Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDS9K1Z)

• DOT Name: Phosphatidylserine lipase ABHD16A (ABHD16A)
• Synonyms: EC 3.1.-.-; Alpha/beta hydrolase domain-containing protein 16A; Abhydrolase domain-containing protein 16A; HLA-B-associated transcript 5; hBAT5; Monoacylglycerol lipase ABHD16A; EC 3.1.1.23; Protein G5
• Gene Name: ABHD16A
• Related Disease:
  Aural atresia, congenital
  Spastic paraplegia 86, autosomal recessive
  Type-1 diabetes
• UniProt ID: ABHGA_HUMAN
• EC Number: 3.1.-.-; 3.1.1.23
• Pfam ID: PF00561
• Sequence:
  MAKLLSCVLGPRLYKIYRERDSERAPASVPETPTAVTAPHSSSWDTYYQPRALEKHADSI
  LALASVFWSISYYSSPFAFFYLYRKGYLSLSKVVPFSHYAGTLLLLLAGVACLRGIGRWT
  NPQYRQFITILEATHRNQSSENKRQLANYNFDFRSWPVDFHWEEPSSRKESRGGPSRRGV
  ALLRPEPLHRGTADTLLNRVKKLPCQITSYLVAHTLGRRMLYPGSVYLLQKALMPVLLQG
  QARLVEECNGRRAKLLACDGNEIDTMFVDRRGTAEPQGQKLVICCEGNAGFYEVGCVSTP
  LEAGYSVLGWNHPGFAGSTGVPFPQNEANAMDVVVQFAIHRLGFQPQDIIIYAWSIGGFT
  ATWAAMSYPDVSAMILDASFDDLVPLALKVMPDSWRGLVTRTVRQHLNLNNAEQLCRYQG
  PVLLIRRTKDEIITTTVPEDIMSNRGNDLLLKLLQHRYPRVMAEEGLRVVRQWLEASSQL
  EEASIYSRWEVEEDWCLSVLRSYQAEHGPDFPWSVGEDMSADGRRQLALFLARKHLHNFE
  ATHCTPLPAQNFQMPWHL
• Function: Phosphatidylserine (PS) lipase that mediates the hydrolysis of phosphatidylserine to generate lysophosphatidylserine (LPS). LPS constitutes a class of signaling lipids that regulates immunological and neurological processes. Has no activity towards diacylglycerol, triacylglycerol or lysophosphatidylserine lipase. Also has monoacylglycerol lipase activity, with preference for 1-(9Z,12Z-octadecadienoyl)-glycerol (1-LG) and 2-glyceryl-15-deoxy-Delta(12,14)-prostaglandin J2 (15d-PGJ(2)-G).
• KEGG Pathway:
  Glycerolipid metabolism (hsa00561)
  Metabolic pathways (hsa01100)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Aural atresia, congenital	DISCP7UV	Strong	Genetic Variation	[1]
Spastic paraplegia 86, autosomal recessive	DIS99GR4	Strong	Autosomal recessive	[2]
Type-1 diabetes	DIS7HLUB	Strong	Genetic Variation	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Phosphatidylserine lipase ABHD16A (ABHD16A).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Phosphatidylserine lipase ABHD16A (ABHD16A).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Phosphatidylserine lipase ABHD16A (ABHD16A).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Phosphatidylserine lipase ABHD16A (ABHD16A).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Phosphatidylserine lipase ABHD16A (ABHD16A).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Phosphatidylserine lipase ABHD16A (ABHD16A).	[9]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Phosphatidylserine lipase ABHD16A (ABHD16A).	[11]
Orlistat	DMRJSP8	Approved	Orlistat decreases the activity of Phosphatidylserine lipase ABHD16A (ABHD16A).	[12]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Phosphatidylserine lipase ABHD16A (ABHD16A).	[14]
RHC80267	DMC471Z	Investigative	RHC80267 decreases the activity of Phosphatidylserine lipase ABHD16A (ABHD16A).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Phosphatidylserine lipase ABHD16A (ABHD16A).	[10]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Phosphatidylserine lipase ABHD16A (ABHD16A).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Phosphatidylserine lipase ABHD16A (ABHD16A).	[10]

References

• [1] Human lymphocyte antigen B-associated transcript 2, 3, and 5 polymorphisms and haplotypes are associated with susceptibility of Kawasaki disease and coronary artery aneurysm.J Clin Lab Anal. 2010;24(4):262-8. doi: 10.1002/jcla.20409.
• [2] ABHD16A deficiency causes a complicated form of hereditary spastic paraplegia associated with intellectual disability and cerebral anomalies. Am J Hum Genet. 2021 Oct 7;108(10):2017-2023. doi: 10.1016/j.ajhg.2021.09.005. Epub 2021 Sep 28.
• [3] A genome-wide association study identifies KIAA0350 as a type 1 diabetes gene.Nature. 2007 Aug 2;448(7153):591-4. doi: 10.1038/nature06010. Epub 2007 Jul 15.
• [4] 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.
• [5] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [6] 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.
• [7] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [8] 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.
• [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] 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.
• [11] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [12] Selectivity of inhibitors of endocannabinoid biosynthesis evaluated by activity-based protein profiling. Bioorg Med Chem Lett. 2008 Nov 15;18(22):5838-41.
• [13] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [14] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.