Molecule Information

General Information of the Molecule (ID: Mol04034)
Name
Glycerol-3-phosphate acyltransferase 3 (GPAT3) ,Homo sapiens
Synonyms
1-acyl-sn-glycerol-3-phosphate O-acyltransferase 10; 1-acyl-sn-glycerol-3-phosphate O-acyltransferase 9; Acyl-CoA:glycerol-3-phosphate acyltransferase 3; Lung cancer metastasis-associated protein 1; Lysophosphatidic acid acyltransferase theta; MAG-1
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Molecule Type
Protein
Gene Name
GPAT3
Gene ID
84803
Location
chr4:83535914-83605875[+]
Sequence
MEGAELAGKILSTWLTLVLGFILLPSVFGVSLGISEIYMKILVKTLEWATIRIEKGTPKE
SILKNSASVGIIQRDESPMEKGLSGLRGRDFELSDVFYFSKKGLEAIVEDEVTQRFSSEE
LVSWNLLTRTNVNFQYISLRLTMVWVLGVIVRYCVLLPLRVTLAFIGISLLVIGTTLVGQ
LPDSSLKNWLSELVHLTCCRICVRALSGTIHYHNKQYRPQKGGICVANHTSPIDVLILTT
DGCYAMVGQVHGGLMGIIQRAMVKACPHVWFERSEMKDRHLVTKRLKEHIADKKKLPILI
FPEGTCINNTSVMMFKKGSFEIGGTIHPVAIKYNPQFGDAFWNSSKYNMVSYLLRMMTSW
AIVCDVWYMPPMTREEGEDAVQFANRVKSAIAIQGGLTELPWDGGLKRAKVKDIFKEEQQ
KNYSKMIVGNGSLS
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Function
Converts glycerol-3-phosphate to 1-acyl-sn-glycerol-3- phosphate (lysophosphatidic acid or LPA) by incorporating an acyl moiety at the sn-1 position of the glycerol backbone (PubMed:17170135). Also converts 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 (PubMed:19318427). Protects cells against lipotoxicity (PubMed:30846318). .
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Uniprot ID
GPAT3_HUMAN
Ensembl ID
ENSG00000138678
HGNC ID
HGNC:28157
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Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens
Type(s) of Resistant Mechanism of This Molecule
  MRAP: Metabolic Reprogramming via Altered Pathways
Drug Resistance Data Categorized by Drug
Approved Drug(s)
1 drug(s) in total
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Sorafenib
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Metabolic Reprogramming via Altered Pathways (MRAP) Click to Show/Hide
Disease Class: Hepatocellular carcinoma [ICD-11: 2C12.02] [1]
Metabolic Type Lipid metabolism
Resistant Disease Hepatocellular carcinoma [ICD-11: 2C12.02]
 Disease Info 
Resistant Drug Sorafenib
 Drug Info 
Molecule Alteration Expression
Up-regulation
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation IL-17 signaling pathway Activation hsa04657
EGFR tyrosine kinase inhibitor resistance Activation hsa01521
In Vivo Model Four-week-old male B-NDG? mice, each subgroup of cells Mice
Experiment for
Molecule Alteration		 Western blot analysis; LC/MS
Mechanism Description In this study, we observed a significant increase in TAG accumulation in SR HCC cells. Through multi-omics analysis, we identified upregulated GPAT3 as the key enzyme involved in sorafenib resistance. Transcriptional activation of GPAT3 in SR is mediated by STAT3, which directly binds to the GPAT3 promoter. Loss- and gain-of-function experiments demonstrated that GPAT3 promotes sorafenib resistance in HCC by enhancing TAG-mediated NF-kappaB/Bcl5 signaling pathway.
Disease Class: Hepatocellular carcinoma [ICD-11: 2C12.02] [1]
Metabolic Type Lipid metabolism
Resistant Disease Hepatocellular carcinoma [ICD-11: 2C12.02]
 Disease Info 
Resistant Drug Sorafenib
 Drug Info 
Molecule Alteration Expression
Up-regulation
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation IL-17 signaling pathway Activation hsa04657
EGFR tyrosine kinase inhibitor resistance Activation hsa01521
In Vitro Model Knockdown GPAT3 in Hep3B SR cells Liver Homo sapiens (Human) CVCL_0326
Knockdown GPAT3 in MHCC97H SR cells Liver Homo sapiens (Human) CVCL_4972
Experiment for
Molecule Alteration		 ChIP and western blot
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description Our data demonstrate that GPAT3 elevation in HCC cells reprograms triglyceride metabolism which contributes to acquired resistance to sorafenib, which suggests GPAT3 as a potential target for enhancing the sensitivity of HCC to sorafenib.
Disease Class: Hepatocellular carcinoma [ICD-11: 2C12.02] [1]
Metabolic Type Lipid metabolism
Resistant Disease Hepatocellular carcinoma [ICD-11: 2C12.02]
 Disease Info 
Resistant Drug Sorafenib
 Drug Info 
Molecule Alteration Expression
Up-regulation
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation IL-17 signaling pathway Activation hsa04657
EGFR tyrosine kinase inhibitor resistance Activation hsa01521
In Vitro Model Hep3B cells Liver Homo sapiens (Human) CVCL_0326
Experiment for
Molecule Alteration		 Western blot analysis; LC/MS
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description In this study, we observed a significant increase in TAG accumulation in SR HCC cells. Through multi-omics analysis, we identified upregulated GPAT3 as the key enzyme involved in sorafenib resistance. Transcriptional activation of GPAT3 in SR is mediated by STAT3, which directly binds to the GPAT3 promoter. Loss- and gain-of-function experiments demonstrated that GPAT3 promotes sorafenib resistance in HCC by enhancing TAG-mediated NF-kappaB/Bcl2 signaling pathway.
Disease Class: Hepatocellular carcinoma [ICD-11: 2C12.02] [1]
Metabolic Type Lipid metabolism
Resistant Disease Hepatocellular carcinoma [ICD-11: 2C12.02]
 Disease Info 
Resistant Drug Sorafenib
 Drug Info 
Molecule Alteration Expression
Up-regulation
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation IL-17 signaling pathway Activation hsa04657
EGFR tyrosine kinase inhibitor resistance Activation hsa01521
In Vitro Model MHCC97H cells Liver Homo sapiens (Human) CVCL_4972
Experiment for
Molecule Alteration		 Western blot analysis; LC/MS
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description In this study, we observed a significant increase in TAG accumulation in SR HCC cells. Through multi-omics analysis, we identified upregulated GPAT3 as the key enzyme involved in sorafenib resistance. Transcriptional activation of GPAT3 in SR is mediated by STAT3, which directly binds to the GPAT3 promoter. Loss- and gain-of-function experiments demonstrated that GPAT3 promotes sorafenib resistance in HCC by enhancing TAG-mediated NF-kappaB/Bcl3 signaling pathway.
Disease Class: Hepatocellular carcinoma [ICD-11: 2C12.02] [1]
Metabolic Type Lipid metabolism
Resistant Disease Hepatocellular carcinoma [ICD-11: 2C12.02]
 Disease Info 
Resistant Drug Sorafenib
 Drug Info 
Molecule Alteration Expression
Up-regulation
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation IL-17 signaling pathway Activation hsa04657
EGFR tyrosine kinase inhibitor resistance Activation hsa01521
In Vitro Model HEK 293T cells Kidney Homo sapiens (Human) CVCL_0063
Experiment for
Molecule Alteration		 Western blot analysis; LC/MS
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description In this study, we observed a significant increase in TAG accumulation in SR HCC cells. Through multi-omics analysis, we identified upregulated GPAT3 as the key enzyme involved in sorafenib resistance. Transcriptional activation of GPAT3 in SR is mediated by STAT3, which directly binds to the GPAT3 promoter. Loss- and gain-of-function experiments demonstrated that GPAT3 promotes sorafenib resistance in HCC by enhancing TAG-mediated NF-kappaB/Bcl4 signaling pathway.
Disease Class: Hepatocellular carcinoma [ICD-11: 2C12.02] [1]
Metabolic Type Lipid metabolism
Resistant Disease Hepatocellular carcinoma [ICD-11: 2C12.02]
 Disease Info 
Resistant Drug Sorafenib
 Drug Info 
Molecule Alteration Expression
Up-regulation
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation IL-17 signaling pathway Activation hsa04657
EGFR tyrosine kinase inhibitor resistance Activation hsa01521
In Vitro Model HEK 293T cells Kidney Homo sapiens (Human) CVCL_0063
Hep3B cells Liver Homo sapiens (Human) CVCL_0326
MHCC97H cells Liver Homo sapiens (Human) CVCL_4972
Hep3B cells Liver Homo sapiens (Human) CVCL_0326
Sorafenib-resistant MHCC97H cells Liver Homo sapiens (Human) CVCL_4972
Experiment for
Molecule Alteration		 ChIP and western blot
Experiment for
Drug Resistance		 IC50 assay
Mechanism Description Our data demonstrate that GPAT3 elevation in HCC cells reprograms triglyceride metabolism which contributes to acquired resistance to sorafenib, which suggests GPAT3 as a potential target for enhancing the sensitivity of HCC to sorafenib.
Disease Class: Hepatocellular carcinoma [ICD-11: 2C12.02] [1]
Metabolic Type Lipid metabolism
Resistant Disease Hepatocellular carcinoma [ICD-11: 2C12.02]
 Disease Info 
Resistant Drug Sorafenib
 Drug Info 
Molecule Alteration Expression
Up-regulation
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation IL-17 signaling pathway Activation hsa04657
EGFR tyrosine kinase inhibitor resistance Activation hsa01521
In Vivo Model MHCC97H subcutaneous tumor-bearing model Mice
Experiment for
Molecule Alteration		 ChIP and western blot
Experiment for
Drug Resistance		 Tumor growth assay
Mechanism Description Our data demonstrate that GPAT3 elevation in HCC cells reprograms triglyceride metabolism which contributes to acquired resistance to sorafenib, which suggests GPAT3 as a potential target for enhancing the sensitivity of HCC to sorafenib.
Disease Class: Hepatocellular carcinoma [ICD-11: 2C12.02] [1]
Metabolic Type Lipid metabolism
Resistant Disease Hepatocellular carcinoma [ICD-11: 2C12.02]
 Disease Info 
Resistant Drug Sorafenib
 Drug Info 
Molecule Alteration Expression
Up-regulation
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation IL-17 signaling pathway Activation hsa04657
EGFR tyrosine kinase inhibitor resistance Activation hsa01521
In Vivo Model SR xenografts, four-week-old male B-NDG? mice; control SR-MHCC97H group, four-week-old male B-NDG? mice Mice
Experiment for
Molecule Alteration		 ChIP and western blot
Experiment for
Drug Resistance		 Tumor volume assay
Mechanism Description Our data demonstrate that GPAT3 elevation in HCC cells reprograms triglyceride metabolism which contributes to acquired resistance to sorafenib, which suggests GPAT3 as a potential target for enhancing the sensitivity of HCC to sorafenib.
References
Ref 1 GPAT3 is a potential therapeutic target to overcome sorafenib resistance in hepatocellular carcinoma. Theranostics. 2024 Jun 1;14(9):3470-3485.

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