Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPW6HEK)

• DOT Name: Lysophosphatidic acid phosphatase type 6 (ACP6)
• Synonyms: EC 3.1.3.2; Acid phosphatase 6, lysophosphatidic; Acid phosphatase-like protein 1; PACPL1
• Gene Name: ACP6
• UniProt ID: PPA6_HUMAN
• PDB ID: 4JOB; 4JOC; 4JOD
• EC Number: 3.1.3.2
• Pfam ID: PF00328
• Sequence:
  MITGVFSMRLWTPVGVLTSLAYCLHQRRVALAELQEADGQCPVDRSLLKLKMVQVVFRHG
  ARSPLKPLPLEEQVEWNPQLLEVPPQTQFDYTVTNLAGGPKPYSPYDSQYHETTLKGGMF
  AGQLTKVGMQQMFALGERLRKNYVEDIPFLSPTFNPQEVFIRSTNIFRNLESTRCLLAGL
  FQCQKEGPIIIHTDEADSEVLYPNYQSCWSLRQRTRGRRQTASLQPGISEDLKKVKDRMG
  IDSSDKVDFFILLDNVAAEQAHNLPSCPMLKRFARMIEQRAVDTSLYILPKEDRESLQMA
  VGPFLHILESNLLKAMDSATAPDKIRKLYLYAAHDVTFIPLLMTLGIFDHKWPPFAVDLT
  MELYQHLESKEWFVQLYYHGKEQVPRGCPDGLCPLDMFLNAMSVYTLSPEKYHALCSQTQ
  VMEVGNEE
• Function: Hydrolyzes lysophosphatidic acid (LPA) containing a medium length fatty acid chain to the corresponding monoacylglycerol. Has highest activity with lysophosphatidic acid containing myristate (C14:0), monounsaturated oleate (C18:1) or palmitate (C16:0), and lower activity with C18:0 and C6:0 lysophosphatidic acid.
• Tissue Specificity: Highly expressed in kidney, heart, small intestine, muscle, liver, prostate, testis, ovary and weakly expressed in thymus and colon.
• Reactome Pathway: Synthesis of PA (R-HSA-1483166)

Molecular Interaction Atlas (MIA) of This DOT

1 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 Lysophosphatidic acid phosphatase type 6 (ACP6).	[1]

6 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 Lysophosphatidic acid phosphatase type 6 (ACP6).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Lysophosphatidic acid phosphatase type 6 (ACP6).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Lysophosphatidic acid phosphatase type 6 (ACP6).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Lysophosphatidic acid phosphatase type 6 (ACP6).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Lysophosphatidic acid phosphatase type 6 (ACP6).	[6]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Lysophosphatidic acid phosphatase type 6 (ACP6).	[7]

References

• [1] 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.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain. Toxicol Lett. 2015 Apr 16;234(2):139-50.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] 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.
• [7] 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.