GPAM encodes glycerol-3-phosphate acyltransferase 1, mitochondrial (GPAT1). This peripheral membrane enzyme sits on the cytosolic face of the mitochondrial outer membrane. It transfers a long-chain fatty acyl group from acyl-CoA, preferentially saturated palmitoyl-CoA, to the sn-1 position of glycerol 3-phosphate, making lysophosphatidic acid. This is the committed first step of de novo glycerolipid synthesis. Other enzymes acylate the lysophosphatidic acid to phosphatidic acid, which feeds triacylglycerol synthesis and glycerophospholipid synthesis. In liver, GPAT1 competes with carnitine palmitoyltransferase 1 on the outer membrane for acyl-CoA and so steers fatty acids toward esterification rather than beta-oxidation. The protein has an N-terminal acyltransferase domain with an HXXXXD catalytic motif and a C-terminal domain needed for folding. It binds the membrane through an amphipathic surface and an N-terminal loop-helix that carries the mitochondrial-targeting signal. The horse protein (A0A9L0TCA8, 828 aa, the canonical GPAM product) is a full-length ortholog of the experimentally characterised human and rodent enzymes. Its functions are inferred from them and have not been tested in horse.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004366 glycerol-3-phosphate O-acyltransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Glycerol-3-phosphate O-acyltransferase activity is the defining catalytic activity of GPAT1; core function. Reason: PAINT curators placed this activity at PTN000970957 from experimental data on human GPAM and mouse/rat GPAT1/GPAT2 (the human record gives EC 2.3.1.15 with ECO:0000269 evidence). No GPAM study exists in horse; this is a phylogenetic transfer. A0A9L0TCA8 is in PANTHER PTHR12563:SF16 with human GPAM and mouse Gpam and descends from PAINT node PTN000970957, and it aligns gap-free to human GPAT1 (94.4% identity) with the HXXXXD motif and CoA-binding residues conserved. The target is inside the clade that inherited the function and shows no sign of divergence. Supporting Evidence: file:HORSE/GPAM__A0A9L0TCA8/GPAM__A0A9L0TCA8-bioinformatics/RESULTS.md for glycerol-3-phosphate O-acyltransferase activity (GO:0004366), mitochondrion (GO:0005739), glycerophospholipid file:HORSE/GPAM__A0A9L0TCA8/GPAM__A0A9L0TCA8-bioinformatics/RESULTS.md UniProt assigns A0A9L0TCA8 to PANTHER PTHR12563:SF16 (GLYCEROL-3-PHOSPHATE ACYLTRANSFERASE 1, MITOCHONDRIAL), file:HORSE/GPAM__A0A9L0TCA8/GPAM__A0A9L0TCA8-bioinformatics/RESULTS.md GPAT1 than the experimentally studied mouse and rat orthologs are, and keeps the HXXXXD catalytic motif and all PMID:36522428 Glycerol-3-phosphate acyltransferase (GPAT)1 is a mitochondrial outer membrane protein that catalyzes the first step of de novo glycerolipid biosynthesis. file:human/GPAM/GPAM-uniprot.txt produce lysophosphatidic acid (PubMed:18238778). |
| GO:0004366 glycerol-3-phosphate O-acyltransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Same core activity from the EC/UniRule/InterPro combined pipeline; consistent with the IBA row. Reason: The EC 2.3.1.15 mapping comes from the PIRNR/UniRule GPAT_DHAPAT family rule. It agrees with the phylogenetically grounded IBA and with conservation of the catalytic HXXXXD motif. No GPAM study exists in horse; this is a phylogenetic transfer. A0A9L0TCA8 is in PANTHER PTHR12563:SF16 with human GPAM and mouse Gpam and descends from PAINT node PTN000970957, and it aligns gap-free to human GPAT1 (94.4% identity) with the HXXXXD motif and CoA-binding residues conserved. Supporting Evidence: PMID:36522428 Glycerol-3-phosphate acyltransferase (GPAT)1 is a mitochondrial outer membrane protein that catalyzes the first step of de novo glycerolipid biosynthesis. file:human/GPAM/GPAM-uniprot.txt produce lysophosphatidic acid (PubMed:18238778). file:HORSE/GPAM__A0A9L0TCA8/GPAM__A0A9L0TCA8-bioinformatics/RESULTS.md GPAT1 than the experimentally studied mouse and rat orthologs are, and keeps the HXXXXD catalytic motif and all |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | MODIFY | Summary: Mitochondrion is correct but the outer membrane is the supported sub-compartment. Reason: PAINT placed mitochondrion at the GPAT1/GPAT2 node, which is correctly scoped for that clade. For GPAT1 specifically, structural and functional work on the human protein puts it on the outer membrane as a peripheral protein, and the N-terminal targeting region is conserved in horse (39/41). The location is refined to mitochondrial outer membrane, which this entry already carries; this matches the human GPAM review. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN000970957 SUPPORTS TRANSFER Eumetazoa GPAT1/GPAT2 node; horse GPAM A0A9L0TCA8 (PTHR12563:SF16) is a descendant. The node-level term is correctly scoped for the clade; refinement to outer membrane uses GPAT1-specific donor evidence and is not a propagation failure. Proposed replacements: mitochondrial outer membrane Supporting Evidence: file:HORSE/GPAM__A0A9L0TCA8/GPAM__A0A9L0TCA8-bioinformatics/RESULTS.md for glycerol-3-phosphate O-acyltransferase activity (GO:0004366), mitochondrion (GO:0005739), glycerophospholipid PMID:36522428 Glycerol-3-phosphate acyltransferase (GPAT)1 is a mitochondrial outer membrane protein that catalyzes the first step of de novo glycerolipid biosynthesis. PMID:36522428 GPAT1 has no transmembrane regions as previously proposed but instead associates with the membrane via an amphipathic surface patch and an N-terminal loop-helix region that contains a mitochondrial-targeting signal file:human/GPAM/GPAM-uniprot.txt outer membrane of hepatic cells via a patch of basic residues. |
| GO:0005741 mitochondrial outer membrane | IEA GO_REF:0000044 | ACCEPT | Summary: GPAT1 is a peripheral protein on the cytosolic face of the mitochondrial outer membrane. Reason: Human GPAT1 associates with the outer membrane through an amphipathic patch and an N-terminal loop-helix that carries the mitochondrial-targeting signal (cryo-EM plus mutagenesis). Horse keeps that region, and PAINT places the ancestral clade in the mitochondrion. Inferred for horse, not tested. Supporting Evidence: PMID:36522428 Glycerol-3-phosphate acyltransferase (GPAT)1 is a mitochondrial outer membrane protein that catalyzes the first step of de novo glycerolipid biosynthesis. PMID:36522428 GPAT1 has no transmembrane regions as previously proposed but instead associates with the membrane via an amphipathic surface patch and an N-terminal loop-helix region that contains a mitochondrial-targeting signal file:human/GPAM/GPAM-uniprot.txt outer membrane of hepatic cells via a patch of basic residues. file:HORSE/GPAM__A0A9L0TCA8/GPAM__A0A9L0TCA8-bioinformatics/RESULTS.md GPAT1 than the experimentally studied mouse and rat orthologs are, and keeps the HXXXXD catalytic motif and all |
| GO:0005886 plasma membrane | IEA GO_REF:0000002 | REMOVE | Summary: Plasma membrane is an InterPro2GO mapping from the bacterial PlsB-type signature and does not apply to mitochondrial GPAT1. Reason: IPR028354 (GPAT_PlsB) covers bacterial PlsB, which acts at the bacterial cytoplasmic membrane. Eukaryotic GPAT1 is targeted to the mitochondrial outer membrane. PAINT curators placed mitochondrion and no plasma-membrane term on any PTHR12563 node, and no study puts GPAT1 at the plasma membrane. This matches the human GPAM review. Supporting Evidence: file:HORSE/GPAM__A0A9L0TCA8/GPAM__A0A9L0TCA8-bioinformatics/RESULTS.md PAINT placed no plasma-membrane term on any PTHR12563 node. PMID:36522428 Glycerol-3-phosphate acyltransferase (GPAT)1 is a mitochondrial outer membrane protein that catalyzes the first step of de novo glycerolipid biosynthesis. file:human/GPAM/GPAM-uniprot.txt outer membrane of hepatic cells via a patch of basic residues. |
| GO:0006629 lipid metabolic process | IEA GO_REF:0000002 | MODIFY | Summary: Lipid metabolic process is correct but too general. Reason: GPAT1 carries out the first acylation of glycerol 3-phosphate. That step belongs to both triacylglycerol synthesis (IBA here, from mouse knockout and human data) and phosphatidic acid synthesis, so both specific processes replace this term. Proposed replacements: phosphatidic acid biosynthetic process triglyceride biosynthetic process Supporting Evidence: PMID:12417724 These data confirm the important role of mtGPAT in the synthesis of triacylglycerol Reactome:R-HSA-1483166 In the de novo synthesis of phosphatidic acid (PA), lysophosphatidic acid (LPA) is initially formed by the esterification of sn-1 by glycerol 3-phosphate acyltransferase (GPAT) from glycerol 3-phosphate (G3P). file:HORSE/GPAM__A0A9L0TCA8/GPAM__A0A9L0TCA8-bioinformatics/RESULTS.md metabolic process (GO:0006650) and triglyceride biosynthetic process (GO:0019432). |
| GO:0006650 glycerophospholipid metabolic process | IBA GO_REF:0000033 | MODIFY | Summary: Glycerophospholipid metabolic process is correctly scoped at the PAINT node, but GPAT1 performs a specific step: the first acylation in de novo phosphatidic acid synthesis. Reason: GPAT1 makes 1-acyl lysophosphatidic acid, which AGPATs convert to phosphatidic acid, so it performs a step of phosphatidic acid biosynthetic process (GO:0006654), an is_a descendant of this term. The same refinement was made in the human GPAM review. This is not a propagation failure; the node-level term is simply broader than the GPAT1-specific step. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN000970957 SUPPORTS TRANSFER Eumetazoa GPAT1/GPAT2 node; horse GPAM A0A9L0TCA8 (PTHR12563:SF16) is a descendant. The node-level term is correctly scoped for the clade; refinement to phosphatidic acid biosynthetic process uses GPAT1-specific donor evidence and is not a propagation failure. Proposed replacements: phosphatidic acid biosynthetic process Supporting Evidence: file:HORSE/GPAM__A0A9L0TCA8/GPAM__A0A9L0TCA8-bioinformatics/RESULTS.md metabolic process (GO:0006650) and triglyceride biosynthetic process (GO:0019432). Reactome:R-HSA-1483166 In the de novo synthesis of phosphatidic acid (PA), lysophosphatidic acid (LPA) is initially formed by the esterification of sn-1 by glycerol 3-phosphate acyltransferase (GPAT) from glycerol 3-phosphate (G3P). 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:0008654 phospholipid biosynthetic process | IEA GO_REF:0000002 | MODIFY | Summary: Phospholipid biosynthetic process is correct but general; refine to phosphatidic acid biosynthetic process. Reason: The lysophosphatidic acid made by GPAT1 is acylated to phosphatidic acid, the precursor of glycerophospholipids. GPAT1 therefore carries out a step of phosphatidic acid biosynthesis, a descendant of this term. This is consistent with the human GPAM review. Proposed replacements: phosphatidic acid biosynthetic process Supporting Evidence: Reactome:R-HSA-1483166 In the de novo synthesis of phosphatidic acid (PA), lysophosphatidic acid (LPA) is initially formed by the esterification of sn-1 by glycerol 3-phosphate acyltransferase (GPAT) from glycerol 3-phosphate (G3P). 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:0016024 CDP-diacylglycerol biosynthetic process | IEA GO_REF:0000104 | KEEP AS NON CORE | Summary: GPAT1 catalyses step 1 of the glycerol-3-phosphate route to CDP-diacylglycerol; true but peripheral. Reason: The UniRule pathway assignment (step 1/3 of CDP-diacylglycerol from sn-glycerol 3-phosphate) is correct as far as the chemistry goes. But in vivo GPAT1 output goes mainly to triacylglycerol, and its knockout leaves hepatic phospholipid content unchanged, so the term is kept as non-core. This matches the human GPAM review. Supporting Evidence: Reactome:R-HSA-1483166 In the de novo synthesis of phosphatidic acid (PA), lysophosphatidic acid (LPA) is initially formed by the esterification of sn-1 by glycerol 3-phosphate acyltransferase (GPAT) from glycerol 3-phosphate (G3P). PMID:12417724 Hepatic cholesterol and phospholipid contents did not differ between the genotypes. |
| GO:0016746 acyltransferase activity | IEA GO_REF:0000002 | MODIFY | Summary: Acyltransferase activity is correct but too general. Reason: The specific activity for the GPAT1 clade, glycerol-3-phosphate O-acyltransferase activity, is conserved here and already carried by this entry. Proposed replacements: glycerol-3-phosphate O-acyltransferase activity Supporting Evidence: file:HORSE/GPAM__A0A9L0TCA8/GPAM__A0A9L0TCA8-bioinformatics/RESULTS.md for glycerol-3-phosphate O-acyltransferase activity (GO:0004366), mitochondrion (GO:0005739), glycerophospholipid 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:0016747 acyltransferase activity, transferring groups other than amino-acyl groups | IEA GO_REF:0000002 | MODIFY | Summary: This parent acyltransferase term is correct but too general. Reason: Replace it with glycerol-3-phosphate O-acyltransferase activity, the specific reaction established for GPAT1 and already carried by this entry. Proposed replacements: glycerol-3-phosphate O-acyltransferase activity Supporting Evidence: file:HORSE/GPAM__A0A9L0TCA8/GPAM__A0A9L0TCA8-bioinformatics/RESULTS.md for glycerol-3-phosphate O-acyltransferase activity (GO:0004366), mitochondrion (GO:0005739), glycerophospholipid 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:0019432 triglyceride biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: Core process: GPAT1 catalyses the first acylation of the glycerol-3-phosphate route to triacylglycerol. Reason: GPAT1 performs a step of the process (acylation of glycerol 3-phosphate), so this is participation and not only necessity. The IBD at PTN000970957 is seeded by mouse Gpam and human GPAM. Gpam knockout mice have less hepatic triacylglycerol, and Gpat1-null hepatocytes cannot put de novo fatty acid into TAG. No GPAM study exists in horse; this is a phylogenetic transfer. A0A9L0TCA8 is in PANTHER PTHR12563:SF16 with human GPAM and mouse Gpam and descends from PAINT node PTN000970957, and it aligns gap-free to human GPAT1 (94.4% identity) with the HXXXXD motif and CoA-binding residues conserved. Supporting Evidence: file:HORSE/GPAM__A0A9L0TCA8/GPAM__A0A9L0TCA8-bioinformatics/RESULTS.md metabolic process (GO:0006650) and triglyceride biosynthetic process (GO:0019432). PMID:12417724 These data confirm the important role of mtGPAT in the synthesis of triacylglycerol PMID:23908354 demonstrate that GPAT1, but not GPAT4, is required to incorporate de novo file:HORSE/GPAM__A0A9L0TCA8/GPAM__A0A9L0TCA8-bioinformatics/RESULTS.md UniProt assigns A0A9L0TCA8 to PANTHER PTHR12563:SF16 (GLYCEROL-3-PHOSPHATE ACYLTRANSFERASE 1, MITOCHONDRIAL), |
| GO:0031966 mitochondrial membrane | IEA GO_REF:0000104 | MODIFY | Summary: Mitochondrial membrane is correct; the outer membrane is the supported compartment. Reason: This is a true-but-general location. Refine it to mitochondrial outer membrane, which this entry already carries. Proposed replacements: mitochondrial outer membrane Supporting Evidence: PMID:36522428 Glycerol-3-phosphate acyltransferase (GPAT)1 is a mitochondrial outer membrane protein that catalyzes the first step of de novo glycerolipid biosynthesis. file:human/GPAM/GPAM-uniprot.txt outer membrane of hepatic cells via a patch of basic residues. |
Loading supporting content…
Download this section (compressed HTML)Q: Is horse GPAT1 regulated by nutrition in liver and adipose tissue as in rodents, and does it contribute to hepatic lipid accumulation in equine metabolic syndrome or hyperlipaemia?
Q: Which horse GPAM transcripts are translated? Is the 790-aa isoform A0A9L0TTC1, which lacks the human 370-407 equivalent, active alongside the canonical A0A9L0TCA8 product?
Experiment: Express canonical horse GPAM (A0A9L0TCA8) and measure N-ethylmaleimide-resistant glycerol-3-phosphate acyltransferase activity with palmitoyl-CoA versus oleoyl-CoA, together with mitochondrial outer-membrane targeting (protease-protection of isolated mitochondria), to confirm the inferred activity and location in this species.
Type: in vitro enzyme assay / subcellular fractionation
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)