GPAM encodes glycerol-3-phosphate acyltransferase 1, mitochondrial (GPAT1), a peripheral membrane enzyme on the cytosolic face of the mitochondrial outer membrane. It transfers a fatty acyl group from long-chain acyl-CoA, preferentially palmitoyl-CoA, to the sn-1 position of glycerol-3-phosphate to form lysophosphatidic acid, the committed first step of de novo glycerolipid synthesis. The lysophosphatidic acid is acylated further to phosphatidic acid by other enzymes and feeds triacylglycerol and glycerophospholipid synthesis; in liver this partitions acyl-CoA toward esterification rather than mitochondrial beta-oxidation. The enzyme has an N-terminal acyltransferase domain with an HXXXXD catalytic motif and a C-terminal domain needed for folding, and associates with the membrane through an amphipathic surface and an N-terminal loop-helix that carries the mitochondrial-targeting signal. This UniProt entry (A0A9L0TTC1, 790 aa) is one of several horse GPAM splice products and lacks a 38-residue segment of the catalytic domain present in the canonical 828-aa product (A0A9L0TCA8); its own activity has not been tested.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004366 glycerol-3-phosphate O-acyltransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Glycerol-3-phosphate O-acyltransferase activity is the defining catalytic activity of GPAT1. Reason: Human GPAT1 catalyses acyl transfer from acyl-CoA to the sn-1 position of glycerol-3-phosphate (cryo-EM structure plus functional assays, PMID:36522428; experimentally supported UniProt function). Horse GPAM is in the same PANTHER subfamily (PTHR12563:SF16) and descends from PAINT node PTN000970957, where curators placed this activity for metazoan GPAT1/GPAT2, so the transfer is phylogenetically grounded rather than a best-hit inference. A0A9L0TTC1 itself is a non-canonical splice product lacking human-equivalent residues 370-407, a conserved catalytic-domain segment with resolved secondary structure; it keeps the HXXXXD motif and all six CoA-binding residues, but whether this isoform is active is untested, so the annotation is accepted as a statement about the GPAM gene product. 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 Mitochondrial membrane protein that catalyzes the essential file:HORSE/GPAM/GPAM-bioinformatics/RESULTS-rereview.md UniProt assigns A0A9L0TTC1 to PANTHER PTHR12563:SF16 (GLYCEROL-3-PHOSPHATE ACYLTRANSFERASE 1, MITOCHONDRIAL), the same subfamily as human GPAM (Q9HCL2). file:HORSE/GPAM/GPAM-bioinformatics/RESULTS-rereview.md node PTN000970957 (taxon 6072, Eumetazoa) carries IBD assertions for glycerol-3-phosphate O-acyltransferase activity (GO:0004366) file:HORSE/GPAM/GPAM-bioinformatics/RESULTS-rereview.md the HXXXXD catalytic motif (human 230-235, 6/6 identical), the six CoA-binding residues (278, 279, 288, 293, 328, 462; 6/6) and the mitochondrial-localization region (80-120; 39/41) |
| GO:0005741 mitochondrial outer membrane | IEA GO_REF:0000044 | ACCEPT | Summary: GPAT1 is a peripheral protein of the cytosolic face of the mitochondrial outer membrane. Reason: The human structure shows membrane association through an amphipathic patch and an N-terminal loop-helix carrying the mitochondrial-targeting signal (PMID:36522428). The corresponding horse region (human 80-120) is retained in A0A9L0TTC1 at 39/41 identity, and PAINT places mitochondrion on the ancestral node; the outer-membrane term is the precise supported location. 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:human/GPAM/GPAM-deep-research-falcon.md The functional site is the **cytosolic face of the mitochondrial outer membrane**, not the matrix or inner membrane. file:HORSE/GPAM/GPAM-bioinformatics/RESULTS-rereview.md the HXXXXD catalytic motif (human 230-235, 6/6 identical), the six CoA-binding residues (278, 279, 288, 293, 328, 462; 6/6) and the mitochondrial-localization region (80-120; 39/41) |
| GO:0005886 plasma membrane | IEA GO_REF:0000002 | REMOVE | Summary: Plasma membrane is a bacterial-PlsB-derived InterPro2GO mapping that does not apply to mitochondrial GPAT1. Reason: This IEA comes from InterPro IPR028354 (GPAT_PlsB), a signature shared with bacterial PlsB, which acts at the bacterial inner (plasma) membrane. Eukaryotic GPAT1 is localized to the mitochondrial outer membrane by direct structural and functional work, the PAINT curators placed mitochondrion and not plasma membrane on the metazoan node, and no study places GPAT1 at the plasma 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. file:HORSE/GPAM/GPAM-bioinformatics/RESULTS-rereview.md PAINT did not place any plasma-membrane term on this node. |
| GO:0006629 lipid metabolic process | IEA GO_REF:0000002 | MODIFY | Summary: Lipid metabolic process is correct but too general; GPAT1 catalyses the first step of glycerolipid synthesis. Reason: GPAT1 performs the committed first acylation of glycerol-3-phosphate, so its product feeds triacylglycerol and glycerophospholipid synthesis. The specific process terms supported for the SF16/PTN000970957 clade are triglyceride biosynthetic process (PAINT IBD; experimental in human and mouse) and phospholipid biosynthetic process (already on this entry), which replace this general term. The human GPAM review accepted this row; it is refined here under the rule that correct-but-general terms are MODIFY. Proposed replacements: triglyceride biosynthetic process phospholipid biosynthetic process 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-deep-research-falcon.md LPA is subsequently acylated by AGPAT enzymes to phosphatidic acid (PA), dephosphorylated by lipins/phosphatidate phosphatases to diacylglycerol (DAG), and either acylated by DGAT to triacylglycerol (TAG) or routed into glycerophospholipid synthesis. file:HORSE/GPAM/GPAM-bioinformatics/RESULTS-rereview.md glycerophospholipid metabolic process (GO:0006650) and triglyceride biosynthetic process (GO:0019432) |
| GO:0008654 phospholipid biosynthetic process | IEA GO_REF:0000002 | ACCEPT | Summary: GPAT1 catalyses the first step of de novo phospholipid (glycerophospholipid) synthesis. Reason: Lysophosphatidic acid made by GPAT1 is acylated to phosphatidic acid, the precursor of glycerophospholipids; GPAT1 therefore performs a step of this pathway (participation, not mere supply). PAINT places glycerophospholipid metabolic process on the ancestral metazoan node. 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-deep-research-falcon.md LPA is subsequently acylated by AGPAT enzymes to phosphatidic acid (PA), dephosphorylated by lipins/phosphatidate phosphatases to diacylglycerol (DAG), and either acylated by DGAT to triacylglycerol (TAG) or routed into glycerophospholipid synthesis. file:HORSE/GPAM/GPAM-bioinformatics/RESULTS-rereview.md glycerophospholipid metabolic process (GO:0006650) and triglyceride biosynthetic process (GO:0019432) |
| GO:0016024 CDP-diacylglycerol biosynthetic process | IEA GO_REF:0000104 | ACCEPT | Summary: GPAT1 catalyses step 1 of CDP-diacylglycerol synthesis from glycerol-3-phosphate. Reason: The human UniProt pathway assignment for this step is experimentally supported (PubMed:18238778), and the reaction is the glycerol-3-phosphate acylation that starts the route to phosphatidic acid and CDP-diacylglycerol. Consistent with the human GPAM review. Quantitatively, hepatic GPAT1 output is directed mainly to triacylglycerol, but catalysing the first step is participation in this process. Supporting Evidence: file:human/GPAM/GPAM-uniprot.txt PATHWAY: Phospholipid metabolism; CDP-diacylglycerol biosynthesis; CDP- 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:0016746 acyltransferase activity | IEA GO_REF:0000002 | MODIFY | Summary: Acyltransferase activity is correct but too general. Reason: The specific activity, established for the GPAT1 clade and retained in sequence here, is glycerol-3-phosphate O-acyltransferase activity, which this entry already carries. Proposed replacements: glycerol-3-phosphate O-acyltransferase activity 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:HORSE/GPAM/GPAM-bioinformatics/RESULTS-rereview.md node PTN000970957 (taxon 6072, Eumetazoa) carries IBD assertions for glycerol-3-phosphate O-acyltransferase activity (GO:0004366) |
| 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 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: 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:HORSE/GPAM/GPAM-bioinformatics/RESULTS-rereview.md node PTN000970957 (taxon 6072, Eumetazoa) carries IBD assertions for glycerol-3-phosphate O-acyltransferase activity (GO:0004366) |
| GO:0031966 mitochondrial membrane | IEA GO_REF:0000104 | MODIFY | Summary: Mitochondrial membrane is correct but the outer membrane is the supported compartment. Reason: The previous review kept this as non-core while arguing it was too general; the correct action for a true-but-general location is MODIFY 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. |
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Download this section (compressed HTML)Q: Is the horse GPAM transcript ENSECAT00000105322 (A0A9L0TTC1), which skips a 38-codon segment encoding part of the catalytic domain (human residues 370-407), expressed as protein, and does it retain glycerol-3-phosphate acyltransferase activity?
Experiment: Express canonical horse GPAM (A0A9L0TCA8) and the 790-aa isoform A0A9L0TTC1 side by side and compare NEM-resistant glycerol-3-phosphate acyltransferase activity with palmitoyl-CoA and mitochondrial outer-membrane targeting; confirm isoform expression by RT-PCR across the skipped exon junction.
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