UniProt functional annotation for P00636



	UniProt functional annotation for P00636

UniProt code: P00636.

Organism: Sus scrofa (Pig).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.

Function: 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. Plays a role in regulating glucose sensing and insulin secretion of pancreatic beta-cells. Appears to modulate glycerol gluconeogenesis in liver. Important regulator of appetite and adiposity; increased expression of the protein in liver after nutrient excess increases circulating satiety hormones and reduces appetite-stimulating neuropeptides and thus seems to provide a feedback mechanism to limit weight gain. {ECO:0000250|UniProtKB:P09467}.

Catalytic activity: Reaction=beta-D-fructose 1,6-bisphosphate + H2O = beta-D-fructose 6- phosphate + phosphate; Xref=Rhea:RHEA:11064, ChEBI:CHEBI:15377, ChEBI:CHEBI:32966, ChEBI:CHEBI:43474, ChEBI:CHEBI:57634; EC=3.1.3.11; Evidence={ECO:0000269|PubMed:15767255, ECO:0000305|PubMed:1313579};

Cofactor: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269|PubMed:12595528, ECO:0000269|PubMed:14530289, ECO:0000269|PubMed:15767255, ECO:0000269|PubMed:9708979}; Note=Binds 3 Mg(2+) ions per subunit. {ECO:0000269|PubMed:12595528, ECO:0000269|PubMed:14530289, ECO:0000269|PubMed:15767255, ECO:0000269|PubMed:9708979};

Activity regulation: Subject to complex allosteric regulation. The enzyme can assume an active R-state, or an inactive T-state. Intermediate conformations may exist. AMP acts as allosteric inhibitor. AMP binding affects the turnover of bound substrate and not the affinity for substrate. Fructose 2,6-bisphosphate acts as competitive inhibitor. Fructose 2,6-bisphosphate and AMP have synergistic effects. {ECO:0000269|PubMed:10913263, ECO:0000269|PubMed:14530289, ECO:0000269|PubMed:15767255, ECO:0000269|PubMed:17933867, ECO:0000269|PubMed:2164670, ECO:0000269|PubMed:9708979}.

Biophysicochemical properties: Kinetic parameters: KM=1.2 uM for fructose-1,6-diphosphate {ECO:0000269|PubMed:15767255};

Pathway: Carbohydrate biosynthesis; gluconeogenesis.

Subunit: Homotetramer. {ECO:0000269|PubMed:10913263, ECO:0000269|PubMed:1312721, ECO:0000269|PubMed:14530289, ECO:0000269|PubMed:15767255, ECO:0000269|PubMed:17933867, ECO:0000269|PubMed:1849642, ECO:0000269|PubMed:2157849, ECO:0000269|PubMed:2164670, ECO:0000269|PubMed:9708979}.

Miscellaneous: The molecule has a highly reactive cysteine residue (Cys-117 or Cys-129), which tends to form mixed disulfides (e.g. with homocystine) but is not essential for enzyme activity.

Similarity: Belongs to the FBPase class 1 family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Sus scrofa (Pig).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.



Function:		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. Plays a role in regulating glucose sensing and insulin secretion of pancreatic beta-cells. Appears to modulate glycerol gluconeogenesis in liver. Important regulator of appetite and adiposity; increased expression of the protein in liver after nutrient excess increases circulating satiety hormones and reduces appetite-stimulating neuropeptides and thus seems to provide a feedback mechanism to limit weight gain. {ECO:0000250\|UniProtKB:P09467}.


Catalytic activity:		Reaction=beta-D-fructose 1,6-bisphosphate + H2O = beta-D-fructose 6- phosphate + phosphate; Xref=Rhea:RHEA:11064, ChEBI:CHEBI:15377, ChEBI:CHEBI:32966, ChEBI:CHEBI:43474, ChEBI:CHEBI:57634; EC=3.1.3.11; Evidence={ECO:0000269\|PubMed:15767255, ECO:0000305\|PubMed:1313579};
Cofactor:		Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269\|PubMed:12595528, ECO:0000269\|PubMed:14530289, ECO:0000269\|PubMed:15767255, ECO:0000269\|PubMed:9708979}; Note=Binds 3 Mg(2+) ions per subunit. {ECO:0000269\|PubMed:12595528, ECO:0000269\|PubMed:14530289, ECO:0000269\|PubMed:15767255, ECO:0000269\|PubMed:9708979};
Activity regulation:		Subject to complex allosteric regulation. The enzyme can assume an active R-state, or an inactive T-state. Intermediate conformations may exist. AMP acts as allosteric inhibitor. AMP binding affects the turnover of bound substrate and not the affinity for substrate. Fructose 2,6-bisphosphate acts as competitive inhibitor. Fructose 2,6-bisphosphate and AMP have synergistic effects. {ECO:0000269\|PubMed:10913263, ECO:0000269\|PubMed:14530289, ECO:0000269\|PubMed:15767255, ECO:0000269\|PubMed:17933867, ECO:0000269\|PubMed:2164670, ECO:0000269\|PubMed:9708979}.
Biophysicochemical properties:		Kinetic parameters: KM=1.2 uM for fructose-1,6-diphosphate {ECO:0000269\|PubMed:15767255};
Pathway:		Carbohydrate biosynthesis; gluconeogenesis.
Subunit:		Homotetramer. {ECO:0000269\|PubMed:10913263, ECO:0000269\|PubMed:1312721, ECO:0000269\|PubMed:14530289, ECO:0000269\|PubMed:15767255, ECO:0000269\|PubMed:17933867, ECO:0000269\|PubMed:1849642, ECO:0000269\|PubMed:2157849, ECO:0000269\|PubMed:2164670, ECO:0000269\|PubMed:9708979}.
Miscellaneous:		The molecule has a highly reactive cysteine residue (Cys-117 or Cys-129), which tends to form mixed disulfides (e.g. with homocystine) but is not essential for enzyme activity.
Similarity:		Belongs to the FBPase class 1 family. {ECO:0000305}.