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Information on EC 2.3.1.15 - glycerol-3-phosphate 1-O-acyltransferase and Organism(s) Mus musculus and UniProt Accession Q14DK4
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2.3.1.15 glycerol-3-phosphate 1-O-acyltransferaseIUBMB Comments
Acyl-[acyl-carrier protein] can also act as acyl donor. The enzyme acts only on derivatives of fatty acids of chain length larger than C10.
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Word Map
- 2.3.1.15
-
gpats
- triacylglycerols
- phospholipid
-
phosphatidic
- glycerolipids
- acyl-coas
- triglyceride
- diacylglycerol
- adipose
-
lysophosphatidic
- peroxisome
-
lipogenesis
-
lipogenic
- adipocytes
- palmitate
- sterol
- phosphatidylcholine
- palmitoyl-coa
-
phosphohydrolase
- glycerophospholipids
- carnitine
- steatosis
- esterification
- stearoyl-coa
- dihydroxyacetone
-
1-acylglycerol-3-phosphate
- cutin
- srebp-1
- phosphatidylglycerol
- palmitoyltransferase
- oleoyl-coa
-
acyl-acyl
- cytidylyltransferase
- squash
-
desaturase-1
- monoacylglycerol
- protein-1c
- acaca
- suberin
- synthesis
- nutrition
-
cholinephosphotransferase
-
insig1
-
lipins
- medicine
- energy production
- biotechnology
The taxonomic range for the selected organisms is: Mus musculus
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Synonyms
glycerol-3-phosphate acyltransferase, gpat1, glycerophosphate acyltransferase, sn-glycerol-3-phosphate acyltransferase, gpat2, gpat3, gpat4, agpat6, agpat, gat1p, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
glycerol-3-phosphate acyltransferase 2
3-glycerophosphate acyltransferase
-
-
-
-
ACP:sn-glycerol-3-phosphate acyltransferase
-
-
-
-
acyltransferase, glycerol phosphate
-
-
-
-
AGPAT6
alpha-glycerophosphate acyltransferase
-
-
-
-
glycerol 3-phosphate acyltransferase
-
-
-
-
glycerol phosphate acyltransferase
-
-
-
-
glycerol phosphate transacylase
-
-
-
-
glycerol-3-phosphate acyltransferase
glycerol-3-phosphate acyltransferase 1
glycerol-3-phosphate acyltransferase 3
glycerol-3-phosphate acyltransferase 4
glycerol-3-phosphate acyltransferase-1
-
-
glycerophosphate acyltransferase
-
-
-
-
glycerophosphate transacylase
-
-
-
-
GPAT-1
GPAT1
GPAT3
GPAT4
Sn-glycerol 3-phosphate acyltransferase
-
-
-
-
glycerol-3-phosphate acyltransferase 2
four isoenzymes are identified in mammals
glycerol-3-phosphate acyltransferase 1
four isoenzymes are identified in mammals
glycerol-3-phosphate acyltransferase 3
four isoenzymes are identified in mammals
glycerol-3-phosphate acyltransferase 4
four isoenzymes are identified in mammals
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
acyl-CoA + sn-glycerol 3-phosphate = CoA + 1-acyl-sn-glycerol 3-phosphate
the active site is composed of homology regions I-IV
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Acyl group transfer
Acyl group transfer
-
-
-
-
PATHWAY SOURCE
PATHWAYS
-
-, -, -, -, -, -, -, -, -
SYSTEMATIC NAME
IUBMB Comments
acyl-CoA:sn-glycerol-3-phosphate 1-O-acyltransferase
Acyl-[acyl-carrier protein] can also act as acyl donor. The enzyme acts only on derivatives of fatty acids of chain length larger than C10.
CAS REGISTRY NUMBER
COMMENTARY
9029-96-3
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
fatty acyl-CoA + glycerol-3-phosphate
CoA + lysophosphatidic acid
-
-
-
?
palmitoyl-CoA + glycerol-3-phosphate
CoA + 1-palmitoyl-sn-glycerol 3-phosphate
activity assay
-
-
?
lauroyl-CoA + sn-glycerol 3-phosphate
CoA + 1-lauroyl-sn-glycerol 3-phosphate
-
-
-
-
?
stearoyl-CoA + sn-glycerol 3-phosphate
CoA + 1-stearoyl-sn-glycerol 3-phosphate
-
less than 20% of activity with palmitoyl-CoA
-
?
acyl-CoA + sn-glycerol 3-phosphate
CoA + 1-acyl-sn-glycerol 3-phosphate
-
-
-
?
acyl-CoA + sn-glycerol 3-phosphate
CoA + 1-acyl-sn-glycerol 3-phosphate
-
-
-
-
?
acyl-CoA + sn-glycerol 3-phosphate
CoA + 1-acyl-sn-glycerol 3-phosphate
-
-
-
?
acyl-CoA + sn-glycerol 3-phosphate
CoA + 1-acyl-sn-glycerol 3-phosphate
-
-
-
?
acyl-CoA + sn-glycerol 3-phosphate
CoA + 1-acyl-sn-glycerol 3-phosphate
GPAT2 shows no acyl-CoA specificity
-
-
?
acyl-CoA + sn-glycerol 3-phosphate
CoA + 1-acyl-sn-glycerol 3-phosphate
-
-
-
-
?
acyl-CoA + sn-glycerol 3-phosphate
CoA + 1-acyl-sn-glycerol 3-phosphate
-
-
-
?
acyl-CoA + sn-glycerol 3-phosphate
CoA + 1-acyl-sn-glycerol 3-phosphate
-
-
-
?
acyl-CoA + sn-glycerol 3-phosphate
CoA + 1-acyl-sn-glycerol 3-phosphate
-
-
-
?
acyl-CoA + sn-glycerol 3-phosphate
CoA + 1-acyl-sn-glycerol 3-phosphate
-
-
-
?
acyl-CoA + sn-glycerol 3-phosphate
CoA + 1-acyl-sn-glycerol 3-phosphate
-
i.e. lysophosphatidic acid
-
?
acyl-CoA + sn-glycerol 3-phosphate
CoA + 1-acyl-sn-glycerol 3-phosphate
-
no activity with hexanoyl-CoA, enzyme prefers saturated fatty acyl-CoAs
-
?
acyl-CoA + sn-glycerol 3-phosphate
CoA + 1-acyl-sn-glycerol 3-phosphate
-
enzyme catalyzes the initial and rate-limiting step of glycerolipid synthesis with long-chain acyl-CoAs
-
-
?
acyl-CoA + sn-glycerol 3-phosphate
CoA + 1-acyl-sn-glycerol 3-phosphate
-
key enzyme in de novo triacylglycerol synthesis
-
-
?
acyl-CoA + sn-glycerol 3-phosphate
CoA + 1-acyl-sn-glycerol 3-phosphate
-
acylation of sn-glycerol 3-phosphate with longchain acyl-CoA
-
-
?
acyl-CoA + sn-glycerol 3-phosphate
CoA + 1-acyl-sn-glycerol 3-phosphate
acyl-CoA specificity of GPAT1 is 16:0 > 18:0 > 18:1
-
-
?
acyl-CoA + sn-glycerol 3-phosphate
CoA + 1-acyl-sn-glycerol 3-phosphate
GPAT3 shows a specificity for 16:0, 18:1, 18:2 acyl-CoAs
-
-
?
acyl-CoA + sn-glycerol 3-phosphate
CoA + 1-acyl-sn-glycerol 3-phosphate
GPAT4 shows no acyl-CoA specificity
-
-
?
fatty acyl-CoA + glycerol-3-phosphate
CoA + lysophosphatidic acid
-
long-chain fatty acyl-CoA
-
-
?
oleoyl-CoA + sn-glycerol 3-phosphate
CoA + 1-oleoyl-sn-glycerol 3-phosphate
-
-
-
-
?
oleoyl-CoA + sn-glycerol 3-phosphate
CoA + 1-oleoyl-sn-glycerol 3-phosphate
-
-
-
?
palmitoyl-CoA + sn-glycerol 3-phosphate
CoA + 1-palmitoyl-sn-glycerol 3-phosphate
-
-
-
?
palmitoyl-CoA + sn-glycerol 3-phosphate
CoA + 1-palmitoyl-sn-glycerol 3-phosphate
-
-
-
?
palmitoyl-CoA + sn-glycerol 3-phosphate
CoA + 1-palmitoyl-sn-glycerol 3-phosphate
-
recombinant mitochondrial acyltransferase prefers palmitoyl-CoA over oleoyl-CoA
-
?
palmitoyl-CoA + sn-glycerol 3-phosphate
CoA + 1-palmitoyl-sn-glycerol 3-phosphate
-
best acyl-donor
-
?
palmitoyl-CoA + sn-glycerol 3-phosphate
CoA + 1-palmitoyl-sn-glycerol 3-phosphate
-
preferred substrate of isozyme mtGPAT1, not of isozyme mtGPAT2
-
-
?
additional information
?
-
-
the mitochondrial and microsomal isozymes show different substrate specificity
-
-
?
additional information
?
-
-
mtGPAT1 is essential for normal acyl-CoA metabolism: The absence of hepatic mtGPAT1 results in the partitioning of fatty acids away from triacylglycerol synthesis and toward oxidation and ketogenesis
-
-
?
additional information
?
-
GPAT1 preferentially catalyzes saturated fatty acids (FAs) (palmitate or C16:0) and selectively transfers acyl-CoA to the sn-1 position of glycerol 3-phosphate. Subsequently, lysophosphatidic acid, phosphatidic acid, and diacylglycerol are produced in the glycerophospholipid pathway
-
-
-
additional information
?
-
GPAT1 preferentially catalyzes saturated fatty acids (FAs) (palmitate or C16:0) and selectively transfers acyl-CoA to the sn-1 position of glycerol 3-phosphate. Subsequently, lysophosphatidic acid, phosphatidic acid, and diacylglycerol are produced in the glycerophospholipid pathway
-
-
-
additional information
?
-
GPAT1 preferentially catalyzes saturated fatty acids (FAs) (palmitate or C16:0) and selectively transfers acyl-CoA to the sn-1 position of glycerol 3-phosphate. Subsequently, lysophosphatidic acid, phosphatidic acid, and diacylglycerol are produced in the glycerophospholipid pathway
-
-
-
additional information
?
-
GPAT1 preferentially catalyzes saturated fatty acids (FAs) (palmitate or C16:0) and selectively transfers acyl-CoA to the sn-1 position of glycerol 3-phosphate. Subsequently, lysophosphatidic acid, phosphatidic acid, and diacylglycerol are produced in the glycerophospholipid pathway
-
-
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
acyl-CoA + sn-glycerol 3-phosphate
CoA + 1-acyl-sn-glycerol 3-phosphate
-
-
-
?
acyl-CoA + sn-glycerol 3-phosphate
CoA + 1-acyl-sn-glycerol 3-phosphate
-
-
-
-
?
acyl-CoA + sn-glycerol 3-phosphate
CoA + 1-acyl-sn-glycerol 3-phosphate
-
-
-
?
acyl-CoA + sn-glycerol 3-phosphate
CoA + 1-acyl-sn-glycerol 3-phosphate
-
-
-
?
acyl-CoA + sn-glycerol 3-phosphate
CoA + 1-acyl-sn-glycerol 3-phosphate
-
-
-
-
?
acyl-CoA + sn-glycerol 3-phosphate
CoA + 1-acyl-sn-glycerol 3-phosphate
-
-
-
?
acyl-CoA + sn-glycerol 3-phosphate
CoA + 1-acyl-sn-glycerol 3-phosphate
-
-
-
?
acyl-CoA + sn-glycerol 3-phosphate
CoA + 1-acyl-sn-glycerol 3-phosphate
-
-
-
?
acyl-CoA + sn-glycerol 3-phosphate
CoA + 1-acyl-sn-glycerol 3-phosphate
-
-
-
?
acyl-CoA + sn-glycerol 3-phosphate
CoA + 1-acyl-sn-glycerol 3-phosphate
-
i.e. lysophosphatidic acid
-
?
acyl-CoA + sn-glycerol 3-phosphate
CoA + 1-acyl-sn-glycerol 3-phosphate
-
enzyme catalyzes the initial and rate-limiting step of glycerolipid synthesis with long-chain acyl-CoAs
-
-
?
acyl-CoA + sn-glycerol 3-phosphate
CoA + 1-acyl-sn-glycerol 3-phosphate
-
key enzyme in de novo triacylglycerol synthesis
-
-
?
acyl-CoA + sn-glycerol 3-phosphate
CoA + 1-acyl-sn-glycerol 3-phosphate
-
acylation of sn-glycerol 3-phosphate with longchain acyl-CoA
-
-
?
additional information
?
-
-
mtGPAT1 is essential for normal acyl-CoA metabolism: The absence of hepatic mtGPAT1 results in the partitioning of fatty acids away from triacylglycerol synthesis and toward oxidation and ketogenesis
-
-
?
additional information
?
-
GPAT1 preferentially catalyzes saturated fatty acids (FAs) (palmitate or C16:0) and selectively transfers acyl-CoA to the sn-1 position of glycerol 3-phosphate. Subsequently, lysophosphatidic acid, phosphatidic acid, and diacylglycerol are produced in the glycerophospholipid pathway
-
-
-
additional information
?
-
GPAT1 preferentially catalyzes saturated fatty acids (FAs) (palmitate or C16:0) and selectively transfers acyl-CoA to the sn-1 position of glycerol 3-phosphate. Subsequently, lysophosphatidic acid, phosphatidic acid, and diacylglycerol are produced in the glycerophospholipid pathway
-
-
-
additional information
?
-
GPAT1 preferentially catalyzes saturated fatty acids (FAs) (palmitate or C16:0) and selectively transfers acyl-CoA to the sn-1 position of glycerol 3-phosphate. Subsequently, lysophosphatidic acid, phosphatidic acid, and diacylglycerol are produced in the glycerophospholipid pathway
-
-
-
additional information
?
-
GPAT1 preferentially catalyzes saturated fatty acids (FAs) (palmitate or C16:0) and selectively transfers acyl-CoA to the sn-1 position of glycerol 3-phosphate. Subsequently, lysophosphatidic acid, phosphatidic acid, and diacylglycerol are produced in the glycerophospholipid pathway
-
-
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2-(nonylsulfonamido)benzoic acid
i.e. FSG67a, GPAT inhibitor, has a broad spectrum inhibitory effect on GPAT activity, metabolic effects in mice, overview
AMP-activated protein kinase
-
AMP-activated protein kinase reciprocally regulates GPAT1
-
cyclohexandione
50 mM, almost complete inhibition of mitochondrial acyltransferase
dihydroxyacetonephosphate
-
competitive inhibition of isozyme mtGPAT2, no inhibition of isozyme mtGPAT1
Phenylglyoxal
50 mM, approx. 70% inhibition of mitochondrial acyltransferase
2-(nonylsulfonamido)benzoic acid
i.e. FSG67a, GPAT inhibitor, has a broad spectrum inhibitory effect on GPAT activity, metabolic effects in mice, overview
2-(nonylsulfonamido)benzoic acid
i.e. FSG67a, GPAT inhibitor, has a broad spectrum inhibitory effect on GPAT activity, metabolic effects in mice, overview. GPAT4 activity is significantly reduced in the liver, brown adipose tissue, and mammary gland as compared to the control group, but is normal in inguinal adipose tissue
additional information
-
recombinant mitochondrial acyl transferase, not inhibited by N-ethylmaleimide
-
additional information
-
no inhibition by malonyl-CoA, substrate inhibition by acyl-CoAs at concentrations above 0.075 mM
-
additional information
mitochondrial GPAT1 is resistant to inactivation induced by sulfhydryl-group modifying reagents like N-ethylmaleimide (NEM)
-
additional information
mitochondrial GPAT1 is resistant to inactivation induced by sulfhydryl-group modifying reagents like N-ethylmaleimide (NEM)
-
additional information
mitochondrial GPAT1 is resistant to inactivation induced by sulfhydryl-group modifying reagents like N-ethylmaleimide (NEM)
-
additional information
mitochondrial GPAT1 is resistant to inactivation induced by sulfhydryl-group modifying reagents like N-ethylmaleimide (NEM)
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
rosiglitazone
GPAT3 activity increase in the white adipose tissue of diabetic mice after treatment with rosiglitazone, which is a PPAR-gamma agonist
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.3
sn-glycerol 3-phosphate
-
pH 7.5, 22°C, isozyme mtGPAT1-knockout-mice mitochondria
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.00013
-
in hearts from wild-type mice, N-ethylmaleimide resistant GPAT activity, 27% of the total activity
0.0002
-
with empty pcDNA3.1 vector transfected COS-7 cells, N-ethylmaleimide resistant
0.00025
-
in hearts from wild-type mice, mitochondrial fraction, N-ethylmaleimide resistant GPAT activity, 43% of the total activity
0.0003
0.003
-
with empty pcDNA3.1 vector transfected COS-7 cells, N-ethylmaleimide sensitive
0.0042
-
with pcDNA3.1-GPAT2 transfected COS-7 cells, N-ethylmaleimide sensitive
additional information
0.0003
-
with pcDNA3.1-GPAT2 transfected COS-7 cells, N-ethylmaleimide resistant
additional information
GPAT2 activity constitutes 60% of GPAT activity in purified mitochondria from wild-type mouse liver
additional information
GPAT2 activity constitutes 60% of GPAT activity in purified mitochondria from wild-type mouse liver
additional information
GPAT2 activity constitutes 60% of GPAT activity in purified mitochondria from wild-type mouse liver
additional information
GPAT2 activity constitutes 60% of GPAT activity in purified mitochondria from wild-type mouse liver
additional information
-
GPAT2 activity constitutes 60% of GPAT activity in purified mitochondria from wild-type mouse liver
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.5
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
the expression of GPAT2 is downregulated when 3T3-L1 cells differentiate into adipocytes, while GPAT1, 3, and 4 are upregulated (10fold, over 60, and 5fold, respectively)
GPAT3 colocalize with the PAT (perilipin) family protein TIP47 (PLIN3) to the apical surface of the enterocyte
during lactation, GPAT4 mRNA is highly expressed in mammary gland epithelium, but not in the surrounding adipocytes of breast tissue
GPAT4 is expressed in around spermatids but not elongated spermatids during later spermiogenesis
additional information
GPAT2 expression in mouse testis fluctuates during sexual maturation, Gpat2 expression in mouse testis is maximal at the pachytene stage
GPAT2 is mainly expressed in pachytene spermatocytes of testis
Gpat3 mRNA increases 60fold during differentiation of 3T3-L1 preadipocytes to mature adipocytes, suggesting a critical role in adipocytes
-
GPAT3 mRNA is dramatically upregulated during adipocyte differentiation
the expression of GPAT2 is downregulated when 3T3-L1 cells differentiate into adipocytes, while GPAT1, 3, and 4 are upregulated (10fold, over 60, and 5fold, respectively)
the expression of GPAT2 is downregulated when 3T3-L1 cells differentiate into adipocytes, while GPAT1, 3, and 4 are upregulated 10fold, over 60fold, and 5fold, respectively
highest expression in white adipose tissue, moderate in brown adipose tissue
brown and white, high expression level
hypothesis: increased hepatic mtGPAT activity associated with obesity and insulin resistance contributes to increased triacylglycerol biosynthesis and inhibition of fatty acid oxidation, responses that would promote hepatic steatosis and dyslipidemia
-
mitochondrial glycerol-3-phosphate acyltransferase-1 is essential in liver for the metabolism of excess acyl-CoAs
GPAT4 accounts for the primary microsomal GPAT activity in liver
high expression level, GPAT3 expression analysis throughout the small intestine reveals that GPAT3 is abundantly expressed in the apical surface of enterocytes in the small intestine
expression detected by RT-PCR: GPAT4 is strongly expressed in testis. First expression is detected in mice at 2 weeks postnatally. Expression is abundant from the third week, plateaus at week 5-6 and then maintains at a high level in the adult
GPAT4 is widely expressed postnatally in spermatocytes and around spermatids in mice testis
additional information
GPAT2 mRNA expression is increased and the content of triacylglycerol is significantly elevated in testis during sexual maturation in mice. Tissue distribution, overview
additional information
GPAT2 mRNA expression is increased and the content of triacylglycerol is significantly elevated in testis during sexual maturation in mice. Tissue distribution, overview
additional information
GPAT2 mRNA expression is increased and the content of triacylglycerol is significantly elevated in testis during sexual maturation in mice. Tissue distribution, overview
additional information
GPAT2 mRNA expression is increased and the content of triacylglycerol is significantly elevated in testis during sexual maturation in mice. Tissue distribution, overview
additional information
the GPAT2 isoform expression is restricted to male germ cells and cancer cells
additional information
-
the GPAT2 isoform expression is restricted to male germ cells and cancer cells
additional information
GPAT3 is predominantly expressed in the small intestine and adipose tissue, tissue distribution and expression pattern, overview
additional information
-
GPAT3 is predominantly expressed in the small intestine and adipose tissue, tissue distribution and expression pattern, overview
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
exogenously expressed protein. Isoform GPAT2 protein has two transmembrane segments and the N-terminal and C-terminal regions face the cytoplasm. The enzymatically active motifs I-III of the GPAT2 protein face the cytosol, while motif IV is within the membrane
GPAT1 possesses a conserved acyltransferase domain and two transmembrane domains, with the N- and C-terminal domains facing the cytosol, and forms a stem loop structure in the mitochondrial intermembrane space. The active site of acyltransferase is close to the N-terminal domain toward the cytosol, while the C-terminal domain is suggested to have a regulatory function
-
2 isozymes in mitochondria, mitochondrial isozymes mtGPAT1 and mtGPAT2
additional information
analysis of subcellular localization of GPAT isozymes, overview. Isozymes GPAT1 and GPAT2 are localized in the mitochondrial outer membrane, and isozymes GPAT3 and GPAT4 are localized in the endoplasmic reticulum membrane
-
additional information
analysis of subcellular localization of GPAT isozymes, overview. Isozymes GPAT1 and GPAT2 are localized in the mitochondrial outer membrane, and isozymes GPAT3 and GPAT4 are localized in the endoplasmic reticulum membrane
-
additional information
analysis of subcellular localization of GPAT isozymes, overview. Isozymes GPAT1 and GPAT2 are localized in the mitochondrial outer membrane, and isozymes GPAT3 and GPAT4 are localized in the endoplasmic reticulum membrane
-
additional information
analysis of subcellular localization of GPAT isozymes, overview. Isozymes GPAT1 and GPAT2 are localized in the mitochondrial outer membrane, and isozymes GPAT3 and GPAT4 are localized in the endoplasmic reticulum membrane
-
additional information
analysis of subcellular localization of GPAT isozymes, overview. Isozymes GPAT1 and GPAT2 are localized in the mitochondrial outer membrane, and isozymes GPAT3 and GPAT4 are localized in the endoplasmic reticulum membrane
-
additional information
analysis of subcellular localization of GPAT isozymes, overview. Isozymes GPAT1 and GPAT2 are localized in the mitochondrial outer membrane, and isozymes GPAT3 and GPAT4 are localized in the endoplasmic reticulum membrane
-
additional information
analysis of subcellular localization of GPAT isozymes, overview. Isozymes GPAT1 and GPAT2 are localized in the mitochondrial outer membrane, and isozymes GPAT3 and GPAT4 are localized in the endoplasmic reticulum membrane
-
additional information
analysis of subcellular localization of GPAT isozymes, overview. Isozymes GPAT1 and GPAT2 are localized in the mitochondrial outer membrane, and isozymes GPAT3 and GPAT4 are localized in the endoplasmic reticulum membrane
-
additional information
in most tissues, GPAT3 and/or GPAT4 activity in the endoplasmic reticulum is 10fold greater than mitochondrial activity
-
additional information
in most tissues, GPAT3 and/or GPAT4 activity in the endoplasmic reticulum is 10fold greater than mitochondrial activity
-
additional information
in most tissues, GPAT3 and/or GPAT4 activity in the endoplasmic reticulum is 10fold greater than mitochondrial activity
-
additional information
in most tissues, GPAT3 and/or GPAT4 activity in the endoplasmic reticulum is 10fold greater than mitochondrial activity
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
the gene is silenced in vivo by inoculating lentiviral particles carrying the sequence of a short-hairpin RNA targeting Gpat2 mRNA into mouse testis. Histological and gene expression analysis shows impaired spermatogenesis and arrest at the pachytene stage. The enzyme deficiency triggers apoptotic mechanisms and affects reproductive capacity
metabolism
physiological function
malfunction
metabolism
physiological function
additional information
metabolism
relation between three isoforms GPAT1, 3, and 4 and insulin resistance, overview. GPAT2 may play an important role in the regulation of reproductive system
metabolism
substrate channeling in the glycerol-3-phosphate pathway regulates the synthesis, storage and secretion of glycerolipids. The successive acylation of glycerol-3-phosphate (G3P) by glycerol-3-phosphate acyltransferases and acylglycerol-3-phosphate acyltransferases produces phosphatidic acid (PA), a precursor for CDP-diacylglycerol-dependent phospholipid synthesis. PA is further dephosphorylated by LIPINs to produce diacylglycerol (DG), a substrate for the synthesis of triglyceride (TG) by DG acyltransferases and a precursor for phospholipid synthesis via the CDP-choline and CDP-ethanolamine (Kennedy) pathways. The channeling of fatty acids into TG for storage in lipid droplets and secretion in lipoproteins or phospholipids for membrane biogenesis is dependent on isoform expression, activity and localization of G3P pathway enzymes, as well as dietary and hormonal and tissue-specific factors. Mechanisms that control partitioning of substrates into lipid products of the G3P pathway, overview
physiological function
glycerol-3-phosphate acyltransferases (GPAT) catalyze the first and rate-limiting step in the de novo glycerolipid synthesis. Glycerol-3-phosphate acyltransferase 2 is essential for normal spermatogenesis. GPAT is regulated by epigenetic mechanisms in combination with vitamin A derivatives, analysis of GPAT2 role in the developing male germ cells, overview. GPAT2 protein is necessary for the normal development of male gonocytes. GPAT2 is necessary to reach or to complete the pachytene stage in which GPAT2 interacts with MILI to synthesize piRNAs by the primary pathway
physiological function
GPATs play a pivotal role in the regulation of triglyceride and phospholipid synthesis. GPATs play a critical role in the development of obesity, hepatic steatosis, and insulin resistance. GPAT2 is a murine MILI (mouse Piwi-like)-binding protein and is also involved in the primary biosynthesis of piRNA, which interacts with PIWI. GPAT2 expression is unchanged in fasted or fasted-refed rodents, further implying that GPAT2 is unrelated to triacylglycerol synthesis or energy storage in the liver, and its transcription might not be under the regulation of SREBP1 or ChREBP. GPAT2 may play an important role in the regulation of reproductive system
malfunction
GPAT1 -/- mice contain reduced amounts of C16:0 and increased C18:0 and C18:1 in liver phosphatidylcholine and phosphatidylethanolamine. Phosphatidylcholine and phosphatidylethanolamine in Gpat1-/- liver also contain 40% more C20:4 at the sn-2 position, suggesting that esterification at the sn-2 position is influenced by fatty acids at the sn-1 position. GPAT1 overexpression in liver of mice leads to increased incorporation of C16:0 fatty acids into lysophosphatidic acid, diacylglycerol, triacylglycerol
malfunction
GPAT1-deficient mice fed a high-fat/high sucrose diet have reduced hepatic triacylglycerol but increased plasma beta-hydroxybutyrate and liver acylcarnitine levels, suggesting enhanced beta-oxidation. In the high-fat-fed GPAT1-deficient mice, elevated beta-oxidation is associated with increased hepatic acyl-CoA content and activation state of AMP-activated protein kinase. These results suggest that enhanced beta-oxidation represents increased energy flow to fatty acid oxidation caused by a blockage of the glycerolipid synthesis pathway. In GPAT1-overexpressing mice, liver fatty acid oxidation measured ex vivo is decreased. Due to the enhanced beta-oxidation in Gpat1-/- mice, liver mitochondria exhibit a greater mitochondrial dysfunction (oxidative stress, increased hepatocyte apoptosis, lower level odf DNA repair genes)
malfunction
Gpat4-/- mice have severely impaired lactation, a reduced size and number of alveoli, reduced numbers of fat droplets in mammary gland, and reduced triacylglycerol and diacylglycerol content in milk. Gonadal white adipose tissue mass and plasma leptin levels are reduced in Gpat4-/- mice, and subdermal adipose tissue, is nearly absent. The reduced body weight of Gpat4-/- mice is associated with increased energy expenditure
malfunction
-
livers and hearts from mice deficient in GPAT1 (Gpat1 -/-) have a decreased content of glycerolipid intermediates and triacylglycerol, an altered composition of liver phospholipids, and elevated markers of oxidative stress. Compared with control C57BL/6 mice, infection of Gpat1 -/- mice with coxsackievirus B3 results in higher mortality, an 50% increase in heart pathology, a significant increase in liver viral titers, and a 100fold increase in heart viral titers. Heart mRNA levels for proinflammatory cytokines TNF-alpha, IL-6, and IL-1B are increased in the Gpat1-/- mice. Loss of Gpat1 also results in dysregulation of specific immune cells
malfunction
-
T-lymphocyte proliferation is inhibited and activation induced apoptosis is increased in GPAT-1 knockout mice. Th-1 (IL-2 and IFN-gamma) cytokine secretion is reduced, and Th-2 (IL-4 and IL-10) cytokine secretion is increased. An increased arachidonate content and subsequent increased prostaglandin E2 secretion is shown in knockout mice, which may inhibit T-lymphocyte proliferation
malfunction
-
enzyme deficiency results in altered or dysfunctional mitochondria
malfunction
in hepatocytes, the absence of isoform GPAT-1, but not GPAT-4, increases fatty acid oxidation and increases ketogenesis during fasting
malfunction
gene disruption Gpat3-/- mutant mice exhibit attenuated plasma triglyceride excursion and accumulate lipid in the enterocytes, and a lack of lipids in the lamina propria and intercellular space in Gpat3-/- mice. Gpat3-/- enterocytes display a compensatory increase in the synthesis of phospholipid and cholesteryl ester. When fed a Western-type diet, hepatic triglyceride and cholesteryl ester accumulation is significantly higher in Gpat3-/- mice compared with the wild-type mice accompanied by elevated levels of alanine aminotransferase, a marker of liver injury. Dysregulation of bile acid metabolism is also evident in Gpat3-null mice. Although wild-type mice show marked lipid staining in the lamina propria, Gpat3-/- mice exhibit a striking reduction in transitory lipids. Phenotype overview. Analysis of effects of GPAT3 deletion on intestinal lipid profile, gene expression, and gut nutrient sensing
malfunction
Gpat3-/- mice have about 80% reduction in GPAT activity in white adipose tissue, are resistant to weight gain and have improved insulin sensitivity in response to a high-fat diet. In enterocytes from Gpat3-/- mice, excess fatty acids are oxidized and esterified to cholesterol, which are stored and secreted in chylomicrons. Gpat3-/- mice fed a high-fat diet have decreased weight gain, fat mass and enlarged livers, indicating an important role in fatty acid storage in white adipose tissue. Liver enlargement in Gpat3-/- mice is due to cholesterol ester storage resulting from dysregulation of intestinal cholesterol secretion. Overexpression of endoplasmic reticulum-localized GPAT3 or GPAT4 in cultured cells does not affect incorporation of exogenous fatty acids into the major phospholipid classes
malfunction
knockdown of GPAT3 and 4 almost completely prevents the formation of lipid droplets. Deficiency of GPAT greatly reduces TAG synthesis and impairs adipogenesis. Phenotype of GPAT4 knockout mice, overview. The body weight is significantly lower (25%) in GPAT4-/- mice fed with normal chow diet compared to that of the mice in the wild-type group. High fat diet-fed GPAT4-null mice exhibit increased thermogenic gene expression in brown adipose tissue and perform a dramatic hyper-metabolism. The levels of triacylglycerol and diacylglycerol of milk decreases by 90% in GPAT4-null mice due to an extraordinary decline in the number and size of fat droplets in mammary epithelial acinars and ducts. Pups nursed by GPAT4-/- mice die within 48 h after birth unless wild-type mice replace the GPAT4-/- mice to feed the pups. GPAT4 overexpression in hepatocytes leads to impaired insulin-suppressed gluconeogenesis and decreased insulin-stimulated glycogen synthesis, as well as inhibited phosphorylation of Akt (Ser473 and Thr308) stimulated by insulin. Eventually, the changes lead to the impaired glucose homeostasis. Overexpression of GPAT4 inhibits the association between rictor and the mTOR, and even the mTORC2 (mTOR complex 2) activity. Like GPAT1, overexpression of GPAT4 increases the content of phosphatidic acid, which is produced in triacylglycerol synthesis pathway, particularly di16:0-phosphatidic acid. The lipid signal (such as di16:0PA) produced by GPAT4 interferes with the insulin signaling in hepatocytes of mice, which results in hepatic insulin resistance and impaired glucose homeostasis
malfunction
knockdown of GPAT3 and 4 almost completely prevents the formation of lipid droplets. Deficiency of GPAT greatly reduces TAG synthesis and impairs adipogenesis. The activity of GPAT decreases dramatically with GPAT3-specific siRNA knockdown in 3T3-L1 cells, which directly inhibits lipid synthesis. GPAT3-/- mice have increased energy expenditure, improved glucose homeostasis (lower fed glucose level, but not fasting glucose and insulin levels), decreased fat pad size, altered serum lipid levels (increased plasma free cholesterol, especially the low-density lipoprotein cholesterol level, and decreased plasma TAG), but enlarged liver size with increased plasma ALT/AST levels. Inhibition of GPAT3 may improve lipid and glucose metabolism, and provide beneficial effects in the treatment of metabolic diseases. Though increased energy expenditure is observed in both female and male mice. A sexual dimorphism in the GPAT3-deficient phenotype is demonstrated. GPAT3-/- female mice are protected from dietary-induced obesity (DIO) and the hepatic cholesterol metabolism is primarily altered only in GPAT3-/- male mice
malfunction
overexpression of GPAT1 in CHO, HEK-293 and primary rodent hepatocytes is sufficient to increase fatty acid incorporation into triglycerides and phospholipids. Gpat1-/- mice have a severe block in hepatic de novo synthesis of total phospholipids. Knockout of GPAT1 activity in cardiomyocytes and hepatocytes increases the arachidonate and oleate content of phosphocholine and phosphoethanolamine. Gpat1-/- mice are less susceptible to carcinogen-induced liver tumorigenesis. Gpat1-/- mice fed a high-sucrose diet to stimulate de novo lipogenesis have a 50% reduction in hepatic and plasma triglycerides, increased hepatic content of long-chain acylcarnitines and reduced very low density lipoprotein (VLDL) secretions. Liver-specific adenoviral expression of GPAT1 results in triglycerides and diacylglycerol accumulation, decreased fatty acid beta-oxidation, and hyperlipidemia
malfunction
the liver and brown adipose tissue of Gpat4-/- mice have a 65% reduction in NEM-sensitive GPAT activity, but activity in white adipose tissue is unaffected due to high levels of GPAT3 expression. Female Gpat4-/- mice fed a high-fat diet have increased PPARgamma-mediated Ucp1 expression and thermogenesis in brown adipose tissue resulting from elevated acyl-CoAs due to diminished esterification. Incorporation of exogenous oleate into phospholipid is unaffected in tissues of Gpat4-/- mice. Overexpression of endoplasmic reticulum-localized GPAT3 or GPAT4 in cultured cells does not affect incorporation of exogenous fatty acids into the major phospholipid classes
malfunction
the phagocytic capacity of Gpat3-/- and Gpat4-/- bone marrow-derived macrophages is impaired. Additionally, inhibiting fatty acid beta-oxidation reduces phagocytosis only partially, suggesting that lipid accumulation is not necessary for the energy requirements for phagocytosis
malfunction
the phagocytic capacity of Gpat3-/- and Gpat4-/- bone marrow-derived macrophages is impaired. Additionally, inhibiting fatty acid beta-oxidation reduces phagocytosis only partially, suggesting that lipid accumulation is not necessary for the energy requirements for phagocytosis. Gpat4-/- bone marrow-derived macrophages express and release more pro-inflammatory cytokines and chemokines after macrophage activation
malfunction
the T-cell phenotype under GPAT1 deficiency is comparable to that in an older mice, where GPAT1 activity decreases largely due to immune depression and results in increased susceptibility to infections. T-cells harvested from GPAT1-/- mice show significant reduction in interleukin-2 secretion upon antigen stimulation, and induced apoptosis accompanied by altered mass and composition of phospholipids. LPA produced as a result of increased expression of GPAT1 via glucosamine prevents mouse embryonic stem cells from hypoxia-induced apoptosis through the mammalian target of repamycin (mTOR) activation. The alteration of lipid composition in GPAT1-/- mice decreases the susceptibility to carcinogen-induced liver tumorigenesis. GPAT1 deficiency in ob/ob mice leads to a decrease in hepatic steatosis, triacylglycerol (about 59%), and diacylglycerol (about 74%), leading to the improvement of hepatic and systemic insulin sensitivity. The GPAT1-null mice also exhibit significant decreased plasma glucose levels and lowered plasma TAG content in ob/ob background. The levels of acyl-CoA are observed to be elevated. The overexpression of GPAT1 leads to impaired insulin signaling, reduced insulin-induced suppression of gluconeogenesis, substantially prevents mTOR complex2 (mTORC2) activity, and disassembles the link of mTOR/rictor mediated by PA, which induces peripheral and hepatic insulin resistance
metabolism
isoform GPAT-1, but not GPAT-4, metabolizes fatty acid synthesized de novo from [14C]acetate and diverts fatty acids away from mitochondrial oxidation
metabolism
enzyme GPAT is involved in the glycerolipid synthesis, it is the first and rate-limiting enzyme of the pathway. Glycerolipid synthesis and GPAT3/GPAT4 activity are induced during macrophage activation. Macrophage activation stimulates lipid droplet formation and increases triacylglycerol and phospholipid content, after Kdo2-lipid A (KLA) activation
metabolism
GPAT3 is involved in intestinal lipid metabolism, role of the intestinal glycerol 3-phosphate pathway in dietary lipid absorption. During lipid absorption, enterocytes transiently store triglycerides in cytosolic lipid droplets before packaging and secretion in chylomicron particles, isozyme Gpat3 localizes in the proximity to lipid droplets
metabolism
relation between three isoforms GPAT1, 3, and 4 and insulin resistance, overview. GPAT1 preferentially catalyzes saturated fatty acids (FAs) (palmitate or C16:0) and selectively transfers acyl-CoA to the sn-1 position of glycerol 3-phosphate. Subsequently, lysophosphatidic acid, phosphatidic acid, and diacylglycerol are produced in the glycerophospholipid pathway. These intermediate substrates serve as the critical component of the ubiquitous biological membranes and mediate intercellular signal transduction. Mitochondrial GPAT1 is a critical regulator of triacylglycerol metabolism and systemic energy homeostasis
metabolism
relation between three isoforms GPAT1, 3, and 4 and insulin resistance, overview. GPAT3 and GPAT4 enzyme activity can be regulated by insulin upon phosphorylation at the Thr and Ser residues. Lysophosphatidic acid (LPA) produced by GPAT4 can stimulate mitogenic activity. LPA serves as a mitogen regulating various cellular processes, such as cell proliferation and cytoskeletal reorganization. Like mitochondrial GPAT1, GPAT4 is also associated with hepatic lipid accumulation and contributes to the development of insulin resistance
metabolism
relation between three isoforms GPAT1, 3, and 4 and insulin resistance, overview. GPAT3 is recognized as a major isoform in the adipocytes for the synthesis of triacylglycerol. GPAT3 and GPAT4 enzyme activity can be regulated by insulin upon phosphorylation at the Thr and Ser residues. GPAT3 serves as an enzyme, playing critical roles in dietary lipid absorption, enteric and hepatic lipid homeostasis, as well as entero-endocrine hormone production. GPAT3 has been shown to be involved in the regulation of intestinal lipid metabolism, thyroid-stimulating hormone (TSH) induces lipid production by activating the PPARgamma/AMPK/GPAT3 pathway in a thyroxine-independent manner
metabolism
substrate channeling in the glycerol-3-phosphate pathway regulates the synthesis, storage and secretion of glycerolipids. The successive acylation of glycerol-3-phosphate (G3P) by glycerol-3-phosphate acyltransferases and acylglycerol-3-phosphate acyltransferases produces phosphatidic acid (PA), a precursor for CDP-diacylglycerol-dependent phospholipid synthesis. PA is further dephosphorylated by LIPINs to produce diacylglycerol (DG), a substrate for the synthesis of triglyceride (TG) by DG acyltransferases and a precursor for phospholipid synthesis via the CDP-choline and CDP-ethanolamine (Kennedy) pathways. The channeling of fatty acids into TG for storage in lipid droplets and secretion in lipoproteins or phospholipids for membrane biogenesis is dependent on isoform expression, activity and localization of G3P pathway enzymes, as well as dietary and hormonal and tissue-specific factors. Mechanisms that control partitioning of substrates into lipid products of the G3P pathway, overview
physiological function
a 60% knockdown of Gpat3 mRNA in 3T3-L1 cells with small interfering (si)RNA results in a 55% decrease in fatty acid incorporation into lysophosphatidic acid. Gpat1 mRNA levels also show a large induction during 3T3-L1 adipocyte differentiation, suggesting that this isoform also contributes to GPAT activity in adipocytes
physiological function
-
cis-acting promoter sequences for the mouse GPAT1 gene are identified: promoter 1a which includes part of the classical sequence and the downstream promoter 1b. Promoter 1a facilitates transcription of two alternative GPAT1 transcript variants, GPAT1-V1 and V2, while promoter 1b produces a third transcript variant, GPAT1-V3
physiological function
GC-1 spermatogonia cells show a marked increase in proliferation after transfection with GPAT4. Cell cycle analysis shows a decrease in the percentage of cells in the G0/G1 phase and an increase in the S phase. Thus, GPAT4 might play an important role in spermatogenesis, especially in mid-meiosis
physiological function
Gpat1 mRNA levels increase more than 20fold in mouse liver in an insulin-dependent manner by refeeding of a high-carbohydrate diet after fasting, which is associated with active hepatic lipogenesis
physiological function
Gpat3 mRNA levels in ob/ob mice are decreased by 70% in white adipose tissue and increased 2fold in liver compared with wild-type animals. Treatment of ob/ob mice with rosiglitazone, a potent peroxisome proliferator-activated receptor (PPAR)gamma agonist, increases Gpat3, but not Gpat1, mRNA in white adipose tissue, suggesting that Gpat3 is a PPARgamma target gene
physiological function
the mouse Gpat1 gene promoter region contains three sterol regulatory elements responsible for SREBP-1-mediated transactivation. Ectopic expression of SREBP-1c in 3T3-L1 adipocytes or in liver of transgenic mice dramatically increases Gpat1 mRNA
physiological function
isoform GPAT1-/- hepatocytes are not able to incorporate de novo synthesized fatty acid into triacylglycerol but oxidize twice as much exogenous fatty acid as controls. The hepatic content of long-chain acylcarnitine in fasted Gpat1-/- mice is 3-fold higher than in controls. When compared with control and isoform Gpat-/- mice, after the fasting-refeeding protocol, Gpat1-/- hepatic triacylglycerol is depleted, and long-chain acylcarnitine content is 3.5fold higher
physiological function
-
the enzyme is essential for the response to the increased metabolic demands associated with T cell activation
physiological function
the metabolic rate of Gpat4-/- mice fed a 45% fat diet is 12% higher than controls, and core body temperature is 1ºC higher. A 45% fat diet increases the Gpat4-/- brown adipose tissue expression of peroxisome proliferator-activated receptor alpha target genes, Cpt1alpha, Pgc1alpha, and Ucp1, and brown adipose tissue mitochondria oxidize oleate and pyruvate at higher rates than controls. Gpat4-/- neonatal brown adipose tissue preadipocytes differentiated to adipocytes incorporate 33% less fatty acid into triacylglycerol and 46% more into the pathway of beta-oxidation
physiological function
a role for GPAT4 in suppressing inflammatory responses. GPAT4 is required for enhanced glycerolipid synthesis in activated macrophages
physiological function
GPAT1 dictates fatty acid composition at the level of AGPATs or by acyl-chain remodeling by lysophospholipid acyltransferases (LPLATs). GPAT1 determines the metabolic fate of exogenous fatty acids
physiological function
GPAT3 is required for enhanced glycerolipid synthesis in activated macrophages
physiological function
GPATs play a pivotal role in the regulation of triglyceride and phospholipid synthesis. GPATs play a critical role in the development of obesity, hepatic steatosis, and insulin resistance. GPAT4 plays a unique role in triacylglycerol synthesis and maintains systemic energy balance during lactation in inguinal adipose tissue. GPAT4 is a positive regulator of body weight. GPAT4 plays a critical role in triacylglycerol synthesis during development
physiological function
GPATs play a pivotal role in the regulation of triglyceride and phospholipid synthesis. GPATs play a critical role in the development of obesity, hepatic steatosis, and insulin resistance. Microsomal GPAT3 catalyzes a broad range of reactions using long-chain acyl-CoA as substrates, including saturated and unsaturated fatty acids. GPAT3 play a crucial role in lipid formation. GPAT3 serves as an enzyme, playing critical roles in dietary lipid absorption, enteric and hepatic lipid homeostasis, as well as entero-endocrine hormone production. GPAT3 plays a critical role in regulating glucose, energy, and lipid homeostasis
physiological function
GPATs play a pivotal role in the regulation of triglyceride and phospholipid synthesis. GPATs play a critical role in the development of obesity, hepatic steatosis, and insulin resistance. Mitochondrial isozyme GPAT1 activity has a huge impact on the regulation of triacylglycerol synthesis, is responsible for 30-50% of the total GPAT activity in the liver and approximately 30% of the total activity in the heart. GPAT1 is regulated at the transcriptional and posttranscriptional levels, and is highly expressed in adipose tissues and liver cells. GPAT1 plays a substantial role in modulating the cytokine production and proliferation of murine T-lymphocytes. Mitochondrial GPAT1 is a critical regulator of triacylglycerol metabolism and systemic energy homeostasis
physiological function
isozyme GPAT3 is primarily involved in triglyceride (TG) storage in adipocytes. Contribution of GPATs to acyl-CoA partitioning into glycerolipid synthesis and beta-oxidation
physiological function
isozyme GPAT4 is a primary contributor to lysophosphatidic acid synthesis in liver and brown adipose tissue. Contribution of GPATs to acyl-CoA partitioning into glycerolipid synthesis and beta-oxidation. GPAT4 expression and high-fat diet-induced insulin resistance are linked to altered levels of palmitate-enriched phosphatidic acid and diacylglycerol and altered mTORC2
additional information
the GPAT/AGPAT family acyltransferases contain four well-conserved domains (motif I-IV), which catalyze the transferase reaction and are involved in binding to the substrate (acyl acceptor, e.g. G3P)
additional information
the GPAT/AGPAT family acyltransferases contain four well-conserved domains (motif I-IV), which catalyze the transferase reaction and are involved in binding to the substrate (acyl acceptor, e.g. G3P)
additional information
the GPAT/AGPAT family acyltransferases contain four well-conserved domains (motif I-IV), which catalyze the transferase reaction and are involved in binding to the substrate (acyl acceptor, e.g. G3P)
additional information
the GPAT/AGPAT family acyltransferases contain four well-conserved domains (motif I-IV), which catalyze the transferase reaction and are involved in binding to the substrate (acyl acceptor, e.g. G3P)
additional information
the GPAT/AGPAT family acyltransferases contain four well-conserved domains (motif I-IV), which catalyze the transferase reaction and are involved in binding to the substrate (acyl acceptor, e.g., G3P)
additional information
the GPAT/AGPAT family acyltransferases contain four well-conserved domains (motif I-IV), which catalyze the transferase reaction and are involved in binding to the substrate (acyl acceptor, e.g., G3P)
additional information
the GPAT/AGPAT family acyltransferases contain four well-conserved domains (motif I-IV), which catalyze the transferase reaction and are involved in binding to the substrate (acyl acceptor, e.g., G3P)
additional information
the GPAT/AGPAT family acyltransferases contain four well-conserved domains (motif I-IV), which catalyze the transferase reaction and are involved in binding to the substrate (acyl acceptor, e.g., G3P)
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). GPAT2_MOUSE
801
0
89150
Swiss-Prot
other Location (Reliability: 3)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
89100
estimated molecular mass, verified by SDS-PAGE and Western blot analysis
50000
52000
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
GPAT1 possesses a conserved acyltransferase domain and two transmembrane domains, with the N- and C-terminal domains facing the cytosol, and forms a stem loop structure in the mitochondrial intermembrane space. The active site of acyltransferase is close to the N-terminal domain toward the cytosol, while the C-terminal domain is suggested to have a regulatory function
additional information
GPAT1 possesses a conserved acyltransferase domain and two transmembrane domains, with the N- and C-terminal domains facing the cytosol, and forms a stem loop structure in the mitochondrial intermembrane space. The active site of acyltransferase is close to the N-terminal domain toward the cytosol, while the C-terminal domain is suggested to have a regulatory function
additional information
GPAT1 possesses a conserved acyltransferase domain and two transmembrane domains, with the N- and C-terminal domains facing the cytosol, and forms a stem loop structure in the mitochondrial intermembrane space. The active site of acyltransferase is close to the N-terminal domain toward the cytosol, while the C-terminal domain is suggested to have a regulatory function
additional information
GPAT1 possesses a conserved acyltransferase domain and two transmembrane domains, with the N- and C-terminal domains facing the cytosol, and forms a stem loop structure in the mitochondrial intermembrane space. The active site of acyltransferase is close to the N-terminal domain toward the cytosol, while the C-terminal domain is suggested to have a regulatory function
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
the gene is silenced in vivo by inoculating lentiviral particles carrying the sequence of a short-hairpin RNA targeting Gpat2 mRNA into mouse testis, expression of 5 different shRNA-Gpat2 vectors, subcloning in HEK-293 cells. Histological and gene expression analysis shows impaired spermatogenesis and arrest at the pachytene stage. Defects in reproductive fitness are also observed, and the analysis of apoptosis-related gene expression demonstrates the activation of apoptosis in Gpat2-silenced germ cells. The decrease in germ cell number in shRNA-Gpat2 mice seminiferous tubules correlates with apoptosis activation, without retrotransposon derepression
additional information
-
the gene is silenced in vivo by inoculating lentiviral particles carrying the sequence of a short-hairpin RNA targeting Gpat2 mRNA into mouse testis, expression of 5 different shRNA-Gpat2 vectors, subcloning in HEK-293 cells. Histological and gene expression analysis shows impaired spermatogenesis and arrest at the pachytene stage. Defects in reproductive fitness are also observed, and the analysis of apoptosis-related gene expression demonstrates the activation of apoptosis in Gpat2-silenced germ cells. The decrease in germ cell number in shRNA-Gpat2 mice seminiferous tubules correlates with apoptosis activation, without retrotransposon derepression
additional information
changes in GPAT4 activity in overexpressing Cos-7 cells and knockout mice
additional information
changes in GPAT4 activity in overexpressing Cos-7 cells and knockout mice
additional information
changes in GPAT4 activity in overexpressing Cos-7 cells and knockout mice
additional information
changes in GPAT4 activity in overexpressing Cos-7 cells and knockout mice
additional information
construction of GPAT4 knockout or null mice. Overexpression of GPAT4 in HEK-293 cells leads to increase the formation of lysophosphatidic acid, phosphatidic acid, and diacylglycerol, while triacylglycerol levels are unchanged. GPAT4-deficient mice have decreased body weight gain and subcutaneous fat pad, lowered hepatic and plasmatic triglycerides levels, and improved insulin resistance compared to controls. In addition, GPAT4-/- mice are protected from dietary-induced obesity (DIO) and the development of insulin resistance in the liver and muscle cells through decreased content of di16:0 PA
additional information
construction of GPAT4 knockout or null mice. Overexpression of GPAT4 in HEK-293 cells leads to increase the formation of lysophosphatidic acid, phosphatidic acid, and diacylglycerol, while triacylglycerol levels are unchanged. GPAT4-deficient mice have decreased body weight gain and subcutaneous fat pad, lowered hepatic and plasmatic triglycerides levels, and improved insulin resistance compared to controls. In addition, GPAT4-/- mice are protected from dietary-induced obesity (DIO) and the development of insulin resistance in the liver and muscle cells through decreased content of di16:0 PA
additional information
construction of GPAT4 knockout or null mice. Overexpression of GPAT4 in HEK-293 cells leads to increase the formation of lysophosphatidic acid, phosphatidic acid, and diacylglycerol, while triacylglycerol levels are unchanged. GPAT4-deficient mice have decreased body weight gain and subcutaneous fat pad, lowered hepatic and plasmatic triglycerides levels, and improved insulin resistance compared to controls. In addition, GPAT4-/- mice are protected from dietary-induced obesity (DIO) and the development of insulin resistance in the liver and muscle cells through decreased content of di16:0 PA
additional information
construction of GPAT4 knockout or null mice. Overexpression of GPAT4 in HEK-293 cells leads to increase the formation of lysophosphatidic acid, phosphatidic acid, and diacylglycerol, while triacylglycerol levels are unchanged. GPAT4-deficient mice have decreased body weight gain and subcutaneous fat pad, lowered hepatic and plasmatic triglycerides levels, and improved insulin resistance compared to controls. In addition, GPAT4-/- mice are protected from dietary-induced obesity (DIO) and the development of insulin resistance in the liver and muscle cells through decreased content of di16:0 PA
additional information
generation of Gpat4-/- mice in a C57BL6/J background
additional information
generation of Gpat4-/- mice in a C57BL6/J background
additional information
GPAT activity increases significantly after GPAT3 overexpression in COS-7 cells. The activity of GPAT decreases dramatically with GPAT3-specific siRNA knockdown in 3T3-L1 cells, which directly inhibits lipid synthesis
additional information
GPAT activity increases significantly after GPAT3 overexpression in COS-7 cells. The activity of GPAT decreases dramatically with GPAT3-specific siRNA knockdown in 3T3-L1 cells, which directly inhibits lipid synthesis
additional information
GPAT activity increases significantly after GPAT3 overexpression in COS-7 cells. The activity of GPAT decreases dramatically with GPAT3-specific siRNA knockdown in 3T3-L1 cells, which directly inhibits lipid synthesis
additional information
GPAT activity increases significantly after GPAT3 overexpression in COS-7 cells. The activity of GPAT decreases dramatically with GPAT3-specific siRNA knockdown in 3T3-L1 cells, which directly inhibits lipid synthesis
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
40.5
-
half-life of microsomal isozyme is 7 min, loss of 80% activity of isozyme mtGPAT2 after 4 min
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
to determine the translated size of GPAT2, in vitro transcription and translation is performed
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
the PCR product is subcloned with the TOPO TA Cloning Kit and sequenced, the vectors pCR2.1-TOPO and pcDNA3.1/Myc-His+ are used, the xGPAT-myc construct is used for transfection of CHO-K1 cells
GPAT3 is localized to the endoplasmic reticulum when overexpressed in COS-7 cells
-
mice are transduced with adenoviruses expressing either murine mtGPAT or a catalytically inactive variant of the enzyme. Overexpressing mtGPAT results in massive 12- and 7-fold accumulation of liver triacylglycerol and diacylglycerol
PCR amplified mouse testis cDNA is cloned into the TOPO vector and subsequently subcloned into pcDNA3.1 for transient transfection of COS-7 and HEK293 cells
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
retinoic acid activates GPAT2 expression in TM4 cells in vitro. GPAT2 mRNA expression is increased and the content of triacylglycerol is significantly elevated in testis during sexual maturation in mice
carbohydrate response element-binding protein (ChREBP) and sterol regulatory element-binding protein-1c (SREBP-1c) are involved in the transcriptional upregulation of GPAT1 levels under increased dietary intake of carbohydrate and increased levels of insulin in plasma
GPAT3 mRNA expression is significantly upregulated (about 60fold) during 3T3-L1 adipocyte differentiation. GPAT3 expression is also upregulated by TSH
RENATURED/Commentary
ORGANISM
UNIPROT
LITERATURE
reconstitution effectiveness of phospholipids in descending order: crude soybean phosphatidylcholin, phosphatidylserine, phosphatidylinositol, phosphatidylethanolamine, cardiolipin
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
-
elucidation of the metabolic pathways of triacylglycerol is critical to the understanding of chronic metabolic disorders such as obesity, cardiovascular disease and diabetes
medicine
-
GPAT1 is not an essential enzyme in hepatic triacylglycerol synthesis and GPAT1-deficiency does not protect against high-fat diet-induced obesity or glucose intolerance and does not increase whole body energy expenditure
medicine
-
Gpat1-/- mouse may be a useful model in which to study novel relationships between hepatic mitochondrial dysfunction, oxidative stress, apoptosis, proliferation, and cancer susceptibility
medicine
-
lack of GPAT1 activity affects both innate and adaptive immune mechanisms
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Yet, S.F.; Lee, S.; Hahm, Y.T.; Sul, H.S.
Expression and identification of p90 as the murine mitochondrial glycerol-3-phosphate acyltransferase
Biochemistry
32
9486-9491
1993
Mus musculus
Yet, S.F.; Moon, Y.K.; Sul, H.S.
Purification and reconstitution of murine mitochondrial glycerol-3-phosphate acyltransferase. Functional expression in baculovirus-infected insect cells
Biochemistry
34
7303-7310
1995
Mus musculus
Dircks, L.K.; Sul, H.S.
Mammalian mitochondrial glycerol-3-phosphate acyltransferase
Biochim. Biophys. Acta
1348
17-26
1997
Cavia porcellus, Mus musculus, Rattus norvegicus
Dircks, L.K.; Ke, J.; Sul, H.S.
A conserved seven amino acid stretch important for murine mitochondrial glycerol-3-phosphate acyltransferase activity. Significance of arginine 318 in catalysis
J. Biol. Chem.
274
34728-34734
1999
Mus musculus (Q61586), Mus musculus
Lewin, T.M.; Schwerbrock, N.M.; Lee, D.P.; Coleman, R.A.
Identification of a new glycerol-3-phosphate acyltransferase isoenzyme, mtGPAT2, in mitochondria
J. Biol. Chem.
279
13488-13495
2004
Mus musculus
Linden, D.; William-Olsson, L.; Ahnmark, A.; Ekroos, K.; Hallberg, C.; Sjoegren, H.P.; Becker, B.; Svensson, L.; Clapham, J.C.; Oscarsson, J.; Schreyer, S.
Liver-directed overexpression of mitochondrial glycerol-3-phosphate acyltransferase results in hepatic steatosis, increased triacylglycerol secretion and reduced fatty acid oxidation
FASEB J.
20
434-443
2006
Mus musculus (Q61586), Mus musculus
Hammond, L.E.; Neschen, S.; Romanelli, A.J.; Cline, G.W.; Ilkayeva, O.R.; Shulman, G.I.; Muoio, D.M.; Coleman, R.A.
Mitochondrial glycerol-3-phosphate acyltransferase-1 is essential in liver for the metabolism of excess acyl-CoAs
J. Biol. Chem.
280
25629-25636
2005
Mus musculus
Cao, J.; Li, J.L.; Li, D.; Tobin, J.F.; Gimeno, R.E.
Molecular identification of microsomal acyl-CoA:glycerol-3-phosphate acyltransferase, a key enzyme in de novo triacylglycerol synthesis
Proc. Natl. Acad. Sci. USA
103
19695-19700
2006
Homo sapiens, Mus musculus
Wang, S.; Lee, D.P.; Gong, N.; Schwerbrock, N.M.; Mashek, D.G.; Gonzalez-Baro, M.R.; Stapleton, C.; Li, L.O.; Lewin, T.M.; Coleman, R.A.
Cloning and functional characterization of a novel mitochondrial N-ethylmaleimide-sensitive glycerol-3-phosphate acyltransferase (GPAT2)
Arch. Biochem. Biophys.
465
347-358
2007
Mus musculus
Yazdi, M.; Ahnmark, A.; William-Olsson, L.; Snaith, M.; Turner, N.; Osla, F.; Wedin, M.; Asztely, A.K.; Elmgren, A.; Bohlooly-Y, M.; Schreyer, S.; Linden, D.
The role of mitochondrial glycerol-3-phosphate acyltransferase-1 in regulating lipid and glucose homeostasis in high-fat diet fed mice
Biochem. Biophys. Res. Commun.
369
1065-1070
2008
Mus musculus
Lewin, T.M.; de Jong, H.; Schwerbrock, N.J.; Hammond, L.E.; Watkins, S.M.; Combs, T.P.; Coleman, R.A.
Mice deficient in mitochondrial glycerol-3-phosphate acyltransferase-1 have diminished myocardial triacylglycerol accumulation during lipogenic diet and altered phospholipid fatty acid composition
Biochim. Biophys. Acta
1781
352-358
2008
Mus musculus
Hammond, L.E.; Albright, C.D.; He, L.; Rusyn, I.; Watkins, S.M.; Doughman, S.D.; Lemasters, J.J.; Coleman, R.A.
Increased oxidative stress is associated with balanced increases in hepatocyte apoptosis and proliferation in glycerol-3-phosphate acyltransferase-1 deficient mice
Exp. Mol. Pathol.
82
210-219
2007
Mus musculus
Nagle, C.A.; Vergnes, L.; Dejong, H.; Wang, S.; Lewin, T.M.; Reue, K.; Coleman, R.A.
Identification of a novel sn-glycerol-3-phosphate acyltransferase isoform, GPAT4, as the enzyme deficient in Agpat6-/- mice
J. Lipid Res.
49
823-831
2008
Mus musculus
Harada, N.; Hara, S.; Yoshida, M.; Zenitani, T.; Mawatari, K.; Nakano, M.; Takahashi, A.; Hosaka, T.; Yoshimoto, K.; Nakaya, Y.
Molecular cloning of a murine glycerol-3-phosphate acyltransferase-like protein 1 (xGPAT1)
Mol. Cell. Biochem.
297
41-51
2007
Mus musculus (Q14DK4), Mus musculus
Qiu, Q.; Liu, G.; Li, W.; Shi, Q.; Zhu, F.; Lu, G.
Glycerol-3-phosphate acyltransferase 4 gene is involved in mouse spermatogenesis
Acta Biochim. Biophys. Sin.
41
668-676
2009
Mus musculus (Q8K2C8), Mus musculus
Takeuchi, K.; Reue, K.
Biochemistry, physiology, and genetics of GPAT, AGPAT, and lipin enzymes in triglyceride synthesis
Am. J. Physiol. Endocrinol. Metab.
296
E1195-E1209
2009
Rattus norvegicus, Rattus norvegicus (P97564), Mus musculus (Q14DK4), Mus musculus (Q61586), Mus musculus (Q8C0N2), Mus musculus (Q8K2C8), Mus musculus, Homo sapiens (Q53EU6), Homo sapiens (Q86UL3), Homo sapiens
Hiromasa, Y.; Yan, X.; Roche, T.E.
Specific ion influences on self-association of pyruvate dehydrogenase kinase isoform 2 (PDHK2), binding of PDHK2 to the L2 lipoyl domain, and effects of the lipoyl group-binding site inhibitor, Nov3r
Biochemistry
47
2312-2324
2008
Mus musculus
Yoshida, M.; Harada, N.; Yamamoto, H.; Taketani, Y.; Nakagawa, T.; Yin, Y.; Hattori, A.; Zenitani, T.; Hara, S.; Yonemoto, H.; Nakamura, A.; Nakano, M.; Mawatari, K.; Teshigawara, K.; Arai, H.; Hosaka, T.; Takahashi, A.; Yoshimoto, K.; Nakaya, Y.
Identification of cis-acting promoter sequences required for expression of the glycerol-3-phosphate acyltransferase 1 gene in mice
Biochim. Biophys. Acta
1791
39-52
2009
Mus musculus
Karlsson, E.A.; Wang, S.; Shi, Q.; Coleman, R.A.; Beck, M.A.
Glycerol-3-phosphate acyltransferase 1 is essential for the immune response to infection with coxsackievirus B3 in mice
J. Nutr.
139
779-783
2009
Mus musculus
Nakagawa, T.; Harada, N.; Miyamoto, A.; Kawanishi, Y.; Yoshida, M.; Shono, M.; Mawatari, K.; Takahashi, A.; Sakaue, H.; Nakaya, Y.
Membrane topology of murine glycerol-3-phosphate acyltransferase 2
Biochem. Biophys. Res. Commun.
418
506-511
2012
Mus musculus (Q14DK4), Mus musculus
Faris, R.; Fan, Y.Y.; De Angulo, A.; Chapkin, R.S.; deGraffenried, L.A.; Jolly, C.A.
Mitochondrial glycerol-3-phosphate acyltransferase-1 is essential for murine CD4(+) T cell metabolic activation
Biochim. Biophys. Acta
1842
1475-1482
2014
Mus musculus
Wendel, A.A.; Cooper, D.E.; Ilkayeva, O.R.; Muoio, D.M.; Coleman, R.A.
Glycerol-3-phosphate acyltransferase (GPAT)-1, but not GPAT4, incorporates newly synthesized fatty acids into triacylglycerol and diminishes fatty acid oxidation
J. Biol. Chem.
288
27299-27306
2013
Mus musculus, Mus musculus (Q61586)
Cooper, D.E.; Grevengoed, T.J.; Klett, E.L.; Coleman, R.A.
Glycerol-3-phosphate acyltransferase isoform-4 (GPAT4) limits oxidation of exogenous fatty acids in brown adipocytes
J. Biol. Chem.
290
15112-15120
2015
Mus musculus (Q8K2C8)
Garcia-Fabiani, M.B.; Montanaro, M.A.; Stringa, P.; Lacunza, E.; Cattaneo, E.R.; Santana, M.; Pellon-Maison, M.; Gonzalez-Baro, M.R.
Glycerol-3-phosphate acyltransferase 2 is essential for normal spermatogenesis
Biochem. J.
474
3093-3107
2017
Mus musculus (Q14DK4), Mus musculus
Quiroga, I.Y.; Pellon-Maison, M.; Suchanek, A.L.; Coleman, R.A.; Gonzalez-Baro, M.R.
Glycerol-3-phosphate acyltransferases 3 and 4 direct glycerolipid synthesis and affect functionality in activated macrophages
Biochem. J.
476
85-99
2019
Mus musculus (Q8C0N2), Mus musculus (Q8K2C8), Mus musculus C57Bl6/J (Q8C0N2), Mus musculus C57Bl6/J (Q8K2C8)
Lee, J.; Ridgway, N.
Substrate channeling in the glycerol-3-phosphate pathway regulates the synthesis, storage and secretion of glycerolipids
Biochim. Biophys. Acta
1865
158438
2020
Mus musculus (Q14DK4), Mus musculus (Q61586), Mus musculus (Q8C0N2), Mus musculus (Q8K2C8), Homo sapiens (Q53EU6), Homo sapiens (Q6NUI2), Homo sapiens (Q86UL3), Homo sapiens (Q9HCL2)
Khatun, I.; Clark, R.; Vera, N.; Kou, K.; Erion, D.; Coskran, T.; Bobrowski, W.; Okerberg, C.; Goodwin, B.
Characterization of a novel intestinal glycerol-3-phosphate acyltransferase pathway and its role in lipid homeostasis
J. Biol. Chem.
291
2602-2615
2016
Mus musculus (Q8C0N2), Mus musculus
Yu, J.; Loh, K.; Song, Z.Y.; Yang, H.Q.; Zhang, Y.; Lin, S.
Update on glycerol-3-phosphate acyltransferases the roles in the development of insulin resistance
Nutr. Diabetes
8
34
2018
Mus musculus (Q14DK4), Mus musculus (Q61586), Mus musculus (Q8C0N2), Mus musculus (Q8K2C8), Homo sapiens (Q53EU6), Homo sapiens (Q86UL3), Homo sapiens (Q9HCL2), Mus musculus C57BL/6J (Q8K2C8)
EXTERNAL LINKS (specific for EC-Number 2.3.1.15)
Transporter Classification Database (TCDB): 9.B.31.1.1
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