Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTU604XM)

DOT Name Group IID secretory phospholipase A2 (PLA2G2D)
Synonyms GIID sPLA2; sPLA2-IID; EC 3.1.1.4; PLA2IID; Phosphatidylcholine 2-acylhydrolase 2D; Secretory-type PLA, stroma-associated homolog
Gene Name PLA2G2D
Related Disease
Arteriosclerosis ( )
Atherosclerosis ( )
Craniosynostosis ( )
Nasal polyp ( )
Adenovirus infection ( )
Advanced cancer ( )
Chronic obstructive pulmonary disease ( )
Adenocarcinoma ( )
Breast cancer ( )
Breast carcinoma ( )
Cholangitis ( )
Colon cancer ( )
Colon carcinoma ( )
Coronary atherosclerosis ( )
Coronary heart disease ( )
Neoplasm ( )
UniProt ID
PA2GD_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
EC Number
3.1.1.4
Pfam ID
PF00068
Sequence
MELALLCGLVVMAGVIPIQGGILNLNKMVKQVTGKMPILSYWPYGCHCGLGGRGQPKDAT
DWCCQTHDCCYDHLKTQGCSIYKDYYRYNFSQGNIHCSDKGSWCEQQLCACDKEVAFCLK
RNLDTYQKRLRFYWRPHCRGQTPGC
Function
Secretory calcium-dependent phospholipase A2 that primarily targets extracellular lipids, exerting anti-inflammatory and immunosuppressive functions. Hydrolyzes the ester bond of the fatty acyl group attached at sn-2 position of phospholipids (phospholipase A2 activity) with preference for phosphatidylethanolamines and phosphatidylglycerols over phosphatidylcholines. In draining lymph nodes, selectively hydrolyzes diacyl and alkenyl forms of phosphatidylethanolamines, releasing omega-3 polyunsaturated fatty acids (PUFAs) such as eicosapentaenoate and docosahexaenoate that are precursors of the anti-inflammatory lipid mediators, resolvins. During the resolution phase of acute inflammation drives docosahexaenoate-derived resolvin D1 synthesis, which suppresses dendritic cell activation and T-helper 1 immune response. May act in an autocrine and paracrine manner. Via a mechanism independent of its catalytic activity, promotes differentiation of regulatory T cells (Tregs) and participates in the maintenance of immune tolerance. May contribute to lipid remodeling of cellular membranes and generation of lipid mediators involved in pathogen clearance. Displays bactericidal activity against Gram-positive bacteria by directly hydrolyzing phospholipids of the bacterial membrane.
Tissue Specificity Highly expressed in pancreas and spleen and less abundantly in colon, thymus, placenta, small intestine, and prostate.
KEGG Pathway
Glycerophospholipid metabolism (hsa00564 )
Ether lipid metabolism (hsa00565 )
Arachidonic acid metabolism (hsa00590 )
Linoleic acid metabolism (hsa00591 )
alpha-Linolenic acid metabolism (hsa00592 )
Metabolic pathways (hsa01100 )
Ras sig.ling pathway (hsa04014 )
Vascular smooth muscle contraction (hsa04270 )
Pancreatic secretion (hsa04972 )
Fat digestion and absorption (hsa04975 )
Reactome Pathway
Acyl chain remodelling of PS (R-HSA-1482801 )
Acyl chain remodelling of PE (R-HSA-1482839 )
Acyl chain remodelling of PI (R-HSA-1482922 )
Acyl chain remodelling of PG (R-HSA-1482925 )
Synthesis of PA (R-HSA-1483166 )
Acyl chain remodelling of PC (R-HSA-1482788 )

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Arteriosclerosis DISK5QGC Strong Biomarker [1]
Atherosclerosis DISMN9J3 Strong Biomarker [1]
Craniosynostosis DIS6J405 Strong Altered Expression [2]
Nasal polyp DISLP3XE Strong Biomarker [2]
Adenovirus infection DISUYSBZ moderate Biomarker [3]
Advanced cancer DISAT1Z9 moderate Altered Expression [4]
Chronic obstructive pulmonary disease DISQCIRF moderate Biomarker [5]
Adenocarcinoma DIS3IHTY Limited Biomarker [6]
Breast cancer DIS7DPX1 Limited Biomarker [7]
Breast carcinoma DIS2UE88 Limited Biomarker [7]
Cholangitis DIS9U3YN Limited Genetic Variation [8]
Colon cancer DISVC52G Limited Biomarker [6]
Colon carcinoma DISJYKUO Limited Biomarker [6]
Coronary atherosclerosis DISKNDYU Limited Biomarker [9]
Coronary heart disease DIS5OIP1 Limited Biomarker [9]
Neoplasm DISZKGEW Limited Biomarker [7]
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⏷ Show the Full List of 16 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Group IID secretory phospholipase A2 (PLA2G2D). [10]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide affects the expression of Group IID secretory phospholipase A2 (PLA2G2D). [11]
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1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Group IID secretory phospholipase A2 (PLA2G2D). [12]
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References

1 Group X secreted phospholipase A2 limits the development of atherosclerosis in LDL receptor-null mice.Arterioscler Thromb Vasc Biol. 2013 Mar;33(3):466-73. doi: 10.1161/ATVBAHA.112.300309. Epub 2013 Jan 24.
2 Group II subfamily secretory phospholipase A2 enzymes: expression in chronic rhinosinusitis with and without nasal polyps.Allergy. 2007 Sep;62(9):999-1006. doi: 10.1111/j.1398-9995.2007.01381.x. Epub 2007 Jun 18.
3 Human group III phospholipase A2 suppresses adenovirus infection into host cells. Evidence that group III, V and X phospholipase A2s act on distinct cellular phospholipid molecular species.Biochim Biophys Acta. 2007 Nov;1771(11):1389-96. doi: 10.1016/j.bbalip.2007.09.006. Epub 2007 Oct 10.
4 Silibinin down-regulates expression of secreted phospholipase A2 enzymes in cancer cells.Anticancer Res. 2014 Apr;34(4):1723-9.
5 Gly80Ser polymorphism of phospholipase A2-IID is associated with cytokine inducibility in A549 cells.Respiration. 2009;78(3):312-21. doi: 10.1159/000213243. Epub 2009 Apr 10.
6 Distinct expression pattern of the full set of secreted phospholipases A2 in human colorectal adenocarcinomas: sPLA2-III as a biomarker candidate.Br J Cancer. 2008 Feb 12;98(3):587-95. doi: 10.1038/sj.bjc.6604184. Epub 2008 Jan 22.
7 Secreted phospholipases Aare differentially expressed and epigenetically silenced in human breast cancer cells.Biochem Biophys Res Commun. 2014 Feb 28;445(1):230-5. doi: 10.1016/j.bbrc.2014.01.182. Epub 2014 Feb 6.
8 Secretory low-molecular-weight phospholipases A2 and their specific receptor in bile ducts of patients with intrahepatic calculi: factors of chronic proliferative cholangitis.Hepatology. 1999 Apr;29(4):1026-36. doi: 10.1002/hep.510290440.
9 Deciphering the Causal Role of sPLA2s and Lp-PLA2 in Coronary Heart Disease.Arterioscler Thromb Vasc Biol. 2015 Nov;35(11):2281-9. doi: 10.1161/ATVBAHA.115.305234. Epub 2015 Sep 3.
10 Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
11 Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
12 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.