GNPAT (glyceronephosphate O-acyltransferase; dihydroxyacetone phosphate acyltransferase, DHAPAT; EC 2.3.1.42) is a peroxisomal enzyme that catalyzes the first committed step of ether-glycerolipid (plasmalogen) biosynthesis. It transfers a long-chain acyl group from an acyl-CoA to dihydroxyacetone phosphate (glycerone phosphate, DHAP) to form 1-acylglycerone 3-phosphate (acyl-DHAP) plus CoA. The acyl-DHAP product is subsequently used by alkyl-dihydroxyacetone phosphate synthase (AGPS) to form the characteristic ether bond of plasmalogens. GNPAT is a peripheral membrane protein anchored on the matrix (lumenal) side of the peroxisomal membrane and carries a C-terminal type-1 peroxisomal targeting signal (PTS1). The active enzyme is part of a heterotrimeric complex with AGPS. Loss of GNPAT activity causes a severe deficiency of plasmalogens and is the primary defect in rhizomelic chondrodysplasia punctata type 2 (RCDP2).
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005778 peroxisomal membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetically inferred peroxisomal membrane localization. This is the correct, experimentally supported location of GNPAT, which is a peripheral membrane protein on the matrix side of the peroxisomal membrane. Supporting Evidence: file:human/GNPAT/GNPAT-uniprot.txt SUBCELLULAR LOCATION: Peroxisome membrane |
| GO:0008611 ether lipid biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetically inferred role in ether lipid biosynthesis. This is the core biological process of GNPAT, which catalyzes the first committed step of plasmalogen (ether lipid) biosynthesis. Supporting Evidence: PMID:15687349 the peroxisomal DHAPAT is essential for the file:human/GNPAT/GNPAT-uniprot.txt Dihydroxyacetonephosphate acyltransferase catalyzing the |
| GO:0016287 glycerone-phosphate O-acyltransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetically inferred glycerone-phosphate O-acyltransferase (DHAPAT) activity. This is the core molecular function of GNPAT and is strongly supported by direct enzymatic assays. Supporting Evidence: file:human/GNPAT/GNPAT-uniprot.txt Reaction=dihydroxyacetone phosphate + an acyl-CoA = a 1-acylglycerone |
| GO:0005777 peroxisome | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic annotation of peroxisomal localization. Correct core location; GNPAT is a peroxisomal enzyme with a C-terminal PTS1, experimentally localized to the peroxisome. Supporting Evidence: file:human/GNPAT/GNPAT-uniprot.txt SUBCELLULAR LOCATION: Peroxisome membrane |
| GO:0005778 peroxisomal membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Electronic annotation (UniProt Subcellular Location mapping) of peroxisomal membrane localization. Correct core location. Supporting Evidence: file:human/GNPAT/GNPAT-uniprot.txt SUBCELLULAR LOCATION: Peroxisome membrane |
| GO:0006629 lipid metabolic process | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro-based electronic annotation to the broad parent term lipid metabolic process. Correct but general; the specific process (ether lipid biosynthesis) is captured by more informative terms. Supporting Evidence: file:human/GNPAT/GNPAT-uniprot.txt Dihydroxyacetonephosphate acyltransferase catalyzing the |
| GO:0008611 ether lipid biosynthetic process | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro-based electronic annotation to ether lipid biosynthetic process. This is the core biological process of GNPAT. Supporting Evidence: PMID:15687349 the peroxisomal DHAPAT is essential for the |
| GO:0016287 glycerone-phosphate O-acyltransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic annotation of the core glycerone-phosphate O-acyltransferase activity, supported by RHEA/EC:2.3.1.42 mapping. Correct core function. Supporting Evidence: file:human/GNPAT/GNPAT-uniprot.txt Reaction=dihydroxyacetone phosphate + an acyl-CoA = a 1-acylglycerone |
| GO:0016746 acyltransferase activity | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: InterPro-based electronic annotation to the generic parent acyltransferase activity. Correct but uninformative; the specific child term (GO:0016287) captures the actual function. Proposed replacements: glycerone-phosphate O-acyltransferase activity |
| GO:0016747 acyltransferase activity, transferring groups other than amino-acyl groups | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: InterPro-based electronic annotation to a generic acyltransferase parent term. Correct but uninformative relative to the specific GO:0016287. Proposed replacements: glycerone-phosphate O-acyltransferase activity |
| GO:0006654 phosphatidic acid biosynthetic process | TAS Reactome:R-HSA-1483166 | KEEP AS NON CORE | Summary: Reactome places GNPAT's acyl-DHAP product in the pathway that feeds phosphatidic acid / glycerolipid synthesis. This is a peripheral, non-core role - experimental evidence shows peroxisomal DHAPAT does not normally contribute to nonether (diacyl) glycerolipid biosynthesis, so its main output is the ether-lipid branch. Supporting Evidence: PMID:15687349 peroxisomal DHAPAT does not normally |
| GO:0008611 ether lipid biosynthetic process | TAS Reactome:R-HSA-75896 | ACCEPT | Summary: Reactome (Plasmalogen biosynthesis) traceable annotation to ether lipid biosynthetic process. Core biological process of GNPAT. Supporting Evidence: PMID:15687349 recovered DHAPAT activity and plasmalogen biosynthesis |
| GO:0006650 glycerophospholipid metabolic process | IEA GO_REF:0000041 | KEEP AS NON CORE | Summary: UniPathway-based electronic annotation to glycerophospholipid metabolic process. Correct but general parent of the specific ether-lipid biosynthetic process; consistent with the UniProt PATHWAY statement. Supporting Evidence: file:human/GNPAT/GNPAT-uniprot.txt PATHWAY: Membrane lipid metabolism; glycerophospholipid metabolism. |
| GO:0016287 glycerone-phosphate O-acyltransferase activity | TAS Reactome:R-HSA-1483002 | ACCEPT | Summary: Reactome traceable annotation of the core glycerone-phosphate O-acyltransferase activity (DHAP -> 1-acyl GO3P). Correct core function. Supporting Evidence: file:human/GNPAT/GNPAT-uniprot.txt Reaction=dihydroxyacetone phosphate + an acyl-CoA = a 1-acylglycerone |
| GO:0016287 glycerone-phosphate O-acyltransferase activity | TAS Reactome:R-HSA-75879 | ACCEPT | Summary: Reactome traceable annotation of the core glycerone-phosphate O-acyltransferase activity (palmitoyl-CoA + DHAP -> 1-palmitoylglycerone phosphate + CoASH). Correct core function. Supporting Evidence: file:human/GNPAT/GNPAT-uniprot.txt Reaction=dihydroxyacetone phosphate + hexadecanoyl-CoA = 1- |
| GO:0005778 peroxisomal membrane | EXP PMID:15687349 Role of dihydroxyacetonephosphate acyltransferase in the bio... | ACCEPT | Summary: Experimental localization of GNPAT/DHAPAT to the peroxisomal membrane. Core location, consistent with its role as a peripheral membrane protein on the matrix side. Supporting Evidence: file:human/GNPAT/GNPAT-uniprot.txt SUBCELLULAR LOCATION: Peroxisome membrane |
| GO:0016287 glycerone-phosphate O-acyltransferase activity | IDA PMID:10395968 Identification and characterization of the mouse cDNA encodi... | ACCEPT | Summary: Direct assay of DHAPAT activity via heterologous expression of the (mouse) cDNA in yeast, defining EC 2.3.1.42. Supports the core molecular function. Supporting Evidence: PMID:10395968 Definitive evidence that this cDNA indeed codes file:human/GNPAT/GNPAT-uniprot.txt Reaction=dihydroxyacetone phosphate + an acyl-CoA = a 1-acylglycerone |
| GO:0016287 glycerone-phosphate O-acyltransferase activity | IDA PMID:11152660 Impaired membrane traffic in defective ether lipid biosynthe... | ACCEPT | Summary: Direct characterization of catalytic activity, including loss of activity in RCDP2 disease variants (e.g. R211H). Supports the core molecular function. Supporting Evidence: file:human/GNPAT/GNPAT-uniprot.txt Reaction=dihydroxyacetone phosphate + an acyl-CoA = a 1-acylglycerone |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9033235 | MARK AS OVER ANNOTATED | Summary: This cytosol annotation derives from the Peroxisomal protein import Reactome pathway and reflects the transient cytosolic state of newly synthesized PTS1 cargo before import into the peroxisome. It does not represent the steady-state location of the mature enzyme, which is the peroxisomal membrane; as a standalone location claim it is an over-annotation. Supporting Evidence: file:human/GNPAT/GNPAT-uniprot.txt SUBCELLULAR LOCATION: Peroxisome membrane |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9033236 | MARK AS OVER ANNOTATED | Summary: As above, this cytosol annotation comes from the peroxisomal protein import docking/translocation step and reflects pre-import cargo, not the steady-state location of the mature peroxisomal enzyme. Supporting Evidence: file:human/GNPAT/GNPAT-uniprot.txt SUBCELLULAR LOCATION: Peroxisome membrane |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | KEEP AS NON CORE | Summary: High-throughput membrane-proteome dataset placed GNPAT in the generic membrane compartment. Consistent with its peripheral membrane association but uninformative relative to the specific peroxisomal membrane term. Supporting Evidence: file:human/GNPAT/GNPAT-uniprot.txt SUBCELLULAR LOCATION: Peroxisome membrane |
| GO:0005777 peroxisome | IDA PMID:15687349 Role of dihydroxyacetonephosphate acyltransferase in the bio... | ACCEPT | Summary: Direct experimental localization of GNPAT/DHAPAT to the peroxisome. Core location. Supporting Evidence: file:human/GNPAT/GNPAT-uniprot.txt SUBCELLULAR LOCATION: Peroxisome membrane |
| GO:0008611 ether lipid biosynthetic process | IDA PMID:15687349 Role of dihydroxyacetonephosphate acyltransferase in the bio... | ACCEPT | Summary: Direct evidence that human DHAPAT cDNA restores plasmalogen (ether lipid) biosynthesis in a DHAPAT-deficient cell line, and that peroxisomal DHAPAT is essential for plasmalogen synthesis. Core biological process. Supporting Evidence: PMID:15687349 recovered DHAPAT activity and plasmalogen biosynthesis PMID:15687349 the peroxisomal DHAPAT is essential for the |
| GO:0016287 glycerone-phosphate O-acyltransferase activity | IDA PMID:15687349 Role of dihydroxyacetonephosphate acyltransferase in the bio... | ACCEPT | Summary: Direct assay of DHAPAT activity restored by human DHAPAT cDNA in the NRel-4 variant. Supports the core molecular function. Supporting Evidence: PMID:15687349 recovered DHAPAT activity and plasmalogen biosynthesis file:human/GNPAT/GNPAT-uniprot.txt Reaction=dihydroxyacetone phosphate + an acyl-CoA = a 1-acylglycerone |
| GO:0005778 peroxisomal membrane | HDA PMID:21525035 PEX14 is required for microtubule-based peroxisome motility ... | ACCEPT | Summary: High-throughput dataset (peroxisomal membrane protein complex analysis) placing GNPAT at the peroxisomal membrane. Consistent with the core location. Supporting Evidence: file:human/GNPAT/GNPAT-uniprot.txt SUBCELLULAR LOCATION: Peroxisome membrane |
| GO:0005777 peroxisome | NAS PMID:9459311 Ether lipid biosynthesis: isolation and molecular characteri... | ACCEPT | Summary: Non-traceable author statement (isolation/characterization paper) placing DAP-AT in peroxisomes, consistent with its C-terminal PTS1 and experimental localization. Core location. Supporting Evidence: PMID:9459311 containing |
| GO:0016287 glycerone-phosphate O-acyltransferase activity | IDA PMID:8186247 Purification of peroxisomal acyl-CoA: dihydroxyacetonephosph... | ACCEPT | Summary: Purification of peroxisomal acyl-CoA:dihydroxyacetonephosphate acyltransferase from human placenta with direct activity measurements. Supports the core molecular function. Supporting Evidence: PMID:8186247 The peroxisomal enzyme acyl-CoA:dihydroxyacetonephosphate acyltransferase |
| GO:0016287 glycerone-phosphate O-acyltransferase activity | IDA PMID:9536089 Acyl-CoA:dihydroxyacetonephosphate acyltransferase: cloning ... | ACCEPT | Summary: Cloning of the human DHAPAT cDNA with expression demonstrating DHAPAT activity, and identification of RCDP2-causing mutations. Supports the core molecular function. Supporting Evidence: PMID:9536089 Expression of this ORF in the yeast Saccharomyces |
| GO:0005778 peroxisomal membrane | TAS Reactome:R-HSA-1483002 | ACCEPT | Summary: Reactome traceable annotation of peroxisomal membrane localization. Core location. Supporting Evidence: file:human/GNPAT/GNPAT-uniprot.txt SUBCELLULAR LOCATION: Peroxisome membrane |
| GO:0005778 peroxisomal membrane | TAS Reactome:R-HSA-9033235 | ACCEPT | Summary: Reactome traceable annotation of peroxisomal membrane localization. Core location. Supporting Evidence: file:human/GNPAT/GNPAT-uniprot.txt SUBCELLULAR LOCATION: Peroxisome membrane |
| GO:0005782 peroxisomal matrix | TAS Reactome:R-HSA-390427 | KEEP AS NON CORE | Summary: Reactome traceable annotation of peroxisomal matrix localization. Compatible with the enzyme being a peripheral membrane protein on the matrix (lumenal) side of the peroxisomal membrane; kept as non-core given the more precise peroxisomal-membrane terms. Supporting Evidence: file:human/GNPAT/GNPAT-uniprot.txt lumenal side of the peroxisomal membrane. |
| GO:0005782 peroxisomal matrix | TAS Reactome:R-HSA-75879 | KEEP AS NON CORE | Summary: Reactome traceable annotation of peroxisomal matrix localization, consistent with the enzyme's matrix (lumenal)-side membrane association. Kept as non-core relative to the peroxisomal-membrane terms. Supporting Evidence: file:human/GNPAT/GNPAT-uniprot.txt lumenal side of the peroxisomal membrane. |
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