GFPT1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0006002 fructose 6-phosphate metabolic process	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Fructose 6-phosphate is the sugar substrate of GFPT1 (F6P + L-Gln -> GlcN6P + L-Glu), so this term is correct but describes the substrate side of the same catalytic reaction that is more informatively captured by the molecular function (GO:0004360) and the downstream HBP process (GO:0006048). Kept as non-core supporting metabolism. Supporting Evidence: PMID:35229715 glutamine fructose-6-phosphate amidotransferase (GFPT) converts fructose-6-phosphate (Frc6P) and L-glutamine (L-Gln) to D-glucosamine-6-phosphate (GlcN6P)
GO:0006048 UDP-N-acetylglucosamine biosynthetic process	IBA GO_REF:0000033	ACCEPT	Summary: Core biological process. GFPT1 catalyzes the first, rate-limiting and committed step of the pathway that produces UDP-GlcNAc. Well supported by phylogenetic inference across GFAT/GlmS orthologs and by direct experimental evidence. Supporting Evidence: file:human/GFPT1/GFPT1-uniprot.txt Rate-limiting enzyme of the hexosamine biosynthetic pathway
GO:0004360 L-glutamine:D-fructose-6-phosphate transaminase (isomerizing) activity	IBA GO_REF:0000033	ACCEPT	Summary: Core molecular function of GFPT1. This is the EC 2.6.1.16 activity (L-glutamine + D-fructose 6-phosphate -> L-glutamate + D-glucosamine 6-phosphate). Phylogenetic inference is fully consistent with direct experimental and structural evidence for the human enzyme. Supporting Evidence: file:human/GFPT1/GFPT1-uniprot.txt Reaction=D-fructose 6-phosphate + L-glutamine = D-glucosamine 6-
GO:0004360 L-glutamine:D-fructose-6-phosphate transaminase (isomerizing) activity	IEA GO_REF:0000120	ACCEPT	Summary: Same core molecular function, inferred electronically from ARBA/InterPro (IPR005855 GFAT) mapped to EC 2.6.1.16 / RHEA:13237. Consistent with the experimentally verified activity. Supporting Evidence: file:human/GFPT1/GFPT1-uniprot.txt EC=2.6.1.16 {ECO:0000269\|PubMed:32019926, ECO:0000269\|PubMed:35229715}
GO:0006002 fructose 6-phosphate metabolic process	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Electronic (ARBA) restatement of the substrate-side process, same as the IBA and TAS annotations to this term. Correct but non-core; the specific MF and HBP process terms are more informative. Supporting Evidence: PMID:35229715 glutamine fructose-6-phosphate amidotransferase (GFPT) converts fructose-6-phosphate (Frc6P) and L-glutamine (L-Gln) to D-glucosamine-6-phosphate (GlcN6P)
GO:0006112 energy reserve metabolic process	IEA GO_REF:0000117	REMOVE	Summary: Biologically incorrect. "Energy reserve metabolic process" concerns storage carbohydrate/lipid (glycogen, starch, triglyceride) metabolism and energy derivation. GFPT1 does the opposite: it diverts fructose 6-phosphate OUT of energy/glycolytic flux into aminosugar biosynthesis (the HBP). This is a clearly wrong electronic (ARBA) inference and should be removed.
GO:0097367 carbohydrate derivative binding	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: Generic InterPro-derived binding term (SIS domain). GFPT1 does bind phosphosugar substrates/products (fructose 6-phosphate, glucose 6-phosphate, UDP-GlcNAc), so this is not wrong, but it is an uninformative parent term subsumed by the specific transaminase molecular function. Kept as non-core. Supporting Evidence: file:human/GFPT1/GFPT1-uniprot.txt /ligand="UDP-N-acetyl-alpha-D-glucosamine"
GO:1901135 carbohydrate derivative metabolic process	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: High-level parent process (carbohydrate derivative metabolism). True but uninformative; subsumed by the specific UDP-GlcNAc biosynthetic process and fructose 6-phosphate metabolic process annotations. Kept as non-core.
GO:1901137 carbohydrate derivative biosynthetic process	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: High-level parent process (carbohydrate derivative biosynthesis). True but uninformative; subsumed by the specific UDP-N-acetylglucosamine biosynthetic process (GO:0006048) annotation. Kept as non-core.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	MARK AS OVER ANNOTATED	Summary: High-throughput affinity-capture interactome (BioPlex). The WITH/FROM is UniProtKB:O94808 = GFPT2, i.e. this records the GFPT1-GFPT2 paralog interaction also documented in UniProt (IntAct, NbExp=3). Bare "protein binding" is uninformative and does not describe GFPT1's molecular function; marked as over-annotated rather than removed (experimental IPI). The cited publication's cached text does not name GFPT1/GFPT2 in prose, so no verbatim quote is given. Supporting Evidence: file:human/GFPT1/GFPT1-uniprot.txt Q06210; O94808: GFPT2
GO:0005515 protein binding	IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func...	MARK AS OVER ANNOTATED	Summary: Second high-throughput interactome study (multimodal cell maps), WITH/FROM UniProtKB:O94808 = GFPT2, again capturing the GFPT1-GFPT2 interaction. Bare "protein binding" is uninformative; marked as over-annotated rather than removed (experimental IPI). No verbatim quote is available because the cached publication text does not name GFPT1/GFPT2 in prose. Supporting Evidence: file:human/GFPT1/GFPT1-uniprot.txt Q06210; O94808: GFPT2
GO:0032922 circadian regulation of gene expression	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Electronically transferred from mouse ortholog (Gfpt1, P47856) via Ensembl Compara. UniProt notes, by similarity, that GFPT1 modulates peripheral clock oscillation through control of the HBP; this is an indirect, downstream role of UDP-GlcNAc/O-GlcNAc signaling rather than a core function of the enzyme. Kept as non-core. Supporting Evidence: file:human/GFPT1/GFPT1-uniprot.txt modulates peripheral clock oscillation
GO:0006048 UDP-N-acetylglucosamine biosynthetic process	TAS Reactome:R-HSA-446210	ACCEPT	Summary: Core biological process, curated by Reactome (Synthesis of UDP-N-acetyl-glucosamine). GFPT1 catalyzes the first committed step of UDP-GlcNAc biosynthesis. Supporting Evidence: file:human/GFPT1/GFPT1-uniprot.txt Nucleotide-sugar biosynthesis; UDP-N-acetyl-alpha-D-
GO:0006048 UDP-N-acetylglucosamine biosynthetic process	IEA GO_REF:0000120	ACCEPT	Summary: Same core process inferred electronically (ARBA + UniPathway UPA00113). Consistent with the curated and experimental annotations. Supporting Evidence: file:human/GFPT1/GFPT1-uniprot.txt Nucleotide-sugar biosynthesis; UDP-N-acetyl-alpha-D-
GO:0004360 L-glutamine:D-fructose-6-phosphate transaminase (isomerizing) activity	TAS Reactome:R-HSA-4085027	ACCEPT	Summary: Core molecular function, curated by Reactome (this reaction annotation describes the defective-GFPT1 case but asserts the wild-type activity of transferring an amino group from L-Gln to F6P to form GlcN6P). Supporting Evidence: file:human/GFPT1/GFPT1-uniprot.txt Reaction=D-fructose 6-phosphate + L-glutamine = D-glucosamine 6-
GO:0004360 L-glutamine:D-fructose-6-phosphate transaminase (isomerizing) activity	TAS Reactome:R-HSA-449715	ACCEPT	Summary: Core molecular function, curated by Reactome (GFPT1,2 transfer an amino group from L-Gln to F6P to form GlcN6P). Consistent with all other GO:0004360 annotations. Supporting Evidence: file:human/GFPT1/GFPT1-uniprot.txt Reaction=D-fructose 6-phosphate + L-glutamine = D-glucosamine 6-
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: Core molecular function with strong experimental support. Ruegenberg et al. determined the full-length human GFAT-1 crystal structure, performed enzyme activity assays, and defined the catalytic reaction and UDP-GlcNAc feedback inhibition. This is the primary experimental basis for the EC 2.6.1.16 assignment. Supporting Evidence: PMID:32019926 GFAT synthesizes d-glucosamine-6-phosphate (GlcN6P) from l-glutamine (l-Gln) and Frc6P, releasing l-glutamate (l-Glu)
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: Core molecular function, direct assay. Kroef et al. is primarily about GFPT2/AMDHD2 but directly measures GFPT1 enzyme activity and its UDP-GlcNAc sensitivity as the comparison point; the paper explicitly frames GFPT (GFPT1/2) as carrying out the F6P + L-Gln -> GlcN6P reaction. Experimental annotation retained. Supporting Evidence: PMID:35229715 Compared with GFPT1, GFPT2 had a much lower sensitivity to UDP-GlcNAc
GO:0006002 fructose 6-phosphate metabolic process	IDA PMID:35229715 GFPT2/GFAT2 and AMDHD2 act in tandem to control the hexosami...	KEEP AS NON CORE	Summary: Fructose 6-phosphate is the substrate consumed by GFPT1; direct assay supports involvement in F6P metabolism, but this is the substrate-side framing of the core transaminase reaction. Kept as non-core. Supporting Evidence: PMID:35229715 glutamine fructose-6-phosphate amidotransferase (GFPT) converts fructose-6-phosphate (Frc6P) and L-glutamine (L-Gln) to D-glucosamine-6-phosphate (GlcN6P)
GO:0006048 UDP-N-acetylglucosamine biosynthetic process	IDA PMID:35229715 GFPT2/GFAT2 and AMDHD2 act in tandem to control the hexosami...	ACCEPT	Summary: Core biological process, direct assay. The study manipulates the HBP and measures UDP-GlcNAc, with GFPT (GFPT1/2) as the rate-limiting entry enzyme. Experimental annotation retained. Supporting Evidence: PMID:35229715 In the first and rate limiting step of the HBP
GO:0006048 UDP-N-acetylglucosamine biosynthetic process	IMP PMID:26887390 Hexosamine biosynthesis in keratinocytes: roles of GFAT and ...	ACCEPT	Summary: Core biological process supported by loss-of-function evidence. siRNA depletion of GFAT1 in human keratinocytes reduced the cellular UDP-GlcNAc pool (and hyaluronan synthesis), directly implicating GFPT1 in UDP-GlcNAc biosynthesis. Experimental (IMP) annotation retained. Supporting Evidence: PMID:26887390 Depletion of GFAT1 reduced the cellular pool of UDP-GlcNAc and hyaluronan synthesis
GO:0005829 cytosol	TAS Reactome:R-HSA-4085027	ACCEPT	Summary: Correct subcellular localization. GFPT1 is a soluble cytosolic enzyme (no signal peptide or transmembrane region); the HBP is a cytosolic branch of glycolysis. Curated by Reactome.
GO:0032922 circadian regulation of gene expression	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Sequence-similarity transfer from the mouse ortholog (P47856), same indirect clock-modulation role as the Ensembl IEA annotation to this term. Downstream/By-similarity role via UDP-GlcNAc rather than a core function. Kept as non-core. Supporting Evidence: file:human/GFPT1/GFPT1-uniprot.txt modulates peripheral clock oscillation
GO:0070062 extracellular exosome	HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote...	KEEP AS NON CORE	Summary: Detected by high-throughput proteomics of B-cell exosomes. GFPT1 is a cytosolic metabolic enzyme; presence in the exosome fraction is a common finding for abundant cytosolic proteins and does not reflect a functional extracellular/exosomal role. Kept as non-core (localization observation only).
GO:0005829 cytosol	TAS Reactome:R-HSA-1791088	ACCEPT	Summary: Cytosolic localization, curated by Reactome (Expression of GFPT1). Consistent with the other cytosol annotations.
GO:0005829 cytosol	TAS Reactome:R-HSA-449715	ACCEPT	Summary: Cytosolic localization, curated by Reactome (GFPT1,2 reaction). Consistent with the other cytosol annotations.
GO:0004360 L-glutamine:D-fructose-6-phosphate transaminase (isomerizing) activity	TAS PMID:8144040 The murine glutamine:fructose-6-phosphate amidotransferase-e...	ACCEPT	Summary: Core molecular function, legacy author statement. Sayeski et al. (murine GFAT cDNA) describe GFAT as the rate-limiting enzyme of hexosamine synthesis (>98% identical to human), supporting the transaminase activity. Supporting Evidence: PMID:8144040 GFAT) is the rate-limiting enzyme in hexosamine synthesis
GO:0006002 fructose 6-phosphate metabolic process	TAS PMID:8144040 The murine glutamine:fructose-6-phosphate amidotransferase-e...	KEEP AS NON CORE	Summary: Substrate-side process annotation from the murine GFAT cDNA paper. Correct but non-core; the transaminase MF and HBP biosynthetic process are more informative. Supporting Evidence: PMID:8144040 GFAT) is the rate-limiting enzyme in hexosamine synthesis
GO:0006112 energy reserve metabolic process	TAS PMID:1460020 Molecular cloning, cDNA sequence, and bacterial expression o...	MARK AS OVER ANNOTATED	Summary: Legacy ProtInc author annotation. The cited paper (McKnight 1992) is about cloning human GFAT and its regulation in insulin resistance; it supports catalytic activity and UDP-GlcNAc feedback inhibition, NOT an energy-reserve (glycogen/storage carbohydrate) role. GFPT1 diverts fructose 6-phosphate away from energy metabolism into aminosugar biosynthesis. Because this is a curator/author (TAS) annotation it is marked as over-annotated rather than removed. Supporting Evidence: PMID:1460020 Recombinant GFAT activity was inhibited 51% by UDP-GlcNAc

Gene Description

Existing Annotations Review

Core Functions

Rate-limiting, first and committed step of the hexosamine biosynthetic pathway: transfers the amido nitrogen of L-glutamine to D-fructose 6-phosphate to produce D-glucosamine 6-phosphate and L-glutamate, feedback inhibited by the downstream product UDP-GlcNAc.

References

📚 Additional Documentation

Notes

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