• DOT Name: Receptor-type tyrosine-protein phosphatase R (PTPRR)
• Synonyms: R-PTP-R; EC 3.1.3.48; Ch-1PTPase; NC-PTPCOM1; Protein-tyrosine phosphatase PCPTP1
• Gene Name: PTPRR
• Related Disease:
  Acute myelogenous leukaemia
  Colorectal carcinoma
  Major depressive disorder
  Oral cancer
  Refractive error
  Uterine fibroids
  Hirschsprung disease
• UniProt ID: PTPRR_HUMAN
• PDB ID: 2A8B
• EC Number: 3.1.3.48
• Pfam ID: PF00102
• Sequence:
  MRRAVCFPALCLLLNLHAAGCFSGNNDHFLAINQKKSGKPVFIYKHSQDIEKSLDIAPQK
  IYRHSYHSSSEAQVSKRHQIVNSAFPRPAYDPSLNLLAMDGQDLEVENLPIPAANVIVVT
  LQMDVNKLNITLLRIFRQGVAAALGLLPQQVHINRLIGKKNSIELFVSPINRKTGISDAL
  PSEEVLRSLNINVLHQSLSQFGITEVSPEKNVLQGQHEADKIWSKEGFYAVVIFLSIFVI
  IVTCLMILYRLKERFQLSLRQDKEKNQEIHLSPITLQPALSEAKTVHSMVQPEQAPKVLN
  VVVDPQGRGAPEIKATTATSVCPSPFKMKPIGLQERRGSNVSLTLDMSSLGNIEPFVSIP
  TPREKVAMEYLQSASRILTRSQLRDVVASSHLLQSEFMEIPMNFVDPKEIDIPRHGTKNR
  YKTILPNPLSRVCLRPKNVTDSLSTYINANYIRGYSGKEKAFIATQGPMINTVDDFWQMV
  WQEDSPVIVMITKLKEKNEKCVLYWPEKRGIYGKVEVLVISVNECDNYTIRNLVLKQGSH
  TQHVKHYWYTSWPDHKTPDSAQPLLQLMLDVEEDRLASQGRGPVVVHCSAGIGRTGCFIA
  TSIGCQQLKEEGVVDALSIVCQLRMDRGGMVQTSEQYEFVHHALCLYESRLSAETVQ
• Function: Sequesters mitogen-activated protein kinases (MAPKs) such as MAPK1, MAPK3 and MAPK14 in the cytoplasm in an inactive form. The MAPKs bind to a dephosphorylated kinase interacting motif, phosphorylation of which by the protein kinase A complex releases the MAPKs for activation and translocation into the nucleus.
• Tissue Specificity: Detected in cerebrospinal fluid (at protein level) . Expressed in brain, placenta, small intestine, stomach, uterus and weakly in the prostate. Isoform alpha has been observed only in the brain. Isoform gamma is expressed in brain, placenta and uterus. Isoform delta is expressed in brain, kidney, placenta, prostate, small intestine and uterus.
• KEGG Pathway: MAPK sig.ling pathway (hsa04010)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Strong	Genetic Variation	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[2]
Major depressive disorder	DIS4CL3X	Strong	Biomarker	[3]
Oral cancer	DISLD42D	Strong	Biomarker	[4]
Refractive error	DISWNEQ1	Strong	Genetic Variation	[5]
Uterine fibroids	DISBZRMJ	Strong	Genetic Variation	[6]
Hirschsprung disease	DISUUSM1	Limited	Biomarker	[7]

7 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 R (PTPRR).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Receptor-type tyrosine-protein phosphatase R (PTPRR).	[9]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Receptor-type tyrosine-protein phosphatase R (PTPRR).	[10]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Receptor-type tyrosine-protein phosphatase R (PTPRR).	[11]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Receptor-type tyrosine-protein phosphatase R (PTPRR).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Receptor-type tyrosine-protein phosphatase R (PTPRR).	[13]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Receptor-type tyrosine-protein phosphatase R (PTPRR).	[14]

References

• [1] Identification of Novel Functional Variants of SIN3A and SRSF1 among Somatic Variants in Acute Myeloid Leukemia Patients.Mol Cells. 2018 May 31;41(5):465-475. doi: 10.14348/molcells.2018.0051. Epub 2018 May 15.
• [2] Immunohistochemical and Western blot analysis of two protein tyrosine phosphatase receptors, R and Z1, in colorectal carcinoma, colon adenoma and normal colon tissues.Histol Histopathol. 2014 May;29(5):635-9. doi: 10.14670/HH-29.10.635. Epub 2013 Nov 18.
• [3] Polymorphism of ERK/PTPRR Genes in Major Depressive Disorder at Resting-State Brain Function.Dev Neuropsychol. 2017;42(3):231-240. doi: 10.1080/87565641.2017.1306527. Epub 2017 May 3.
• [4] Hypermethylated ZNF582 and PAX1 are effective biomarkers for detection of oral dysplasia and oral cancer.Oral Oncol. 2016 Nov;62:34-43. doi: 10.1016/j.oraloncology.2016.09.007. Epub 2016 Oct 6.
• [5] Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia.Nat Genet. 2013 Mar;45(3):314-8. doi: 10.1038/ng.2554. Epub 2013 Feb 10.
• [6] Genome-wide association and epidemiological analyses reveal common genetic origins between uterine leiomyomata and endometriosis.Nat Commun. 2019 Oct 24;10(1):4857. doi: 10.1038/s41467-019-12536-4.
• [7] Downregulation of Protein Tyrosine Phosphatase Receptor Type R Accounts for the Progression of Hirschsprung Disease.Front Mol Neurosci. 2019 Apr 10;12:92. doi: 10.3389/fnmol.2019.00092. eCollection 2019.
• [8] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [9] 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.
• [10] Endometrial receptivity is affected in women with high circulating progesterone levels at the end of the follicular phase: a functional genomics analysis. Hum Reprod. 2011 Jul;26(7):1813-25.
• [11] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [12] Curcumin suppresses growth of mesothelioma cells in vitro and in vivo, in part, by stimulating apoptosis. Mol Cell Biochem. 2011 Nov;357(1-2):83-94. doi: 10.1007/s11010-011-0878-2. Epub 2011 May 19.
• [13] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [14] Regulation of chromatin assembly and cell transformation by formaldehyde exposure in human cells. Environ Health Perspect. 2017 Sep 21;125(9):097019.