FBP1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0000122 negative regulation of transcription by RNA polymerase II	IMP PMID:25043030 Fructose-1,6-bisphosphatase opposes renal carcinoma progress...	KEEP AS NON CORE	Summary: Negative regulation of RNA polymerase II transcription (IMP, PMID:25043030): nuclear FBP1 binds the HIF inhibitory domain and represses HIF target genes. Reason: Moonlighting, catalytic-activity-independent function reported in ccRCC cells; well supported but not the gene's core (enzymatic) role. Supporting Evidence: PMID:25043030 FBP1 restrains cell proliferation, glycolysis and the pentose phosphate pathway in a catalytic-activity-independent manner, by inhibiting nuclear HIF function via direct interaction with the HIF inhibitory domain. PMID:25043030 These results suggest that FBP1 interferes with HIF function through a catalytic activity-independent mechanism.
GO:0005515 protein binding	IPI PMID:10222032 cDNA sequence and kinetic properties of human lung fructose(...	REMOVE	Summary: IPI 'protein binding' with PFKFB1 (PMID:10222032). Reason: Bare 'protein binding' carries no functional information about FBP1. The interaction may well be real (FBP1 is reported in large binary interactome screens), but it does not describe an activity of FBP1, and the source supports no more informative molecular function term for it. Removal does not mean the interaction is false. The cited abstract is a kinetic study reporting inhibition by fructose 2,6-bisphosphate (the PFKFB product) and AMP; it does not report physical binding to PFKFB in the abstract, so the partner cannot be verified here. Supporting Evidence: PMID:10222032 Like the liver isoenzyme, lung Fru(1,6)Pase is significantly less inhibited by AMP than the muscle enzyme.
GO:0005515 protein binding	IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in...	REMOVE	Summary: IPI 'protein binding' with FXR2 (PMID:16189514). Reason: Bare 'protein binding' carries no functional information about FBP1. The interaction may well be real (FBP1 is reported in large binary interactome screens), but it does not describe an activity of FBP1, and the source supports no more informative molecular function term for it. Removal does not mean the interaction is false. Supporting Evidence: file:human/FBP1/FBP1-uniprot.txt Catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate in the presence of divalent cations, acting as a rate-limiting enzyme in gluconeogenesis.
GO:0005515 protein binding	IPI PMID:16275660 Identification of VCP/p97, carboxyl terminus of Hsp70-intera...	REMOVE	Summary: IPI 'protein binding' with BIN1 (PMID:16275660). Reason: Bare 'protein binding' carries no functional information about FBP1. The interaction may well be real (FBP1 is reported in large binary interactome screens), but it does not describe an activity of FBP1, and the source supports no more informative molecular function term for it. Removal does not mean the interaction is false. Supporting Evidence: file:human/FBP1/FBP1-uniprot.txt Catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate in the presence of divalent cations, acting as a rate-limiting enzyme in gluconeogenesis.
GO:0005515 protein binding	IPI PMID:25043030 Fructose-1,6-bisphosphatase opposes renal carcinoma progress...	REMOVE	Summary: IPI 'protein binding' with HIF1A (PMID:25043030). Reason: Bare 'protein binding' carries no functional information about FBP1. The interaction may well be real (FBP1 is reported in large binary interactome screens), but it does not describe an activity of FBP1, and the source supports no more informative molecular function term for it. Removal does not mean the interaction is false. The functional content of this HIF interaction (FBP1 binding the HIF inhibitory domain to repress HIF target genes) is already captured more informatively by the GO:0061629 annotation from the same paper. Supporting Evidence: PMID:25043030 FBP1 restrains cell proliferation, glycolysis and the pentose phosphate pathway in a catalytic-activity-independent manner, by inhibiting nuclear HIF function via direct interaction with the HIF inhibitory domain.
GO:0005515 protein binding	IPI PMID:25043030 Fructose-1,6-bisphosphatase opposes renal carcinoma progress...	REMOVE	Summary: IPI 'protein binding' with EPAS1 (HIF-2 alpha) (PMID:25043030). Reason: Bare 'protein binding' carries no functional information about FBP1. The interaction may well be real (FBP1 is reported in large binary interactome screens), but it does not describe an activity of FBP1, and the source supports no more informative molecular function term for it. Removal does not mean the interaction is false. The functional content of this HIF interaction (FBP1 binding the HIF inhibitory domain to repress HIF target genes) is already captured more informatively by the GO:0061629 annotation from the same paper. Supporting Evidence: PMID:25043030 FBP1 restrains cell proliferation, glycolysis and the pentose phosphate pathway in a catalytic-activity-independent manner, by inhibiting nuclear HIF function via direct interaction with the HIF inhibitory domain.
GO:0005515 protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	REMOVE	Summary: IPI 'protein binding' with FBP2 (muscle FBPase isozyme) (PMID:25416956). Reason: Bare 'protein binding' carries no functional information about FBP1. The interaction may well be real (FBP1 is reported in large binary interactome screens), but it does not describe an activity of FBP1, and the source supports no more informative molecular function term for it. Removal does not mean the interaction is false. FBP1/FBP2 co-assembly is a hetero-oligomerisation of two FBPase isozymes, recurrently detected in yeast two-hybrid screens; its physiological significance is not established. Supporting Evidence: file:human/FBP1/FBP1-uniprot.txt SUBUNIT: Homotetramer.
GO:0005515 protein binding	IPI PMID:25910212 Widespread macromolecular interaction perturbations in human...	REMOVE	Summary: IPI 'protein binding' with FBP2 (muscle FBPase isozyme) (PMID:25910212). Reason: Bare 'protein binding' carries no functional information about FBP1. The interaction may well be real (FBP1 is reported in large binary interactome screens), but it does not describe an activity of FBP1, and the source supports no more informative molecular function term for it. Removal does not mean the interaction is false. FBP1/FBP2 co-assembly is a hetero-oligomerisation of two FBPase isozymes, recurrently detected in yeast two-hybrid screens; its physiological significance is not established. Supporting Evidence: file:human/FBP1/FBP1-uniprot.txt SUBUNIT: Homotetramer.
GO:0005515 protein binding	IPI PMID:28514442 Architecture of the human interactome defines protein commun...	REMOVE	Summary: IPI 'protein binding' with FBP2 (muscle FBPase isozyme) (PMID:28514442). Reason: Bare 'protein binding' carries no functional information about FBP1. The interaction may well be real (FBP1 is reported in large binary interactome screens), but it does not describe an activity of FBP1, and the source supports no more informative molecular function term for it. Removal does not mean the interaction is false. FBP1/FBP2 co-assembly is a hetero-oligomerisation of two FBPase isozymes, recurrently detected in yeast two-hybrid screens; its physiological significance is not established. Supporting Evidence: file:human/FBP1/FBP1-uniprot.txt SUBUNIT: Homotetramer.
GO:0005515 protein binding	IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari...	REMOVE	Summary: IPI 'protein binding' with FBP2 (muscle FBPase isozyme) (PMID:31515488). Reason: Bare 'protein binding' carries no functional information about FBP1. The interaction may well be real (FBP1 is reported in large binary interactome screens), but it does not describe an activity of FBP1, and the source supports no more informative molecular function term for it. Removal does not mean the interaction is false. FBP1/FBP2 co-assembly is a hetero-oligomerisation of two FBPase isozymes, recurrently detected in yeast two-hybrid screens; its physiological significance is not established. Supporting Evidence: file:human/FBP1/FBP1-uniprot.txt SUBUNIT: Homotetramer.
GO:0005515 protein binding	IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari...	REMOVE	Summary: IPI 'protein binding' with FXR2 (PMID:31515488). Reason: Bare 'protein binding' carries no functional information about FBP1. The interaction may well be real (FBP1 is reported in large binary interactome screens), but it does not describe an activity of FBP1, and the source supports no more informative molecular function term for it. Removal does not mean the interaction is false. Supporting Evidence: file:human/FBP1/FBP1-uniprot.txt Catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate in the presence of divalent cations, acting as a rate-limiting enzyme in gluconeogenesis.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: IPI 'protein binding' with FBP2 (muscle FBPase isozyme) (PMID:32296183). Reason: Bare 'protein binding' carries no functional information about FBP1. The interaction may well be real (FBP1 is reported in large binary interactome screens), but it does not describe an activity of FBP1, and the source supports no more informative molecular function term for it. Removal does not mean the interaction is false. FBP1/FBP2 co-assembly is a hetero-oligomerisation of two FBPase isozymes, recurrently detected in yeast two-hybrid screens; its physiological significance is not established. Supporting Evidence: file:human/FBP1/FBP1-uniprot.txt SUBUNIT: Homotetramer.
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	REMOVE	Summary: IPI 'protein binding' with HTT (PMID:32814053). Reason: Bare 'protein binding' carries no functional information about FBP1. The interaction may well be real (FBP1 is reported in large binary interactome screens), but it does not describe an activity of FBP1, and the source supports no more informative molecular function term for it. Removal does not mean the interaction is false. Supporting Evidence: file:human/FBP1/FBP1-uniprot.txt Catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate in the presence of divalent cations, acting as a rate-limiting enzyme in gluconeogenesis.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	REMOVE	Summary: IPI 'protein binding' with FBP2 (muscle FBPase isozyme) (PMID:33961781). Reason: Bare 'protein binding' carries no functional information about FBP1. The interaction may well be real (FBP1 is reported in large binary interactome screens), but it does not describe an activity of FBP1, and the source supports no more informative molecular function term for it. Removal does not mean the interaction is false. FBP1/FBP2 co-assembly is a hetero-oligomerisation of two FBPase isozymes, recurrently detected in yeast two-hybrid screens; its physiological significance is not established. Supporting Evidence: file:human/FBP1/FBP1-uniprot.txt SUBUNIT: Homotetramer.
GO:0005515 protein binding	IPI PMID:8387495 Isolation of a human liver fructose-1,6-bisphosphatase cDNA ...	REMOVE	Summary: IPI 'protein binding' with PFKFB2 (PMID:8387495). Reason: Bare 'protein binding' carries no functional information about FBP1. The interaction may well be real (FBP1 is reported in large binary interactome screens), but it does not describe an activity of FBP1, and the source supports no more informative molecular function term for it. Removal does not mean the interaction is false. The cited abstract is a kinetic study reporting inhibition by fructose 2,6-bisphosphate (the PFKFB product) and AMP; it does not report physical binding to PFKFB in the abstract, so the partner cannot be verified here. Supporting Evidence: PMID:8387495 the human enzyme was more sensitive to inhibition by fructose-2,6-bisphosphate (Ki = 0.3 microM) and AMP (Ki = 12 microM) than the rat liver form
GO:0005576 extracellular region	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Extracellular region (IEA, Ensembl orthology transfer). Reason: FBP1 is a cytosolic enzyme with no signal peptide; extracellular detection reflects exosome cargo at most and is not a site of action. Supporting Evidence: Reactome:R-HSA-70479 Cytosolic FBP (fructose-1,6-bisphosphatase) tetramers catalyze the physiologically irreversible hydrolysis of F1,6PP (fructose-1,6-bisphosphate) to form Fru(6)P (fructose-6-phosphate) and Pi (orthophosphate).
GO:0005634 nucleus	IMP PMID:25043030 Fructose-1,6-bisphosphatase opposes renal carcinoma progress...	KEEP AS NON CORE	Summary: Nuclear localization (IMP, PMID:25043030): in VHL-deficient ccRCC cells a nuclear FBP1 pool co-localizes with HIF at hypoxia-response elements. Reason: A real but context-specific nuclear pool supporting a catalytic-activity-independent repression of HIF targets; FBP1's principal site of action is the cytosol. Supporting Evidence: PMID:25043030 FBP1 restrains cell proliferation, glycolysis and the pentose phosphate pathway in a catalytic-activity-independent manner, by inhibiting nuclear HIF function via direct interaction with the HIF inhibitory domain.
GO:0005737 cytoplasm	IBA GO_REF:0000033	ACCEPT	Summary: Cytoplasm localization (IBA). Reason: Gluconeogenic FBPase acts in the cytosol, where the second part of gluconeogenesis takes place. Supporting Evidence: Reactome:R-HSA-70479 Cytosolic FBP (fructose-1,6-bisphosphatase) tetramers catalyze the physiologically irreversible hydrolysis of F1,6PP (fructose-1,6-bisphosphate) to form Fru(6)P (fructose-6-phosphate) and Pi (orthophosphate).
GO:0005737 cytoplasm	IDA PMID:20096900 Novel compound heterozygous mutations in the fructose-1,6-bi...	ACCEPT	Summary: Cytoplasmic localization (IDA, PMID:20096900). Reason: FBP1 is a soluble cytosolic enzyme; consistent with Reactome and UniProt. Supporting Evidence: Reactome:R-HSA-70479 Cytosolic FBP (fructose-1,6-bisphosphatase) tetramers catalyze the physiologically irreversible hydrolysis of F1,6PP (fructose-1,6-bisphosphate) to form Fru(6)P (fructose-6-phosphate) and Pi (orthophosphate).
GO:0005829 cytosol	IBA GO_REF:0000033	ACCEPT	Summary: Cytosol localization (IBA). Reason: Gluconeogenic FBPase acts in the cytosol, where the second part of gluconeogenesis takes place. Supporting Evidence: Reactome:R-HSA-70479 Cytosolic FBP (fructose-1,6-bisphosphatase) tetramers catalyze the physiologically irreversible hydrolysis of F1,6PP (fructose-1,6-bisphosphate) to form Fru(6)P (fructose-6-phosphate) and Pi (orthophosphate).
GO:0005829 cytosol	TAS Reactome:R-HSA-70479	ACCEPT	Summary: Cytosol localization (TAS). Reason: Gluconeogenic FBPase acts in the cytosol, where the second part of gluconeogenesis takes place. Supporting Evidence: Reactome:R-HSA-70479 Cytosolic FBP (fructose-1,6-bisphosphatase) tetramers catalyze the physiologically irreversible hydrolysis of F1,6PP (fructose-1,6-bisphosphate) to form Fru(6)P (fructose-6-phosphate) and Pi (orthophosphate).
GO:0005829 cytosol	TAS Reactome:R-HSA-9944719	ACCEPT	Summary: Cytosol location derived from the Reactome event in which TCF19:NuRD represses FBP1 gene expression (the cytosolic FBP1 protein is the event output). Reason: The location of the protein product is correct (cytosol), even though the event itself concerns gene repression. Supporting Evidence: Reactome:R-HSA-9944719 FBP1 encodes fructose-1,6-bisphosphatase 1, a rate-limiting enzyme in gluconeogenesis Reactome:R-HSA-70479 Cytosolic FBP (fructose-1,6-bisphosphatase) tetramers catalyze the physiologically irreversible hydrolysis of F1,6PP (fructose-1,6-bisphosphate) to form Fru(6)P (fructose-6-phosphate) and Pi (orthophosphate).
GO:0005975 carbohydrate metabolic process	IEA GO_REF:0000002	MODIFY	Summary: Over-general InterPro-derived process term (carbohydrate metabolic process). Reason: Correct but too general; the specific process is gluconeogenesis. Proposed replacements: gluconeogenesis Supporting Evidence: file:human/FBP1/FBP1-uniprot.txt Catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate in the presence of divalent cations, acting as a rate-limiting enzyme in gluconeogenesis.
GO:0006000 fructose metabolic process	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Fructose metabolic process (IEA). Reason: Hepatic FBP1 is required for disposal of dietary fructose carbon into glucose, and its loss causes fructose intolerance (liver-specific Fbp1 knockout mice; patients must avoid fructose). Valid but secondary to gluconeogenesis. Supporting Evidence: PMID:36964915 By contrast, liver-specific deletion of Fbp1 in adult mice leads to fructose intolerance, as manifested by substantial weight loss, hepatomegaly, and liver injury after exposure to a high-fructose diet.
GO:0006000 fructose metabolic process	TAS PMID:7558035 Human fructose-1,6-bisphosphatase gene (FBP1): exon-intron o...	KEEP AS NON CORE	Summary: Fructose metabolic process (TAS). Reason: Hepatic FBP1 is required for disposal of dietary fructose carbon into glucose, and its loss causes fructose intolerance (liver-specific Fbp1 knockout mice; patients must avoid fructose). Valid but secondary to gluconeogenesis. Supporting Evidence: PMID:7558035 Fructose-1,6-bisphosphatase (EC 3.1.3.11) is a key regulatory enzyme of gluconeogenesis that catalyzes the hydrolysis of fructose-1,6-bisphosphate to generate fructose-6-phosphate and inorganic phosphate.
GO:0006002 fructose 6-phosphate metabolic process	IDA PMID:16442285 Benzoxazole benzenesulfonamides are novel allosteric inhibit...	KEEP AS NON CORE	Summary: Fructose 6-phosphate metabolic process (IDA). Reason: Fructose 6-phosphate is the product of the FBPase reaction; accurate but less informative than gluconeogenesis. Supporting Evidence: PMID:16442285 We have identified benzoxazole benzenesulfonamide 1 as a novel allosteric inhibitor of fructose-1,6-bisphosphatase (FBPase-1).
GO:0006002 fructose 6-phosphate metabolic process	IDA PMID:8387495 Isolation of a human liver fructose-1,6-bisphosphatase cDNA ...	KEEP AS NON CORE	Summary: Fructose 6-phosphate metabolic process (IDA). Reason: Fructose 6-phosphate is the product of the FBPase reaction; accurate but less informative than gluconeogenesis. Supporting Evidence: PMID:8387495 Approximately 50% of the expressed human fructose-1,6-bisphosphatase was soluble and enzymatically active
GO:0006002 fructose 6-phosphate metabolic process	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Fructose 6-phosphate metabolic process (IEA). Reason: Fructose 6-phosphate is the product of the FBPase reaction; accurate but less informative than gluconeogenesis. Supporting Evidence: file:human/FBP1/FBP1-uniprot.txt Catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate in the presence of divalent cations, acting as a rate-limiting enzyme in gluconeogenesis.
GO:0006094 gluconeogenesis	IBA GO_REF:0000033	ACCEPT	Summary: Core process. Phylogenetically inferred participation in gluconeogenesis. Reason: FBP1 catalyses a committed, irreversible step of gluconeogenesis (fructose 1,6-bisphosphate to fructose 6-phosphate); the enzyme does part of the work of the pathway. Supporting Evidence: file:human/FBP1/FBP1-uniprot.txt Catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate in the presence of divalent cations, acting as a rate-limiting enzyme in gluconeogenesis. PMID:7558035 Fructose-1,6-bisphosphatase (EC 3.1.3.11) is a key regulatory enzyme of gluconeogenesis that catalyzes the hydrolysis of fructose-1,6-bisphosphate to generate fructose-6-phosphate and inorganic phosphate.
GO:0006094 gluconeogenesis	IEA GO_REF:0000120	ACCEPT	Summary: Core process. Electronic (UniPathway) annotation to gluconeogenesis. Reason: FBP1 catalyses a committed, irreversible step of gluconeogenesis (fructose 1,6-bisphosphate to fructose 6-phosphate); the enzyme does part of the work of the pathway. Supporting Evidence: file:human/FBP1/FBP1-uniprot.txt Catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate in the presence of divalent cations, acting as a rate-limiting enzyme in gluconeogenesis. PMID:7558035 Fructose-1,6-bisphosphatase (EC 3.1.3.11) is a key regulatory enzyme of gluconeogenesis that catalyzes the hydrolysis of fructose-1,6-bisphosphate to generate fructose-6-phosphate and inorganic phosphate.
GO:0006094 gluconeogenesis	IMP PMID:19259699 Novel FBP1 gene mutations in Arab patients with fructose-1,6...	ACCEPT	Summary: Core process. Patient FBP1 loss-of-function variants (PMID:19259699) cause impaired gluconeogenesis. Reason: FBP1 catalyses the irreversible fructose-1,6-bisphosphatase step of gluconeogenesis; its loss blocks the pathway, which is the basis of FBPase deficiency. Supporting Evidence: PMID:19259699 Deficiency of fructose-1,6-bisphosphatase (FBP) results in impaired gluconeogenesis, which is characterized by episodes of hyperventilation, apnea, hypoglycemia, and metabolic and lactic acidosis.
GO:0006094 gluconeogenesis	IMP PMID:20096900 Novel compound heterozygous mutations in the fructose-1,6-bi...	ACCEPT	Summary: Core process. Patient FBP1 loss-of-function variants (PMID:20096900) cause impaired gluconeogenesis. Reason: FBP1 catalyses the irreversible fructose-1,6-bisphosphatase step of gluconeogenesis; its loss blocks the pathway, which is the basis of FBPase deficiency. Supporting Evidence: PMID:20096900 Fructose-1,6-bisphosphatase (FBPase) deficiency is an autosomal recessive disorder caused by a mutation of the fructose-1,6-bisphosphatase 1 (FBP1) gene and results in impaired gluconeogenesis.
GO:0006094 gluconeogenesis	ISS GO_REF:0000024	ACCEPT	Summary: Core process. Sequence-similarity transfer from rat FBP1. Reason: FBP1 catalyses a committed, irreversible step of gluconeogenesis (fructose 1,6-bisphosphate to fructose 6-phosphate); the enzyme does part of the work of the pathway. Supporting Evidence: file:human/FBP1/FBP1-uniprot.txt Catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate in the presence of divalent cations, acting as a rate-limiting enzyme in gluconeogenesis. PMID:7558035 Fructose-1,6-bisphosphatase (EC 3.1.3.11) is a key regulatory enzyme of gluconeogenesis that catalyzes the hydrolysis of fructose-1,6-bisphosphate to generate fructose-6-phosphate and inorganic phosphate.
GO:0006094 gluconeogenesis	TAS Reactome:R-HSA-70263	ACCEPT	Summary: Core process. Reactome gluconeogenesis pathway. Reason: FBP1 catalyses a committed, irreversible step of gluconeogenesis (fructose 1,6-bisphosphate to fructose 6-phosphate); the enzyme does part of the work of the pathway. Supporting Evidence: Reactome:R-HSA-70263 Hydrolysis of fructose 1,6 bisphosphate to fructose 6 phosphate is catalyzed by fructose 1,6 bisphosphatase PMID:7558035 Fructose-1,6-bisphosphatase (EC 3.1.3.11) is a key regulatory enzyme of gluconeogenesis that catalyzes the hydrolysis of fructose-1,6-bisphosphate to generate fructose-6-phosphate and inorganic phosphate.
GO:0006111 regulation of gluconeogenesis	IMP PMID:7558035 Human fructose-1,6-bisphosphatase gene (FBP1): exon-intron o...	MARK AS OVER ANNOTATED	Summary: IMP annotation to regulation of gluconeogenesis from the FBP1 gene-structure/mutation-screening paper. Reason: FBP1 is described as a 'key regulatory enzyme' in the pathway sense (an allosterically controlled, flux-controlling step), which GO captures as direct participation in gluconeogenesis plus its own catalytic activity, not as regulation of the process by a separate regulator. The cached abstract also reports no causal mutation in the subjects screened. Supporting Evidence: PMID:7558035 Fructose-1,6-bisphosphatase (EC 3.1.3.11) is a key regulatory enzyme of gluconeogenesis that catalyzes the hydrolysis of fructose-1,6-bisphosphate to generate fructose-6-phosphate and inorganic phosphate.
GO:0016208 AMP binding	IDA PMID:10222032 cDNA sequence and kinetic properties of human lung fructose(...	KEEP AS NON CORE	Summary: AMP binding (IDA, PMID:10222032): AMP is the physiological allosteric inhibitor of FBPase, binding a site distinct from the active site. Reason: Allosteric AMP binding is a well-established regulatory property of FBP1 (UniProt; inhibitor studies exploit the AMP site), but it regulates rather than constitutes the catalytic function. Supporting Evidence: PMID:10222032 Like the liver isoenzyme, lung Fru(1,6)Pase is significantly less inhibited by AMP than the muscle enzyme. file:human/FBP1/FBP1-uniprot.txt AMP acts as an allosteric inhibitor.
GO:0016208 AMP binding	IDA PMID:18650089 Allosteric FBPase inhibitors gain 10(5) times in potency whe...	KEEP AS NON CORE	Summary: AMP binding (IDA, PMID:18650089): AMP is the physiological allosteric inhibitor of FBPase, binding a site distinct from the active site. Reason: Allosteric AMP binding is a well-established regulatory property of FBP1 (UniProt; inhibitor studies exploit the AMP site), but it regulates rather than constitutes the catalytic function. Supporting Evidence: PMID:18650089 In its active form FBPase exists as a homotetramer and is allosterically regulated by AMP.
GO:0016208 AMP binding	IDA PMID:8387495 Isolation of a human liver fructose-1,6-bisphosphatase cDNA ...	KEEP AS NON CORE	Summary: AMP binding (IDA, PMID:8387495): AMP is the physiological allosteric inhibitor of FBPase, binding a site distinct from the active site. Reason: Allosteric AMP binding is a well-established regulatory property of FBP1 (UniProt; inhibitor studies exploit the AMP site), but it regulates rather than constitutes the catalytic function. Supporting Evidence: PMID:8387495 the human enzyme was more sensitive to inhibition by fructose-2,6-bisphosphate (Ki = 0.3 microM) and AMP (Ki = 12 microM) than the rat liver form
GO:0016791 phosphatase activity	IEA GO_REF:0000002	MODIFY	Summary: Over-general InterPro-derived hydrolase term (GO:0016791). Reason: Correct but uninformative parent of the specific activity. Proposed replacements: fructose 1,6-bisphosphate 1-phosphatase activity Supporting Evidence: file:human/FBP1/FBP1-uniprot.txt Catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate in the presence of divalent cations, acting as a rate-limiting enzyme in gluconeogenesis.
GO:0030308 negative regulation of cell growth	IDA PMID:19881551 Warburg effect revisited: an epigenetic link between glycoly...	MARK AS OVER ANNOTATED	Summary: Negative regulation of cell growth (IDA, PMID:19881551): restoring FBP1 expression reduces growth of gastric cancer cells. Reason: Re-expression in transformed cells that have epigenetically silenced FBP1 shows a tumour-suppressive effect, but this is an indirect metabolic consequence rather than a process FBP1 regulates in normal physiology. Supporting Evidence: PMID:19881551 Restoration of FBP1 expression reduced growth and glycolysis in gastric cancer cells.
GO:0031667 response to nutrient levels	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: response to nutrient levels (IEA, Ensembl orthology transfer from rodent expression studies). Reason: FBP1 expression is hormonally and nutritionally regulated (induced by fasting/glucagon-cAMP, repressed by insulin), but being transcriptionally regulated by a signal is not participation in the cellular response to it. Supporting Evidence: file:human/FBP1/FBP1-uniprot.txt Catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate in the presence of divalent cations, acting as a rate-limiting enzyme in gluconeogenesis.
GO:0032869 cellular response to insulin stimulus	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: cellular response to insulin stimulus (IEA, Ensembl orthology transfer from rodent expression studies). Reason: FBP1 expression is hormonally and nutritionally regulated (induced by fasting/glucagon-cAMP, repressed by insulin), but being transcriptionally regulated by a signal is not participation in the cellular response to it. Supporting Evidence: file:human/FBP1/FBP1-uniprot.txt Catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate in the presence of divalent cations, acting as a rate-limiting enzyme in gluconeogenesis.
GO:0042132 fructose 1,6-bisphosphate 1-phosphatase activity	EXP PMID:17350621 Glu 69 is essential for the high sensitivity of muscle fruct...	ACCEPT	Summary: Core molecular function: hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate and phosphate (EC 3.1.3.11). EXP annotation from PMID:17350621, whose abstract concerns the muscle isozyme (FBP2) and calcium inhibition; UniProt nevertheless cites it for FBP1 catalytic activity and kinetic constants, presumably with the liver enzyme as comparator in the full text. Reason: The activity is unequivocally correct for FBP1 and is independently established by recombinant expression of the human liver enzyme (PMID:8387495). The curator saw the full text, which is not cached; deferring to the annotation. Supporting Evidence: PMID:17350621 Muscle fructose-1,6-bisphosphatase (FBPase) is highly sensitive toward inhibition by AMP and calcium ions. PMID:8387495 Approximately 50% of the expressed human fructose-1,6-bisphosphatase was soluble and enzymatically active
GO:0042132 fructose 1,6-bisphosphate 1-phosphatase activity	IBA GO_REF:0000033	ACCEPT	Summary: Core molecular function: hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate and phosphate (EC 3.1.3.11). Phylogenetic inference from the FBPase class 1 family. Reason: Catalytic activity is conserved across the class 1 FBPase family and is experimentally established for the human enzyme itself (the target appears among the IBD sources, as expected). Supporting Evidence: file:human/FBP1/FBP1-uniprot.txt Catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate in the presence of divalent cations, acting as a rate-limiting enzyme in gluconeogenesis. PMID:8387495 Approximately 50% of the expressed human fructose-1,6-bisphosphatase was soluble and enzymatically active
GO:0042132 fructose 1,6-bisphosphate 1-phosphatase activity	IDA PMID:16442285 Benzoxazole benzenesulfonamides are novel allosteric inhibit...	ACCEPT	Summary: Core molecular function: hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate and phosphate (EC 3.1.3.11). Activity measured on purified human FBPase in allosteric-inhibitor studies (PMID:16442285). Reason: Inhibitor studies necessarily assay the catalytic activity of the human enzyme. Supporting Evidence: PMID:16442285 We have identified benzoxazole benzenesulfonamide 1 as a novel allosteric inhibitor of fructose-1,6-bisphosphatase (FBPase-1).
GO:0042132 fructose 1,6-bisphosphate 1-phosphatase activity	IDA PMID:18650089 Allosteric FBPase inhibitors gain 10(5) times in potency whe...	ACCEPT	Summary: Core molecular function: hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate and phosphate (EC 3.1.3.11). Activity measured on purified human FBPase in allosteric-inhibitor studies (PMID:18650089). Reason: Inhibitor studies necessarily assay the catalytic activity of the human enzyme. Supporting Evidence: PMID:18650089 Human fructose-1,6-bisphosphatase (FBPase, EC 3.1.3.11) is a key gluconeogenic enzyme, responsible for the hydrolysis of fructose-1,6-bisphosphate to fructose-6-phosphate
GO:0042132 fructose 1,6-bisphosphate 1-phosphatase activity	IDA PMID:8387495 Isolation of a human liver fructose-1,6-bisphosphatase cDNA ...	ACCEPT	Summary: Core molecular function: hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate and phosphate (EC 3.1.3.11). Recombinant human liver FBPase expressed in E. coli is enzymatically active; Asp118/Asp121 mutants lose activity. Reason: Direct biochemical demonstration of the activity of the human enzyme. Supporting Evidence: PMID:8387495 Approximately 50% of the expressed human fructose-1,6-bisphosphatase was soluble and enzymatically active PMID:8387495 Crystallographic analyses have suggested that Asp-118 and Asp-121 are catalytic residues located in a negatively charged pocket that binds divalent metal cations.
GO:0042132 fructose 1,6-bisphosphate 1-phosphatase activity	IEA GO_REF:0000120	ACCEPT	Summary: Core molecular function: hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate and phosphate (EC 3.1.3.11). Electronic (EC mapping) annotation. Reason: Correct; matches EC 3.1.3.11 assigned from characterization of the human enzyme. Supporting Evidence: file:human/FBP1/FBP1-uniprot.txt Catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate in the presence of divalent cations, acting as a rate-limiting enzyme in gluconeogenesis.
GO:0042132 fructose 1,6-bisphosphate 1-phosphatase activity	IMP PMID:19259699 Novel FBP1 gene mutations in Arab patients with fructose-1,6...	ACCEPT	Summary: Core molecular function: hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate and phosphate (EC 3.1.3.11). IMP from disease-causing FBP1 variants in Arab FBPase-deficient patients. Reason: Loss-of-function patient variants confirm that FBP1 carries the FBPase activity whose loss causes the disease. Supporting Evidence: PMID:19259699 Deficiency of fructose-1,6-bisphosphatase (FBP) results in impaired gluconeogenesis, which is characterized by episodes of hyperventilation, apnea, hypoglycemia, and metabolic and lactic acidosis.
GO:0042132 fructose 1,6-bisphosphate 1-phosphatase activity	IMP PMID:20096900 Novel compound heterozygous mutations in the fructose-1,6-bi...	ACCEPT	Summary: Core molecular function: hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate and phosphate (EC 3.1.3.11). IMP: patient G164S and 838delT FBP1 proteins are enzymatically inactive in COS-7 cells. Reason: Direct mutational evidence for the activity. Supporting Evidence: PMID:20096900 Transient transfection studies using COS-7 cells demonstrated that FBPase proteins with G164S or 838delT mutations were enzymatically inactive.
GO:0042132 fructose 1,6-bisphosphate 1-phosphatase activity	IMP PMID:7558035 Human fructose-1,6-bisphosphatase gene (FBP1): exon-intron o...	ACCEPT	Summary: Core molecular function: hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate and phosphate (EC 3.1.3.11). IMP from a gene-structure and mutation-screening paper; the abstract reports that no causal coding mutation was found in the two subjects screened. Reason: The cached abstract does not show the mutant phenotype the IMP rests on, but the function is unequivocally correct for FBP1 and the curator had the full text; deferring. Supporting Evidence: PMID:7558035 Fructose-1,6-bisphosphatase (EC 3.1.3.11) is a key regulatory enzyme of gluconeogenesis that catalyzes the hydrolysis of fructose-1,6-bisphosphate to generate fructose-6-phosphate and inorganic phosphate.
GO:0042132 fructose 1,6-bisphosphate 1-phosphatase activity	TAS Reactome:R-HSA-70479	ACCEPT	Summary: Core molecular function: hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate and phosphate (EC 3.1.3.11). Reactome: cytosolic FBP tetramers hydrolyze F1,6PP. Reason: Reactome correctly describes the gluconeogenic FBPase reaction. Supporting Evidence: Reactome:R-HSA-70479 Cytosolic FBP (fructose-1,6-bisphosphatase) tetramers catalyze the physiologically irreversible hydrolysis of F1,6PP (fructose-1,6-bisphosphate) to form Fru(6)P (fructose-6-phosphate) and Pi (orthophosphate).
GO:0042578 phosphoric ester hydrolase activity	IEA GO_REF:0000002	MODIFY	Summary: Over-general InterPro-derived hydrolase term (GO:0042578). Reason: Correct but uninformative parent of the specific activity. Proposed replacements: fructose 1,6-bisphosphate 1-phosphatase activity Supporting Evidence: file:human/FBP1/FBP1-uniprot.txt Catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate in the presence of divalent cations, acting as a rate-limiting enzyme in gluconeogenesis.
GO:0042802 identical protein binding	IPI PMID:16169070 A human protein-protein interaction network: a resource for ...	KEEP AS NON CORE	Summary: Self-interaction (PMID:16169070) reflecting the FBP1 homotetramer. Reason: FBPase is an obligate homotetramer whose allosteric R/T transition depends on the tetrameric assembly; the self-interaction is real and structurally established but is a structural property supporting the catalytic function rather than a distinct activity. Supporting Evidence: PMID:18650089 In its active form FBPase exists as a homotetramer and is allosterically regulated by AMP. file:human/FBP1/FBP1-uniprot.txt SUBUNIT: Homotetramer.
GO:0042802 identical protein binding	IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in...	KEEP AS NON CORE	Summary: Self-interaction (PMID:16189514) reflecting the FBP1 homotetramer. Reason: FBPase is an obligate homotetramer whose allosteric R/T transition depends on the tetrameric assembly; the self-interaction is real and structurally established but is a structural property supporting the catalytic function rather than a distinct activity. Supporting Evidence: PMID:18650089 In its active form FBPase exists as a homotetramer and is allosterically regulated by AMP. file:human/FBP1/FBP1-uniprot.txt SUBUNIT: Homotetramer.
GO:0042802 identical protein binding	IPI PMID:16442285 Benzoxazole benzenesulfonamides are novel allosteric inhibit...	KEEP AS NON CORE	Summary: Self-interaction (PMID:16442285) reflecting the FBP1 homotetramer. Reason: FBPase is an obligate homotetramer whose allosteric R/T transition depends on the tetrameric assembly; the self-interaction is real and structurally established but is a structural property supporting the catalytic function rather than a distinct activity. Supporting Evidence: PMID:18650089 In its active form FBPase exists as a homotetramer and is allosterically regulated by AMP. file:human/FBP1/FBP1-uniprot.txt SUBUNIT: Homotetramer.
GO:0042802 identical protein binding	IPI PMID:18650089 Allosteric FBPase inhibitors gain 10(5) times in potency whe...	KEEP AS NON CORE	Summary: Self-interaction (PMID:18650089) reflecting the FBP1 homotetramer. Reason: FBPase is an obligate homotetramer whose allosteric R/T transition depends on the tetrameric assembly; the self-interaction is real and structurally established but is a structural property supporting the catalytic function rather than a distinct activity. Supporting Evidence: PMID:18650089 In its active form FBPase exists as a homotetramer and is allosterically regulated by AMP. file:human/FBP1/FBP1-uniprot.txt SUBUNIT: Homotetramer.
GO:0042802 identical protein binding	IPI PMID:21516116 Next-generation sequencing to generate interactome datasets.	KEEP AS NON CORE	Summary: Self-interaction (PMID:21516116) reflecting the FBP1 homotetramer. Reason: FBPase is an obligate homotetramer whose allosteric R/T transition depends on the tetrameric assembly; the self-interaction is real and structurally established but is a structural property supporting the catalytic function rather than a distinct activity. Supporting Evidence: PMID:18650089 In its active form FBPase exists as a homotetramer and is allosterically regulated by AMP. file:human/FBP1/FBP1-uniprot.txt SUBUNIT: Homotetramer.
GO:0042802 identical protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	KEEP AS NON CORE	Summary: Self-interaction (PMID:25416956) reflecting the FBP1 homotetramer. Reason: FBPase is an obligate homotetramer whose allosteric R/T transition depends on the tetrameric assembly; the self-interaction is real and structurally established but is a structural property supporting the catalytic function rather than a distinct activity. Supporting Evidence: PMID:18650089 In its active form FBPase exists as a homotetramer and is allosterically regulated by AMP. file:human/FBP1/FBP1-uniprot.txt SUBUNIT: Homotetramer.
GO:0042802 identical protein binding	IPI PMID:25502805 A massively parallel pipeline to clone DNA variants and exam...	KEEP AS NON CORE	Summary: Self-interaction (PMID:25502805) reflecting the FBP1 homotetramer. Reason: FBPase is an obligate homotetramer whose allosteric R/T transition depends on the tetrameric assembly; the self-interaction is real and structurally established but is a structural property supporting the catalytic function rather than a distinct activity. Supporting Evidence: PMID:18650089 In its active form FBPase exists as a homotetramer and is allosterically regulated by AMP. file:human/FBP1/FBP1-uniprot.txt SUBUNIT: Homotetramer.
GO:0042802 identical protein binding	IPI PMID:25910212 Widespread macromolecular interaction perturbations in human...	KEEP AS NON CORE	Summary: Self-interaction (PMID:25910212) reflecting the FBP1 homotetramer. Reason: FBPase is an obligate homotetramer whose allosteric R/T transition depends on the tetrameric assembly; the self-interaction is real and structurally established but is a structural property supporting the catalytic function rather than a distinct activity. Supporting Evidence: PMID:18650089 In its active form FBPase exists as a homotetramer and is allosterically regulated by AMP. file:human/FBP1/FBP1-uniprot.txt SUBUNIT: Homotetramer.
GO:0042802 identical protein binding	IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari...	KEEP AS NON CORE	Summary: Self-interaction (PMID:31515488) reflecting the FBP1 homotetramer. Reason: FBPase is an obligate homotetramer whose allosteric R/T transition depends on the tetrameric assembly; the self-interaction is real and structurally established but is a structural property supporting the catalytic function rather than a distinct activity. Supporting Evidence: PMID:18650089 In its active form FBPase exists as a homotetramer and is allosterically regulated by AMP. file:human/FBP1/FBP1-uniprot.txt SUBUNIT: Homotetramer.
GO:0042802 identical protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	KEEP AS NON CORE	Summary: Self-interaction (PMID:32296183) reflecting the FBP1 homotetramer. Reason: FBPase is an obligate homotetramer whose allosteric R/T transition depends on the tetrameric assembly; the self-interaction is real and structurally established but is a structural property supporting the catalytic function rather than a distinct activity. Supporting Evidence: PMID:18650089 In its active form FBPase exists as a homotetramer and is allosterically regulated by AMP. file:human/FBP1/FBP1-uniprot.txt SUBUNIT: Homotetramer.
GO:0045820 negative regulation of glycolysis	IDA PMID:19881551 Warburg effect revisited: an epigenetic link between glycoly...	KEEP AS NON CORE	Summary: Negative regulation of glycolysis (IDA, PMID:19881551). Reason: FBP1 opposes glycolytic flux, partly because it catalyses the reverse of the phosphofructokinase step (futile-cycle direction) and, in ccRCC, partly through HIF repression. Real in the cancer-cell settings studied, but secondary to the gluconeogenic role. Supporting Evidence: PMID:19881551 Fructose-1,6-bisphosphatase-1 (FBP1), which functions to antagonize glycolysis was downregulated through NF-kappaB pathway in Ras-transformed NIH3T3 cells.
GO:0045820 negative regulation of glycolysis	IMP PMID:25043030 Fructose-1,6-bisphosphatase opposes renal carcinoma progress...	KEEP AS NON CORE	Summary: Negative regulation of glycolysis (IMP, PMID:25043030). Reason: FBP1 opposes glycolytic flux, partly because it catalyses the reverse of the phosphofructokinase step (futile-cycle direction) and, in ccRCC, partly through HIF repression. Real in the cancer-cell settings studied, but secondary to the gluconeogenic role. Supporting Evidence: PMID:25043030 First, FBP1 antagonizes glycolytic flux in renal tubular epithelial cells, the presumptive ccRCC cell of origin, thereby inhibiting a potential Warburg effect.
GO:0046580 negative regulation of Ras protein signal transduction	IDA PMID:19881551 Warburg effect revisited: an epigenetic link between glycoly...	MARK AS OVER ANNOTATED	Summary: Negative regulation of Ras protein signal transduction (IDA, PMID:19881551). Reason: The abstract reports that Ras, via NF-kappaB, downregulates FBP1 (FBP1 is downstream of, and repressed by, Ras signalling) and that FBP1 restoration suppresses anchorage-independent growth of Ras-transformed cells. That supports FBP1 opposing a Ras-driven phenotype, not FBP1 regulating Ras signal transduction itself. Supporting Evidence: PMID:19881551 Fructose-1,6-bisphosphatase-1 (FBP1), which functions to antagonize glycolysis was downregulated through NF-kappaB pathway in Ras-transformed NIH3T3 cells.
GO:0046872 metal ion binding	IMP PMID:8387495 Isolation of a human liver fructose-1,6-bisphosphatase cDNA ...	KEEP AS NON CORE	Summary: Metal ion binding (IMP, PMID:8387495): Asp118/Asp121 form a divalent-cation pocket required for catalysis. Reason: Correct (FBPase binds three Mg2+ per subunit) and part of the catalytic mechanism; a more specific term would be magnesium ion binding (GO:0000287), but the general term is accurate. Supporting Evidence: PMID:8387495 Crystallographic analyses have suggested that Asp-118 and Asp-121 are catalytic residues located in a negatively charged pocket that binds divalent metal cations. file:human/FBP1/FBP1-uniprot.txt Note=Binds 3 Mg(2+) ions per subunit.
GO:0048029 monosaccharide binding	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Monosaccharide binding (IEA), transferred from rat FBP1. Reason: Binding of the sugar-phosphate substrate and of fructose 2,6-bisphosphate is intrinsic to the catalytic/regulatory function and is better represented by the catalytic activity term; 'monosaccharide binding' adds no information. Supporting Evidence: file:human/FBP1/FBP1-uniprot.txt Catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate in the presence of divalent cations, acting as a rate-limiting enzyme in gluconeogenesis. PMID:8387495 the human enzyme was more sensitive to inhibition by fructose-2,6-bisphosphate (Ki = 0.3 microM) and AMP (Ki = 12 microM) than the rat liver form
GO:0048029 monosaccharide binding	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: Monosaccharide binding (ISS), transferred from rat FBP1. Reason: Binding of the sugar-phosphate substrate and of fructose 2,6-bisphosphate is intrinsic to the catalytic/regulatory function and is better represented by the catalytic activity term; 'monosaccharide binding' adds no information. Supporting Evidence: file:human/FBP1/FBP1-uniprot.txt Catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate in the presence of divalent cations, acting as a rate-limiting enzyme in gluconeogenesis. PMID:8387495 the human enzyme was more sensitive to inhibition by fructose-2,6-bisphosphate (Ki = 0.3 microM) and AMP (Ki = 12 microM) than the rat liver form
GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding	IMP PMID:25043030 Fructose-1,6-bisphosphatase opposes renal carcinoma progress...	KEEP AS NON CORE	Summary: RNA polymerase II-specific DNA-binding transcription factor binding (IMP, PMID:25043030): FBP1 binds the HIF-1 alpha / HIF-2 alpha inhibitory domain. Reason: An informative MF for the HIF interaction; context-specific moonlighting function, not the core enzymatic role. Supporting Evidence: PMID:25043030 FBP1 restrains cell proliferation, glycolysis and the pentose phosphate pathway in a catalytic-activity-independent manner, by inhibiting nuclear HIF function via direct interaction with the HIF inhibitory domain.
GO:0070062 extracellular exosome	HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos...	KEEP AS NON CORE	Summary: Extracellular exosome (HDA, PMID:19056867) from proteomic surveys of urinary/prostatic exosomes. Reason: Abundant cytosolic enzymes are routinely captured in exosome proteomes; the observation is real but has no known functional significance for FBP1. Supporting Evidence: Reactome:R-HSA-70479 Cytosolic FBP (fructose-1,6-bisphosphatase) tetramers catalyze the physiologically irreversible hydrolysis of F1,6PP (fructose-1,6-bisphosphate) to form Fru(6)P (fructose-6-phosphate) and Pi (orthophosphate).
GO:0070062 extracellular exosome	HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres...	KEEP AS NON CORE	Summary: Extracellular exosome (HDA, PMID:23533145) from proteomic surveys of urinary/prostatic exosomes. Reason: Abundant cytosolic enzymes are routinely captured in exosome proteomes; the observation is real but has no known functional significance for FBP1. Supporting Evidence: Reactome:R-HSA-70479 Cytosolic FBP (fructose-1,6-bisphosphatase) tetramers catalyze the physiologically irreversible hydrolysis of F1,6PP (fructose-1,6-bisphosphate) to form Fru(6)P (fructose-6-phosphate) and Pi (orthophosphate).
GO:0071286 cellular response to magnesium ion	IDA PMID:10222032 cDNA sequence and kinetic properties of human lung fructose(...	MARK AS OVER ANNOTATED	Summary: Cellular response to magnesium ion (IDA, PMID:10222032), from kinetic characterization of purified lung FBPase. Reason: Mg2+ is a catalytic cofactor of FBPase; dependence of in vitro enzyme kinetics on Mg2+ is cofactor usage, not a cellular response process. Supporting Evidence: PMID:10222032 Like the liver isoenzyme, lung Fru(1,6)Pase is significantly less inhibited by AMP than the muscle enzyme. file:human/FBP1/FBP1-uniprot.txt Note=Binds 3 Mg(2+) ions per subunit.
GO:0071320 cellular response to cAMP	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: cellular response to cAMP (IEA, Ensembl orthology transfer from rodent expression studies). Reason: FBP1 expression is hormonally and nutritionally regulated (induced by fasting/glucagon-cAMP, repressed by insulin), but being transcriptionally regulated by a signal is not participation in the cellular response to it. Supporting Evidence: file:human/FBP1/FBP1-uniprot.txt Catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate in the presence of divalent cations, acting as a rate-limiting enzyme in gluconeogenesis.
GO:0071466 cellular response to xenobiotic stimulus	IDA PMID:16442285 Benzoxazole benzenesulfonamides are novel allosteric inhibit...	REMOVE	Summary: Cellular response to xenobiotic stimulus (IDA, PMID:16442285): medicinal-chemistry studies of synthetic allosteric FBPase inhibitors. Reason: Inhibition of the purified enzyme by drug candidates binding the AMP site is a pharmacological property of the protein, not a cellular response process carried out by FBP1. The cited abstracts describe in vitro inhibitor binding only. Supporting Evidence: PMID:16442285 We have identified benzoxazole benzenesulfonamide 1 as a novel allosteric inhibitor of fructose-1,6-bisphosphatase (FBPase-1).
GO:0071466 cellular response to xenobiotic stimulus	IDA PMID:18650089 Allosteric FBPase inhibitors gain 10(5) times in potency whe...	REMOVE	Summary: Cellular response to xenobiotic stimulus (IDA, PMID:18650089): medicinal-chemistry studies of synthetic allosteric FBPase inhibitors. Reason: Inhibition of the purified enzyme by drug candidates binding the AMP site is a pharmacological property of the protein, not a cellular response process carried out by FBP1. The cited abstracts describe in vitro inhibitor binding only. Supporting Evidence: PMID:18650089 Human fructose-1,6-bisphosphatase (FBPase, EC 3.1.3.11) is a key gluconeogenic enzyme, responsible for the hydrolysis of fructose-1,6-bisphosphate to fructose-6-phosphate
GO:0071475 cellular hyperosmotic salinity response	IEA GO_REF:0000107	REMOVE	Summary: cellular hyperosmotic salinity response (IEA, Ensembl orthology transfer). Reason: Propagated from expression-change observations in another species; no evidence that FBP1 participates in this response in human, and the response is unrelated to its gluconeogenic function. Supporting Evidence: file:human/FBP1/FBP1-uniprot.txt Catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate in the presence of divalent cations, acting as a rate-limiting enzyme in gluconeogenesis.
GO:0071477 cellular hypotonic salinity response	IEA GO_REF:0000107	REMOVE	Summary: cellular hypotonic salinity response (IEA, Ensembl orthology transfer). Reason: Propagated from expression-change observations in another species; no evidence that FBP1 participates in this response in human, and the response is unrelated to its gluconeogenic function. Supporting Evidence: file:human/FBP1/FBP1-uniprot.txt Catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate in the presence of divalent cations, acting as a rate-limiting enzyme in gluconeogenesis.
GO:0097403 cellular response to raffinose	IEA GO_REF:0000107	REMOVE	Summary: cellular response to raffinose (IEA, Ensembl orthology transfer). Reason: Propagated from expression-change observations in another species; no evidence that FBP1 participates in this response in human, and the response is unrelated to its gluconeogenic function. Supporting Evidence: file:human/FBP1/FBP1-uniprot.txt Catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate in the presence of divalent cations, acting as a rate-limiting enzyme in gluconeogenesis.
GO:1904628 cellular response to phorbol 13-acetate 12-myristate	IEA GO_REF:0000107	REMOVE	Summary: cellular response to phorbol 13-acetate 12-myristate (IEA, Ensembl orthology transfer). Reason: Propagated from expression-change observations in another species; no evidence that FBP1 participates in this response in human, and the response is unrelated to its gluconeogenic function. Supporting Evidence: file:human/FBP1/FBP1-uniprot.txt Catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate in the presence of divalent cations, acting as a rate-limiting enzyme in gluconeogenesis.

Gene Description

Existing Annotations Review

Core Functions

Mg2+-dependent hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate in the cytosol, the irreversible, AMP- and fructose 2,6-bisphosphate-regulated step of gluconeogenesis in liver and kidney.

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