Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKBAB0F)

DOT Name	Cytosolic phospholipase A2 delta (PLA2G4D)
Synonyms	cPLA2-delta; EC 3.1.1.4; Phospholipase A2 group IVD
Gene Name	PLA2G4D
Related Disease	Atopic dermatitis ( ) Hepatocellular carcinoma ( ) Mycosis fungoides ( )
UniProt ID	PA24D_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	5IXC; 5IZ5; 5IZR
EC Number	3.1.1.4
Pfam ID	PF00168 ; PF18695 ; PF01735
Sequence	MESLSPGGPPGHPYQGEASTCWQLTVRVLEARNLRWADLLSEADPYVILQLSTAPGMKFK TKTLTDTSHPVWNEAFRFLIQSQVKNVLELSIYDEDSVTEDDICFKVLYDISEVLPGKLL RKTFSQSPQGEEELDVEFLMEETSDRPENLITNKVIVARELSCLDVHLDSTGSTAVVADQ DKLELELVLKGSYEDTQTSFLGTASAFRFHYMAALETELSGRLRSSRSNGWNGDNSAGYL TVPLRPLTIGKEVTMDVPAPNAPGVRLQLKAEGCPEELAVHLGFNLCAEEQAFLSRRKQV VAKALKQALQLDRDLQEDEVPVVGIMATGGGARAMTSLYGHLLALQKLGLLDCVTYFSGI SGSTWTMAHLYGDPEWSQRDLEGPIRYAREHLAKSKLEVFSPERLASYRRELELRAEQGH PTTFVDLWALVLESMLHGQVMDQKLSGQRAALERGQNPLPLYLSLNVKENNLETLDFKEW VEFSPYEVGFLKYGAFVPPELFGSEFFMGRLMRRIPEPRICFLEAIWSNIFSLNLLDAWY DLTSSGESWKQHIKDKTRSLEKEPLTTSGTSSRLEASWLQPGTALAQAFKGFLTGRPLHQ RSPNFLQGLQLHQDYCSHKDFSTWADYQLDSMPSQLTPKEPRLCLVDAAYFINTSSPSMF RPGRRLDLILSFDYSLSAPFEALQQTELYCRARGLPFPRVEPSPQDQHQPRECHLFSDPA CPEAPILLHFPLVNASFKDHSAPGVQRSPAELQGGQVDLTGATCPYTLSNMTYKEEDFER LLRLSDYNVQTSQGAILQALRTALKHRTLEARPPRAQT
Function	Calcium-dependent phospholipase A2 that selectively hydrolyzes glycerophospholipids in the sn-2 position. Has a preference for linoleic acid at the sn-2 position.
Tissue Specificity	Expressed in stratified squamous epithelia, such as those in skin and cervix, but not in other tissues . Strongly expressed in the upper spinous layer of the psoriatic epidermis, expressed weakly and discontinuously in atopic dermatitis and mycosis fungoides, and not detected in the epidermis of normal skin .
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 ) MAPK sig.ling pathway (hsa04010 ) Ras sig.ling pathway (hsa04014 ) Phospholipase D sig.ling pathway (hsa04072 ) Necroptosis (hsa04217 ) Vascular smooth muscle contraction (hsa04270 ) VEGF sig.ling pathway (hsa04370 ) Platelet activation (hsa04611 ) Fc epsilon RI sig.ling pathway (hsa04664 ) Fc gamma R-mediated phagocytosis (hsa04666 ) Glutamatergic sy.pse (hsa04724 ) Serotonergic sy.pse (hsa04726 ) Long-term depression (hsa04730 ) Inflammatory mediator regulation of TRP channels (hsa04750 ) GnRH sig.ling pathway (hsa04912 ) Ovarian steroidogenesis (hsa04913 ) Oxytocin sig.ling pathway (hsa04921 ) Choline metabolism in cancer (hsa05231 )
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 ) Hydrolysis of LPC (R-HSA-1483115 ) Synthesis of PA (R-HSA-1483166 ) Acyl chain remodelling of PC (R-HSA-1482788 )

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Atopic dermatitis	DISTCP41	Strong	Altered Expression	[1]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[2]
Mycosis fungoides	DIS62RB8	Strong	Altered Expression	[1]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Cytosolic phospholipase A2 delta (PLA2G4D).	[3]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Cytosolic phospholipase A2 delta (PLA2G4D).	[5]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Cytosolic phospholipase A2 delta (PLA2G4D).	[7]
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2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Cytosolic phospholipase A2 delta (PLA2G4D).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Cytosolic phospholipase A2 delta (PLA2G4D).	[6]
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References

1	Cloning of a gene for a novel epithelium-specific cytosolic phospholipase A2, cPLA2delta, induced in psoriatic skin.J Biol Chem. 2004 Mar 26;279(13):12890-7. doi: 10.1074/jbc.M305801200. Epub 2004 Jan 6.
2	Elevated Expression of Cytosolic Phospholipase A2 Delta Is Associated with Lipid Metabolism Dysregulation during Hepatocellular Carcinoma Progression.Cell J. 2020 Apr;22(1):17-22. doi: 10.22074/cellj.2020.6527. Epub 2019 Sep 8.
3	17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
4	Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
5	Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
6	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.
7	Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.