Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6VJTPA)

DOT Name	Phospholipase A2 group XV (PLA2G15)
Synonyms	1-O-acylceramide synthase; ACS; LCAT-like lysophospholipase; LLPL; EC 3.1.1.5; Lysophospholipase 3; Lysosomal phospholipase A and acyltransferase; EC 2.3.1.-, EC 3.1.1.32, EC 3.1.1.4; Lysosomal phospholipase A2; LPLA2
Gene Name	PLA2G15
Related Disease	Acute lymphocytic leukaemia ( ) Acute myocardial infarction ( ) Alzheimer disease ( ) Appendicitis ( ) Arteriosclerosis ( ) Atherosclerosis ( ) Atrial fibrillation ( ) Carcinoma of esophagus ( ) Cardiac arrest ( ) Childhood acute lymphoblastic leukemia ( ) Chronic kidney disease ( ) Clear cell renal carcinoma ( ) Congestive heart failure ( ) Coronary atherosclerosis ( ) Coronary heart disease ( ) Depression ( ) Diabetic kidney disease ( ) Esophageal cancer ( ) High blood pressure ( ) Inflammatory bowel disease ( ) Mental disorder ( ) Myocardial infarction ( ) Neoplasm ( ) Neoplasm of esophagus ( ) Neuroendocrine neoplasm ( ) Obesity ( ) Obstructive sleep apnea ( ) Prostate cancer ( ) Prostate carcinoma ( ) Rectal carcinoma ( ) Renal cell carcinoma ( ) Schizophrenia ( ) Stroke ( ) Venous thromboembolism ( ) Cardiovascular disease ( ) Colon cancer ( ) Colon carcinoma ( ) Crohn disease ( ) Endometrial cancer ( ) Endometrial carcinoma ( ) Abdominal aortic aneurysm ( ) Advanced cancer ( ) Breast cancer ( ) Breast carcinoma ( ) Chronic obstructive pulmonary disease ( ) Colorectal carcinoma ( ) Hepatocellular carcinoma ( )
UniProt ID	PAG15_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	4X90; 4X91; 4X92; 4X93; 4X94; 4X95; 4X97; 6MTW
EC Number	2.3.1.-; 3.1.1.32; 3.1.1.4; 3.1.1.5
Pfam ID	PF02450
Sequence	MGLHLRPYRVGLLPDGLLFLLLLLMLLADPALPAGRHPPVVLVPGDLGNQLEAKLDKPTV VHYLCSKKTESYFTIWLNLELLLPVIIDCWIDNIRLVYNKTSRATQFPDGVDVRVPGFGK TFSLEFLDPSKSSVGSYFHTMVESLVGWGYTRGEDVRGAPYDWRRAPNENGPYFLALREM IEEMYQLYGGPVVLVAHSMGNMYTLYFLQRQPQAWKDKYIRAFVSLGAPWGGVAKTLRVL ASGDNNRIPVIGPLKIREQQRSAVSTSWLLPYNYTWSPEKVFVQTPTINYTLRDYRKFFQ DIGFEDGWLMRQDTEGLVEATMPPGVQLHCLYGTGVPTPDSFYYESFPDRDPKICFGDGD GTVNLKSALQCQAWQSRQEHQVLLQELPGSEHIEMLANATTLAYLKRVLLGP
Function	Has dual calcium-independent phospholipase and O-acyltransferase activities with a potential role in glycerophospholipid homeostasis and remodeling of acyl groups of lipophilic alcohols present in acidic cellular compartments. Catalyzes hydrolysis of the ester bond of the fatty acyl group attached at sn-1 or sn-2 position of phospholipids (phospholipase A1 or A2 activity) and transfer it to the hydroxyl group at the first carbon of lipophilic alcohols (O-acyltransferase activity). Among preferred fatty acyl donors are phosphatidylcholines, phosphatidylethanolamines, phosphatidylglycerols and phosphatidylserines. Favors sn-2 over sn-1 deacylation of unsaturated fatty acyl groups of phosphatidylcholines and phosphatidylethanolamines. Among preferred fatty acyl acceptors are natural lipophilic alcohols including short-chain ceramide N-acetyl-sphingosine (C2 ceramide), alkylacylglycerols, monoacylglycerols, and acylethanolamides such as anandamide and oleoylethanolamide. Selectively hydrolyzes the sn-1 fatty acyl group of truncated oxidized phospholipids and may play a role in detoxification of reactive oxidized phospholipids during oxidative stress. Required for normal phospholipid degradation in alveolar macrophages with potential implications in pulmonary surfactant clearance. At neutral pH, hydrolyzes the sn-1 fatty acyl group of the lysophosphatidylcholines.
Tissue Specificity	Detected in blood plasma (at protein level) . Ubiquitous. Highly expressed in heart, placenta, skeletal muscle, kidney and pancreas. Detected at lower levels in spleen, thymus, prostate, testis, ovary, small intestine, colon and peripheral blood leukocytes .
KEGG Pathway	Glycerophospholipid metabolism (hsa00564 ) Lysosome (hsa04142 ) Efferocytosis (hsa04148 )
Reactome Pathway	Hydrolysis of LPC (R-HSA-1483115 )

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Acute lymphocytic leukaemia	DISPX75S	Strong	Genetic Variation	[1]
Acute myocardial infarction	DISE3HTG	Strong	Biomarker	[2]
Alzheimer disease	DISF8S70	Strong	Biomarker	[3]
Appendicitis	DIS4GOLF	Strong	Genetic Variation	[4]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[5]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[5]
Atrial fibrillation	DIS15W6U	Strong	Biomarker	[6]
Carcinoma of esophagus	DISS6G4D	Strong	Biomarker	[7]
Cardiac arrest	DIS9DIA4	Strong	Biomarker	[8]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Strong	Genetic Variation	[1]
Chronic kidney disease	DISW82R7	Strong	Biomarker	[9]
Clear cell renal carcinoma	DISBXRFJ	Strong	Genetic Variation	[10]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[11]
Coronary atherosclerosis	DISKNDYU	Strong	Genetic Variation	[12]
Coronary heart disease	DIS5OIP1	Strong	Biomarker	[13]
Depression	DIS3XJ69	Strong	Biomarker	[14]
Diabetic kidney disease	DISJMWEY	Strong	Altered Expression	[15]
Esophageal cancer	DISGB2VN	Strong	Biomarker	[7]
High blood pressure	DISY2OHH	Strong	Genetic Variation	[16]
Inflammatory bowel disease	DISGN23E	Strong	Biomarker	[17]
Mental disorder	DIS3J5R8	Strong	Biomarker	[18]
Myocardial infarction	DIS655KI	Strong	Biomarker	[19]
Neoplasm	DISZKGEW	Strong	Biomarker	[20]
Neoplasm of esophagus	DISOLKAQ	Strong	Biomarker	[7]
Neuroendocrine neoplasm	DISNPLOO	Strong	Biomarker	[21]
Obesity	DIS47Y1K	Strong	Genetic Variation	[22]
Obstructive sleep apnea	DIS0SVD1	Strong	Biomarker	[23]
Prostate cancer	DISF190Y	Strong	Biomarker	[24]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[24]
Rectal carcinoma	DIS8FRR7	Strong	Genetic Variation	[25]
Renal cell carcinoma	DISQZ2X8	Strong	Genetic Variation	[10]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[26]
Stroke	DISX6UHX	Strong	Biomarker	[27]
Venous thromboembolism	DISUR7CR	Strong	Biomarker	[28]
Cardiovascular disease	DIS2IQDX	moderate	Biomarker	[29]
Colon cancer	DISVC52G	moderate	Biomarker	[30]
Colon carcinoma	DISJYKUO	moderate	Biomarker	[30]
Crohn disease	DIS2C5Q8	moderate	Genetic Variation	[31]
Endometrial cancer	DISW0LMR	Disputed	Biomarker	[32]
Endometrial carcinoma	DISXR5CY	Disputed	Biomarker	[32]
Abdominal aortic aneurysm	DISD06OF	Limited	Biomarker	[33]
Advanced cancer	DISAT1Z9	Limited	Genetic Variation	[34]
Breast cancer	DIS7DPX1	Limited	Biomarker	[35]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[35]
Chronic obstructive pulmonary disease	DISQCIRF	Limited	Biomarker	[36]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[37]
Hepatocellular carcinoma	DIS0J828	Limited	Biomarker	[38]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas 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 Phospholipase A2 group XV (PLA2G15).	[39]
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7 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 Phospholipase A2 group XV (PLA2G15).	[40]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Phospholipase A2 group XV (PLA2G15).	[41]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Phospholipase A2 group XV (PLA2G15).	[42]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Phospholipase A2 group XV (PLA2G15).	[43]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Phospholipase A2 group XV (PLA2G15).	[44]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone affects the expression of Phospholipase A2 group XV (PLA2G15).	[45]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Phospholipase A2 group XV (PLA2G15).	[46]
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⏷ Show the Full List of 7 Drug(s)

References

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4	Imaging utilization affects negative appendectomy rates in appendicitis: An ACS-NSQIP study.Am J Surg. 2019 Jun;217(6):1094-1098. doi: 10.1016/j.amjsurg.2018.12.072. Epub 2019 Jan 3.
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8	Editor's Choice-Prospective registry of cardiac critical illness in a modern tertiary care Cardiac Intensive Care Unit.Eur Heart J Acute Cardiovasc Care. 2019 Dec;8(8):755-761. doi: 10.1177/2048872618789053. Epub 2018 Jul 23.
9	Impact of serum albumin levels on long-term outcomes in patients undergoing percutaneous coronary intervention.Heart Vessels. 2017 Sep;32(9):1085-1092. doi: 10.1007/s00380-017-0981-8. Epub 2017 Apr 20.
10	Predicted versus observed 30-day perioperative outcomes using the ACS NSQIP surgical risk calculator in patients undergoing partial nephrectomy for renal cell carcinoma.Int Urol Nephrol. 2018 Jul;50(7):1249-1256. doi: 10.1007/s11255-018-1898-6. Epub 2018 Jun 4.
11	Early versus delayed invasive strategy in patients with non-ST-elevation acute coronary syndrome and concomitant congestive heart failure.J Cardiol. 2019 Oct;74(4):320-327. doi: 10.1016/j.jjcc.2019.03.006.
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13	Predictive value of global and territorial longitudinal strain imaging in detecting significant coronary artery disease in patients with myocardial infarction without persistent ST-segment elevation.Echocardiography. 2019 Mar;36(3):512-520. doi: 10.1111/echo.14275. Epub 2019 Feb 25.
14	Impact of depression at early and late phases following acute coronary syndrome on long-term cardiac outcomes.J Affect Disord. 2020 Jan 1;260:592-596. doi: 10.1016/j.jad.2019.09.059. Epub 2019 Sep 12.
15	Resveratrol reverts Streptozotocin-induced diabetic nephropathy.Front Biosci (Landmark Ed). 2020 Jan 1;25(4):699-709. doi: 10.2741/4829.
16	First-in-man study of dedicated bifurcation cobalt-chromium sirolimus-eluting stent BiOSS LIM C - three-month results.Kardiol Pol. 2018;76(2):464-470. doi: 10.5603/KP.a2017.0226. Epub 2017 Dec 1.
17	The ACS National Surgical Quality Improvement Program-Inflammatory Bowel Disease Collaborative: Design, Implementation, and Validation of a Disease-specific Module.Inflamm Bowel Dis. 2019 Oct 18;25(11):1731-1739. doi: 10.1093/ibd/izz044.
18	Non-cardiac chest pain patients in the emergency department: Do physicians have a plan how to diagnose and treat them? A retrospective study.PLoS One. 2019 Feb 1;14(2):e0211615. doi: 10.1371/journal.pone.0211615. eCollection 2019.
19	Variability in High-Sensitivity Cardiac Troponin T Testing in Stable Patients With and Without Coronary Artery Disease.Can J Cardiol. 2019 Nov;35(11):1505-1512. doi: 10.1016/j.cjca.2019.08.022. Epub 2019 Aug 22.
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21	Do All Abdominal Neuroendocrine Tumors Require Extended Postoperative VTE Prophylaxis? A NSQIP Analysis.J Gastrointest Surg. 2019 Apr;23(4):788-793. doi: 10.1007/s11605-018-04075-y. Epub 2019 Jan 22.
22	Outcomes in Cardiogenic Shock from Acute Coronary Syndrome Depending on Severity of Obesity.Am J Cardiol. 2019 Apr 15;123(8):1267-1272. doi: 10.1016/j.amjcard.2019.01.010. Epub 2019 Jan 24.
23	Association of Obstructive Sleep Apnea With Cardiovascular Outcomes in Patients With Acute Coronary Syndrome.J Am Heart Assoc. 2019 Jan 22;8(2):e010826. doi: 10.1161/JAHA.118.010826.
24	Modified frailty index associated with Clavien-Dindo IV complications in robot-assisted radical prostatectomies: A retrospective study.Urol Oncol. 2017 Jun;35(6):425-431. doi: 10.1016/j.urolonc.2017.01.005. Epub 2017 Feb 9.
25	Trends and outcomes in laparoscopic versus open surgery for rectal cancer from 2005 to 2016 using the ACS-NSQIP database, a retrospective cohort study.Int J Surg. 2019 Mar;63:71-76. doi: 10.1016/j.ijsu.2019.02.006. Epub 2019 Feb 13.
26	Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection.Nat Genet. 2018 Mar;50(3):381-389. doi: 10.1038/s41588-018-0059-2. Epub 2018 Feb 26.
27	Influence of Environmental Factors on Social Participation Post-Stroke.Behav Neurol. 2019 Jan 16;2019:2606039. doi: 10.1155/2019/2606039. eCollection 2019.
28	Is Obesity Associated With Increased Risk of Deep Vein Thrombosis or Pulmonary Embolism After Hip and Knee Arthroplasty? A Large Database Study.Clin Orthop Relat Res. 2019 Mar;477(3):523-532. doi: 10.1097/CORR.0000000000000615.
29	Performance on management strategies with Class I Recommendation and A Level of Evidence among hospitalized patients with non-ST-segment elevation acute coronary syndrome in China: Findings from the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome (CCC-ACS) project.Am Heart J. 2019 Jun;212:80-90. doi: 10.1016/j.ahj.2019.02.012. Epub 2019 Mar 4.
30	Association of Survival With Adherence to the American Cancer Society Nutrition and Physical Activity Guidelines for Cancer Survivors After Colon Cancer Diagnosis: The CALGB 89803/Alliance Trial.JAMA Oncol. 2018 Jun 1;4(6):783-790. doi: 10.1001/jamaoncol.2018.0126.
31	Immunosuppressed Patients with Crohn's Disease Are at Increased Risk of Postoperative Complications: Results from the ACS-NSQIP Database.J Gastrointest Surg. 2019 Jun;23(6):1188-1197. doi: 10.1007/s11605-019-04186-0. Epub 2019 Mar 18.
32	Preoperative frailty is a risk factor for non-home discharge in patients undergoing surgery for endometrial cancer.J Geriatr Oncol. 2018 Sep;9(5):513-515. doi: 10.1016/j.jgo.2018.02.005. Epub 2018 Mar 9.
33	Development and Validation of Procedure-Specific Risk Score for Predicting Postoperative Pulmonary Complication: ANSQIP Analysis.J Am Coll Surg. 2019 Oct;229(4):355-365.e3. doi: 10.1016/j.jamcollsurg.2019.05.028. Epub 2019 Jun 18.
34	Association of preoperative biliary drainage technique with postoperative outcomes among patients with resectable hepatobiliary malignancy.HPB (Oxford). 2020 Feb;22(2):249-257. doi: 10.1016/j.hpb.2019.06.011. Epub 2019 Jul 23.
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37	NFATC3-PLA2G15 Fusion Transcript Identified by RNA Sequencing Promotes Tumor Invasion and Proliferation in Colorectal Cancer Cell Lines.Cancer Res Treat. 2019 Jan;51(1):391-401. doi: 10.4143/crt.2018.103. Epub 2018 Jun 14.
38	Evaluation of the ACS NSQIP Surgical Risk Calculator in Elderly Patients Undergoing Hepatectomy for Hepatocellular Carcinoma.J Gastrointest Surg. 2020 Mar;24(3):551-559. doi: 10.1007/s11605-019-04174-4. Epub 2019 Apr 1.
39	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.
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