Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJ9CKLU)

• DOT Name: Low molecular weight phosphotyrosine protein phosphatase (ACP1)
• Synonyms: LMW-PTP; LMW-PTPase; EC 3.1.3.48; Adipocyte acid phosphatase; Low molecular weight cytosolic acid phosphatase; EC 3.1.3.2; Red cell acid phosphatase 1
• Gene Name: ACP1
• Related Disease:
  Immune system disorder
  Melanoma
  Non-insulin dependent diabetes
  Noonan syndrome
  Schizophrenia
  Adenocarcinoma
  Adult glioblastoma
  Asthma
  Autism
  Bipolar disorder
  Cardiovascular disease
  Colitis
  Colorectal neoplasm
  Coronary heart disease
  Endometrial carcinoma
  Endometriosis
  Epilepsy
  Gastric cancer
  Glioblastoma multiforme
  Hepatocellular carcinoma
  leukaemia
  Leukemia
  Lung cancer
  Lung carcinoma
  Major depressive disorder
  Mental disorder
  Retinopathy
  Rheumatoid arthritis
  Stomach cancer
  Systemic lupus erythematosus
  Thyroid gland carcinoma
  Tourette syndrome
  Type-1/2 diabetes
  Arteriosclerosis
  Atherosclerosis
  Autoimmune disease
  Breast cancer
  Breast carcinoma
  Chromosomal disorder
  Coronary atherosclerosis
  Fetal growth restriction
  Neuroblastoma
  Small lymphocytic lymphoma
  Advanced cancer
  Colonic neoplasm
  Neoplasm
  Castration-resistant prostate carcinoma
  Tuberculosis
• UniProt ID: PPAC_HUMAN
• PDB ID: 1XWW; 3N8I; 4Z99; 4Z9A; 4Z9B; 5JNR; 5JNS; 5JNT; 5KQG; 5KQL; 5KQM; 5KQP; 5PNT; 6Y2V; 6Y2W; 7KH8; 7UW6
• EC Number: 3.1.3.2; 3.1.3.48
• Pfam ID: PF01451
• Sequence:
  MAEQATKSVLFVCLGNICRSPIAEAVFRKLVTDQNISENWRVDSAATSGYEIGNPPDYRG
  QSCMKRHGIPMSHVARQITKEDFATFDYILCMDESNLRDLNRKSNQVKTCKAKIELLGSY
  DPQKQLIIEDPYYGNDSDFETVYQQCVRCCRAFLEKAH
• Function: Acts on tyrosine phosphorylated proteins, low-MW aryl phosphates and natural and synthetic acyl phosphates with differences in substrate specificity between isoform 1 and isoform 2; [Isoform 3]: Does not possess phosphatase activity.
• Tissue Specificity: .Expressed in T-lymphocytes.
• KEGG Pathway:
  Thiamine metabolism (hsa00730)
  Riboflavin metabolism (hsa00740)
  Metabolic pathways (hsa01100)
  Adherens junction (hsa04520)
  Chemical carcinogenesis - reactive oxygen species (hsa05208)

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Immune system disorder	DISAEGPH	Definitive	Biomarker	[1]
Melanoma	DIS1RRCY	Definitive	Biomarker	[2]
Non-insulin dependent diabetes	DISK1O5Z	Definitive	Biomarker	[3]
Noonan syndrome	DIS7Q7DN	Definitive	Genetic Variation	[4]
Schizophrenia	DISSRV2N	Definitive	Genetic Variation	[5]
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[6]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[7]
Asthma	DISW9QNS	Strong	Genetic Variation	[8]
Autism	DISV4V1Z	Strong	Genetic Variation	[9]
Bipolar disorder	DISAM7J2	Strong	Genetic Variation	[5]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[10]
Colitis	DISAF7DD	Strong	Genetic Variation	[11]
Colorectal neoplasm	DISR1UCN	Strong	Genetic Variation	[12]
Coronary heart disease	DIS5OIP1	Strong	Genetic Variation	[13]
Endometrial carcinoma	DISXR5CY	Strong	Genetic Variation	[14]
Endometriosis	DISX1AG8	Strong	Genetic Variation	[15]
Epilepsy	DISBB28L	Strong	Genetic Variation	[16]
Gastric cancer	DISXGOUK	Strong	Genetic Variation	[17]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[7]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[18]
leukaemia	DISS7D1V	Strong	Altered Expression	[19]
Leukemia	DISNAKFL	Strong	Altered Expression	[19]
Lung cancer	DISCM4YA	Strong	Biomarker	[20]
Lung carcinoma	DISTR26C	Strong	Biomarker	[20]
Major depressive disorder	DIS4CL3X	Strong	Biomarker	[21]
Mental disorder	DIS3J5R8	Strong	Biomarker	[22]
Retinopathy	DISB4B0F	Strong	Biomarker	[23]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[10]
Stomach cancer	DISKIJSX	Strong	Genetic Variation	[17]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[24]
Thyroid gland carcinoma	DISMNGZ0	Strong	Biomarker	[25]
Tourette syndrome	DISX9D54	Strong	Genetic Variation	[21]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[26]
Arteriosclerosis	DISK5QGC	moderate	Biomarker	[1]
Atherosclerosis	DISMN9J3	moderate	Biomarker	[1]
Autoimmune disease	DISORMTM	moderate	Genetic Variation	[27]
Breast cancer	DIS7DPX1	moderate	Altered Expression	[28]
Breast carcinoma	DIS2UE88	moderate	Altered Expression	[28]
Chromosomal disorder	DISM5BB5	moderate	Genetic Variation	[29]
Coronary atherosclerosis	DISKNDYU	moderate	Genetic Variation	[1]
Fetal growth restriction	DIS5WEJ5	moderate	Genetic Variation	[30]
Neuroblastoma	DISVZBI4	moderate	Altered Expression	[31]
Small lymphocytic lymphoma	DIS30POX	moderate	Biomarker	[29]
Advanced cancer	DISAT1Z9	Disputed	Biomarker	[2]
Colonic neoplasm	DISSZ04P	Disputed	Genetic Variation	[32]
Neoplasm	DISZKGEW	Disputed	Biomarker	[33]
Castration-resistant prostate carcinoma	DISVGAE6	Limited	Biomarker	[34]
Tuberculosis	DIS2YIMD	Limited	Genetic Variation	[35]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Low molecular weight phosphotyrosine protein phosphatase (ACP1) affects the response to substance of Doxorubicin.	[49]
Vinblastine	DM5TVS3	Approved	Low molecular weight phosphotyrosine protein phosphatase (ACP1) affects the response to substance of Vinblastine.	[49]

This DOT Affected the Biotransformations of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
4-nitrophenyl phosphate	DMBX4UJ	Investigative	Low molecular weight phosphotyrosine protein phosphatase (ACP1) increases the hydrolysis of 4-nitrophenyl phosphate.	[42]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Low molecular weight phosphotyrosine protein phosphatase (ACP1).	[36]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Low molecular weight phosphotyrosine protein phosphatase (ACP1).	[44]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Low molecular weight phosphotyrosine protein phosphatase (ACP1).	[46]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Low molecular weight phosphotyrosine protein phosphatase (ACP1).	[37]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Low molecular weight phosphotyrosine protein phosphatase (ACP1).	[38]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Low molecular weight phosphotyrosine protein phosphatase (ACP1).	[39]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Low molecular weight phosphotyrosine protein phosphatase (ACP1).	[40]
Aminoglutethimide	DMWFHMZ	Approved	Aminoglutethimide decreases the expression of Low molecular weight phosphotyrosine protein phosphatase (ACP1).	[41]
Benzoic acid	DMKB9FI	Approved	Benzoic acid decreases the activity of Low molecular weight phosphotyrosine protein phosphatase (ACP1).	[42]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Low molecular weight phosphotyrosine protein phosphatase (ACP1).	[40]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Low molecular weight phosphotyrosine protein phosphatase (ACP1).	[45]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Low molecular weight phosphotyrosine protein phosphatase (ACP1).	[47]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Low molecular weight phosphotyrosine protein phosphatase (ACP1).	[48]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of Low molecular weight phosphotyrosine protein phosphatase (ACP1).	[43]

References

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• [2] Targeting LMW-PTP to sensitize melanoma cancer cells toward chemo- and radiotherapy.Cancer Med. 2018 May;7(5):1933-1943. doi: 10.1002/cam4.1435. Epub 2018 Mar 24.
• [3] LMW-PTP modulates glucose metabolism in cancer cells.Biochim Biophys Acta Gen Subj. 2018 Dec;1862(12):2533-2544. doi: 10.1016/j.bbagen.2018.08.003. Epub 2018 Aug 4.
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• [5] Replication of rs300774, a genetic biomarker near ACP1, associated with suicide attempts in patients with schizophrenia: Relation to brain cholesterol biosynthesis.J Psychiatr Res. 2017 Nov;94:54-61. doi: 10.1016/j.jpsychires.2017.06.005. Epub 2017 Jun 16.
• [6] Increase in receptor-like protein tyrosine phosphatase activity and expression level on density-dependent growth arrest of endothelial cells.Biochem J. 1995 Oct 1;311 ( Pt 1)(Pt 1):97-103. doi: 10.1042/bj3110097.
• [7] Polysaccharide sulphated derivative from Aconitumcoreanum induces cell apoptosis in the human brain glioblastoma U87MG cell line via the NF-B/Bcl-2 cell apoptotic signaling pathway.Oncol Rep. 2018 Mar;39(3):1469-1474. doi: 10.3892/or.2017.6165. Epub 2017 Dec 19.
• [8] Protein tyrosine phosphatase 11 acts through RhoA/ROCK to regulate eosinophil accumulation in the allergic airway.FASEB J. 2019 Nov;33(11):11706-11720. doi: 10.1096/fj.201900698R. Epub 2019 Jul 30.
• [9] No association of FOXP2 and PTPRZ1 on 7q31 with autism from the Japanese population.Neurosci Res. 2005 Sep;53(1):91-4. doi: 10.1016/j.neures.2005.05.003.
• [10] Association of acid phosphatase locus 1*C allele with the risk of cardiovascular events in rheumatoid arthritis patients.Arthritis Res Ther. 2011 Jul 18;13(4):R116. doi: 10.1186/ar3401.
• [11] Protein tyrosine phosphatase targets apical junction complex proteins in the intestine and regulates epithelial permeability.Proc Natl Acad Sci U S A. 2014 Jan 14;111(2):693-8. doi: 10.1073/pnas.1315017111. Epub 2014 Jan 2.
• [12] Crystal structure of the PTPL1/FAP-1 human tyrosine phosphatase mutated in colorectal cancer: evidence for a second phosphotyrosine substrate recognition pocket.J Biol Chem. 2005 Mar 4;280(9):8180-7. doi: 10.1074/jbc.M412211200. Epub 2004 Dec 20.
• [13] Association between phosphatase related gene variants and coronary artery disease: case-control study and meta-analysis.Int J Mol Sci. 2014 Aug 13;15(8):14058-76. doi: 10.3390/ijms150814058.
• [14] Acid phosphatase locus 1 genetic polymorphism and cancer grading.Am J Med Sci. 2012 Jul;344(1):32-4. doi: 10.1097/MAJ.0b013e31823e5cfa.
• [15] The effect of ACP1, ADA6 and PTPN22 genetic polymorphisms on the association between p53 codon 72 polymorphism and endometriosis.Arch Gynecol Obstet. 2016 Feb;293(2):399-402. doi: 10.1007/s00404-015-3827-6. Epub 2015 Jul 28.
• [16] Genetic polymorphism and idiopathic generalized epilepsy. Evidence of interaction between haptoglobin and ACP1 systems.Neuropediatrics. 2008 Dec;39(6):357-8. doi: 10.1055/s-0029-1202834. Epub 2009 Jun 30.
• [17] Associations of a PTPN11 G/A polymorphism at intron 3 with Helicobactor pylori seropositivity, gastric atrophy and gastric cancer in Japanese.BMC Gastroenterol. 2009 Jul 9;9:51. doi: 10.1186/1471-230X-9-51.
• [18] Hypermethylation of ACP1, BMP4, and TSPYL5 in Hepatocellular Carcinoma and Their Potential Clinical Significance.Dig Dis Sci. 2016 Jan;61(1):149-57. doi: 10.1007/s10620-015-3878-3. Epub 2015 Sep 19.
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• [20] Implication of a protein-tyrosine-phosphatase in human lung cancer.Cell Mol Biol (Noisy-le-grand). 1994 Jul;40(5):677-85.
• [21] Association between the low molecular weight cytosolic acid phosphatase gene ACP1*A and comorbid features of Tourette syndrome.Neurosci Lett. 2002 Sep 20;330(2):198-200. doi: 10.1016/s0304-3940(02)00750-4.
• [22] Genetic markers in schizophrenia: ACP1, ESD, TF and GC polymorphisms.Hum Hered. 1990;40(3):136-40. doi: 10.1159/000153920.
• [23] Smoking and the genetics of signal transduction: an association study on retinopathy in type 1 diabetes.Am J Med Sci. 2002 Dec;324(6):310-3. doi: 10.1097/00000441-200212000-00004.
• [24] Novel association of acid phosphatase locus 1*C allele with systemic lupus erythematosus.Hum Immunol. 2012 Jan;73(1):107-10. doi: 10.1016/j.humimm.2011.10.012. Epub 2011 Oct 21.
• [25] Overexpression of leucocyte common antigen (LAR) P-subunit in thyroid carcinomas.Br J Cancer. 2003 Apr 22;88(8):1223-8. doi: 10.1038/sj.bjc.6600876.
• [26] Cytosolic low molecular weight protein-tyrosine phosphatase activity and clinical manifestations of diabetes.Am J Med Sci. 2014 Feb;347(2):147-50. doi: 10.1097/MAJ.0b013e31828ff36e.
• [27] Lack of association of ACP1 gene with inflammatory bowel disease: a case-control study.Tissue Antigens. 2012 Jul;80(1):61-4. doi: 10.1111/j.1399-0039.2012.01861.x. Epub 2012 Mar 19.
• [28] Focal adhesion kinase regulates the phosphorylation protein tyrosine phosphatase- at Tyr789 in breast cancer cells.Mol Med Rep. 2015 Jun;11(6):4303-8. doi: 10.3892/mmr.2015.3262. Epub 2015 Jan 27.
• [29] Array comparative genomic hybridization analysis identifies recurrent gain of chromosome 2p25.3 involving the ACP1 and MYCN genes in chronic lymphocytic leukemia.Clin Lymphoma Myeloma Leuk. 2011 Jun;11 Suppl 1(Suppl 1):S17-24. doi: 10.1016/j.clml.2011.03.031. Epub 2011 May 5.
• [30] The genetics of signal transduction and the effect of smoking on intrauterine growth.Int J Epidemiol. 2001 Apr;30(2):400-2. doi: 10.1093/ije/30.2.400.
• [31] Up-regulated expression of low molecular weight protein tyrosine phosphatases in different human cancers.Biochem Biophys Res Commun. 2005 Sep 2;334(3):875-83. doi: 10.1016/j.bbrc.2005.06.176.
• [32] ACP1 genetic polymorphism and colon cancer.Cancer Genet Cytogenet. 2008 Oct;186(1):61-2. doi: 10.1016/j.cancergencyto.2008.06.006.
• [33] DEP-1 protein tyrosine phosphatase inhibits proliferation and migration of colon carcinoma cells and is upregulated by protective nutrients.Oncogene. 2006 Oct 12;25(47):6319-24. doi: 10.1038/sj.onc.1209647. Epub 2006 May 8.
• [34] Prediction of Time to Castration-Resistant Prostate Cancer Using Low-Molecular-Weight Protein Tyrosine Phosphatase Expression for Men with Metastatic Hormone-Nave Prostate Cancer.Urol Int. 2019;102(1):37-42. doi: 10.1159/000493324. Epub 2018 Oct 16.
• [35] [The use of discrete characters in discriminant analysis for diagnosis of pulmonary tuberculosis and for classification of patients differing in treatment efficiency based on polymorphisms at nine codominant loci-HP, GC, TF, PI, PGM1, GLO1, C3, ACP1 and ESD].Genetika. 2003 Jul;39(7):996-1002.
• [36] 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.
• [37] 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.
• [38] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [39] Proteomic analysis revealed association of aberrant ROS signaling with suberoylanilide hydroxamic acid-induced autophagy in Jurkat T-leukemia cells. Autophagy. 2010 Aug;6(6):711-24. doi: 10.4161/auto.6.6.12397. Epub 2010 Aug 17.
• [40] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [41] Proteomic profile of aminoglutethimide-induced apoptosis in HL-60 cells: role of myeloperoxidase and arylamine free radicals. Chem Biol Interact. 2015 Sep 5;239:129-38.
• [42] Synthesis, biological activity and structure-activity relationships of new benzoic acid-based protein tyrosine phosphatase inhibitors endowed with insulinomimetic effects in mouse C2C12 skeletal muscle cells. Eur J Med Chem. 2014 Jan;71:112-27. doi: 10.1016/j.ejmech.2013.11.001. Epub 2013 Nov 11.
• [43] Proteomic analysis of the cellular response to a potent sensitiser unveils the dynamics of haptenation in living cells. Toxicology. 2020 Dec 1;445:152603. doi: 10.1016/j.tox.2020.152603. Epub 2020 Sep 28.
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• [45] 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.
• [46] 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.
• [47] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [48] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [49] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.
• [50] Synthesis, biological activity and structure-activity relationships of new benzoic acid-based protein tyrosine phosphatase inhibitors endowed with insulinomimetic effects in mouse C2C12 skeletal muscle cells. Eur J Med Chem. 2014 Jan;71:112-27. doi: 10.1016/j.ejmech.2013.11.001. Epub 2013 Nov 11.