Gpam encodes glycerol-3-phosphate acyltransferase 1 (GPAT1, mtGPAT), the N-ethylmaleimide-resistant glycerol-3-phosphate acyltransferase of the mitochondrial outer membrane and a member of the GPAT/DHAPAT (PlsB-like) acyltransferase family (PANTHER PTHR12563:SF16). It transfers a long-chain acyl group, preferentially palmitoyl, from acyl-CoA to the sn-1 position of sn-glycerol 3-phosphate to form lysophosphatidic acid, the committed first step of de novo glycerolipid synthesis that leads to phosphatidic acid, diacylglycerol, triacylglycerol and glycerophospholipids. GPAT1 is most abundant in liver and adipose tissue, where it accounts for a large share of total GPAT activity. In mice, loss of Gpam abolishes mitochondrial GPAT activity, lowers hepatic, plasma and cardiac triacylglycerol, prevents incorporation of newly synthesised fatty acids into triacylglycerol and diverts acyl-CoA toward mitochondrial beta-oxidation, and reduces sn-1 palmitate in liver and heart phospholipids. Outer-membrane placement and a peripheral, non-transmembrane mode of membrane association are established for the rat and human orthologues.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001817 regulation of cytokine production | IMP PMID:18971390 Glycerol-3-phosphate acyltransferase-1 regulates murine T-ly... | MARK AS OVER ANNOTATED | Summary: Gpam-/- T cells secrete less Th1 and more Th2 cytokines. Reason: Downstream phenotype of a whole-body knockout. The authors attribute it to altered membrane phospholipid composition and increased arachidonate/PGE2, i.e. indirect effects of the lipid-synthesis defect; GPAT1 does not carry out a step of T-cell signalling or cytokine production. Supporting Evidence: PMID:18971390 These changes may be due to alterations in membrane lipid composition since we found changes in the relative content of individual phospholipid species |
| GO:0004366 glycerol-3-phosphate O-acyltransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Glycerol-3-phosphate O-acyltransferase activity propagated from PAINT node PTN000970957 (Eumetazoa GPAT1/GPAT2 clade), of which mouse Gpam (MGI:109162) is itself an experimental seed. Reason: Core catalytic activity. Mouse Gpam is in PANTHER subfamily PTHR12563:SF16 (GPAT1, mitochondrial) and is one of the IBD seeds of this node, so the IBA is grounded in mouse experimental data and agrees with knockout loss of mitochondrial GPAT activity (PMID:12417724). Supporting Evidence: file:mouse/Gpam/Gpam-uniprot.txt PTHR12563:SF16; GLYCEROL-3-PHOSPHATE ACYLTRANSFERASE 1, MITOCHONDRIAL PMID:12417724 demonstrating successful elimination of mtGPAT activity |
| GO:0004366 glycerol-3-phosphate O-acyltransferase activity | IDA PMID:12417724 Mitochondrial glycerol-3-phosphate acyltransferase-deficient... | ACCEPT | Summary: Liver membranes from Gpam-/- mice lose the N-ethylmaleimide-resistant (mitochondrial) GPAT activity measured in wild type; the paper also reports activity of the recombinant mouse enzyme with a palmitoyl-CoA preference. Reason: Direct enzymatic assay in mouse tissue with genetic ablation as control; establishes GO:0004366 for mouse GPAT1 experimentally. Supporting Evidence: PMID:12417724 demonstrating successful elimination of mtGPAT activity PMID:12417724 The activity of mouse recombinant mtGPAT expressed in Sf9 insect cells is 5.5-fold higher with 16:0-CoA than with 18:1-, 18:2n6-, or 18:3n3-CoA |
| GO:0004366 glycerol-3-phosphate O-acyltransferase activity | IDA PMID:15152008 A novel cardiolipin-remodeling pathway revealed by a gene en... | ACCEPT | Summary: Annotation from the ALCAT1 cardiolipin acyltransferase paper; the cached abstract does not describe the GPAT1 measurement, which was probably a comparator assay in the full text. Reason: Full text not available here; the abstract foregrounds ALCAT1 and reports that ALCAT1 itself has no glycerol-3-phosphate acyltransferase activity. The MGI curator saw the full text, and the activity is in any case firmly established for mouse GPAT1 (PMID:12417724), so the row is accepted and deferred to the curator. Supporting Evidence: PMID:12417724 demonstrating successful elimination of mtGPAT activity |
| GO:0004366 glycerol-3-phosphate O-acyltransferase activity | IDA PMID:24939733 Glycerol-3-phosphate acyltransferase-4-deficient mice are pr... | ACCEPT | Summary: Annotation from a GPAT4 knockout study (Coleman lab); the abstract does not describe the GPAT1 assay, which likely served as comparator. The same paper is used by MGI in GO-CAM 6446bfcb00000006 as evidence for the Gpam activity node. Reason: Full text not available here. The function is clearly correct for mouse GPAT1 (PMID:12417724, PMID:16935266), so the curator is not overruled. Supporting Evidence: PMID:12417724 demonstrating successful elimination of mtGPAT activity |
| GO:0004366 glycerol-3-phosphate O-acyltransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA (Ensembl Compara ortholog of human Q9HCL2, InterPro IPR028354, Rhea reactions/EC 2.3.1.15). Reason: Consistent with direct mouse evidence and with the 1:1 orthology to human GPAM within PTHR12563:SF16. Supporting Evidence: file:mouse/Gpam/Gpam-uniprot.txt PTHR12563:SF16; GLYCEROL-3-PHOSPHATE ACYLTRANSFERASE 1, MITOCHONDRIAL PMID:12417724 demonstrating successful elimination of mtGPAT activity |
| GO:0004366 glycerol-3-phosphate O-acyltransferase activity | IMP PMID:12417724 Mitochondrial glycerol-3-phosphate acyltransferase-deficient... | ACCEPT | Summary: Gpam-/- liver membranes lack mitochondrial GPAT activity. Reason: Loss-of-function with a direct enzyme assay as readout; consistent with IDA from the same paper. Supporting Evidence: PMID:12417724 demonstrating successful elimination of mtGPAT activity |
| GO:0004366 glycerol-3-phosphate O-acyltransferase activity | IMP PMID:16935266 Hepatic knockdown of mitochondrial GPAT1 in ob/ob mice impro... | ACCEPT | Summary: Adenoviral shRNA knockdown of Gpam in ob/ob mouse liver produces a dose-dependent loss of mtGPAT1 activity. Reason: Independent mouse loss-of-function evidence with an activity readout. Supporting Evidence: PMID:16935266 Reduced expression of mtGPAT1 mRNA in liver of ob/ob mice resulted in dramatic and dose dependent reduction in mtGPAT1 activity |
| GO:0004366 glycerol-3-phosphate O-acyltransferase activity | IMP PMID:18339309 The role of mitochondrial glycerol-3-phosphate acyltransfera... | ACCEPT | Summary: Independent AstraZeneca Gpat1-/- mouse line; the abstract describes GPAT as catalysing the first committed step and reports metabolic phenotypes. Reason: Abstract-only; the activity measurement is presumably in the full text. Activity is well established for mouse GPAT1, so accepted. Supporting Evidence: PMID:18339309 Glycerol-3-phosphate acyltransferase (GPAT) is involved in triacylglycerol (TAG) and phospholipid synthesis, catalyzing the first committed step PMID:12417724 demonstrating successful elimination of mtGPAT activity |
| GO:0004366 glycerol-3-phosphate O-acyltransferase activity | IMP PMID:23908354 Glycerol-3-phosphate acyltransferase (GPAT)-1, but not GPAT4... | ACCEPT | Summary: Gpat1-/- primary hepatocytes cannot incorporate de novo synthesised fatty acid into TAG. Reason: Consistent with the activity; the knockout phenotype is the expected consequence of losing the first acylation step. Supporting Evidence: PMID:23908354 GPAT1, but not GPAT4, is required to incorporate de novo synthesized fatty acids into TAG and to divert them away from oxidation |
| GO:0004366 glycerol-3-phosphate O-acyltransferase activity | ISO GO_REF:0000096 | ACCEPT | Summary: Transferred from rat Gpam (RGD:61847), same PANTHER subfamily SF16. Reason: 1:1 orthologue within PTHR12563:SF16; matches direct mouse evidence. Supporting Evidence: file:mouse/Gpam/Gpam-uniprot.txt PTHR12563:SF16; GLYCEROL-3-PHOSPHATE ACYLTRANSFERASE 1, MITOCHONDRIAL |
| GO:0004366 glycerol-3-phosphate O-acyltransferase activity | ISO GO_REF:0000119 | ACCEPT | Summary: Transferred from human GPAM (Q9HCL2), same PANTHER subfamily SF16. Reason: 1:1 orthologue within PTHR12563:SF16; matches direct mouse evidence. Supporting Evidence: file:mouse/Gpam/Gpam-uniprot.txt PTHR12563:SF16; GLYCEROL-3-PHOSPHATE ACYLTRANSFERASE 1, MITOCHONDRIAL PMID:36522428 Glycerol-3-phosphate acyltransferase (GPAT)1 is a mitochondrial outer membrane protein that catalyzes the first step of de novo glycerolipid biosynthesis. |
| GO:0005739 mitochondrion | HDA PMID:14651853 Integrated analysis of protein composition, tissue diversity... | MODIFY | Summary: Detected in mouse mitochondrial proteomic inventories. Reason: Correct but general. The active GPAT1 pool is on the outer mitochondrial membrane (rat liver subfractionation, PMID:17493869; human cryo-EM structure, PMID:36522428); refine to GO:0005741, which the gene already carries. Proposed replacements: mitochondrial outer membrane Supporting Evidence: PMID:14651853 we performed a proteomic survey of mitochondria from mouse brain, heart, kidney, and liver PMID:17493869 two pools of GPAT1 are present in rat liver mitochondria: an active one, located in OMM |
| GO:0005739 mitochondrion | HDA PMID:18614015 A mitochondrial protein compendium elucidates complex I dise... | MODIFY | Summary: Detected in mouse mitochondrial proteomic inventories. Reason: Correct but general. The active GPAT1 pool is on the outer mitochondrial membrane (rat liver subfractionation, PMID:17493869; human cryo-EM structure, PMID:36522428); refine to GO:0005741, which the gene already carries. Proposed replacements: mitochondrial outer membrane Supporting Evidence: PMID:18614015 we performed mass spectrometry, GFP tagging, and machine learning to create a mitochondrial compendium of 1098 genes PMID:17493869 two pools of GPAT1 are present in rat liver mitochondria: an active one, located in OMM |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | MODIFY | Summary: Mitochondrion propagated from PAINT node PTN000970957, with mouse Gpam among the seeds. Reason: Correct but general. The active GPAT1 pool is on the outer mitochondrial membrane (rat liver subfractionation, PMID:17493869; human cryo-EM structure, PMID:36522428); refine to GO:0005741, which the gene already carries. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN000970957 SUPPORTS TRANSFER Eumetazoa GPAT1/GPAT2 node with mouse Gpam as a seed; the node-level term is correct for the clade, and refinement to the outer membrane uses GPAT1-specific evidence. Proposed replacements: mitochondrial outer membrane Supporting Evidence: file:mouse/Gpam/Gpam-uniprot.txt PTHR12563:SF16; GLYCEROL-3-PHOSPHATE ACYLTRANSFERASE 1, MITOCHONDRIAL PMID:17493869 two pools of GPAT1 are present in rat liver mitochondria: an active one, located in OMM |
| GO:0005739 mitochondrion | IDA PMID:12417724 Mitochondrial glycerol-3-phosphate acyltransferase-deficient... | MODIFY | Summary: Mitochondrial localization from the Gpam knockout paper (activity in mitochondria-containing membrane fractions). Reason: Correct but general. The active GPAT1 pool is on the outer mitochondrial membrane (rat liver subfractionation, PMID:17493869; human cryo-EM structure, PMID:36522428); refine to GO:0005741, which the gene already carries. Proposed replacements: mitochondrial outer membrane Supporting Evidence: PMID:12417724 One isoform is located in the outer mitochondrial membrane (mtGPAT) PMID:17493869 two pools of GPAT1 are present in rat liver mitochondria: an active one, located in OMM |
| GO:0005739 mitochondrion | IMP PMID:18339309 The role of mitochondrial glycerol-3-phosphate acyltransfera... | MODIFY | Summary: Mitochondrial location from the AstraZeneca Gpat1-/- study. Reason: Correct but general. The active GPAT1 pool is on the outer mitochondrial membrane (rat liver subfractionation, PMID:17493869; human cryo-EM structure, PMID:36522428); refine to GO:0005741, which the gene already carries. Proposed replacements: mitochondrial outer membrane Supporting Evidence: PMID:18522808 Glycerol-3-phosphate acyltransferase-1 (GPAT1), which is located on the outer mitochondrial membrane comprises up to 30% of total GPAT activity in the heart. PMID:17493869 two pools of GPAT1 are present in rat liver mitochondria: an active one, located in OMM |
| GO:0005741 mitochondrial outer membrane | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular location mapping (SL-0172, mitochondrion outer membrane), assigned by similarity to human. Reason: Outer mitochondrial membrane is the site of the active enzyme in rat liver and in the human structure; same subfamily. Supporting Evidence: PMID:17493869 two pools of GPAT1 are present in rat liver mitochondria: an active one, located in OMM PMID:36522428 Glycerol-3-phosphate acyltransferase (GPAT)1 is a mitochondrial outer membrane protein that catalyzes the first step of de novo glycerolipid biosynthesis. |
| GO:0005741 mitochondrial outer membrane | IMP PMID:18339309 The role of mitochondrial glycerol-3-phosphate acyltransfera... | ACCEPT | Summary: Outer mitochondrial membrane activity location from the AstraZeneca Gpat1-/- study. Reason: Abstract-only, but outer membrane location is consistent with all targeted localization data for GPAT1. Supporting Evidence: PMID:18522808 Glycerol-3-phosphate acyltransferase-1 (GPAT1), which is located on the outer mitochondrial membrane comprises up to 30% of total GPAT activity in the heart. PMID:17493869 two pools of GPAT1 are present in rat liver mitochondria: an active one, located in OMM |
| GO:0005741 mitochondrial outer membrane | ISO GO_REF:0000096 | ACCEPT | Summary: Transferred from rat Gpam. Reason: Rat liver subfractionation places active GPAT1 in the OMM; 1:1 orthologue. Supporting Evidence: PMID:17493869 two pools of GPAT1 are present in rat liver mitochondria: an active one, located in OMM PMID:17493869 GPAT1 was rapidly incorporated into mitochondria, but not into microsomes |
| GO:0005741 mitochondrial outer membrane | ISO PMID:17493869 Mitochondrial glycerol-3-P acyltransferase 1 is most active ... | ACCEPT | Summary: Transferred from rat Gpam using the rat liver subfractionation study. Reason: Direct rat evidence that the active pool is in the OMM and that the protein is imported into mitochondria but not microsomes; orthologue in the same subfamily. Supporting Evidence: PMID:17493869 two pools of GPAT1 are present in rat liver mitochondria: an active one, located in OMM PMID:17493869 GPAT1 was rapidly incorporated into mitochondria, but not into microsomes |
| GO:0005743 mitochondrial inner membrane | HDA PMID:12865426 Proteomic analysis of the mouse liver mitochondrial inner me... | REMOVE | Summary: Identified in a proteomic list of purified mouse liver mitochondrial inner membranes. Reason: Contradicted by targeted localization: active GPAT1 is in the outer membrane (PMID:17493869) and the human structure shows a peripheral, cytosol-facing outer-membrane enzyme (PMID:36522428). Detection in an inner-membrane preparation most likely reflects co-purifying outer membrane or contact sites; no study places GPAT1 activity in the inner membrane. Supporting Evidence: PMID:12865426 Here we have focused our study on the identification of proteins of the mitochondrial inner membrane (MIM). PMID:17493869 two pools of GPAT1 are present in rat liver mitochondria: an active one, located in OMM |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-MMU-9907201 | REMOVE | Summary: Location attached to a Reactome gene-expression event (Gpam transcription stimulated by Pparg2 and Mll4). Reason: The Reactome event describes transcription of Gpam, not the location of the protein. GPAT1 is imported into mitochondria but not microsomes (PMID:17493869) and acts at the outer mitochondrial membrane; the ER-resident GPATs are GPAT3/GPAT4 (Agpat9/Gpat4), not GPAT1. Supporting Evidence: Reactome:R-MMU-9907201 expression of the Gpam gene is stimulated by Pparg2 and the Kmt2d (Mll4) complex PMID:17493869 GPAT1 was rapidly incorporated into mitochondria, but not into microsomes |
| GO:0005886 plasma membrane | IEA GO_REF:0000002 | REMOVE | Summary: InterPro2GO mapping from IPR028354 (GPAT_PlsB). Reason: The mapping reflects bacterial PlsB, an inner (plasma) membrane enzyme of bacteria. Mammalian GPAT1 is a mitochondrial outer membrane enzyme (PMID:17493869, PMID:36522428); there is no evidence for plasma membrane location. Supporting Evidence: PMID:17493869 two pools of GPAT1 are present in rat liver mitochondria: an active one, located in OMM PMID:36522428 Glycerol-3-phosphate acyltransferase (GPAT)1 is a mitochondrial outer membrane protein that catalyzes the first step of de novo glycerolipid biosynthesis. |
| GO:0006629 lipid metabolic process | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO lipid metabolic process. Reason: Correct but very general; the specific processes are TAG and phosphatidic acid biosynthesis. Proposed replacements: triglyceride biosynthetic process phosphatidic acid biosynthetic process Supporting Evidence: PMID:12417724 The synthesis of triacylglycerol and the glycerophospholipids begins with the acylation of glycerol-3-phosphate by glycerol-3-phosphate acyltransferase (GPAT) to form LPA |
| GO:0006631 fatty acid metabolic process | IMP PMID:12417724 Mitochondrial glycerol-3-phosphate acyltransferase-deficient... | KEEP AS NON CORE | Summary: Gpam-/- liver lipids have altered fatty acid composition (less sn-1 palmitate, more sn-2 arachidonate). Reason: GPAT1 esterifies long-chain (preferentially 16:0) acyl-CoA and so channels fatty acids into glycerolipids; a real but peripheral facet relative to TAG/PA synthesis. Supporting Evidence: PMID:12417724 in the positioning of specific fatty acids, particularly palmitate and arachidonate, in phospholipids |
| GO:0006637 acyl-CoA metabolic process | IMP PMID:15878874 Mitochondrial glycerol-3-phosphate acyltransferase-1 is esse... | KEEP AS NON CORE | Summary: Hepatic acyl-CoA is ~3-fold higher in Gpam-/- mice. Reason: GPAT1 consumes long-chain acyl-CoA as substrate, so it participates in acyl-CoA metabolism; peripheral to the core role. Supporting Evidence: PMID:15878874 mtGPAT1 is essential for normal acyl-CoA metabolism |
| GO:0006641 triglyceride metabolic process | IMP PMID:15878874 Mitochondrial glycerol-3-phosphate acyltransferase-1 is esse... | MODIFY | Summary: Gpam-/- liver on a high-fat/high-sucrose diet has 60% less TAG with fatty acids partitioned to oxidation. Reason: Correct but general; the gene acts in TAG biosynthesis (GO:0019432), already on the gene. Proposed replacements: triglyceride biosynthetic process Supporting Evidence: PMID:15878874 the absence of hepatic mtGPAT1 results in the partitioning of fatty acids away from triacylglycerol synthesis and toward oxidation and ketogenesis |
| GO:0006641 triglyceride metabolic process | IMP PMID:16935266 Hepatic knockdown of mitochondrial GPAT1 in ob/ob mice impro... | MODIFY | Summary: Hepatic knockdown in ob/ob mice reduces hepatic TAG. Reason: Correct but general; refine to TAG biosynthesis. Proposed replacements: triglyceride biosynthetic process Supporting Evidence: PMID:16935266 acute reduction of mtGPAT1 in liver of ob/ob mice reduces TAG synthesis |
| GO:0006641 triglyceride metabolic process | IMP PMID:18522808 Mice deficient in mitochondrial glycerol-3-phosphate acyltra... | MODIFY | Summary: Gpat1-/- hearts accumulate 20-80% less TAG on lipogenic diets and incorporate less palmitate into TAG. Reason: Correct but general; the paper measures TAG synthesis (labelled palmitate incorporation), so refine to GO:0019432. Proposed replacements: triglyceride biosynthetic process Supporting Evidence: PMID:18522808 our data suggest that GPAT1 contributes significantly to cardiomyocyte TAG synthesis during lipogenic or high fat diets |
| GO:0006650 glycerophospholipid metabolic process | IBA GO_REF:0000033 | MODIFY | Summary: Glycerophospholipid metabolic process from PAINT node PTN000970957. Reason: Correct but general; GPAT1 acts specifically in the first step of phosphatidic acid biosynthesis (GO:0006654), which the gene already carries. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN000970957 SUPPORTS TRANSFER Eumetazoa GPAT1/GPAT2 node with mouse Gpam as a seed; node-level term is correctly scoped, refinement to phosphatidic acid biosynthesis is gene-specific. Proposed replacements: phosphatidic acid biosynthetic process Supporting Evidence: PMID:12417724 The synthesis of triacylglycerol and the glycerophospholipids begins with the acylation of glycerol-3-phosphate by glycerol-3-phosphate acyltransferase (GPAT) to form LPA |
| GO:0006650 glycerophospholipid metabolic process | IMP PMID:18971390 Glycerol-3-phosphate acyltransferase-1 regulates murine T-ly... | MODIFY | Summary: Gpam-/- T cells show altered phospholipid species composition. Reason: Correct but general; the enzyme initiates phosphatidic acid synthesis. Proposed replacements: phosphatidic acid biosynthetic process Supporting Evidence: PMID:18971390 These changes may be due to alterations in membrane lipid composition since we found changes in the relative content of individual phospholipid species |
| GO:0006651 diacylglycerol biosynthetic process | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Diacylglycerol biosynthesis transferred from rat. Reason: DAG is produced from GPAT1-derived phosphatidic acid by lipin; GPAT1 catalyses the first step of this branch. Mouse loss-of-function lowers hepatic DAG. Kept as non-core because GPAT1 acts upstream of the DAG-forming step and the core processes are TAG/PA synthesis. Supporting Evidence: PMID:16054099 mtGPAT1(-/-) mice displayed markedly lower hepatic triacylglycerol and diacylglycerol concentrations |
| GO:0006651 diacylglycerol biosynthetic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Diacylglycerol biosynthesis transferred from rat. Reason: DAG is produced from GPAT1-derived phosphatidic acid by lipin; GPAT1 catalyses the first step of this branch. Mouse loss-of-function lowers hepatic DAG. Kept as non-core because GPAT1 acts upstream of the DAG-forming step and the core processes are TAG/PA synthesis. Supporting Evidence: PMID:16054099 mtGPAT1(-/-) mice displayed markedly lower hepatic triacylglycerol and diacylglycerol concentrations |
| GO:0006654 phosphatidic acid biosynthetic process | ISO GO_REF:0000096 | ACCEPT | Summary: Phosphatidic acid biosynthesis transferred from rat GPAT1. Reason: GPAT1 forms lysophosphatidic acid, the first step of de novo phosphatidic acid synthesis (UniProt pathway: CDP-diacylglycerol from sn-glycerol 3-phosphate step 1/3). Mouse data support it indirectly (altered phospholipid acyl composition, PMID:12417724). Supporting Evidence: PMID:12417724 The synthesis of triacylglycerol and the glycerophospholipids begins with the acylation of glycerol-3-phosphate by glycerol-3-phosphate acyltransferase (GPAT) to form LPA |
| GO:0006654 phosphatidic acid biosynthetic process | ISS GO_REF:0000024 | ACCEPT | Summary: Phosphatidic acid biosynthesis transferred from rat GPAT1. Reason: GPAT1 forms lysophosphatidic acid, the first step of de novo phosphatidic acid synthesis (UniProt pathway: CDP-diacylglycerol from sn-glycerol 3-phosphate step 1/3). Mouse data support it indirectly (altered phospholipid acyl composition, PMID:12417724). Supporting Evidence: PMID:12417724 The synthesis of triacylglycerol and the glycerophospholipids begins with the acylation of glycerol-3-phosphate by glycerol-3-phosphate acyltransferase (GPAT) to form LPA file:mouse/Gpam/Gpam-uniprot.txt PTHR12563:SF16; GLYCEROL-3-PHOSPHATE ACYLTRANSFERASE 1, MITOCHONDRIAL |
| GO:0006655 phosphatidylglycerol biosynthetic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Phosphatidylglycerol biosynthesis transferred from human GPAM. Reason: Rests only on the human enzyme: UniProt curates a human GPAT1 lysophosphatidylglycerol acyltransferase reaction (RHEA:33203; ECO:0000269 PMID:19075029). This side activity is not demonstrated for mouse GPAT1, and PAINT did not propagate GO:0006655 at node PTN000970957. Kept as non-core and flagged as orthologue-inferred. Supporting Evidence: file:human/GPAM/GPAM-uniprot.txt Reaction=1-acyl-sn-glycero-3-phospho-(1'-sn-glycerol) + an acyl-CoA = a |
| GO:0006655 phosphatidylglycerol biosynthetic process | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Phosphatidylglycerol biosynthesis transferred from human GPAM. Reason: Rests only on the human enzyme: UniProt curates a human GPAT1 lysophosphatidylglycerol acyltransferase reaction (RHEA:33203; ECO:0000269 PMID:19075029). This side activity is not demonstrated for mouse GPAT1, and PAINT did not propagate GO:0006655 at node PTN000970957. Kept as non-core and flagged as orthologue-inferred. Supporting Evidence: file:human/GPAM/GPAM-uniprot.txt Reaction=1-acyl-sn-glycero-3-phospho-(1'-sn-glycerol) + an acyl-CoA = a |
| GO:0006655 phosphatidylglycerol biosynthetic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Phosphatidylglycerol biosynthesis transferred from human GPAM. Reason: Rests only on the human enzyme: UniProt curates a human GPAT1 lysophosphatidylglycerol acyltransferase reaction (RHEA:33203; ECO:0000269 PMID:19075029). This side activity is not demonstrated for mouse GPAT1, and PAINT did not propagate GO:0006655 at node PTN000970957. Kept as non-core and flagged as orthologue-inferred. Supporting Evidence: file:human/GPAM/GPAM-uniprot.txt Reaction=1-acyl-sn-glycero-3-phospho-(1'-sn-glycerol) + an acyl-CoA = a |
| GO:0008654 phospholipid biosynthetic process | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO phospholipid biosynthesis. Reason: Correct but general; refine to phosphatidic acid biosynthetic process. Proposed replacements: phosphatidic acid biosynthetic process Supporting Evidence: PMID:12417724 The synthesis of triacylglycerol and the glycerophospholipids begins with the acylation of glycerol-3-phosphate by glycerol-3-phosphate acyltransferase (GPAT) to form LPA |
| GO:0009749 response to glucose | IMP PMID:15878874 Mitochondrial glycerol-3-phosphate acyltransferase-1 is esse... | MARK AS OVER ANNOTATED | Summary: Gpam-/- mice on a high-fat/high-sucrose diet show hyperinsulinemia and reduced glucose tolerance. Reason: Whole-animal glucose tolerance is a downstream physiological phenotype of altered hepatic lipid flux; GPAT1 does not carry out a step of the cellular response to glucose. Supporting Evidence: PMID:15878874 Hyperinsulinemia and reduced glucose tolerance on the HH diet was greater in the mtGPAT1-/- mice |
| GO:0009749 response to glucose | IMP PMID:16054099 Prevention of hepatic steatosis and hepatic insulin resistan... | MARK AS OVER ANNOTATED | Summary: Gpam-/- mice are protected from fat-induced hepatic insulin resistance. Reason: Downstream metabolic phenotype (lower DAG and PKC activation); not participation in a response to glucose. Supporting Evidence: PMID:16054099 were protected from hepatic insulin resistance possibly due to a lower diacylglycerol-mediated PKC activation |
| GO:0010867 positive regulation of triglyceride biosynthetic process | ISO GO_REF:0000096 | MODIFY | Summary: Positive regulation of TAG biosynthesis transferred from rat (overexpression raises TAG synthesis). Reason: GPAT1 is the enzyme of the first, rate-limiting step, not a regulator of the pathway; increased flux on overexpression reflects more catalyst. Lateral correction to TAG biosynthetic process. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: RGD:61847 SUPPORTS SOURCE BUT NOT TARGET Rat Gpam overexpression raises TAG synthesis; an enzyme of the pathway was recorded as a positive regulator. The underlying biology transfers, the regulatory framing does not. Proposed replacements: triglyceride biosynthetic process Supporting Evidence: PMID:12417724 The synthesis of triacylglycerol and the glycerophospholipids begins with the acylation of glycerol-3-phosphate by glycerol-3-phosphate acyltransferase (GPAT) to form LPA PMID:12417724 These data confirm the important role of mtGPAT in the synthesis of triacylglycerol |
| GO:0014823 response to activity | ISO GO_REF:0000096 | MARK AS OVER ANNOTATED | Summary: Response to activity transferred from rat. Reason: Likely based on expression change after exercise in rat; expression change does not show participation, and no mouse evidence exists. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: RGD:61847 SOURCE WEAK OR INFERRED Rat source annotation (exercise-related response) not inspected; likely expression-based and does not establish participation. Supporting Evidence: PMID:12417724 The synthesis of triacylglycerol and the glycerophospholipids begins with the acylation of glycerol-3-phosphate by glycerol-3-phosphate acyltransferase (GPAT) to form LPA |
| GO:0016024 CDP-diacylglycerol biosynthetic process | IEA GO_REF:0000041 | KEEP AS NON CORE | Summary: UniPathway: CDP-diacylglycerol from sn-glycerol 3-phosphate, step 1/3. Reason: GPAT1 catalyses the first step of the route to PA, which feeds CDP-DAG; valid but peripheral to the main TAG role. No mouse-specific evidence on CDP-DAG. Supporting Evidence: file:mouse/Gpam/Gpam-uniprot.txt PATHWAY: Phospholipid metabolism; CDP-diacylglycerol biosynthesis; CDP- |
| GO:0016746 acyltransferase activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro-based generic acyltransferase activity (IPR002123). Reason: Correct but general; the specific activity, glycerol-3-phosphate O-acyltransferase activity (GO:0004366), is experimentally established for mouse GPAT1 and already on the gene. Proposed replacements: glycerol-3-phosphate O-acyltransferase activity Supporting Evidence: PMID:12417724 demonstrating successful elimination of mtGPAT activity |
| GO:0016747 acyltransferase activity, transferring groups other than amino-acyl groups | IEA GO_REF:0000002 | MODIFY | Summary: InterPro-based acyltransferase (non-amino-acyl groups) activity (IPR022284). Reason: Correct but general; refine to GO:0004366, which the gene already carries with experimental support. Proposed replacements: glycerol-3-phosphate O-acyltransferase activity Supporting Evidence: PMID:12417724 demonstrating successful elimination of mtGPAT activity |
| GO:0019432 triglyceride biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: TAG biosynthesis from PAINT node PTN000970957, with mouse Gpam as seed. Reason: Core process; GPAT1 catalyses its first step and mouse knockouts lose TAG synthesis. Supporting Evidence: PMID:12417724 These data confirm the important role of mtGPAT in the synthesis of triacylglycerol PMID:23908354 GPAT1, but not GPAT4, is required to incorporate de novo synthesized fatty acids into TAG and to divert them away from oxidation |
| GO:0019432 triglyceride biosynthetic process | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl Compara transfer from human GPAM. Reason: Consistent with mouse experimental data. Supporting Evidence: PMID:12417724 These data confirm the important role of mtGPAT in the synthesis of triacylglycerol |
| GO:0019432 triglyceride biosynthetic process | IMP PMID:12417724 Mitochondrial glycerol-3-phosphate acyltransferase-deficient... | ACCEPT | Summary: Gpam-/- mice have lower hepatic and plasma TAG and reduced VLDL-TAG secretion. Reason: GPAT1 catalyses the committed first step of the glycerol-3-phosphate pathway to TAG, so it participates directly (enzyme of the pathway). Supporting Evidence: PMID:12417724 These data confirm the important role of mtGPAT in the synthesis of triacylglycerol PMID:12417724 The synthesis of triacylglycerol and the glycerophospholipids begins with the acylation of glycerol-3-phosphate by glycerol-3-phosphate acyltransferase (GPAT) to form LPA |
| GO:0019432 triglyceride biosynthetic process | IMP PMID:23908354 Glycerol-3-phosphate acyltransferase (GPAT)-1, but not GPAT4... | ACCEPT | Summary: Gpat1-/- hepatocytes cannot incorporate de novo synthesised fatty acid into TAG. Reason: Direct mouse evidence for participation in TAG synthesis. Supporting Evidence: PMID:23908354 GPAT1, but not GPAT4, is required to incorporate de novo synthesized fatty acids into TAG and to divert them away from oxidation |
| GO:0019432 triglyceride biosynthetic process | ISO GO_REF:0000119 | ACCEPT | Summary: Transferred from human GPAM. Reason: Same subfamily; consistent with mouse data. Supporting Evidence: PMID:12417724 These data confirm the important role of mtGPAT in the synthesis of triacylglycerol |
| GO:0031966 mitochondrial membrane | ISO GO_REF:0000096 | MODIFY | Summary: Mitochondrial membrane transferred from rat Gpam. Reason: Correct but general; rat data specifically place active GPAT1 in the outer membrane, so refine to GO:0005741. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: RGD:61847 SUPPORTS TRANSFER Rat Gpam is an outer mitochondrial membrane enzyme (PMID:17493869); the term transfers correctly but is less specific than GO:0005741. Proposed replacements: mitochondrial outer membrane Supporting Evidence: PMID:17493869 two pools of GPAT1 are present in rat liver mitochondria: an active one, located in OMM |
| GO:0032869 cellular response to insulin stimulus | ISO GO_REF:0000096 | MARK AS OVER ANNOTATED | Summary: Cellular response to insulin transferred from rat (Gpam is insulin/SREBP-1c induced). Reason: Induction of Gpam expression by insulin makes it a target of insulin signalling, not a participant in the response; no evidence that GPAT1 executes a step of insulin signalling. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: ROLE CONFLATION Sources checked: RGD:61847 SOURCE WEAK OR INFERRED Rat source reflects insulin induction of Gpam expression, which makes Gpam a target of insulin signalling rather than a participant in the response. Supporting Evidence: PMID:18522808 Gpat1 mRNA, protein, and activity in liver and adipose tissue increase with carbohydrate feeding and with insulin stimulation via SREBP-1c |
| GO:0040018 positive regulation of multicellular organism growth | IMP PMID:12417724 Mitochondrial glycerol-3-phosphate acyltransferase-deficient... | REMOVE | Summary: Gpam-/- mice weigh less than controls. Reason: The full text attributes lower body weight to reduced adipose mass (less TAG storage), not to altered regulation of organismal growth; mice were viable, fertile and of normal litter size. This is an indirect organismal phenotype, not regulation of growth. Supporting Evidence: PMID:12417724 Genotype had a significant effect on gonadal fat mass and on total fat per unit of body weight |
| GO:0042104 positive regulation of activated T cell proliferation | IMP PMID:18971390 Glycerol-3-phosphate acyltransferase-1 regulates murine T-ly... | MARK AS OVER ANNOTATED | Summary: Gpam-/- T-lymphocyte proliferation is inhibited. Reason: Downstream phenotype of a whole-body knockout. The authors attribute it to altered membrane phospholipid composition and increased arachidonate/PGE2, i.e. indirect effects of the lipid-synthesis defect; GPAT1 does not carry out a step of T-cell signalling or cytokine production. Supporting Evidence: PMID:18971390 These changes may be due to alterations in membrane lipid composition since we found changes in the relative content of individual phospholipid species |
| GO:0051607 defense response to virus | IMP PMID:19193813 Glycerol-3-phosphate acyltransferase 1 is essential for the ... | MARK AS OVER ANNOTATED | Summary: Gpat1-/- mice infected with coxsackievirus B3 have higher mortality and viral titres. Reason: Organismal infection phenotype; the authors propose indirect mechanisms (membrane composition, redox status). Not participation in antiviral defence. Supporting Evidence: PMID:19193813 Innate mechanisms may be affected by altered membrane composition or host redox status |
| GO:0055089 fatty acid homeostasis | IMP PMID:18522808 Mice deficient in mitochondrial glycerol-3-phosphate acyltra... | MARK AS OVER ANNOTATED | Summary: Gpat1-/- hearts and plasma have altered fatty acid profiles. Reason: The paper shows altered acyl composition of complex lipids, not control of free fatty acid levels; the authors note systemic contributions they cannot exclude. Fatty acid homeostasis is an indirect consequence. Supporting Evidence: PMID:18522808 we cannot with certainty attribute these changes to the absence of heart GPAT1 |
| GO:0055091 phospholipid homeostasis | IMP PMID:18522808 Mice deficient in mitochondrial glycerol-3-phosphate acyltra... | KEEP AS NON CORE | Summary: Gpat1-/- hearts have altered phospholipid fatty acid composition. Reason: The sn-1 acyl selectivity of GPAT1 shapes membrane phospholipid acyl composition; reasonable as a non-core consequence of its activity. Supporting Evidence: PMID:18522808 it appears that heart GPAT1 plays an important role in establishing the fatty acid composition of its membrane phospholipids |
| GO:0070236 negative regulation of activation-induced cell death of T cells | IMP PMID:18971390 Glycerol-3-phosphate acyltransferase-1 regulates murine T-ly... | MARK AS OVER ANNOTATED | Summary: Activation-induced apoptosis of Gpam-/- T cells is increased. Reason: Downstream phenotype of a whole-body knockout. The authors attribute it to altered membrane phospholipid composition and increased arachidonate/PGE2, i.e. indirect effects of the lipid-synthesis defect; GPAT1 does not carry out a step of T-cell signalling or cytokine production. Supporting Evidence: PMID:18971390 These changes may be due to alterations in membrane lipid composition since we found changes in the relative content of individual phospholipid species |
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Download this section (compressed HTML)Q: Does mouse GPAT1 have physiologically relevant lysophosphatidylglycerol acyltransferase activity, as reported for the human enzyme in vitro, or is GO:0006655 an over-transfer from human?
Q: How is lysophosphatidic acid made by GPAT1 on the mitochondrial outer membrane delivered to the ER for TAG synthesis, and is the low-activity GPAT1 pool at ER-mitochondria contact sites involved?
Experiment: Assay purified mouse GPAT1 with 1-acyl-lysophosphatidylglycerol and acyl-CoA, alongside glycerol 3-phosphate, to test whether the lysoPG acyltransferase side activity reported for the human enzyme is conserved.
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