Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5CTQKO)

DOT Name	1-acyl-sn-glycerol-3-phosphate acyltransferase delta (AGPAT4)
Synonyms	EC 2.3.1.51; 1-acylglycerol-3-phosphate O-acyltransferase 4; 1-AGP acyltransferase 4; 1-AGPAT 4; Lysophosphatidic acid acyltransferase delta; LPAAT-delta
Gene Name	AGPAT4
Related Disease	Bladder cancer ( ) Urinary bladder cancer ( ) Urinary bladder neoplasm ( )
UniProt ID	PLCD_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
EC Number	2.3.1.51
Pfam ID	PF16076 ; PF01553
Sequence	MDLAGLLKSQFLCHLVFCYVFIASGLIINTIQLFTLLLWPINKQLFRKINCRLSYCISSQ LVMLLEWWSGTECTIFTDPRAYLKYGKENAIVVLNHKFEIDFLCGWSLSERFGLLGGSKV LAKKELAYVPIIGWMWYFTEMVFCSRKWEQDRKTVATSLQHLRDYPEKYFFLIHCEGTRF TEKKHEISMQVARAKGLPRLKHHLLPRTKGFAITVRSLRNVVSAVYDCTLNFRNNENPTL LGVLNGKKYHADLYVRRIPLEDIPEDDDECSAWLHKLYQEKDAFQEEYYRTGTFPETPMV PPRRPWTLVNWLFWASLVLYPFFQFLVSMIRSGSSLTLASFILVFFVASVGVRWMIGVTE IDKGSAYGNSDSKQKLND
Function	Converts 1-acyl-sn-glycerol-3-phosphate (lysophosphatidic acid or LPA) into 1,2-diacyl-sn-glycerol-3-phosphate (phosphatidic acid or PA) by incorporating an acyl moiety at the sn-2 position of the glycerol backbone. Exhibits high acyl-CoA specificity for polyunsaturated fatty acyl-CoA, especially docosahexaenoyl-CoA (22:6-CoA, DHA-CoA).
Tissue Specificity	Widely expressed with highest levels in skeletal muscle, followed by heart, liver, prostate and thymus.
KEGG Pathway	Glycerolipid metabolism (hsa00561 ) Glycerophospholipid metabolism (hsa00564 ) Metabolic pathways (hsa01100 ) Phospholipase D sig.ling pathway (hsa04072 )
Reactome Pathway	Synthesis of PA (R-HSA-1483166 )
BioCyc Pathway	MetaCyc:HS00452-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Bladder cancer	DISUHNM0	moderate	Altered Expression	[1]
Urinary bladder cancer	DISDV4T7	moderate	Altered Expression	[1]
Urinary bladder neoplasm	DIS7HACE	moderate	Altered Expression	[1]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

11 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 1-acyl-sn-glycerol-3-phosphate acyltransferase delta (AGPAT4).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of 1-acyl-sn-glycerol-3-phosphate acyltransferase delta (AGPAT4).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of 1-acyl-sn-glycerol-3-phosphate acyltransferase delta (AGPAT4).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of 1-acyl-sn-glycerol-3-phosphate acyltransferase delta (AGPAT4).	[5]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of 1-acyl-sn-glycerol-3-phosphate acyltransferase delta (AGPAT4).	[6]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of 1-acyl-sn-glycerol-3-phosphate acyltransferase delta (AGPAT4).	[7]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of 1-acyl-sn-glycerol-3-phosphate acyltransferase delta (AGPAT4).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of 1-acyl-sn-glycerol-3-phosphate acyltransferase delta (AGPAT4).	[9]
PMID27336223-Compound-5	DM6E50A	Patented	PMID27336223-Compound-5 increases the expression of 1-acyl-sn-glycerol-3-phosphate acyltransferase delta (AGPAT4).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of 1-acyl-sn-glycerol-3-phosphate acyltransferase delta (AGPAT4).	[7]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of 1-acyl-sn-glycerol-3-phosphate acyltransferase delta (AGPAT4).	[10]
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⏷ Show the Full List of 11 Drug(s)

References

1	Establishment of a novel experimental model for muscle-invasive bladder cancer using a dog bladder cancer organoid culture.Cancer Sci. 2019 Sep;110(9):2806-2821. doi: 10.1111/cas.14118. Epub 2019 Jul 23.
2	Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
3	Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
4	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.
5	Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
6	Aberrantly expressed genes in HaCaT keratinocytes chronically exposed to arsenic trioxide. Biomark Insights. 2011 Feb 8;6:7-16.
7	Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
8	PPARgamma controls CD1d expression by turning on retinoic acid synthesis in developing human dendritic cells. J Exp Med. 2006 Oct 2;203(10):2351-62.
9	Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
10	Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.