General Information of the Ferroptosis Target (ID: TAR10032)
Target Name Lysophospholipid acyltransferase 5 (LPCAT3)
Synonyms
1-acylglycerophosphocholine O-acyltransferase; 1-acylglycerophosphoethanolamine O-acyltransferase; 1-acylglycerophosphoserine O-acyltransferase; Lysophosphatidylcholine acyltransferase; Lysophosphatidylcholine acyltransferase 3; Lysophosphatidylserine acyltransferase; Membrane-bound O-acyltransferase domain-containing protein 5
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Gene Name LPCAT3
Sequence
MASSAEGDEGTVVALAGVLQSGFQELSLNKLATSLGASEQALRLIISIFLGYPFALFYRH
YLFYKETYLIHLFHTFTGLSIAYFNFGNQLYHSLLCIVLQFLILRLMGRTITAVLTTFCF
QMAYLLAGYYYTATGNYDIKWTMPHCVLTLKLIGLAVDYFDGGKDQNSLSSEQQKYAIRG
VPSLLEVAGFSYFYGAFLVGPQFSMNHYMKLVQGELIDIPGKIPNSIIPALKRLSLGLFY
LVGYTLLSPHITEDYLLTEDYDNHPFWFRCMYMLIWGKFVLYKYVTCWLVTEGVCILTGL
GFNGFEEKGKAKWDACANMKVWLFETNPRFTGTIASFNINTNAWVARYIFKRLKFLGNKE
LSQGLSLLFLALWHGLHSGYLVCFQMEFLIVIVERQAARLIQESPTLSKLAAITVLQPFY
YLVQQTIHWLFMGYSMTAFCLFTWDKWLKVYKSIYFLGHIFFLSLLFILPYIHKAMVPRK
EKLKKME

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Family Membrane-bound acyltransferase family
Function
Lysophospholipid O-acyltransferase (LPLAT) that catalyzes the reacylation step of the phospholipid remodeling process also known as the Lands cycle. Catalyzes transfer of the fatty acyl chain from fatty acyl-CoA to 1- acyl lysophospholipid to form various classes of phospholipids. Converts 1-acyl lysophosphatidylcholine (LPC) into phosphatidylcholine (PC) (LPCAT activity), 1-acyl lysophosphatidylserine (LPS) into phosphatidylserine (PS) (LPSAT activity) and 1-acyl lysophosphatidylethanolamine (LPE) into phosphatidylethanolamine (PE) (LPEAT activity). Favors polyunsaturated fatty acyl-CoAs as acyl donors compared to saturated fatty acyl-CoAs . Has higher activity for LPC acyl acceptors compared to LPEs and LPSs. Can also transfer the fatty acyl chain from fatty acyl-CoA to 1-O-alkyl lysophospholipid or 1-O-alkenyl lysophospholipid with lower efficiency. Acts as a major LPC O-acyltransferase in liver and intestine. As a component of the liver X receptor/NR1H3 or NR1H2 signaling pathway, mainly catalyzes the incorporation of arachidonate into PCs of endoplasmic reticulum (ER) membranes, increasing membrane dynamics and enabling triacylglycerols transfer to nascent very low- density lipoprotein (VLDL) particles. Promotes processing of sterol regulatory protein SREBF1 in hepatocytes, likely by facilitating the translocation of SREBF1-SCAP complex from ER to the Golgi apparatus. Participates in mechanisms by which the liver X receptor/NR1H3 or NR1H2 signaling pathway counteracts lipid-induced ER stress response and inflammation. Down-regulates hepatic inflammation by limiting arachidonic acid availability for synthesis of inflammatory eicosanoids, such as prostaglandins. In enterocytes, acts as a component of a gut-brain feedback loop that coordinates dietary lipid absorption and food intake. Regulates the abundance of PCs containing linoleate and arachidonate in enterocyte membranes, enabling passive diffusion of fatty acids and cholesterol across the membrane for efficient chylomicron assembly. In the intestinal crypt, acts as a component of dietary-responsive phospholipid-cholesterol axis, regulating the biosynthesis of cholesterol and its mitogenic effects on intestinal stem cells.

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Gene ID 10162
Uniprot ID
Q6P1A2
Target Type Driver Suppressor Marker
Mechanism Diagram Click to View the Original Diagram
Tissue Relative Abundances of This Target
Full List of Regulator(s) of This Ferroptosis Target and Corresponding Disease/Drug Response(s)
LPCAT3 can be involved in and affect the ferroptosis by the following regulators, and result in corresponding disease/drug response(s). You can browse corresponding disease or drug response(s) resulting from the regulation of certain regulators.
Browse Regulator related Disease
hsa-miR-124-3p (miRNA)
Sepsis [ICD-11: 1G40]
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [1]
Regulator for Ferroptosis Suppressor
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
HK-2 cells Normal Homo sapiens CVCL_0302
Response Description MiR-124-3p can regulate LPCAT3 expression and affect lipid metabolism, which leads to ferroptosis. These results could provide the scientific basis for early diagnosis and renal replacement therapy in sepsis-associated acute renal injury.
Fatty acid-binding protein, heart (FABP3)
Lung cancer [ICD-11: 2C25]
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [2]
Regulator for Ferroptosis Suppressor
Pathway Response Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
H1650-ER1 cells Minimally invasive lung adenocarcinoma Homo sapiens CVCL_4V01
PC-9 cells Lung adenocarcinoma Homo sapiens CVCL_B260
NCI-H1975 cells Lung adenocarcinoma Homo sapiens CVCL_1511
NCI-H358 cells Minimally invasive lung adenocarcinoma Homo sapiens CVCL_1559
A-549 cells Lung adenocarcinoma Homo sapiens CVCL_0023
NCI-H1299 cells Lung large cell carcinoma Homo sapiens CVCL_0060
MRC-5 cells Normal Homo sapiens CVCL_0440
In Vivo Model
All athymic nude mice (6-week-old) were purchased from Jiesijie (Shanghai, China). To generate routine cell-derived xenograft (CDX) mouse models, established LUAD cells (initial 5 x 106) were subcutaneously injected into the bilateral dorsal flank of athymic nude mice. To generate H1975/A549 cell-implanted intrapulmonary LUAD mice, athymic nude mice were intrapulmonarily injected with cells (5 x 106) under anesthesia and then intranasally administered adeno-associated virus 5 (AAV5) particles (2 x 1012 viral particles/mL, Genomeditech, Shanghai, China) 3 weeks later. To generate patient-derived xenograft (PDX) mouse models, fresh LUAD tissues with a size of 2-3 mm3 were subcutaneously implanted into athymic nude mice. After successful passage, the PDX mice were used for further studies.

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Response Description Intracellular cir93-FABP3 interactions are critical to upregulate FABP3 to reduce global AA via reactions with taurine. The product of AA and taurine (i.e., NAT) prevents AA incorporation into the plasma membrane, thus further reducing the opportunity for PUFA peroxidation in the membrane. NAT reduces ACSL4, LPCAT3 and PLTP. Exosome and cir93 are critical to desensitize lung adenocarcinoma to ferroptosis.
Cir93 (circRNA)
Lung cancer [ICD-11: 2C25]
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [2]
Regulator for Ferroptosis Suppressor
Pathway Response Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
H1650-ER1 cells Minimally invasive lung adenocarcinoma Homo sapiens CVCL_4V01
PC-9 cells Lung adenocarcinoma Homo sapiens CVCL_B260
NCI-H1975 cells Lung adenocarcinoma Homo sapiens CVCL_1511
NCI-H358 cells Minimally invasive lung adenocarcinoma Homo sapiens CVCL_1559
A-549 cells Lung adenocarcinoma Homo sapiens CVCL_0023
NCI-H1299 cells Lung large cell carcinoma Homo sapiens CVCL_0060
MRC-5 cells Normal Homo sapiens CVCL_0440
In Vivo Model
All athymic nude mice (6-week-old) were purchased from Jiesijie (Shanghai, China). To generate routine cell-derived xenograft (CDX) mouse models, established LUAD cells (initial 5 x 106) were subcutaneously injected into the bilateral dorsal flank of athymic nude mice. To generate H1975/A549 cell-implanted intrapulmonary LUAD mice, athymic nude mice were intrapulmonarily injected with cells (5 x 106) under anesthesia and then intranasally administered adeno-associated virus 5 (AAV5) particles (2 x 1012 viral particles/mL, Genomeditech, Shanghai, China) 3 weeks later. To generate patient-derived xenograft (PDX) mouse models, fresh LUAD tissues with a size of 2-3 mm3 were subcutaneously implanted into athymic nude mice. After successful passage, the PDX mice were used for further studies.

    Click to Show/Hide
Response Description Intracellular cir93-FABP3 interactions are critical to upregulate FABP3 to reduce global AA via reactions with taurine. The product of AA and taurine (i.e., NAT) prevents AA incorporation into the plasma membrane, thus further reducing the opportunity for PUFA peroxidation in the membrane. NAT reduces ACSL4, LPCAT3 and PLTP. Exosome and cir93 are critical to desensitize lung adenocarcinoma to ferroptosis.
References
Ref 1 The regulation of LPCAT3 by miR-124-3p.1 in acute kidney injury suppresses cell proliferation by disrupting phospholipid metabolism. Biochem Biophys Res Commun. 2022 May 14;604:37-42. doi: 10.1016/j.bbrc.2022.03.009. Epub 2022 Mar 9.
Ref 2 Essential roles of exosome and circRNA_101093 on ferroptosis desensitization in lung adenocarcinoma. Cancer Commun (Lond). 2022 Apr;42(4):287-313. doi: 10.1002/cac2.12275. Epub 2022 Feb 20.