Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5E2EKR)

DOT Name	60 kDa lysophospholipase (ASPG)
Synonyms	LysoLP; EC 3.1.1.5; Lysophospholipase-transacylase
Gene Name	ASPG
Related Disease	Chronic kidney disease ( ) Chronic renal failure ( ) Acute leukaemia ( ) Acute myelogenous leukaemia ( ) Adult lymphoma ( ) Breast cancer ( ) Burkitt lymphoma ( ) Cholelithiasis ( ) Cholestasis ( ) Coagulation defect ( ) Cowden disease ( ) Extranodal NK/T-cell Lymphoma ( ) Fatty liver disease ( ) Gastric cancer ( ) Glioma ( ) Hyperglycemia ( ) Liver cancer ( ) Lymphoblastic lymphoma ( ) Lymphoma ( ) Medulloblastoma ( ) Neoplasm ( ) Obesity ( ) Pancreatic cancer ( ) Pediatric lymphoma ( ) Promyelocytic leukaemia ( ) Stomach cancer ( ) T-cell acute lymphoblastic leukaemia ( ) T-cell lymphoma ( ) Tuberculosis ( ) Venous thromboembolism ( ) Adult glioblastoma ( ) Advanced cancer ( ) Glioblastoma multiforme ( ) Hepatocellular carcinoma ( ) Laryngeal squamous cell carcinoma ( ) Stroke ( ) Anemia ( ) leukaemia ( ) Leukemia ( ) Leukopenia ( ) Lymphoid leukemia ( ) Lymphoma, non-Hodgkin, familial ( ) Non-hodgkin lymphoma ( ) Thrombocytopenia ( )
UniProt ID	LPP60_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
EC Number	3.1.1.47; 3.1.1.5; 3.5.1.1
Pfam ID	PF12796 ; PF00710 ; PF17763
Sequence	MARAVGPERRLLAVYTGGTIGMRSELGVLVPGTGLAAILRTLPMFHDEEHARARGLSEDT LVLPPASRNQRILYTVLECQPLFDSSDMTIAEWVCLAQTIKRHYEQYHGFVVIHGTDTMA FAASMLSFMLENLQKTVILTGAQVPIHALWSDGRENLLGALLMAGQYVIPEVCLFFQNQL FRGNRATKVDARRFAAFCSPNLLPLATVGADITINRELVRKVDGKAGLVVHSSMEQDVGL LRLYPGIPAALVRAFLQPPLKGVVMETFGSGNGPTKPDLLQELRVATERGLVIVNCTHCL QGAVTTDYAAGMAMAGAGVISGFDMTSEAALAKLSYVLGQPGLSLDVRKELLTKDLRGEM TPPSVEERRPSLQGNTLGGGVSWLLSLSGSQEADALRNALVPSLACAAAHAGDVEALQAL VELGSDLGLVDFNGQTPLHAAARGGHTEAVTMLLQRGVDVNTRDTDGFSPLLLAVRGRHP GVIGLLREAGASLSTQELEEAGTELCRLAYRADLEGLQVWWQAGADLGQPGYDGHSALHV AEAAGNLAVVAFLQSLEGAVGAQAPCPEVLPGV
Function	Exhibits lysophospholipase, transacylase, PAF acetylhydrolase and asparaginase activities. Can catalyze three types of transacylation reactions: (1) acyl transfer from 1-acyl-sn-glycero-3-phosphocholine (1-acyl-GPC) to the sn-1(3) positions of glycerol and 2-acylglycerol (sn-1 to -1(3) transfer), (2) acyl transfer from 1-acyl-GPC to the sn-2 positions of 1-acyl-GPC, 1-acyl-sn-glycero-3-phosphoethanolamine (1-acyl-GPE), and other lysophospholipids (sn-1 to -2 transfer) and (3) acyl transfer from 2-acyl-GPC to the sn-1 position of 2-acyl-GPC and 2-acyl-GPE (sn-2 to -1 transfer). Mediates the synthesis of 1-arachidonoyl species of phospholipids by transferring the arachidonoyl residue from 2-arachidonoyl lysophospholipid to the sn-1 position of 2-acyl lysophospholipid.
Reactome Pathway	Aspartate and asparagine metabolism (R-HSA-8963693 )
BioCyc Pathway	MetaCyc:HS15413-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

44 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Chronic kidney disease	DISW82R7	Definitive	Genetic Variation	[1]
Chronic renal failure	DISGG7K6	Definitive	Genetic Variation	[1]
Acute leukaemia	DISDQFDI	Strong	Altered Expression	[2]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[3]
Adult lymphoma	DISK8IZR	Strong	Biomarker	[4]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[5]
Burkitt lymphoma	DIS9D5XU	Strong	Biomarker	[6]
Cholelithiasis	DISERLZB	Strong	Biomarker	[7]
Cholestasis	DISDJJWE	Strong	Biomarker	[8]
Coagulation defect	DIS9X3H6	Strong	Biomarker	[9]
Cowden disease	DISMYKCE	Strong	Biomarker	[10]
Extranodal NK/T-cell Lymphoma	DIS72GCL	Strong	Genetic Variation	[11]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[12]
Gastric cancer	DISXGOUK	Strong	Biomarker	[13]
Glioma	DIS5RPEH	Strong	Biomarker	[14]
Hyperglycemia	DIS0BZB5	Strong	Biomarker	[15]
Liver cancer	DISDE4BI	Strong	Biomarker	[16]
Lymphoblastic lymphoma	DISB9ZYC	Strong	Biomarker	[17]
Lymphoma	DISN6V4S	Strong	Biomarker	[4]
Medulloblastoma	DISZD2ZL	Strong	Biomarker	[14]
Neoplasm	DISZKGEW	Strong	Biomarker	[18]
Obesity	DIS47Y1K	Strong	Biomarker	[19]
Pancreatic cancer	DISJC981	Strong	Biomarker	[20]
Pediatric lymphoma	DIS51BK2	Strong	Biomarker	[4]
Promyelocytic leukaemia	DISYGG13	Strong	Biomarker	[9]
Stomach cancer	DISKIJSX	Strong	Biomarker	[13]
T-cell acute lymphoblastic leukaemia	DIS17AI2	Strong	Biomarker	[21]
T-cell lymphoma	DISSXRTQ	Strong	Biomarker	[22]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[23]
Venous thromboembolism	DISUR7CR	Strong	Biomarker	[24]
Adult glioblastoma	DISVP4LU	moderate	Biomarker	[25]
Advanced cancer	DISAT1Z9	moderate	Genetic Variation	[26]
Glioblastoma multiforme	DISK8246	moderate	Biomarker	[25]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[27]
Laryngeal squamous cell carcinoma	DIS9UUVF	moderate	Biomarker	[28]
Stroke	DISX6UHX	moderate	Genetic Variation	[29]
Anemia	DISTVL0C	Limited	Biomarker	[30]
leukaemia	DISS7D1V	Limited	Biomarker	[9]
Leukemia	DISNAKFL	Limited	Biomarker	[2]
Leukopenia	DISJMBMM	Limited	Biomarker	[30]
Lymphoid leukemia	DIS65TYQ	Limited	Biomarker	[31]
Lymphoma, non-Hodgkin, familial	DISCXYIZ	Limited	Biomarker	[32]
Non-hodgkin lymphoma	DISS2Y8A	Limited	Biomarker	[32]
Thrombocytopenia	DISU61YW	Limited	Biomarker	[30]
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⏷ Show the Full List of 44 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

3 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 60 kDa lysophospholipase (ASPG).	[33]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of 60 kDa lysophospholipase (ASPG).	[36]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of 60 kDa lysophospholipase (ASPG).	[37]
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2 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of 60 kDa lysophospholipase (ASPG).	[34]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid decreases the expression of 60 kDa lysophospholipase (ASPG).	[35]
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References

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2	Synthetic Lethality of Wnt Pathway Activation and Asparaginase in Drug-Resistant Acute Leukemias.Cancer Cell. 2019 Apr 15;35(4):664-676.e7. doi: 10.1016/j.ccell.2019.03.004.
3	Asparaginase Erwinia chrysanthemi effectively depletes plasma glutamine in adult patients with relapsed/refractory acute myeloid leukemia.Cancer Chemother Pharmacol. 2018 Jan;81(1):217-222. doi: 10.1007/s00280-017-3459-6. Epub 2017 Nov 8.
4	HLA-DRB1*07:01 is associated with a higher risk of asparaginase allergies.Blood. 2014 Aug 21;124(8):1266-76. doi: 10.1182/blood-2014-03-563742. Epub 2014 Jun 26.
5	Cell growth stimulation by CRASH, an asparaginase-like protein overexpressed in human tumors and metastatic breast cancers.Anticancer Res. 2009 Apr;29(4):951-63.
6	Mechanisms of cell death induced by arginase and asparaginase in precursor B-cell lymphoblasts.Apoptosis. 2019 Feb;24(1-2):145-156. doi: 10.1007/s10495-018-1506-3.
7	Cholelithiasis and choledocholithiasis after sequential cytarabine and asparaginase.J Pediatr Hematol Oncol. 2003 Aug;25(8):637-9. doi: 10.1097/00043426-200308000-00010.
8	Asparaginase-induced hepatotoxicity: rapid development of cholestasis and hepatic steatosis.Hepatol Int. 2019 Sep;13(5):641-648. doi: 10.1007/s12072-019-09971-2. Epub 2019 Aug 7.
9	Acquired Hypofibrinogenemia Before Asparaginase Exposure During Induction Therapy for Pediatric Acute Lymphoblastic Leukemia: A Report of 2 Cases and Review of the Literature.J Pediatr Hematol Oncol. 2018 Oct;40(7):e470-e472. doi: 10.1097/MPH.0000000000001114.
10	Different profile of thrombin generation in children with acute lymphoblastic leukaemia treated with native or pegylated asparaginase: A cohort study.Pediatr Blood Cancer. 2017 Feb;64(2):294-301. doi: 10.1002/pbc.26228. Epub 2016 Sep 8.
11	Circulating Low Absolute CD4+ T Cell Counts May Predict Poor Prognosis in Extranodal NK/T-Cell Lymphoma Patients Treating with Pegaspargase-Based Chemotherapy.Cancer Res Treat. 2019 Jan;51(1):368-377. doi: 10.4143/crt.2018.010. Epub 2018 May 14.
12	Age modulates liver responses to asparaginase-induced amino acid stress in mice.J Biol Chem. 2019 Sep 20;294(38):13864-13875. doi: 10.1074/jbc.RA119.009864. Epub 2019 Aug 14.
13	Role of -glutamyltranspeptidase in the pathogenesis of Helicobacter pylori infection.Microbiol Immunol. 2013 Oct;57(10):665-73. doi: 10.1111/1348-0421.12089.
14	Efficacy of Asparaginase Erwinia chrysanthemi With and Without Temozolomide Against Glioma Cells and Intracranial Mouse Medulloblastoma.Anticancer Res. 2018 May;38(5):2627-2634. doi: 10.21873/anticanres.12504.
15	Insulin-dependent diabetes: A chronic complication to acute pancreatitis in childhood acute lymphoblastic leukemia.Pediatr Blood Cancer. 2019 Jan;66(1):e27437. doi: 10.1002/pbc.27437. Epub 2018 Sep 14.
16	The landscape of cancer cell line metabolism.Nat Med. 2019 May;25(5):850-860. doi: 10.1038/s41591-019-0404-8. Epub 2019 May 8.
17	Feasibility and safety of delivering full-dose anticoagulation therapy in children treated according to Dana-Farber Cancer Institute acute lymphoblastic leukemia consortium therapy protocols.Pediatr Blood Cancer. 2019 Feb;66(2):e27483. doi: 10.1002/pbc.27483. Epub 2018 Oct 25.
18	Rhodospirillum rubruml-asparaginase targets tumor growth by a dual mechanism involving telomerase inhibition.Biochem Biophys Res Commun. 2017 Oct 14;492(2):282-288. doi: 10.1016/j.bbrc.2017.08.078. Epub 2017 Aug 23.
19	Obesity challenges the hepatoprotective function of the integrated stress response to asparaginase exposure in mice.J Biol Chem. 2017 Apr 21;292(16):6786-6798. doi: 10.1074/jbc.M116.768408. Epub 2017 Feb 27.
20	Human pancreatic carcinoma (MIA PaCa-2) in continuous culture: sensitivity to asparaginase.Int J Cancer. 1977 Jan;19(1):128-35. doi: 10.1002/ijc.2910190118.
21	Comparative features and outcomes between paediatric T-cell and B-cell acute lymphoblastic leukaemia.Lancet Oncol. 2019 Mar;20(3):e142-e154. doi: 10.1016/S1470-2045(19)30031-2.
22	Comparison of Native Escherichia coli L-Asparaginase versus Pegylated Asparaginase, in Combination with Ifosfamide, Methotrexate, Etoposide, and Prednisolone, in Extranodal NK/T-Cell Lymphoma, Nasal Type.Cancer Res Treat. 2018 Jul;50(3):670-680. doi: 10.4143/crt.2017.051. Epub 2017 Jul 3.
23	Identification and validation of l-asparaginase as a potential metabolic target against Mycobacterium tuberculosis.J Cell Biochem. 2019 Jan;120(1):143-154. doi: 10.1002/jcb.27169. Epub 2018 Sep 19.
24	Risk factors for symptomatic venous thromboembolism during therapy for childhood acute lymphoblastic leukemia.Thromb Res. 2019 Jun;178:132-138. doi: 10.1016/j.thromres.2019.04.011. Epub 2019 Apr 11.
25	Autophagy suppression potentiates the anti-glioblastoma effect of asparaginase in vitro and in vivo.Oncotarget. 2017 Jul 20;8(53):91052-91066. doi: 10.18632/oncotarget.19409. eCollection 2017 Oct 31.
26	Thromboembolism Incidence and Risk Factors in Children with Cancer: A Population-Based Cohort Study.Thromb Haemost. 2018 Sep;118(9):1646-1655. doi: 10.1055/s-0038-1668543. Epub 2018 Aug 13.
27	Computational discovery of niclosamide ethanolamine, a repurposed drug candidate that reduces growth of hepatocellular carcinoma cells initro and in mice by inhibiting cell division cycle 37 signaling. Gastroenterology. 2017 Jun;152(8):2022-2036.
28	Deprivation of asparagine triggers cytoprotective autophagy in laryngeal squamous cell carcinoma.Appl Microbiol Biotechnol. 2017 Jun;101(12):4951-4961. doi: 10.1007/s00253-017-8221-9. Epub 2017 Mar 28.
29	Aldosterone synthase gene polymorphism, stroke volume and age-related changes in aortic pulse wave velocity in subjects with hypertension.J Hypertens. 2005 Jun;23(6):1159-66. doi: 10.1097/01.hjh.0000170378.08214.13.
30	The sonographic appearance of cyclophosphamide-induced acute haemorrhagic cystitis.Clin Radiol. 1990 Apr;41(4):289-90. doi: 10.1016/s0009-9260(05)81670-8.
31	Universal premedication and therapeutic drug monitoring for asparaginase-based therapy prevents infusion-associated acute adverse events and drug substitutions.Pediatr Blood Cancer. 2019 Aug;66(8):e27797. doi: 10.1002/pbc.27797. Epub 2019 May 16.
32	Prolonged versus standard native E. coli asparaginase therapy in childhood acute lymphoblastic leukemia and non-Hodgkin lymphoma: final results of the EORTC-CLG randomized phase III trial 58951.Haematologica. 2017 Oct;102(10):1727-1738. doi: 10.3324/haematol.2017.165845. Epub 2017 Jul 27.
33	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.
34	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.
35	Pharmacotoxicology of clinically-relevant concentrations of obeticholic acid in an organotypic human hepatocyte system. Toxicol In Vitro. 2017 Mar;39:93-103.
36	Gene expression and cytosine DNA methylation alterations in induced pluripotent stem-cell-derived human hepatocytes treated with low doses of chemical carcinogens. Arch Toxicol. 2019 Nov;93(11):3335-3344. doi: 10.1007/s00204-019-02569-5. Epub 2019 Sep 25.
37	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.