GFPT1 (GFAT1) is a cytosolic glutamine–fructose-6-phosphate aminotransferase that initiates hexosamine biosynthesis. It converts glutamine and fructose 6-phosphate into glutamate and glucosamine 6-phosphate, supplying the pathway to UDP-N-acetylglucosamine and hence substrates for glycosylation. UDP-N-acetylglucosamine inhibits the enzyme through feedback regulation. Human GFPT1 forms an asymmetric homodimer. Alternative splicing produces 699- and 681-residue proteins. Biallelic GFPT1 variants cause a congenital myasthenic syndrome with impaired neuromuscular transmission.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004360 L-glutamine:D-fructose-6-phosphate transaminase (isomerizing) activity | EXP PMID:32019926 Loss of GFAT-1 feedback regulation activates the hexosamine ... | ACCEPT | Summary: Purified recombinant human GFPT1 catalyzes glucosamine-6-phosphate production. Reason: Retain directly measured human catalysis, with separate complete-reaction and glutamate readouts; engineered isoform-2 reagent scope is detailed in the companion. Supporting Evidence: |
| GO:0004360 L-glutamine:D-fructose-6-phosphate transaminase (isomerizing) activity | IBA GO_REF:0000033 | ACCEPT | Summary: GFPT1 retains the ancestral glutamine:fructose-6-phosphate aminotransferase function. Reason: The actual PTHR10937 AN6/PTN000101302 IBD is ancestral to the human AN67/PTN002475099 target; the target alignment matches the displayed 699-residue sequence. Its literal donor set includes human GFPT1 as legitimate experimental grounding. The two retained family IKR records occur outside the target lineage. Direct human enzyme measurements independently support the same reaction, with no target-specific catalytic loss established. |
| GO:0004360 L-glutamine:D-fructose-6-phosphate transaminase (isomerizing) activity | IDA PMID:35229715 GFPT2/GFAT2 and AMDHD2 act in tandem to control the hexosami... | ACCEPT | Summary: The human GFPT1 comparator is directly assayed in the GFPT2-focused study. Reason: Human GFPT1 was directly assayed alongside GFPT2; the title and mouse cellular experiments do not invalidate that comparator. Supporting Evidence: |
| GO:0004360 L-glutamine:D-fructose-6-phosphate transaminase (isomerizing) activity | IEA GO_REF:0000120 | ACCEPT | Summary: The electronic reaction assignment matches the experimentally established GFPT1 catalysis. Reason: The incoming EC2.6.1.16 and RHEA13237 identify conversion of fructose 6-phosphate and glutamine to glucosamine 6-phosphate and glutamate. The official catalytic record and direct human measurements agree. Preserve the InterPro and ARBA identifiers without claiming to have reconstructed every rule condition. |
| GO:0004360 L-glutamine:D-fructose-6-phosphate transaminase (isomerizing) activity | TAS PMID:8144040 The murine glutamine:fructose-6-phosphate amidotransferase-e... | ACCEPT | Summary: The historical TAS identifies the conserved catalytic function. Reason: The accessible PMID8144040 abstract describes mouse cDNA and comparison with human GFAT; it is not presented here as a directly inspected human kinetic experiment. Independent primary measurements on human GFPT1 establish the annotated reaction. Retain the true gene-level function and original source while keeping the historical article access limit explicit. |
| GO:0004360 L-glutamine:D-fructose-6-phosphate transaminase (isomerizing) activity | TAS Reactome:R-HSA-4085027 | ACCEPT | Summary: The disease-reaction context refers to GFPT1’s normal aminotransferase function. Reason: Reactome4085027 models defective GFPT1 in congenital myasthenia and notes that not every patient mutation markedly reduces measured enzyme activity. Its disease-event wording is not a negation of wild-type GFPT1 catalysis. The normal reaction and direct human enzyme assays establish the claim; no uniform catalytic-null mechanism is assigned to all disease variants. |
| GO:0004360 L-glutamine:D-fructose-6-phosphate transaminase (isomerizing) activity | TAS Reactome:R-HSA-449715 | ACCEPT | Summary: GFPT1 catalyzes the entry reaction of hexosamine synthesis. Reason: Reactome449715 places GFPT1 and GFPT2 as catalysts transferring glutamine-derived nitrogen to fructose 6-phosphate. This curated reaction agrees with the independently measured human GFPT1 activity. It does not imply that the two paralogs have identical feedback sensitivity or tissue roles. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Preserve the positive association while removing the uninformative binding label. Reason: The BioPlex GFPT2–GFPT1 association remains positive, with GeneID grouping and the literal Q06210-2 table accession preserved. Independent GFPT2 catalysis establishes partner class, but no useful GFPT1-specific function beyond copurification is established here. Remove the generic label as uninformative, without rejecting the association or asserting absence of a physiological heteromer. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: Preserve the positive association while removing the uninformative binding label. Reason: The original U2OS AP-MS edge remains positive and identifies the GFPT2–GFPT1 gene pair. Partner enzyme class alone does not establish a useful GFPT1-specific functional refinement. Remove the generic label as uninformative; binary contact, natural-product participation and physiological assembly remain unresolved, rather than disproved. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1791088 | ACCEPT | Summary: The expression model places the GFPT1 protein in cytosol. Reason: The actual Reactome output chain reaches human Q06210 residues2–699 with GO0005829. The nucleoplasmic input is the gene, not an alternative protein-location assertion. This is a curated model location, without a newly verified localization experiment or unique natural-product claim. Supporting Evidence: Reactome:R-HSA-1791088 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-4085027 | ACCEPT | Summary: The disease model preserves the cytosolic GFPT1 compartment. Reason: The actual catalyst chain reaches a GFPT1 mutant set and its D348Y member, explicitly linked to human Q06210 in cytosol. The separate normal model assigns the same compartment. Retaining this location does not establish that every disease allele has the same catalytic defect. Supporting Evidence: Reactome:R-HSA-4085027 Reactome:R-HSA-449715 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-449715 | ACCEPT | Summary: The normal reaction model places GFPT1 catalysis in cytosol. Reason: The actual catalyst set contains separate GFPT1 and GFPT2 members; the GFPT1 member reaches human Q06210 and GO0005829. This supports the core compartment without interpreting the alternative set as an obligate heteromer. Supporting Evidence: Reactome:R-HSA-449715 |
| GO:0006002 fructose 6-phosphate metabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: Fructose-6-phosphate metabolism is an inherited catalytic role. Reason: The inspected AN14/PTN000859281 IBD lies on the human target lineage and retains the exact GFPT1, GFPT2 and rat donor set. Human self evidence is legitimate grounding. GFPT1 directly transforms fructose 6-phosphate in its established aminotransferase reaction; no target-specific loss is supported. |
| GO:0006002 fructose 6-phosphate metabolic process | IDA PMID:35229715 GFPT2/GFAT2 and AMDHD2 act in tandem to control the hexosami... | ACCEPT | Summary: Human GFPT1 directly converts fructose 6-phosphate. Reason: Retain the independently assayed human substrate conversion, without transferring mouse stem-cell functions. Supporting Evidence: |
| GO:0006002 fructose 6-phosphate metabolic process | IEA GO_REF:0000117 | ACCEPT | Summary: The electronic fructose-6-phosphate process assignment agrees with human biochemistry. Reason: Current ARBA00084568 assigns this process. Its complete FunFam condition match was not independently reconstructed, but direct human substrate turnover establishes the same function. This is metabolism of fructose 6-phosphate, without implying that GFPT1 performs glycolysis or fructose breakdown. |
| GO:0006002 fructose 6-phosphate metabolic process | TAS PMID:8144040 The murine glutamine:fructose-6-phosphate amidotransferase-e... | ACCEPT | Summary: Retain the established fructose-6-phosphate metabolic role. Reason: The accessible historical abstract concerns mouse GFAT cDNA and human sequence comparison; its full assays were not inspected. Independent human enzyme measurements establish the annotated substrate conversion, so the true function can be retained without upgrading that historical access scope. |
| GO:0006048 UDP-N-acetylglucosamine biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: GFPT1 inherits the hexosamine-biosynthetic entry reaction. Reason: The actual AN6/PTN000101302 IBD and literal donor set map to the human lineage, including valid target self evidence. The conserved catalytic step supplies glucosamine 6-phosphate for UDP-N-acetylglucosamine synthesis. GFPT1 performs this step rather than merely being required as a substrate. |
| GO:0006048 UDP-N-acetylglucosamine biosynthetic process | IDA PMID:35229715 GFPT2/GFAT2 and AMDHD2 act in tandem to control the hexosami... | ACCEPT | Summary: Human GFPT1 catalyzes a step in UDP-N-acetylglucosamine biosynthesis. Reason: Human substrate conversion executes the pathway entry step; the assay does not measure final UDP-GlcNAc synthesis. |
| GO:0006048 UDP-N-acetylglucosamine biosynthetic process | IEA GO_REF:0000120 | ACCEPT | Summary: The electronic UDP-N-acetylglucosamine biosynthesis assignment is biologically supported. Reason: The current ARBA00084680 output and incoming UniPathway identifier are preserved. GFPT1 catalyzes the entry reaction of the independently documented pathway. This judgment does not claim a complete reconstruction of every automated rule condition. Supporting Evidence: GO_REF:0000120 Reactome:R-HSA-446210 Reactome:R-HSA-449715 |
| GO:0006048 UDP-N-acetylglucosamine biosynthetic process | IMP PMID:26887390 Hexosamine biosynthesis in keratinocytes: roles of GFAT and ... | ACCEPT | Summary: GFPT1 supports UDP-N-acetylglucosamine production in human keratinocytes. Reason: The authentic abstract reports that GFAT1 silencing reduces the cellular UDP-GlcNAc pool. Combined with independently established entry-step catalysis, this supports pathway participation. Full assay protocols remain uninspected; the accompanying hyaluronan and migration effects are not additional direct functions. |
| GO:0006048 UDP-N-acetylglucosamine biosynthetic process | TAS Reactome:R-HSA-446210 | ACCEPT | Summary: The curated pathway correctly includes GFPT1 catalysis. Reason: Reactome446210 describes synthesis from fructose 6-phosphate, glutamine, acetyl-CoA and UTP; the linked reaction summary names GFPT1 as an entry-step catalyst. This agrees with primary human enzyme measurements without assigning every subsequent pathway reaction to GFPT1. |
| GO:0006112 energy reserve metabolic process | IEA GO_REF:0000117 | REMOVE | Summary: The electronic energy-reserve mapping misplaces the hexosamine synthetic reaction. Reason: GO:0006112 describes energy derivation from stored compounds. GFPT1 catalyzes hexosamine synthesis, rather than a reserve-energy reaction. The ARBA mapping is unsupported by the inspected catalytic evidence; metabolic or insulin-related consequences do not supply that missing process role. |
| GO:0006112 energy reserve metabolic process | TAS PMID:1460020 Molecular cloning, cDNA sequence, and bacterial expression o... | REMOVE | Summary: The cited human enzyme work does not support energy-reserve utilization. Reason: The inspected original demonstrates human hexosamine synthesis and discusses insulin resistance. Neither establishes GFPT1 executing energy derivation from glycogen or fat. Remove this process assignment while preserving the reported metabolic associations. Supporting Evidence: |
| GO:0032922 circadian regulation of gene expression | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain a contextual metabolic contribution to clock-gene regulation. Reason: Human GFAT1 knockdown reduces Bmal1/Cry1 transcripts, supporting non-core clock-gene regulation through hexosamine supply. Supporting Evidence: GO_REF:0000107 PMID:23395176 The siRNA-mediated knockdown of GFAT1 decreases expression of Bmal1 and Cry1 |
| GO:0032922 circadian regulation of gene expression | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain the transferred circadian role as non-core with endpoint limits. Reason: Human perturbation corroborates this contextual role. Mouse Gfat1 periodicity describes its own regulation; no GFPT1-specific period or phase effect is asserted. |
| GO:0070062 extracellular exosome | HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote... | KEEP AS NON CORE | Summary: Retain GFPT1 occurrence in the reported B-cell exosome preparation. Reason: Retain positive GFPT1 identification in the RN B-cell EV preparation, with peptide-table access unresolved. This supports contextual occurrence, without a topology, isoform or extracellular catalytic claim. |
| GO:0070062 extracellular exosome | HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote... | UNDECIDED | Summary: The literal cell-type extension conflicts with the inspected B-cell source. Reason: The literal part_of(CL:0000639) restricts this assertion to a pituitary basophil, whereas the source concerns RN B cells. Positive unqualified EV occurrence does not establish that different cell context. Keep the qualified assertion UNDECIDED and its source defect explicit; the defect report does not waive the restriction. |
| GO:0097367 carbohydrate derivative binding | IEA GO_REF:0000002 | MODIFY | Summary: Resolve carbohydrate-derivative binding to the demonstrated fructose-6-phosphate substrate. Reason: Substrate kinetics and the curated UniProt F6P BINDING features support GO:0070095. The latter use inference/structure evidence; ambiguous sugar identity in the 2020 experiment is not direct ligand identification. UDP-GlcNAc binding and feedback remain supported separately; no corresponding specific GO descendant was identified in the bounded search, so this refinement does not assert exclusivity. Proposed replacements: fructose-6-phosphate binding |
| GO:1901135 carbohydrate derivative metabolic process | IEA GO_REF:0000002 | TOO GENERAL | Summary: The broad carbohydrate-derivative category adds no useful process resolution. Reason: The mapped SIS domains are real and the claim is true. Accepted UDP-N-acetylglucosamine biosynthesis already entails this parent through the asserted GO0006048→GO0006047→GO0006040→GO1901135 is_a path. The specific hexosamine pathway conveys the relevant process; this is an informativeness judgment, not rejection of the domain mapping. |
| GO:1901137 carbohydrate derivative biosynthetic process | IEA GO_REF:0000002 | TOO GENERAL | Summary: Retain the specific hexosamine pathway rather than this uninformative biosynthetic parent. Reason: IPR005855 correctly identifies the GFAT family. Accepted GO0006048 entails this broad parent through the asserted is_a path GO0006048→GO0009226→GO1901137. The parent adds no distinct pathway information here and is not judged biologically false. Supporting Evidence: GO_REF:0000002 Reactome:R-HSA-446210 |
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