Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10355)
Regulator Name 1-acyl-sn-glycerol-3-phosphate acyltransferase gamma (AGPAT3)
Synonyms
LPAAT3; 1-acylglycerol-3-phosphate O-acyltransferase 3; Lysophosphatidic acid acyltransferase gamma
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Gene Name AGPAT3
Gene ID 56894
Regulator Type Protein coding
Uniprot ID Q9NRZ7
Sequence
MGLLAFLKTQFVLHLLVGFVFVVSGLVINFVQLCTLALWPVSKQLYRRLNCRLAYSLWSQ
LVMLLEWWSCTECTLFTDQATVERFGKEHAVIILNHNFEIDFLCGWTMCERFGVLGSSKV
LAKKELLYVPLIGWTWYFLEIVFCKRKWEEDRDTVVEGLRRLSDYPEYMWFLLYCEGTRF
TETKHRVSMEVAAAKGLPVLKYHLLPRTKGFTTAVKCLRGTVAAVYDVTLNFRGNKNPSL
LGILYGKKYEADMCVRRFPLEDIPLDEKEAAQWLHKLYQEKDALQEIYNQKGMFPGEQFK
PARRPWTLLNFLSWATILLSPLFSFVLGVFASGSPLLILTFLGFVGAASFGVRRLIGVTE
IEKGSSYGNQEFKKKE

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Family 1-acyl-sn-glycerol-3-phosphate acyltransferase family
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. Acts on LPA containing saturated or unsaturated fatty acids C16:0-C20:4 at the sn-1 position using C18:1, C20:4 or C18:2-CoA as the acyl donor. Also acts on lysophosphatidylcholine, lysophosphatidylinositol and lysophosphatidylserine using C18:1 or C20:4-CoA. Has a preference for arachidonoyl-CoA as a donor. Has also a modest lysophosphatidylinositol acyltransferase (LPIAT) activity, converts lysophosphatidylinositol (LPI) into phosphatidylinositol.

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HGNC ID
HGNC:326
KEGG ID hsa:56894
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
AGPAT3 can regulate the following target(s), and cause disease/drug response(s). You can browse detail information of target(s) or disease/drug response(s).
Browse Target
Browse Disease
Unspecific Target [Unspecific Target]
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Responsed Disease Hereditary Leiomyomatosis ICD-11: 2C90
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 786-O cells Renal cell carcinoma Homo sapiens CVCL_1051
769-P cells Renal cell carcinom Homo sapiens CVCL_1050
SNU-685 cells Uterine carcinosarcoma Homo sapiens CVCL_5083
Huh-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0336
HEK-293T cells Normal Homo sapiens CVCL_0063
OVCAR-8 cells High grade ovarian serous adenocarcinoma Homo sapiens CVCL_1629
SH-SY5Y cells Neuroblastoma Homo sapiens CVCL_0019
In Vivo Model
3-4 week-old, male athymic nude mice were used for hosting the 786-O tumor xenografts. In the experiment that leads to isolation of ferroptosis-resistant 1 (FR1) cells , 5 x 106 wildtype or GPX4-/-single-cell clone (originally named as #3A7 clone3, then renamed as ferroptosis-sensitive (FS) GPX4-/-cells in the present study) of 786-O-Cas9 cells were resuspended in 50 ul sterile PBS containing 50 uM Fer-1, mixed with 50 ul Matrigel (BD Biosciences), and subcutaneously injected into both flanks of the mouse.

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Response regulation Using lipidomic analysis, we found that AGPAT3-depletion selectively reduced the levels of the polyunsaturated species among both ether-linked and diacyl-phospholipids in renal cell carcinoma 786-O cells . Consistently, genetic AGPAT3-depletion suppressed sensitivity to ferroptosis.
Hereditary Leiomyomatosis [ICD-11: 2C90]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator 1-acyl-sn-glycerol-3-phosphate acyltransferase gamma (AGPAT3) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 786-O cells Renal cell carcinoma Homo sapiens CVCL_1051
769-P cells Renal cell carcinom Homo sapiens CVCL_1050
SNU-685 cells Uterine carcinosarcoma Homo sapiens CVCL_5083
Huh-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0336
HEK-293T cells Normal Homo sapiens CVCL_0063
OVCAR-8 cells High grade ovarian serous adenocarcinoma Homo sapiens CVCL_1629
SH-SY5Y cells Neuroblastoma Homo sapiens CVCL_0019
In Vivo Model
3-4 week-old, male athymic nude mice were used for hosting the 786-O tumor xenografts. In the experiment that leads to isolation of ferroptosis-resistant 1 (FR1) cells , 5 x 106 wildtype or GPX4-/-single-cell clone (originally named as #3A7 clone3, then renamed as ferroptosis-sensitive (FS) GPX4-/-cells in the present study) of 786-O-Cas9 cells were resuspended in 50 ul sterile PBS containing 50 uM Fer-1, mixed with 50 ul Matrigel (BD Biosciences), and subcutaneously injected into both flanks of the mouse.

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Response regulation Using lipidomic analysis, we found that AGPAT3-depletion selectively reduced the levels of the polyunsaturated species among both ether-linked and diacyl-phospholipids in renal cell carcinoma 786-O cells . Consistently, genetic AGPAT3-depletion suppressed sensitivity to ferroptosis.
References
Ref 1 Plasticity of ether lipids promotes ferroptosis susceptibility and evasion. Nature. 2020 Sep;585(7826):603-608. doi: 10.1038/s41586-020-2732-8. Epub 2020 Sep 16.