Literature summary for 2.3.1.15 extracted from

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 (2018), Nutr. Diabetes, 8, 34 .

Activating Compound

Activating Compound	Comment	Organism	Structure
rosiglitazone	GPAT3 activity increase in the white adipose tissue of diabetic mice after treatment with rosiglitazone, which is a PPAR-gamma agonist	Mus musculus

Cloned(Commentary)

Cloned (Comment)	Organism
GPAT3 overexpression in COS-7 cells	Mus musculus

Protein Variants

Protein Variants	Comment	Organism
additional information	construction of GPAT2 knockout mice	Mus musculus
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	Mus musculus
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	Mus musculus
additional information	overexpression and knockout of GPAT1	Mus musculus

Inhibitors

Inhibitors	Comment	Organism
2-(nonylsulfonamido)benzoic acid	i.e. FSG67a, GPAT inhibitor, has a broad spectrum inhibitory effect on GPAT activity; i.e. FSG67a, GPAT inhibitor, has a broad spectrum inhibitory effect on GPAT activity; i.e. FSG67a, GPAT inhibitor, has a broad spectrum inhibitory effect on GPAT activity	Homo sapiens
2-(nonylsulfonamido)benzoic acid	i.e. FSG67a, GPAT inhibitor, has a broad spectrum inhibitory effect on GPAT activity, metabolic effects in mice, overview; i.e. FSG67a, GPAT inhibitor, has a broad spectrum inhibitory effect on GPAT activity, metabolic effects in mice, overview; i.e. FSG67a, GPAT inhibitor, has a broad spectrum inhibitory effect on GPAT activity, metabolic effects in mice, overview; 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	Mus musculus
additional information	mitochondrial GPAT1 is resistant to inactivation induced by sulfhydryl-group modifying reagents like N-ethylmaleimide (NEM)	Homo sapiens
additional information	mitochondrial GPAT1 is resistant to inactivation induced by sulfhydryl-group modifying reagents like N-ethylmaleimide (NEM)	Mus musculus
NEM	microsomal GPAT3 activity is sensitive to NEM; mitochondrial GPAT2 is sensitive to NEM	Homo sapiens

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
endoplasmic reticulum membrane	-	Mus musculus	5789	-
endoplasmic reticulum membrane	-	Homo sapiens	5789	-
microsome	-	Mus musculus	-	-
microsome	-	Homo sapiens	-	-
mitochondrial outer membrane	-	Mus musculus	5741	-
mitochondrial outer membrane	-	Homo sapiens	5741	-
mitochondrial outer 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	Mus musculus	5741	-
mitochondrial outer 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	Homo sapiens	5741	-
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	Mus musculus	-	-
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	Homo sapiens	-	-

Molecular Weight [Da]

Molecular Weight [Da]	Molecular Weight Maximum [Da]	Comment	Organism
50000	-	-	Mus musculus
50000	-	-	Homo sapiens
52000	-	-	Mus musculus
52000	-	-	Homo sapiens
88000	-	-	Homo sapiens
89000	-	-	Mus musculus
94000	-	-	Mus musculus
94000	-	-	Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.
acyl-CoA + sn-glycerol 3-phosphate	Mus musculus	-	CoA + 1-acyl-sn-glycerol 3-phosphate	-	?
acyl-CoA + sn-glycerol 3-phosphate	Homo sapiens	-	CoA + 1-acyl-sn-glycerol 3-phosphate	-	?
acyl-CoA + sn-glycerol 3-phosphate	Mus musculus C57BL/6J	-	CoA + 1-acyl-sn-glycerol 3-phosphate	-	?
additional information	Mus musculus	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	Homo sapiens	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	?	-	-

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	Q53EU6	-	-
Homo sapiens	Q86UL3	-	-
Homo sapiens	Q9HCL2	-	-
Mus musculus	Q14DK4	-	-
Mus musculus	Q61586	-	-
Mus musculus	Q8C0N2	-	-
Mus musculus	Q8K2C8	-	-
Mus musculus C57BL/6J	Q8K2C8	-	-

Source Tissue

Source Tissue	Comment	Organism	Textmining
3T3-L1 cell	-	Mus musculus	-
adipocyte	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)	Mus musculus	-
adipocyte	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	Mus musculus	-
adipose tissue	-	Mus musculus	-
adipose tissue	-	Homo sapiens	-
adipose tissue	brown and white, high expression level	Mus musculus	-
adipose tissue	brown and white, high expression level	Homo sapiens	-
brain	-	Mus musculus	-
brain	-	Homo sapiens	-
brown adipose tissue	-	Mus musculus	-
brown adipose tissue	-	Homo sapiens	-
carcinoma cell	isozyme GPAT2 is highly expressed in several cancer types (such as lung, melanoma, breast, and prostate cancer) and cancer-derived human cell lines	Homo sapiens	-
heart	-	Mus musculus	-
heart	-	Homo sapiens	-
hepatocyte	-	Mus musculus	-
intestine	-	Mus musculus	-
intestine	-	Homo sapiens	-
kidney	-	Homo sapiens	-
kidney	-	Mus musculus	-
liver	-	Mus musculus	-
liver	-	Homo sapiens	-
liver	high expression level	Mus musculus	-
liver	high expression level	Homo sapiens	-
liver	GPAT4 accounts for the primary microsomal GPAT activity in liver	Mus musculus	-
liver	GPAT4 accounts for the primary microsomal GPAT activity in liver	Homo sapiens	-
mammary gland	during lactation, GPAT4 mRNA is highly expressed in mammary gland epithelium, but not in the surrounding adipocytes of breast tissue	Mus musculus	-
mammary gland	during lactation, GPAT4 mRNA is highly expressed in mammary gland epithelium, but not in the surrounding adipocytes of breast tissue	Homo sapiens	-
additional information	tissue distribution, overview	Mus musculus	-
additional information	tissue distribution, overview	Homo sapiens	-
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	Mus musculus	-
additional information	human GPAT3 is abundantly expressed in the kidney, heart, skeletal muscle, and thyroid gland. Tissue distribution, overview	Homo sapiens	-
additional information	mitochondrial GPAT1 activity 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. Tissue distribution, overview	Homo sapiens	-
muscle	-	Mus musculus	-
muscle	-	Homo sapiens	-
skeletal muscle	-	Homo sapiens	-
small intestine	-	Mus musculus	-
small intestine	-	Homo sapiens	-
spermatocyte	-	Mus musculus	-
T-lymphocyte	-	Mus musculus	-
testis	-	Homo sapiens	-
testis	GPAT2 is mainly expressed in pachytene spermatocytes of testis	Mus musculus	-
testis	GPAT2 is mainly expressed in pachytene spermatocytes of testis	Homo sapiens	-
testis	GPAT4 is widely expressed postnatally in spermatocytes and around spermatids in mice testis	Mus musculus	-
thyroid gland	-	Homo sapiens	-
TM-4 cell	-	Mus musculus	-
white adipose tissue	low level	Mus musculus	-
white adipose tissue	low level	Homo sapiens	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.
acyl-CoA + sn-glycerol 3-phosphate	-	Mus musculus	CoA + 1-acyl-sn-glycerol 3-phosphate	-	?
acyl-CoA + sn-glycerol 3-phosphate	-	Homo sapiens	CoA + 1-acyl-sn-glycerol 3-phosphate	-	?
acyl-CoA + sn-glycerol 3-phosphate	GPAT3 uses oleoyl-CoA as the preferred substrate compared to all other acyl-CoAs such as palmitoyl-CoA, myristoyl-CoA, and stearoyl-CoA	Homo sapiens	CoA + 1-acyl-sn-glycerol 3-phosphate	-	?
acyl-CoA + sn-glycerol 3-phosphate	-	Mus musculus C57BL/6J	CoA + 1-acyl-sn-glycerol 3-phosphate	-	?
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	Mus musculus	?	-	-
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	Homo sapiens	?	-	-
additional information	the isozyme GPAT3 possesses both AGPAT and GPAT activities. Microsomal GPAT3 catalyzes a broad range of reactions using long-chain acyl-CoA as substrates, including saturated and unsaturated FAs. GPAT3 uses oleoyl-CoA as the preferred substrate compared to all other acyl-CoAs such as palmitoyl-CoA, myristoyl-CoA, and stearoyl-CoA	Homo sapiens	?	-	-

Subunits

Subunits	Comment	Organism
More	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	Mus musculus
More	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	Homo sapiens

Synonyms

Synonyms	Comment	Organism
AGPAT10	-	Homo sapiens
AGPAT6	-	Mus musculus
AGPAT6	-	Homo sapiens
AGPAT8	-	Homo sapiens
cancer-testicular antigen	-	Homo sapiens
glycerol-3-phosphate acyltransferase	-	Mus musculus
glycerol-3-phosphate acyltransferase	-	Homo sapiens
GPAT1	-	Mus musculus
GPAT1	-	Homo sapiens
GPAT2	-	Mus musculus
GPAT2	-	Homo sapiens
GPAT3	-	Mus musculus
GPAT3	-	Homo sapiens
GPAT3/AGPAT10	-	Mus musculus
GPAT3/AGPAT10	-	Homo sapiens
GPAT4	-	Mus musculus
GPAT4	-	Homo sapiens
microsomal GPAT3	-	Mus musculus
microsomal GPAT3	-	Homo sapiens
microsomal GPAT3/AGPAT10	-	Homo sapiens
microsomal GPAT4	-	Mus musculus
microsomal GPAT4	-	Homo sapiens
mitochondrial GPAT1	-	Mus musculus
mitochondrial GPAT1	-	Homo sapiens
mitochondrial GPAT2	-	Mus musculus
mitochondrial GPAT2	-	Homo sapiens

Expression

Organism	Comment	Expression
Homo sapiens	the expression of mitochondrial GPAT, both at the mRNA and protein levels, is downregulated when targeted by upregulated miRNAs, such as miR-23b, in Epstein-Barr virus-infected B-cells under several culture conditions	down
Mus musculus	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	up
Homo sapiens	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	up
Mus musculus	GPAT3 mRNA expression is significantly upregulated (about 60fold) during 3T3-L1 adipocyte differentiation. GPAT3 expression is also upregulated by TSH	up
Mus musculus	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	up

General Information

General Information	Comment	Organism
malfunction	knockdown of GPAT3 and 4 almost completely prevents the formation of lipid droplets. Deficiency of GPAT greatly reduces TAG synthesis and impairs adipogenesis	Homo sapiens
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	Mus musculus
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	Mus musculus
malfunction	the alteration of lipid composition in GPAT1-/- mice decreases the susceptibility to carcinogen-induced liver tumorigenesis. Furthermore, although the changes in cellular metabolism associated with increased GPAT1 expression lead to overall ameliorative survival in breast cancer	Homo sapiens
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	Mus musculus
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	Mus musculus
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	Homo sapiens
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	Mus musculus
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	Homo sapiens
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	Mus musculus
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	Mus musculus
metabolism	relation between three isoforms GPAT1, 3, and 4 and insulin resistance, role of GPAT2 in lipid metabolism, overview	Homo sapiens
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)	Mus musculus
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)	Mus musculus
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)	Homo sapiens
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). GPAT3 probably contains two transmembrane domains, and the active site of GPAT3 is located in the N-terminal domain	Homo sapiens
additional information	the GPAT/AGPAT family acyltransferases contain four wellconserved domains (motif I-IV), which catalyze the transferase reaction and are involved in binding to the substrate (acyl acceptor, e.g. G3P). GPAT4 possesses a series of membrane insertion helices which form hairpin loops in the membrane or monolayer. The active acyltransferase domain is located close to the C-terminus	Homo sapiens
additional information	the N-terminal domain of GPAT2 associates with the active site, which possesses the maximum homology to that of GPAT1. 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). The motif IV of GPAT2 is restricted to the mitochondrial membrane, but the remaining acyltransferase motifs are exposed to the cytoplasmic side of the mitochondria	Homo sapiens
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. 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. Mitochondrial isozyme GPAT1 activity has a huge impact on the regulation of TAG 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. Mitochondrial GPAT1 is a critical regulator of triacylglycerol metabolism and systemic energy homeostasis	Homo sapiens
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	Mus musculus
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. GPAT3 play a crucial role in lipid formation. GPAT3 plays a critical role in regulating glucose, energy, and lipid homeostasis	Homo sapiens
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 is a positive regulator of body weight	Homo sapiens
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	Mus musculus
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. Isozyme GPAT2 is highly expressed in several cancer types (such as lung, melanoma, breast, and prostate cancer) and cancer-derived human cell lines, in which GPAT2 expression is associated with histological grading of the tumor. The expression level of GPAT2 promotes the proliferation, tumorigenicity, and migration rates of breast tumor cells	Homo sapiens
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	Mus musculus
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	Mus musculus