Gfat1 encodes glutamine-fructose-6-phosphate amidotransferase isoforms associated with hexosamine metabolism. The native 434-residue PF isoform preserves the C-terminal sugar-isomerase region but lacks most of the N-terminal glutaminase domain, including its catalytic cysteine. It lacks the catalytic machinery required to execute the complete intrinsic glutamine-dependent reaction of the full-length enzyme. Its retained sugar-binding region may support ligand binding or other functions, while its physiological contribution remains unresolved.
Summary: This IEA assigns the complete glutamine-dependent reaction to PF, but its sequence lacks the N-terminal catalytic cysteine and most of the glutaminase domain.
Reason: This IEA assigns the complete glutamine-dependent reaction to PF, but its sequence lacks the N-terminal catalytic cysteine and most of the glutaminase domain. Both nitrogen extraction from glutamine and transfer to the sugar site are required for the stated intrinsic activity. Retained SIS domains do not provide the missing glutamine-hydrolysis machinery.
Supporting Evidence:
file:DROME/Gfat1/Gfat1-bioinformatics/RESULTS.md
Only 40 of 299 residues of the annotated glutamine-amidotransferase domain remain, and its N-terminal catalytic Cys2 is absent.
Glucosamine-6P synthase catalyzes the synthesis of glucosamine-6P from fructose-6P and glutamine and uses a channel to transfer ammonia from its glutaminase to its synthase active site.
Summary: The PF isoform lacks the glutaminase module needed for the complete reaction, while retaining the sugar-isomerase region.
Reason: The PF isoform lacks the glutaminase module needed for the complete reaction, while retaining the sugar-isomerase region. Domain retention does not establish whether this short product contributes through ligand binding, regulation or a partner to the biological process. Isoform-specific functional evidence is missing; catalytic loss alone is not evidence that all process participation is impossible.
Supporting Evidence:
file:DROME/Gfat1/Gfat1-bioinformatics/RESULTS.md
Only 40 of 299 residues of the annotated glutamine-amidotransferase domain remain, and its N-terminal catalytic Cys2 is absent.
Glucosamine-6P synthase catalyzes the synthesis of glucosamine-6P from fructose-6P and glutamine and uses a channel to transfer ammonia from its glutaminase to its synthase active site.
GO:0006048 UDP-N-acetylglucosamine biosynthetic process
IEA GO_REF:0000041
UNDECIDED
Summary: The PF isoform lacks the glutaminase module needed for the complete reaction, while retaining the sugar-isomerase region.
Reason: The PF isoform lacks the glutaminase module needed for the complete reaction, while retaining the sugar-isomerase region. Domain retention does not establish whether this short product contributes through ligand binding, regulation or a partner to the biological process. Isoform-specific functional evidence is missing; catalytic loss alone is not evidence that all process participation is impossible.
Supporting Evidence:
file:DROME/Gfat1/Gfat1-bioinformatics/RESULTS.md
Only 40 of 299 residues of the annotated glutamine-amidotransferase domain remain, and its N-terminal catalytic Cys2 is absent.
Glucosamine-6P synthase catalyzes the synthesis of glucosamine-6P from fructose-6P and glutamine and uses a channel to transfer ammonia from its glutaminase to its synthase active site.
Summary: Both C-terminal SIS domains are intact in PF.
Reason: Both C-terminal SIS domains are intact in PF. Structures of the homologous isolated human isomerase domain demonstrate sugar-phosphate binding, providing a justified domain-based transfer of this broad binding property. This does not assert the complete glutamine-dependent reaction or physiological pathway flux by PF.
Supporting Evidence:
file:DROME/Gfat1/Gfat1-bioinformatics/RESULTS.md
Only 40 of 299 residues of the annotated glutamine-amidotransferase domain remain, and its N-terminal catalytic Cys2 is absent.
We now report the first structures of the isomerase domain of the human GFAT in the presence of cyclic glucose-6-phosphate and linear glucosamine-6-phosphate.
Summary: Both C-terminal SIS domains are intact in PF.
Reason: Both C-terminal SIS domains are intact in PF. Structures of the homologous isolated human isomerase domain demonstrate sugar-phosphate binding, providing a justified domain-based transfer of this broad binding property. This does not assert the complete glutamine-dependent reaction or physiological pathway flux by PF.
Supporting Evidence:
file:DROME/Gfat1/Gfat1-bioinformatics/RESULTS.md
Only 40 of 299 residues of the annotated glutamine-amidotransferase domain remain, and its N-terminal catalytic Cys2 is absent.
We now report the first structures of the isomerase domain of the human GFAT in the presence of cyclic glucose-6-phosphate and linear glucosamine-6-phosphate.
GO:1901135 carbohydrate derivative metabolic process
IEA GO_REF:0000002
UNDECIDED
Summary: The PF isoform lacks the glutaminase module needed for the complete reaction, while retaining the sugar-isomerase region.
Reason: The PF isoform lacks the glutaminase module needed for the complete reaction, while retaining the sugar-isomerase region. Domain retention does not establish whether this short product contributes through ligand binding, regulation or a partner to the biological process. Isoform-specific functional evidence is missing; catalytic loss alone is not evidence that all process participation is impossible.
Supporting Evidence:
file:DROME/Gfat1/Gfat1-bioinformatics/RESULTS.md
Only 40 of 299 residues of the annotated glutamine-amidotransferase domain remain, and its N-terminal catalytic Cys2 is absent.
Glucosamine-6P synthase catalyzes the synthesis of glucosamine-6P from fructose-6P and glutamine and uses a channel to transfer ammonia from its glutaminase to its synthase active site.
GO:1901137 carbohydrate derivative biosynthetic process
IEA GO_REF:0000002
UNDECIDED
Summary: The PF isoform lacks the glutaminase module needed for the complete reaction, while retaining the sugar-isomerase region.
Reason: The PF isoform lacks the glutaminase module needed for the complete reaction, while retaining the sugar-isomerase region. Domain retention does not establish whether this short product contributes through ligand binding, regulation or a partner to the biological process. Isoform-specific functional evidence is missing; catalytic loss alone is not evidence that all process participation is impossible.
Supporting Evidence:
file:DROME/Gfat1/Gfat1-bioinformatics/RESULTS.md
Only 40 of 299 residues of the annotated glutamine-amidotransferase domain remain, and its N-terminal catalytic Cys2 is absent.
Glucosamine-6P synthase catalyzes the synthesis of glucosamine-6P from fructose-6P and glutamine and uses a channel to transfer ammonia from its glutaminase to its synthase active site.
Core Functions
Retains the sugar-phosphate-binding isomerase region; the native role of this glutaminase-deficient isoform is unresolved.
We now report the first structures of the isomerase domain of the human GFAT in the presence of cyclic glucose-6-phosphate and linear glucosamine-6-phosphate.
These computational predictions are reviewed separately from the GOA annotation set used for this review. The assessments below are from this project and do not constitute official GO annotations or endorsement by GO/UniProt. They are not included in the existing annotation review above.
The ProtNLM2 API snapshot retrieved 2026-09-08 contains no GO-term predictions for A8Y5A1, the native 434-residue Gfat1-PF product. Omission of the complete glutamine-dependent amidotransferase activity (GO:0004360) is not a supported deficiency: this exact product lacks the catalytic cysteine and most of the glutaminase module needed for that reaction. The retained SIS domains and ligand-bound structures of homologous human isomerase domains support carbohydrate derivative binding (GO:0097367) as a broad, qualified omission candidate, not proof of target-specific binding or catalysis. Participation in UDP-N-acetylglucosamine biosynthesis remains unresolved for this isoform. The separate FUNCTION claim of the complete glutamine-dependent reaction is NPI because of the missing catalytic architecture. This completed record assesses the absence of GO output; predictions is empty because no GO or EC prediction was emitted. The narrative judgment remains in the linked function review and is not a score assigned to the omission.