Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLPA1LJ)

• DOT Name: Lysosomal acid phosphatase (ACP2)
• Synonyms: LAP; EC 3.1.3.2
• Gene Name: ACP2
• Related Disease:
  CLN2 Batten disease
  Prostate cancer
  Keratoconus
  Maroteaux-lamy syndrome
  Lysosomal acid phosphatase deficiency
• UniProt ID: PPAL_HUMAN
• EC Number: 3.1.3.2
• Pfam ID: PF00328
• Sequence:
  MAGKRSGWSRAALLQLLLGVNLVVMPPTRARSLRFVTLLYRHGDRSPVKTYPKDPYQEEE
  WPQGFGQLTKEGMLQHWELGQALRQRYHGFLNTSYHRQEVYVRSTDFDRTLMSAEANLAG
  LFPPNGMQRFNPNISWQPIPVHTVPITEDRLLKFPLGPCPRYEQLQNETRQTPEYQNESS
  RNAQFLDMVANETGLTDLTLETVWNVYDTLFCEQTHGLRLPPWASPQTMQRLSRLKDFSF
  RFLFGIYQQAEKARLQGGVLLAQIRKNLTLMATTSQLPKLLVYSAHDTTLVALQMALDVY
  NGEQAPYASCHIFELYQEDSGNFSVEMYFRNESDKAPWPLSLPGCPHRCPLQDFLRLTEP
  VVPKDWQQECQLASGPADTEVIVALAVCGSILFLLIVLLLTVLFRMQAQPPGYRHVADGE
  DHA
• KEGG Pathway:
  Riboflavin metabolism (hsa00740)
  Metabolic pathways (hsa01100)
  Lysosome (hsa04142)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
CLN2 Batten disease	DISZC5YB	Strong	Biomarker	[1]
Prostate cancer	DISF190Y	Strong	Altered Expression	[2]
Keratoconus	DISOONXH	moderate	Altered Expression	[3]
Maroteaux-lamy syndrome	DISSLP8Z	Limited	Altered Expression	[4]
Lysosomal acid phosphatase deficiency	DISWK1QP	No Known	Unknown	[5]

8 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 Lysosomal acid phosphatase (ACP2).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Lysosomal acid phosphatase (ACP2).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Lysosomal acid phosphatase (ACP2).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Lysosomal acid phosphatase (ACP2).	[9]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Lysosomal acid phosphatase (ACP2).	[10]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Lysosomal acid phosphatase (ACP2).	[11]
Sulindac	DM2QHZU	Approved	Sulindac increases the expression of Lysosomal acid phosphatase (ACP2).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Lysosomal acid phosphatase (ACP2).	[13]

References

• [1] Increased expression of lysosomal acid phosphatase in CLN3-defective cells and mouse brain tissue.J Neurochem. 2007 Dec;103(6):2177-88. doi: 10.1111/j.1471-4159.2007.04920.x. Epub 2007 Sep 11.
• [2] Gene expression and prostate specificity of human prostatic acid phosphatase (PAP): evaluation by RNA blot analyses.Biochim Biophys Acta. 1990 Jan 30;1048(1):72-7. doi: 10.1016/0167-4781(90)90024-v.
• [3] Cathepsin G, acid phosphatase, and alpha 1-proteinase inhibitor messenger RNA levels in keratoconus corneas.Invest Ophthalmol Vis Sci. 1997 Feb;38(2):529-34.
• [4] The Lysosomal Protein Arylsulfatase B Is a Key Enzyme Involved in Skeletal Turnover.J Bone Miner Res. 2018 Dec;33(12):2186-2201. doi: 10.1002/jbmr.3563. Epub 2018 Aug 24.
• [5] A genome-wide association study of corneal astigmatism: The CREAM Consortium. Mol Vis. 2018 Feb 5;24:127-142. eCollection 2018.
• [6] 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.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [12] Expression profile analysis of colon cancer cells in response to sulindac or aspirin. Biochem Biophys Res Commun. 2002 Mar 29;292(2):498-512.
• [13] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.