Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSIM0YG)

• DOT Name: Prostatic acid phosphatase (ACP3)
• Synonyms: PAP; EC 3.1.3.2; 5'-nucleotidase; 5'-NT; EC 3.1.3.5; Acid phosphatase 3; Ecto-5'-nucleotidase; Protein tyrosine phosphatase ACP3; EC 3.1.3.48; Thiamine monophosphatase; TMPase
• Gene Name: ACP3
• UniProt ID: PPAP_HUMAN
• PDB ID: 1CVI; 1ND5; 1ND6; 2HPA; 2L3H; 2L77; 2L79; 2MG0; 3PPD; 7ZZV
• EC Number: 3.1.3.2; 3.1.3.48; 3.1.3.5
• Pfam ID: PF00328
• Sequence:
  MRAAPLLLARAASLSLGFLFLLFFWLDRSVLAKELKFVTLVFRHGDRSPIDTFPTDPIKE
  SSWPQGFGQLTQLGMEQHYELGEYIRKRYRKFLNESYKHEQVYIRSTDVDRTLMSAMTNL
  AALFPPEGVSIWNPILLWQPIPVHTVPLSEDQLLYLPFRNCPRFQELESETLKSEEFQKR
  LHPYKDFIATLGKLSGLHGQDLFGIWSKVYDPLYCESVHNFTLPSWATEDTMTKLRELSE
  LSLLSLYGIHKQKEKSRLQGGVLVNEILNHMKRATQIPSYKKLIMYSAHDTTVSGLQMAL
  DVYNGLLPPYASCHLTELYFEKGEYFVEMYYRNETQHEPYPLMLPGCSPSCPLERFAELV
  GPVIPQDWSTECMTTNSHQGTEDSTD
• Function: A non-specific tyrosine phosphatase that dephosphorylates a diverse number of substrates under acidic conditions (pH 4-6) including alkyl, aryl, and acyl orthophosphate monoesters and phosphorylated proteins. Has lipid phosphatase activity and inactivates lysophosphatidic acid in seminal plasma ; [Isoform 2]: Tyrosine phosphatase that acts as a tumor suppressor of prostate cancer through dephosphorylation of ERBB2 and deactivation of MAPK-mediated signaling. In addition to its tyrosine phosphatase activity has ecto-5'-nucleotidase activity in dorsal root ganglion (DRG) neurons. Generates adenosine from AMP which acts as a pain suppressor; [PAPf39]: (Microbial infection) Forms amyloid beta-sheet fibrils in semen. These fibrils, termed SEVI (semen-derived enhancer of viral infection) capture HIV virions, attach them to target cells and enhance infection. SEVI amyloid fibrils are degraded by polyphenol epigallocatechin-3-gallate (EGCG), a constituent of green tea. Target cell attachment and enhancement of HIV infection is inhibited by surfen. Also similarly boosts XMRV (xenotropic murine leukemia virus-related virus) infection.
• Tissue Specificity: Highly expressed in the prostate, restricted to glandular and ductal epithelial cells. Also expressed in bladder, kidney, pancreas, lung, cervix, testis and ovary. Weak expression in a subset of pancreatic islet cells, squamous epithelia, the pilosebaceous unit, colonic neuroendocrine cells and skin adnexal structures. Low expression in prostate carcinoma cells and tissues.; [Isoform 2]: Widely expressed. Expressed in the sarcolemma of skeletal muscle.
• Reactome Pathway: Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Prostatic acid phosphatase (ACP3).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Prostatic acid phosphatase (ACP3).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Prostatic acid phosphatase (ACP3).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Prostatic acid phosphatase (ACP3).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Prostatic acid phosphatase (ACP3).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Prostatic acid phosphatase (ACP3).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Prostatic acid phosphatase (ACP3).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Prostatic acid phosphatase (ACP3).	[8]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Prostatic acid phosphatase (ACP3).	[9]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Prostatic acid phosphatase (ACP3).	[10]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Prostatic acid phosphatase (ACP3).	[11]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Prostatic acid phosphatase (ACP3).	[12]
Gemcitabine	DMSE3I7	Approved	Gemcitabine decreases the expression of Prostatic acid phosphatase (ACP3).	[13]
Bicalutamide	DMZMSPF	Approved	Bicalutamide decreases the expression of Prostatic acid phosphatase (ACP3).	[14]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone decreases the expression of Prostatic acid phosphatase (ACP3).	[6]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Prostatic acid phosphatase (ACP3).	[6]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Prostatic acid phosphatase (ACP3).	[16]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Prostatic acid phosphatase (ACP3).	[17]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Prostatic acid phosphatase (ACP3).	[18]
ELLAGIC ACID	DMX8BS5	Investigative	ELLAGIC ACID increases the expression of Prostatic acid phosphatase (ACP3).	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Prostatic acid phosphatase (ACP3).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Prostatic acid phosphatase (ACP3).	[15]

References

• [1] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [2] Evaluation of a human iPSC-derived BBB model for repeated dose toxicity testing with cyclosporine A as model compound. Toxicol In Vitro. 2021 Jun;73:105112. doi: 10.1016/j.tiv.2021.105112. Epub 2021 Feb 22.
• [3] 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.
• [4] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [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] The mutant androgen receptor T877A mediates the proliferative but not the cytotoxic dose-dependent effects of genistein and quercetin on human LNCaP prostate cancer cells. Mol Pharmacol. 2002 Nov;62(5):1027-35. doi: 10.1124/mol.62.5.1027.
• [7] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [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] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [10] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [11] Progesterone regulation of implantation-related genes: new insights into the role of oestrogen. Cell Mol Life Sci. 2007 Apr;64(7-8):1009-32.
• [12] 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.
• [13] Metronomic gemcitabine suppresses tumour growth, improves perfusion, and reduces hypoxia in human pancreatic ductal adenocarcinoma. Br J Cancer. 2010 Jun 29;103(1):52-60.
• [14] Microarray analysis of bicalutamide action on telomerase activity, p53 pathway and viability of prostate carcinoma cell lines. J Pharm Pharmacol. 2005 Jan;57(1):83-92.
• [15] 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.
• [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] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [18] The role of androgen in determining differentiation and regulation of androgen receptor expression in the human prostatic epithelium transient amplifying population. J Cell Physiol. 2007 Sep;212(3):572-8. doi: 10.1002/jcp.21154.
• [19] Interactive gene expression pattern in prostate cancer cells exposed to phenolic antioxidants. Life Sci. 2002 Mar 1;70(15):1821-39.