Gene Ontology annotation through association of InterPro records with GO terms
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Automatic Gene Ontology annotation based on Rhea mapping
Combined Automated Annotation using Multiple IEA Methods
A visual intracellular classification strategy for uncharacterized human proteins.
Identification and characterization of a gene encoding human LPGAT1, an endoplasmic reticulum-associated lysophosphatidylglycerol acyltransferase.
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Recombinant human LPGAT1 increased lysophosphatidylglycerol acyltransferase activity in two heterologous expression systems.
"Expression of the LPGAT1 cDNA in Sf9 insect and COS-7 cells led to a significant increase in LPG acyltransferase activity."
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The original study reported no detectable activity against several other lysophospholipid classes under its assay conditions.
"In contrast, no significant acyltransferase activities were detected against glycerol 3-phosphate or a variety of lysophospholipids, including lysophosphatidylcholine, lysophosphatidylethanolamine, lysophosphatidylinositol, and lysophosphatidylserine."
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The recombinant human enzyme preferred long-chain saturated acyl-CoAs and oleoyl-CoA among tested donors.
"The recombinant human LPGAT1 enzyme recognized various acyl-CoAs and LPGs as substrates but demonstrated clear preference to long chain saturated fatty acyl-CoAs and oleoyl-CoA as acyl donors"
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Human LPGAT1 localized to the endoplasmic reticulum by fractionation and immunohistochemistry.
"LPGAT1 was localized to the endoplasmic reticulum by subcellular fractionation and immunohistochemical analyses."
Defining the membrane proteome of NK cells.
MicroRNA-30c reduces hyperlipidemia and atherosclerosis in mice by decreasing lipid synthesis and lipoprotein secretion.
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Hepatic miR-30c expression reduced Lpgat1 transcript abundance in mice, and the same direction was observed in human Huh-7 cells.
"Analysis of hepatic mRNA showed that miR-30c reduced Lpgat1, Elovl5, Stard3 and Mboat1 mRNA levels"
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LPGAT1 knockdown reduced de novo lipogenesis in the Huh-7 experimental context.
"siELOVL5 and siLPGAT1 reduced de novo lipogenesis"
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LPGAT1 knockdown did not itself reduce secreted apoB, separating the lipid-synthesis phenotype from the MTP-dependent secretion effect.
"siLPGAT1 had no effect on media apoB"
Identification and characterization of LPLAT7 as an sn-1-specific lysophospholipid acyltransferase.
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LPLAT7/LPGAT1 incorporated fatty acids mainly into the sn-1 position of LPC and LPE in vitro.
"In vitro, we found LPLAT7 mainly incorporated several fatty acids into the sn-1 position of lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE), with weak activities toward other lyso-PLs."
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Loss of LPLAT7 specifically reduced C18:0-containing PC and PE in mutant cells and knockout-mouse tissues.
"only C18:0-containing phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were specifically reduced in the LPLAT7-mutant cells and tissues from knockout mice, with a concomitant increase in the level of C16:0- and C18:1-containing PC and PE."
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The study resolved three biochemical preferences: unsaturated sn-2 LPC acceptors, choline/ethanolamine head groups, and C18:0/C16:0 acyl-CoA donors.
"In the present study, we identified three biochemical preferences of LPLAT7: (1) sn-2-rich LPCs with unsaturated fatty acids as acyl acceptors (Fig. 4I), (2) choline and ethanolamine as head groups of lyso-PLs (Fig. 4E), and (3) C18:0-CoA and C16:0-CoA as acyl donors (Fig. 4G)."
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Human isoform 1 was assayed in HEK293A-cell membrane fractions, but that construct choice does not establish isoform-specific biology.
"cDNA for human LPLAT7 (hLPGAT1 isoform1; NCBI accession number NM_014873) was amplified by PCR using PrimeStar HS Polymerase (TAKARA BIO Inc) and HEK293A cell cDNA as a template."
1-acyl LPG is acylated to PG by LPGAT
2-acyl LPG is acylated to PG by LPGAT
Acyl chain remodelling of PG
Novel acyl-coenzyme A:monoacylglycerol acyltransferase plays an important role in hepatic triacylglycerol secretion.
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This mouse study identified LPGAT1 as a monoacylglycerol acyltransferase candidate.
"In this study, we identified a novel MGAT gene, which is identical with lysophosphatidylglycerol acyltransferase1 (LPGAT1)."
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Liver-directed Lpgat1 shRNA in db/db mice lowered serum triacylglycerol and cholesterol while raising hepatic cholesterol.
"treatment with LPGAT1 shRNA adenovirus caused a marked reduction in serum triacylglycerol and cholesterol levels and a significant increase in hepatic cholesterol level."
Defective Phosphatidylglycerol Remodeling Causes Hepatopathy, Linking Mitochondrial Dysfunction to Hepatosteatosis.
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Whole-body Lpgat1 knockout in mice protected against diet-induced obesity but caused hepatopathy, insulin resistance, NAFLD, and mitochondrial defects.
"LPGAT1 deficiency protected mice from diet-induced obesity, but led to hepatopathy, insulin resistance, and NAFLD as a consequence of oxidative stress, mitochondrial DNA depletion, and mitochondrial dysfunction."
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The authors interpreted the mouse phenotype as a role for PG remodeling in obesity and NAFLD.
"This study identified an unexpected role of PG remodeling in obesity, linking mitochondrial dysfunction to NAFLD."
LPGAT1 controls the stearate/palmitate ratio of phosphatidylethanolamine and phosphatidylcholine in sn-1 specific remodeling.
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The study identifies LPGAT1 as an sn-1 acyltransferase controlling stearate/palmitate ratios in PE and PC.
"Here, we demonstrate that lysophosphatidylglycerol acyltransferase 1 (LPGAT1) is an sn-1 specific acyltransferase that controls the stearate/palmitate ratio of phosphatidylethanolamine (PE) and phosphatidylcholine."
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Bacterially expressed mouse LPGAT1 preferred sn-1 LPE and stearoyl-CoA rather than LPG under the reported assay conditions.
"Bacterially expressed murine LPGAT1 transferred saturated acyl-CoAs specifically into the sn-1 position of lysophosphatidylethanolamine (LPE) rather than lysophosphatidylglycerol and preferred stearoyl-CoA over palmitoyl-CoA as the substrate."
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Mouse knockout abolished 1-LPE:stearoyl-CoA activity and shifted PE, dimethyl-PE, and PC from stearate toward palmitate species.
"genetic ablation of LPGAT1 in mice abolished 1-LPE:stearoyl-CoA acyltransferase activity and caused a shift from stearate to palmitate species in PE, dimethyl-PE, and phosphatidylcholine."
LPGAT1 controls MEGDEL syndrome by coupling phosphatidylglycerol remodeling with mitochondrial transport.
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The authors report an interaction-based model coupling ER PG remodeling by LPGAT1 to mitochondrial transport through prohibitin/TIMM14 machinery.
"We show that PG remodeling by LPGAT1 at the ER is closely coordinated with mitochondrial transport through interaction with the prohibitin/TIMM14 mitochondrial import motor."
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Lpgat1 or Timm14 ablation caused abnormal fatty-acyl composition, ER retention of newly remodeled PG, and mitochondrial structural and respiratory defects in the reported systems.
"ablation of LPGAT1 or TIMM14 not only causes aberrant fatty acyl compositions but also ER retention of newly remodeled PG, leading to profound loss in mitochondrial crista structure and respiration."
LPLAT7 reutilizes unsaturated 1-lysophospholipids formed during lysosomal phospholipid degradation.
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LPLAT7/LPGAT1 is an ER acyltransferase that reacylates lysosome-derived unsaturated 1-lysophospholipids.
"We found that LPLAT7 (LPGAT1), an acyltransferase of the endoplasmic reticulum, reacylates specifically lysosome-derived 1-lysophospholipids that carry an unsaturated chain."
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Its reported native substrate selectivity is for stearoyl-CoA and unsaturated 1-lyso-2-acyl positional isomers.
"The enzymatic activity of LPLAT7 was specific for stearoyl-CoA and 1-lyso-2-acyl positional isomers of unsaturated lysophospholipids."
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Mouse knockout lowered 1-stearoyl-2-unsaturated PC, PE, and PS and impaired membrane regeneration.
"In mice, Lplat7 knockout increased the concentration of unsaturated lysophospholipids, reduced the abundance of 1-stearoyl-2-unsaturated species of phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine, and inhibited the regeneration of cellular membranes."
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The authors attribute the historical LPG assignment to possible intramolecular acyl migration and report no in-vivo PG support.
"We speculate that LPLAT7 was misidentified as LPGAT1 (6) because LPG, having 3 unesterified hydroxyl groups, is prone to intramolecular acyl migration. As a result, 1-lyso-PG may become available when 2-lyso-PG is used as substrate. However, our lipidomics data do not demonstrate any involvement of LPLAT7 with PG in vivo."
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Lysosomal phospholipid degradation is proposed as the principal source of LPLAT7 substrates.
"Our data suggest that lysosomal phospholipid degradation is the principal source of LPLAT7 substrates."
LPGAT1 secondary acylation capacities and lipid pathway scope: OpenScientist focused report